X: -5.0954556 Y: 8.011856title: The Potential Role of Circulating MicroRNAs in Male Rat Infertility Treated with Kaempferia parviflora publish year: 2021 keyword: Kaemferia_parviflora content: Background. Therapeutic strategies based on herbal plants and diets containing sufficient amounts of antioxidants and essential vitamins are very important factors in treating reproduction and male infertility worldwide. Thus, the aim of this study was to investigate the potential effects of Kaempferia parviflora (KP) on the role of some microRNAs in treated and nontreated infertile rats. In addition, the correlation of expressed microRNAs with sperm count, sperm motility, and sperm viability was identified. The probable use of these microRNAs as a diagnostic marker for predicting the clinical response of infertility to the treatment with KP was also achieved. Methods. In the present study, the potential effects of Kaempferia parviflora (KP) at different doses (140, 280, and 420 mg/kg) for six weeks on male rats with subinfertility were explored. In addition, the effect of KP on the expression of circulating microRNAs and its correlation with the parameters of sexual infertility was identified by performing both in vitro and in vivo assays. In vitro antioxidant activity, sperm functional analysis, serum testosterone, and expression of circulating microRNAs were conducted using colorimetric, ELISA, and real-time RT-PCR analysis, respectively. Results. Kaempferia parviflora (KP) at nontoxic doses of 140–420 mg/kg/day for six weeks significantly improved serum testosterone and epididymal sperm parameters (sperm count, motility, and sperm viability), increased testicular weight, and provided a reduction in the percentage of abnormal spermatozoon in infertile male rats. The expression of miR-328 and miR-19b significantly decreased, and miR-34 significantly increased in infertile rats treated with KP compared to infertile nontreated rats. After six weeks of KP therapy, the change in the expression levels of miRNAs was correlated positively with higher levels of serum testosterone and the measures of epididymal sperm parameters. The respective area under the receiver operating characteristic curve (AUC-ROC) was applied to predict the potential use of miR-328, miR-19b, and miR-34 in the diagnosis of male infertility in treated and nontreated infertile male rats. The data showed that AUC cutoff values of 0.91 for miR-328, 0.89 for miR-19b, and 0.86 for miR34 were the best estimated values for the clinical diagnosis of male rats with infertility. In rats treated with KP for six weeks, AUC cutoff values of 0.76 for miR-328, 0.79 for miR-19b, and 0.81 for miR-34 were the best cutoff values reported for the clinical response of infertility to KP therapy after six weeks. Conclusions. In this study, the improvement of male infertility might proceed via antioxidant and antiapoptotic pathways, which significantly improve spermatogenesis and aphrodisiac properties of males. In addition, the expression of miRNAs, miR-328, miR-34, and miR-19b, in KP-treated and nontreated infertile rats significantly correlated with increased serum testosterone levels and epididymal sperm parameters as well. MicroRNAs, miR-328, miR-34, and miR-19b, might be related to oxidative and apoptotic pathways that proceeded in spermatogenesis. Thus, the use of miRNAs could have a role as diagnostic, therapeutic, and predictive markers for assessing the clinical response of Kaempferia parviflora treatment for six weeks. This may have potential applications in the therapeutic strategies based on herbal plants for male infertility. However, in subsequent studies, the genetic regulatory mechanisms of the expressed miRNAs should be fully characterized.

1. Introduction
In life, infertility is considered one of the most health problems facing 30–50% of males world wide [1, 2]. Previously, defects in male spermatogenesis, reduction in sperm quality, and seminal production were greatly affected by several treating conditions such as hypogonadism, varicocele, infections, and obstructions [1–3]. In addition, spermatogenesis and sperm normal production were shown to be affected by inadequate vitamins intake, chemotherapy, type of drugs used, toxins, and polluted air [3]. Diets containing sufficient amounts of antioxidants and vitamins A, B, C, and E can enhance barrier stability of testis by increasing blood flow and protect sperm DNA from cellular oxidative-free radical activity [4, 5]. Antioxidants were shown to protect DNA and other cellular components from oxidation and damage, improving sperm quality, which in turn raises the rates of fertility among males [6–8].
Therefore, therapeutic strategies based on herbal plants are very important factors in treating reproduction and male infertility. Natural plants are concomitantly used as a possibility traditional medicine for treating male infertility and other human diseases in up to 60% of the world’s population [9–12]. Medicinal plants related to the family Zingiberaceae are used worldwide as spices and are shown to have versatile medical activities, particularly as antioxidative [13], free radical scavenging activities [14, 15], androgenic activity [16], aphrodisiac [17, 18], anticancer [19], and anti-inflammatory [20].
Kaempferia parviflora (KP) is one of the most popular plants in the family Zingiberaceae. It has many active constituents like 7-dimethoxyflavone and 5,7,40-trimethoxyflavone [17–24]. Traditionally, KP and its compounds are used as a folk medicine for managing a variety of diseases, particularly male infertility, due to its aphrodisiac, antioxidant, and anti-inflammatory activities [17–22].
Previously, a number of biological activities of KP were identified, particularly antioxidant, anti-inflammatory, and inhibition of NO production, increasing male libido and erectile dysfunction, having aphrodisiac properties, and being used to improve sexual activities and performance [24–28].
In rabbit semen, KP (Krachaidum, KD) showed previously a quiet tendency to increase ejaculation volume and a subsequent increase of the total number, viability, and progressive motility of spermatozoa [29]. Additionally, the seminal vesicle and spermatogenesis significantly improved in rats, following the use of tea or extracts from KP (Krachaidum, KD) [30].
This might be due to the presence of active components like phenolics and flavonoids present mainly in the KP extracts [24]. In other studies, like other plants (curcuma and ginger) in the Zingiberaceae family, it was reported that KP extracts modulate changes in reproductive function by relaxation of the smooth muscles of the blood vessels [31–33], leading to an increase in blood flow to the reproductive organs and finally an improvement in functions of male reproductive organs. Also, KP in association with physical exercise interventions significantly stimulated both increase in sexual motivation and enhancement of sexual performance as well [34].
However, little is known about the roles of circulating miRNAs in reproductive function and male infertility in cases treated with traditional medicine particularly, KP extracts. It was reported previously in many studies that microRNAs as short noncoding transcripts of up to 22 nucleotides have considerable potential as diagnostic and therapeutic tools against many diseases [35, 36]. At the posttranscriptional level, microRNAs might regulate gene expression. So, it could be used for monitoring diagnosis and for treatment of male infertility with therapeutic or herbal medicine [35–37]. In addition, a set of miRNAs was shown to regulate significantly more biological processes like embryonic development, cell differentiation, cell cycle, cell growth, and apoptosis [38–40]. Thus, dysregulation of miRNA functions can lead to the development of disease. miRNAs are shown to contribute to human spermatogenesis and to be retained after the completion of spermatogenesis, and any changes in the expression of spermatozoal RNAs have been associated with male infertility [41–44].
The role of small noncoding RNAs was significantly reported in male germ cell development [45, 46]. In previous studies, miRNAs were reported to have a role in male and female gametogenesis and the development of the embryo [46, 47]. miRNAs were identified in the male reproductive system and in testis, epididymis, sperm cells, seminal plasma, and extracellular vesicles (i.e., exosomes and microvesicles) were suggested to represent known functions. Thus, any alterations in spermatogenesis and embryogenesis could be attributed to the change in the expression of miRNAs [48–54]. These signs could clearly have the potential association of miRNAs in various forms of infertility [53, 54]. In the testis, the critical role of miRNAs was demonstrated during mitotic proliferation and formation of spermatogonia from germ cells. Additionally, their roles also start during spermatogonial stem cells (SSCs) in the epithelium of seminiferous tubules or during spermatocyte meiosis and spermiogenesis [55].
In normozoospermic controls and in infertile males, miR-19b and other miRNAs were clearly expressed in human seminal plasma from fertile controls; however, they significantly increased in the seminal plasma of the infertile men [56]. Thus, a significant increase in the expression levels of miR-19b may be a possible indicator of the degrees of spermatogenic failure in treated and nontreated cases. In addition, other studies reported the expression of many miRNAs, including miR-34, which were associated with many vital processes of male fertility, particularly the regulation of germ cell function as well as cell differentiation during spermatogenesis [56, 57]. It was reported that lower expression and hypermethylation of the promotor of cellular miR-34 types were significantly identified in infertile males. Thus, it was reported that obvious lower expression with hypermethylation of the promoter region makes miR-34 types be an indicator of the deficiency of spermatogenesis [58].
In animal models, inactivation and lower expression of miR34-b,c along with others miRNAs clusters caused low sperm counts, abnormal sperm morphology with low motility, and subsequent male infertility [57, 59, 60]. This might be due to unsuitable or hypermethylation of CpG in their promoter regions. In n somatic cells, miR-34 types additionally act as tumor suppressor genes aside from the P53 gene [61].
Also, an increase in the expression levels of miR-328 was reported to govern the pathogenesis of male erectile dysfunction (ED) in many ways. It was found that miR-328 might impair stem cell or neuronal survival, control zonation morphogenesis, and affect calcium homeostasis [62–66].
For aforementioned facts [45–67], identifying the vital role of miR-19b, miR-328, and miR-34 enforces studying their expression profile in treated and nontreated infertility male rats with conventional KP herbal medicine. In addition, there are no scientific reports on the effect of therapeutic or herbal-based treatments such as KP on the role of these circulating microRNAs in reproductive function and male infertility. Therefore, the aim of this study was to investigate the potential effects of KP on the role of microRNAs, miR-19b, miR-328, and miR-34, in treated and nontreated infertile rats and also the correlation of expressed microRNAs with sperm count, sperm motility, and sperm viability, as well as its potential use as diagnostic biomarkers in predicting the clinical response of Kaempferia parviflora treatment.

2. Materials and Methods

2.1. Plant Material
The Kaempferia parviflora (KP) rhizomes obtained were purchased from a convenience store (Othaim Markets) in Riyadh, KSA. The plant rhizomes were cut into small pieces and dried in a hot air oven at 55°C [28, 65]. Then, the dried materials were macerated in ethanol twice, for 3 days each, and filtered. To prepare a 1% of fresh KP suspension, the dry KP powder was suspended in distilled water with Tween 80 [28, 65].

2.2. Assessment of Total Phenolic Content (TPC) and Total Flavonoid (TF) Content

2.2.1. Preparation of KP Extract
In this test, a mechanical blender was used to prepare a fine powder of the dried rhizomes of KP. At room temperature, the rhizomes of the plant were dried in the shade and then chopped into small pieces. KP was ground to a fine powder and became ready for the extraction step. By using a Soxhlet apparatus, 20 g of the dried rhizome powder was extracted in 300 mL methanol at 60–65°C for 3-4 h. Then, Whatman filter paper No. 1 was used to filtrate the extract and exposed to pressure at 40°C for the concentration process. Finally, the extract was further dried, weighed (2.6 g), and stored in storage vials at 4°C for reuse in the study [28, 65, 66].

2.2.2. Total Phenolic Content
In this experiment, the total phenolic content of the KP extract was estimated by using Folin–Ciocalteu method as previously reported [68, 69]. “A total of 200 μL of crude KP extract (1 mg/mL/3 mL dH2O) was mixed thoroughly with 0.5 mL of Folin–Ciocalteu reagent for 3 min. To the mixture, 2 mL of 20% (w/v) sodium carbonate was added, and the whole mixture was stored in the dark for 60 min as mentioned previously” [68, 69]. Then, “the absorbance of the produced mixture was measured at 650 nm. Finally, calibration curves were used to calculate the concentrations of the total phenolic contents and expressed as mg of gallic acid equivalent per g dry weight as mentioned before” [68, 69].

2.2.3. Total Flavonoid Content
In this test, the aluminum chloride colorimetric method was used to estimate the total flavonoid content of crude KP extract, as mentioned previously [70]. In this experiment, “50 μL of KP extract (1 mg/mL ethanol) was completed to 1 mL with methanol and mixed with 4 mL of dH2O. Moreover, after 5 min of incubation, 0.3 mL of 5% NaNO2 solution and 0.3 mL of 10% AlCl3 solution were added, and the mixture was allowed to stand for 6 min [70], followed by the addition of 2 mL of 1 mol/L NaOH solution and the final volume of the mixture reached to 10 mL by adding dH2O” [70]. “The absorbance of the mixture was measured after 15 min. Finally, from a calibration curve, the concentration of the total flavonoid content present was calculated, and the result was expressed as mg rutin equivalent per g dry weight” [70].

2.3. Assessment of Antioxidant Activity

2.3.1. DPPH Assay
The 1,1-diphenyl-2-picryl-hydrazyl (DPPH) was used to estimate the antioxidant activity of the KP extract as mentioned before [71]. “In this test, a mixture of the KP extract was prepared, whereas 3.8 mL DPPH solution was added to 200 μL of each extract (100–500 μg/mL) and the whole mixture left in the dark for one hour at room temperature as mentioned before. In the final stage, the KP mixture was subjected to measure the absorbance at 517 nm against ascorbic acid as a positive control” [71]. Finally, “the ability of the sample to scavenge DPPH radical was determined as follows” [71]: {DPPH scavenging effect = Control OD − Sample OD/Control OD × 100}---[71].

2.3.2. Nitroblue Tetrazolium (NBT) Assay
The free radical scavenging activity of KP extract to superoxide anion was identified by nitroblue tetrazolium (NBT) as previously reported [72]. “In this test, a total of 100–500 μg/mL of the KP extract reacted with a mixture of 1.5 mmol/L riboflavin, 50 mmol/L nitroblue tetrazolium (NBT), 10 mmol/L D,l-methionine, and 0.025% (v/v) Triton X-100 in 50 mmol/L phosphate buffer at pH 7.8, respectively” [72]. “Then, the reaction mixture was initiated by the illuminating process to produce a colored formazan compound. The absorbance of formazan was recorded at 560 nm against ascorbic acid as a positive control. Finally, the percentage of the scavenging activity was identified as the inverse of the produced formazan” [72].

2.3.3. FRAP Assay
In this experiment, the antioxidant capacity of the KP extract was identified by estimation of ferric (Fe +3) reducing antioxidant power (FRAP), as mentioned previously [73]. “In this method, 100 μL of the KP extract (100–500 μg/mL) was incubated with 2.5 mL of 200 mmol/L phosphate buffer (pH 6.6) and 2.5 mL of1% potassium ferricyanide for 20 min at 50°C. After that, 2.5 mL of 10% trichloroacetic acid was added to the reaction mixture and was centrifuged at 10,000 rpm for10 min” [73]. “Then, a mixture from the upper layer was performed, whereas 5 mL of this layer was mixed with 5.0 mL dH2O and 1 mL of 0.1% Fe Cl3. The reaction mixtures were subjected to measure the absorbance at 700 nm against ascorbic acid as a positive control” [73].

2.4. Acute Toxicity Test
In this test, although different concentrations of KP (140, 280, and 420 mg/rat) were previously studied as improving agents for sexual performance in streptozotocin- (STZ-) induced diabetic male rats with infertility [28], the cytotoxicity of KP extract at doses of 140, 280, and 420 mg/rat was subjected to measure cellular toxicity in a healthy group of rats (10 rats) as previously reported in many toxicity studies [74, 75]. After the first 4 h of dosing, all animals have been observed for the appearance of any symptoms of toxicity. In addition, the survived animals were recorded following 24 h and maintained under daily observations for two weeks [74–76].

2.5. Animals Care and Experimental Design
Fifty adult male Wistar rats weighing about 180–200 g were included in this study. One week before starting the experiment, all rats were allowed to acclimatize to the laboratory environment like controlled conditions of the light cycle (12 hr : 12 hr, light : dark), room temperature (25 ± 2°C), and relative humidity (60%–70%) with free access water and rat chow. Animals were randomly classified into five groups of 10 animals each. Group 1 (normal group) was administered with the vehicle (distilled water), and group 2 (subinfertility group) received para-amino salicylic acid (PAS) at a dose of 400 mg/kg bw, while groups 3, 4, and 5 were given PAS at a dose of 400 mg/kg bw with an aqueous suspension of KP extract at doses of 140, 280, and 420 mg/kg, respectively [28, 75]. The animals were orally administered KP once a day for 6 weeks. “The experiment and the experimental procedures were performed according to the guidelines of the Experimental Animal Care Center, College of Applied Medical Sciences, and were approved by the Ethics Committee of the Experimental Animal Care Society, RRC, College of Applied Medical Sciences, King Saud Univ., Riyadh, Saudi Arabia, under file number (RRC-2019-021)” [76].

2.6. Sperm Collection and Functional Analysis
An overdose of “pentobarbital sodium was applied for anesthesia; then, all animals were sacrificed to collect the testes and epididymis” [28]. “Before the collection of spermatozoa, the testes and epididymis were weighted. In addition, to collect rat spermatozoa, a cauda part of the epididymis was minced into small pieces and mixed in 1 ml of Hanks’ balanced salt solution prewarmed at 37°C. Also, sperm parameters such as sperm count, motility, and viability were examined by microscope as previously mentioned” [77].
A Neubauer cell counting chamber under 10× magnification was used to collect sperm counts, as mentioned previously [78]. In addition, “the one-step eosin-nigrosin staining technique was applied to assess the percentage of sperm viability and morphology like normality and abnormality” [77, 78]. “In this test, sperm viability and morphology were then evaluated by counting alive and dead cells, whereas nonstained cells were considered alive and orange-red colored cells were considered dead cells” [77].

2.7. Assessment of Serum Testosterone
Serum samples were collected from the blood by “centrifugation at 2200 g for 15 min at 4°C and subjected to testosterone analysis using immunoassay ELISA Kit (Testosterone ELISA Kit, Abcam, Cambridge, UK)” [28, 65]. The level of testosterone in each sample was calculated according to the manufacturer’s instructions, as mentioned before [28, 65].

2.8. Real-Time RT-PCR Analysis of Circulating miRNAs

2.8.1. Extraction of RNA and Synthesis of cDNA
In this experiment, “RNA of all samples was estimated by using a reverse transcription-polymerase chain reaction (RT-PCR) analyses and the miRNease isolation kit (Qiagen, Hilden, Germany) as mentioned previously” [79–82]. Then, “reverse transcription miScriptII RT kits (Qiagen) were applied to generate a complementary DNA (cDNA), and then the levels of miRNAs were evaluated by optical density” [79–82].

2.8.2. Real-Time RT-PCR Analysis
The expression of “miRNAs in the serum was identified by using quantitative real-time RT-PCR analyses and primers of circulating miRNAs, miR-328, miR-34, and miR-19b (Applied Biosystems, Foster City, CA, USA)” [79]. In this test, “GAPDH gene was applied as an internal housekeeping gene to normalize the average copy number of the resultant PCR components as previously stated in the literature” [80–82].
In PCR process, “templets of respective cDNA were subjected to four thermal phases: primary denaturation phase (I) (at 94°C for 2 minutes); denaturation phase (II) (at 94°C for 30 seconds); annealing phase (III) (at 59°C for 30 seconds); and amplification phase (IV) (at 72°C for 30 seconds)” [80–82]. “The PCR phases (II to IV) proceeded for 45 cycles, and all reactions were measured in a triplicate manner” [80–82].

2.8.3. Statistical Analysis
In this study, “the data obtained were analyzed by using an SPSS statistical program (SPSS, IBM Statistics V.17) and the results of the continuous variables were expressed as mean ± SD” [82]. In addition, the “nonparametric test (Mann–Whitney-Wilcoxon test) and the χ2 test were performed to estimate the frequency differences between the groups, respectively” [82]. Moreover, “to compare between the studied variables like serum testosterone levels, sperm viability and morphology, and expression levels of miRNAs, two independent sample t-tests were used for all groups. Additionally, multiple stepwise regressions and Pearson’s correlations analysis were used to estimate the association between the expressed miRNAs and the studied independent variables in KP-treated and nontreated rats” [82]. “The area under the receiver operating characteristic (ROC) curve was used to measure the susceptibility and sensitivity of the studied parameters like testosterone, sperm viability, morphology, and miRNAs, miR-328, miR-34, and miR-19b, for the diagnosis of male infertility in treated and nontreated rats as previously reported” [82]. All tests were two-tailed; because of multiple assessments, results were only considered statistically significant at a value of < 0.05.

3. Results

3.1. Phenolic and Flavonoid Contents
Total phenolic and flavonoids constituents were calculated from the calibration curves at R² = 0.965 for total phenolic content and R² = 0.986 for the total flavonoid content, respectively. The total phenolic content estimated from the methanolic KP extract was 76.8 ± 3.8 gallic acid equivalents/g, and the total flavonoid content was 42.8 ± 2.7 rutin equivalents/g (Table 1).

Phytoconstituents
Quantity

Total phenolics contenta
76.8 ± 3.8 (R² = 0.965)
Total flavonoids contentb
42.8 ± 2.7(R² = 0.986)

Values are means of three biological replicates. amg gallic acid equivalent (GAE)/g DW. bmg rutin equivalent/g DW.


X: -4.1481323 Y: 8.430997title: Potential Therapeutic Agents, Polymethoxylated Flavones Isolated from Kaempferia parviflora for Cataract Prevention through Inhibition of Matrix Metalloproteinase-9 in Lens Epithelial Cells publish year: 2019 keyword: Kaemferia_parviflora content: Natural flavonoids have powerful antioxidant activity and have been reported to show promising protective effects against cataracts. The plant Kaempferia parviflora (K. parviflora) is indigenous to southeast Asia, including Thailand, and typically contains polymethoxylated flavones. The flavones in K. parviflora are reported to have various biological properties. Recently, polymethoxylated flavones of K. parviflora (KPMFs) were shown to have potent Sirtuin 1 enzyme-stimulating and anti-glycation activities that led to the suppression of cataract formation. Matrix metalloproteinases (MMPs) are upregulated in several pathologic ocular diseases, including cataracts, and have been established as an attractive target for the prevention and/or treatment of specific cataract phenotypes, such as anterior subcapsular cataract (ASC) and posterior capsular opacification (PCO). In the present study, we investigated the effect of KPMFs on MMP (gelatinase) activity in the human lens epithelial cell line, SRA01/04. We demonstrated that KPMFs inhibited the phorbol ester-induced MMP-9 activity and the mRNA expression through the suppression of mitogen-activated protein kinases (MAPKs) phosphorylation in human lens epithelial cells; 5,7-dimethoxyflavone was found to exert the most potent inhibition, but 3,5,7,4′-tetramethoxyflavone and 3,5,7,3′,4′-pentamethoxyflavone also resulted in considerable inhibition. Our results suggested that the consumption of PMFs isolated from K. parviflora, may be an effective strategy to delay the development of cataracts, such as ASC and PCO.

Graphical Abstract Fullsize Image


X: -2.8292756 Y: 9.456079title: Development and clinical trials on anti-inflammatory effect of transdermal patch containing a combination of Kaempferia parviflora and Curcuma longa extracts publish year: 2022 keyword: Kaemferia_parviflora content: Kaempferia parviflora and Curcuma longa have been widely reported to have a potent anti-inflammatory effect. However, both extracts have been shown to have low bioavailability and high-level first pass metabolism upon oral administration. This study aimed to develop transdermal delivery of a combination of both extracts in matrix-patch formulations with five different volatile oils which possess analgesic and anti-inflammatory properties. Fourteen formulations exhibited good physicochemical properties and stability. The release of methoxyflavones increased significantly when the concentration of PVP (polyvinylpyrrolidone) in the patches increased. The drug release kinetics were best-fitted with the zero-order and Higuchi models, depending on the amount of PVP. When combined with Curcuma longa, the patch provided the highest accumulation of methoxyflavones and curcuminoids within the skin. In the clinical, randomized controlled trial, a significant pain improvement was found after seven days of application on the pain area. The pain scores decreased from 5.84 ± 1.57 to 2.74 ± 1.37 and the mean pain pressure threshold increased significantly from 1.79 ± 0.51 N to 2.55 ± 0.41 N. Our results indicated that the developed herbal patches were useful for transdermal application and can be considered as an alternative treatment for pain relief, highlighted by a decrease in pain intensity and an increase in pain tolerance, without skin irritation.


X: -0.08523648 Y: 7.2155657title: Kaempferia sipraiana (Zingiberaceae), a new species from Thailand and a new record of Kaempferia pseudoparviflora for Myanmar publish year: 2022 keyword: Kaemferia_parviflora content: Boonma T, Saensouk S, Saensouk P. 2022. Kaempferia sipraiana (Zingiberaceae), a new species from Thailand and a new record of Kaempferia pseudoparviflora for Myanmar. Biodiversitas 23: 2203-2211. Kaempferia sipraiana Boonma & Saensouk, a new species of Kaempferia subgenus Protanthium (Zingiberaceae) from northern Thailand and K. pseudoparviflora Saensouk P. & Saensouk, a new record species of Kaempferia subgenus Kaempferia for Myanmar are described, illustrated, and photographed. The dominant characters of Kaempferia sipraiana were leaves narrowly elliptic, green with short white stripes arranged parallel along the leaf edges, between the midrib and both sides of the edges, apex acuminate with slightly mucronate, base attenuate-oblique; peduncle glabrous; bracts apex mucronate, glabrous, red with dark red veins; bracteoles glabrous; floral tube shorter than calyx; calyx glabrous; staminodes oblanceolate, apex 3-lobes like curly brackets; labellum white at the base with pinkish purple in the middle gradually fade to pale pink and to reach to white tip and edge respectively, apex 3-lobes like curly brackets, each lobe 3.0-3.3 cm long; apex 4 lobes, outer lobes acute, inner lobes obtuse rarely combined to truncate; stigma with pink lips. The dominant characters of K. pseudoparviflora were one leaf and dark green with light grey markings, the inflorescence looks like inflorescence of K. parviflora. The information on vernacular name, distribution, phenology, ecology, conservation status, specimens examined, and an identification key to both species of Kaempferia in Thailand is revised and presented.


X: -4.0457454 Y: 7.6818147title: Selective Cytotoxicity of Kaempferia parviflora Extracts in Human Cell Lines publish year: 2021 keyword: Kaemferia_parviflora content: Objective:
Aims of this study were to (1) compare anti-proliferative activity between aqueous and ethanol Kaempferia parviflora (KP) extracts in both cancer (Human urinary bladder cancer cell, T24) and normal cell lines (Human umbilical vein endothelial cell, HUVEC). (2) confirm selective cytotoxicity of ethanol KP extract to normal and different cancer cell lines (3) investigate its cellular mechanism through p53 and SIRT1 gene expression.

Methods:
Phytochemical difference between aqueous and ethanol extract was determined by thin layer chromatography (TLC). Screening for cytotoxic activity in human cell lines was performed by cell viability assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reagent. P53 and SIRT1 gene expression were quantified using RT-PCR.

Results:
Results from the cell viability assay were shown as follows: (1) ethanol extract possessed higher toxicity to cancerous cells than aqueous extract (2) ethanol extract exhibited higher cytotoxicity to cancerous cells than normal cells (3) ethanol extract also showed cytotoxicity, with different levels, to three prostate cancer cell lines varying in aggressiveness. (4) ethanol KP extract induced cell death in T24 via p53 gene expression and prolonged cell survival in HUVEC through SIRT1 gene expression.

Conclusion:
These findings implied that ethanol KP extract might possibly be an alternative for cancer adjuvant therapy through the mechanism of selective p53 and SIRT1 gene expression.


X: -3.9052863 Y: 9.893483title: Phyllanthus tenellus Roxb. and Kaempferia parviflora Wall. ex Baker compounds as inhibitors of SARS-CoV-2 main protease and RNA-dependent RNA polymerase: A molecular docking study publish year: 2022 keyword: Kaemferia_parviflora content: Context: The outbreak of a novel coronavirus, SARS-CoV-2 has caused an unprecedented COVID-19 pandemic. To put an end to this pandemic, effective antivirals should be identified or developed for COVID-19 treatment. However, specific and effective antivirals or inhibitors against SARS-CoV-2 are still lacking.

Aims: To evaluate bioactive compounds from Phyllanthus tenellus and Kaempferia parviflora as inhibitorsagainst two essential SARS-CoV-2 proteins, main protease (Mpro) and RNA-dependent RNA polymerase (RdRp), through molecular docking studies and to predict the drug-likeness properties of the compounds.

Methods: The inhibition potential and interaction of P. tenellus and K. parviflora compounds against Mpro and RdRp were assessed through molecular docking. The drug-likeness properties of the compounds were predicted using SwissADME and AdmetSAR tools.

Results: Rutin and ellagic acid glucoside from P. tenellus and 4-hydroxy-6-methoxyflavone and 5-hydroxy-3,7,4’-trimethoxyflavone from K. parviflora exhibited the highest binding conformations to Mpro by interacting with its substrate binding site that was predicted to halt the Mpro activity. As for RdRp, ellagitannin and rutin from P. tenellus and peonidin and 5,3’-dihydroxy-3,7,4’-trimethoxyflavone from K. parviflora were the best-docked compounds that bound to the RdRp catalytic domain (Asp760 and Asp761) and NTP-entry channel that were anticipated to stop RNA polymerization. However, in the context of drug developability, 4-hydroxy-6-methoxyflavone, 5-hydroxy-3,7,4’-trimethoxyflavone, peonidin and 5,3’-dihydroxy-3,7,4’-trimethoxyflavone from K. parviflora were highly potential to be oral active drugs compared to rutin, ellagic acid glucoside and ellagitannin from P. tenellus.

Conclusions: P. tenellus and K. parviflora compounds, particularly the aforementioned compounds, were suggested as potential inhibitors of SARS-CoV-2 Mpro and RdRp.


X: -4.6035824 Y: 8.438217title: Evaluation of the Safety of Daily Consumption of Kaempferia parviflora Extract (KPFORCE): A Randomized Double-Blind Placebo-Controlled Trial publish year: 2019 keyword: Kaemferia_parviflora content: This study's aim was to evaluate the safety of daily consumption of Kaempferia parviflora extract (KPE) using a randomized double-blind placebo-controlled study with 52 recruited healthy Japanese subjects. Each subject received five KPE tablets (containing 150 mg of KPFORCE™/tablet) or placebo daily for 4 weeks. There were no adverse events related to KPE intake or any abnormalities compared with placebo group in anthropometric, cardiovascular, blood, and urine parameters during the course of the study. Thus, daily KPE ingestion was found to be safe in healthy Japanese men and women.


X: 1.6051813 Y: 8.085076title: Establishment of a Rapid Micropropagation System for Kaempferia parviflora Wall. Ex Baker: Phytochemical Analysis of Leaf Extracts and Evaluation of Biological Activities publish year: 2021 keyword: Kaemferia_parviflora content: This study aimed to establish a rapid in vitro plant regeneration method from rhizome buds of Kaempferia parviflora to obtain the valuable secondary metabolites with antioxidant and enzyme inhibition properties. The disinfection effect of silver oxide nanoparticles (AgO NPs) on rhizome and effects of plant growth regulators on shoot multiplication and subsequent rooting were investigated. Surface sterilization of rhizome buds with sodium hypochlorite was insufficient to control contamination. However, immersing rhizome buds in 100 mg L−1 AgO NPs for 60 min eliminated contamination without affecting the survival of explants. The number of shoots (12.2) produced per rhizome bud was higher in Murashige and Skoog (MS) medium containing 8 µM of 6-Benzyladenine (6-BA) and 0.5 µM of Thidiazuron (TDZ) than other treatments. The highest number of roots (24), with a mean root length of 7.8 cm and the maximum shoot length (9.8 cm), were obtained on medium MS with 2 µM of Indole-3-butyric acid (IBA). A survival rate of 98% was attained when plantlets of K. parviflora were acclimatized in a growth room. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to determine the chemical profile of K. parviflora leaf extracts. Results showed that several biologically active flavonoids reported in rhizomes were also present in leaf tissues of both in vitro cultured and ex vitro (greenhouse-grown) plantlets of K. parviflora. We found 40 and 36 compounds in in vitro cultured and ex vitro grown leaf samples, respectively. Greenhouse leaves exhibited more potent antioxidant activities than leaves from in vitro cultures. A higher acetylcholinesterase inhibitory ability was obtained for greenhouse leaves (1.07 mg/mL). However, leaves from in vitro cultures exhibited stronger butyrylcholinesterase inhibitory abilities. These results suggest that leaves of K. parviflora, as major byproducts of black ginger cultivation, could be used as valuable alternative sources for extracting bioactive compounds.


X: -4.7525005 Y: 8.262155title: Effects of Kaempferia parviflora Wall. Ex. Baker on electrophysiology of the swine hearts publish year: 2013 keyword: Kaemferia_parviflora content: Background & objectives:
Pre-clinical studies in swine have demonstrated that a supratherapeutic concentration of sildenafil citrate decreased defibrillation efficacy and facilitated cardiac arrhythmia. We therefore, decided to investigate the effects of Kaempferia parviflora (KP) extract on these parameters in the swine heart. The underlying assumption was that in the heart, KP might be producing effects similar to sildanafil citrate as KP has long been used in southeast Asian traditional medicine to correct erectile dysfunction.

Methods:
The study was conducted as the defibrillation study, and ventricular fibrillation (VF) induction study. In both studies, the defibrillation threshold (DFT), the upper limit of vulnerability (ULV) and VF threshold were determined before and after KP extract administration.

Results:
In both studies KP extract at high concentrations (100 and 50 mg/kg) significantly increased the DFT and ULV, without altering the VF threshold. At these concentrations, systolic and diastolic blood pressures were also attenuated.

Interpretation & conclusions:
High concentrations of KP extract attenuated defibrillation efficacy and increased cardiac vulnerability to arrhythmia in a normal swine heart. When used in appropriate concentrations, its blood pressure lowering effect may be useful in hypertensive states. Further studies need to be done to elucidate its mechanism of action.


X: -4.0045485 Y: 8.402616title: Quercetin 3,5,7,3′,4′-pentamethyl ether from Kaempferia parviflora directly and effectively activates human SIRT1 publish year: 2021 keyword: Kaemferia_parviflora content: Sirtuin 1 (SIRT1), an NAD⁺-dependent deacetylase, is a crucial regulator that produces multiple physiological benefits, such as the prevention of cancer and age-related diseases. SIRT1 is activated by sirtuin-activating compounds (STACs). Here, we report that quercetin 3,5,7,3′,4′-pentamethyl ether (KPMF-8), a natural STAC from Thai black ginger Kaempferia parviflora, interacts with SIRT1 directly and stimulates SIRT1 activity by enhancing the binding affinity of SIRT1 with Ac-p53 peptide, a native substrate peptide without a fluorogenic moiety. The binding affinity between SIRT1 and Ac-p53 peptide was enhanced 8.2-fold by KPMF-8 but only 1.4-fold by resveratrol. The specific binding sites of KPMF-8 to SIRT1 were mainly localized to the helix2–turn–helix3 motif in the N-terminal domain of SIRT1. Intracellular deacetylase activity in MCF-7 cells was promoted 1.7-fold by KPMF-8 supplemented in the cell medium but only 1.2-fold by resveratrol. This work reveals that KPMF-8 activates SIRT1 more effectively than resveratrol does.


X: -3.6679912 Y: 8.480878title: Improvement of Damage in Human Dermal Fibroblasts by 3,5,7-Trimethoxyflavone from Black Ginger (Kaempferia parviflora) publish year: 2022 keyword: Kaemferia_parviflora content: Reactive oxygen species (ROS) are generated during intrinsic (chronological aging) and extrinsic (photoaging) skin aging. Therefore, antioxidants that inhibit ROS production may be involved in delaying skin aging. In this study, we investigated the potential effects of compounds isolated from black ginger, Kaempferia parviflora, a traditional medicinal plant, on normal human dermal fibroblasts in the context of inflammation and oxidative stress. The isolated compounds were structurally characterized as 5-hydroxy-7-methoxyflavone (1), 3,7-dimethoxy-5-hydroxyflavone (2), 5-hydroxy-3,7,3,4-tetramethoxyflavone (3), 7,4-dimethylapigenin (4), 3,7,4-trimethylkaempferol (5), and 3,5,7-trimethoxyflavone (6), using nuclear magnetic resonance spectroscopy (NMR) and liquid chromatography–mass spectrometry (LC/MS) analyses. These flavonoids were first evaluated for their ability to suppress extracellular matrix degradation in normal human dermal fibroblasts. Of these, 3,5,7-trimethoxyflavone (6) significantly inhibited the tumor necrosis factor (TNF)-α-induced high expression and secretion of matrix metalloproteinase (MMP)-1 by cells. We further found that 3,5,7-trimethoxyflavone suppressed the excessive increase in ROS, mitogen-activated protein kinases (MAPKs), Akt, and cyclooxygenase-2 (COX-2)and increased heme oxygenase (HO)-1 expression. The expression of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and IL-8, was also suppressed by 3,5,7-trimethoxyflavone (6). Taken together, our results indicate that 3,5,7-trimethoxyflavone (6) isolated from K. parviflora is a potential candidate for ameliorating skin damage.


X: -3.2509372 Y: 8.100805title: Exploring Volatile Organic Compounds in Rhizomes and Leaves of Kaempferia parviflora Wall. Ex Baker Using HS-SPME and GC–TOF/MS Combined with Multivariate Analysis publish year: 2023 keyword: Kaemferia_parviflora content: Volatile organic compounds (VOCs) play an important role in the biological activities of the medicinal Zingiberaceae species. In commercial preparations of VOCs from Kaempferia parviflora rhizomes, its leaves are wasted as by-products. The foliage could be an alternative source to rhizome, but its VOCs composition has not been explored previously. In this study, the VOCs in the leaves and rhizomes of K. parviflora plants grown in a growth room and in the field were analyzed using the headspace solid-phase microextraction (HS-SPME) method coupled with gas chromatography and time-of-flight mass spectrometry (GC-TOF-MS). The results showed a total of 75 and 78 VOCs identified from the leaves and rhizomes, respectively, of plants grown in the growth room. In the field samples, 96 VOCs were detected from the leaves and 98 from the rhizomes. These numbers are higher compared to the previous reports, which can be attributed to the analytical techniques used. It was also observed that monoterpenes were dominant in leaves, whereas sesquiterpenes were more abundant in rhizomes. Principal component analysis (PCA) revealed significantly higher abundance and diversity of VOCs in plants grown in the field than in the growth room. A high level of similarity of identified VOCs between the two tissues was also observed, as they shared 68 and 94 VOCs in the growth room and field samples, respectively. The difference lies in the relative abundance of VOCs, as most of them are abundant in rhizomes. Overall, the current study showed that the leaves of K. parviflora, grown in any growth conditions, can be further utilized as an alternative source of VOCs for rhizomes.


X: -4.509613 Y: 8.805851title: Glucose Tolerance Test and Pharmacokinetic Study of Kaempferia parviflora Extract in Healthy Subjects publish year: 2019 keyword: Kaemferia_parviflora content: Kaempferia parviflora Wall. ex Baker (KP), Krachaidam in Thai or Thai ginseng, is a herbal medicine that has many potential pharmacological effects. The effect of KP extract on blood glucose level in rodent was reported. This study focused on the oral glucose tolerance test and pharmacokinetic study in healthy volunteers administered with KP extract (90 and 180 mg/day, placebo). The oral glucose tolerance tests were performed at baselines and 28-days of administration. The pharmacokinetics were determined after a single dose administration of the tested products using 3,5,7,3′,4′-pentamethoxyflavone (PMF) and 5,7,4′-trimethoxylflavone (TMF) as markers. The results showed that glucose metabolism via oral glucose tolerance test was not affected by KP extract. Blood glucose levels of volunteers at 120 min after glucose loading were able to be returned to initial levels in placebo, KP 90 mg/day, and KP 180 mg/day groups both at baseline and 28-days of administration. The results of the pharmacokinetic study revealed that only TMF and PMF, but not 5,7-dimethoxyflavone (DMF) levels could be detected in human blood. The given doses of KP extract at 90 and 180 mg/day showed a linear dose-relationship of blood PMF concentration whereas blood TMF was detected only at high given dose (180 mg/day). The half-lives of PMF and TMF were 2–3 h. The maximum concentration (Cmax), area under the curve of blood concentration and time (AUC), and time to maximum concentration (Tmax) values of PMF and TMF estimated for the 180 mg/day dose were 71.2 ± 11.3, 63.0 ± 18.0 ng/mL; 291.9 ± 48.2, 412.2 ± 203.7 ng∙h/mL; and 4.02 ± 0.37, 6.03 ± 0.96 h, respectively. PMF was quickly eliminated with higher Ke and Cl than TMF at the dose of 180 mg/day of KP extract. In conclusion, the results demonstrated that KP extract had no effect on the glucose tolerance test. In addition, this is the first demonstration of the pharmacokinetic parameters of methoxyflavones of KP extract in healthy volunteers. The data suggest the safety of the KP extract and will be of benefit for further clinical trials using KP extract as food and sport supplements as well as a drug in health product development.


X: -4.042505 Y: 7.2039447title: Anticholinesterase activity of 7-methoxyflavones isolated from Kaempferia parviflora publish year: 2009 keyword: Kaemferia_parviflora content: The rhizome of Kaempferia parviflora or kra-chai-dum (in Thai) is used traditionally as a folk medicine. The preliminary cholinesterase inhibitory screening of this plant extract exhibited significant acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Thirteen known methoxyflavones (1-13) were isolated and their structures were completely elucidated based on NMR analysis and compared with literature reports. Minor compounds 12-13 were reported for the first time from this species. The cholinesterase inhibitory test results showed that the highest potential inhibitors toward AChE and BChE were 5,7,4'-trimethoxyflavone (6) and 5,7-dimethoxyflavone (7), respectively, with the percentage inhibitory activity varying over 43-85%. The structure-activity relationship study led to the conclusion that compounds bearing 5,7-dimethoxy groups and a free substituent at C-3 had a significant inhibitory effect at a concentration of 0.1 mg/mL, but those bearing a 5-hydroxyl group reduced the inhibitory potency. On the other hand, flavones bearing a 3'- or 5'-methoxy group did not influence the inhibitory effect. Interestingly, 5,7-dimethoxyflavone (7) exhibited strong selectivity for BChE over AChE which may be of great interest to modify as a treatment agent for Alzheimer's disease.


X: -4.5049157 Y: 8.815351title: Evaluation of the Safety and Efficacy of Kaempferia parviflora Extract（SIRTMAX®）in Human -A Randomized Double-blind, Placebo-controlled Crossover Clinical Study- publish year: 2015 keyword: Kaemferia_parviflora content: Objective
Kaempferia parviflora is a plant belonging to the family Zingiberaceae. Its rhizome has been used in strength precision drugs and tonics and has been reported to exhibit prevention effect on metabolic diseases in mice. In this study, we examined the safety and efficacy of Kaempferia parviflora extract（SIRTMAX®）on obesity, glucose and lipid metabolism, and arterial stiffness in human.

Methods
We performed a randomized double-blind, placebo-controlled crossover clinical study. Twenty-seven healthy volunteers were given either a test product containing 100 mg of SIRTMAX® or a placebo by oral administration for 7 weeks.

Results
Body weight and fasting blood glucose declined significantly（P＝0.0033, and P＝0.04）in the SIRTMAX® group. For the subjects whose HbA1c values（NGSP）were more than 5.4％, improvement trends in the fasting blood glucose（127.9±17.8 mg/dL before and 120.7±14.9 mg/dL after ingestion）and the cardio-ankle vascular index（CAVI, 8.0±0.2 before and 7.8±0.2 after ingestion）were observed in the SIRTMAX® group. Furthermore, only a slight increase in the production of advanced glycation end products（AGEs）was observed in the SIRTMAX® group（26.0±3.4μg/mL before and 27.4±1.8μg/mL after ingestion, P＝0.64）, compared with a significant increase in the placebo group（22.4±2.6μg/mL before and 29.1±2.1μg/mL after ingestion, P＝0.02）. No abnormal values were observed during the test.

Conclusion
SIRTMAX® had the ameliorative effects on body weight and blood glucose level for all 27 subjects, and improved the vascular function for the subjects with mild hyperglycemia（HbA1c≧5.4％）. No severe adverse effects caused by SIRTMAX® were found during the test.


X: -3.511784 Y: 7.8624187title: FLAVONOIDS FROM THE RHIZOMES OF BLACK GINGER KAEMPFERIA PARVIFLORA WALL. EX BAKER, ZINGIBERACEAE publish year: 2023 keyword: Kaemferia_parviflora content: Kaempferia parviflora Wall. ex Baker, Zingiberaeceae has been used in traditional medicine in Vietnam for the treatment of inflammation, abdominal pain, indigestion, menstrual cramps, fatigue. From the n-hexane fraction of the rhizomes of Kaempferia parviflora, six compounds were isolated and determined as 5-hydroxy-3,7-dimethoxyflavone (1), 5,7-dimethoxy chrysin (2), 5-hydroxy-7-methoxyflavone (3), 5-hydroxy-3,4',7-trimethoxyflavone (4), 4',5,7-trimethoxyflavone (5), and 3,4',5,7-tetramethoxyflavone (6). The structures of 1-6 were elucidated by extensive spectroscopic methods (MS, 1D, and 2D NMR)


X: -1.9181641 Y: 8.68859title: RETRACTED: Immunotoxicity activity of sesquiterpenoids from black galingale ( Kaempferia parviflora Wall. Ex. Baker) against Aedes aegypti L. publish year: 2010 keyword: Kaemferia_parviflora content: The roots of black galingale (Kaempferia parviflora) were chloroform-extracted and the isolated two sesquiterpene and immunotoxicity effects were studied. The structures and stereochemistry of these compounds were established on the basis of analysis of spectra including UV, MS, (1)H-NMR, and (13)C-NMR as follows: 1 (4α-acetoxycadina-2,9-diene-1,8-dione), 2 (1α,3α,4β-trihydroxy-9-cadinen-8-one). Compound 2 had a significant toxic effect against early fourth-stage larvae of Aedes aegypti L. with an LC(50) value of 0.7 μM and an LC(90) value of 3.8 μM. The results could be useful in search for newer, safer, and more effective natural immunotoxicity agents against A. aegypti.


X: -4.140833 Y: 8.085026title: DAF-16 and SKN-1 mediate Anti-aging and Neuroprotective efficacies of “thai ginseng” Kaempferia parviflora Rhizome extract in Caenorhabditis elegans publish year: 2022 keyword: Kaemferia_parviflora content: BACKGROUND: The rhizomes of Kaempferia parviflora (KP), have been traditionally used for treating various ailments with 5,7-dimethoxyflavone (DMF) as a prominent compound. OBJECTIVE: To investigate the anti-aging and neuroprotective properties of KP and DMF in Caenorhabditis elegans. METHODS: C. elegans (wild-type (N2), transgenic and mutant strains) were treated with KP and DMF and were monitored for lifespan and neuroprotection through physiological assays, fluorescence microscopy and qPCR analysis. Molecular docking studies were employed to identify the interaction mode of DMF with DAF-16 and SKN-1. RESULTS: KP and DMF significantly increased the lifespan of N2 along with modulating pharyngeal pumping and lipofuscin accumulation. They also exhibited neuroprotection in Aβ transgenic strains by improving lifespan and delaying paralysis. Further, they reduced ROS accumulation significantly in worms exposed to UV-A, thereby exhibiting anti-photoaging potential. KP and DMF could activate SKN-1, DAF-16 which was evident from molecular docking and qPCR analysis. The DAF-2 and DAF-16 mutants did not exhibit any variations in lifespan upon treatment with KP and DMF suggesting the involvement of the DAF-16 mediated pathway in regulating the anti-aging and neuroprotective effects. CONCLUSION: Our findings suggest that KP with DMF as an active ingredient is a potential nutraceutical for aging and associated disorders.


X: -3.730151 Y: 7.790914title: Amino and Nitro Derivatives of 5,7-Dimethoxyflavone from Kaempferia parviflora and Cytotoxicity against KB Cell Line publish year: 2009 keyword: Kaemferia_parviflora content: Structural modification of 5,7-dimethoxyflavone isolated from Kaempferia parviflora furnished two nitro and seven amino derivatives. Among these, six new (3, 5-6, 8-10) and three known (2, 4, 7) flavonoid derivatives were synthesized. All compounds were evaluated for cytotoxicity against KB cell line using colorimetric method. Compounds 6 and 8 exhibited strong cytotoxicity with IC50 values of 6.80 and 5.84 μg/mL, respectively. © 2009 The Pharmaceutical Society of Korea and Springer Netherlands.


X: -3.970836 Y: 8.510697title: Kaempferia parviflora Extract Alleviated Rat Arthritis, Exerted Chondroprotective Properties In Vitro, and Reduced Expression of Genes Associated with Inflammatory Arthritis publish year: 2021 keyword: Kaemferia_parviflora content: Kaempferia parviflora Wall. ex Baker (KP) has been reported to attenuate cartilage destruction in rat model of osteoarthritis. Previously, we demonstrated that KP rhizome extract and its active components effectively suppressed mechanisms associated with RA in SW982 cells. Here, we further evaluated the anti-arthritis potential of KP extract by using multi-level models, including a complete Freund’s adjuvant-induced arthritis and a cartilage explant culture model, and to investigate the effects of KP extract and its major components on related gene expressions and underlying mechanisms within cells. In arthritis rats, the KP extract reduced arthritis indexes, with no significant changes in biological parameters. In the cartilage explant model, the KP extract exerted chondroprotective potential by suppressing sulfated glycosaminoglycans release while preserving high accumulation of proteoglycans. In human chondrocyte cell line, a mixture of the major components equal to their amounts in KP extract showed strong suppression the expression of genes-associated inflammatory joint disease similar to that of the extract. Additionally, KP extract significantly suppressed NF-κB and MAPK signaling pathways. The suppressing expression of necroptosis genes and promoted anti-apoptosis were also found. Collectively, these results provided supportive evidence of the anti-arthritis properties of KP extract, which are associated with its three major components.


X: -3.4697514 Y: 8.146686title: Soluble epoxide hydrolase inhibitory activity by rhizomes of Kaempferia parviflora Wall. ex Baker publish year: 2016 keyword: Kaemferia_parviflora content: In our search for natural soluble epoxide hydrolase (sEH) inhibitors from plants, we found that the methanolic extract of the rhizomes of Kaempferia parviflora Wall. ex Baker (Zingiberaceae) significantly inhibits sEH in vitro. In a phytochemical investigation of dichloromethane fraction of K. parviflora rhizomes, we isolated sixteen compounds (1–16), including flavonoid derivatives (1–12), anthraquinones (13 and 14), triterpene (15), and triterpene glycoside (16). The structures of the isolated compounds were established in an extensive 1D and 2D NMR, as well as MS analysis. The sEH inhibitory activities of all isolated compounds were evaluated. Among the isolated flavonoid derivatives, 4, 6, 8, 10, and 12 were identified as potent inhibitors of sEH, with IC50 values ranging from 0.9 ± 0.1 to 4.5 ± 0.1 μM. In addition, a kinetic analysis of the flavonoid derivatives (1–12) revealed that the inhibitory activity of flavonoid derivatives 1–4 and 6–12 is mixed with K
i values ranging from 0.1 ± 0.0 to 14.3 ± 0.3 μM, whereas compound 8 was a non-competitive with K
i = 0.3 ± 0.0 μM. These findings suggest that flavonoid derivatives from K. parviflora rhizomes are potential novel sEH inhibitors.


X: -4.7057505 Y: 8.346741title: Effects of Kaempferia parviflora Wall. Ex. Baker on electrophysiology of the swine hearts publish year: 2013 keyword: Kaemferia_parviflora content: Background & objectives:
Pre-clinical studies in swine have demonstrated that a supratherapeutic concentration of sildenafil citrate decreased defibrillation efficacy and facilitated cardiac arrhythmia. We therefore, decided to investigate the effects of Kaempferia parviflora (KP) extract on these parameters in the swine heart. The underlying assumption was that in the heart, KP might be producing effects similar to sildanafil citrate as KP has long been used in southeast Asian traditional medicine to correct erectile dysfunction.

Methods:
The study was conducted as the defibrillation study, and ventricular fibrillation (VF) induction study. In both studies, the defibrillation threshold (DFT), the upper limit of vulnerability (ULV) and VF threshold were determined before and after KP extract administration.

Results:
In both studies KP extract at high concentrations (100 and 50 mg/kg) significantly increased the DFT and ULV, without altering the VF threshold. At these concentrations, systolic and diastolic blood pressures were also attenuated.

Interpretation & conclusions:
High concentrations of KP extract attenuated defibrillation efficacy and increased cardiac vulnerability to arrhythmia in a normal swine heart. When used in appropriate concentrations, its blood pressure lowering effect may be useful in hypertensive states. Further studies need to be done to elucidate its mechanism of action.


X: -3.907863 Y: 8.278014title: Ethyl acetate extract of Kaempferia parviflora inhibits Helicobacter pylori-associated mammalian cell inflammation by regulating proinflammatory cytokine expression and leukocyte chemotaxis publish year: 2020 keyword: Kaemferia_parviflora content: Background:
Kaempferia parviflora (KP) has been used in traditional Thai medicine to cure gastrointestinal disorders since ancient times. Helicobacter pylori is an initiating factor in gastric pathogenesis via activation of massive inflammation, the cumulative effect of which leads to gastric disease progression, including gastric carcinogenesis. Accordingly, the effect of a crude ethyl acetate extract of KP (CEAE-KP) on proinflammatory cytokine production and cell chemotaxis was the focus of this study.

Methods:
The cytotoxicity of CEAE-KP (8-128 μg/ml) on AGS (gastric adenocarcinoma) cells was determined at 6, 12 and 24 h using an MTT assay. The effect of CEAE-KP on H. pylori-induced interleukin (IL)-8 production by AGS cells was evaluated by ELISA and RT-PCR. The effect of CEAE-KP on monocyte and neutrophil chemotaxis to H. pylori soluble protein (sHP) and IL-8, respectively, was determined using a Boyden chamber assay with THP-1 or HL-60 cells.

Results:
CEAE-KP reduced AGS cell viability in a concentration- and time-dependent manner, but at 8-16 μg/ml, it was not cytotoxic after 6-24 h of exposure. Coculture of AGS cells with CEAE-KP at a noncytotoxic concentration of 16 μg/ml and H. pylori reduced IL-8 secretion by ~ 60% at 12 h, which was consistent with the decreased level of mRNA expression, and inhibited neutrophil chemotaxis to IL-8. sHP (100 ng/ml) induced marked monocyte chemoattraction, and this was decreased by ~ 60% by CEAE-KP.

Conclusion:
CEAE-KP might serve as a potent alternative medicine to ameliorate the inflammation mediated by H. pylori infection.


X: -0.9638127 Y: 3.8300598title: A Review on Cimetidine and its Toxicological Effects on Male Reproductive System Ikuomola, Emmanuel Orire publish year: 2023 keyword: Kaemferia_parviflora content: Cimetidine is recommended for the treatment of chronic peptic ulceration, haemorrhage from erosive gastritis, and the control of gastric hypersecretion and peptic ulceration in the Zollinger-Ellison syndrome, cimetidine1 is a specific competitive histamine H2-receptor antagonist that effectively inhibits gastric acid secretion. Therefore, this review further highlights the mechanisms of action, adverse effect profile, and other significant elements important to the interprofessional team members in patient management utilizing cimetidine.


X: -5.157162 Y: 8.1875305title: Effects of Black ginger (Kaempferia parviflora) on the testicular function in streptozotocin-induced diabetic male rats publish year: 2016 keyword: Kaemferia_parviflora content: Abstract The present study aimed to investigate the efficacy of Black ginger (Kaempferia parviflora; KP) on testicular function in streptozotocin (STZ)-induced diabetes rats (DM). Six-week-old male Wistar rats were used in this experiment. All rats were randomly divided into six group; group 1: Normal group, group 2: DM (control), group 3: DM rats received gibencamide 5 mg/kg, group 4-6: DM rats received KP 140, 280 and 420 mg/kg, respectively. DM was induced by intraperitoneal injection of STZ (60 mg/kg). All animals were treated for 6 weeks. Blood glucose, epididymal sperm parameter, testicular microstructure and testosterone level were evaluated. The result showed that KP treatment has no effect on blood glucose in DM rats. KP treatment showed significantly increased sperm density, serum testosterone and ameliorates testicular structure in DM rats (p<0.05). The present study indicates that the aphrodisiac properties of KP could improve of sperm density, testosterone level and testicular function in STZ-induced diabetes rats.


X: -3.6235175 Y: 7.6730776title: New flav-3-en-3-ol glycosides, kaempferiaosides C and D, and acetophenone glycosides, kaempferiaosides E and F, from the rhizomes of Kaempferia parviflora publish year: 2011 keyword: Kaemferia_parviflora content: Two new flav-3-en-3-ol glycosides, kaempferiaosides C (3) and D(4), and two new acetophenone glycosides, kaempferiaosides E (5) and F (6), were isolated from the Thai natural medicine Krachai Dum, the rhizomes of Kaempferia parviflora Wall. ex Baker. Their structures were established mainly on the basis of 1D and 2D NMR spectral data.


X: -1.799826 Y: 8.904176title: Anti-allergic activity of some selected plants in the Zingiberaceae family publish year: 2007 keyword: Kaemferia_parviflora content: Ethanolic and water extracts, together with volatile oils from the rhizomes of six selected Zingiberaceous plants, including Curcuma mangga, Kaempferia galanga, Kaempferia parviflora, Zingiber cassumunar, Zingiber officinale and Zingiber zerumbet were investigated for their anti-allergic activities using a RBL-2H3 cell line. The ethanolic (EtOH) extract of Kaempferia parviflora exhibited the most potent anti-allergic effect against antigen-induced beta-hexosaminidase release as a marker of degranulation in RBL-2H3 cells, with an IC(50) value of 10.9 microg/ml, followed by Zingiber cassumunar (EtOH, IC(50)=12.9 microg/ml) and Curcuma mangga (water, IC(50)=36.1 microg/ml). The volatile oils of these six plants were apparently inactive (IC(50)>100 microg/ml). The crude extracts were also tested on beta-hexosaminidase activity to clarify whether their effects were due to the inhibition of enzyme activity or of degranulation. As a result, the plant extracts were inactive against the enzyme activity of beta-hexosaminidase. These findings support the use in Thai traditional medicine of these selected Zingiberaceous plants, especially Kaempferia parviflora and Zingiber cassumunar, for treatment of allergy and allergic-related diseases.


X: -5.250856 Y: 7.9623437title: Sperm density and ultrastructure of Sertoli cells in male rats treated with Kaempferia parviflora Wall. Ex Baker extract publish year: 2007 keyword: Kaemferia_parviflora content: The purpose of this study was to determine the effects of Kaempferia parviflora Wall. Ex Baker on the sperm density and ultrastructure of Sertoli cells in male albino rats. Three treated groups were orally administered with the rhizome extract of K. parviflora at various doses (60, 120, and 240 mg/kg bw/day) for 60 days. A control group received distilled water of 1 ml/day. At the end of the treatment period, the epididymal sperm density was determined and small pieces of testis were processed for ultrastructure study of Sertoli cells under the transmission electron microscope (TEM). The results showed that male rats treated with K. parviflora extract at the dose of 60 mg/kg bw/day had significantly higher sperm density than that of the control group. Electron micrographs demonstrated that all K. parviflora treated groups had prominent granules in the Sertoli cells, which secreted their substances to spermatogonia in the basal compartment of the seminiferous epithelium. Male rats treated with K. parviflora extract at the dose of 60 mg/kg bw/day also had highly condensed lysosome in the basal part of Sertoli cells. It was concluded that the ethanolic extract of K. parviflora involves sperm density and ultrastructure of Sertoli cells in male rats.


X: -1.1961769 Y: 7.3027577title: Emotion and Wellness Profiles of Herbal Drinks Measured Using Different Questionnaire Designs publish year: 2022 keyword: Kaemferia_parviflora content: The emotion and wellness profiles of herbal drinks were assessed using six different questionnaire designs. The questionnaire designs were constructed from two formats of questionnaire items, including words and sentences, and three types of measuring scales, including a rating scale (5-point intensity; 1 = ‘not at all’, 5 = ‘extremely’), a checklist scale (check-all-that-apply, CATA), and a combination of CATA and rating scales (rate-all-that-apply, RATA; 5-point intensity; 1 = ‘slightly’, 5 = ‘extremely’). The 39 emotional terms of the EsSense Profile® and the 45 wellness terms of the WellSense ProfileTM were translated into Thai, then screened for relevance to herbal drinks. The seven positive emotional terms (active, energetic, good, happy, polite, satisfied, and warm), three negative emotional terms (bored, disgusted, and worried), and five wellness terms (comforted, healthy, invigorated, relaxed, and refreshed) were selected and included in the questionnaire. A central location test was performed to determine the emotion and wellness profiles of five herbal drinks: roselle (Hibiscus sabdariffa) drink, chrysanthemum (Chrysanthemum morifolium Ramat) drink, ginger (Zingiber officinale) drink, Jubliang (a mixture of eight herbs) drink, and Krachai Dam (Kaempferia parviflora) drink. For herbal drinks, measuring emotion and wellness with a questionnaire using full sentences did not show increased benefit over questionnaires using words alone. All three measuring methods—a rating scale, CATA, and RATA—produced similar emotion and wellness profiles. However, each method has different advantages and limitations, which researchers should carefully consider.


X: -5.2333956 Y: 8.009007title: Sperm density and ultrastructure of Sertoli cells in male rats treated with Kaempferia parviflora Wall. Ex Baker extract publish year: 2007 keyword: Kaemferia_parviflora content: The purpose of this study was to determine the effects of Kaempferia parviflora Wall. Ex Baker on the sperm density and ultrastructure of Sertoli cells in male albino rats. Three treated groups were orally administered with the rhizome extract of K. parviflora at various doses (60, 120, and 240 mg/kg bw/day) for 60 days. A control group received distilled water of 1 ml/day. At the end of the treatment period, the epididymal sperm density was determined and small pieces of testis were processed for ultrastructure study of Sertoli cells under the transmission electron microscope (TEM). The results showed that male rats treated with K. parviflora extract at the dose of 60 mg/kg bw/day had significantly higher sperm density than that of the control group. Electron micrographs demonstrated that all K. parviflora treated groups had prominent granules in the Sertoli cells, which secreted their substances to spermatogonia in the basal compartment of the seminiferous epithelium. Male rats treated with K. parviflora extract at the dose of 60 mg/kg bw/day also had highly condensed lysosome in the basal part of Sertoli cells. It was concluded that the ethanolic extract of K. parviflora involves sperm density and ultrastructure of Sertoli cells in male rats.


X: -1.1914979 Y: 7.3162627title: Emotion and Wellness Profiles of Herbal Drinks Measured Using Different Questionnaire Designs publish year: 2022 keyword: Kaemferia_parviflora content: The emotion and wellness profiles of herbal drinks were assessed using six different questionnaire designs. The questionnaire designs were constructed from two formats of questionnaire items, including words and sentences, and three types of measuring scales, including a rating scale (5-point intensity; 1 = ‘not at all’, 5 = ‘extremely’), a checklist scale (check-all-that-apply, CATA), and a combination of CATA and rating scales (rate-all-that-apply, RATA; 5-point intensity; 1 = ‘slightly’, 5 = ‘extremely’). The 39 emotional terms of the EsSense Profile® and the 45 wellness terms of the WellSense ProfileTM were translated into Thai, then screened for relevance to herbal drinks. The seven positive emotional terms (active, energetic, good, happy, polite, satisfied, and warm), three negative emotional terms (bored, disgusted, and worried), and five wellness terms (comforted, healthy, invigorated, relaxed, and refreshed) were selected and included in the questionnaire. A central location test was performed to determine the emotion and wellness profiles of five herbal drinks: roselle (Hibiscus sabdariffa) drink, chrysanthemum (Chrysanthemum morifolium Ramat) drink, ginger (Zingiber officinale) drink, Jubliang (a mixture of eight herbs) drink, and Krachai Dam (Kaempferia parviflora) drink. For herbal drinks, measuring emotion and wellness with a questionnaire using full sentences did not show increased benefit over questionnaires using words alone. All three measuring methods—a rating scale, CATA, and RATA—produced similar emotion and wellness profiles. However, each method has different advantages and limitations, which researchers should carefully consider.


X: -4.9360657 Y: 8.523845title: Supplementation of Kaempferia parviflora Extract Enhances Physical Fitness and Modulates Parameters of Heart Rate Variability in Adolescent Student-Athletes: A Randomized, Double-Blind, Placebo-Controlled Clinical Study publish year: 2020 keyword: Kaemferia_parviflora content: This randomized double-blind controlled study aimed to investigate the effects of a standardized Kaempferia parviflora (KP) extract on the physical fitness and heart rate variability (HRV) parameters in adolescent sport school students. 194 male students were recruited and randomized into two groups (n = 97), matched by age and sports. The KP-treated group received KP extract capsules at a dose of 360 mg/day and the control group received placebo capsules, continuously for 12 weeks. Physical fitness performance and HRV parameters were monitored with blood biochemical analysis for product safety. KP extract significantly increased the right-hand grip strength, the back-leg strength and maximal oxygen consumption (VO2 max) and decreased the time used for 50-meter sprint test without changing the sit-and-reach test and the 40 yard technical test. For HRV parameters, KP extract significantly increased standard deviation of normal to normal intervals (SDNN), square root of the mean of square of successive normal to normal interval differences (RMSSD) and high frequency (HF) norm, without changing low frequency (LF) norm and LF/HF ratio. The increase in stress resistance and decrease in stress index were found in the KP-treated group, without changing the autonomic nervous system (ANS) activity and balance. Blood biochemical analysis showed normal values of all participants. This data indicates the safety and positive effects of KP on muscle strength, endurance and speed, but not on the flexibility and agility. The modulatory effects of KP extract on HRV parameters suggest its anti-stress effects and would encourage the application in a sport training and exercise.


X: -3.966675 Y: 7.5769877title: Kaempferia parviflora Extract Exhibits Anti-cancer Activity against HeLa Cervical Cancer Cells publish year: 2017 keyword: Kaemferia_parviflora content: Kaempferia parviflora (KP) has been traditionally used as a folk remedy to treat several diseases including cancer, and several studies have reported cytotoxic activities of extracts of KP against a number of different cancer cell lines. However, many aspects of the molecular mechanism of action of KP remain unclear. In particular, the ability of KP to regulate cancer cell growth and survival signaling is still largely unexplored. The current study aimed to investigate the effects of KP on cell viability, cell migration, cell invasion, cell apoptosis, and on signaling pathways related to growth and survival of cervical cancer cells, HeLa. We discovered that KP reduced HeLa cell viability in a concentration-dependent manner. The potent cytotoxicity of KP against HeLa cells was associated with a dose-dependent induction of apoptotic cell death as determined by flow cytometry and observation of nuclear fragmentation. Moreover, KP-induced cell apoptosis was likely to be mediated through the intrinsic apoptosis pathway since caspase 9 and caspase 7, but not BID, were shown to be activated after KP exposure. Based on the observation that KP induced apoptosis in HeLa cell, we further investigated the effects of KP at non-cytotoxic concentrations on suppressing signal transduction pathways relevant to cell growth and survival. We found that KP suppressed the MAPK and PI3K/AKT signaling pathways in cells activated with EGF, as observed by a significant decrease in phosphorylation of ERK1/2, Elk1, PI3K, and AKT. The data suggest that KP interferes with the growth and survival of HeLa cells. Consistent with the inhibitory effect on EGF-stimulated signaling, KP potently suppressed the migration of HeLa cells. Concomitantly, KP was demonstrated to markedly inhibit HeLa cell invasion. The ability of KP in suppressing the migration and invasion of HeLa cells was associated with the suppression of matrix metalloproteinase-2 production. These data strongly suggest that KP may slow tumor progression and metastasis in patients with cervical cancer. Taken together, the present report provides accumulated evidence revealing the potent anti-cancer activities of Kaempferia parviflora against cervical cancer HeLa cells, and suggests its potential use as an alternative way for cervical cancer prevention and therapy.


X: -4.0367627 Y: 8.624647title: Kaempferia parviflora ethanolic extract promoted nitric oxide production in human umbilical vein endothelial cells publish year: 2007 keyword: Kaemferia_parviflora content: The rhizomes of Kaempferia parviflora (KP) (Zingiberaceae) have been used in Thai traditional medicine for health promotion and for the treatment of digestive disorders and gastric ulcer. This study investigated effect of KP on endothelial function. Studies in human umbilical vein endothelial cells (HUVEC) showed that KP dose-dependently increased nitrite concentrations in culture media after 48 h incubation. eNOS mRNA and protein expression were also enhanced. The induction of eNOS mRNA was detected at 4 h and plateau at 48 h while iNOS expression was not observed. These data demonstrate that KP has a great potential for a supplemental use in vascular endothelial health promotion.


X: -4.3725677 Y: 8.2616825title: Research progress and discussion on traditional Chinese medicine properties of Kaempferia parviflora publish year: 2021 keyword: Kaemferia_parviflora content: Kaempferiae Parviflorae Rhizoma is the dried rhizome of Kaempferia parviflora in Zingiberaceae. It is originated and widely distributed in Thailand and other tropical and subtropical regions, where it has been used as food and medicine for thousands of years. K. parviflora is also planted in Yunnan and other places of China, but its traditional Chinese medicine properties are not clear, which greatly limits its compatibility with traditional Chinese medicines. In this article, the English and Chinese literatures of K. parviflora were searched from Web of Science, PubMed, Scopus, CNKI, Wanfang, and VIP databases for research and analysis. The medicinal properties of K. parviflora were preliminarily discussed based on the theory of traditional Chinese medicine under the guidance of clinical application and research literatures. The traditional Chinese medicine properties of K. parviflora were inferred as follows: flat, acrid, sweet. The channel tropisms of K. parviflora included kidney, spleen, stomach, and liver. The function of K. parviflora included tonifying kidney to strengthen essence, tonifying Qi and invigorating spleen, soothing liver and relieving depression. K. parviflora was clinically applied for the diseases such as syndrome of kidney essence deficiency, sex apathy, deficiency of spleen Qi, lassitude and asthenia, a weary spirit, obesity, diabetes, liver Qi stagnation, depression, and restless. The equivalent of dry power is 1.5 g·d~(-1) and the equivalent of decoction is 1.5-6 g·d~(-1). The determination of traditional Chinese medicine properties of K. parviflora has indeed laid a theoretical foundation for its application in the field of traditional Chinese medicine and enriched traditional Chinese medicine resources.


X: -3.8286273 Y: 8.053165title: LC-MS for Determination of three Methoxyflavones from Kaempferia Parviflora in Rat Plasma and Application to Pharmacokinetic Study publish year: 2015 keyword: Kaemferia_parviflora content: Background: Methoxyflavones are isolated from Kaempferia parviflora, a Thai herb used in traditional medicine. The method of quantification of low level of methoxyflavones in biological samples needs to be optimized. Objectives: To develop and validate a sensitive liquid chromatography-tandem mass spectrometry (LCMS) for the determination of methoxyflavones in rat plasma and apply for pharmacokinetic study. Method: Chromatographic separation was achieved on a reverse phase C18 column, using acetonitrile and 0.5% formic acid in water in a ratio of 10:90 v/v to 50:50 v/v as the mobile phase, and a flow-rate of 0.2 ml/min at 25°C. LC–MS detection was performed under positive ionization with selective ion monitoring using target ions. Results: The calibration curve showed good linearity in the concentration range of 10–3000 ng/ml. The limits of detection (LOD) and quantification (LOQ) were 0.43-0.78 ng/ml and 0.93-2.35 ng/ml, respectively. The intra-day and the inter-day variances were less than 6.41% and 12.96%. The mean recovery of methoxyflavones was 73.73- 99.76%. The assay was successfully applied to a pharmacokinetics study in rats that used a topical application of 15% K. parviflora extract in IPM-based vehicle. After topical administration, the plasma concentration of methoxyflavones continuously increased up to 48 h, indicating prolonged absorption of methoxyflavones into systemic circulation, with the maximum concentration (Cmax) of methoxyflavones being 401.94 ng/ml at 1 h. Conclusion: The current method has been successfully applied to the determination of methoxyflavones in rat plasma and was used to study its pharmacokinetics under topical administration.


X: 1.2061121 Y: 7.9311976title: Morphological description for Kunyit Hitam (Kaempferia parviflora) and breaking bud dormancy with BAP and Ethephon treatment publish year: 2013 keyword: Kaemferia_parviflora content: There are an estimated number of 300 species of gingers distributed in Malaysia. Among these, Kaempferia commonly known as peacock gingers are the less notable members of the Zingeberaceae family with a number of 60 species distributed from India to Southeast Asia. Kaempferia parviflora or Kunyit Hitam is widely grown in Thailand for its medicinal value. Locally it is renowned for its mystical properties. There is great potential to develop K.parviflora into a pharmaceutical product and as a shade tolerant ornamental. Noted for its showy foliage with red margins, K.parviflora is a low growing, understory plant which has short fleshy rhizomes dark purple in colour, tuberous roots, leaves erect or apprised to the soil and inconspicuous flowers usually white with violet labellum. Despite the tremendous demand for the rhizomes of K. parviflora, there is a scarcity of its planting materials in Malaysia. K. parviflora has a dormancy period for five to six months typically from November to early May. Breaking bud dormancy of rhizomes in K. parviflora is very important as to overcome the problem of long dormancy period and to provide planting material throughout the year. This study reports on the study of plant morphology and the effects of BAP (6-Benzylaminopurine) and ethephon in breaking bud dormancy of K.parviflora. Results show that BAP at 150 mg/l gave higher number of visible bud appearance as compared to control and other concentrations. No significant differences were observed in ethephon treatment. However, Ethephon at 700 mg/l gave a higher number of buds compared to other treatments. In conclusion BAP was superior to Ethephon in promoting breaking of bud dormancy in K. parviflora.


X: -3.9078097 Y: 9.887834title: Phyllanthus tenellus Roxb. and Kaempferia parviflora Wall. ex Baker compounds as inhibitors of SARS-CoV-2 main protease and RNA-dependent RNA polymerase: A molecular docking study publish year: 2022 keyword: Kaemferia_parviflora content: Context: The outbreak of a novel coronavirus, SARS-CoV-2 has caused an unprecedented COVID-19 pandemic. To put an end to this pandemic, effective antivirals should be identified or developed for COVID-19 treatment. However, specific and effective antivirals or inhibitors against SARS-CoV-2 are still lacking.

Aims: To evaluate bioactive compounds from Phyllanthus tenellus and Kaempferia parviflora as inhibitorsagainst two essential SARS-CoV-2 proteins, main protease (Mpro) and RNA-dependent RNA polymerase (RdRp), through molecular docking studies and to predict the drug-likeness properties of the compounds.

Methods: The inhibition potential and interaction of P. tenellus and K. parviflora compounds against Mpro and RdRp were assessed through molecular docking. The drug-likeness properties of the compounds were predicted using SwissADME and AdmetSAR tools.

Results: Rutin and ellagic acid glucoside from P. tenellus and 4-hydroxy-6-methoxyflavone and 5-hydroxy-3,7,4’-trimethoxyflavone from K. parviflora exhibited the highest binding conformations to Mpro by interacting with its substrate binding site that was predicted to halt the Mpro activity. As for RdRp, ellagitannin and rutin from P. tenellus and peonidin and 5,3’-dihydroxy-3,7,4’-trimethoxyflavone from K. parviflora were the best-docked compounds that bound to the RdRp catalytic domain (Asp760 and Asp761) and NTP-entry channel that were anticipated to stop RNA polymerization. However, in the context of drug developability, 4-hydroxy-6-methoxyflavone, 5-hydroxy-3,7,4’-trimethoxyflavone, peonidin and 5,3’-dihydroxy-3,7,4’-trimethoxyflavone from K. parviflora were highly potential to be oral active drugs compared to rutin, ellagic acid glucoside and ellagitannin from P. tenellus.

Conclusions: P. tenellus and K. parviflora compounds, particularly the aforementioned compounds, were suggested as potential inhibitors of SARS-CoV-2 Mpro and RdRp.


X: -4.3371615 Y: 8.833566title: Evaluating the Effect of Volten VR4® Kaempferia parviflora Extracts on Blood Glucose Levels in Human Type-2 Diabetes Mellitus and Healthy Individual: A Case-Control Study publish year: 2021 keyword: Kaemferia_parviflora content: Background: Volten VR4® capsules contain extract of Kaempferia parviflora (KP), which has been claimed to reduce blood glucose in patients with diabetes.
Objective: To evaluate the efficacy of Volten VR4® on healthy individuals and Type-2 Diabetes Mellitus volunteers.
Materials and Methods: The extracts of 400 mg capsules of KP were consumed for five days. The fasting and blood glucose levels of 2-hour postprandial were measured at baseline and day 5. A group of 15 healthy young adults between the age of 20- and 30 years old were the control group of the present study, while 12 volunteers aged 35 to 75 years old diagnosed with Type-2 Diabetes Mellitus constituted the experimental group. Data were validated through the Willcoxon and Friedman test statistics and error distribution.
Results: It had been shown that the specificity of KP reduced blood glucose levels and has associated with the flavonoids and polymethoxyflavones components. The results showed that consuming VR4® capsules significantly reduced blood glucose, either at the state of fasting or postprandially in diabetic individual.
Conclusion: Volten VR4® Kaempferia parviflora extract is safe to be consumed at 400 mg at one time. The study also has shown that the participants are free from adverse reactions and hypoglycaemia.


X: -2.9904995 Y: 8.116998title: Total Phenolic Content and Antioxidant Activity of Leaves and Rhizomes of some Ginger species in Peninsular Malaysia publish year: 2007 keyword: Kaemferia_parviflora content: The total phenolic content (TPC) and antioxidant activity (AOA) of leaves and rhizomes of five
wild and six cultivated ginger species belonging to seven genera were compared. Altitudinal
variation in leaf TPC and AOA of four Etlingera species was also studied. TPC was measured
using the Folin-Ciocalteu method. AOA was measured using the 1,1-diphenyl-2-picrylhydrazyl
(DPPH) radical scavenging assay and expressed as ascorbic acid equivalent antioxidant capacity
(AEAC). Of the 11 wild and cultivated species screened, leaves of Etlingera had the highest TPC
and AEAC, which were seven to eight times higher than those of rhizomes. Eight species had
significantly higher leaf TPC and/or AEAC than rhizomes. Leaves of highland populations of
Etlingera species had higher values than those of lowland counterparts.


X: -0.24584995 Y: 7.624336title: Morphological and Molecular datasets for Kaempferia species publish year: 2018 keyword: Kaemferia_parviflora content: This study compared morphological and molecular data for identification of Kaempferia species. Each species was deposited in Institute of Bioscience (IBS), Universiti Putra Malaysia (UPM) as voucher specimens and ITS sequences of each species deposited in NCBI (https://www.ncbi.nlm.nih.gov/) as GenBank accessions. DNA was extracted using a modified CTAB method and PCR amplification was completed using Internal Transcribed Spacer (ITS4 and ITS5) markers. PCR amplification of products were viewed under gel electrophoresis. Sequencing was performed and sequence characteristics of ITS rDNA in Kaempferia is shown. Qualitative and qualitative scoring of morphological characters and measuring techniques for Kaempferia species are included. In addition, a brief review of molecular markers used in phylogenetic studies of Zingiberaceae is included in this dataset.


X: -3.4848027 Y: 8.366503title: Development and quality assessment of Lactobacillus paracasei HII01 mediated fermented Kaempferia parviflora wall. Ex. Baker juice publish year: 2019 keyword: Kaemferia_parviflora content: Objective: To develop and evaluate Lactobacillus paracasei HII01 mediated fermented Kaempferia parviflora wall. Ex. Baker rhizome juice. Methods: The changes in pH, acidity, ethanol, and reducing sugar content were measured by pH meter, titration, gas chromatography, and Dinitrosalicylic acid method, respectively. The total polyphenol content was measured by colorimetric method. ABTS (2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid)), and FRAP (ferric reducing antioxidant power) assays were performed to calculate the total antioxidant capacity, and reducing power, respectively. Results: The pH and acidity of fermented K. parviflora juice (FKJ) were gradually reduced, and increased, respectively. The high total phenolic content was observed in F1, and F3 after 15 days of fermentation (1.14, and 1.02 mg GAE per ml sample, respectively). The total antioxidant capacity of F1 and F3 were 1.07, and 1. 2 mg TEAC per ml sample, respectively, after 20 days of fermentation. The sugar content was reduced during fermentation. The ethanol content of samples was ranging from 0.05-2.26 % (V/V). The microbial load was reduced during fermentation, and no pathogenic microbes were detected. The results suggested that about-20 days of fermentation period is sufficient to produce high-quality FKJ. Conclusion: The first L. paracasei mediated fermented K. parviflora juice was developed with a high content of phenolic compounds, and antioxidants. FKJ was microbiologically safe, and it contains an acceptable level of ethanol and acidity. FKJ can be a potent functional food supplement if further characterization and pharmacological evaluation are made.


X: -3.5106761 Y: 8.069055title: Synergistic Effects of Some Methoxyflavones Extracted from Rhizome of Kaempferia parviflora Combined with Gentamicin against Carbapenem-Resistant Strains of Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii publish year: 2022 keyword: Kaemferia_parviflora content: The present study aimed to investigate the antibacterial activity of ethanolic Kaempferia parviflora extracts and the combined effects of the plant’s specific compounds with gentamicin against clinical strains of carbapenem-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. The minimal inhibitory concentrations (MIC) of gentamicin and Kaempferia parviflora extracts against the tested bacterial strains were determined by using broth microdilution. The combined effects of Kaempferia parviflora extract and gentamicin were investigated by using a checkerboard assay and expressed as a fractional inhibitory concentration index (FICI). Crude ethanolic extract of Kaempferia parviflora showed the lowest median values of MIC towards the tested isolates (n = 10) of these tested bacteria at doses of 64 µg/mL, compared to those of other Kaempferia extracts. Among the isolated compounds, only three compounds, namely 3,5,7-trimethoxyflavone, 3,5,7,3′4′-pentamethoxyflavone, and 5,7,4′-trimethoxyflavone, were identified by NMR structural analysis. According to their FICIs, the synergistic effects of gentamicin combined with 3,5,7,3′4′-pentamethoxyflavone were approximately 90%, 90%, and 80% of tested carbapenem-resistant Klebsiella pneumoniae (CRKP), Pseudomonas aeruginosa (CRPA), and Acinetobacter baumannii (CRAB), respectively. The present study concluded that 3,5,7,3′4′-pentamethoxyflavone extracted from Kaempferia parviflora potentiated the antibacterial action of gentamicin to combat bacterial resistance against the tested bacteria.


X: -5.076991 Y: 8.119149title: An open label study to evaluate the effect of Kaempferia parviflora in support of erectile function and male sexual health among overall healthy males 50–70 publish year: 2018 keyword: Kaemferia_parviflora content: Background
Kaempferia parviflora (KP ) is an herbaceous plant from the family of Zingiberaceae. The KP rhizomes contain numerous flavonoids, two of which, 5,7‐dimethoxyflavone (DMF) and 5,7,4‐trrimethoxyflavone (TMF), are major constituents. Studies on isolated rat aortic rings revealed DMF causes endothelium‐dependent relaxation and vasodilation, effects partly mediated by the NO‐cGMP and cyclooxygenase pathways. In vitro studies noted an increased mRNA and protein expression of endothelial nitric oxide synthase (eNOS), which is present in the endothelium of the penile vasculature and sinusoidal endothelium within the corpora carvernosa, and concluded this may result in an improvement in endothelial function. Experiments on rats suggested this plant extract may enhance copulatory behavior partly via the induction of hypothalamic dopaminergic D1 receptor expression. Additionally, a study on healthy elderly male volunteers revealed KP may increase blood flow to enhance penile circumference, length, and rigidity.

Objectives
The primary objective of this study was to investigate the effectiveness of KP on erectile function among overall healthy males aged 50–70 utilizing the International Index of Erectile Function (IIEF) questionnaire. Secondary objectives included assessment of mean changes in blood levels of free testosterone, total testosterone, estradiol, DHEA‐S, PSA, total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides, as well as mean response to the Global Assessment Question. Also assessed were changes in health‐related quality of life scores and mean changes in body weight.

Methods
Each subject received a formulation containing KP for 30 consecutive days. Assessments, questionnaires, and laboratory testing were completed on Day 30. Baseline and Day 30 values were compared for all subjects who completed the clinical trial.

Results
A total of 13 subjects completed the trial. The Day 30 analysis showed a statistically significant mean increase in scores attained on the IIEF questionnaire related to total score, erectile function domain, intercourse satisfaction domain, and orgasmic function domain. For the Global Assessment Question, 61.5% of subjects noted the product improved their erections. There were no statistically significant changes observed for the other parameters measured.

Conclusion
The treatment demonstrated improvement in certain study parameters related to erectile function and male sexual health. Results point towards the need for additional controlled studies with larger sample sizes. The study treatment was generally well tolerated.
Support or Funding Information
Supplement Formulators, Inc.


X: -3.3002522 Y: 8.071639title: Recent Advances in Kaempferia Phytochemistry and Biological Activity: A Comprehensive Review publish year: 2019 keyword: Kaemferia_parviflora content: Abstract: Background: Plants belonging to the genus Kaempferia (family: Zingiberaceae) are
distributed in Asia, especially in the southeast region, and Thailand. They have been widely used
in traditional medicines to cure metabolic disorders, inflammation, urinary tract infections, fevers,
coughs, hypertension, erectile dysfunction, abdominal and gastrointestinal ailments, asthma,
wounds, rheumatism, epilepsy, and skin diseases. Objective: Herein, we reported a comprehensive
review, including the traditional applications, biological and pharmacological advances, and
phytochemical constituents of Kaempheria species from 1972 up to early 2019. Materials and
methods: All the information and reported studies concerning Kaempheria plants were summarized
from library and digital databases (e.g., Google Scholar, Sci-finder, PubMed, Springer, Elsevier,
MDPI, Web of Science, etc.). The correlation between the Kaempheria species was evaluated via
principal component analysis (PCA) and agglomerative hierarchical clustering (AHC), based on the
main chemical classes of compounds. Results: Approximately 141 chemical constituents have been
isolated and reported from Kaempferia species, such as isopimarane, abietane, labdane and clerodane
diterpenoids, flavonoids, phenolic acids, phenyl-heptanoids, curcuminoids, tetrahydropyranophenolic,
and steroids. A probable biosynthesis pathway for the isopimaradiene skeleton is illustrated. In addition, 15 main documented components of volatile oils of Kaempheria were
summarized. Biological activities including anticancer, anti-inflammatory, antimicrobial,
anticholinesterase, antioxidant, anti-obesity-induced dermatopathy, wound healing,
neuroprotective, anti-allergenic, and anti-nociceptive were demonstrated. Conclusions: Up to date,
significant advances in phytochemical and pharmacological studies of different Kaempheria species
have been witnessed. So, the traditional uses of these plants have been clarified via modern in vitro
and in vivo biological studies. In addition, these traditional uses and reported biological results
could be correlated via the chemical characterization of these plants. All these data will support the
biologists in the elucidation of the biological mechanisms of these plants.


X: -0.17327881 Y: 7.507507title: Phylogenetic relationships of Kaempferia species based on AFLP marker publish year: 2016 keyword: Kaemferia_parviflora content: Kaempferia species are aromatic perennial herbs belonging to the Zingiberaceae, that have been used as folk medicine in Thailand. Identifi cation and classifi cation of Kaempferia is diffi cult because of the synonymy and morphological similarity between species. In this study, Amplifi ed Fragment Length Polymorphism (AFLP) technique was employed for determination of the phylogenetic relationships among nine Kaempferia species. Thirty primer combinations were screened and four primer combinations produced a total of distinct and reproducible 253 bands ranging from 56 to 70 bands with an average 63.25 bands per primer combination. Genetic distance based on AFLP bands amplifi ed using four primer combinations was calculated and the similarity index (SI) ranged from 0.0277–0.9375. A dendrogram was constructed using Unweighted Pair Group Method of the Arithmetic Average (UPGMA). The results from the cluster analysis showed the studied species could be divided into two main groups. The phylogenetic relationships were associated with the morphological characteristics. In conclusion, AFLP fi ngerprint is a useful technique for identifi cation of Kaempferia species and is an ideal marker system for extended studies including all Kaempferia species for infrageneric classifi cation.


X: -4.6465144 Y: 9.088245title: Polymethoxyflavonoids from Kaempferia parviflora Induce Adipogenesis on 3T3-L1 Preadipocytes by Regulating Transcription Factors at an Early Stage of Differentiation publish year: 2012 keyword: Kaemferia_parviflora content: We previously reported that Kaempferia parviflora WALL. ex BAKER (KP) and its ethyl acetate extract (KPE) improve various metabolic disorders in obesity-model mice. However the mechanism is not certain, and, in this study, in order to elucidate the mechanism of the suppressive effect of KP on fat accumulation, we focused on adipocytes, which are closely linked to metabolic diseases. The finding was that KPE and its components, 3,5,7,4'-tetramethoxyflavone and 3,5,7,3',4'-pentamethoxyflavone, strongly induced differentiation of 3T3-L1 preadipocytes to adipocytes. The above two polymethoxyflavonoids (PMFs) also induced adiponectin mRNA levels, and release of adiponectin into the medium. In addition, these PMFs enhanced the expression of peroxisome proliferator-activated receptor γ (PPARγ), but did not show PPARγ ligand activity. We then investigated the expression of the differentiation-regulator located upstream of PPARγ. Expression of CCAAT/enhancer-binding protein (C/EBP) β and -δ mRNA, a transcriptional regulator of PPARγ, was induced, and expression of GATA-2 mRNA, a down-regulator of adipogenesis, was suppressed by these PMFs. These functions of the KP PMFs that enhance adipogenesis and secretion of adiponectin are, to some extent at least, involved in the mechanisms of anti-metabolic disorders effects.


X: -3.077438 Y: 8.414861title: Kaempferia Sp. Extracts as UV Protecting and Antioxidant Agents in Sunscreen publish year: 2020 keyword: Kaemferia_parviflora content: The ethanolic rhizome extracts of Kaempferia species (K. angustiflora, K. elegans, K. galanga-1, K. galanga-2, K. galanga-3, K. marginata, K. parviflora, K. pulchra, and K. rotunda) were evaluated for their UV protective and antioxidant properties. The effective extracts K. elegans, K. galanga-1, and K. parviflora were further isolated and 18 pure compounds were obtained. Flavokawain B (1), a chalcone found in K. elegans, exhibited the most effective UVA and UVB protection, and were more potent than commercial sunscreens. Compound 1 demonstrated the highest antioxidant activities in ABTS, DPPH, and FRAP assays.

Abbreviations
ABTS: 2,2´-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid; DPPH (1,1-diphenyl-2-picrylhydrazyl); FRAP: ferric reducing antioxidant power; UV: Ultraviolet; UVA: Ultraviolet A; UVB: Ultraviolet B