Kaempferia parviflora extract and its component polymethoxyflavones suppress adipogenic differentiation of human bone marrow-derived mesenchymal stem cells via the AMPK pathway.

BACKGROUND: Kaempferia parviflora Wall. ex. Baker (KP) has been reported to exhibit anti-obesity effects. However, the detailed mechanism of the anti-obesity effect of KP extract (KPE) is yet to be clarified. Here, we investigated the effect of KPE and its component polymethoxyflavones (PMFs) on the adipogenic differentiation of human mesenchymal stem cells (MSCs). METHODS AND RESULTS: KPE and PMFs fraction (2.5 µg/mL) significantly inhibited lipid and triacylglyceride accumulation in MSCs; lipid accumulation in MSCs was suppressed during the early stages of differentiation (days 0-3) but not during the mid (days 3-7) or late (days 7-14) stages. Treatment with KPE and PMFs fractions significantly suppressed peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), and various adipogenic metabolic factors. Treatment with KPE and PMFs fraction induced the activation of AMP-activated protein kinase (AMPK) signaling, and pretreatment with an AMPK signaling inhibitor significantly attenuated KPE- and PMFs fraction-induced suppression of lipid formation. CONCLUSIONS: Our findings demonstrate that KPE and PMFs fraction inhibit lipid formation by inhibiting the differentiation of undifferentiated MSCs into adipocyte lineages via AMPK signaling, and this may be the mechanism underlying the anti-obesity effects of KPE and PMFs. Our study lays the foundation for the elucidation of the anti-obesity mechanism of KPE and PMFs.

Effect of Kencur (Kaempferia galanga L.) Ethanolic Extract Treatment on Cerebral Caspase-3 Expression in Traumatic Brain Injury Rat Models.

Background: Traumatic brain injury is one of the most common forms of trauma and causes significant morbidity and mortality. Kencur (Kaempferia galanga L.) ethanolic extract is known to contain substances that could theoretically inhibit unfavourable cellular processes, including oxidative stress and inflammation. This research aimed to study Kencur's anti-apoptosis activity through the inhibition of caspase-3. Methods: This is a true experimental post-test-only group design study, using male Wistar rats (Ratus novergicus) with weight-drop-induced traumatic brain injury. The subjects in this study were divided into four groups: two Control groups (Groups A and B) and two Therapy groups (Groups C and D). Groups C and D differed in the dose of Kencur ethanolic extract administered (600 mg/kgBW/day and 1,200 mg/kgBW/day, respectively). The Therapy groups were then subdivided into those receiving therapy for 24 h (C-24 and D-24) and those receiving therapy for 48 h (C-48 and D-48). Caspase-3 expression in brain tissue was evaluated at the end of the therapy using immunohistochemistry. All groups were subjected to a Kruskal-Wallis comparison test and the investigation continued with a Mann-Whitney U test to compare the two groups. Results: In traumatic brain injury rat models treated with Kaempferia galanga L. ethanolic extract at doses of 1,200 mg/kgBW/day within 48 h of therapy (D-48) compared to those who were not treated, there was a significant change in the cerebral expression of caspase-3 (P = 0.016). There was also a significant difference between the two doses of intervention (C-24 at 600 mg/kgBW/day and D-48 at 1,200 mg/kgBW/day; P = 0.016). Conclusion: With a minimum of 48 h of treatment split into two doses, Kencur (Kaempferia galanga L.) ethanolic extract can decrease caspase-3 expression in rats with traumatic brain injury.

Novosphingobium kaempferiae sp. nov., a phosphate-solubilizing bacterium isolated from stem of Kaempferia marginata Carey.

A Gram-stain-negative, aerobic, rod-shaped, non-spore-forming and yellow-pigment-producing bacterium, designated as Sx8-5T, was isolated from stem tissue of Kaempferia marginata Carey in Kanchanaburi Province, Thailand. The strain exhibited tricalcium phosphate solubilizing activity. Its taxonomic position was investigated using a polyphasic approach. Sx8-5T grew at 25-37 °C (optimum 30 °C), pH 6-9 (optimum 7) and with 0 and 1% NaCl (optimum 0 %). According to the 16S rRNA gene phylogeny, Sx8-5T represents a member of genus Novosphingobium and shared the highest sequence similarities to Novosphingobium barchaimii LL02T of 99.4 % and shared sequence similarities with other species of the genus Novosphingobium of less than 99.4 %. The whole-genome size was 5.7 Mb, comprised of one contig, with a DNA G+C content of 66 %. The average nucleotide identity using BLASTn (ANIb) or MUMMER (ANIm) values for whole genome comparisons between Sx8-5T and Novosphingobium barchaimii LL02T and six closely related type strains were 72.33-82.14 % and 83.82-87.38 %, respectively, and the digital DNA-DNA hybridization (dDDH) values ranged from 21.0 to 28.6% when compared with the type strains of the members of the genus Novosphingobium. Major fatty acids were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), C16 : 0 and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), respectively. Polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylglycerol, unidentified phospholipids and unidentified polar lipids. The major isoprenoid quinone was Q-10. According to results obtained using a polyphasic approach, Sx8-5T represents a novel species of the genus Novosphingobium, the name Novosphingobium kaempferiae sp. nov. is proposed. The type strain is Sx8-5T (=JCM 35076T =TBRC 15600T).

Preparation of Self-microemulsion Solids of Kaempferia galanga (L.) Volatile Oil and Its Effect on Rats with Gastric Ulcer.

Kaempferia galanga volatile oil (KVO), the main effective component of the medicinal plant Kaempferia galanga L., possesses a variety of pharmacological activities such as anti-inflammatory, antioxidant, and anti-angiogenic activities and has therapeutic potential for gastric ulcer (GU). However, poor solubility as well as instability limits the clinical application of KVO. In this study, K. galanga volatile oil self-microemulsion solids (KVO-SSMEDDS) were prepared to improve its bioavailability and stability, and the therapeutic effects were evaluated in a rat model with GU. The ratio of oil phase, emulsifier, and co-emulsifier in the KVO-SMEDDS prescription were optimized by plotting the pseudo-ternary phase diagram with the star point design-response surface method. Based on the optimal prescription, self-microemulsifying drug delivery system (SMEDDS) was prepared as solid particles (S-SMEDDS). The prepared KVO-SSMEDDS had a rounded and non-adhesive appearance, formed an O/W emulsion after dissolution in water, and had a uniform particle size distribution with good stability and solubility. It was administered to GU model animals, and the results showed that a certain dose of KVO-SSMEDDS solution could increase the content of gastric mucosal protective factors PGE2, TGF-α, and EGF in gastric tissues and serum, and the expression of inflammatory factors IL-8 and TNF-α was downregulated. Meanwhile, the expression of the NF-κB/COX-2 pathway proteins was inhibited. In conclusion, the prepared KVO-SSMEDDS has good dispersion, solubility, and stability and has a therapeutic effect on rats with GU.

Biologically synthesized black ginger-selenium nanoparticle induces apoptosis and autophagy of AGS gastric cancer cells by suppressing the PI3K/Akt/mTOR signaling pathway.

BACKGROUND: Despite being a promising strategy, current chemotherapy for gastric cancer (GC) is limited due to adverse side effects and poor survival rates. Therefore, new drug-delivery platforms with good biocompatibility are needed. Recent studies have shown that nanoparticle-based drug delivery can be safe, eco-friendly, and nontoxic making them attractive candidates. Here, we develop a novel selenium-nanoparticle based drug-delivery agent for cancer treatment from plant extracts and selenium salts. RESULTS: Selenium cations were reduced to selenium nanoparticles using Kaempferia parviflora (black ginger) root extract and named KP-SeNP. Transmission electron microscopy, selected area electron diffraction, X-ray diffraction, energy dispersive X-ray, dynamic light scattering, and Fourier-transform infrared spectrum were utilized to confirm the physicochemical features of the nanoparticles. The KP-SeNPs showed significant cytotoxicity in human gastric adenocarcinoma cell (AGS cells) but not in normal cells. We determined that the intracellular signaling pathway mechanisms associated with the anticancer effects of KP-SeNPs involve the upregulation of intrinsic apoptotic signaling markers, such as B-cell lymphoma 2, Bcl-associated X protein, and caspase 3 in AGS cells. KP-SeNPs also caused autophagy of AGS by increasing the autophagic flux-marker protein, LC3B-II, whilst inhibiting autophagic cargo protein, p62. Additionally, phosphorylation of PI3K/Akt/mTOR pathway markers and downstream targets was decreased in KP-SeNP-treated AGS cells. AGS-cell xenograft model results further validated our in vitro findings, showing that KP-SeNPs are biologically safe and exert anticancer effects via autophagy and apoptosis. CONCLUSIONS: These results show that KP-SeNPs treatment of AGS cells induces apoptosis and autophagic cell death through the PI3K/Akt/mTOR pathway, suppressing GC progression. Thus, our research strongly suggests that KP-SeNPs could act as a novel potential therapeutic agent for GC.

Quantitative analysis of methoxyflavones discriminates between the two types of Kaempferia parviflora.

INTRODUCTION: Kaempferia parviflora or black ginger is abundantly cultivated because its rhizomes contain methoxyflavones that have many pharmacological properties. K. parviflora can be divided into two types, based on morphological characteristics, but differences in their chemical compositions have never been explored. OBJECTIVES: This research aims to find chemical markers that can be used to differentiate between the two types of K. parviflora, the red-leaf and green-leaf types, by quantifying the amounts of methoxyflavones. MATERIAL AND METHODS: K. parviflora samples were collected from 39 locations in Thailand. Their genetic diversity was assessed by a genotyping-by-sequencing (GBS) technique to construct the population structure. Their chemical compositions were analyzed by high performance liquid chromatography-photodiode array detection to determine the methoxyflavone contents. RESULTS: The population structure based on >3,000 single nucleotide polymorphism (SNP) markers showed that the samples can be divided into two groups, which were consistent with the classification by leaf margin color (red-leaf and green-leaf types). HPLC analysis revealed 3,5,7,3',4'-pentamethoxyflavone (PMF), 5,7-dimethoxyflavone (DMF), 5,7,4'-trimethoxyflavone (TMF), 3,5,7-trimethoxyflavone and 3,5,7,4'-tetramethoxyflavone as major methoxyflavones that can be used as chemical markers. The red-leaf type showed higher amounts of PMF, TMF and 3,5,7,4'-tetramethoxyflavone than the green-leaf type, while the green-leaf type showed higher amounts of DMF and 3,5,7-trimethoxyflavone than the red-leaf type. CONCLUSION: These results provide another approach to discriminate the two types of K. parviflora using chemical profiles alongside genetic and morphological analyses. Therefore, a specific type of K. parviflora can be selected over the other based on preferences for a certain methoxyflavone.

Kaempferia parviflora Rhizome Extract as Potential Anti-Acne Ingredient.

Kaempferia parviflora (Black ginger) is used widely in medical fields as an anti-microorganism and anti-inflammation. In this study, the aim was to evaluate the in vitro and in vivo anti-acne efficacy of black ginger extract. The results indicate that the methanol and ethanol extracts showed the highest total phenolic contents, without a significant difference, whereas the n-hexane extract showed the highest total flavonoid content. Nine flavones were detected using UPLC-QTOF-MS, and the ethyl acetate extract showed the highest amount of 5,7-dimethoxyflavone (DMF) according to HPLC. Antibacterial activity against Staphylococcus aureus, S. epidermidis, and Cutibacterium acnes was observed. All the extracts showed antimicrobial activity against C. acnes, revealing MICs in the range of 0.015 to 0.030 mg/mL, whereas the ethyl acetate extract inhibited the growth of S. epidermidis with a MIC of 3.84 mg/mL. In addition, the ethyl acetate extract showed the highest activity regarding nitric oxide inhibition (IC50 = 12.59 ± 0.35 µg/mL). The ethyl acetate extract was shown to be safe regarding cell viability at 0.1 mg/mL. The anti-acne efficacy was evaluated on volunteers. The volunteers were treated in two groups: one administered a 0.02% ethyl acetate extract gel-cream (n = 9) and one administered a placebo (n = 9) for 6 weeks. The group treated with the gel-cream containing the extract showed 36.52 and 52.20% decreases in acne severity index (ASI) after 4 and 6 weeks, respectively, and 18.19 and 18.54% decreases in erythema, respectively. The results suggest that K. parviflora could be a potent active ingredient in anti-inflammatory and anti-acne products.

Optimization of Ultrasound-Assisted Extraction of Yields and Total Methoxyflavone Contents from Kaempferia parviflora Rhizomes.

The major bioactive components of Kaempferia parviflora (KP) rhizomes, 3,5,7,3',4'-pentamethoxyflavone (PMF), 5,7-dimethoxyflavone (DMF), and 5,7,4'-trimethoxyflavone (TMF), were chosen as the quantitative and qualitative markers for this plant material. In order to extract bioactive components (total methoxyflavones) from KP rhizomes, ultrasound-assisted extraction (UAE) was proposed as part of this study. Plackett-Burman design (PBD) and Box-Behnken design (BBD) were utilized to optimize the effects of UAE on extraction yields and total methoxyflavone contents in KP rhizomes. First, PBD was utilized to determine the effect of five independent variables on total yields and total methoxyflavone contents. The results indicated that the concentration of the extracting solvent (ethanol), the extraction time, and the ratio of solvent to solid were significant independent terms. Subsequently, BBD with three-level factorial experiments was used to optimize the crucial variables. It was discovered that the concentration of ethanol was the most influential variable on yields and total methoxyflavone contents. Optimum conditions for extraction yield were ethanol concentration (54.24% v/v), extraction time (25.25 min), and solvent-to-solid ratio (49.63 mL/g), while optimum conditions for total methoxyflavone content were ethanol concentration (95.00% v/v), extraction time (15.99 min), and solvent-to-solid ratio (50.00 mL/g). The relationship between the experimental and theoretical values was perfect, which proved that the regression models used were correct and that PBD and BBD were used to optimize the conditions in the UAE to obtain the highest yield and total methoxyflavone content in the KP rhizomes.

Derivatives of Cinnamic Acid Esters and Terpenic Diversity in Volatiles of Thirty-Six Sand Ginger (Kaempferia galanga L.) Accessions of Eastern India Revealing Quality Chemovars.

The essential oil of Kaempferia galanga L. commonly known as sand ginger has increased its demand in national and international market for decades. Cinnamic acid esters like ethyl-p-methoxy cinnamate (EPMC) and ethyl cinnamate (EC) are major constituents in its essential oil. In spite of the high demand for the plant as raw material, identification of quality chemovars having high essential oil (EO) yield and constituents is still at an infant stage. With this in mind, we have evaluated the EO yield of 36 accessions from three provinces of Eastern India, which varied within a range of 0.41 ± 0.01 to 2.63 ± 0.03 v/w. Further, a total of 65 compounds were detected by gas chromatography and mass spectrometry (GC-MS) with area percentages varying from 76.16 to 97.3%. EPMC was found to be the major component in 14 accessions with area percentages varying from 10.7% to 41.1%, whereas other 22 accessions showed EC as the major constituent, varying from 16% to 29.1%. Further, a diversity study among accessions was performed by agglomerative hierarchical clustering (AHC) and principal component analysis (PCA) analysis based on the abundance of identified constituents, which categorized all 36 accessions into three clusters. Thus, the present study helps to identify quality chemovar K.g16 and K.g14 with respect to oil yield and constituents, respectively, which could be used to guide commercial cultivation and further improvement of the taxa.

Biotransformation of 1α,11α-dihydroxyisopimara-8(14),15-diene by Cunninghamella echinulata NRRL 1386 and their neuroprotective activity.

The isopimarane diterpene, 1α,11α-dihydroxyisopimara-8(14),15-diene (1), is the major constituents from the rhizomes of Kaempferia marginata (Zingiberaceae), a Thai medicinal plant. The microbial transformation of parent compound 1 by the fungus Cunninghamella echinulata NRRL 1386 gave five new metabolites, 7α,11α-dihydroxy-1-oxoisopimara-8(14),15-diene (2), 3ß,7α,11α-trihydroxy-1-oxoisopimara-8(14),15-diene (3), 7ß,11α-dihydroxy-1-oxoisopimara-8(14),15-diene (4), 7α-hydroxy-1,11-dioxoisopimara-8(14),15-diene (5) and 1α,7ß,11α-trihydroxyisopimara-8(14),15-diene (6), together with three known metabolites, 7-9. The structures of the new metabolites were elucidated by spectroscopic techniques. The known compounds were identified by comparison of the spectroscopic and physical data with those of reported values. The parent compound 1 and the metabolites have been neuroprotective activities evaluated against Aß25-35-induced damage in human neuroblastoma cells (SK-N-SH). Among them, compounds 1-3, 5 and 7-9 had significant neuroprotective activities at a concentration of 2.5 µM. The results demonstrated that these compounds might be worth for further development into therapeutic agents for the treatment of neurodegenerative diseases.

Shanpanootols G and H, Diterpenoids from the Rhizomes of Kaempferia pulchra Collected in Myanmar and Their Vpr Inhibitory Activities.

Two new trihydroxy derivative of Δ8(14),15-isopimarane diterpenoids, shanpanootols G (1) and H (2), along with three known analogues were isolated from the ethyl acetate-soluble extract of Kaempferia pulchra rhizomes collected in Shan State of Myanmar. The structures of these compounds including their absolute configurations were elucidated by the combination of one dimensional (1D) and 2D-NMR spectroscopic methods, high resolution mass spectrometric technique, and the experimental and the calculated electronic circular dichroism (ECD) data. The isopimarane diterpenoids (1-5) were tested for their Viral protein R (Vpr) inhibitory activities against TREx-HeLa-Vpr cells. Shanpanootol H (2) and (1R,2S,5S,9R,10S,13R)-1,2-dihydroxypimara-8(14),15-dien-7-one (4) exhibited anti-Vpr activities at the 5 µM treated dose.

Kaempferia parviflora Extract Alleviated Rat Arthritis, Exerted Chondroprotective Properties In Vitro, and Reduced Expression of Genes Associated with Inflammatory Arthritis.

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.

[Research progress and discussion on traditional Chinese medicine properties of Kaempferia parviflora].

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.

Anti-inflammatory activities of isopimara-8(14),-15-diene diterpenoids and mode of action of kaempulchraols P and Q from Kaempferia pulchra rhizomes.

Inflammation is an extensively recognized link to many pathological diseases. It is a host response for protection from infections and tissue damage. Infections trigger acute inflammation; however, persistent infection will contribute to chronic inflammation and higher disease susceptibility. Deregulated inflammatory responses can cause excessive or long-lasting tissue damage, manifested as cancer, immune disorders, diabetes, etc. NF-κB is a central mediator of pro-inflammatory gene induction and functions in both innate and adaptive immune cells; therefore, the anti-inflammatory regulation of NF-κB is needed. Natural products reportedly play an important role in controlling the inflammatory response pathways. However, the anti-inflammatory activities of isopimara-8-(14),15-diene diterpenoids have not yet been fully elucidated. To elucidate the anti-inflammatory activities of the isopimara-8(14),15-diene diterpenoids, we investigated 21 isopimara-8(14),15-diene diterpenoids previously isolated from Kaempferia pulchra rhizomes. Eleven compounds exhibited NO inhibitory activity against lipopolysaccharide (LPS)-induced RAW264.7 cells, with IC50 values ranging from 30 to 100 µM. Furthermore, the most potent kaempulchraols P and Q, with IC50 values of 39.88 and 36.05 µM, respectively, inhibited the NF-κB-mediated transactivation of a luciferase reporter gene, IL-6 production, and COX-2 expression, with an effective dose of 25 µM. These findings provide new insights into the anti-inflammatory activities of the isopimara-8(14),15-diene diterpenoids.

Effect of methoxyflavones contained in Kaempferia parviflora on CRE-mediated transcription in PC12D cells.

The cAMP-response element (CRE) is critical in the formation of long-term memory. To prove the pharmacological effects of the methoxyflavones-rich residue (MRR) and its constituent methoxyflavones (1-9) extracted from the rhizomes of Kaempferia parviflora on the nervous system, we examined the effects of the MRR and methoxyflavones (1-9) on CRE-mediated transcription in PC12D cells. The MRR increased CRE-mediated transcription in PC12D cells. In addition, among methoxyflavones (1-9) isolated from MRR, compounds 1-4 increased CRE-mediated transcription. These results suggest that K. parviflora and methoxyflavone might be very useful materials for preventing and recovering from cognitive decline.

Anti-inflammatory effect of isopimarane diterpenoids from Kaempferia galanga.

Two new isopimarane diterpenes, 1α-hydroxy-14α-methoxyisopimara-8(9),15-diene (7) and 1α,14α-dihydroxyisopimara-8(9),15-diene (9) and eight known isopimarane diterpenes including (-)-sandaracopimaradiene (1), 6ß-acetoxysandaracopimaradiene-9α-ol (2), sandaracopimaradiene-7ß,9α-diol (3), sandaracopimaradiene-1α,9α-diol (4), 6ß-acetoxysandaracopimaradiene-9α-ol-1-one (5), 6ß-acetoxysandaracopimaradiene-1α,9α-diol (6), 6ß,14α-dihydroxyisopimara-8(9),15-diene (8), and 6ß,14ß-dihydroxyisopimara-8(9),15-diene (10) were isolated from hexane fraction of Kaempferia galanga ethanol extract. Compounds 5, 6, 8, and 9 exerted the good anti-inflammatory effect on lipopolysaccharide-stimulated nitric oxide production from RAW264.7 cells with IC50 of 11.2, 7.7, 14.3, and 12.1 µM, respectively. These four compounds inhibited nitric oxide synthase (iNOS) mRNA expression. Compounds 5 and 6 also suppressed cyclooxygenase 2 (COX-2) mRNA expression; in addition, compound 6 had mild inhibitory effect on TNF-α mRNA. Among these compounds, 5 dramatically inhibited iNOS and COX-2 mRNA expression. The influential structures were proposed to be oxygen substitute at C-1, C-6, and α-OH at C-14.

In vivo effect of Kaempferia parviflora extract on pharmacokinetics of acetaminophen.

Kaempferia parviflora is widely used as a food supplement and a herbal medicine for vitalization. Previous study has shown that K. parviflora had CYP2E1 inducer activity. It is likely to affect the metabolism of CYP2E1 substrates such as acetaminophen which is a common household pain relief medicine. This study investigated the possible pharmacokinetic interaction between K. parviflora and acetaminophen in rats. Acetaminophen (100 mg/kg, p.o) was administered to rats for nine consecutive days. On days 4-9, K. parviflora extract (250 mg/kg, p.o) was given to the acetaminophen-treated rats. After co-administration with K. parviflora, the concentrations of acetaminophen during day 5-8 markedly decreased compared with acetaminophen-only group. At day 9, the pharmacokinetic parameters of acetaminophen in the presence of K. parviflora extract also decreased, including area under the concentration-time curve (from 1.68 ± 0.16 to 0.34 ± 0.04 mg.min/mL), the maximum concentration (from 19.10 ± 1.90 to 4.48 ± 0.56 µg/mL), and half-life (from 21.29 ± 1.36 to 10.81 ± 1.24 min). In addition, clearance and the elimination rate constant of acetaminophen were significantly increased (from 0.003 ± 0.000 to 0.006 ± 0.001 L/min and 0.03 ± 0.00 to 0.07 ± 0.01 min-1, respectively) in the presence of K. parviflora extract. These findings provide the data for in vivo herb-drug interaction between K. parviflora extract and acetaminophen. Therefore, the concomitant use of K. parviflora as a food supplement and acetaminophen should occasion therapeutic and safety concerns.

Enhancing oral absorption of poorly water-soluble herb (Kaempferia parviflora) extract using self-nanoemulsifying formulation.

Kaempferia parviflora, a medicinal herb, treats hypertension and promotes longevity with good health and well-being. Its bioactive component is poorly soluble in water, resulting in poor absorption. This study aimed to enhance the bioavailability of K. parviflora dichloromethane (KPD) extract using a self-nanoemulsifying drug delivery system (SNEDDS). KPD was dissolved in diethylene glycol monoethyl, polyoxyl-35 castor oil and caprylic/capric glyceride, and clear yellow SNEDDS solution was obtained. The methoxyflavone markers were used for content and dissolution analysis. Solid SNEDDS was prepared by stepwise mixing of KPD using a mortar and pestle (1:1 ratio) with five solid carriers: Aerosil® 200, Florite® RE, Neusilin® US2 (NEUS), Fujicalin®, and Neusilin® UFL2. The USP apparatus II with simulated gastric fluid USP (SGF without pepsin, pH 1.2) was used in order to perform the in vitro dissolution. The methoxyflavones dissolution at 60 min from KPD, SEDDS, and SNEDDS/NEUS were approximately 16, 92, and 73%, respectively. The pharmacokinetic profiles of methoxyflavones for oral administration were studied using Wistar rats; the areas under the curve of SNEDDS/NEUS (1.77-fold) and SNEDDS (5.38-fold) were significantly higher than that of KPD. The developed formulations showed good stability after storage for 6 months under accelerated and normal conditions.

Kaempferia parviflora Nanosuspension Formulation for Scalability and Improvement of Dissolution Profiles and Intestinal Absorption.

Kaempferia parviflora (KP) is an herbal medicine for enhancement of physical fitness and male sexual function improvement with low oral absorption of the main active compounds, methoxyflavones. The purpose of this study is to optimize the preparation of nanosuspensions of KP extract for enhancing intestinal absorption using antisolvent precipitation technique which is an accessible nanomanufacturing methodology in the small industrial factory. Nanosuspensions were prepared using various types and concentrations of stabilizers. Then, the dry powder of KP nanosuspension was produced by spray drying. Its dissolution rate was determined using USP dissolution apparatus II. The rat everted intestinal sac was tested to confirm the improvement of intestinal absorption of KP nanosuspension. The result showed that 3% sodium lauryl sulfate (SLS) was the optimal condition for covering the nano-size of KP nanosuspension. KP nanosuspensions had particle sizes ranging from 100 to 300 nm with narrow size distribution (PDI < 0.60) and zeta potential at - 58 to - 70 mV. These characteristics were stable at 4°C and 25°C/60%RH for 1-month storage. Its methoxyflavones content also unchanged at 4°C and 25°C/60%RH for 1-month storage. KP nanosuspension released > 80% of the methoxyflavones within 30 min both in 0.1 N HCl and 0.01 M phosphate buffer solution (pH 6.8). Moreover, the developed nanosuspension dramatically improved the rat intestinal absorption about 10-fold. Therefore, the KP nanosuspension was successfully prepared. It has relatively high stability, fast dissolution rate, and high intestinal absorption.

Jiangella endophytica sp. nov., an endophytic actinomycete isolated from the rhizome of Kaempferia elegans.

An endophytic actinobacterium, designated strain KE2-3T, was isolated from surface-sterilised rhizome of Kaempferia elegans. The polyphasic approach was used for evaluating the taxonomic position of this strain. The taxonomic affiliation of this strain at genus level could be confirmed by its chemotaxonomic characteristic, i.e. the presence of ll-diaminopimelic acid in the cell peptidoglycan, MK-9(H4) as the major menaquinone, iso-C16 : 0, anteiso-C15 : 0, iso-C14 : 0 and iso-C15 : 0 as the predominant fatty acids in cells, and the presence of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannoside in its membranes. Based on 16S rRNA gene sequence analysis, strain KE2-3T was identified as a member of the genus Jiangella and showed the highest similarities to Jiangella muralis DSM 45357T (99.3 %) followed by Jiangella albaDSM 45237T (99.2 %), Jiangella alkaliphilia DSM 45079T (99.0 %), Jiangella gansuensisDSM 44835T (98.8 %) and Jiangella mangrovi3SM4-07T (98.6 %). However, the draft genome sequence of strain KE2-3T exhibited low average nucleotide identity values to the reference strains (85.5-90.2 %), which were well below the 95-96 % species circumscription threshold. The DNA G+C content of genomic DNA was 72.3 mol%. With the differences of physiological, biochemical and genotypic data, strain KE2-3T could be discriminated from its closest neighbour. Thus, strain KE2-3T should be recognised as a novel species of genus Jiangella, for which the name Jiangellaendophytica sp. nov. is proposed. The type strain is KE2-3T (=BCC 66359T=NBRC 110004T).