Pharmacokinetics of Ginsenoside Rb1, Rg3, Rk1, Rg5, F2, and Compound K from Red Ginseng Extract in Healthy Korean Volunteers.

Individual differences in ginsenoside pharmacokinetics following ginseng administration in humans are still unclear. We aimed to investigate the pharmacokinetic properties of various ginsenosides, including Rb1, Rg3, Rg5, Rk1, F2, and compound K (CK), after a single oral administration of red ginseng (RG) and bioconverted red ginseng extract (BRG). This was a randomized, open-label, single-dose, single-sequence crossover study with washout every 1 week, and 14 healthy Korean men were enrolled. All subjects were equally assigned to two groups and given RG or BRG capsules. The pharmacokinetic parameters of ginsenosides were measured from the plasma drug concentration-time curve of individual subjects. Ginsenosides Rg3, Rk1 + Rg5, F2, and CK in the BRG group showed a higher C max, AUC(0-t), and AUC(0-∞) and shorter T max (for CK) than those in the RG group. These results suggest that BRG may lead to a higher absorption rate of bioactive ginsenosides. This study provides valuable information on the pharmacokinetics of various bioactive ginsenosides, which is needed to enhance the therapeutic efficacy and pharmacological activity of ginseng.

Gynostemma pentaphyllum extract and Gypenoside L enhance skeletal muscle differentiation and mitochondrial metabolism by activating the PGC-1α pathway in C2C12 myotubes.

BACKGROUND/OBJECTIVES: Peroxisome proliferator-activated receptor-gamma co-activator-1α (PGC-1α) has a central role in regulating muscle differentiation and mitochondrial metabolism. PGC-1α stimulates muscle growth and muscle fiber remodeling, concomitantly regulating lactate and lipid metabolism and promoting oxidative metabolism. Gynostemma pentaphyllum (Thumb.) has been widely employed as a traditional herbal medicine and possesses antioxidant, anti-obesity, anti-inflammatory, hypolipemic, hypoglycemic, and anticancer properties. We investigated whether G. pentaphyllum extract (GPE) and its active compound, gypenoside L (GL), affect muscle differentiation and mitochondrial metabolism via activation of the PGC-1α pathway in murine C2C12 myoblast cells. MATERIALS/METHODS: C2C12 cells were treated with GPE and GL, and quantitative reverse transcription polymerase chain reaction and western blot were used to analyze the mRNA and protein expression levels. Myh1 was determined using immunocytochemistry. Mitochondrial reactive oxygen species generation was measured using the 2'7'-dichlorofluorescein diacetate assay. RESULTS: GPE and GL promoted the differentiation of myoblasts into myotubes and elevated mRNA and protein expression levels of Myh1 (type IIx). GPE and GL also significantly increased the mRNA expression levels of the PGC-1α gene (Ppargc1a), lactate metabolism-regulatory genes (Esrra and Mct1), adipocyte-browning gene fibronectin type III domain-containing 5 gene (Fndc5), glycogen synthase gene (Gys), and lipid metabolism gene carnitine palmitoyltransferase 1b gene (Cpt1b). Moreover, GPE and GL induced the phosphorylation of AMP-activated protein kinase, p38, sirtuin1, and deacetylated PGC-1α. We also observed that treatment with GPE and GL significantly stimulated the expression of genes associated with the anti-oxidative stress response, such as Ucp2, Ucp3, Nrf2, and Sod2. CONCLUSIONS: The results indicated that GPE and GL enhance exercise performance by promoting myotube differentiation and mitochondrial metabolism through the upregulation of PGC-1α in C2C12 skeletal muscle.

Gynostemma Pentaphyllum Extract Ameliorates High-Fat Diet-Induced Obesity in C57BL/6N Mice by Upregulating SIRT1.

Gynostemma pentaphyllum is widely used in Asia as a herbal medicine to treat type 2 diabetes, dyslipidemia, and inflammation. Here, we investigated the anti-obesity effect and underlying mechanism of G. pentaphyllum extract (GPE) enriched in gypenoside L, gypenoside LI, and ginsenoside Rg3 and obtained using a novel extraction method. Five-week-old male C57BL/6N mice were fed a control diet (CD), high-fat diet (HFD), HFD + 100 mg/kg body weight (BW)/day GPE (GPE 100), HFD + 300 mg/kg BW/day GPE (GPE 300), or HFD + 30 mg/kg BW/day Orlistat (Orlistat 30) for 8 weeks. The HFD-fed mice showed significant increases in body weight, fat mass, white adipose tissue, and adipocyte hypertrophy compared to the CD group; but GPE inhibited those increases. GPE reduced serum levels of triglyceride, total cholesterol, and LDL-cholesterol, without affecting HDL-cholesterol. GPE significantly increased AMPK activation and suppressed adipogenesis by decreasing the mRNA expression of CCAAT/enhancer binding protein-α (C/EBPα), peroxisome proliferator-activated receptor-γ (PPARγ), sterol regulatory element-binding protein-1c (SREBP1c), PPARγ coactivator-1α, fatty acid synthase (FAS), adipocyte protein 2 (AP2), and sirtuin 1 (SIRT1) and by increasing that of carnitine palmitoyltransferase (CPT1) and hormone- sensitive lipase (HSL). This study demonstrated the ameliorative effect of GPE on obesity and elucidated the underlying molecular mechanism.

Pistacia weinmannifolia root exerts a protective role in ovalbumin­induced lung inflammation in a mouse allergic asthma model.

Pistacia weinmannifolia (Anacardiaceae) has been used in herbal medicine for the treatment of influenza, dysentery and enteritis in China. It was recently observed that P. weinmannifolia root extract (PWRE) exerts anti­inflammatory effects both in in vitro and in vivo models. Based on the results from previous studies, the present study investigated the protective effect of PWRE on airway inflammation and mucus hypersecretion. Treatment with PWRE significantly decreased the number of eosinophils and the levels of Th2 cytokines, such as interleukin (IL)­4, IL­5 and IL­13, in the bronchoalveolar lavage fluid (BALF) of OVA­exposed mice. PWRE decreased the high serum levels of total and OVA­specific immunoglobulin E. PWRE also effectively inhibited the influx of inflammatory cells into the lung, as well as airway mucus hypersecretion. In addition, the increased level of monocyte chemoattractant protein­1 was significantly decreased with the PWRE treatment in the BALF of OVA­exposed mice and in lipopolysaccharide­stimulated RAW264.7 macrophages. These protective effects of PWRE on OVA­induced pulmonary inflammation were accompanied by the downregulation of mitogen associated protein kinases and nuclear factor­κB activation. Thus, the results from the present study indicate that PWRE could be valuable adjuvant for the treatment of asthma.

Pistacia weinmannifolia ameliorates cigarette smoke and lipopolysaccharide­induced pulmonary inflammation by inhibiting interleukin­8 production and NF­κB activation.

Pistacia weinmannifolia (PW) has been used in traditional Chinese medicine to treat headaches, dysentery, enteritis and influenza. However, PW has not been known for treating respiratory inflammatory diseases, including chronic obstructive pulmonary disease (COPD). The present in vitro analysis confirmed that PW root extract (PWRE) exerts anti­inflammatory effects in phorbol myristate acetate­ or tumor necrosis factor α (TNF­α)­stimulated human lung epithelial NCI­H292 cells by attenuating the expression of interleukin (IL)­8, IL­6 and Mucin A5 (MUC5AC), which are closely associated with the pulmonary inflammatory response in the pathogenesis of COPD. Thus, the aim of the present study was to evaluate the protective effect of PWRE on pulmonary inflammation induced by cigarette smoke (CS) and lipopolysaccharide (LPS). Treatment with PWRE significantly reduced the quantity of neutrophils and the levels of inflammatory molecules and toxic molecules, including tumor TNF­α, IL­6, IL­8, monocyte chemoattractant protein­1, neutrophil elastase and reactive oxygen species, in the bronchoalveolar lavage fluid of mice with CS­ and LPS­induced pulmonary inflammation. PWRE also attenuated the influx of inflammatory cells in the lung tissues. Furthermore, PWRE downregulated the activation of nuclear factor­κB and the expression of phosphodiesterase 4 in the lung tissues. Therefore, these findings suggest that PWRE may be a valuable adjuvant treatment for COPD.

Discrimination of Polygonatum species and identification of novel markers using (1) H NMR- and UPLC/Q-TOF MS-based metabolite profiling.

BACKGROUND: Rhizomes of Polygonatum species are commonly used as herbal supplements in Asia. They have different medicinal effects by species but have been misused and mixed owing to their similar taste and smell. Therefore accurate and reliable analytical methods to discriminate between Polygonatum species are required. RESULTS: In this study, global and targeted metabolite profiling using (1) H nuclear magnetic resonance ((1) H NMR) spectroscopy and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) was applied to discriminate between different Polygonatum species. Partial least squares discriminant analysis (PLS-DA) models were used to classify and predict species of Polygonatum. Cross-validation derived from PLS-DA revealed good predictive accuracy. Polygonatum species were classified into unique patterns based on K-means clustering analysis. 4-Hydrobenzoic acid and trigonelline were identified as novel marker compounds and quantified accurately. CONCLUSION: The results demonstrate that metabolite profiling approaches coupled with chemometric analysis can be used to classify and discriminate between different species of various herbal medicines. © 2015 Society of Chemical Industry.