Gynura procumbens aqueous extract alleviates nonalcoholic steatohepatitis through CFLAR-JNK pathway in vivo and in vitro / 中草药·英文版

Objective: The present work was to investigate the protective effects of the aqueous extract of Gynura procumbens (GPAE) against nonalcoholic steatohepatitis (NASH) in mice and NCTC-1469 cells. Methods: C57BL/6J mice were fed with methionine and choline-deficient (MCD) diet and administered simultaneously with GPAE (500 and 1000 mg/kg/d, respectively) by gavage for six weeks. The biomarkers of NASH in serum and liver were determined. NCTC-1469 cells were pretreated with 0.25 mmol/L palmitic acid (PA) plus 0.5 mmol/L oleic acid (OA) for 24 h or treated with adenovirus expressing short-hairpin RNA against CFLAR (Ad-shCFLAR) for 24 h and then treated with GPAE (80 and 160 µg/mL, respectively) for 24 h, and the content of cellular biomarkers of NASH was detected. Results: In mice treated with MCD, GPAE could decrease the levels of serum ALT, AST, the content of hepatic TG, TC and MDA, repress the activities and protein expression of CYP2E1 and CYP4A and the phosphorylation of JNK, increase the activities of HO-1, CAT and GSH-Px, up-regulate the mRNA expression of PPARα, FABP5, CPT1α, ACOX, SCD-1, mGPAT, MTTP and the protein expression of CFLAR and NRF2. In NCTC-1469 cells treated with PA and OA, GPAE could decrease the content of cellular TG and ROS, promote the uptake of 2-NBDG, up-regulate the protein expression of CFLAR and NRF2. In NCTC-1469 cells treated with Ad-shCFLAR, GPAE up-regulated the mRNA and protein expression of CFLAR, down-regulated the phosphorylation of JNK, and increased the protein expression of NRF2 and pIRS1. Conclusion: These results indicated that the activation on CFLAR-JNK pathway might be the main anti-NASH mechanism of GPAE, which on the one hand promote the β-oxidation and efflux of fatty acids in liver, and finally reduce hepatic lipid accumulation, on the other hand increase the activities of anti-oxidant enzymes and inhibit the activities of ROS generation enzymes by activating NRF2, and therefore attenuates hepatic oxidative stress damage.

Chemical constituents of Gynura procumbens (II) / 中草药

Objective To investigate the chemical constituents from the whole plants of Gynura procumbens. Methods The chemical constituents were isolated and purified by silica gel, Sephadex LH-20, and ODS. Their structures were determined by physicochemical properties and spectroscopic analysis. Results Twenty-seven compounds were identified as dibutyl phthalate (1), ursolic acid (2), kaempferol 3-O-β-D-glucopyranoside (3), 5-hydroxymaltol (4), 4-hydroxylbenzoic acid (5), 4-aminocinnamic acid (6), (E)-2-hexenyl β-D-glucoside (7), 1-(3-indolyl)-2,3-dihydroxy-propan-1-one (8), kaempferol-7-O-β-D-glucoside (9), quercetin-3-O-β-D- glucopyranoside (10), 3,4,5-tri-caffeoylquinic acid methyl ester (11), rutin (12), hesperidin (13), 3,4-dihydroxyphenylacetic acid methyl ester (14), euscophic acid (15), tormentic acid (16), 2-methoxy-4-(2-propenyl)-phenyl-O-β-D-glucopyranoside (17), negletein (18), 4,5-dihydroxy-3-methoxybenzoic acid (19), caesalpiniaphenol D (20), gentisic acid (21), 3,4-dihydroxybenzaldehyde (22), isohematinic acid (23), icariside B1 (24), dendranthemoside B (25), 4-methoxycinnamic acid (26), and baicalin (27). Conclusion Compounds 1, 2, 10, and 12 are obtained from the plants of G. procumbens for the first time, and compounds 4, 6-9, 11, 13-16, and 17-27 are obtained from Gynura genus for the first time.

Chemical constituents from whole plant of Gynura procumbens (I) / 中草药

Objective: To investigate the chemical constituents from the whole plants of Gynura procumbens. Methods: The chemical constituents were isolated and purified by repeated silica gel column chromatography, Sephadex LH-20 gel column chromatography, medium pressure column chromatography, and semi-preparative HPLC, and their structures were elucidated by chemical properties and spectroscopic analyses. Results: Sixteen compounds were identified to be quercetin (1), apigenin (2), luteolin (3), kaempferol (4), astragaline (5), kaempferol-5-O-(6″-O-acetyl)-β-D-glucopyranoside (6), negletein (7), 4-methoxycinnamic acid (8), benzyl-O-β-D-glucopyranoside (9), 2-phenylethyl-O-β-D-glucopyranoside (10), 3,5-dicaffeoylquinic acid methyl ester (11), 3,5-dicaffeoylquinic acid ethyl ester (12), 3,4-dicaffeoylquinic acid methyl ester (13), 4,5-dicaffeoylquinic acid methyl ester (14), protocatechuic acid (15), and eugenol glucoside (16). Conclusion: Compounds 7, 8, 12, 14, and 16 are obtained from the plants in Gynura Cass. for the first time, and compounds 3, 6, 9-11 and 13 are obtained from this plant for the first time.

Gynura procumbens extract improves insulin sensitivity and suppresses hepatic gluconeogenesis in C57BL/KsJ-db/db mice

BACKGROUND/OBJECTIVES: This study was designed to investigate whether Gynura procumbens extract (GPE) can improve insulin sensitivity and suppress hepatic glucose production in an animal model of type 2 diabetes. MATERIALS/METHODS: C57BL/Ksj-db/db mice were divided into 3 groups, a regular diet (control), GPE, and rosiglitazone groups (0.005 g/100 g diet) and fed for 6 weeks. RESULTS: Mice supplemented with GPE showed significantly lower blood levels of glucose and glycosylated hemoglobin than diabetic control mice. Glucose and insulin tolerance test also showed the positive effect of GPE on increasing insulin sensitivity. The homeostatic index of insulin resistance was significantly lower in mice supplemented with GPE than in the diabetic control mice. In the skeletal muscle, the expression of phosphorylated AMP-activated protein kinase, pAkt substrate of 160 kDa, and PM-glucose transporter type 4 increased in mice supplemented with GPE when compared to that of the diabetic control mice. GPE also decreased the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the liver. CONCLUSIONS: These findings demonstrate that GPE might improve insulin sensitivity and inhibit gluconeogenesis in the liver.

Hypoglycemic and anti-hyperglycemic study of Gynura procumbens leaf extracts

<p><b>OBJECTIVE</b>To study the antidiabetic activity of Gynura procumbens (G. procumbens) used in the traditional management of diabetes in Southern Asia.</p><p><b>METHODS</b>G. procumbens leaves were extracted sequentially with graded percentage of ethanol in water (95%, 75%, 50%, 25% and 0%), and the extracts were tested for antidiabetic activity using acute (7 h), subcutaneous glucose tolerance test and sub-chronic (14 d) test in non-diabetic and streptozotocin-induced diabetic rats. The extracts were further subjected to phytochemical studies.</p><p><b>RESULTS</b>In acute dose (1 g/kg), the extracts significantly lowered fasting blood glucose (FBG) in streptozotocin-induced diabetic rats (P<0.05). However, the FBG-lowering effect of the 25% extract compared to the other extracts, was rapid (47% after 2 h) and the highest: 53%, 53% and 60% in the 3rd, 5th, and 7th h, respectively (P<0.05), comparable only to the effect of metformin. Furthermore, the extracts suppressed peak FBG in subcutaneous glucose tolerance test, but only the 0% and 25% extracts, and metformin sustained the decrease until the 90th min (P<0.05). Moreover, in the 14 days study, the 25% extract exerted the highest FBG-lowering effect, namely 49.38% and 65.43% on days 7 and 14, respectively (P<0.05), similar to the effect of metformin (46.26% and 65.42%). Total flavanoid and phenolic contents in the extracts were found to decrease with increase in polarity of extraction solvents. The composition of reference compounds (chlorogenic acid, rutin, astragalin and kaempferol-3-O-rutinoside) followed a similar trend.</p><p><b>CONCLUSIONS</b>G. procumbens contains antidiabetic principles, most extracted in 25% ethanol. Interaction among active components appears to determine the antidiabetic efficacy, achieved likely by a metformin-like mechanism.</p>

Gynura procumbens Merr. decreases blood pressure in rats by vasodilatation via inhibition of calcium channels

INTRODUCTION: Gynura procumbens has been shown to decrease blood pressure via inhibition of the angiotensinconverting enzyme. However, other mechanisms that may contribute to the hypotensive effect have not been studied. OBJECTIVES: To investigate the cardiovascular effects of a butanolic fraction of Gynura procumbens in rats. METHODS: Anaesthetized rats were given intravenous bolus injections of butanolic fraction at doses of 2.5-20 mg/kg in vivo. The effect of butanolic fraction on vascular reactivity was recorded in isolated rat aortic rings in vitro. RESULTS: Intravenous administrations of butanolic fraction elicited significant (p<0.001) and dose-dependent decreases in the mean arterial pressure. However, a significant (p<0.05) decrease in the heart rate was observed only at the higher doses (10 and 20 mg/kg). In isolated preparations of rat aortic rings, phenylephrine (1×10-6 M)- or potassium chloride (8×10-2 M)-precontracted endothelium-intact and -denuded tissue; butanolic fraction (1×10-6-1×10-1 g/ml) induced similar concentration-dependent relaxation of the vessels. In the presence of 2.5×10-3 and 5.0×10-3 g/ml butanolic fraction, the contractions induced by phenylephrine (1×10-9-3×10-5 M) and potassium chloride (1×10-2-8×10-2 M) were significantly antagonized. The calcium-induced vasocontractions (1×10-4-1×10-2 M) were antagonized by butanolic fraction concentration-dependently in calcium-free and high potassium (6×10-2 M) medium, as well as in calcium- and potassium-free medium containing 1×10-6 M phenylephrine. However, the contractions induced by noradrenaline (1×10-6 M) and caffeine (4.5×10-2 M) were not affected by butanolic fraction. CONCLUSION: Butanolic fraction contains putative hypotensive compounds that appear to inhibit calcium influx via receptor-operated and/or voltage-dependent calcium channels to cause vasodilation and a consequent fall in blood pressure.

Inhibitory Effects of an Aqueous Extract of Gynura procumbens on Human Mesangial Cell Proliferation

Gynura procumbens (Lour.) Merr. has been used in some parts of Southeast Asia as a folk medicine to treat kidney diseases, diabetes mellitus, and hyperlipidemia. The present work was undertaken to prove the mechanisms of G. procumbens in the management of glomerular diseases. We investigated the effect of an aqueous extract of G. procumbens on cell proliferation, DNA synthesis, and the expressions of TGF-beta1, PDGF-BB, CDK1, CDK2, and CDK4 in fetal bovine serum-activated human mesangial cells (MCs). The G. procumbens extract inhibited proliferation, DNA synthesis, expressions of PDGF-BB, CDK1, and CDK2 mRNA, and expression of TGF-beta1 protein in MCs. The inhibitory effect of G. procumbens on MC proliferation may be mediated by suppression of PDGF-BB and TGF-beta1 expressions and the modulation of CDK1 and CDK2 expression. Therefore, G. procumbens shows promise as an adjunct therapy in preventing progressive renal diseases.

Removing anion superoxide free radicals activity and anti-oxidative hepato- and cerebro- protector properties in rats (in vitro) of fluid extract from Gynura procumbens (Lour.) Merr

The extract of dried herb of Gynura procubens, ratio 1:1, is used for antioxidative activity. In special, to strongly inhibit the free formation of anion superoxide O2, reaches 49.63% among 160mg/ml. To inhibit the peroxide lipid the same mouse liver's cells: 33.30mg/ml (inhibition 14.78%); and with 166.50mg/ml, the MDA is about 58.90%. There is inhibiting effect for peroxide lipid in the liquid of mice brain's cells