AIM OF THE STUDY: This study is designed to investigate the vasorelaxation effect of G. uralensis from various extracts and to study its pharmacology effect.

MATERIALS AND METHODS: The vasorelaxation effect of G. uralensis extracts were evaluated on thoracic aortic rings isolated from Sprague Dawley rats.

RESULTS: Among these three extracts of G. uralensis, 50% ethanolic extract (EFG) showed the strongest vasorelaxation activity. EFG caused the relaxation of the aortic rings pre-contracted with phenylephrine either in the presence or absence of endothelium and pre-contracted with potassium chloride in endothelium-intact aortic ring. Nω-nitro-L-arginine methyl ester, methylene blue, or 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one inhibit the vasorelaxation effect of EFG in the presence of endothelium. On the other hand, in the presence of the potassium channel blockers (tetraethylammonium and barium chloride), the vasorelaxation effect of EFG was not affected, but glibenclamide and 4-aminopyridine did inhibit the vasorelaxation effect of EFG. With indomethacin, atropine and propranolol, the vasorelaxation effect by EFG was significantly reduced. EFG was also found to be effective in reducing Ca(2+) release from sarcoplasmic reticulum and the blocking of calcium channels.

OBJECTIVE: This study investigates the vasorelaxant mechanism of VA ethanol extract (VAE) and analyzes its tri-step FTIR spectroscopy fingerprint.

MATERIALS AND METHODS: Dried VA leaves were extracted with ethanol through maceration and concentrated using rotary evaporator before freeze-dried. The vasorelaxant activity and the underlying mechanisms of VAE using the cumulative concentration (0.01-2.55 mg/mL at 20-min intervals) were evaluated on aortic rings isolated from Sprague Dawley rats in the presence of antagonists.

RESULTS: The tri-step FTIR spectroscopy showed that VAE contains alkaloids, flavonoids, and saponins. VAE caused the relaxation of pre-contracted aortic rings in the presence and absence of endothelium with EC50 of 0.057 ± 0.006 and 0.430 ± 0.196 mg/mL, respectively. In the presence of Nω-nitro-l-arginine methyl ester (EC50 0.971 ± 0.459 mg/mL), methylene blue (EC50 1.203 ± 0.426 mg/mL), indomethacin (EC50 2.128 ± 1.218 mg/mL), atropine (EC50 0.470 ± 0.325 mg/mL), and propranolol (EC50 0.314 ± 0.032 mg/mL), relaxation stimulated by VAE was significantly reduced. VAE acted on potassium channels, with its vasorelaxation effects significantly reduced by tetraethylammonium, 4-aminopyridine, barium chloride, and glibenclamide (EC50 0.548 ± 0.184, 0.158 ± 0.012, 0.847 ± 0.342, and 0.304 ± 0.075 mg/mL, respectively). VAE was also found to be active in reducing Ca2+ released from the sarcoplasmic reticulum and blocking calcium channels.

AIM OF THE STUDY: This study is designed to investigate the vasorelaxant effect of Chen pi and to study its pharmacology effects.

MATERIALS AND METHODS: The vasorelaxant effect of water extract of Chen pi (CRW) were evaluated on thoracic aortic rings isolated from Sprague Dawley rats. The fingerprint of Chen pi and the extracts were developed with quantification of hesperidin content by HPTLC.

RESULTS: CRW exhibited the strongest vasorelaxant activity. CRW caused the relaxation of the phenylephrine pre-contracted aortic rings in the presence and absence of endothelium as well as in potassium chloride pre-contracted endothelium-intact aortic ring. The incubation of propranolol (β-adrenergic receptor blocker), atropine (muscarinic receptor blocker), Nω-nitro-L-arginine methyl ester (NO synthase inhibitor), ODQ (sGC inhibitor), indomethacin (COX inhibitor), 4-aminopyridine (KV blocker), barium chloride (Kir blocker), and glibenclamide (KATP blocker) significantly reduced the vasorelaxant effects of CRW. CRW was also found to be active in reducing Ca2+ releases from the sarcoplasmic reticulum and suppressing the voltage-operated calcium channels.

MATERIALS AND METHODS: In silico target prediction was first employed to predict the probability of the polyphenols interacting with key protein targets related to insulin signalling, based on a model trained on known bioactivity data and chemical similarity considerations. Next, CA was investigated in in vivo studies where induced type 2 diabetic rats were treated with CA for 28 days and the expression levels of genes regulating insulin signalling pathway, glucose transporters of hepatic (GLUT2) and muscular (GLUT4) tissue, insulin receptor substrate (IRS), phosphorylated insulin receptor (AKT), gluconeogenesis (G6PC and PCK-1), along with inflammatory mediators genes (NF-κB, IL-6, IFN-γ and TNF-α) and peroxisome proliferators-activated receptor gamma (PPAR-γ) were determined by qPCR.

RESULTS: In silico analysis shows that several of the top 20 enriched targets predicted for the constituents of CA are involved in insulin signalling pathways e.g. PTPN1, PCK-α, AKT2, PI3K-γ. Some of the predictions were supported by scientific literature such as the prediction of PI3K for epigallocatechin gallate. Based on the in silico and in vivo findings, we hypothesized that CA may enhance glucose uptake and glucose transporter expressions via the IRS signalling pathway. This is based on AKT2 and PI3K-γ being listed in the top 20 enriched targets. In vivo analysis shows significant increase in the expression of IRS, AKT, GLUT2 and GLUT4. CA may also affect the PPAR-γ signalling pathway. This is based on the CA-treated groups showing significant activation of PPAR-γ in the liver compared to control. PPAR-γ was predicted by the in silico target prediction with high normalisation rate although it was not in the top 20 most enriched targets. CA may also be involved in the gluconeogenesis and glycogenolysis in the liver based on the downregulation of G6PC and PCK-1 genes seen in CA-treated groups. In addition, CA-treated groups also showed decreased cholesterol, triglyceride, glucose, CRP and Hb1Ac levels, and increased insulin and C-peptide levels. These findings demonstrate the insulin secretagogue and sensitizer effect of CA.