Effects of 18alpha-glycyrrhizin on the pharmacodynamics and pharmacokinetics of glibenclamide in alloxan-induced diabetic rats.

This paper investigated the effects of 18alpha-glycyrrhizin (18alpha-GL) on the pharmacodynamics and pharmacokinetics of glibenclamide in experimental diabetic rats. 18alpha-GL (25 mg/kg) and/or glibenclamide (1 mg/kg) were given to alloxan-induced diabetic rats for consecutive 5 days. When the rats were co-treated with 18alpha-GL and glibenclamide, fasting plasma glucose concentration was further reduced, plasma insulin content and liver glycogen level were increased markedly as compared with glibenclamide-treated animals. Meanwhile, in co-treated group, elimination rate constant (Ke) of glibenclamide was reduced while peak plasma concentration (C(max)), area under the plasma concentration vs time curve (AUC(0-14 h)) and elimination half-life (T(1/2Ke)) were increased significantly vs glibenclamide alone administered rats. The activities of hepatic CYP3A and the markers of liver injury, plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were significantly decreased in rats treated with 18alpha-GL alone and in combination with glibenclamide. Results of immunohistochemistry showed that 18alpha-GL improved the effects of glibenclamide on the pathological morphology of pancreatic islet beta cells and the intensities of positive immunostaining for insulin. Our results revealed that 18alpha-GL led to the enhancement of the hypoglycemic effect of glibenclamide by inhibiting the activity of CYP3A; on the other hand, 18alpha-GL protected the pancreatic islet beta cells and liver from damage in diabetes which suggested that 18alpha-GL might be beneficial as an adjuvant drug of glibenclamide in a proper dose, especially to the diabetic patients associated with liver dysfunction.

[Activation of the immunologic function of rat Kupffer cells by the polysaccharides of Angelica sinensis].

AIM: To observe the influence of polysaccharides of Angelica sinensis (ASP) on the immunologic function of rat Kupffer cells. METHODS: Normal rat Kupffer cells were treated with ASP in vitro. Absorbance at 540 nm ( A540) of neutral red absorption and supernatant NO, TNF-alpha in the cells were measured to evaluate the immunologic function of Kupffer cells; LDH leakage was measured to estimate the severity of cellular damage; Rats were given ASP 0.025, 0.1, 0.25 and 1.0 g x kg(-1) ig (qd x 7 d) in vivo. The above indices and ACP of Kupffer cells were measured, sGST and sALT activity were detected as indices of hepatotoxicity. RESULTS: ASP markedly enhanced the phagocytic activity, ACP and supernatant NO, TNF-alpha of Kupffer cells both in vitro and in vivo . The increase of sGST was observed after administration of ASP 1.0 g x kg(-1), but the LDH leakage of the hepatocytes was not increased in vitro. CONCLUSION: ASP with suitable dose could activate the function of Kupffer cells. Slight liver injury was caused by ASP 1.0 g x kg(-1) in vivo, which was likely caused by factors, such as NO, TNF-alpha, indirectly.

[Effects of Angelica sinensis polysaccharides on hepatic drug metabolism enzymes activities in mice].

OBJECTIVE: To study the effects of Angelica sinensis Polysaccharides (ASP) on the hepatic drug metabolism enzymes activities in normal mice and those prednisolone (PSL)-induced liver injury. METHOD: The activities of phase II enzymes (GSH-related enzymes) and cytochrome P450 enzymes were measured by biochemical method. RESULT: ASP increased the activities of glutathione S-transferase in liver microsomes and mitochondria. The cytochrome P450 content, NADPH-cytochrome c reductase, aminopyrine N-demethylase, and aniline hydroxylase activities in liver microsomes were also increased. PSL significantly increased serum ALT levels, and decreased the liver mitochondrial glutathione content. At the same time, other enzymes activities were all increased. When mice were treated with ASP 2.0 g.kg-1, the PSL-induced changes on cytochrome P450 enzymes, glutathione S-transferase, and GSH content were restored. CONCLUSION: ASP can modulate the activities of drug metabolism enzymes.

[The effects of silymarin on hepatic microsomal and mitochondrial membrane fluidity in mice].

OBJECTIVE: To observe the effects of silymarin on hepatic microsomal and mitochondrial membrane fluidity in mice. METHOD: Liver microsomal and mitochondrial membranes were labled by ANS and DPH. Membrane fluorensent intensity (F), fluorensent polarization(P) and microviscosily(eta) of liver microsome and mitochondria were determined. RESULT: Sil increased the external membrane fluidities of liver microsome and mitochondria, and decreased the internal membrane fluidities of liver microsome and mitochondria. Pretreatment with CCl4, the external membrane fluidity of liver microsome and mitochondria were increased, and the internal membrane fluidities of liver microsome and mitochondria were decreased. After given sil 140,280 mg.kg-1, the increased external membrane fluidities of liver microsome and mitochondria were lowered, and the decreased internal membrane fluidities of liver microsome and mitochondria were enhanced in a dose-dependent manner. CONCLUSION: The protective effects of sil on liver injury may be related to the recovery of the membrane fluidities of liver microsome and mitochondria.