Simvastatin alleviates liver function injury in ApoE knockout mice by inhibiting calpain activity / 中国药理学通报

Aim To study the protective effect of simvastatin(Sim)on liver function injury in apolipoprotein E gene knockout(ApoE KO)mice fed with high-fat diet and the underlying mechanism.Methods Twenty-four 8-week-old male ApoE KO mice were randomly divided into ApoE KO group,ApoE KO+Sim group and ApoE KO+PD150606 group.The contents of total cholesterol(TC)and triglyceride(TG)in serum and liver,and the activities of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)in serum were measured.The contents of malondialdehyde(MDA)and reactive oxygen species(ROS)and the activity of superoxide dismutase(SOD)in liver were determined.The contents of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)and the activity of calpain in liver were examined.Results Compared with C57 group,ApoE KO group showed significant increase in the contents of TC and TG in both serum and liver.In addition,the activities of AST and ALT in serum and the contents of MDA and ROS in liver significantly increased,while SOD activity in liver decreased in ApoE KO group.The contents of TNF-α and IL-6 and the activity of calpain in liver significantly increased.Compared with ApoE KO group,Sim group had no significant effects on TC and TG,while reduced the activities of AST and ALT,decreased the contents of MDA and ROS,increased the activity of SOD and decreased the contents of TNF-α and IL-6 as well as the activity of calpain in liver.PD,the calpain inhibitor,had the similar effects with Sim regarding the above mentioned parameters.Conclusions Sim improved the liver function injury of ApoE KO mice,which might be related to the inhibition of calpain activity,subsequently increasing the antioxidant capacity and reducing the inflammatory response.

Berberine ameliorates renal injury in streptozotocin-induced diabetic rats by suppression of both oxidative stress and aldose reductase / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Berberine is one of the main constituents of Coptidis rhizoma (CR) and Cortex phellodendri. In this study, we investigated the beneficial effects of berberine on renal function and its possible mechanisms in rats with diabetic nephropathy (DN).</p><p><b>METHODS</b>Male Wistar rats were divided into three groups: normal, diabetic model, and berberine treatment groups. Rats in the diabetic model and berberine treatment groups were induced to diabetes by intraperitonal injection with streptozotocin (STZ). Glomerular area, glomerular volume, fasting blood glucose (FBG), blood urea nitrogen (BUN), serum creatinine (Cr) and urine protein for 24 hours (UP24h) were measured using commercially available kits. Meanwhile, the activity of superoxide dismutase (SOD), content of malondialdehyde (MDA) in serum, activity of aldose reductase (AR) and the expression of AR mRNA and protein in kidney were detected by different methods.</p><p><b>RESULTS</b>The results showed that oral administration of berberine (200 mg x kg(-1) x d(-1)) significantly ameliorated the ratio of kidney weight to body weight. Glomerular area, glomerular volume, FBG, BUN, Cr and UP24h were significantly decreased in the berberine treatment group compared with the diabetic model group (P < 0.05). Berberine treatment significantly increased serum SOD activity and decreased the content of MDA compared with diabetic model group (P < 0.05). AR activity as well as the expression of AR mRNA and protein in the kidney was markedly decreased in the berberine treatment group compared with diabetic model group (P < 0.05).</p><p><b>CONCLUSION</b>These results suggested that berberine could ameliorate renal dysfunction in DN rats through controlling blood glucose, reduction of oxidative stress and inhibition of the activation of the polyol pathway.</p>

Effect of crocin on intracellular calcium concentration in cultured bovine aortic smooth muscle cells / 药学学报

<p><b>AIM</b>To study the effect of crocin on intracellular calcium concentration ([Ca2+]i) in cultured bovine aortic smooth muscle cells (BASMCs).</p><p><b>METHODS</b>Cells were loaded with fluorescence probe Fluo-3/AM and [Ca2+]i was measured by laser scanning confocal microscope (LSCM).</p><p><b>RESULTS</b>In the presence or absence of extracellular Ca2+, crocin (1 x 10(-8), 1 x 10(-7), 1 x 10(-6) mol x L(-1)) concentration-dependently inhibited the [Ca2+]i elevation induced by 1 x 10(-2) mol x L(-1) H2O2 (for the former, the inhibition rates were 34.1%, 57.1% and 74.3%, while for the latter were 26.2%, 32.1%, 50.0%). In the absence of extracellular Ca2+, crocin (1 x 10(-8), 1 x 10(-7), 1 x 10(-6) mol x L(-1)) could inhibit the [Ca2+]i elevation induced by 70 mmol x L(-1) CHCl3, the inhibition rates were 27.8%, 27.8% and 50.0% respectively.</p><p><b>CONCLUSION</b>Crocin could inhibit the extracellular Ca2+ influx and release of intracellular Ca2+ stores in endoplasmic reticulum.</p>