Protective effect of Dioscorea zingiberensis ethanol extract on the disruption of blood-testes barrier in high-fat diet/streptozotocin-induced diabetic mice by upregulating ZO-1 and Nrf2.

Testicular injury is the primary pathogenesis of diabetes-induced male infertility. Dioscorea zingiberensis (DZ), a traditional Chinese medicine (TCM) including saponins, flavonoids and cellulose, is used to treat diseases in the reproductive system. But the protective effects of DZ on diabetes-induced testicular injury remain poorly understood. In this study, the therapeutic effects of chronic oral DZ treatment on testis impairment in a diabetic mouse model were explored by assessing sperm morphology, blood-testes barrier (BTB) integrity and testicular histological examination. Our results showed that DZ significantly reversed BTB disruption, testicular tissue injury and abnormal sperm morphology in diabetic mice. Interestingly, diabetes-induced disruption of the BTB was associated with a decrease in the tight junction (TJ) protein zonula occludens-1 (ZO-1). Dioscorea zingiberensis effectively increased ZO-1 expression in testis tissue to restore the integrity of the BTB. Moreover, DZ treatment significantly reduced hyperglycaemia-induced increases in malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. Further mechanistic studies revealed that DZ substantially enhanced the expression of Nrf2, NOQ1 and HO-1, which indicated that DZ exerts potential antioxidant effects against testicular tissue damage via the activation of Nrf2. In conclusion, the protective effects of DZ rely on repairing the integrity of the BTB and on reducing oxidative stress damage by mediating ZO-1 and Nrf2. The study contributes to discovering the DZ possible mechanism of action.

Baicalin Attenuates High Fat Diet-Induced Obesity and Liver Dysfunction: Dose-Response and Potential Role of CaMKKß/AMPK/ACC Pathway.

BACKGROUND/AIMS: Obesity-associated fatty liver disease affects millions of individuals. This study aimed to evaluate the therapeutic effects of baicalin to treat obesity and fatty liver in high fat diet-induced obese mice, and to study the potential molecular mechanisms. METHODS: High fat diet-induced obese animals were treated with different doses of baicalin (100, 200 and 400 mg/kg/d). Whole body, fat pad and liver were weighed. Hyperlipidemia, liver steatosis, liver function, and hepatic Ca(2+)/CaM-dependent protein kinase kinase ß (CaMKKß) / AMP-activated protein kinase (AMPK) / acetyl-CoA carboxylase (ACC) were further evaluated. RESULTS: Baicalin significantly decreased liver, epididymal fat and body weights in high fat diet-fed mice, which were associated with decreased serum levels of triglycerides, total cholesterol, LDL, alanine transaminase and aspartate transaminase, but increased serum HDL level. Pathological analysis revealed baicalin dose-dependently decreased the degree of hepatic steatosis, with predominantly diminished macrovesicular steatosis at lower dose but both macrovesicular and microvesicular steatoses at higher dose of baicalin. Baicalin dose-dependently inhibited hepatic CaMKKß/AMPK/ACC pathway. CONCLUSION: These data suggest that baicalin up to 400 mg/kg/d is safe and able to decrease the degree of obesity and fatty liver diseases. Hepatic CaMKKß/AMPK/ACC pathway may mediate the therapeutic effects of baicalin in high fat diet animal model.

Dioscorea zingiberensis ameliorates diabetic nephropathy by inhibiting NLRP3 inflammasome and curbing the expression of p66Shc in high-fat diet/streptozotocin-induced diabetic mice.

OBJECTIVES: Diabetic nephropathy (DN) is a severe diabetic complication. Dioscorea zingiberensis (DZ) possesses excellent pharmacological properties with lower toxicity. The purpose of this study was to investigate the efficacy and mechanism of DZ in DN. METHODS: DN was established by the high-fat diet combining intraperitoneal injection of streptozotocin in mice. The DZ (125 and 250 mg/kg/day) were intragastrical administered for 8 consecutive weeks. After treatment, blood, urine and kidney tissue were collected for biological detection, renal morphology, fibrosis and molecular mechanism research, respectively. KEY FINDINGS: This study has shown that DZ significantly ameliorated kidney hypertrophy, renal structural damage and abnormal function of the kidney indicators (creatinine, urinary protein and blood urea nitrogen). Further molecular mechanism data suggested that the NLRP3/Cleaved-caspase-1 signal pathway was remarkably activated in DN, and DZ treatment reversed these changes, which indicated that it effectively attenuated inflammatory response caused by hyperglycaemia. In addition, DN inhibits hyperglycaemia-induced activation of oxidative stress by suppressing the expression of p66Shc proteins. CONCLUSIONS: DZ could efficiently suppress oxidative stress and inflammatory responses to postpone the development of DN, and its mechanism might be related to inhibition of NLRP3 and p66Shc activities. Thus, DZ could be developed into a new therapeutic agent for DN.

Baicalin attenuates high fat diet-induced insulin resistance and ectopic fat storage in skeletal muscle, through modulating the protein kinase B/Glycogen synthase kinase 3 beta pathway.

Insulin resistance is the pathophysiological basis of many diseases. Overcoming early insulin resistance highly significant in prevention diabetes, non-alcoholic fatty liver, and atherosclerosis. The present study aimed at evaluating the therapeutic effects of baicalin on insulin resistance and skeletal muscle ectopic fat storage in high fat diet-induced mice, and exploring the potential molecular mechanisms. Insulin resistance in mice was induced with a high fat diet for 16 weeks. Animals were then treated with three different doses of baicalin (100, 200, and 400 mg·kg(-1)·d(-1)) for 14 weeks. Fasting blood glucose, fasting serum insulin, glucose tolerance test (GTT), insulin tolerance test (ITT), and skeletal muscle lipid deposition were measured. Additionally, the AMP-activated protein kinase/acetyl-CoA carboxylase and protein kinase B/Glycogen synthase kinase 3 beta pathways in skeletal muscle were further evaluated. Baicalin significantly reduced the levels of fasting blood glucose and fasting serum insulin and attenuated high fat diet induced glucose tolerance and insulin tolerance. Moreover, insulin resistance was significantly reversed. Pathological analysis revealed baicalin dose-dependently decreased the degree of the ectopic fat storage in skeletal muscle. The properties of baicalin were mediated, at least in part, by inhibition of the AMPK/ACC pathway, a key regulator of de novo lipogenesis and activation of the Akt/GSK-3ß pathway, a key regulator of Glycogen synthesis. These data suggest that baicalin, at dose up to 400 mg·kg(-1)·d(-1), is safe and able to attenuate insulin resistance and skeletal muscle ectopic fat storage, through modulating the skeletal muscle AMPK/ACC pathway and Akt/GSK-3ß pathway.