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 Ca²⁺/CaM-dependent protein kinase kinase β (CaMKKβ) / 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 CaMKKβ/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 CaMKKβ/AMPK/ACC pathway may mediate the therapeutic effects of baicalin in high fat diet animal model.

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.

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.

Insulin resistance is a common pathophysiological basis of type 2 diabetes. Related studies have confirmed that high lipid environment can decrease insulin sensitivity in liver, fat and skeletal muscle. TBC1D1 was recently discovered as a member of the TBC1 Rab‐GTPase family, which involved in the regulation of glucose transport and highly expressed in skeletal muscle.The phosphorylation of TBC1D1 may play a key role in regulating insulin‐stimulated glucose transport. TBC1D1 Thr590 is match for the Akt recognition motifs. Akt may activate its downstream substrate TBC1D1 Thr590 phosphorylation, and trigger glucose transporter protein GLUT4 translocation to cell surface. Baicalin is a natural compound extracted from scutellaria root, which is a kind of flavonoids. It has been reported that baicalin can show improvement diabetic rats, and also increase the glucose uptake in fat cells. However ,the effect of baicalin on skeletal muscle less reported. The aim of our study was to identify whether the beneficial effects of baicalin are related to regulate the phosphorylation of Akt and TBC1D1 in skeletal muscle. Our study results showed that baicalin can improve blood lipid, reduce the fasting blood glucose and postprandial glucose tolerance, and simultaneously increase Akt and TBC1D1 phosphorylation in skeletal muscle. These data demonstrate for the first time that intervention with baicalin may improve insulin sensitivity in skeletal muscle, which is related in part to regulate Akt /TBC1D1 signaling pathway.