Equisetin is an anti-obesity candidate through targeting 11β-HSD1

Obesity is increasingly prevalent globally, searching for therapeutic agents acting on adipose tissue is of great importance. Equisetin (EQST), a meroterpenoid isolated from a marine sponge-derived fungus, has been reported to display antibacterial and antiviral activities. Here, we revealed that EQST displayed anti-obesity effects acting on adipose tissue through inhibiting adipogenesis in vitro and attenuating HFD-induced obesity in mice, doing so without affecting food intake, blood pressure or heart rate. We demonstrated that EQST inhibited the enzyme activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a therapeutic target of obesity in adipose tissue. Anti-obesity properties of EQST were all offset by applying excessive 11β-HSD1's substrates and 11β-HSD1 inhibition through knockdown in vitro or 11β-HSD1 knockout in vivo. In the 11β-HSD1 bypass model constructed by adding excess 11β-HSD1 products, EQST's anti-obesity effects disappeared. Furthermore, EQST directly bond to 11β-HSD1 protein and presented remarkable better intensity on 11β-HSD1 inhibition and better efficacy on anti-obesity than known 11β-HSD1 inhibitor. Therefore, EQST can be developed into anti-obesity candidate compound, and this study may provide more clues for developing higher effective 11β-HSD1 inhibitors.

Research progress on natural products with selective inhibition against 11β-HSD1 / 中草药

11β-Hydroxysteroid dehydrogenase (11β-HSD) is a metabolic enzyme of glucocorticoid. Growing evidence suggests that inhibiting over-expression of 11β-HSD1 and reducing partial effects of glucocorticoid could be the strategy to treat type 2 diabetes, as well as metabolic syndrome. Researching and developmenting selective 11β-HSD1 inhibitors may become a new direction. As natural products (NPs) have represented a cornerstone of pharmaceutical research, literatures on the development of natural products with selective inhibition against 11β-HSD1 published during the last 10 years were selected, and the inhibitors were classified according to the way how to find them. This paper will provide reference for the further research on the selective 11β-HSD1 inhibitors.

Study on the Potential Targets of Guizhi Decoction Regulating Ying and Wei Based on Reverse Molecular Docking Technology / 中国药房

OBJECTIVE:To study the potential targets of Guizhi decoction regulating Ying and Wei based oncorrespondence between formulation and syndromerelationship and reverse molecular docking technology. METHODS:Active ingredients related to Guizhi decoction were obtained by literature retrievals,and PharmMapper Server was used for reverse molecular docking for ac-tive ingredients. The potential receptors of Guizhi decoction were found on the basis of docking scores,then AutoDock Vina was conducted for positive molecular docking test to observe the affinity between the ligand and the receptor molecule. 75 rats were ran-domly divided into normal group,model group,Guizhi decoction high-dose,medium-dose,low-dose groups(12,8,4 g/kg),15 in each group. Except for normal group,rats in other groups were induced for models with disharmony between Ying and Wei. Af-ter modeling,rats were intragastrically administrated once a day,for 5 d. After administration,11β-HSD1 expression levels in adi-pose tissue and muscle tissue of rats were detected. RESULTS:Reverse molecular docking for active ingredients of Guizhi decoc-tion found that 11β-HSD1 was the frequent receptor,and positive docking test confirmed that uralsaponin b,glycyrrhetnic acid and carbenoxolone and so on had higher affinity with 11β-HSD1. Results of animal test showed,compared with normal group,11β-HSD1 expression levels in adipose tissue and muscle tissue in model group were increased (P<0.05);and compared with model group,11β-HSD1 expression levels in adipose tissue and muscle tissue in Guizhi decoction high-dose group were decreased (P<0.05). CONCLUSIONS:Guizhi decoction regulating Ying and Wei has certain correlation with 11β-HSD1,while the reverse molec-ular docking technology can provide a feasible technical way to studycorrespondence between formulation and syndromerelation-ship.

The role of 11β-HSD1 in metabolic syndrome / 中国糖尿病杂志

[Summary] MS ,which is highly related tothe occurrence of cardiovascular disease and T2DM ,is characterized by glucose and fat metabolic dysregulation ,central obesity ,hypertension and hyperuricemia.11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) is regarded as a new therapeutic target for MS.11β‐HSD1 converts inactive glucocorticoid to active glucocorticoid. 11β‐HSD1 knockout improves obesity , hyperlipidemia andhyperglycemia. The inhibition of 11β‐HSD1 alleviates IR in human and rodents ,but the application of 11β‐HSD1 inhibitors is limited by the side effects.

The effects of gossypol acetate on the morphological features and the gene expression in the bone tissues of the femoral head of Sprague-Dawley rat in vivo after treated with dexamethasone / 重庆医学

Objective To explore the effects of gossypol acetate on the morphological features and the gene expression in the femoral head of Sprague-Dawley rat in vivo after treated with dexamethasone .Methods Dexamethasone(Dex) was injected into the abdominal cavity of SD rats at an dose of 10 mg/kg ,twice a week ,and feed gossypol acetate 5 mg · kg -1 · d-1 .The controls re-ceived saline 2 mL injection .The treatment lasted for 12 and 20 weeks .The slices of the femoral head were made for HE and immu-nohistochemical study .The total mRNA was extracted for RT-PCR assessment .Results The cancellous bone trabecular became sparse ,trabecular bone area ratio decreased ,bone marrow fat tissue increased .These changes were fitted for pathological character of bone necrosis .The gossypol acetate could not affect the pathological changes .The proportion of the positive stained osteoblasts increased ,adipocytes decreased .PPARγ,C/EBPα,11β-HSD1 expression enhanced ,Runx2 down regulated in the treatment groups and GAA group .Conclusion Dex can induce evident pathological changes conform to the characters of femoral head necrosis .They may have closed correlation between 11β-HSD1 and the gene expression .But GAA could not affected the pathological changes and abnormality of the gene expression .

Effect of 11β-hydroxysteroid dehydrogenase type 1 gene silencing on glucose stimulated insulin secretion of pancreatic β cell line NIT-1 / 基础医学与临床

Objective To investigate the effect of small interference RNA (siRNA) targeting at 11β-hydroxysteroid dehydrogenase type 1 on the glucose-stimulated insulin secretion (GSIS) in pancreatic β cell line NIT-1 cell.Methods siRNA plasmid vectors specifically targeting at 11β-HSD1 gene were constructed,named as olig886,oligo866 and scrabble control for oligo886,then tansfected into NIT-1 cells.The expression of 11β-HSD1 was detected by RT-PCR and Western blot.O1igo886 vector was transfected into the NIT-1 cells in 25 mmol/L glucose concentrations medium.The insulin secretion level was measured in GSIS test.Results After treatment with 11β-HSD1 siRNA,the mRNA level of 11β-HSD1 in NIT-1 cell was decreased by 78.1%±2.9% and 51.7% ±2.7% inolig886 and oligo866 group respectively.The protein of 11β-HSD1 were decreased by 82.2% ±2.1% and 56.5%±2.0 % respectively.After transfected by olig 8 8 6 vector,the insulin secretion increased in NIT -1 cell.Conclusion 11β-HSD1 gene silencing may improve GSIS in NIT-1 cell 11β-HSD1 regulate local glucocorticoid metabolism in pan-creatic islet and affect the function of insulin secretion.