Gedunin attenuates streptozotocin-induced diabetic hepatopathy in rats

Objective:To examine the hepatoprotective effects of gedunin in streptozotocin(STZ)-induced diabetic rats.Methods:Rats were divided into 4 groups:control,STZ,gedunin,and STZ+gedunin.Biochemical parameters for liver function and liver histology were studied.The molecular interaction of gedunin with the liver glucose transporters GLUT2 and SGLT1 was examined using AutoDock Vina.Results:Gedunin attenuated STZ-induced increase in the levels of aspartate transaminase,alanine transaminase,alkaline phosphatase,lactate dehydrogenase and gamma-glutamyl transferase in the serum and liver tissue,reduced lipid peroxidation,and enhanced antioxidant activity.Histopathological studies showed considerable restoration of liver architecture in gedunin-treated diabetic rats.In silico studies revealed stable binding of gedunin with GLUT2 and SGLT1.Conclusions:Gedunin exerts hepatoprotective effects in STZ-induced diabetic rats by reducing liver enzymatic activities and oxidative stress.Further studies are warranted to verify the mechanism of its hepatoprotective action.

Gedunin Degrades Aggregates of Mutant Huntingtin Protein and Intranuclear Inclusions via the Proteasomal Pathway in Neurons and Fibroblasts from Patients with Huntington’s Disease

Huntington's disease(HD) is a deadly neurodegenerative disease with abnormal expansion of CAG repeats in the huntingtin gene. Mutant Huntingtin protein(m HTT) forms abnormal aggregates and intranuclear inclusions in specific neurons, resulting in cell death. Here,we tested the ability of a natural heat-shock protein 90 inhibitor, Gedunin, to degrade transfected m HTT in Neuro-2 a cells and endogenous m HTT aggregates and intranuclear inclusions in both fibroblasts from HD patients and neurons derived from induced pluripotent stem cells from patients. Our data showed that Gedunin treatment degraded transfected m HTT in Neuro-2 a cells, endogenous m HTT aggregates and intranuclear inclusions in fibroblasts from HD patients, and in neurons derived from induced pluripotent stem cells from patients in a dose-and time-dependent manner, and its activity depended on the proteasomal pathway rather than the autophagy route. These findings also showed that although Gedunin degraded abnormal m HTT aggregates and intranuclear inclusions in cells from HD patient, it did not affect normal cells, thus providing a new perspective for using Gedunin to treat HD.

木果楝属柠檬苦素类似物及其生物活性的研究进展

木果楝属Xylocarpus植物中包含丰富的萜类、生物碱类、多酚类、黄酮类、甾体类等化学成分,其中具有广泛生物活性和多环体系的柠檬苦素类化合物是其最主要的次生代谢产物。柠檬苦素是一类具有独特结构的高度氧化的四降三萜类化合物,葛杜宁、andirobin、墨西哥内酯、phragmalin等多种结构类型的柠檬苦素及其类似物在木果楝属植物中普遍存在,具有抗肿瘤、抗病毒、抗氧化、镇痛、抗炎、抗焦虑、镇静、保护神经、改善睡眠等药理作用,还具有昆虫拒食、杀虫等生物活性。对2010—2021年报道的木果楝属216个柠檬苦素类化合物及其生物活性的研究进展进行综述,为丰富该类资源的新药开发提供思路。