基于网络药理学的肿节风治疗前列腺癌的作用机制探讨

目的利用网络药理学方法探讨肿节风治疗前列腺癌的可能作用机制。方法通过TCMSP、Uniprot、GeneCards在线数据库筛选肿节风活性化合物治疗前列腺癌的潜在靶点,利用Cytoscape软件构建前列腺癌-肿节风-靶点网络图,然后结合STRING数据库和Cytoscape软件构建蛋白质相互作用网络;最后利用R软件对靶点进行GO分类富集分析和KEGG通路富集分析,预测其作用机制,并构建靶点通路网络。结果从肿节风中筛选出活性成分10个,其与前列腺癌共同作用靶点170个,GO功能分析发现靶点主要与膜伐、对氧水平、泛素样蛋白连接酶结合等有关。KEGG通路分析发现肿节风治疗前列腺癌主要与糖尿病并发症中的AGE-RAGE信号通路、前列腺癌(PCa)、流体剪切应力(FSS)与动脉粥样硬化(AS)等通路密切相关。结论肿节风活性成分可能通过多靶点、多通路达到治疗及辅助治疗前列腺癌的目的。     

Protocatechuic acid improves hepatic insulin resistance and restores vascular oxidative status in type-2 diabetic rats

This work explored influences of protocatechuic acid (PCA) on type 2 diabetes (T2D)-associated hepatic insulin resistance and other metabolic, hepatic and vascular irregularities using the rat model of high fat diet (HFD)+high fructose+low dose streptozotocin (STZ).Twenty-four male Wister rats were used. Twelve rats were ad libitum supplied with HFD and high fructose drinking water (25 % w/v) for 60 days. On day 30, they received a single injection of STZ (35 mg/kg, i.p). On day 32, they were divided into two subgroups (n = 6/each): T2D + PCA, received PCA (100 mg/kg/day, orally) and T2D, received PCA vehicle till the end of experiment. Rats provided with regular diet and fructose-free drinking water, with or without PCA treatment, served as PCA and control groups (n = 6/each), respectively.PCA treatment significantly reduced the elevated levels of fasting glycemia and insulin, AUC_OGTT, AUC_ITT, and HOMA-IR index, while it boosted HOMA-β and insulinogenic index values in T2D rats. PCA ameliorated serum lipid levels and hepatic function parameters and mitigated hepatosteatosis in T2D rats. Mechanistically, PCA mitigated hepatic lipid peroxidation and restored reduced glutathione (GSH) and superoxide dismutase (SOD) to near-normal levels. Moreover, PCA enhanced hepatic protein levels of P-AKT_ser473 and hepatic mRNA expression of insulin receptor substrate 1 (IRS1), phosphatidylinositol 3 kinase (PI3K)-p85 and AKT2.Furthermore, PCA ameliorated aortic oxidative stress in T2D rats, possibly via reducing serum levels of advanced glycation end products (AGEs) and diminishing vascular expression of RAGE and NOX4 mRNA.Collectively, PCA may improve hepatic insulin resistance and vascular oxidative status by modulating IRS1/PI3K/AKT2 and AGE-RAGE-NOX4 pathways, respectively.