Exploration of the Mechanisms of Bu-Yang-Huan-Wu Decoction in the Treatment of Diabetic Peripheral Neuropathy by Integrating of Serum Pharmacochemistry and Network Pharmacology.

Diabetic peripheral neuropathy (DPN) is a significant and frequent complication of diabetes. Bu-Yang-Huan-Wu Decoction (BHD) is a classic traditional Chinese herbal prescription that is commonly used in modern clinical practice for the effective treatment of DPN, but the underlying mechanism is not yet clearly defined. The chemical constituents of BHD were characterized by UPLC-Q-Orbitrap HR MS/MS, and a total of 101 chemical components were identified, including 30 components absorbed into blood. An interaction network of "compound-target-disease" interactions was constructed based on the compounds detected absorbed in blood and their corresponding targets of diabetic neuropathy acquired from disease gene databases, and the possible biological targets and potential signalling pathways of BHD were predicted via network pharmacology analysis. Subsequently, methylglyoxal-induced (MGO-induced) Schwann cells (SCs) were used to identify the active ingredients in blood components of BHD and verify the molecular mechanisms of BHD. Through network topological analysis, 30 shared targets strongly implicated in the anti-DPN effects of BHD were identifed. Combined network pharmacology and in vitro cellular analysis, we found that the active ingredient of BHD may treat DPN by modulating the AGEs/RAGE pathway. This study provides valuable evidence for future mechanistic studies and potential therapeutic applications for patients with DPN.

Effects of soy isoflavone supplementation on patients with diabetic nephropathy: a systematic review and meta-analysis of randomized controlled trials.

Diabetic nephropathy (DN) is a microvascular complication that is becoming a worldwide public health concern. The aim of this study was to assess the effects of dietary soy isoflavone intervention on renal function and metabolic syndrome markers in DN patients. Seven databases including Medline, the Cochrane Central Register of Controlled Trials, Science Direct, Web of Science, Embase, China National Knowledge Infrastructure, and WanFang were searched for controlled trials that assessed the effects of soy isoflavone treatment in DN patients. Finally, a total of 141 patients from 7 randomized controlled trials were included. The meta-analysis showed that dietary soy isoflavones significantly decreased 24-hour urine protein, C-reactive protein (CRP), blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and fasting blood glucose (FBG) in DN patients. The standard mean difference was -2.58 (95% CI: -3.94, -1.22; P = 0.0002) for 24-hour urine protein, -0.67 (95% CI: -0.94, -0.41; P < 0.00001) for BUN, -6.16 (95% CI: -9.02, -3.31; P < 0.0001) for CRP, -0.58 (95% CI: -0.83, -0.33; P < 0.00001) for TC, -0.41 (95% CI: -0.66, -0.16; P < 0.00001) for TG, -0.68 (95% CI: -0.94, -0.42; P < 0.00001) for LDL-C, and -0.39 (95% CI: -0.68, -0.10; P = 0.008) for FBG. Therefore, soy isoflavones may ameliorate DN by significantly decreasing 24-hour urine protein, BUN, CRP, TC, TG, LDL-C, and FBG.

Rapid screening of neuroprotective components from Huang-Lian-Jie-Du Decoction by living cell biospecific extraction coupled with HPLC-Q-Orbitrap-HRMS/MS analysis.

Huang-Lian-Jie-Du Decoction (HLJDD), a well-known traditional Chinese formulation, has been proved to exert neuroprotective effects, however, the bioactive components in HLJDD still remain to be elucidated. In the present study, a rapid and effective method involving live cell biospecific extraction and HPLC-Q-Orbitrap HRMS/MS was utilized to rapidly screen and identify the neuroprotective compounds from the HLJDD crude extract directly. Firstly, sixteen principal components in HLJDD crude extract were identified by HPLC-Q-Orbitrap HRMS/MS analysis. After co-incubation with PC12 cells, which have been validated as the key target cells for neurodegenerative diseases, seven compounds of them were demonstrated to exhibit binding affinity to the target cells. Furthermore, three representative compounds named baicalin, wogonoside, and berberine were subsequently verified to exert cytoprotective effects on PC12 cells injured by hydrogen peroxide via inhibiting oxidative stress and cell apoptosis, indicating that these screened compounds may possess a potential for the treatment of neurodegenerative diseases and were responsible, in part at least, for the neuroprotective beneficial effects of HLJDD. Taken together, our study provides evidence that live cell biospecific extraction coupled with LC-HRMS/MS technique is an efficient method for rapid screening potential bioactive components in traditional Chinese medicines.