![]() ![]() Workflow of the systematic strategies to elucidate the mechanisms of RC in the treatment of DN. Therefore, in this study, the effect of RC on DN and its protective mechanism were probed using network pharmacology analysis and relevant animal experiments (see Figure 1). To date, the network pharmacology about the effect of RC on DN has not been reported yet. This analysis of complex network is helpful to discover the relationship among multitarget drugs, drug combinations, and their signal pathways. The network pharmacology is very suitable for the mechanism study of TCM. ![]() In order to get over the defects, in the current study, we used the existing data in the database to establish a pharmacological network and to analyse the connections between active ingredients of both reagents and potential targets of the disease. Long clinic practice in TCM attests that coadministration of Radix Rehmanniae and Corni Fructus (RC) achieves better curative efficacy to ameliorate DN than treatment with either reagent, while the mechanism remains unclear.Īs well all know, it is difficult to clarify the specific pharmacological mechanism of TCM for their multicomponent and multitarget characteristics. Besides, Radix Rehmanniae (RR) can inhibit the progression of DN by reducing blood glucose, urea nitrogen, and 5-hydroxy methyl furfural levels. For example, iridoid glycosides and polyphenols extracted from Corni Fructus (CF) can significantly improve the metabolic parameters of diabetic renal damage. Increasing evidence in experimental and clinical studies show that Traditional Chinese Medicine (TCM) herbs play an efficacious effect on diabetes mellitus. Therefore, looking for novel ways to treat DN is urgently needed. However, some patients with DN are unsuitable for the treatment with ACE inhibitors as who meet side-effects of these medicines, such as low blood pressure and low cardiac oxygen demand. Angiotensin-converting enzyme (ACE) inhibitors are used to reduce proteinuria levels and to restrain the progress of DN in clinics. At present, the treatment strategy for this complication is mainly focused on controlling blood glucose levels and inhibiting the renin-angiotensin system (RAS). The pathological hallmarks of DN are proliferating mesangial cells, thickening basement membranes, injured glomerular, and tubular cells, leading to microalbuminuria. Introductionĭiabetic nephropathy (DN) is a refractory chronic microvascular complication of diabetic mellitus, resulting in end-stage renal disease (ESRD) eventually. The administratiom of RC might remit the DM-induced renal damage through the AGE-RAGE signaling pathway to improve metabolic parameters and protect renal structure and function. The results revealed the relationship between multicomponents and multitargets of RC. ![]() The animal experiments revealed that RC significantly improved metabolic parameters, inflammation renal structure, and function to protect the kidney against DN. The pathway enrichment analysis showed that RC regulated advanced glycosylation end product (AGE-) RAGE and IL-17 signaling pathways to treat DN. ![]() In this study, 29 active compounds from RC and 64 key targets related to DN were collected using the network pharmacology method. The therapeutic effects of RC active compounds and their key signal pathways were preliminarily probed via network pharmacology analysis and animal experiments. Gene ontology (GO) analysis was performed to realize the key targets of RC, and an active compound-potential target network was created. The active compounds of RC were screened by oral bioavailability (OB) and drug-likeness (DL). The information about RC was obtained from a public database. But the mechanism of how RC plays the therapeutic role against DN is unclear as yet. Radix Rehmanniae and Corni Fructus (RC) have been widely applied to treat diabetic nephropathy (DN) for centuries. ![]()
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