The pathogenesis of type 2 diabetes mellitus (T2DM) is very complicated. The currently well-accepted etiology is the “Ominous Octet” theory proposed by Professor Defronzo. Since presently used drugs for T2DM have limitations and harmful side effects, studies regarding alternative treatments are being conducted. Analyzing the pharmacological mechanism of biomolecules in view of pathogenesis is an effective way to assess new drugs. Sphingosine 1 phosphate (S1P), an endogenous lipid substance in the human body, has attracted increasing attention in the T2DM research field. This article reviews recent study updates of S1P, summarizing its effects on T2DM with respect to pathogenesis, promoting β cell proliferation and inhibiting apoptosis, reducing insulin resistance, protecting the liver and pancreas from lipotoxic damage, improving intestinal incretin effects, lowering basal glucagon levels, etc. With increasing research, S1P may help treat and prevent T2DM in the future.

Background . Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus and is a major cause of end-stage kidney disease. Cordyceps sinensis (Cordyceps, Dong Chong Xia Cao) is a widely applied ingredient for treating patients with DN in China, while the molecular mechanisms remain unclear. This study is aimed at revealing the therapeutic mechanisms of Cordyceps in DN by undertaking a network pharmacology analysis. Materials and Methods . In this study, active ingredients and associated target proteins of Cordyceps sinensis were obtained via Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Swiss Target Prediction platform, then reconfirmed by using PubChem databases. The collection of DN-related target genes was based on DisGeNET and GeneCards databases. A DN-Cordyceps common target interaction network was carried out via the STRING database, and the results were integrated and visualized by utilizing Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to determine the molecular mechanisms and therapeutic effects of Cordyceps on the treatment of DN. Results . Seven active ingredients were screened from Cordyceps, 293 putative target genes were identified, and 85 overlapping targets matched with DN were considered potential therapeutic targets, such as TNF, MAPK1, EGFR, ACE, and CASP3. The results of GO and KEGG analyses revealed that hub targets mainly participated in the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, PI3K-Akt signaling pathway, and IL-17 signaling pathway. These targets were correlated with inflammatory response, apoptosis, oxidative stress, insulin resistance, and other biological processes. Conclusions . Our study showed that Cordyceps is characterized as multicomponent, multitarget, and multichannel. Cordyceps may play a crucial role in the treatment of DN by targeting TNF, MAPK1, EGFR, ACE, and CASP3 signaling and involved in the inflammatory response, apoptosis, oxidative stress, and insulin resistance.