Comparison of efficacy of SHENQI compound and rosiglitazone in the treatment of diabetic vasculopathy analyzing multi-factor mediated disease-causing modules

Abstract

Atherosclerosis-predominant vasculopathy is a common complication of diabetes with high morbidity and high mortality, which is ruining the patient's daily life. As is known to all, traditional Chinese medicine (TCM) SHENQI compound and western medicine rosiglitazone play an important role in the treatment of diabetes. In particular, SHENQI compound has a significant inhibitory effect on vascular lesions. Here, to explore and compare the therapeutic mechanism of SHENQI compound and rosiglitazone on diabetic vasculopathy, we first built 7 groups of mouse models. The behavioral, physiological and pathological morphological characteristics of these mice showed that SHENQI compound has a more comprehensive curative effect than rosiglitazone and has a stronger inhibitory effect on vascular lesions. While rosiglitazone has a more effective but no significant effect on hypoglycemic. Further, based on the gene expression of mice in each group, we performed differential expression analysis. The functional enrichment analysis of these differentially expressed genes (DEGs) revealed the potential pathogenesis and treatment mechanisms of diabetic angiopathy. In addition, we found that SHENQI compound mainly exerts comprehensive effects by regulating MCM8, IRF7, CDK7, NEDD4L by pivot regulator analysis, while rosiglitazone can rapidly lower blood glucose levels by targeting PSMD3, UBA52. Except that, we also identified some pivot TFs and ncRNAs for these potential disease-causing DEG modules, which may the mediators bridging drugs and modules. Finally, similar to pivot regulator analysis, we also identified the regulation of some drugs (e.g. bumetanide, disopyramide and glyburide etc.) which have been shown to have a certain effect on diabetes or diabetic angiopathy, proofing the scientific and objectivity of this study. Overall, this study not only provides an in-depth comparison of the efficacy of SHENQI compound and rosiglitazone in the treatment of diabetic vasculopathy, but also provides clinicians and drug designers with valuable theoretical guidance.

Traditional Chinese medicine Shenqi compound to improve lower extremity atherosclerosis of patients with type 2 diabetes by affecting blood glucose fluctuation

“…Previous research by the research group has confirmed that Shenqi compound can regulate glucose and lipid metabolism disorders, improve vascular function, and effectively prevent and treat diabetic vascular disease. [ 9 ] In 2015, the National Natural Science Foundation of China (No. 81503566) [ 10 ] found that it can regulate serum insulin level, inhibit mTOR activation and autophagy, and regulate the circadian clock Id2 and Usp2 genes of the pancreatic tissue to stabilize blood glucose.…”

Key circRNAs, lncRNAs, and mRNAs of ShenQi Compound in protecting vascular endothelial cells from high glucose identified by whole transcriptome sequencing

“…The Metformin group received 0.1 g/kg/d metformin, whereas the Model and Control groups received an equal volume of sterile water. All rats were fed standard rodent water during the entire experimental period.SQC concentrations, doses, routes, and frequencies were determined based on our previous [29][30][31]. All groups were assured that the same volume (5.0 ml/kg/d) of medication was given daily.…”

“…DC., Di Huang, DH), Salviae Miltiorrhizae Radix et Rhizoma (Salvia miltiorrhiza Bunge, Dan Shen, DS), Radix Trichosanthis (Trichosanthes baviensis Gagnep.,Tian Hua Fen, THF) and Rhei Radix et Rhizoma (Rheum o cinale Baill., Da Huang, DH), with a dose proportion of 15:15:10:10:10:10:10:6. Several previous studies have shown the prevention and treatment of SQC for diabetic vascular complications [28,29], and the underlying mechanisms may be associated with oxidative stress and cell apoptosis. However, there are still signi cant gaps in our knowledge of how ncRNAs affect SQC's ability to protect VEC from excessive glucose.…”

Network Pharmacology‐Based Identification of the Mechanisms of Shen‐Qi Compound Formula in Treating Diabetes Mellitus

“…Regarding the mechanism, in the above clinical studies, SQC was seen to be able to improve outcomes such as superoxide dismutase (SOD), nitric oxide (NO), reactive oxygen species (ROS), malondialdehyde (MDA), total antioxidant capacity (T-AOC), and glucose like peptide-1. Animal experiments showed that the mechanisms might be related to inhibiting adiponectin, reducing the inflammation and other mechanisms [14,15]. However, due to the complexity of its components, its comprehensive mechanisms have not yet been fully elucidated.…”