The Mitigatory Effect of Shen-Qi Compound on the Diabetic Thoracic Aortic Complications through Inhibiting the Inflammatory Microenvironment by miR-223-3p/RBP-J/IRF8 Axis

Abstract

Background. Disruption of the vascular immunological inflammatory microenvironment is linked to metabolic memory impairment. Even though it has been proven that the Shen-Qi compound (SQC) can efficiently halt metabolic memory and preserve vascular endothelial cells, extensive studies need to be done to investigate if it can also change the vascular immune-inflammatory microenvironment by regulating the immune system. This will help figure out the role of stopping metabolic memory. Methods. After 4 weeks on a high-fat diet (HFD), GK rats were used to create a model for diabetic thoracic aortic problems. The effect and mechanisms of SQC on diabetic thoracic aortic complications were assessed by hematoxylin-eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), biochemical analysis, terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), reverse transcription, real-time polymerase chain reaction (RT-qPCR), immunofluorescence (IF), western blot, and luciferase reporter assays. Results. SQC treatment ameliorates the HFD-induced pathological symptoms as well as the HFD-induced increased concentrations of fasting blood glucose (FBG), fasting insulin (FINS), total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C) and decreased concentrations of high-density lipoprotein cholesterol (HDL-C). Besides, SQC counteracted the HFD-induced average fluorescence intensity of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), as well as the concentrations of endothelin-1 (ET-1) and monocyte chemoattractant protein-1 (MCP-1), while rescuing the HFD-induced concentrations of nitric oxide (NO) and nitric oxide synthetase (NOS). Also, SQC decreases apoptosis and oxidative stress in rats with diabetic thoracic aortic complications. In addition, SQC facilitated the polarization of macrophages, stimulated the activation of dendritic cells, and regulated the inflammatory milieu in rats with diabetic thoracic aortic complications. Furthermore, SQC also modulated the miR-223-3p/RBP-J/IRF8 axis in the macrophages of rats with diabetic thoracic aortic complications. Conclusion. SQC ameliorated diabetic thoracic aortic complications through the regulation of apoptosis, oxidative stress, and inflammatory microenvironment mediating by the miR-223-3p/RBP-J/IRF8 axis.

High-Density Lipoprotein Is Located Alongside Insulin in the Islets of Langerhans of Normal and Rodent Models of Diabetes

“…Several studies have shown that Wistar rats fed on a high-fat diet for a prolonged period develop obesity, dyslipidemia and diabetes [ 33 ]. In another study, GK rats fed on HFD for four weeks developed diabetic thoracic aortic lesion [ 34 ]. However, it is also possible to find a non-obese, diabetic person.…”

Chinese herbal medicine Shenqi compound for early intervention in patients at high cardiovascular risk of type 2 diabetes mellitus: the protocol of a multicenter, randomized, double-blind, placebo-controlled trial

“…Clinical trials have shown that SQC has multiple regulatory benefits in treating diabetic patients by lowering blood glucose, regulating lipids, improving insulin resistance, regulating oxidative stress levels, and reducing carotid intima thickness ( 19 , 20 ). Further animal studies have shown that SQC can reduce glucose variability, ameliorate gut mucosal barrier damage, regulate gut microbiota and metabolites, protect pancreatic islet function in Goto-Kakizaki rats, and ameliorate vascular damage through mechanisms related to improved apoptosis, oxidative stress, and inflammatory microenvironment in the thoracic aorta ( 21 – 24 ). It also showed significant vasoprotective effects in diabetic mice and was superior to rosiglitazone ( 25 ).…”