Protective effect of gossypin against high-fat diet-induced atherosclerosis in rats: Role of the phosphoinositide 3-kinase/AKT/mechanistic target of rapamycin pathway and gut microbiota

BACKGROUND: Over the last decade, there has been a global prevalence of high morbidity and mortality associated with atherosclerotic disease. Gossypin exhibits the anti-inflammatory and protective effect against various disease. The current protocol demonstrated the antiatherosclerotic effect of gossypin against high-fat diet (HFD)-induced atherosclerosis (AS) in rats and explored the underlying mechanism. MATERIALS AND METHODS: HFD and Vitamin D3 (600,000 IU/kg) were used to induce AS in rats, and the rats were treated with different doses of gossypin and rosuvastatin, respectively. Body weight, organ weights, inflammatory, cardiac, and lipid parameters, as well as micro-RNA (mRNA) expression, were estimated. The rat faces were collected for the determination of gut microbiota. RESULTS: Gossypin treatment markedly reduced body weight and altered organ weights. Gossypin treatment Remarkably modulated the level of cardiac parameters such as creatine kinase (CK), CK myocardial band, lactate dehydrogenase, cardiac troponin I, thromboxane B2, endothelin-1; lipid parameters such as total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), very LDL, TC/HDL, TG/HDL, free fatty acid; hepatic parameters, namely, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase; inflammatory parameters such as cyclooxygenase-2, inducible nitric oxide synthetase, C-reactive protein, prostaglandin E2, nuclear factor kappa-B (NF-κB); inflammatory cytokines include interleukin (IL)-1β, 6, 5, 10, 17, tumor necrosis factor-α (TNF-α), C-X-C Motif chemokine ligand 1 (CXCL1), respectively. Gossypin treatment also altered the mRNA expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, ATP-binding cassette transporter A1 (ABCA-1), liver X receptor-α, peroxisome proliferator-activated receptor-γ, toll-like receptor 4 (TLR4), NOD-like receptor family pyrin domain containing 3, NF-κBp65, myeloid differentiation primary response 88, IL-1 β, IL-6, IL-17, TNF-α, phosphorylated AMP-activated protein kinase, phosphorylated mechanistic target of rapamycin (p-mTOR), phosphorylated phosphoinositide 3-kinase (p-PI3K), and phosphorylated protein kinase B (p-AKT), respectively. Gossypin treatment remarkably modulated the abundance of Firmicutes, Bacteroidetes, F/B ratio, deferribacteraceae and cyanobacteria. CONCLUSION: Gossypin exhibited the anti-AS effect through alteration of PI3K/AKT/mTOR signaling pathway and gut microbiota.