The Anti-inflammatory and Anti-apoptotic Role of Crocin against Expression of MMp-9, TIMP-1, MCP-1, Caspase-3, PPARα in Heart Tissue, and Metamorphoses of MicroRNA 188 in Hyperhomocysteinemic Rats

Abstract

Crocin (a water-soluble carotenoid) is the most abundant antioxidant among active constituents of Crocus sativus. Crocin has protective effects on brain, skeletal muscle, and kidney ischemia-reperfusion injury models via its antioxidant properties. The protective and anti-inflammatory effect of crocin against L-methionine-induced hyperhomocysteinemia (HHcy) in rats was evaluated. Thirty male albino rats were divided into three equal groups. Group I (control normal): rats fed ordinary diet without any treatment. Group II (L-methionine-induced HHcy): rats received L-methionine (1.7 g/kg body weight/day) orally for 8 weeks continuously. Group III (HHcy 1 crocin): rats received crocin in dose (50 mg/kg body weight/day, I.P.) for 4 weeks after induction of HHcy. The results obtained showed a significant increase in serum Hcy concentration and upregulation of NF-kβ gene expression in liver tissue and also in the gene expression level of TIMP-1, MMp-9, MCP-1, Caspase-3, and PPARα in heart tissues with significant downregulation of serum miRNA188 gene expression level in hyperhomocysteinemic (HHcy) rats. However, crocin treatment to HHcy induced in rats significantly improved all previous indicators to its normal ranges. The histopathological findings revealed that crocin treatment markedly reduced the HHcy-induced pathological changes and displayed marked improvement with normal histological architecture of the heart and brain tissues. These results suggested that crocin had a potentially ameliorating role with powerful anti-inflammatory and anti-apoptotic effects on cardiac tissue, as revealed by suppression of proinflammatory mediators and secretion through inhibition of NF-kB signaling pathways, which may lead to upregulated miR-188 gene expression, suppress proapoptotic Caspase-3, and may protect from heart tissue injury against HHcy.

Crocins for Ischemic Stroke: A Review of Current Evidence

“…In addition, it has been suggested that matrix MMPs activation plays a role in IS (Yang and Rosenberg, 2015) and amelioration of MMP-2 and MMP-9 expressions by CR may provide neuroprotection and protection of BBB functions under cerebral ischemia (Zhang et al, 2017b). The key inflammatory signaling molecules influenced by CR and related compounds include TNF-α, IL-1β, IL-1α, IL-6, IL-1, and MMP-9, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory proten-1α (MIP-1α), vascular adhesion molecule-1 (VCAM-1), E-selectin and fractalkine (CX3CL1) and related signaling pathways namely NFκB, MAPK, TLR4, c-Jun N-terminal kinase (JNK), and P38 (Che et al, 2001;Hussein et al, 2019;Barthels and Das, 2020). In addition, autophagy is another important cellular mechanism involved in various cellular functions (Shen et al, 2021), and is a significant adaptive mechanism in IS (Ajoolabady et al, 2021).…”