Ameliorative effects of gallic acid on GLUT-4 expression and insulin resistance in high fat diet-induced obesity animal model mice, Mus musculus.

Reduced activity of glucose transporter type 4 isoform (GLUT-4), an insulin-sensitive glucose transporter distributed on the adipocytes, is associated with impaired insulin signaling. Insulin resistance resulting from alteration in glucose transport is responsible for exacerbating the emergence of metabolic abnormalities. The present study aimed to investigate the effects of the antidote gallic acid (GA) on expression-related changes in GLUT-4 and insulin receptor substrate-1 (IRS-1) in the visceral adipose tissue and on the subsequent development of insulin resistance in a high-fat diet (HFD)-induced obesity animal model. Methods: Twenty-four female Swiss albino mice were used and separated into the following four groups (six animals in each group): control group (standard pellet diet), HFD group, (60% HFD), HFD + GA group (60% HFD and GA 50 mg/kg body weight for 60 days), and GA group (GA 50 mg/kg body weight for 60 days). The effect of HFD on serum glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL), low-density lipoprotein (LDL) cholesterol, and insulin was evaluated. Additionally, homeostasis model assessment for insulin resistance (HOMA-IR) and glucose tolerance test (GTT) was performed. The serum antioxidative profile, which comprises oxidative parameters (superoxide dismutase [SOD], catalase [CAT], and glutathione peroxidase [GPx]) was measured. The effectiveness of GA against HFD-induced alteration in GLUT-4 and IRS-1 expression was also evaluated. Results: The experimental group that fed on GA + HFD had improved levels of serum triglycerides (p˂0.001), cholesterol (p˂0.05), and LDL cholesterol. GA administration also significantly improved hyperinsulinemia and HOMA-IR index (p˂0.001) in HFD mice. GA improved GTT results (p˂0.05); activity of SOD, CAT, and GPx (p˂0.05); and upregulated mRNA expression of GLUT-4 and IRS-1(p˂0.05) in the visceral adipose tissue in the HFD + GA experimental group. Conclusion: A link exists between insulin resistance, GLUT-4, and IRS-1 expression in the adipose tissue, and the initiation of metabolic syndrome, a condition characterized by obesity. GA may promote insulin signaling, glucose uptake, and lipid metabolism in the adipose tissues by mitigating oxidative stress. GA can also be used to manage obesity-related comorbidities including type 2 diabetes and dyslipidemia. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01194-5.

Therapeutic Role of Phytophenol Gallic Acid for the Cure of COVID-19 Pathogenesis.

The SARS CoV-2 virus, the causative agent of COVID-19 uses the ACE-2 receptor of the host to penetrate and infect the cell, mainly in the pulmonary, renal, and cardiac tissues. The earlier reported Delta and the recent Omicron are the variants of concern. The mutations in the RBD region of spike protein are associated with increased RBD-ACE-2 receptor interaction. This binding affinity between spike protein and the receptor is greater in Omicron than in the Delta variant. Moreover, the Omicron variant has numerous hydrophobic amino acids in the RBD region of the spike protein, which maintain its structural integrity. Gallic acid is a phytophenol and shows high binding affinity toward the ACE-2 receptors, which may be helpful for better outcomes in the treatment of COVID-19 pathogenesis. In the present study, significant data were collected from different databases i.e., PubMed, Scopus, Science Direct, and Web of Science by using keywords like anti-oxidative, anti-inflammatory, and antimicrobial properties of gallic acid, in addition to receptor-based host cell interaction of SARS CoV-2 virus. The finding shows that gallic acid can reduce inflammation by attenuating NF-κB and MAPK signaling pathways to suppress the release of ICAM-1, a cell surface glycoprotein; various pro-inflammatory cytokines like TNF-α, IL 1-ß, IL-6, IL-10, and chemokines like CCL-2,5, CXCL-8 along with tissue infiltration by immune cells. The purpose of this review is to highlight the therapeutic potential of gallic acid in COVID-19 pathogenesis based on its strong anti-oxidative, anti-inflammatory, and anti- microbial properties.