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.

Effects of oxytocin and antagonist antidote atosiban on body weight and food intake of female mice, Mus musculus.

Growing evidence suggests that oxytocin (OT) plays an important factor for the control of food intake, body weight, and energy metabolism in human and non-human animals. It has reported previously, the downregulation in oxytocin receptors (OTRs) expression is linked with the development of obesity, but exogenous OT reverse body weight and food intake in obese animal model. It is important to know that, whether intraperitoneal administration crosses blood brain barrier. Therefore, in the present experiment, we study the impact of intraperitoneal administration of synthetic OT 0.0116 mg/kg and antagonist atosiban (OTA) 1 mg/kg on food intake, and body weight of female mice, Mus musculus for different duration i.e. 30, 60, and 90 days. In this study, it was observed that there was significant decrease (p<0.001, one-way analysis of variance [ANOVA]) in the body weight (BW), food intake, and gonadosmatic indices (GSI) after the intraperitoneal exposure of OT at dose 0.0116 mg/kg up to 90 days and inhibits via antagonist atosiban. These results indicates that intraperitoneal administration of OT can be used for treatment for longer duration without any side effects and maintains homeostasis in physiologic system regulates body weight and gonadal weight in female mice, which represent an important therapeutic tool for the obesity and metabolic disorder in female.

Oxytocin as a Potential Adjuvant Against COVID-19 Infection.

This study summarized the benefits of oxytocin in the attenuation of coronavirus disease (COVID-19) pathogenesis. The recent outbreak of COVID-19 has become a pandemic with 7,323,761 infected patients and has created a health emergency worldwide. On the basis of the clinical study, COVID-19 shows homology with other coronavirus pathogenesis, i.e., inflammation, oxidative stress, and hyperactivation of the immune system, resulting in cytokine storm and causing acute lung infection (ALI), acute respiratory distress syndrome (ARDS), and kidney dysfunction. Oxytocin is a peptide of nine amino acids and a well-known anti-inflammatory, anti-oxidant, and immune-modulator, which is protective against ALI/ARDS, nephrotoxicity, sepsis, and ischemia- reperfusion medical condition. Oxytocin is a neuromodulator, effective for stress, anxiety, social behavior, and depression, which may be helpful for better outcomes in patients with COVID-19. Significant data show that oxytocin can be useful in the treatment of COVID-19 pathogenesis. A direct application of OT in COVID-19 is unclear; however, its use in an experimental model and humans has continuously demonstrated its safety, and its use in patients with COVID-19 is predicted to be highly beneficial.

Effects of exogenous oxytocin and atosiban antagonist on GABA in different region of brain.

Gamma amino butyric acid (GABA) is the primary inhibitory neurotransmitter in the vertebral central nervous system. It functions by altering the membrane conductance of Cl- ions, maintaining the membrane potential close to the resting potential. The hormone oxytocin (OT) has a central action where it acts as a neuromodulatory peptide and exerts its action depending upon the distribution of OT receptors (OTR) in the target site. OTRs are G-protein-coupled receptors (GPCRs) comprising different subunits (Gq, Gi, and Gs). The G- protein isoforms have the ability to activate different pathways, but specific agonists and antagonists may show different affinities to OTRs, depending on the specific G-protein isoform to which they are coupled. It is well documented that OTR distribution varies with age and species and in regions of the brain. In this study, we attempted to observe the impact of OT and atosiban (OTA), an OT antagonist, on GABA levels in different regions of the brain. Study animals were exposed intraperitoneally (i.p.) to normal saline (0.89%), OT 0.0116 mg/kg, and OTA 1 mg/kg in different combinations, for 30days. It was observed that OT and OTA administration modulated GABA levels in different regions of brain, while normal saline had no effect. It may be due to OTR receptor expression in different regions of the brain. This is significant because region-specific expression of different receptors could be important in the development of new drugs targeting specific neuropsychiatric disorders.

Parthenium hysterophorus induced changes in neurotransmitter levels in mouse brain.

Parthenium hysterophorus (10 mg/0.1 ml/kg body weight) was administered daily to 20 adult male mice and levels of 5-hydroxytryptamine, noradrenaline and dopamine in total brain were quantified on days 31 and 61 after administration. All neurotransmitter levels were decreased significantly, with the effects more prominent in the later part of the experiment. The results suggest that Parthenium hysterophorus interferes in the functioning of the hypothalamo-hypophyseal axis by impairing the biogenic amine levels which may in turn affect the physiology of the peripheral endocrine glands.