Protective effect of nimbolide against streptozotocin induced gestational diabetes mellitus in rats via alteration of inflammatory reaction, oxidative stress, and gut microbiota

Gestational diabetes mellitus (GDM) is a significant pregnancy-related condition, which showed effect on the development of fetal. Anti-inflammatory and antioxidant therapy commonly used for the treatment of GDM. Nimbolide already confirmed their anti-inflammatory and anti-oxidant effect against various animal disease model. Our objective in this research is to investigate the protective effect of nimbolide against STZ induced GDM and elucidate the mechanism.In this experimental study, pregnant female Wistar rats were used and STZ (40 mg/kg) was used to induce the GDM. Blood glucose level (BGL), body weight and plasma insulin were assessed at regular time (gestational day 0, 9, and 18). Water intake, food intake, fecal and urine output were also estimated. In the female rats, hemoglobin (Hb), glycalated hemoglobin (HbA1c), hepatic glycogen, fructosamine, adiponectin, leptin, lipid, antioxidant and inflammatory cytokines parameters were estimated. In the fetuses, the fetues weight, implementation loss, and fetal weight were estimated. At the completion of the protocol, biochemical parameters were calculated. Gut microbiota was estimated in end of the study.Nimbolide treatment significantly (p < .001) improved the fetuses level and suppressed the fetal weight and implantation loss. Nimbolide treatment significantly (p < .001) suppressed the BGL and enhanced the body weight, insulin level. Nimbolide treatment suppressed the water intake, food intake, urinary and fecal output. Nimbolide significantly (p < .001) suppressed the fructosamine, leptin and enhanced the adiponectin level. Nimbolide treatment significantly (p < .001) decreased the malonaldehyde (MDA) level and boosted the total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST) and catalase (CAT); suppressed the level of TNF-α, IL-1β, IL-6, and boosted the level of IL-10. Furthermore, nimbolide treatment reversed the gut microbiota alteration induced via STZ in female rats. At the phylum level, the Firmicutes and Bacteroidetes relative abundance was altered via nimbolide treatment. The ratio of F/B boosted in GDM group and nimbolide treatment significantly (p < .001) suppressed. Nimbolide considerably suppressed the firmicutes and enhanced the Bacteroidetes, CAG-352, Lacnospirace.Based on the findings, we may conclude that nimbolide protects the pregnant rats from GDM via alteration of inflammation, oxidative stress, and gut microbiota.