Anti-hyperglycemic effect of NiO-sodium alginate-polyethylene glycol-crocin nanocomposite via attenuating TLR4/MyD88/NFκB signaling in gestational diabetes triggered rats

NiO-海藻酸钠-聚乙二醇-藏红花素纳米复合材料通过减弱TLR4/MyD88/NFκB信号通路发挥抗妊娠糖尿病大鼠高血糖作用

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Abstract

Crocin are a group of prominent apocarotenoid-derived pigments primarily produced in the stigmas of Crocus sativus and the fruits of Gardenia jasminoides, displaying significant pharmacological activities, such as anticancer, antioxidant, anti-diabetic, and anti-atherosclerosis effects. The bioavailability of crocin is limited; therefore, in this study, we developed a nanocomposite, NiO-SAG-PEG-Cr, and evaluated its potential to improve conditions associated with gestational diabetes. The formulated nanocomposite underwent characterization analysis and was further assessed for its anti-diabetic potency in gestational rats. Hyperglycemia was induced in the gestational rats using streptozotocin (STZ) injections, and they were treated with 10 µg/kg and 20 µg/kg of the formulated nanocomposite. The weight of the rats was monitored throughout the treatment. Fasting blood sugar levels and free fatty acids were quantified to evaluate the induction of gestational diabetes. Fetal weight and placental index were monitored to examine the effect of the nanocomposite on fetal health in GDM rats. Diabetic and lipid profile tests were conducted to assess the anti-glycemic and anti-cholesterolemic efficacy of the formulated nanocomposite in GDM rats. Antioxidant levels were measured to analyze the free radical scavenging capacity of the nanocomposite. Since inflammation-induced insulin resistance is a primary challenge in treating gestational diabetes, the impact of the formulated nanocomposite on inflammatory cytokines and TLR4/MyD88/NFκB signaling proteins was examined in GDM rats. Histological analysis of the pancreas was performed to measure the ameliorative effects of the formulated nanocomposite in GDM rats. Treatment with the NiO-SAG-PEG-Cr nanocomposite significantly suppressed glucose levels and enhanced insulin levels in GDM rats. It demonstrated anti-diabetic, anti-hypercholesterolemic, and antioxidant effects in these animals. Inflammatory cytokines were reduced, while the anti-inflammatory cytokine IL-10 was increased in the nanocomposite-treated GDM rats. The levels of TLR4/MyD88/NFκB signaling proteins were significantly decreased in the nanocomposite-treated rats. Additionally, the nanocomposite treatment alleviated hyperglycemia-induced hepatic, pancreatic, and nephrotic damage in GDM rats. Nanocomposite treatment positively impacted fetal health as well. Overall, our study results suggest that the formulated nanocomposite is a potent anti-diabetic agent that improves both maternal and fetal health in GDM rats.

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