Lusianthridin Exerts Streptozotocin-Induced Gestational Diabetes Mellitus in Female Rats via Alteration of TLR4/MyD88/NF-κB Signaling Pathway.

Abstract

Gestational diabetes mellitus (GDM) is characterized via enhanced the glucose intolerance in the pregnant women, which further lead the expansion of gestational hypertension, hepatic damage, pre-eclampsia and renal damage. Lusianthridin is the active phytoconstituent of Dendrabium venustu and exhibited the antioxidant and anti-inflammatory effects. In this protocol, we examined the GDM protective effect of lusianthridin (LSD) against streptozotocin (STZ) induced GDM in the female rats. Single intraperitoneal injection of STZ (40 mg/kg) was used for the induction of diabetes in the pregnant female rats. The rats were orally treated with the LSD (10, 20 and 40 mg/kg, body weight) for 18 days and blood glucose level, body weight and plasma insulin were estimated at regular time intervals. at end of the study, fetal weight, placental weight, number of live and dead fetuses were estimated. The antioxidant, lipid and cytokines level were also estimated. GDM rats treated with LSD remarkably improved the body weight of female rats along with fetal weight and suppressed the placental weight. LSD enhanced the live fetuses and suppressed the dead fetuses with reduction of reduced the dead ratio. LSD considerably suppressed the glucose level and improved the insulin level and suppressed the HOMA-IR. LSD significantly (p < 0.001) increased the level of hemoglobin, glycogen and suppressed the level of glycalated hemoglobin. LSD significantly (p < 0.001) altered the level of lipid parameters and inflammatory cytokines. LSD altered the level of antioxidant parameters in the liver and pancreas tissue. LSD significantly (p < 0.001) decreased the mRNA expression of troll like receptor (TLR)4, myeloid differentiation primary response 88 (MyD88), Nuclear factor kappa B (NF-κB)p65 and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), respectively. The results suggest that LSD has a protective effect on GDM in female rats induced by STZ, possibly through reducing the activity of the TLR4/MyD88/NF-κB signaling pathway.