Shenling Guchang prescription ameliorates intestinal barrier inflammation in gestational diabetes rats via TLR4/NF-κB pathway.

Abstract

Gestational diabetes mellitus (GDM) is linked to a greater risk of various maternal and fetal complications, including the possibility of long-term metabolic issues in offspring. Our initial research suggests that the Traditional Chinese Medicine formula, Shenling Guchang prescription (SLGP), may have an impact on the gut microbiota. However, the specific mechanisms through which it affects intestinal barrier inflammation in GDM are still not fully understood. This study explored SLGP's mechanisms in GDM. Firstly, network pharmacology predicted key bioactive constituents targeting toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB), guiding experimental design. Subsequently, the pregnant female rats were induced with GDM through intraperitoneal streptozotocin injection and then divided into control, model, metformin, and SLGP treatment groups. Blood samples were collected for ELISA analysis to measure levels of inflammatory markers, intestinal tissues were examined histologically using hematoxylin-eosin (HE) staining, and western blot analysis was conducted to evaluate TLR4 and NF-κB expression. Relative to control rats, model group animals exhibited significant increases in the levels of inflammatory markers (IL-1β, IL-6, TNF-α, TGF-β, CRP), as well as enhanced TLR4 and p-NF-κB p65 expression, along with intestinal histopathological changes. Treatment with SLGP notably reduced inflammatory markers and protein expression in the colonic tissue of GDM rats, leading to a decrease in histopathological damage. Overall, SLGP was found to modulate the TLR4/NF-κB pathway, resulting in enhancements in insulin resistance and a reduction in inflammatory responses in GDM rats, thereby providing protection for the intestines. This study demonstrates the potential therapeutic effectiveness of SLGP in addressing intestinal inflammation linked to GDM.