Glomerulonephritis refers to a group of disorders marked by glomerular inflammation and injury. Matrine, a herbal compound with well-documented anti-inflammatory properties, has been proposed as a potential therapeutic agent. This study aimed to verify the protective effects of matrine against glomerulonephritis in a cellular model, while exploring its associated molecular mechanisms. A glomerulonephritis cellular model was constructed by treating human glomerular mesangial cells (HGMCs) with lipopolysaccharide (LPS). The impacts of matrine on LPS-induced HGMC viability and inflammatory cytokine secretion were assessed via CCK-8 assay and enzyme-linked immunosorbent assay (ELISA), respectively. Western blotting was utilized to quantify protein expression levels of monocyte chemoattractant protein-1 (MCP-1)/C-C motif chemokine receptor 2 (CCR2), as well as key components of the pro-inflammatory toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway, in the LPS-challenged HGMCs. Complementary rescue experiments involving MCP-1 overexpression and CCR2 silencing were performed to validate the functional relationships within this axis. In LPS-induced HGMCs, the treatment of matrine (3 μM) restored the impaired viability and suppressed the production of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α). Furthermore, matrine downregulated the protein levels associated with the MCP-1/CCR2 and TLR4/NF-κB pathway. Notably, the beneficial effects of matrine were abolished upon overexpression of MCP-1. Conversely, silencing CCR2 effectively reversed the detrimental effects caused by MCP-1 overexpression in matrine-treated cells, thereby restoring the protective phenotype. This study demonstrates that matrine protects against LPS-induced damage in HGMCs in vitro by suppressing the MCP-1/CCR2 axis and the TLR4/NF-κB pathway. The rescue experiments confirm that CCR2 acts as a critical downstream effector of MCP-1 in mediating this protection.
Wei et al. (Sun,) studied this question.