Effects of Silymarin Combined with Herbal Medicine on Th17/Treg Cell Imbalance and Inflammatory Response in Patients with Nonalcoholic Fatty Liver Disease: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Background: Nonalcoholic fatty liver disease (NAFLD), recently reclassified as metabolic dysfunction-associated steatotic liver disease (MASLD), is a globally prevalent chronic liver condition with a poor prognosis if it progresses to nonalcoholic steatohepatitis (NASH). Silymarin, a flavonoid complex derived from Silybum marianum, exhibits anti-inflammatory and hepatoprotective properties. However, limited research exists on its combined use with traditional Chinese medicines (TCMs), such as Pueraria lobata, Salvia miltiorrhiza, and Schisandra chinensis, for NAFLD treatment. Objectives: The present study aimed to evaluate the therapeutic effects of silymarin combined with TCM and silymarin alone in patients with NAFLD. Methods: In this randomized, double-blind, placebo-controlled trial, 94 NAFLD patients were allocated to three groups: Silymarin + TCM (n = 32), silymarin alone (n = 31), or placebo (n = 31) for 12 weeks. Primary outcomes included liver enzyme levels and lipid profiles. Secondary outcomes comprised Th17/Treg cell ratios in peripheral blood and mRNA expression of NLRP3 inflammasome-related genes in peripheral blood mononuclear cells (PBMCs). Results: After 12 weeks, the silymarin + TCM group showed a 48.01% reduction in serum interleukin (IL)-18 (P < 0.05), decreased Th17 cell proportions (P < 0.05), and a reduced Th17/Treg ratio (P < 0.01). Both silymarin + TCM and silymarin alone significantly downregulated mRNA expression of NLRP3 (P < 0.01, P < 0.05), CASP1 (P < 0.001, P < 0.01), and IL1B (P < 0.001, P < 0.05) in PBMCs. IL18 mRNA expression was notably lower in the silymarin + TCM group compared to the placebo group (P < 0.01). Conclusions: The combination of silymarin with P. lobata, S. miltiorrhiza, and S. chinensis modulates Th17/Treg balance and suppresses NLRP3 inflammasome activation, potentially attenuating inflammatory progression in NAFLD. This regimen offers a safe and cost-effective therapeutic strategy for NAFLD management.