Pharmacological Effects of Bidirectional Solid-State Fermentation Product of Irpex lacteus and Panax notoginseng on Mice with Lupus Nephritis

Objectives: Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) and remains a critical challenge in clinical treatment. This study aimed to investigate the early-intervention effects and underlying mechanisms of Panax notoginseng fermented by Irpex lacteus (FS) in MRL/lpr mice with LN, to provide a theoretical basis for the medicinal development of FS and clinical intervention for LN. Methods: MRL/lpr mice were administered low-dose and high-dose FS for 8 consecutive weeks. Therapeutic efficacy of FS was systematically evaluated by detecting renal function indicators, autoantibody levels, and inflammatory factor expression. Meanwhile, Western blot (WB) was performed to detect the expression of key proteins in the renal PI3K/AKT/NF-κB signaling pathway, and 16S rRNA sequencing was used to analyze structural changes in intestinal microbiota. Results: Pharmacodynamic results revealed that, compared with the model group and raw Panax notoginseng group, high-dose FS significantly improved renal function in LN mice, reduced the levels of urine protein, creatinine, blood urea nitrogen, autoantibodies and inflammatory factors (p < 0.05). Observations from representative histological specimens suggested amelioration of renal pathological manifestations including glomerular proliferation, inflammatory infiltration and renal fibrosis. Mechanistic analyses revealed associations between FS treatment and reduced phosphorylation of proteins within the renal PI3K/AKT/NF-κB signaling pathway (p < 0.05), as well as partial shifts in gut-microbiota composition suggestive of improved intestinal microecology. Conclusions: FS exerts anti-inflammatory, immunomodulatory and renal-protective effects. Our observations suggest associations between FS treatment, altered PI3K/AKT/NF-κB pathway activity and shifts in gut-microbiota composition related to the gut–kidney axis. This study provides important theoretical and experimental evidence for the medicinal development of FS and targeted early-intervention strategies for lupus nephritis.