Immunomodulatory and Metabolic Effects of Ginsenosides Rg1/Rb1 in IBD, RA, and MASLD: Targeting Gut Microbiota–Autoimmunity Axis

Abstract

Panax ginseng Meyer has been commonly used as a traditional herbal medicine in East Asia for millennia. Ginsenosides Rg1 and Rb1 are the primary pharmacologically active ingredients and exhibit broad therapeutic efficacy against immunometabolic disorders, including inflammatory bowel disease (IBD), metabolic dysfunction-associated steatotic liver disease (MASLD), and rheumatoid arthritis (RA). To summarize the protective roles of these ginsenosides and investigate their underlying mechanisms, we integrated literature evidence with network pharmacology and gut microbiota–host gene association analyses. Published experimental studies have identified multiple mechanisms by which Rg1 and Rb1 ameliorate IBD, MASLD, and RA, including modulation of the phosphoinositide 3-kinase (PI3K)/Akt, AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor γ (PPARγ)/nuclear factor kappa-B (NF-κB) pathways, as well as direct toll-like receptor 4 (TLR4) binding and aryl hydrocarbon receptor (AHR)-mediated transcriptional regulation. Our network pharmacology analysis predicted target overlap among IBD, MASLD, and RA, prioritizing TNF, NFKB1, PPARG, and MAPK1 as putative hubs. Our gut microbiota–host gene association analysis identified conserved microbial taxa sharing host gene targets with Rg1 and Rb1, such as Akkermansia and Faecalibacterium. Integrating these computational findings with published evidence, we propose that ginsenoside-associated shifts in these taxa may be linked to modulation of host signaling pathways, though causal relationships require experimental validation. This review summarizes the convergent mechanisms of Rg1 and Rb1 in ameliorating barrier-immunity-metabolism dysfunction across the gut-liver-joint axis. We also highlight the translational gap between preclinical research and clinical practice. This integrated analysis provides a novel research paradigm for understanding Rg1 and Rb1 as multi-target therapeutics for complex immunometabolic diseases.