Inflammatory bowel disease (IBD) comprises ulcerative colitis (UC) and Crohn’s disease (CD), chronic immune-mediated disorders characterized by persistent intestinal inflammation, epithelial barrier disruption, and symptoms such as abdominal pain and bloody diarrhea. The etiology is multifactorial, involving genetics, immune dysregulation, environmental factors, and gut microbiome alterations. Global burden estimates and recent trends indicate rising incidence and prevalence, with substantial healthcare costs reported in high-income settings.
Conventional treatments—corticosteroids, aminosalicylates, immunosuppressants, biologics targeting TNF and integrins, cytokine inhibitors (IL-12/23, IL-23), JAK inhibitors, and S1P modulators—have improved disease control but are limited by adverse effects, incomplete response, immunogenicity, expense, and long-term safety concerns. Consequently, interest in alternative or adjunctive therapies with favorable safety profiles has increased. Ginseng, a traditional medicinal herb, and its principal bioactive class, ginsenosides, have been investigated in preclinical IBD models for anti-inflammatory, immunomodulatory, barrier-protective, and microbiota-modulating effects.
The review synthesized evidence from searches of PubMed, Scopus, Web of Science, and Google Scholar using combinations of terms including “ginseng,” “Panax species,” “ginsenosides,” “ginseng polysaccharides,” “bioactive compounds,” “IBD,” “Crohn’s disease,” “ulcerative colitis,” “colitis,” “inflammation,” “gut microbiota,” and “intestinal barrier.” Studies addressing IBD pathogenesis, ginseng chemistry, mechanisms of action, immune regulation, gut microbiota effects, and intestinal protection were selected and summarized to provide an overview of current knowledge and therapeutic potential.
Ginsenosides are saponin glycosides distributed throughout Panax species and vary by plant part and species. Structurally, they are glycosylated triterpenoids with a hydrophobic aglycone (≈30-carbon backbone) and one or more sugar moieties (glucose, rhamnose, xylose, arabinose) attached primarily at C-3, C-6, or C-20. Classification hinges on aglycone frameworks: the majority are dammarane-type saponins, subdivided into protopanaxadiol (PPD) and protopanaxatriol (PPT) groups; minor types include ocotillol- and oleanane-type ginsenosides. Representative examples include Rb1, Rg1, Rg3, Rh2, Re, Ro, and ocotillol derivatives. Structural variation—aglycone backbone and sugar chain composition—substantially influences pharmacological activity.
The intestinal mucosal barrier is a coordinated system of epithelial, microbial, chemical, and immune components that permits nutrient absorption while limiting pathogen and antigen entry. Disruption of barrier integrity increases permeability, facilitating translocation of luminal antigens and microbes into the mucosa and triggering immune activation. Pathogenesis of IBD involves epithelial barrier breakdown, dysregulated innate and adaptive immune responses, aberrant cytokine production and signaling pathway activation, and gut microbiota dysbiosis characterized by reduced short-chain fatty acid–producing bacteria and increased pro-inflammatory microbes. These events create a self-perpetuating cycle of chronic inflammation.
The intestinal epithelium is a single-cell layer composed of specialized cell types—absorptive enterocytes, goblet cells, Paneth cells, enteroendocrine cells, M cells, tuft cells—responsible for mucus secretion, antimicrobial peptide production, immune signaling, and barrier maintenance. Tight junctions, mucus layers, and antimicrobial peptides preserve barrier function. In IBD, altered tight junctions, increased IEC apoptosis, and dysfunctional epithelial differentiation increase permeability. Pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6, and IFN-γ exacerbate epithelial injury and permeability, facilitating microbial penetration and ongoing inflammation.
Dysregulated innate and adaptive immunity is central to IBD. Innate immune effectors include IECs, Paneth cells, macrophages, dendritic cells (DCs), neutrophils, monocytes, innate lymphoid cells (ILCs), and natural killer (NK) cells. In IBD, neutrophil accumulation and release of reactive oxygen species and extracellular traps contribute to epithelial damage and ulceration. NK cells demonstrate metabolic impairment yet elevated pro-inflammatory cytokine production. ILC subset imbalances (increased ILC1, decreased ILC3) alter cytokine milieus and barrier protection. DCs shift from tolerogenic CD103+ phenotypes toward pro-inflammatory states with increased TLR2/4 signaling, stimulating NF-κB and production of IL-12, IL-23, and TNF, thereby promoting Th1/Th17 responses. Macrophage polarization toward pro-inflammatory M1 phenotypes raises TNF-α, IL-6, IL-1β, and IL-23 levels, further driving adaptive immune activation. Adaptive T-cell subsets, including Th1, Th17, and cytotoxic CD8+ populations, contribute to epithelial injury through cytokine-mediated inflammation.
Preclinical in vitro and in vivo studies indicate that ginseng and ginsenosides may ameliorate experimental colitis through multiple mechanisms: inhibition of inflammatory signaling pathways (including NF-κB-related pathways), modulation of pro- and anti-inflammatory cytokine production, regulation of immune cell differentiation and activity, reinforcement of intestinal barrier function, and reshaping of the gut microbiota toward a more anti-inflammatory profile. Ginseng also contains polysaccharides, peptides, fatty acids, polyacetylenes, and gintonin, which may contribute to its biological activities. Historically used for diverse conditions, ginseng’s pharmacological profile supports investigation in inflammatory disorders.
Numerous experimental models—predominantly UC models—have reported protective effects of ginsenosides. Mechanistic findings across studies include decreased production of pro-inflammatory mediators, suppression of inflammatory signaling cascades, attenuation of immune cell–driven inflammation, enhancement of epithelial barrier markers, and partial restoration of beneficial gut microbiota taxa and metabolites (such as short-chain fatty acids). Table summaries in the source catalog preclinical agents, model systems, and proposed mechanisms. However, the source notes that most evidence pertains to UC models, and extrapolation to CD is limited.
Clinical evidence for ginseng and ginsenosides in human IBD is extremely limited. Key translational barriers identified include low oral bioavailability of many ginsenosides, inadequate intestinal uptake, and dependence on gut microbiota–mediated metabolism to generate active metabolites. Additional concerns are interindividual and interspecies pharmacokinetic variability, structural heterogeneity among ginsenosides, and product variability that can produce inconsistent therapeutic outcomes. The authors emphasize that improving ginsenoside bioavailability and addressing pharmacokinetic inconsistencies are critical priorities for future research. Well-designed clinical trials are needed to validate efficacy and safety in patients with IBD.
Ginseng and its principal bioactive compounds, ginsenosides, demonstrate multi-faceted anti-inflammatory and immunomodulatory effects in preclinical IBD models, particularly UC. These effects include modulation of inflammatory signaling, cytokine profiles, immune cell function, epithelial barrier integrity, and gut microbiota composition. Despite promising preclinical results, clinical translation is constrained by limited human data, low oral bioavailability, microbiota-dependent metabolism, and pharmacokinetic variability. Future research should prioritize strategies to enhance bioavailability and rigorous clinical evaluation to determine therapeutic utility in IBD. The source did not report specific clinical trial results or dosing recommendations.