Work

Fermentation of ginsenoside Rb1 by a probiotic mixture alleviates atopic dermatitis via synergistic effects of rare ginsenoside F2 and gut microbiota-derived 12-ketolithocholic acid in mice

Year: 2026

Type: article

Abstract: Atopic Dermatitis (AD) is a chronic, relapsing inflammatory skin disorder with increasing global incidence. Emerging evidence highlights a strong association between AD and gut dysbiosis. In this context, compounds from Chinese herbal medicine (CHM), such as ginsenosides, have gained attention for their anti-inflammatory and immunomodulatory properties. However, the poor bioavailability of major ginsenosides limits their therapeutic effectiveness. Recent advances in probiotic-based herbal medicine fermentation suggest that, in addition to manipulation of gut dysbiosis, probiotics also show promising potential for enhancing the bioconversion of major ginsenosides into rare ginsenosides. The objective of this study was to determine whether probiotic-fermented ginsenoside Rb1 broth (Rb1FB) could alleviate 2,4-dinitrochlorobenzene (DNCB) atopic dermatitis-like disease and to investigate the associated gut–skin mechanisms. Rb1FB improved visible skin lesions and reduced dermatitis severity and significantly reduced epidermal thickening, dermal mast-cell infiltration, serum immunoglobulin E (IgE) and tumor necrosis factor-α (TNF-α) in AD mice. Rb1FB also increased gut microbial richness and diversity, enriched Bacteroides , increased fecal 12-ketolithocholic acid (12-KLCA), and enhanced systemic exposure to the rare ginsenoside F2. Therefore, the principal biological outcomes were improvements in the clinical-like, histopathological, allergic, and inflammatory features of AD, while the microbiome, metabolomic, and serum ginsenoside findings provided potential mechanistic explanations. Methods Probiotic strains Lactiplantibacillus plantarum DMU22441 , Lactobacillus acidophilus DMU22440 , and Lactiplantibacillus plantarum DMU22439 were screened for Rb1 utilization, and their fermentation conditions for maximum release of rare ginsenosides were optimized to prepare Rb1FB. A DNCB-induced AD mouse model was established to assess the therapeutic effects of Rb1FB. 16 S ribosomal RNA (rRNA) gene sequencing, metabolomics, transcriptomics and in vitro studies were employed to explore the mechanism of action. Results Rb1FB significantly alleviated AD symptoms in mice, reduced serum IgE and TNF-α levels, modulated the gut microbiota, and increased systemic exposure to the rare ginsenoside F2. In TNF-α-stimulated HaCaT cells, combined treatment with F2 and gut microbiota-associated 12-KLCA produced greater suppression of selected inflammatory genes than either treatment alone and was associated with reduced NUAK family kinase 2 (NUAK2). Conclusion Rb1FB modulates the gut microbiota and its metabolites, enhances rare ginsenoside absorption, and alleviates AD symptoms in mice. F2 and 12-KLCA produced an enhanced combined inhibitory effect on inflammatory responses in vitro. These findings support the therapeutic potential of probiotic-fermented ginsenoside Rb1 for AD.

Source: Journal of Ginseng Research

DOI: 10.1016/j.jgr.2026.101153