Oxyberberine, a novel gut microbiota-mediated metabolite of berberine, possesses superior anti-colitis effect: Impact on intestinal epithelial barrier, gut microbiota profile and TLR4-MyD88-NF-κB pathway
Abstract
Berberine (BBR), a naturally-occurring isoquinoline alkaloid isolated from several Chinese herbal medicines, has been widely used for the treatment of dysentery and colitis. However, its blood concentration was less than 1 %, and intestinal microflora-mediated metabolites of BBR were considered to be the important material basis for the bioactivities of BBR. Here, we investigated the anti-colitis activity and potential mechanism of oxyberberine (OBB), a novel gut microbiota metabolite of BBR, in DSS-induced colitis mice. Balb/C mice treated with 3 % DSS in drinking water to induce acute colitis were orally administrated with OBB once daily for 8 days. Clinical symptoms were analyzed, and biological samples were collected for microscopic, immune-inflammation, intestinal barrier function, and gut microbiota analysis. Results showed that OBB significantly attenuated DSS-induced clinical manifestations, colon shortening and histological injury in the mice with colitis, which achieved similar therapeutic effect to azathioprine (AZA) and was superior to BBR. Furthermore, OBB remarkably ameliorated colonic inflammatory response and intestinal epithelial barrier dysfunction. OBB appreciably inhibited TLR4-MyD88-NF-κB signaling pathway through down-regulating the protein expressions of TLR4 and MyD88, inhibiting the phosphorylation of IκBα, and the translocation of NF-κB p65 from cytoplasm to nucleus. Moreover, OBB markedly modulated the gut dysbiosis induced by DSS and restored the dysbacteria to normal level. Taken together, the result for the first time revealed that OBB effectively improved DSS-induced experimental colitis, at least partly through maintaining the colonic integrity, inhibiting inflammation response, and modulating gut microflora profile.
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Astragaloside IV induced TJ protein expression by suppressing RhoA/NLRP3 inflammasome signaling pathways in a sepsis model.
“It was shown that a bioactive compound from Astragalus membranaceus, Astragaloside IV (AS-IV) induced TJ protein expression by suppressing RhoA/NLRP3 inflammasome signaling pathways in a sepsis model.197”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [197]
Oxyberberine ameliorated gut barrier dysfunction via inhibition of the TLR4, MyD88, and NF-κB signaling pathways and downregulated inflammatory cytokines such as TNFα, IL-6, and IL-1β.
“Oxyberberine, another microbial metabolite derived from berberine ameliorated gut barrier dysfunction via inhibition of the TLR4, MyD88, and NF-κB signaling pathways197 and downregulated inflammatory cytokines such as TNFα, IL-6, and IL-1β.”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [197]
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Regulation of Intestinal Barrier Function by Microbial Metabolites
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- Authors
- Li, C., Ai, G., Wang, Y., Lu, Q., Luo, C., Tan, L., Lin, G., Liu, Y., Li, Y., Zeng, H., Chen, J., Lin, Z., Xian, Y., Huang, X., Xie, J., & Su, Z.
- Affiliations
- Guangzhou University of Chinese Medicine (CN)
- Corresponding author
- Xie, Jianhui
- Su, Ziren
- ORCID
- Venue
- Pharmacological Research
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 152
- Pages
- 104603
- ISSN
- 1043-6618 (ISSN-L)
- OpenAlex
- W2996171161
- Cited by
- 262
- References
- 70
- Citations by year
- 2026: 25 · 2025: 34 · 2024: 49 · 2023: 55 · 2022: 54 · 2021: 37 · 2020: 8
- FWCI
- 15.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacological Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Science and Technology Development Special Project of Guangdong Province (2017A050506044)
- Science and Technology Plan Project of Guangzhou (201704030028)
- Characteristic Cultivation Program for Subject Research of Guangzhou University of Chinese Medicine (XKP2019007)
- Topics
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- berberine, gut microbiota metabolites, colitis, DSS-induced colitis, intestinal epithelial barrier, TLR4/MyD88/NF-κB signaling, gut dysbiosis, intestinal inflammation, isoquinoline alkaloids
- MeSH terms
- Gastrointestinal Microbiome, Animals, Anti-Inflammatory Agents, Berberine, Biotransformation, Cecum, Colitis, Colon, Male, Mice, Inbred BALB C, Signal Transduction, Dextran Sulfate, NF-kappa B, Toll-Like Receptor 4, Myeloid Differentiation Factor 88
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