Oxyberberine ameliorates TNBS-induced colitis in rats through suppressing inflammation and oxidative stress via Keap1/Nrf2/NF-κB signaling pathways
Related Experiment Video
Updated: Jul 28, 2025
Investigating the Alleviating Effects of Bacillus cereus Administration on Colitis through Gut Microbiota Modulation
Published on: July 27, 2022
Cailan Li1, Meigui Liu2, Li Deng3
1Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, China; Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi 563000, China.
Background:
Ulcerative colitis (UC) is a chronic, unspecific inflammatory bowel disorder lacking effective therapeutic targets and radical drugs. Oxyberberine (OBB), a novel intestinal flora-elicited oxidative metabolite of berberine (BBR), has been revealed to exhibit diverse pharmacological properties.
Purpose:
In this follow-up study, we attempted to shed light on the possible therapeutic effect and latent mechanism of OBB on 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-evoked UC in rats.
Methods:
UC rats were established via a gentle enema of TNBS. Rats were sacrificed after intragastric administration of drugs for seven days. The weight reduction, disease activity index, macroscopic and histological colonic alterations were assessed. Further investigation on molecular mechanisms was conducted by ELISA, qRT-PCR, immunohistochemistry, or Western blot.
Results:
OBB treatment remarkably decreased the weight loss, macroscopic scores, and colonal weight/length ratio, as well as mitigated the colonic pathological deterioration and MPO vitality in colitis rats, achieving a superior protective effect to BBR. Additionally, OBB modulated the disequilibrium between pro- and anti-inflammatory factors by promoting the production of IL-13 and IL-4, and lowering the contents of TNF-α, IL-2, IL-8, and IL-22. Furthermore, OBB pretreatment dramatically ameliorated oxidative stress via enhancing antioxidant defense genes expressions (including HO-1, GCLM, GCLC, and NQO-1), thereby increasing SOD and GSH, and decreasing MDA and ROS activities. Furthermore, OBB strikingly restrained the translocation of NF-κB p65 and phosphorylation of IκBα, promoted HO-1 expression, Keap1 degradation and Nrf2 nuclear translocation.
Conclusion:
The study firstly indicated that OBB had a superior therapeutic effect than BBR against TNBS-elicited colitis in rats. The protective effect of OBB might be closely related to the modulation of Keap1/Nrf2/NF-κB-mediated inflammatory response and oxidant stress. The evidences highlight the potentiality of OBB as a prospective candidate for the amelioration of colitis.
Insights
Oxyberberine (OBB) shows superior therapeutic effects compared to berberine (BBR) in treating ulcerative colitis (UC) in rats. OBB ameliorates inflammation and oxidative stress by modulating the Keap1/Nrf2/NF-κB pathway, highlighting its potential for colitis treatment.
Area of Science:
- Pharmacology
- Gastroenterology
- Molecular Biology
Background:
- Ulcerative colitis (UC) is a chronic inflammatory bowel disorder with limited effective treatments.
- Oxyberberine (OBB), a metabolite of berberine (BBR), exhibits promising pharmacological activities.
Purpose of the Study:
- To investigate the therapeutic potential of OBB against 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced UC in a rat model.
- To elucidate the underlying molecular mechanisms of OBB's action in colitis.
Main Methods:
- UC was induced in rats using TNBS enema.
- Rats received daily intragastric administration of OBB or BBR for seven days.
- Disease activity, colonic alterations, inflammatory markers, oxidative stress, and the Keap1/Nrf2/NF-κB pathway were assessed using various biochemical and molecular techniques.
Main Results:
- OBB significantly reduced UC symptoms, including weight loss and colonic damage, outperforming BBR.
- OBB modulated cytokine profiles, promoting anti-inflammatory IL-13 and IL-4 while reducing pro-inflammatory TNF-α, IL-2, IL-8, and IL-22.
- OBB enhanced antioxidant defenses by increasing SOD and GSH, decreasing MDA and ROS, and activating the Nrf2 pathway, evidenced by increased HO-1 and nuclear translocation of Nrf2.
Conclusions:
- OBB demonstrates a superior therapeutic effect over BBR in TNBS-induced colitis in rats.
- OBB's protective mechanism involves the modulation of the Keap1/Nrf2/NF-κB pathway, mitigating inflammatory responses and oxidative stress.
- OBB presents a promising therapeutic candidate for managing ulcerative colitis.
Related Concept Videos
02:26NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
01:31Regulation of the Unfolded Protein Response