4.7 Article

Albiflorin ameliorates inflammation and oxidative stress by regulating the NF-ΚB/NLRP3 pathway in Methotrexate-induced enteritis

Journal

INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 109, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.intimp.2022.108824

Keywords

Albiflorin; Enteritis; Inflammation; Oxidative stress; NF-kappa B; NLRP3

Funding

  1. Top Talent Project for Youths of Hebei Province [180443]
  2. Third Batch of Giant Project of Hebei Province [180416]
  3. High School Hundred Excellent Inno-vation Talent Program of Hebei Province [SLRC2019048]
  4. Doctoral Startup Foundation of Hebei Normal University of Science and Technology [2018YB018]
  5. Shaanxi Science and Technology Innovation Team [2022TD-56]

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This study found that albiflorin can inhibit methotrexate-induced enteritis, reduce inflammation, and exert its effects through inhibiting the NF-kappa B/NLRP3 pathway.
Methotrexate (MTX) treats various diseases but also damages intestinal barrier and leads to enteritis. Albiflorin (ALB) has a variety of pharmacological effects, including antioxidant, anti-inflammation and anti-apoptosis. In the present study, we evaluated the therapeutic effect of ALB on MTX-induced enteritis and investigated the possible mechanisms involved. Male SD rats were intraperitoneally injected with 7 mg/kg MTX for three consecutive days to establish the enteritis model. ALB (20 or 40 mg/kg/day) was intragastrically administrated since two days prior MTX treatment and lasted for six days. We found that ALB treatment increased body weight and intestinal weight of rats with MTX injection. The disease activity index (DAI) score was also decreased after ALB administration. In histological examination, ALB treatment attenuated inflammatory cells infiltration and promoted survival of goblet cells. In detection of inflammatory-associated factors, ALB treatment decreased CD68(+) cells infiltration, inhibited myeloperoxidase activity, and suppressed intercellular cell adhesion molecule 1 and cyclooxygenase-2 expression. Additionally, ALB reduced malondialdehyde, glutathione levels, inhibited superoxide dismutase activity and suppressed reactive oxygen species production. Moreover, ALB treatment effectively inhibited NLRP3, as well as caspase 1 p20 and interleukin (IL)-113 and 18 expression. Finally, nuclear factor-kappa B (NF-kappa B) p65 phosphorylation and nuclear translocation were also demonstrated to be blocked upon ALB treatment. In conclusion, our findings indicated that ALB alleviated MTX-induced enteritis via inhibiting the NF-kappa B/NLRP3 pathway.

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