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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1386604
This article is part of the Research Topic Quality control for Efficacy and Safety of Herbal Medicinal Products: Volume II View all 9 articles

Barleriside A, an aryl hydrocarbon receptor antagonist, ameliorates podocyte injury through inhibiting oxidative stress and inflammation

Provisionally accepted
Xiao Jun Li Xiao Jun Li 1Yanni Wang Yanni Wang 2Wenfeng Wang Wenfeng Wang 3Xiaoli Nie Xiaoli Nie 1Hua Miao Hua Miao 2*Ying-Yong Zhao Ying-Yong Zhao 2*
  • 1 Department of Nephrology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
  • 2 School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
  • 3 Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China

The final, formatted version of the article will be published soon.

    Increasing evidence shows that hyperactive aryl hydrocarbon receptor (AHR) signalling is involved in renal disease. However, no currently available intervention strategy is effective in halting disease progression by targeting the AHR signalling. Our previous study showed that barleriside A (BSA), a major component of Plantaginis semen, exhibits renoprotective effects. In this study, we determined the effects of BSA on AHR expression in 5/6 nephrectomized (NX) rats. We further determined the effect of BSA on AHR, nuclear factor kappa B (NF-ƙB), and the nuclear factor erythroid 2-related factor 2 (Nrf2) signalling cascade in zymosan-activated serum (ZAS)-stimulated MPC5 cells. The results showed that BSA treatment improved renal function and inhibited intrarenal nuclear AHR protein expression in NX-treated rats. BSA mitigated podocyte lesions and suppressed AHR mRNA and protein expression in ZAS-stimulated MPC5 cells. BSA inhibited inflammation by improving the NF-ƙB and Nrf2 pathways in ZAS-stimulated MPC5 cells. However, BSA did not markedly upregulate the expression of podocyte-specific proteins in the ZAS-mediated MPC5 cells treated with CH223191 or AHR siRNA compared to untreated ZAS-induced MPC5 cells. Similarly, the inhibitory effects of BSA on nuclear NF-ƙB p65, Nrf2, and AHR, as well as cytoplasmic cyclooxygenase-2, heme oxygenase-1, and AHR, were partially abolished in ZAS-induced MPC5 cells treated with CH223191 or AHRsiRNA compared with untreated ZAS-induced MPC5 cells. These results indicated that BSA attenuated the inflammatory response, partly by inhibiting AHR signalling. Taken together, both pharmacological and siNRA findings suggested that BSA mitigated podocyte lesions by improving the NF-ƙB and Nrf2 pathways via inhibiting AHR signalling. Therefore, BSA is a high-affinity AHR antagonist that abolishes oxidative stress and inflammation.

    Keywords: Aryl hydrocarbon receptor, nuclear factor kappa B, Nrf2, Chronic Kidney Disease, Podocyte injury, barleriside A

    Received: 15 Feb 2024; Accepted: 12 Aug 2024.

    Copyright: © 2024 Li, Wang, Wang, Nie, Miao and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Hua Miao, School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
    Ying-Yong Zhao, School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.