Chikusetsusaponin IVa Targets Nrf2 to Inhibit H9N2 Avian Influenza Virus Infection

ABSTRACT

Background: Chikusetsusaponin IVa (CHS) is a triterpenoid saponin that has been demonstrated to possess multiple properties. Objectives: This study focused on inhibiting H9N2 avian influenza virus (AIV) by CHS and investigated the underlying mechanisms, specifically targeting the nuclear factor erythroid2-related factor 2 (Nrf2) signaling pathway. Materials and Methods: The antiviral activity of CHS was evaluated by determining its half inhibitory concentration and therapeutic index (TI) in vitro. Markers of oxidative stress, encompassing superoxide dismutase, glutathione peroxidase, and malondialdehyde levels, were assessed. Analyses of pathways from the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology were conducted to elucidate the underlying mechanisms, followed by network investigation and simulations of molecular docking. Moreover, the effects of CHS on Nrf2 and mitogen-activated protein kinase (MAPK) signaling pathways were assessed in human lung carcinoma A549 cells and a mouse model of H9N2 AIV infection. Results: CHS showed inhibitory effects on H9N2 AIV in vitro, with TI values of 4.00 (co-treatment) and 6.29 (posttreatment). CHS reduced H9N2 AIV-induced oxidative stress and was predicted to target Nrf2, MAPK/phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signaling pathways, and oxidation–reduction processes. Molecular docking analysis revealed a high affinity between CHS and Nrf2. In A549 cells, CHS enhanced Nrf2 activation, inhibited MAPK signaling, and reduced H9N2 AIV-induced oxidative stress. The therapeutic mechanism of CHS was found to be mediated by Nrf2. In a mouse model, CHS mitigated pulmonary impairment, improving the organism’s antioxidant activity. CHS also regulated the Nrf2 and MAPK signaling pathways in lung tissue. Conclusion: CHS inhibits H9N2 AIV and alleviates virus-induced oxidative stress by targeting the Nrf2 signaling pathway. These observations lay the groundwork for devising prospective therapeutic interventions targeting H9N2 AIV infection.

KEYWORDS

• Chikusetsusaponin IVa
• Nrf2
• H9N2
• avian influenza virus
• bioactivity

Showing references and in-text citations exactly as published.

• DOI10.1177/09731296241277316Copy

RELATED ARTICLES

Matched on section and article type within this issue of Pharmacogn. Mag..

• Article · VOLUME 21, ISSUE 2Pinobanksin Attenuates Cerebral Ischemia– Reperfusion Injury in Rats through Mitigating the Inflammatory ResponsesTianmin Bie, Feng Jia, Yongmei Wang, Zhuoyan Pan · pp. 413–422Original Research ArticleSame type: Article
• Article · VOLUME 21, ISSUE 2Extraction and in vitro and in vivo Antioxidant Activity Evaluation of Polyphenols from Lychee PericarpYing Wang, Hong Deng, Chuqin Yu, Junfeng Ban, Shu Zhang · pp. 423–432Original Research ArticleSame type: Article
• Article · VOLUME 21, ISSUE 2Discussion about the Role of Ghrelin in Myocardial Ischemia/Reperfusion and its Possible MechanismGang Huang, Nan Zheng, Yinqing Huang · pp. 433–442Original Research ArticleSame type: Article
• Article · VOLUME 21, ISSUE 2Sanggenol L Reduces LPS-induced Myocardial Injury and Inflammation by Activating PI3K/ AKT/mTOR and Inhibiting NF-κB in RatsHaojun Wang, Tao Jin, Yuehan Mao, Yi Wei · pp. 443–453Original Research ArticleSame type: Article