2. Academic Validation
  3. Astragaloside IV: a natural shield against ochratoxin A-induced hepatotoxicity in chicks by targeting the NRF2/NLRP3 signaling pathway

Astragaloside IV: a natural shield against ochratoxin A-induced hepatotoxicity in chicks by targeting the NRF2/NLRP3 signaling pathway

  • Toxicon. 2025 Aug 6:266:108513. doi: 10.1016/j.toxicon.2025.108513.
Jingyi Yang 1,  Hao Xu 1,  Ruiqi Ye 1,  Yu Zhang 1,  Jiale Wu 1,  Erhui Jin 2,  Xiaojin Li 2,  Mixia Cao 2,  Shenghe Li 2,  Chang Liu 3,  Lei Li 4
Affiliations

Affiliations

  • 1 College of Animal Science, Anhui Science and Technology University, Fengyang, 233100, China; Anhui Province Key Laboratory of Animal Nutrition Regulation and Health, Fengyang, 233100, China.
  • 2 College of Animal Science, Anhui Science and Technology University, Fengyang, 233100, China; Anhui Province Key Laboratory of Animal Nutrition Regulation and Health, Fengyang, 233100, China; Quality & Safety Control for Pork Engineering Technology Research Center of Anhui Province, Fengyang, 233100, China; Local Goose Gene Bank in Anhui Province, Fengyang, 233100, China.
  • 3 College of Animal Science, Anhui Science and Technology University, Fengyang, 233100, China; Anhui Province Key Laboratory of Animal Nutrition Regulation and Health, Fengyang, 233100, China; Quality & Safety Control for Pork Engineering Technology Research Center of Anhui Province, Fengyang, 233100, China; Local Goose Gene Bank in Anhui Province, Fengyang, 233100, China. Electronic address: liuchang052@126.com.
  • 4 College of Animal Science, Anhui Science and Technology University, Fengyang, 233100, China; Anhui Province Key Laboratory of Animal Nutrition Regulation and Health, Fengyang, 233100, China; Quality & Safety Control for Pork Engineering Technology Research Center of Anhui Province, Fengyang, 233100, China; Local Goose Gene Bank in Anhui Province, Fengyang, 233100, China. Electronic address: lil@ahstu.edu.cn.
PMID: 40780305 DOI: 10.1016/j.toxicon.2025.108513
Abstract

Ochratoxin A (OTA) is a prevalent contaminant in feed and poses a serious threat to the poultry industry and public health. The liver is the primary target of OTA, and oxidative stress alongside consequent inflammation, is considered the main contributor to OTA-induced liver damage. Astragaloside IV (AS-IV), a key constituent of the traditional Chinese medicinal herb Astragalus membranaceus, exhibits diverse pharmacological properties, including anti-inflammatory, antioxidant, immunoregulatory, and organ-protective effects. However, whether AS-IV can ameliorate OTA-induced liver damage remains uncertain. In the current investigation, we investigated the effect of AS-IV on OTA-induced liver damage in chicks and elucidated the underlying mechanisms. The results revealed that AS-IV inhibited OTA-induced increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and Alkaline Phosphatase (AKP) activities. Additionally, AS-IV reversed the OTA-induced decrease in Glutathione Peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) activities, as well as the increase in malondialdehyde (MDA) content (P < 0.05). The results demonstrated that AS-IV is capable of mitigating mitochondrial damage and reducing the elevation of Reactive Oxygen Species (ROS) in the chicken liver cell line LMH induced by OTA. Moreover, AS-IV was discovered to reverse the OTA-induced decrease in nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), NADPH quinone oxidoreductase 1 (NQO1) expression, and the increase in Kelch-like ECH-associated protein 1(Keap1) expression. Meanwhile, AS-IV also counteracted OTA-induced NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome expression. Taken together, our findings suggested that AS-IV ameliorated OTA-induced hepatotoxicity in chicks by regulating the Nrf2 and NLRP3 signaling pathways.

Keywords

Astragaloside IV; Hepatic injury; NLRP3; Nrf2; Ochratoxin A.

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