94% of researchers rate our articles as excellent or good
Learn more about the work of our research integrity team to safeguard the quality of each article we publish.
Find out more
ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1563158
Salidroside alleviates hypoxic injury in mammary epithelial cells of milk buffalo by inhibiting BNIP3/NIX-mediated mitophagy and reprogramming mitochondrial metabolism
Provisionally accepted- 1 Guangxi University, Nanning, China
- 2 Zhejiang University of Science and Technology, Hangzhou, Zhejiang Province, China
You have multiple emails registered with Frontiers:
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Hypoxic damage in milk buffalo mammary epithelial cells (BMECs) during peak lactation period is an important factor affecting production performance. Salidroside (Sal) has the function of alleviating hypoxic injury, but its mechanism of alleviating hypoxic injury in BMECs is still unclear. In this study, a hypoxic model of BMECs was established in vitro, and the mechanism of salidroside alleviating hypoxic injury of BMECs was explored by combining flow cytometry, immunofluorescence, transmission electron microscopy, gene silence and overexpression, and metabolomics.The results showed that hypoxia significantly increased apoptosis and cycle arrest of S phase (P < 0.05). It also altered the ultrastructure of BMECs, induced autophagy and colocalization of mitochondria and lysosomes. In addition, hypoxia significantly promoted the conversion of LC3-I to LC3-II. Overexpression and silencing of BNIP3 and NIX suggest that receptor-mediated mitophagy plays a crucial role in alleviating hypoxic injury. Salidroside can relieve the damage of BMECs caused by hypoxia through BNIP3/NIX-mediated mitophagy. Metabolomics results show that valine, leucine and isoleucine biosynthesis, glycine, serine and threonine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis and phenylalanine metabolism, pyrimidine metabolism and glycerophospholipid metabolism contribute to a key role in alleviating hypoxic injury by salidroside. These results suggest that salidroside may relieve hypoxic stress in BMECs by inhibiting the BNIP3/NIX-mediated mitophagy, and regulating mitochondrial metabolism. This study can provide a special insight for the development and utilization of salidroside, and provide theoretical foundation for the development of new drug for milk buffalo hypoxic injury.
Keywords: Salidroside, mitophagy, Hypoxic injury, mitochondrial metabolism, Milk buffalo
Received: 19 Jan 2025; Accepted: 25 Mar 2025.
Copyright: © 2025 Kong, Min, Wang, Pan, Abula, Yang and Wei. 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:
Zhiwei Kong, Guangxi University, Nanning, 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.