2. Academic Validation
  3. Hesperidin attenuates lipopolysaccharide-induced endometritis by inhibiting mitochondrial oxidative stress via activating the AMPK/PGC-1α signalling pathway

Hesperidin attenuates lipopolysaccharide-induced endometritis by inhibiting mitochondrial oxidative stress via activating the AMPK/PGC-1α signalling pathway

  • Eur J Pharmacol. 2025 Aug 29:1005:178100. doi: 10.1016/j.ejphar.2025.178100.
Linfang Wu 1,  Jing Wang 2,  Yonghuan Yan 3,  Lu Wang 4,  Qi Huang 5,  Jinyong Peng 6,  Lili Li 7
Affiliations

Affiliations

  • 1 College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, PR China. Electronic address: 19156750785@163.com.
  • 2 College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, PR China. Electronic address: 1714728841@qq.com.
  • 3 College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, PR China. Electronic address: 949835805@qq.com.
  • 4 College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, PR China. Electronic address: 18340809687@163.com.
  • 5 College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, PR China; Anhui Province Key Laboratory of Chinese Medicinal Formula, Anhui Academy of Chinese Medicine, Hefei, 230012, PR China. Electronic address: ahhq0016@163.com.
  • 6 College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, PR China; College of Pharmacy, Dalian Medical University, Dalian, 116044, PR China. Electronic address: jinyongpeng2008@126.com.
  • 7 College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, PR China; Institute of Traditional Chinese Medicine Resources Protection and Development, Anhui Academy of Chinese Medicine, Hefei, 230012, PR China; Anhui Province Key Laboratory of Chinese Medicinal Formula, Anhui Academy of Chinese Medicine, Hefei, 230012, PR China. Electronic address: lily5637@ahtcm.edu.cn.
PMID: 40886876 DOI: 10.1016/j.ejphar.2025.178100
Abstract

Endometritis is a prevalent condition of the reproductive system that leads to significant tissue damage in the uterus, thereby seriously impacting the health and quality of life of these patients. Hesperidin (HES), a natural flavonoid glycoside, displays various biological activities. Nonetheless, the protective effect of HES treatment against endometritis remains uncertain. In this study, we examined the protective effects of HES on endometritis induced by lipopolysaccharide (LPS) both in vivo and in vitro. In vitro experimental results showed that HES reduced the levels of inflammatory factors, improved mitochondrial morphology, increased mitochondrial activity and inhibited ROS levels; moreover, it activated the AMPK/PGC-1 α signalling pathway in LPS-induced human endometrial endothelial cells (HEECs). AMPK served as a potential target of HES, which was further validated using molecular docking, molecular dynamic simulation, CETSA and SPR. Moreover, in vivo experimental results indicated that HES significantly mitigated the histopathological alterations in the uterus caused by LPS, as well as reduced the levels of inflammatory factors, MPO activity, the expression levels of CD38, and CD138 and activated the AMPK/PGC-1α signalling pathway. Overall, HES mitigated mitochondrial oxidative stress and inflammatory response primarily through activation of the AMPK/PGC-1α signalling pathway, thereby exerting protective effects against endometritis.

Keywords

AMPK/PGC-1α signalling pathway; Endometritis; Hesperidin; Lipopolysaccharide; Mitochondrial oxidative stress.

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