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Article

Isorhamnetin Ameliorates Non-Esterified Fatty Acid-Induced Apoptosis, Lipid Accumulation, and Oxidative Stress in Bovine Endometrial Epithelial Cells via Inhibiting the MAPK Signaling Pathway

by
Haimiao Lv
1,
Lijuan Liu
1,
Wenna Zou
1,
Ying Yang
1,
Yuan Li
1,
Shengji Yang
1,
Aixin Liang
1,2,* and
Liguo Yang
1,2,*
1
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
2
National Center for International Research on Animal Genetics, Breeding and Reproduction, Huazhong Agricultural University, Wuhan 430070, China
*
Authors to whom correspondence should be addressed.
Antioxidants 2025, 14(2), 156; https://doi.org/10.3390/antiox14020156
Submission received: 31 October 2024 / Revised: 12 January 2025 / Accepted: 22 January 2025 / Published: 28 January 2025
(This article belongs to the Topic Recent Advances in Veterinary Pharmacology and Toxicology)

Abstract

High concentrations of non-esterified fatty acids (NEFAs) in the blood contribute to various metabolic disorders and are linked to endometritis in dairy cows. Isorhamnetin (ISO), a flavonoid found in many plants, is known for its antioxidant, anti-inflammatory, and anti-obesity properties. This study systematically assessed NEFA-induced damage in bovine endometrial epithelial cells (bEECs) and investigated whether ISO alleviates NEFA-induced cell damage and its underlying molecular mechanisms. Our observations revealed that excessive NEFA inhibited proliferation and induced apoptosis in bEECs, accompanied by an increase in the expression of BAX and cleaved caspase-3. We further observed that NEFA could induce lipid accumulation, reactive oxygen species (ROS) generation, and the release of pro-inflammatory factors IL-1β, IL-6, and TNF-α in bEECs. RNA sequencing and Western blot analysis revealed that NEFA induced damage in bEECs by activating MAPK signaling pathway. Notably, ISO treatment ameliorated these effects induced by NEFA, as evidenced by decreased protein levels of BAX, cleaved caspase-3, and PPAR-γ, along with reductions in triglyceride content, ROS generation, and levels of IL-1β, IL-6, and TNF-α. Mechanistically, our experimental results demonstrated that ISO inhibited NEFA-induced activation of MAPK signaling. Overall, ISO shows promise for therapeutic development to address NEFA-related endometritis in dairy cows.
Keywords: non-esterified fatty acids; isorhamnetin; endometrial epithelial cells; MAPK signaling; bovine non-esterified fatty acids; isorhamnetin; endometrial epithelial cells; MAPK signaling; bovine

Share and Cite

MDPI and ACS Style

Lv, H.; Liu, L.; Zou, W.; Yang, Y.; Li, Y.; Yang, S.; Liang, A.; Yang, L. Isorhamnetin Ameliorates Non-Esterified Fatty Acid-Induced Apoptosis, Lipid Accumulation, and Oxidative Stress in Bovine Endometrial Epithelial Cells via Inhibiting the MAPK Signaling Pathway. Antioxidants 2025, 14, 156. https://doi.org/10.3390/antiox14020156

AMA Style

Lv H, Liu L, Zou W, Yang Y, Li Y, Yang S, Liang A, Yang L. Isorhamnetin Ameliorates Non-Esterified Fatty Acid-Induced Apoptosis, Lipid Accumulation, and Oxidative Stress in Bovine Endometrial Epithelial Cells via Inhibiting the MAPK Signaling Pathway. Antioxidants. 2025; 14(2):156. https://doi.org/10.3390/antiox14020156

Chicago/Turabian Style

Lv, Haimiao, Lijuan Liu, Wenna Zou, Ying Yang, Yuan Li, Shengji Yang, Aixin Liang, and Liguo Yang. 2025. "Isorhamnetin Ameliorates Non-Esterified Fatty Acid-Induced Apoptosis, Lipid Accumulation, and Oxidative Stress in Bovine Endometrial Epithelial Cells via Inhibiting the MAPK Signaling Pathway" Antioxidants 14, no. 2: 156. https://doi.org/10.3390/antiox14020156

APA Style

Lv, H., Liu, L., Zou, W., Yang, Y., Li, Y., Yang, S., Liang, A., & Yang, L. (2025). Isorhamnetin Ameliorates Non-Esterified Fatty Acid-Induced Apoptosis, Lipid Accumulation, and Oxidative Stress in Bovine Endometrial Epithelial Cells via Inhibiting the MAPK Signaling Pathway. Antioxidants, 14(2), 156. https://doi.org/10.3390/antiox14020156

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