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Food Science and Human Wellness 2024, 13(3): 1292-1302 https://doi.org/10.26599/FSHW.2022.9250108
Research Article | Open Access | Issue | Published: 08 February 2024

Betulinic acid protects against ovarian impairment by decreasing F-2 toxin-induced oxidative stress and inflammation associated with the downregulation of p38 expression in mice

Show Author's Information Li Kong,1,  Xinyu Gao,1,  Lijuan Zhu,  Xing Lin,  You Huang,  Chunlin Huang,  Wenjiang Yang,  Yazhi Chen,  Haoqiang Zhao,  Jing Wu,  Zhihang Yuan( ),  Jin’e Yi,( )
Hunan Engineering Research Center of Livestock and Poultry Health Care, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China

1 These authors contributed equally to this work.

Peer review under responsibility of Tsinghua University Press.

Keywords:
Betulinic acid, F-2 toxin, Ovarian damage, p38 MAPK signaling pathway
Cite this article:
Kong L, Gao X, Zhu L, et al. Betulinic acid protects against ovarian impairment by decreasing F-2 toxin-induced oxidative stress and inflammation associated with the downregulation of p38 expression in mice. Food Science and Human Wellness, 2024, 13(3): 1292-1302. https://doi.org/10.26599/FSHW.2022.9250108
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Abstract Full text About this article

F-2 toxin is an estrogenic mycotoxin that causes reproductive disorders in animals. Betulinic acid (BA) is a natural pentacyclic lupane-structure triterpenoid that has diverse pharmacological activities. In this study, the antioxidative and anti-inflammatory effects of BA and its underlying mechanism are explored in F-2 toxin-triggered mouse ovarian damage. We found that BA alleviated the F-2 toxin-induced ovarian impairment by stimulating follicle growth, reducing inflammatory cell infiltration, repairing damaged mitochondria and endoplasmic reticulum. Simultaneously, BA not only reversed F-2 toxin-induced reduction of follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels in the serum, but also restrained the protein expression of the estrogen receptors α (ERα) and ERβ. Moreover, BA restored the balance of F-2 toxin-induced ovarian redox system disorders. Subsequently, we found that 0.25 mg/kg BA played an anti-inflammatory role in the F-2 toxin-induced ovarian impairment by decreasing interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) mRNA expression, as well as inhibiting p38 protein expression.These data demonstrated that BA exerts its protective effect on F-2 toxin-induced ovarian oxidative impairment and inflammation by inhibiting p38 expression, which implies a natural product-based medicine to ameliorate F-2 toxin-caused female reproductive toxicity and provides a detoxifying method for food contaminated by mycotoxin.


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About this article

Betulinic acid protects against ovarian impairment by decreasing F-2 toxin-induced oxidative stress and inflammation associated with the downregulation of p38 expression in mice

Show Author's information Li Kong,1, Xinyu Gao,1, Lijuan Zhu, Xing Lin, You Huang, Chunlin Huang, Wenjiang Yang, Yazhi Chen, Haoqiang Zhao, Jing Wu, Zhihang Yuan( ), Jin’e Yi,( )
Hunan Engineering Research Center of Livestock and Poultry Health Care, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China

1 These authors contributed equally to this work.

Peer review under responsibility of Tsinghua University Press.

Highlights

BA mitigated F-2 toxin-evoked oxidative stress and inflammation in mouse ovary.

BA regulated F-2 toxin-caused hormone secretion disorder in ovary.

BA reduced F-2 toxin-induced ovarian impairment via downregulating p38 protein expression.

Abstract

F-2 toxin is an estrogenic mycotoxin that causes reproductive disorders in animals. Betulinic acid (BA) is a natural pentacyclic lupane-structure triterpenoid that has diverse pharmacological activities. In this study, the antioxidative and anti-inflammatory effects of BA and its underlying mechanism are explored in F-2 toxin-triggered mouse ovarian damage. We found that BA alleviated the F-2 toxin-induced ovarian impairment by stimulating follicle growth, reducing inflammatory cell infiltration, repairing damaged mitochondria and endoplasmic reticulum. Simultaneously, BA not only reversed F-2 toxin-induced reduction of follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels in the serum, but also restrained the protein expression of the estrogen receptors α (ERα) and ERβ. Moreover, BA restored the balance of F-2 toxin-induced ovarian redox system disorders. Subsequently, we found that 0.25 mg/kg BA played an anti-inflammatory role in the F-2 toxin-induced ovarian impairment by decreasing interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) mRNA expression, as well as inhibiting p38 protein expression.These data demonstrated that BA exerts its protective effect on F-2 toxin-induced ovarian oxidative impairment and inflammation by inhibiting p38 expression, which implies a natural product-based medicine to ameliorate F-2 toxin-caused female reproductive toxicity and provides a detoxifying method for food contaminated by mycotoxin.

Keywords: Betulinic acid, F-2 toxin, Ovarian damage, p38 MAPK signaling pathway

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Publication history

Received: 30 April 2022
Revised: 23 July 2022
Accepted: 10 November 2022
Published: 08 February 2024
Issue date: May 2024

Copyright

© 2024 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

Acknowledgements

This study was supported by the National Natural Science Foundation of China (32273084), the Special Funds for Construction of Innovative Provinces in Hunan Province, China (2020NK2032), the Natural Science Foundation of Hunan Province, China (2020JJ4368),Innovation Foundation for Postgraduate of Hunan Province, China (CX20220670) and Innovation Foundation for Postgraduate of Hunan Agricultural University, China (2022XC010).

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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