Glabridin ameliorates oxidative stress and inflammation in a bovine intestinal cell line and a colitis mouse model

Document Type : Full paper (Original article)

Authors

1 MSc Student in Animal Nutrition, Henan International Joint Laboratory of Animal Welfare and Health Breeding, Faculty of Animal Nutrition, Henan University of Science and Technology, Luoyang, 471023, China

2 Henan International Joint Laboratory of Animal Welfare and Health Breeding, Faculty of Animal Nutrition, Henan University of Science and Technology, Luoyang, 471023, China

10.22099/ijvr.2025.50560.7464

Abstract

Background: Oxidative stress (OS) adversely affects the intestinal health and mucosal barrier function in dairy cows. Glabridin (Glab), a natural flavonoid derived from licorice, has been shown to mitigate stress-related damage due to its antioxidant properties. Aims: This study aims to assess the impact of Glab on OS-induced damage in the bovine immortalized cell line (BIECs-21), validate its effectiveness in vivo, and elucidate the underlying mechanisms. Methods: The in vitro OS model of BIECs-21 was established using 400 μM H2O2. The study evaluated cell viability, lactate dehydrogenase (LDH) activity, oxidative markers, inflammatory responses, and apoptosis in BIECs-21 under various treatment conditions. Additionally, the effects of Glab were investigated in a murine model of experimental colitis induced by dextran sulfate sodium (DSS). Results: Glab improved cell viability, reduced LDH release, and mitigated the adverse effects of H2O2 on total anti-oxidation capacity (T-AOC), superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) levels. qRT-PCR analysis revealed that H2O2 exposure resulted in decreased expression of nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 1 (SOD1), NADPH quinine oxidoreductase-1 (NQO1), and heme oxygenase-1 (HO-1), while it increased the expression of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8), ultimately leading to apoptosis in BIECs-21. Notably, Glab supplementation partially reversed these effects. Similar benefits of Glab were observed in a DSS-induced colitis mouse model. Conclusion: Glab reduces OS-induced apoptosis in vitro and in vivo by enhancing antioxidant capacity and reducing inflammation.

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References

Bhatt, S; Sharma, A; Dogra, A; Sharma, P; Kumar, A; Kotwal, P; Bag, S; Misra, P; Singh, G; Kumar, A; Sangwan, PL and Nandi, U (2022). Glabridin attenuates paracetamol-induced liver injury in mice via CYP2E1-mediated inhibition of oxidative stress. Drug Chem. Toxicol., 45: 2352-2360.
Carmeli, E and Fogelman, Y (2009). Antioxidant effect of polyphenolic glabridin on LDL oxidation. Toxicol. Ind. Health. 25: 321-324.
Chao, L; Li, Z; Zhou, J; Chen, W; Li, Y; Lv, W; Guo, A; Qu, Q and Guo, S (2020). Shen-Ling-Bai-Zhu-San improves dextran sodium sulfate-induced colitis by inhibiting caspase-1/caspase-11-mediated pyroptosis. Front. Pharmacol., 11: 814.
Choi, J; Kim, BR; Akuzum, B; Chang, L; Lee, JY and Kwon, HK (2022). T(REG)king from gut to brain: the control of regulatory T cells along the gut-brain axis. Front. Immunol., 13: 916066.
Dai, J; Zhang, Y; Chen, D; Chen, D; Li, X; Wang, J and Sun, Y (2021). Glabridin inhibits osteoarthritis development by protecting chondrocytes against oxidative stress, apoptosis and promoting mTOR mediated autophagy. Life Sci., 268: 118992.
Dogan, MF; Parlar, A; Cam, SA; Tosun, EM; Uysal, F and Arslan, SO (2020). Glabridin attenuates airway inflammation and hyperresponsiveness in a mice model of ovalbumin-induced asthma. Pulm. Pharmacol. Ther., 63: 101936.
Du, J; Cao, L; Gao, J; Jia, R; Zhu, H; Nie, Z; Xi, B; Yin, G; Ma, Y and Xu, G (2022). Protective effects of glycyrrhiza total flavones on liver injury induced by streptococcus agalactiae in tilapia (Oreochromis niloticus). Antibiotics (Basel). 11: 1648.
Gao, Z; Wang, Y and Yu, H (2022). A chinese classical prescription chaihu shugan powder in treatment of post-stroke depression: an overview. Medicina (Kaunas). 59: 55.
Jafri, MS and Kumar, R (2014). Modeling mitochondrial function and its role in disease. Prog. Mol. Biol. Transl. Sci., 123: 103-125.
Jiang, L; Gong, Y; Rao, J; Yang, Q; Gao, N; Li, G and Ma, Y (2021). 1-O-Hexyl-2,3,5-trimethylhydroquinone ameliorates the development of preeclampsia through suppression of oxidative stress and endothelial cell apoptosis. Oxid. Med. Cell. Longev., 2021: 8839394.
Kim, SY; Cha, HJ; Hwangbo, H; Park, C; Lee, H; Song, KS; Shim, JH; Noh, JS; Kim, HS; Lee, BJ; Kim, S; Kim, GY; Jeon, YJ and Choi, YH (2021). Protection against oxidative stress-induced apoptosis by fermented sea tangle (Laminaria japonica Aresch) in osteoblastic MC3T3-E1 cells through activation of Nrf2 signaling pathway. Foods. 10: 2807.
Koh, ES; Kim, S; Kim, M; Hong, YA; Shin, SJ; Park, CW; Chang, YS; Chung, S and Kim, HS (2018). D-Pinitol alleviates cyclosporine A-induced renal tubulointerstitial fibrosis via activating Sirt1 and Nrf2 antioxidant pathways. Int. J. Mol. Med., 41: 1826-1834.
Kong, SZ; Li, JC; Li, SD; Liao, MN; Li, CP; Zheng, PJ; Guo, MH; Tan, WX; Zheng, ZH and Hu, Z (2018). Anti-aging effect of chitosan oligosaccharide on d-galactose-induced subacute aging in mice. Mar. Drugs. 16: 181.
Leathem, A; Simone, M; Dennis, JM and Witting, PK (2022). The cyclic nitroxide TEMPOL ameliorates oxidative stress but not inflammation in a cell model of parkinson’s disease. Antioxidants (Basel). 11: 257.
Lin, H; Chen, D; Du, Q; Pan, T; Tu, H; Xu, Y; Teng, T; Tu, J; Li, J; Lin, Z; Wang, X; Xu, L and Chen, YP (2020). Dietary copper plays an important role in maintaining intestinal barrier integrity during alcohol-induced liver disease through regulation of the intestinal HIF-1α signaling pathway and oxidative stress. Front. Physiol., 11: 369.
Mei, L; Zheng, Y; Ma, T; Xia, B; Gao, X; Hao, Y; Luo, Z and Huang, J (2021). The novel antioxidant compound JSH-23 prevents osteolysis by scavenging ROS during both osteoclastogenesis and osteoblastogenesis. Front. Pharmacol., 12: 734774.
Meng, S; Wang, YU; Wang, S; Qian, W; Shao, Q; Dou, M; Zhao, S; Wang, J; Li, M; An, Y; He, L and Zhang, C (2023). Establishment and characterization of an immortalized bovine intestinal epithelial cell line. J. Anim.
Sci., 101: skad215.
Ni, Q; Su, X; Chen, J and Tian, W (2015). Prediction of metabolic gene biomarkers for neurodegenerative disease by an integrated network-based approach. Biomed. Res. Int., 2015: 432012.
Qiao, K; Jiang, R; Contreras, GA; Xie, L; Pascottini, OB; Opsomer, G and Dong, Q (2024). The complex interplay of insulin resistance and metabolic inflammation in tansition dairy cows. Animals (Basel). 14: 832.
Qiu, P; Liu, L; Fang, J; Zhang, M; Wang, H; Peng, Y; Chen, M; Liu, J; Wang, F and Zhao, Q (2021). Identification of pharmacological autophagy regulators of active ulcerative colitis. Front. Pharmacol., 12: 769718.
Shao, D; Shen, W; Miao, Y; Gao, Z; Pan, M; Wei, Q; Yan, Z; Zhao, X and Ma, B (2023). Sulforaphane prevents LPS-induced inflammation by regulating the Nrf2-mediated autophagy pathway in goat mammary epithelial cells and a mouse model of mastitis. J. Anim. Sci. Biotechnol., 14: 61.
Shawky, E; Nada, AA and Ibrahim, RS (2020). Potential role of medicinal plants and their constituents in the mitigation of SARS-CoV-2: identifying related therapeutic targets using network pharmacology and molecular docking analyses. RSC Adv., 10: 27961-27983.
Simmler, C; Pauli, GF; Chen, SN (2013). Phytochemistry and biological properties of glabridin. Fitoterapia. 90: 160-184.
Sotillo, J; Ferreira, I; Potriquet, J; Laha, T; Navarro, S; Loukas, A and Mulvenna, J (2017). Changes in protein expression after treatment with Ancylostoma caninum excretory/secretory products in a mouse model of colitis. Sci. Rep., 7: 41883.
Sun, Y; Lu, Q; He, L; Shu, Y; Zhang, S; Tan, S and Tang, L (2017). Active fragment of Veronica ciliata fisch. attenuates t-BHP-induced oxidative stress injury in HepG2 cells through antioxidant and antiapoptosis activities. Oxid. Med. Cell. Longev., 2017: 4727151.
Surai, PF; Kochish, II; Fisinin, VI and Juniper, DT (2019). Revisiting oxidative stress and the use of organic selenium in dairy cow nutrition. Animals (Basel). 9: 462.
Wang, X; Zhu, L; Hu, J; Guo, R; Ye, S; Liu, F; Wang, D; Zhao, Y; Hu, A; Wang, X; Guo, K and Lin, L (2020). FGF21 attenuated LPS-induced depressive-like behavior via inhibiting the inflammatory pathway. Front. Pharmacol., 11: 154.
Wesdorp, MA; Schwab, A; Bektas, EI; Narcisi, R; Eglin, D; Stoddart, MJ; Osch, GJVMV and D’Este, M (2023). A culture model to analyze the acute biomaterial-dependent reaction of human primary neutrophils in vitro. Bioact. Mater., 20: 627-637.
Yang, CH; Schrepfer, T and Schacht, J (2015). Age-related hearing impairment and the triad of acquired hearing loss. Front. Cell. Neurosci., 9: 276.
Zhang, L; Zhang, H; Gu, J; Xu, W; Yuan, N; Sun, J and Li, H (2022). Glabridin inhibits liver fibrosis and hepatic stellate cells activation through suppression of inflammation and oxidative stress by activating PPARγ in carbon tetrachloride-treated mice. Int. Immunopharmacol., 113: 109433.
Zheng, H; Zhao, Y and Guo, L (2022). A bioactive substance derived from brown seaweeds: Phlorotannins. Mar. Drugs. 20: 742.

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