Study the protective efficacy of α-Bisabolol on non-alcoholic fatty liver disease induced by high-fat diet in C57/BL6 mice

Year 2026, Volume: 30 Issue: 2, 404 - 416, 15.03.2026

Yara Annouf , K. Eswar Kumar

https://doi.org/10.12991/jrespharm.1673440

https://izlik.org/JA23AA77SR

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a condition that manifests in varying degrees, from accumulation of fat to liver inflammation and injury, progression to fibrosis, and ultimately cirrhosis. α-bisabolol has gained a lot of interest because of its pharmacological properties. However, its potential protective effects on NAFLD haven't been investigated yet. This research aims to examine the protective efficacy of α-Bisabolol on a mouse model of NAFLD. For induction of NAFLD in C57BL/6 mice, a high-fat diet (HFD) was used for a period of 16 weeks. α-Bisabolol was administered in two different doses (50 mg/kg and 100 mg/kg)) with HFD for 16 weeks. Liver injury was evaluated by liver index, biochemical assays, hepatic histological changes, and liver triglyceride (TG) content. Oxidative stress and inflammatory status in the hepatic tissue along with hepatic Sterol Regulatory Element-binding Protein 1C (SREBP-1C) levels were also studied. The results revealed that α-Bisabolol in a high dose (100 mg/kg) significantly decreased liver index and effectively enhanced the liver function by decreasing serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Moreover, α-Bisabolol in a high dose lowered the levels of TG in serum. In addition, it attenuated hepatic steatosis and inflammation as well as decreased liver TG content. Additionally, it significantly inhibited oxidative stress and the inflammatory response, as well as downregulated hepatic SREBP-1c expression. This study found that α-Bisabolol can protect mice from NAFLD caused by high-fat diet by inhibiting lipogenesis, reducing inflammation, and mitigating oxidative stress.

Keywords

Steatosis , α-Bisabolol , oxidative stress , inflammation , lipogenesis

References

• 1. Méndez‐Sánchez N, Arrese M, Zamora‐Valdés D, Uribe M. Current concepts in the pathogenesis of nonalcoholic fatty liver disease. Liver Int. 2007; 27(4):423-433. https://doi.org/10.1111/j.1478-3231.2007.01483.x
• 2. Choi SS, Diehl AM. Hepatic triglyceride synthesis and nonalcoholic fatty liver disease. Curr Opin Lipidol. 2008; 19(3):295-300. https://doi.org/10.1097/mol.0b013e3282ff5e55
• 3. Takahashi Y, Sugimoto K, Inui H, Fukusato T. Current pharmacological therapies for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol. 2015; 21(13):3777- 3785. https://doi.org/10.3748/wjg.v21.i13.3777
• 4. Loomba R, Friedman SL, Shulman GI. Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell. 2021 13; 184(10):2537-2564. https://doi.org/10.1016/j.cell.2021.04.015
• 5. Guo X, Yin X, Liu Z, Wang J. Non-alcoholic fatty liver disease (NAFLD) pathogenesis and natural products for prevention and treatment. Int. J. Mol. Sci. 2022; 23(24): 1-18. https://doi.org/10.3390/ijms232415489
• 6. Zhang L, Yao Z, Ji G. Herbal extracts and natural products in alleviating non-alcoholic fatty liver disease via activating autophagy. Front. Pharmacol. 2018; 9: 1-7. https://doi.org/10.3389/fphar.2018.01459
• 7. Li H, Guan T, Qin S, Xu Q, Yin L, Hu Q. Natural products in pursuing novel therapies of nonalcoholic fatty liver disease and steatohepatitis. Drug Discov. Today. 2023; 28(3):103471. https://doi.org/10.1016/j.drudis.2022.103471
• 8. Fernandes MY, do Carmo MR, Fonteles AA, de Sousa Neves JC, da Silva AT, Pereira JF, de Oliveira Ferreira E, de Lima NM, Neves KR, de Andrade GM. (-)-α-Bisabolol prevents neuronal damage and memory deficits through reduction of proinflammatory markers induced by permanent focal cerebral ischemia in mice. Eur. J. Pharmacol. 2019; 842: 270-280. https://doi.org/10.1016/j.ejphar.2018.09.036
• 9. Javed H, Meeran MF, Azimullah S, Bader Eddin L, Dwivedi VD, Jha NK, Ojha S. α-Bisabolol, a dietary bioactive phytochemical attenuates dopaminergic neurodegeneration through modulation of oxidative stress, neuroinflammation and apoptosis in rotenone-induced rat model of Parkinson’s disease. Biomol. 2020; 10 (10): 1-23. https://doi.org/10.3390/biom10101421
• 10. Nagoor Meeran MF, Arunachalam S, Azimullah S, Saraswathiamma D, Albawardi A, Almarzooqi S, Jha NK, Subramanya S, Beiram R, Ojha S. α-Bisabolol, a dietary sesquiterpene, attenuates doxorubicin-induced acute cardiotoxicity in rats by inhibiting cellular signaling pathways, Nrf2/Keap-1/HO-1, Akt/mTOR/GSK-3β, NF-κB/p38/MAPK, and NLRP3 inflammasomes regulating oxidative stress and inflammatory cascades. Int. J. Mol. Sci. 2023; 24(18): 1-20. https://doi.org/10.3390/ijms241814013
• 11. Meeran MN, Azimullah S, Laham F, Tariq S, Goyal SN, Adeghate E, Ojha S. α-Bisabolol protects against β-adrenergic agonist-induced myocardial infarction in rats by attenuating inflammation, lysosomal dysfunction, NLRP3 inflammasome activation and modulating autophagic flux. Food & Function. 2020; 11(1): 965-976. https://doi.org/10.1039/c9fo00530g
• 12. Huang CZ, Tung YT, Hsia SM, Wu CH, Yen GC. The hepatoprotective effect of Phyllanthus emblica L. fruit on high fat diet-induced non-alcoholic fatty liver disease (NAFLD) in SD rats. Food & function. 2017; 8(2): 842-850. https://doi.org/10.1039/c6fo01585a
• 13. Kim B, Kwon J, Kim MS, Park H, Ji Y, Holzapfel W, Hyun CK. Protective effects of Bacillus probiotics against high-fat diet-induced metabolic disorders in mice. PloS one. 2018; 13(12): 1-17. https://doi.org/10.1371/journal.pone.0210120
• 14. Choe SY, Seo Y, Bang CY, Woo SH, Kang M. Protective effects of Gymnaster koraiensis extract on high fat diet-induced fatty liver in mice. ADV TRADIT MED. 2021 Jun;21(2): 1-9. https://doi.org/10.1007/s13596-020-00434-w
• 15. Magnani L, Gaydou EM, Hubaud JC. Spectrophotometric measurement of antioxidant properties of flavones and flavonols against superoxide anion. Anal. Chim. Acta . 2000; 411(1-2):209-216. https://doi.org/10.1016/s0003-2670(00)00717-0
• 16. Cohen G, Dembiec D, Marcus J. Measurement of catalase activity in tissue extracts. Anal. Biochem. 1970; 34(1): 30-38. https://doi.org/10.1016/0003-2697(70)90083-7
• 17. Li X. Improved pyrogallol autoxidation method: a reliable and cheap superoxide-scavenging assay suitable for all antioxidants. J Agric Food Chem. 2012; 60(25): 6418-6424. https://doi.org/10.1021/jf204970r
• 18. Nagababu E, Rifkind JM, Boindala S, Nakka L. Assessment of antioxidant activity of eugenol in vitro and in vivo methods. Methods Mol Biol. 2010; 610: 165–180. https://doi.org/10.1007/978-1-60327-029-8_10
• 19. Hagar HH, El Medany A, El Eter E, Arafa M. Ameliorative effect of pyrrolidinedithiocarbamate on acetic acid-induced colitis in rats. Eur. J. Pharmacol. 2007; 554(1):69-77. https://doi.org/10.1016/j.ejphar.2006.09.066
• 20. Rahman I, Kode A, Biswas SK. Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method. Nat. Protoc. 2006; 1(6):3159-3165. https://doi.org/10.1038/nprot.2006.378
• 21. Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim. Biophys. Acta. 1979; 582(1):67-78. https://doi.org/10.1016/0304-4165(79)90289-7
• 22. Flessa CM, Nasiri-Ansari N, Kyrou I, Leca BM, Lianou M, Chatzigeorgiou A, Kaltsas G, Kassi E, Randeva HS. Genetic and diet-induced animal models for non-alcoholic fatty liver disease (NAFLD) research. Int. J. Mol. Sci. 2022; 23(24):15791. https://doi.org/10.3390/ijms232415791
• 23. Zhou Y, Xie L. High fat diet mouse model in the study of nonalcoholic fatty liver disease and hepatocellular carcinoma. Am J Digest Dis. 2015;2(1): 60-67.
• 24. Chen Z, Tian R, She Z, Cai J, Li H. Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease. Free Radic. Biol. Med. 2020; 152: 116-141. https://doi.org/10.1016/j.freeradbiomed.2020.02.025
• 25. Hong T, Chen Y, Li X, Lu Y. The role and mechanism of oxidative stress and nuclear receptors in the development of NAFLD. OXID MED CELL LONGEV. 2021; 2021(1): 1-25. https://doi.org/10.1155/2021/6889533
• 26. Braga PC, Dal Sasso M, Fonti E, Culici M. Antioxidant activity of bisabolol: inhibitory effects on chemiluminescence of human neutrophil bursts and cell-free systems. PHA. 2009; 83(2): 110-115. https://doi.org/10.1159/000186049
• 27. Elazab ST, Hsu WH. Antagonism of cadmium-induced liver injury in ducks by α-bisabolol. Front. Vet. Sci. 2022 ;9: 1-13. https://doi.org/10.3389/fvets.2022.1024549
• 28. Meeran MF, Laham F, Al‐Taee H, Azimullah S, Ojha S. Protective effects of α‐bisabolol on altered hemodynamics, lipid peroxidation, and nonenzymatic antioxidants in isoproterenol‐induced myocardial infarction: In vivo and in vitro evidences. J. Biochem. Mol. Toxico. 2018; 32(10): 1-6. https://doi.org/10.1002/jbt.22200
• 29. Wang J, Jiang Y, Jin L, Qian C, Zuo W, Lin J, Xie L, Jin B, Zhao Y, Huang L, Wang Y. Alantolactone attenuates high-fat diet-induced inflammation and oxidative stress in non-alcoholic fatty liver disease. Nutr. Diabetes. 2024; 14(1): 1-10. https://doi.org/10.1038/s41387-024-00300-7
• 30. Reda D, Elshopakey GE, Albukhari TA, Almehmadi SJ, Refaat B, Risha EF, Mahgoub HA, El-Boshy ME, Abdelhamid FM. Vitamin D3 alleviates nonalcoholic fatty liver disease in rats by inhibiting hepatic oxidative stress and inflammation via the SREBP-1-c/PPARα-NF-κB/IR-S2 signaling pathway. Front. pharmacol. 2023 May 16;14:1164512. https://doi.org/10.3389/fphar.2023.1164512
• 31. Heida A, Gruben N, Catrysse L, Koehorst M, Koster M, Kloosterhuis NJ, Gerding A, Havinga R, Bloks VW, Bongiovanni L, Wolters JC. The hepatocyte IKK: NF-κ B axis promotes liver steatosis by stimulating _de novo_ lipogenesis and cholesterol synthesis, Mol Metab. 2021; 54: 1-14. https://doi.org/10.1016/j.molmet.2021.101349
• 32. Xu C, Sheng S, Dou H, Chen J, Zhou K, Lin Y, Yang H. α-Bisabolol suppresses the inflammatory response and ECM catabolism in advanced glycation end products-treated chondrocytes and attenuates murine osteoarthritis. Int. Immunopharmacol. 2020; 84: 1-9. https://doi.org/10.1016/j.intimp.2020.106530
• 33. Venkataraman B, Almarzooqi S, Raj V, Dudeja PK, Bhongade BA, Patil RB, Ojha SK, Attoub S, Adrian TE, Subramanya SB. α‐Bisabolol Mitigates Colon Inflammation by Stimulating Colon PPAR‐γ Transcription Factor: In Vivo and In Vitro Study. PPAR Res. 2022; 2022(1): 1-22. https://doi.org/10.1155/2022/5498115
• 34. K. Maurya A, Singh M, Dubey V, Srivastava S, Luqman S, U. Bawankule D. α-(-)-bisabolol reduces pro-inflammatory cytokine production and ameliorates skin inflammation. Curr. Pharm. Biotechnol. 2014; 15(2): 173-181. https://doi.org/10.2174/1389201015666140528152946
• 35. Cheng K, Song Z, Zhang H, Li S, Wang C, Zhang L, Wang T. The therapeutic effects of resveratrol on hepatic steatosis in high-fat diet-induced obese mice by improving oxidative stress, inflammation and lipid-related gene transcriptional expression. Med. Mol. Morphol. 2019; 52: 187-197. https://doi.org/10.1007/s00795-019-00216-7
• 36. Aragno M, Tomasinelli CE, Vercellinatto I, Catalano MG, Collino M, Fantozzi R, Danni O, Boccuzzi G. SREBP-1c in nonalcoholic fatty liver disease induced by Western-type high-fat diet plus fructose in rats. Free Radic. Biol. Med. 2009; 47(7): 1067-1074. https://doi.org/10.1016/j.freeradbiomed.2009.07.016