The Effect of β-caryophyllene on Nonalcoholic Steatohepatitis

Overview

Journal J Toxicol Pathol

Date 2017 Nov 4

PMID 29097836

Citations 9

Authors

Naoya Arizuka

Tomoaki Murakami

Kazuhiko Suzuki

Affiliations

Soon will be listed here.

Abstract

The pathogenesis of nonalcoholic steatohepatitis (NASH) is not fully understood, but many studies have suggested that oxidative stress plays a key role. The methionine- and choline-deficient diet (MCD) administration model can reproduce histopathological features of human NASH and is widely used for investigating NASH. C57BL/6J mice have been used in many studies, but strain differences in pathogenesis have not been sufficiently investigated. We administred MCD to two mouse strains and then compared difference between strains and investigated the effects of β-caryophyllene (BCP), which possesses an antioxidant effect, on development and progression of NASH. ICR and C57BL/6J mice were administred a control diet, MCD, MCD containing 0.02% BCP, or MCD containing 0.2% BCP. After 4 or 8 weeks, mice were sacrificed. In both strains, MCD administration induced hepatic steatosis and inflammation. These lesions were more severe in C57BL/6J mice than ICR mice, and liver fibrosis was observed at 8 weeks in C57BL/6J mice. These changes were attenuated by BCP coadministration. The mRNA expression of monocyte chemotactic and activating factor (MCP)-1 and fibrosis-related factors increased in C57BL/6J mice, and these increases were reduced by BCP coadministration. The mRNA expression of antioxidant-related factors decreased in both strains, and these decreases were attenuated by BCP coadministration. Based on these results, the C57BL/6J mouse was a more suitable model for MCD-induced NASH than the ICR mouse. In addition, it was suggested that antioxidant effect of BCP might suppressed the damage of hepatocytes caused by oxidative stress and following inflammation and fibrosis.

Citing Articles

Exploring β-caryophyllene: a non-psychotropic cannabinoid's potential in mitigating cognitive impairment induced by sleep deprivation.

Lim C, Ogawa S, Kumari Y Arch Pharm Res. 2024; 48(1):1-42.

PMID: 39653971 DOI: 10.1007/s12272-024-01523-z.

Exploring the therapeutic potential of natural compounds modulating the endocannabinoid system in various diseases and disorders: review.

Wilson G, Yang L, Su X, Ding S, Li L, Yang Y Pharmacol Rep. 2023; 75(6):1410-1444.

PMID: 37906390 DOI: 10.1007/s43440-023-00544-7.

A Critical Appraisal of the Most Recent Investigations on the Hepatoprotective Action of Brazilian Plants.

Garcia-Manieri J, Correa V, Backes E, de Sa-Nakanishi A, Bracht L, Fernando Comar J Plants (Basel). 2022; 11(24).

PMID: 36559593 PMC: 9785989. DOI: 10.3390/plants11243481.

β-Caryophyllene Acts as a Ferroptosis Inhibitor to Ameliorate Experimental Colitis.

Wu Y, Zhong L, Huang C, Guo Y, Jin F, Hu Y Int J Mol Sci. 2022; 23(24).

PMID: 36555694 PMC: 9784863. DOI: 10.3390/ijms232416055.

Enhanced Oral Bioavailability of β-Caryophyllene in Healthy Subjects Using the VESIsorb Formulation Technology, a Novel Self-Emulsifying Drug Delivery System (SEDDS).

Modinger Y, Knaub K, Dharsono T, Wacker R, Meyrat R, Land M Molecules. 2022; 27(9).

PMID: 35566210 PMC: 9104399. DOI: 10.3390/molecules27092860.

References

Singh G, Marimuthu P, De Heluani C, Catalan C . Antioxidant and biocidal activities of Carum nigrum (seed) essential oil, oleoresin, and their selected components. J Agric Food Chem. 2006; 54(1):174-81. DOI: 10.1021/jf0518610. View

Pichette A, Larouche P, Lebrun M, Legault J . Composition and antibacterial activity of Abies balsamea essential oil. Phytother Res. 2006; 20(5):371-3. DOI: 10.1002/ptr.1863. View

Baeck C, Wehr A, Karlmark K, Heymann F, Vucur M, Gassler N . Pharmacological inhibition of the chemokine CCL2 (MCP-1) diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury. Gut. 2011; 61(3):416-26. DOI: 10.1136/gutjnl-2011-300304. View

Liang S, Kisseleva T, Brenner D . The Role of NADPH Oxidases (NOXs) in Liver Fibrosis and the Activation of Myofibroblasts. Front Physiol. 2016; 7:17. PMC: 4735448. DOI: 10.3389/fphys.2016.00017. View

De Minicis S, Brenner D . Oxidative stress in alcoholic liver disease: role of NADPH oxidase complex. J Gastroenterol Hepatol. 2008; 23 Suppl 1:S98-103. DOI: 10.1111/j.1440-1746.2007.05277.x. View

Pessayre D . Role of mitochondria in non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2007; 22 Suppl 1:S20-7. DOI: 10.1111/j.1440-1746.2006.04640.x. View

Wu Z, Peng-Chen , Yang-Li , Li J, Xin-Wang , Yong-Wang . Two cinnamoyloctopamine antioxidants from garlic skin attenuates oxidative stress and liver pathology in rats with non-alcoholic steatohepatitis. Phytomedicine. 2015; 22(1):178-82. DOI: 10.1016/j.phymed.2014.11.013. View

Calleja M, Vieites J, Montero-Melendez T, Montero-Meterdez T, Torres M, Faus M . The antioxidant effect of β-caryophyllene protects rat liver from carbon tetrachloride-induced fibrosis by inhibiting hepatic stellate cell activation. Br J Nutr. 2012; 109(3):394-401. DOI: 10.1017/S0007114512001298. View

Pradere J, Kluwe J, De Minicis S, Jiao J, Gwak G, Dapito D . Hepatic macrophages but not dendritic cells contribute to liver fibrosis by promoting the survival of activated hepatic stellate cells in mice. Hepatology. 2013; 58(4):1461-73. PMC: 3848418. DOI: 10.1002/hep.26429. View

10.

Marchesini G, Forlani G . NASH: from liver diseases to metabolic disorders and back to clinical hepatology. Hepatology. 2002; 35(2):497-9. DOI: 10.1053/jhep.2002.31551. View

11.

Koruk M, Taysi S, Savas M, Yilmaz O, Akcay F, Karakok M . Oxidative stress and enzymatic antioxidant status in patients with nonalcoholic steatohepatitis. Ann Clin Lab Sci. 2004; 34(1):57-62. View

12.

von Montfort C, Matias N, Fernandez A, Fucho R, Conde de la Rosa L, Martinez-Chantar M . Mitochondrial GSH determines the toxic or therapeutic potential of superoxide scavenging in steatohepatitis. J Hepatol. 2012; 57(4):852-9. PMC: 3445734. DOI: 10.1016/j.jhep.2012.05.024. View

13.

Ghelardini C, Galeotti N, Di Cesare Mannelli L, Mazzanti G, Bartolini A . Local anaesthetic activity of beta-caryophyllene. Farmaco. 2001; 56(5-7):387-9. DOI: 10.1016/s0014-827x(01)01092-8. View

14.

Cho J, Chang H, Lee S, Kim H, Hwang J, Chun H . Amelioration of dextran sulfate sodium-induced colitis in mice by oral administration of beta-caryophyllene, a sesquiterpene. Life Sci. 2006; 80(10):932-9. DOI: 10.1016/j.lfs.2006.11.038. View

15.

Kirsch R, Clarkson V, Shephard E, Marais D, Jaffer M, Woodburne V . Rodent nutritional model of non-alcoholic steatohepatitis: species, strain and sex difference studies. J Gastroenterol Hepatol. 2003; 18(11):1272-82. DOI: 10.1046/j.1440-1746.2003.03198.x. View

16.

Harrison S, Neuschwander-Tetri B . Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Clin Liver Dis. 2004; 8(4):861-79, ix. DOI: 10.1016/j.cld.2004.06.008. View

17.

Vizzutti F, Provenzano A, Galastri S, Milani S, Delogu W, Novo E . Curcumin limits the fibrogenic evolution of experimental steatohepatitis. Lab Invest. 2009; 90(1):104-15. DOI: 10.1038/labinvest.2009.112. View

18.

Chitturi S, Abeygunasekera S, Farrell G, Holmes-Walker J, Hui J, Fung C . NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology. 2002; 35(2):373-9. DOI: 10.1053/jhep.2002.30692. View

19.

London R, George J . Pathogenesis of NASH: animal models. Clin Liver Dis. 2007; 11(1):55-74, viii. DOI: 10.1016/j.cld.2007.02.010. View

20.

Tambe Y, Tsujiuchi H, Honda G, Ikeshiro Y, Tanaka S . Gastric cytoprotection of the non-steroidal anti-inflammatory sesquiterpene, beta-caryophyllene. Planta Med. 1996; 62(5):469-70. DOI: 10.1055/s-2006-957942. View