Malabaricone C as Natural Sphingomyelin Synthase Inhibitor against Diet-Induced Obesity and Its Lipid Metabolism in Mice

Othman, Muhamad Aqmal and Yuyama, Kohei and Murai, Yuta and Igarashi, Yasuyuki and Mikami, Daisuke and Sivasothy, Yasodha and Awang, Khalijah and Monde, Kenji (2019) Malabaricone C as Natural Sphingomyelin Synthase Inhibitor against Diet-Induced Obesity and Its Lipid Metabolism in Mice. ACS Medicinal Chemistry Letters, 10 (8). pp. 1154-1158. ISSN 1948-5875, DOI https://doi.org/10.1021/acsmedchemlett.9b00171.

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Official URL: https://doi.org/10.1021/acsmedchemlett.9b00171

Abstract

The interaction between natural occurring inhibitors and targeted membrane proteins could be an alternative medicinal strategy for the treatment of metabolic syndrome, notably, obesity. In this study, we identified malabaricones A-C and E (1-4) isolated from the fruits of Myristica cinnamomea King as natural inhibitors for sphingomyelin synthase (SMS), a membrane protein responsible for sphingolipid biosynthesis. Having the most promising inhibition, oral administration of compound 3 exhibited multiple efficacies in reducing weight gain, improving glucose tolerance, and reducing hepatic steatosis in high fat diet-induced obesity mice models. Liver lipid analysis revealed a crucial link between the SMS activities of compound 3 and its lipid metabolism in vitro and in vivo. The nontoxic nature of compound 3 makes it a suitable candidate in search of drugs which can be employed in the treatment and prevention of obesity. © 2019 American Chemical Society.

Item Type: Article
Funders: UNSPECIFIED
Uncontrolled Keywords: malabaricone C; Membrane protein; myristica cinnamomea; obesity; sphingomyelin synthase
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
Divisions: Faculty of Science > Department of Chemistry
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 13 Feb 2020 02:52
Last Modified: 13 Feb 2020 02:52
URI: http://eprints.um.edu.my/id/eprint/23781

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