2. Academic Validation
  3. Malabaricone C as Natural Sphingomyelin Synthase Inhibitor against Diet-Induced Obesity and Its Lipid Metabolism in Mice

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

  • ACS Med Chem Lett. 2019 Jul 3;10(8):1154-1158. doi: 10.1021/acsmedchemlett.9b00171.
Muhamad Aqmal Othman 1,  Kohei Yuyama 2,  Yuta Murai 3,  Yasuyuki Igarashi 2,  Daisuke Mikami 2,  Yasodha Sivasothy 4,  Khalijah Awang 5,  Kenji Monde 3
Affiliations

Affiliations

  • 1 Graduate School of Life Science, Hokkaido University, Kita 21 Nishi 11, Sapporo 001-0021, Japan.
  • 2 Lipid Biofunction Section, Faculty of Advanced Life Science, Hokkaido University, Kita 21 Nishi 11, Sapporo, 001-0021, Japan.
  • 3 Faculty of Advanced Life Science, Hokkaido University, Kita 21 Nishi 11, Sapporo 001-0021, Japan.
  • 4 Research Centre for Crystalline Materials, Faculty of Science and Technology, Sunway University, 47500 Bandar Sunway, Selangor Darul Ehsan Malaysia.
  • 5 Department of Chemistry, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia.
PMID: 31413799 DOI: 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.

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