Malabaricone C as natural sphingomyelin synthase inhibitor against diet-induced obesity and its lipid metabolism in mice

Muhamad Aqmal Othman, Kohei Yuyama, Yuta Murai, Yasuyuki Igarashi, Daisuke Mikami, Yasodha Sivasothy, Khalijah Awang, Kenji Monde

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7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1154-1158
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume10
Issue number8
DOIs
Publication statusPublished - Aug 2019
Externally publishedYes

Keywords

  • malabaricone C
  • Membrane protein
  • myristica cinnamomea
  • obesity
  • sphingomyelin synthase

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