TY - JOUR
T1 - Malabaricone C as natural sphingomyelin synthase inhibitor against diet-induced obesity and its lipid metabolism in mice
AU - Othman, Muhamad Aqmal
AU - Yuyama, Kohei
AU - Murai, Yuta
AU - Igarashi, Yasuyuki
AU - Mikami, Daisuke
AU - Sivasothy, Yasodha
AU - Awang, Khalijah
AU - Monde, Kenji
N1 - Funding Information:
This work was supported by a grant-in-aid for scientific research KAKENHI (grant 23651211 and 17K19188) from the MEXT of Japan and MEXT Doctoral program for Data Related Innovation Expert Hokkaido University (D-DRIVE-HU) program. The authors thank the International Graduate Program (IGP), Hokkaido University for the scholarship given.
Publisher Copyright:
© 2019 American Chemical Society.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/8
Y1 - 2019/8
N2 - 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.
AB - 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.
KW - malabaricone C
KW - Membrane protein
KW - myristica cinnamomea
KW - obesity
KW - sphingomyelin synthase
UR - https://www.scopus.com/pages/publications/85071085326
U2 - 10.1021/acsmedchemlett.9b00171
DO - 10.1021/acsmedchemlett.9b00171
M3 - Article
AN - SCOPUS:85071085326
SN - 1948-5875
VL - 10
SP - 1154
EP - 1158
JO - ACS Medicinal Chemistry Letters
JF - ACS Medicinal Chemistry Letters
IS - 8
ER -
SDG 3 Good Health and Well-being