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Br J Pharmacol. 2018 May;175(9):1439-1450. doi: 10.1111/bph.14139. Epub 2018 Mar 14.

The natural compound, formononetin, extracted from Astragalus membranaceus increases adipocyte thermogenesis by modulating PPARγ activity.

Nie T1,2,3, Zhao S2,3, Mao L2,3, Yang Y3, Sun W2,3, Lin X4, Liu S4, Li K2,3, Sun Y2,3, Li P2,3, Zhou Z5, Lin S1, Hui X6,7, Xu A6,7, Ma CW4, Xu Y2,3, Wang C1, Dunbar PR8, Wu D2,3,9.

Author information

1
Central Laboratory of the First Affiliated Hospital of Jinan University, Guangzhou, China.
2
Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
3
Guangzhou Medical University, Guangzhou, China.
4
Research and Development Centre, Infinitus (China) Company Ltd., Guangzhou, China.
5
Institute of Metabolism and Endocrinology, 2nd Xiangya Hospital, Central South University, Diabetes Center, Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China.
6
State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, Hong Kong.
7
Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong.
8
School of Biological Sciences and Maurice Wilkins Centre, University of Auckland, Auckland, New Zealand.
9
GUANGZHOU Regenerative Medicine and Health Laboratory, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.

Abstract

BACKGROUND AND PURPOSE:

Increasing energy expenditure through adipocyte thermogenesis is generally accepted as a promising strategy to mitigate obesity and its related diseases. However, few clinically effective and safe agents are known to promote adipocyte thermogenesis. In this study, 20 traditional Chinese herbal medicines were screened to examine whether they induced adipocyte thermogenesis.

EXPERIMENTAL APPROACH:

The effects of Chinese herbal medicines or components isolated from extracts of A. membranaceus, on adipocyte thermogenesis were analysed by assessing expression of uncoupling protein 1 (UCP1) by qPCR. Eight-week-old C57BL6/J male mice were fed a high-fat diet for 8 weeks and then randomized to two groups treated with vehicle or formononetin for another 8 weeks. Glucose tolerance tests and staining of adipose tissue with haematoxylin and eosin were carried out. Whole-body oxygen consumption was measured with an open-circuit indirect calorimetry system.

KEY RESULTS:

Extracts of A. membranaceus increased expression of Ucp1 in primary cultures of mouse adipocytes. Formononetin was the only known component of A. membranaceus extracts to increase adipocyte Ucp1 expression. Diet-induced obese mice treated with formononetin gained less weight and showed higher energy expenditure than untreated mice. In addition, formononetin binds directly with PPARγ.

CONCLUSIONS AND IMPLICATION:

Taken together, our study demonstrates that the Chinese herbal medicine from A. membranaceus and its constituent formononetin have the potential to reduce obesity and associated metabolic disorders. Our results suggest that formononetin regulates adipocyte thermogenesis as a non-classical PPARγ agonist.

PMID:
29315511
PMCID:
PMC5900995
DOI:
10.1111/bph.14139
[Indexed for MEDLINE]
Free PMC Article

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