Equisetin is an anti-obesity candidate through targeting 11β-HSD1.
10.1016/j.apsb.2022.01.006
- Author:
Zhenlu XU
1
;
Dongyun LIU
2
;
Dong LIU
2
;
Xue REN
3
;
Haibo LIU
1
;
Guihong QI
1
;
Yue ZHOU
1
;
Chongming WU
1
;
Kui ZHU
4
;
Zhongmei ZOU
1
;
Jing YUAN
3
;
Wenhan LIN
2
;
Peng GUO
1
Author Information
1. Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China.
2. State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
3. Capital Institute of Pediatrics, Beijing 100020, China.
4. National Center for Veterinary Drug Safety Evaluation, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
- Publication Type:Journal Article
- Keywords:
11β-HSD1;
11β-HSD1 inhibitor;
Adipocyte;
Adipose tissue;
EQST;
Lipid accumulation;
Obesity;
Preadipocyte differentiation
- From:
Acta Pharmaceutica Sinica B
2022;12(5):2358-2373
- CountryChina
- Language:English
-
Abstract:
Obesity is increasingly prevalent globally, searching for therapeutic agents acting on adipose tissue is of great importance. Equisetin (EQST), a meroterpenoid isolated from a marine sponge-derived fungus, has been reported to display antibacterial and antiviral activities. Here, we revealed that EQST displayed anti-obesity effects acting on adipose tissue through inhibiting adipogenesis in vitro and attenuating HFD-induced obesity in mice, doing so without affecting food intake, blood pressure or heart rate. We demonstrated that EQST inhibited the enzyme activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a therapeutic target of obesity in adipose tissue. Anti-obesity properties of EQST were all offset by applying excessive 11β-HSD1's substrates and 11β-HSD1 inhibition through knockdown in vitro or 11β-HSD1 knockout in vivo. In the 11β-HSD1 bypass model constructed by adding excess 11β-HSD1 products, EQST's anti-obesity effects disappeared. Furthermore, EQST directly bond to 11β-HSD1 protein and presented remarkable better intensity on 11β-HSD1 inhibition and better efficacy on anti-obesity than known 11β-HSD1 inhibitor. Therefore, EQST can be developed into anti-obesity candidate compound, and this study may provide more clues for developing higher effective 11β-HSD1 inhibitors.
