1. Academic Validation
  2. Rubrofusarin-6-β-gentiobioside inhibits lipid accumulation and weight gain by regulating AMPK/mTOR signaling

Rubrofusarin-6-β-gentiobioside inhibits lipid accumulation and weight gain by regulating AMPK/mTOR signaling

  • Phytomedicine. 2019 Sep;62:152952. doi: 10.1016/j.phymed.2019.152952.
Yo-Han Han 1 Ji-Ye Kee 1 Seong-Hwan Park 2 Jeong-Geon Mun 1 Hee-Dong Jeon 1 Jinbong Park 3 Qin-Peng Zou 4 Xiang-Qian Liu 5 Seung-Heon Hong 6
Affiliations

Affiliations

  • 1 Department of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Republic of Korea.
  • 2 Department of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Republic of Korea; Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea.
  • 3 Department of Pharmacology, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
  • 4 Changsha Broad-Ocean Bio-science and Technique Co., Ltd., Changsha 410205, China.
  • 5 School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China.
  • 6 Department of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Republic of Korea. Electronic address: jooklim@wku.ac.kr.
Abstract

Background: Although rubrofusarin-6-β-gentiobioside (RFG), which is a component of Cassiae tora seed, could likely regulate hyperlipidemia, its anti-obesity effect and related mechanism have not been elucidated.

Purpose: The aim of this study was to examine whether RFG can ameliorate obesity and the mechanism of lipid accumulation regulated by RFG.

Study design: In in vitro experiments, we confirmed the anti-adipogenic effect of RFG using 3T3-L1 cells and human adipose mesenchymal stem cells (hAMSCs). To confirm the anti-obesity effect, High-Fat Diet (HFD)-induced obese mice were selected as a model.

Methods: We investigated anti-adipogenic effects of RFG using MTS assay, Oil Red O Staining, real-time RT-PCR, western blot analysis, and immunofluorescence staining. The anti-obesity effect of RFG was confirmed in HFD-induced mice model using hematoxylin and eosin staining and serum analysis.

Results: RFG inhibited lipid accumulation in 3T3-L1 cells and hAMSCs by reducing expression of mammalian targets of rapamycin (mTOR), Peroxisome Proliferator-activated Receptor (PPAR)γ, and CCAAT-enhancer binding protein (C/EBP)α. RFG phosphorylated AMP-activated protein kinase (AMPK) in a liver kinase B (LKB) 1-independent manner. Moreover, the anti-adipogenic effect of RFG was blocked by AMPK Inhibitor. These results suggest that RFG inhibits lipid accumulation via AMPK signaling. Furthermore, RFG reduced the body weight, size of epididymal white adipose tissue (eWAT), and fatty liver in the mice. RFG also suppressed levels of adipogenic factors PPARγ, C/EBPα, FAS, LPL, and aP2) by activating AMPK in the eWAT and liver.

Conclusion: RFG can ameliorate obesity, and thus, could be used as a therapeutic agent for treating obesity.

Keywords

3T3-L1; AMPK; Cassiae tora seed; Human adipose mesenchymal stem cells; Rubrofusarin-6-β-gentiobioside; mTOR.

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