Veratri Nigri Rhizoma Et Radix (Veratrum Nigrum L.) and Its Constituent Jervine Prevent Adipogenesis Via Activation of the LKB1-AMPKα-ACC Axis In Vivo and In Vitro

Overview

Journal Evid Based Complement Alternat Med

Specialty Rehabilitation Medicine

Date 2016 May 5

PMID 27143989

Citations 8

Authors

Jinbong Park

Yong-Deok Jeon

Hye-Lin Kim

Dae-Seung Kim

Yo-Han Han

Yunu Jung

Dong-Hyun Youn

JongWook Kang

Daeyeon Yoon

Mi-Young Jeong

Jong-Hyun Lee

Seung-Heon Hong

Junhee Lee

Jae-Young Um

Affiliations

Soon will be listed here.

Abstract

This study was performed in order to investigate the antiobese effects of the ethanolic extract of Veratri Nigri Rhizoma et Radix (VN), a herb with limited usage, due to its toxicology. An HPLC analysis identified jervine as a constituent of VN. By an Oil Red O assay and a Real-Time RT-PCR assay, VN showed higher antiadipogenic effects than jervine. In high-fat diet- (HFD-) induced obese C57BL/6J mice, VN administration suppressed body weight gain. The levels of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT-enhancer-binding protein alpha (C/EBPα), adipocyte fatty-acid-binding protein (aP2), adiponectin, resistin, and LIPIN1 were suppressed by VN, while SIRT1 was upregulated. Furthermore, VN activated phosphorylation of the liver kinase B1- (LKB1-) AMP-activated protein kinase alpha- (AMPKα-) acetyl CoA carboxylase (ACC) axis. Further investigation of cotreatment of VN with the AMPK agonist AICAR or AMPK inhibitor Compound C showed that VN can activate the phosphorylation of AMPKα in compensation to the inhibition of Compound C. In conclusion, VN shows antiobesity effects in HFD-induced obese C57BL/6J mice. In 3T3-L1 adipocytes, VN has antiadipogenic features, which is due to activating the LKB1-AMPKα-ACC axis. These results suggest that VN has a potential benefit in preventing obesity.

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References

Ramirez-Zacarias J, Castro-Munozledo F . Quantitation of adipose conversion and triglycerides by staining intracytoplasmic lipids with Oil red O. Histochemistry. 1992; 97(6):493-7. DOI: 10.1007/BF00316069. View

Xing Y, Yan F, Liu Y, Liu Y, Zhao Y . Matrine inhibits 3T3-L1 preadipocyte differentiation associated with suppression of ERK1/2 phosphorylation. Biochem Biophys Res Commun. 2010; 396(3):691-5. DOI: 10.1016/j.bbrc.2010.04.163. View

Brun R, Kim J, Hu E, Altiok S, Spiegelman B . Adipocyte differentiation: a transcriptional regulatory cascade. Curr Opin Cell Biol. 1996; 8(6):826-32. DOI: 10.1016/s0955-0674(96)80084-6. View

Long Y, Zierath J . AMP-activated protein kinase signaling in metabolic regulation. J Clin Invest. 2006; 116(7):1776-83. PMC: 1483147. DOI: 10.1172/JCI29044. View

Hou X, Xu S, Maitland-Toolan K, Sato K, Jiang B, Ido Y . SIRT1 regulates hepatocyte lipid metabolism through activating AMP-activated protein kinase. J Biol Chem. 2008; 283(29):20015-26. PMC: 2459285. DOI: 10.1074/jbc.M802187200. View

Gowans G, Hawley S, Ross F, Grahame Hardie D . AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation. Cell Metab. 2013; 18(4):556-66. PMC: 3791399. DOI: 10.1016/j.cmet.2013.08.019. View

Diez J, Iglesias P . The role of the novel adipocyte-derived protein adiponectin in human disease: an update. Mini Rev Med Chem. 2010; 10(9):856-69. DOI: 10.2174/138955710791608325. View

Huang B, Yuan H, Kim D, Quan H, Chung S . Cinnamaldehyde prevents adipocyte differentiation and adipogenesis via regulation of peroxisome proliferator-activated receptor-γ (PPARγ) and AMP-activated protein kinase (AMPK) pathways. J Agric Food Chem. 2011; 59(8):3666-73. DOI: 10.1021/jf104814t. View

Spiegelman B, Flier J . Obesity and the regulation of energy balance. Cell. 2001; 104(4):531-43. DOI: 10.1016/s0092-8674(01)00240-9. View

10.

Wang H, Li S, Zhao C, Zeng X . A system for screening agonists targeting beta2-adrenoceptor from Chinese medicinal herbs. J Zhejiang Univ Sci B. 2009; 10(4):243-50. PMC: 2666200. DOI: 10.1631/jzus.B0820340. View

11.

Fulco M, Sartorelli V . Comparing and contrasting the roles of AMPK and SIRT1 in metabolic tissues. Cell Cycle. 2008; 7(23):3669-79. PMC: 2607479. DOI: 10.4161/cc.7.23.7164. View

12.

Buhl E, Jessen N, Pold R, Ledet T, Flyvbjerg A, Pedersen S . Long-term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome. Diabetes. 2002; 51(7):2199-206. DOI: 10.2337/diabetes.51.7.2199. View

13.

Jeong M, Kim H, Park J, Jung Y, Youn D, Lee J . Rubi Fructus (Rubus coreanus) activates the expression of thermogenic genes in vivo and in vitro. Int J Obes (Lond). 2014; 39(3):456-64. DOI: 10.1038/ijo.2014.155. View

14.

Tang J, Li H, Shen Y, Jin H, Yan S, Liu R . Antitumor activity of extracts and compounds from the rhizomes of Veratrum dahuricum. Phytother Res. 2008; 22(8):1093-6. DOI: 10.1002/ptr.2463. View

15.

Witters L, WATTS T, Daniels D, Evans J . Insulin stimulates the dephosphorylation and activation of acetyl-CoA carboxylase. Proc Natl Acad Sci U S A. 1988; 85(15):5473-7. PMC: 281779. DOI: 10.1073/pnas.85.15.5473. View

16.

Winder W, Wilson H, Hardie D, Rasmussen B, Hutber C, Call G . Phosphorylation of rat muscle acetyl-CoA carboxylase by AMP-activated protein kinase and protein kinase A. J Appl Physiol (1985). 1997; 82(1):219-25. DOI: 10.1152/jappl.1997.82.1.219. View

17.

Tang J, Li H, Shen Y, Jin H, Yan S, Liu X . Antitumor and antiplatelet activity of alkaloids from veratrum dahuricum. Phytother Res. 2009; 24(6):821-6. DOI: 10.1002/ptr.3022. View

18.

Ruderman N, Carling D, Prentki M, Cacicedo J . AMPK, insulin resistance, and the metabolic syndrome. J Clin Invest. 2013; 123(7):2764-72. PMC: 3696539. DOI: 10.1172/JCI67227. View

19.

Price N, Gomes A, Ling A, Duarte F, Martin-Montalvo A, North B . SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab. 2012; 15(5):675-90. PMC: 3545644. DOI: 10.1016/j.cmet.2012.04.003. View

20.

Luque C, Rey J . Sibutramine: a serotonin-norepinephrine reuptake-inhibitor for the treatment of obesity. Ann Pharmacother. 1999; 33(9):968-78. DOI: 10.1345/aph.18319. View