THE EFFECTS OF EVODIAMINE ON SERUM TOTAL CHOLESTEROL AND TRIGLYCERIDE LEVELS ARE ASSOCIATED WITH THE ACTIVATION OF THE AMPK SIGNALING PATHWAY IN RATS WITH HYPERLIPEMIA

Hui Yu, Hai Hu, Wuzhuang Gong, Li Yang, Zhanli Wang, Cuifeng Wang

Abstract


Evodiamine, a naturally occurring indole alkaloid, has been reported to have numerous biological activities, including antitumor, antimicrobial and anti-inflammatory effects. Previous studies also suggest that evodiamine prevents obesity. In this study, we confirmed that evodiamine lowered the levels of serum total cholesterol (TC) and triglycerides (TG) in rats with hyperlipemia. Furthermore, our findings suggest that the activation of the AMP-activated protein kinase (AMPK) pathway might contribute in part to the effect of evodiamine on the serum levels of TC and TG.

 

Key words: evodiamine; AMP-activated protein kinase; total cholesterol; triglycerides

 

Received: September 4, 2015; Revised: October 14, 2015; Accepted: October 26, 2015; Published online: May 9, 2016


Full Text:

PDF

References


Shoji N, Umeyama A, Takemoto T, Kajiwara A, Ohizumi Y. Isolation of evodiamine, a powerful cardiotonic principle, from Evodia rutaecarpa Bentham (Rutaceae). J Pharm Sci. 1986;75(6):612-3.

Pearce LV, Petukhov PA, Szabo T, Kedei N, Bizik F, Kozikowski AP, Blumberg PM. Evodiamine functions as an agonist for the vanilloid receptor TRPV1. Org Biomol Chem. 2004;2(16):2281-6.

Wang Z, Sun L, Yu H, Zhang Y, Gong W, Jin H, Zhang L, Liang H. Binding mode prediction of evodiamine within vanilloid receptor TRPV1. Int J Mol Sci. 2012;13(7):8958-69.

Yu H, Tu Y, Zhang C, Fan X, Wang X, Wang Z, Liang H. Evodiamine as a novel antagonist of aryl hydrocarbon receptor. Biochem Biophys Res Commun. 2010;402(1):94-8.

Dong G, Wang S, Miao Z, Yao J, Zhang Y, Guo Z, Zhang W, Sheng C. New tricks for an old natural product: discovery of highly potent evodiamine derivatives as novel antitumor agents by systemic structure-activity relationship analysis and biological evaluations. J Med Chem. 2012;55(17):7593-613.

Yu H, Jin H, Gong W, Wang Z, Liang H. Pharmacological actions of multi-target-directed evodiamine. Molecules. 2013;18(2):1826-43.

Kobayashi Y, Nakano Y, Kizaki M, Hoshikuma K, Yokoo Y, Kamiya T. Capsaicin-like anti-obese activities of evodiamine from fruits of Evodia rutaecarpa, a vanilloid receptor agonist. Planta Med. 2001;67(7):628-33.

Shi J, Yan J, Lei Q, Zhao J, Chen K, Yang D, Zhao X, Zhang Y. Intragastric administration of evodiamine suppresses NPY and AgRP gene expression in the hypothalamus and decreases food intake in rats. Brain Res. 2009;1247:71-8.

Wang T, Wang Y, Kontani Y, Kobayashi Y, Sato Y, Mori N, Yamashita H. Evodiamine improves diet-induced obesity in a uncoupling protein-1-independent manner: involvement of antiadipogenic mechanism and extracellularly regulated kinase/mitogen-activated protein kinase signaling. Endocrinology. 2008;149(1):358-66.

Wu CL, Hung CR, Chang FY, Lin LC, Pau KY, Wang PS. Effects of evodiamine on gastrointestinal motility in male rats. Eur J Pharmacol. 2002;457(2-3):169-76.

Srivastava RA, Pinkosky SL, Filippov S, Hanselman JC, Cramer CT, Newton RS. AMP-activated protein kinase: an emerging drug target to regulate imbalances in lipid and carbohydrate metabolism to treat cardio-metabolic diseases. J Lipid Res. 2012;53(12):2490-514.

Sakamoto K, McCarthy A, Smith D, Green KA, Grahame Hardie D, Ashworth A, Alessi DR. Deficiency of LKB1 in skeletal muscle prevents AMPK activation and glucose uptake during contraction. EMBO J. 2005;24:1810-20.

Zhou L, Deepa SS, Etzler JC, Ryu J, Mao X, Fang Q, Liu DD, Torres JM, Jia W, Lechleiter JD, Liu F, Dong LQ. Adiponectin activates AMP-activated protein kinase in muscle cells via APPL1/LKB1-dependent and phospholipase C/Ca2+/Ca2+/calmodulin-dependent protein kinase kinase-dependent pathways. J Biol Chem. 2009;284:22426-35.

Makinde AO, Gamble J, Lopaschuk GD. Upregulation of 5'-AMP-activated protein kinase is responsible for the increase in myocardial fatty acid oxidation rates following birth in the newborn rabbit. Circ Res. 1997;80(4):482-9.

Cao S, Zhou Y, Xu P, Wang Y, Yan J, Bin W, Qiu F, Kang N. Berberine metabolites exhibit triglyceride-lowering effects via activation of AMP-activated protein kinase in Hep G2 cells. J Ethnopharmacol. 2013;149(2):576-82.

Kurokawa H, Sugiyama S, Nozaki T, Sugamura K, Toyama K, Matsubara J, Fujisue K, Ohba K, Maeda H, Konishi M, Akiyama E, Sumida H, Izumiya Y, Yasuda O, Kim-Mitsuyama S, Ogawa H. Telmisartan enhances mitochondrial activity and alters cellular functions in human coronary artery endothelial cells via AMP-activated protein kinase pathway. Atherosclerosis. 2015;239(2):375-85.

Sullivan JE, Brocklehurst KJ, Marley AE, Carey F, Carling D, Beri RK. Inhibition of lipolysis and lipogenesis in isolated rat adipocytes with AICAR, a cell-permeable activator of AMP-activated protein kinase. FEBS Lett. 1994;353(1):33-6.

Ching LC, Chen CY, Su KH, Hou HH, Shyue SK, Kou YR, Lee TS. Implication of AMP-activated protein kinase in transient receptor potential vanilloid type 1-mediated activation of endothelial nitric oxide synthase. Mol Med. 2012;18:805-15.

Wang T, Kusudo T, Takeuchi T, Yamashita Y, Kontani Y, Okamatsu Y, Saito M, Mori N, Yamashita H. Evodiamine inhibits insulin-stimulated mTOR-S6K activation and IRS1 serine phosphorylation in adipocytes and improves glucose tolerance in obese/diabetic mice. PLoS One. 2013;8(12):e83264.

Wang Z, Wang X, Qu K, Zhu P, Guo N, Zhang R, Abliz Z, Yu H, Zhu H. Binding of cordycepin monophosphate to AMP-activated protein kinase and its effect on AMP-activated protein kinase activation. Chem Biol Drug Des. 2010;76(4):340-4.

Wang Z, Bao Y, Zhang Y, Zhang J, Yao G, Wang S, Zhang H. Effect of Soymilk Fermented with Lactobacillus plantarum P-8 on Lipid Metabolism and Fecal Microbiota in Experimental Hyperlipidemic Rats. Food Biophysics. 2012;8(1):43-9.

O'Neill LA, Hardie DG. Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature. 2013;493(7432):346-55.

Jiang DF, Li WT, Yang HL, Zhang ZZ, Chen D, Sun C. Long-term effects of evodiamine on expressions of lipogenesis and lipolysis genes in mouse adipose and liver tissues. Genet Mol Res. 2014;13(1):1038-46.

Estañ MC, Calviño E, de Blas E, Boyano-Adánez Mdel C, Mena ML, Gómez-Gómez M, Rial E, Aller P. 2-Deoxy-D-glucose cooperates with arsenic trioxide to induce apoptosis in leukemia cells: involvement of IGF-1R-regulated Akt/mTOR, MEK/ERK and LKB-1/AMPK signaling pathways. Biochem Pharmacol. 2012;84(12):1604-16.

Sid V, Wu N, Sarna LK, Siow YL, House JD, O K. Folic acid supplementation during high fat diet feeding restores AMP-activated protein kinase (AMPK) activation via an AMP-LKB1 dependent mechanism. Am J Physiol Regul Integr Comp Physiol. 2015;309(10):R1215-25.


Refbacks

  • There are currently no refbacks.


Copyright (c) 2016 ARCHIVES OF BIOLOGICAL SCIENCES

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.