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http://dx.doi.org/10.1016/j.jgr.2022.03.007

Regulation of appetite-related neuropeptides by Panax ginseng: A novel approach for obesity treatment  

Phung, Hung Manh (Department of Preventive Medicine, College of Korean Medicine, Gachon University)
Jang, Dongyeop (Department of Physiology, College of Korean Medicine, Gachon University)
Trinh, Tuy An (Department of Preventive Medicine, College of Korean Medicine, Gachon University)
Lee, Donghun (Department of Herbal Pharmacology, College of Korean Medicine, Gachon University)
Nguyen, Quynh Nhu (Department of Preventive Medicine, College of Korean Medicine, Gachon University)
Kim, Chang-Eop (Department of Physiology, College of Korean Medicine, Gachon University)
Kang, Ki Sung (Department of Preventive Medicine, College of Korean Medicine, Gachon University)
Publication Information
Journal of Ginseng Research / v.46, no.4, 2022 , pp. 609-619 More about this Journal
Abstract
Obesity is a primary factor provoking various chronic disorders, including cardiovascular disease, diabetes, and cancer, and causes the death of 2.8 million individuals each year. Diet, physical activity, medications, and surgery are the main therapies for overweightness and obesity. During weight loss therapy, a decrease in energy stores activates appetite signaling pathways under the regulation of neuropeptides, including anorexigenic [corticotropin-releasing hormone, proopiomelanocortin (POMC), cholecystokinin (CCK), and cocaine- and amphetamine-regulated transcript] and orexigenic [agoutirelated protein (AgRP), neuropeptide Y (NPY), and melanin-concentrating hormone] neuropeptides, which increase food intake and lead to failure in attaining weight loss goals. Ginseng and ginsenosides reverse these signaling pathways by suppressing orexigenic neuropeptides (NPY and AgRP) and provoking anorexigenic neuropeptides (CCK and POMC), which prevent the increase in food intake. Moreover, the results of network pharmacology analysis have revealed that constituents of ginseng radix, including campesterol, beta-elemene, ginsenoside Rb1, biotin, and pantothenic acid, are highly correlated with neuropeptide genes that regulate energy balance and food intake, including ADIPOQ, NAMPT, UBL5, NUCB2, LEP, CCK, GAST, IGF1, RLN1, PENK, PDYN, and POMC. Based on previous studies and network pharmacology analysis data, ginseng and its compounds may be a potent source for obesity treatment by regulating neuropeptides associated with appetite.
Keywords
Panax ginseng; Ginsenosides; Neuropeptide; Appetite; Food intake; Obesity; Network pharmacology analysis;
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Times Cited By KSCI : 11  (Citation Analysis)
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1 Ha KS, Jo SH, Kang BH, Apostolidis E, Lee MS, Jang HD, Kwon YI. In vitro and in vivo antihyperglycemic effect of 2 Amadori rearrangement compounds, arginyl-fructose and arginyl-fructosyl-glucose. J Food Sci 2011;76:H188-93.   DOI
2 Xiong Y, Shen L, Liu KJ, Tso P, Xiong Y, Wang G, Woods SC, Liu M. Antiobesity and antihyperglycemic effects of ginsenoside Rb1 in rats. Diabetes 2010;59:2505-12.   DOI
3 Huang Y-C, Lin C-Y, Huang S-F, Lin H-C, Chang W-L, Chang T-C. Effect and mechanism of ginsenosides CK and Rg1 on stimulation of glucose uptake in 3T3-L1 adipocytes. J Agric Food Chem 2010;58:6039-47.   DOI
4 Hwang JT, Lee MS, Kim HJ, Sung MJ, Kim HY, Kim MS, Kwon DY. Antiobesity effect of ginsenoside Rg3 involves the AMPK and PPAR-g signal pathways. Phytother Res 2009;23:262-6.   DOI
5 Oh J, Lee H, Park D, Ahn J, Shin SS, Yoon M. Ginseng and its active components ginsenosides inhibit adipogenesis in 3T3-L1 cells by regulating MMP-2 and MMP-9. Evid Based Complement Alternat Med 2012;2012.
6 Park D, Yoon M. Compound K, a novel ginsenoside metabolite, inhibits adipocyte differentiation in 3T3-L1 cells: involvement of angiogenesis and MMPs. Biochem Biophys Res Commun 2012;422:263-7.   DOI
7 Lee MR, Kim BC, Kim R, Oh HI, Kim HK, Choi KJ, Sung CK. Anti-obesity effects of black ginseng extract in high fat diet-fed mice. J Ginseng Res 2013;37:308.   DOI
8 Liu R, Zhang J, Liu W, Zheng Y. Anti-obesity effects of protopanaxatriol type ginsenosides isolated from American ginseng leaves in mice fed a high-fat diet. Int J Biomed Pharmaceut Sci 2012;6:106-12.
9 Lee Y-S, Cha B-Y, Yamaguchi K, Choi S-S, Yonezawa T, Teruya T, Nagai K, Woo J-T. Effects of Korean white ginseng extracts on obesity in high-fat diet-induced obese mice. Cytotechnology 2010;62:367-76.   DOI
10 Hwang J-T, Kim S-H, Lee M-S, Kim SH, Yang H-J, Kim M-J, Kim H-S, Ha J, Kim MS, Kwon DY. Anti-obesity effects of ginsenoside Rh2 are associated with the activation of AMPK signaling pathway in 3T3-L1 adipocyte. Biochem Biophys Res Commun 2007;364:1002-8.   DOI
11 Shon JC, Shin H-S, Seo YK, Yoon Y-R, Shin H, Liu K-H. Direct infusion MS-based lipid profiling reveals the pharmacological effects of compound K-reinforced ginsenosides in high-fat diet induced obese mice. J Agric Food Chem 2015;63:2919-29.   DOI
12 Kim D-Y, Park J-S, Yuan H-D, Chung S-H. Fermented ginseng attenuates hepatic lipid accumulation and hyperglycemia through AMPK activation. Food Sci Biotechnol 2009;18:172-8.
13 Kim SJ, Yuan HD, Chung SH. Ginsenoside Rg1 suppresses hepatic glucose production via AMP-activated protein kinase in HepG2 cells. Biol Pharm Bull 2010;33:325-8.   DOI
14 Henness S, Perry CM. Orlistat. Drugs 2006;66:1625-56.   DOI
15 Yuan HD, Quan HY, Jung MS, Kim SJ, Huang B, Kim DY, Chung SH. Anti-diabetic effect of pectinase-processed ginseng radix (GINST) in high fat diet-fed ICR mice. J Ginseng Res 2011;35:308.   DOI
16 Quan H-Y, Yuan H-D, Jung MS, Ko SK, Park YG, Chung SH. Ginsenoside Re lowers blood glucose and lipid levels via activation of AMP-activated protein kinase in HepG2 cells and high-fat diet fed mice. Int J Mol Med 2012;29:73-80.   DOI
17 Montan PD, Sourlas A, Olivero J, Silverio D, Guzman E, Kosmas CE. Pharmacologic therapy of obesity: mechanisms of action and cardiometabolic effects. Ann Transl Med 2019;7.
18 Heymsfield SB, Wadden TA. Mechanisms, pathophysiology, and management of obesity. N Engl J Med 2017;376:254-66.   DOI
19 Lin N, Cai D-L, Jin D, Chen Y, Shi J-J. Ginseng panaxoside Rb1 reduces body weight in diet-induced obese mice. Cell Biochem Biophys 2014;68:189-94.   DOI
20 Park H-J, Kim JH, Shim I. Anti-obesity effects of ginsenosides in high-fat diet-fed rats. Chin J Integr Med 2019;25:895-901.   DOI
21 Qureshi A, Abuirmeileh N, Din Z, Ahmad Y, Burger W, Elson C. Suppression of cholesterogenesis and reduction of LDL cholesterol by dietary ginseng and its fractions in chicken liver. Atherosclerosis 1983;48:81-94.   DOI
22 Liu K, Kim M, Jeon B, Shon J, Cha I, Cho K, Lee S, Shin J. Inhibition of human cytochrome P450 isoforms and NADPH-CYP reductase in vitro by 15 herbal medicines, including Epimedii herba. J Clin Pharm Therapeut 2006;31:83-91.   DOI
23 Arora S. Role of neuropeptides in appetite regulation and obesity-a review. Neuropeptides 2006;40:375-401.   DOI
24 Kim SN, Lee JH, Shin H, Son SH, Kim YS. Effects of in vitro-digested ginsenosides on lipid accumulation in 3T3-L1 adipocytes. Planta Med 2009;75:596-601.   DOI
25 Lau D, Douketis J, Morrison K, Hramiak I, Sharma A, et al. Canadian clinical practice guidelines on the management and prevention of obesity in adults and children. Can Med Assoc J 2007;176(8):S1-13. 2006.   DOI
26 Liu H, Wang J, Liu M, Zhao H, Yaqoob S, Zheng M, Cai D, Liu J. Antiobesity effects of ginsenoside Rg1 on 3T3-L1 preadipocytes and high fat diet-induced obese mice mediated by AMPK. Nutrients 2018;10:830.   DOI
27 Song YB, An YR, Kim SJ, Park HW, Jung JW, Kyung JS, Hwang SY, Kim YS. Lipid metabolic effect of Korean Red Ginseng extract in mice fed on a high-fat diet. J Sci Food Agric 2012;92:388-96.   DOI
28 Lee SH, Lee HJ, Lee Yh, Lee BW, Cha BS, Kang ES, Ahn CW, Park JS, Kim HJ, Lee EY. Korean Red Ginseng (Panax ginseng) improves insulin sensitivity in high fat fed Sprague-Dawley rats. Phytother Res 2012;26:142-7.   DOI
29 Jensen M, Ryan D, Apovian C, Ard J, Comuzzie A, Donato K, Yanovski M. AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American college of cardiology/American heart association task force on practice guidelines and the obesity society. Circulation 2014;129:S139-40.   DOI
30 Zheng H, Lenard N, Shin A, Berthoud H-R. Appetite control and energy balance regulation in the modern world: reward-driven brain overrides repletion signals. Int J Obes 2009;33:S8-13.   DOI
31 Li Z, Ji GE. Ginseng and obesity. J Ginseng Res 2018;42:1-8.   DOI
32 Kim S-J, Lee YH, Han M-D, Mar W, Kim W-K, Nam K-W. Resveratrol, purified from the stem of Vitis coignetiae Pulliat, inhibits food intake in C57BL/6J Mice. Arch Pharm Res (Seoul) 2010;33:775-80.   DOI
33 Liu L, Anderson GA, Fernandez TG, Dore S. Efficacy and mechanism of Panax ginseng in experimental stroke. Front Neurosci 2019;13:294.   DOI
34 Yin J, Zhang H, Ye J. Traditional Chinese medicine in treatment of metabolic syndrome. Endocr Metab Immune Disord - Drug Targets 2008;8:99-111.   DOI
35 do Valle IF, Roweth HG, Malloy MW, Moco S, Barron D, Battinelli E, Loscalzo J, Barabasi A-L. Network medicine framework shows that proximity of polyphenol targets and disease proteins predicts therapeutic effects of polyphenols. Nat Food 2021;2:143-55.   DOI
36 Bickerton G, Paolini G, Besnard J, Muresan S, Hopkins A. Quantifying the chemical beauty of drugs. Nat Chem 2012;4(2):90-8 [Crossref, Medline].   DOI
37 Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, Himmelfarb CD, Khera A, Lloyd-Jones D, McEvoy JW. Correction to: 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American college of cardiology/American heart association task force on clinical practice guidelines. Circulation 2019;140:e649-50.
38 Kim E-J, Lee H-I, Chung K-J, Noh Y-H, Ro Y-T, Koo J-H. The ginsenoside-Rb2 lowers cholesterol and triacylglycerol levels in 3T3-L1 adipocytes cultured under high cholesterol or fatty acids conditions. BMB Rep 2009;42:194-9.   DOI
39 Lee S, Lee M-S, Kim C-T, Kim I-H, Kim Y. Ginsenoside Rg3 reduces lipid accumulation with AMP-activated protein kinase (AMPK) activation in HepG2 cells. Int J Mol Sci 2012;13:5729-39.   DOI
40 Afshin A, et al., GBD 2015 Obesity Collaborators. Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med 2017;377(1):13-27.   DOI
41 Lee HJ, Park SK, Han SJ, Kim SH, Hur KY, Kang ES, Ahn CW, Cha BS, Kim KS, Lee HC. Korean Red Ginseng activates AMPK in skeletal muscle and liver. Diabetes 2007;56.
42 Winder Wa, Hardie D. AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. Am J Physiol Endocrinol Metab 1999;277:E1-10.   DOI
43 Lee M-S, Kim C-T, Kim I-H, Kim Y. Effects of Korean Red Ginseng extract on hepatic lipid accumulation in HepG2 cells. Biosci Biotechnol Biochem 2015;79:816-9.   DOI
44 Quan H-Y, Yuan H-D, Kim DY, Zhang Y, Chung SH. Korean Red Ginseng attenuates hepatic lipid accumulation via AMPK activation in human hepatoma cells. Food Sci Biotechnol 2010;19:207-12.   DOI
45 Li X, Luo J, Anandh Babu PV, Zhang W, Gilbert E, Cline M, McMillan R, Hulver M, Alkhalidy H, Zhen W. Dietary supplementation of Chinese ginseng prevents obesity and metabolic syndrome in high-fat diet-fed mice. J Med Food 2014;17:1287-97.   DOI
46 Wu Y, Yu Y, Szabo A, Han M, Huang X-F. Central inflammation and leptin resistance are attenuated by ginsenoside Rb1 treatment in obese mice fed a high-fat diet. PLoS One 2014;9:e92618.   DOI
47 Amin T, Mercer JG. Hunger and satiety mechanisms and their potential exploitation in the regulation of food intake. Curr Obes Rep 2016;5:106-12.   DOI
48 Panickar KS. Effects of dietary polyphenols on neuroregulatory factors and pathways that mediate food intake and energy regulation in obesity. Mol Nutr Food Res 2013;57:34-47.   DOI
49 Im D-S. Pro-Resolving Effect of ginsenosides as an anti-inflammatory mechanism of Panax ginseng. Biomolecules 2020;10:444.   DOI
50 Park S-Y, Park J-H, Kim H-S, Lee C-Y, Lee H-J, Kang KS, Kim C-E. Systems-level mechanisms of action of Panax ginseng: a network pharmacological approach. J Ginseng Res 2018;42:98-106.   DOI
51 Guney E, Menche J, Vidal M, Barabasi A-L. Network-based in silico drug efficacy screening. Nat Commun 2016;7:1-13.
52 Chang W-L, Ho Y-H, Huang Y-C, Huang S-F, Lin J-Y, Lin H-C, Chang T-C. The inhibitory effect of ginsenoside Rg1 on glucose and lipid production in human HepG2 cells. Adaptive Med 2013;5:181-8.   DOI
53 Im D-s, Nah S-y. Yin and Yang of ginseng pharmacology: ginsenosides vs gintonin. Acta Pharmacol Sin 2013;34:1367-73.   DOI
54 Karu N, Reifen R, Kerem Z. Weight gain reduction in mice fed Panax ginseng saponin, a pancreatic lipase inhibitor. J Agric Food Chem 2007;55:2824-8.   DOI
55 Jones JR, Barrick C, Kim K-A, Lindner J, Blondeau B, Fujimoto Y, Shiota M, Kesterson RA, Kahn BB, Magnuson MA. Deletion of PPARg in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance. Proc Natl Acad Sci Unit States Am 2005;102:6207-12.   DOI
56 Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature 2000;404:661-71.   DOI
57 Lee MS, Shin Y, Kim Y. Effect of the high hydrostatic pressure extract of Korean ginseng on hepatic lipid metabolism and AMP-activated protein kinase activation in HepG2 cells (1045.25). FASEB J 2014;28. 1045.1025.
58 Kim CM, Yi SJ, Cho IJ, Ku SK. Red-koji fermented red ginseng ameliorates high fat diet-induced metabolic disorders in mice. Nutrients 2013;5:4316-32.   DOI
59 Yun SN, Ko SK, Lee KH, Chung SH. Vinegar-processed ginseng radix improves metabolic syndrome induced by a high fat diet in ICR mice. Arch Pharm Res (Seoul) 2007;30:587-95.   DOI
60 Szklarczyk D, Santos A, Von Mering C, Jensen LJ, Bork P, Kuhn M. Stitch 5: augmenting protein-chemical interaction networks with tissue and affinity data. Nucleic Acids Res 2016;44:D380-4.   DOI
61 Burbach JPH. Neuropeptides from concept to online database. Eur J Pharmacol 2010;626:27-48. www.neuropeptides.nl.   DOI
62 Adela Hruby P, Mph, Frank B, Hu MD, PhD Mph. The epidemiology of obesity: a big picture. Pharmacoeconomics 2015;33:673-89.   DOI
63 Hillebrand J, De Wied D, Adan R Neuropeptides. Food intake and body weight regulation: a hypothalamic focus. Peptides 2002;23:2283-306.   DOI
64 Shen L, Xiong Y, Wang DQ, Howles P, Basford JE, Wang J, Xiong YQ, Hui DY, Woods SC, Liu M. Ginsenoside Rb1 reduces fatty liver by activating AMP-activated protein kinase in obese rats. J Lipid Res 2013;54:1430-8.   DOI
65 Durante PE, Mustard KJ, Park S-H, Winder WW, Hardie DG. Effects of endurance training on activity and expression of AMP-activated protein kinase isoforms in rat muscles. Am J Physiol Endocrinol Metab 2002;283:E178-86.   DOI
66 Lee H, Kim M, Shin SS, Yoon M. Ginseng treatment reverses obesity and related disorders by inhibiting angiogenesis in female db/db mice. J Ethnopharmacol 2014;155:1342-52.   DOI
67 Russo AF. Overview of Neuropeptides: a wakening the Senses? J Headache Pain 2017;57:37-46.   DOI
68 Burbach JPH. What are neuropeptides? Methods Mol Biol 2011;789:1-36.   DOI
69 Hwang E, Park S-Y, Yin CS, Kim H-T, Kim YM, Yi TH. Antiaging effects of the mixture of Panax ginseng and Crataegus pinnatifida in human dermal fibroblasts and healthy human skin. J Ginseng Res 2017;41:69-77.   DOI
70 Kim H-J, Jung S-W, Kim S-Y, Cho I-H, Kim H-C, Rhim H, Kim M, Nah S-Y. Panax ginseng as an adjuvant treatment for Alzheimer's disease. J Ginseng Res 2018;42:401-11.   DOI
71 Bak M-J, Hong S-G, Lee J-W, Jeong W-S. Red ginseng marc oil inhibits iNOS and COX-2 via NFkB and p38 pathways in LPS-stimulated RAW 264.7 macrophages. Molecules 2012;17:13769-86.   DOI
72 Li P, Liu J. Ginseng nutritional components and functional factors. Springer; 2020.
73 Morais M, Faria G, Preto J, Costa-Maia J. Gallstones and bariatric surgery: to treat or not to treat? World J Surg 2016;40:2904-10.   DOI
74 Poakwah A. The effect of a dietary supplement with alpha lipoic acid and other neutraceuticals on weight control and serum lipid profile in Sprague dawley rats. University of Ghana; 2019.
75 Kim J-S. Investigation of phenolic, flavonoid, and vitamin contents in different parts of Korean ginseng (Panax ginseng CA Meyer). Prev Nutr Food Sci 2016;21:263.   DOI
76 Council, A.M.P. Resolved, that the alberta mackenzie provincial council of the catholic women's league of Canada, in 71st annual convention assembled, urge the alberta provincial and northwest territories governments to officially recognize obesity as a chronic disease.
77 Stein EM, Silverberg SJ. Bone loss after bariatric surgery: causes, consequences, and management. Lancet Diabetes Endocrinol 2014;2:165-74.   DOI
78 Martin KA, Mani MV, Mani A. New targets to treat obesity and the metabolic syndrome. Eur J Pharmacol 2015;763:64-74.   DOI
79 Catalani E, De Palma C, Perrotta C, Cervia D. Current evidence for a role of neuropeptides in the regulation of autophagy. BioMed Res Int 2017;2017.
80 Kalarchian MA, Marcus MD, Courcoulas AP, Cheng Y, Levine MD. Self-report of gastrointestinal side effects after bariatric surgery. Surg Obes Relat Dis 2014;10:1202-7.   DOI
81 Daneschvar HL, Aronson MD, Smetana GW. FDA-approved anti-obesity drugs in the United States. Am J Med 2016;129:879. e871-6.
82 Karri S, Sharma S, Hatware K, Patil K. Natural anti-obesity agents and their therapeutic role in management of obesity: a future trend perspective. Biomed Pharmacother 2019;110:224-38.   DOI
83 Lee B-B, Kim H, Shim I-S, Lee H-J, Hahm D-H. Wild ginseng attenuates anxiety- and depression-like behaviors during morphine withdrawal. J Microbiol Biotechnol 2011;21:1088-96.   DOI
84 Kim JH, Kang SA, Han SM, Shim I. Comparison of the antiobesity effects of the protopanaxadiol-and protopanaxatriol-type saponins of red ginseng. Phytother Res 2009;23:78-85.   DOI
85 Kim JH, Hahm DH, Yang DC, Kim JH, Lee HJ, Shim I. Effect of crude saponin of Korean Red Ginseng on high fat diet-induced obesity in the rat. J Pharmacol Sci 2005;97(1):124-31.   DOI
86 Dai D, Zhang C-F, Williams S, Yuan C-S, Wang C-Z. Ginseng on cancer: potential role in modulating inflammation-mediated angiogenesis. Am J Chin Med 2017;45:13-22.   DOI
87 Kim J-H. Pharmacological and medical applications of Panax ginseng and ginsenosides: a review for use in cardiovascular diseases. J Ginseng Res 2018;42:264-9.   DOI
88 Wang Y, Fang M-Y. Effect of ginseng saponin, arsenic trioxide, beta-elemene combined with CTX on telomere-telomerase system in K562 cell line. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2006;14:1089-95.
89 Lee B, Sur B, Cho S-G, Yeom M, Shim I, Lee H, Hahm D-H. Ginsenoside Rb1 rescues anxiety-like responses in a rat model of post-traumatic stress disorder. J Nat Med 2016;70:133-44.   DOI
90 Jung S, Lee M-S, Shin Y, Kim C-T, Kim I-H, Kim YS, Kim Y. Anti-obesity and anti-inflammatory effects of high hydrostatic pressure extracts of ginseng in high-fat diet induced obese rats. J Funct Foods 2014;10:169-77.   DOI