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http://dx.doi.org/10.1016/j.jgr.2018.12.011

Autophagy and its regulation by ginseng components  

Qomaladewi, Nurinanda Prisky (Department of Integrative Biotechnology, Sungkyunkwan University)
Kim, Mi-Yeon (School of Systems Biomedical Science, Soongsil University)
Cho, Jae Youl (Department of Integrative Biotechnology, Sungkyunkwan University)
Publication Information
Journal of Ginseng Research / v.43, no.3, 2019 , pp. 349-353 More about this Journal
Abstract
Autophagy is the sequential process whereby cell components are degraded, which can occur due to nutrient deprivation. Its regulation has an essential role in many diseases, functioning in both cell survival and cell death. Autophagy starts when mTORC1 is inhibited, resulting in the activation of several complexes to form a cargo that fuses with a lysosome, where it undergoes degradation. In this review, we describe a plant extract that is well known in Korea, namely Korean ginseng extract; we studied how its derivatives and metabolites can regulate autophagy and thus mediate the pathogenesis of certain diseases.
Keywords
Autophagosome; Autophagy; Ginsenosides; Panax ginseng;
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1 Ouimet M, Franklin V, Mak E, Liao X, Tabas I, Marcel Yves L. Autophagy regulates cholesterol efflux from macrophage foam cells via lysosomal acid lipase. Cell Metab 2011;13:655-67.   DOI
2 Li W, Sultana N, Siraj N, Ward LJ, Pawlik M, Levy E, Jovinge S, Bengtsson E, Yuan X-M. Autophagy dysfunction and regulatory cystatin C in macrophage death of atherosclerosis. J Cell Mol Med 2016;20:1664-72.   DOI
3 Razani B, Feng C, Coleman T, Emanuel R, Wen H, Hwang S, Ting Jenny P, Virgin Herbert W, Kastan Michael B, Semenkovich Clay F. Autophagy links inflammasomes to atherosclerotic progression. Cell Metab 2012;15:534-44.   DOI
4 Gottesman MM. Mechanisms of cancer drug resistance. Ann Rev Med 2002;53:615-27.   DOI
5 Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001;414:105.   DOI
6 Mai TT, Moon J, Song Y, Viet PQ, Phuc PV, Lee JM, Yi T-H, Cho M, Cho SK. Ginsenoside F2 induces apoptosis accompanied by protective autophagy in breast cancer stem cells. Cancer Lett 2012;321:144-53.   DOI
7 Balaburski GM, Hontz RD, Murphy ME. P53 and ARF: unexpected players in autophagy. Trends Cell Biol 2010;20:363-9.   DOI
8 Lu Z, Chen C, Wu Z, Miao Y, Muhammad I, Ding L, Tian E, Hu W, Ni H, Li R, et al. A dual role of p53 in regulating colistin-induced autophagy in PC-12 cells. Front Pharmacol 2017;8. 768-768.   DOI
9 Xia T, Wang J-C, Xu W, Xu L-H, Lao C-H, Ye Q-X, Fang J-P. 20(S)-ginsenoside Rh2 induces apoptosis in human leukaemia reh cells through mitochondrial signaling pathways. Biol Pharmaceut Bull 2014;37:248-54.   DOI
10 Chung K-S, Cho S-H, Shin J-S, Kim D-H, Choi J-H, Choi SY, Rhee YK, Hong H-D, Lee K-T. Ginsenoside Rh2 induces cell cycle arrest and differentiation in human leukemia cells by upregulating $TGF-{\beta}$ expression. Carcinogenesis 2013;34:331-40.   DOI
11 Zhuang J, Yin J, Xu C, Mu Y, Lv S. 20(S)-ginsenoside Rh2 induce the apoptosis and autophagy in U937 and K562 cells. Nutrients 2018:10.
12 Cho C-W, Kim Y-C, Kang J-H, Rhee YK, Choi SY, Kim K-T, Lee Y-C, Hong H-D. Characteristic study on the chemical components of Korean curved ginseng products. J Ginseng Res 2013;37:349-54.   DOI
13 Zheng M, Xin Y, Li Y, Xu F, Xi X, Guo H, Cui X, Cao H, Zhang X, Han C. Ginsenosides: a potential neuroprotective agent. BioMed Res Int 2018;2018:11.
14 Ahuja A, Kim JH, Kim J-H, Yi Y-S, Cho JY. Functional role of ginseng-derived compounds in cancer. J Ginseng Res 2018;42:248-54.   DOI
15 Xie J-T, Shao Z-H, Vanden Hoek TL, Chang W-T, Li J, Mehendale S, Wang C-Z, Hsu C-W, Becker LB, Yin J-J, et al. Antioxidant effects of ginsenoside re in cardiomyocytes. Eur J Pharmacol 2006;532:201-7.   DOI
16 Leung KW, Wong AS-T. Pharmacology of ginsenosides: a literature review. Chin Med 2010;5. 20-20.   DOI
17 Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell 2008;132:27-42.   DOI
18 Tooze SA, Abada A, Elazar Z. Endocytosis and autophagy: exploitation or cooperation? Cold Spring Harbor Perspect Biol 2014;6:a018358.   DOI
19 Maria Cuervo A. Autophagy: in sickness and in health. Trends Cell Biol 2004;14:70-7.   DOI
20 Lamb CA, Dooley HC, Tooze SA. Endocytosis and autophagy: shared machinery for degradation. BioEssays 2013;35:34-45.   DOI
21 Yang Z, Klionsky DJ. An overview of the molecular mechanism of autophagy. Curr Top Microbiol Immunol 2009;335:1-32.   DOI
22 Glick D, Barth S, Macleod KF. Autophagy: cellular and molecular mechanisms. J Pathol 2010;221:3-12.   DOI
23 Lynch-Day MA, Klionsky DJ. The Cvt pathway as a model for selective autophagy. FEBS Lett 2010;584:1359-66.   DOI
24 Baehrecke EH. Autophagy: dual roles in life and death? Nat Rev Mol Cell Biol 2005;6:505.   DOI
25 Shen L, Haas M, Wang DQH, May A, Lo CC, Obici S, Tso P, Woods SC, Liu M. Ginsenoside Rb1 increases insulin sensitivity by activating AMP-activated protein kinase in male rats. Physiol Rep 2015;3:e12543.   DOI
26 Lee K-T, Jung TW, Lee H-J, Kim S-G, Shin Y-S, Whang W-K. The antidiabetic effect of ginsenoside Rb2 via activation of AMPK. Arch Pharmacol Res 2011;34:1201.   DOI
27 Saba E, Kim S-H, Kim S-D, Park S-J, Kwak D, Oh J-H, Park C-K, Rhee MH. Alleviation of diabetic complications by ginsenoside Rg3-enriched red ginseng extract in western diet-fed ldle/e mice. J Ginseng Res 2018;42:352-5.   DOI
28 Mohanan P, Subramaniyam S, Mathiyalagan R, Yang D-C. Molecular signaling of ginsenosides Rb1, Rg1, andRrg3 and their mode of actions. J Ginseng Res 2018;42:123-32.   DOI
29 Jiang S, Ren D, Li J, Yuan G, Li H, Xu G, Han X, Du P, An L. Effects of compound K on hyperglycemia and insulin resistance in rats with type 2 diabetes mellitus. Fitoterapia 2014;95:58-64.   DOI
30 Paquette M, El-Houjeiri L, Pause A. mTOR pathways in cancer and autophagy. Cancers 2018;10:18.   DOI
31 Maiuri MC, Le Toumelin G, Criollo A, Rain J-C, Gautier F, Juin P, Tasdemir E, Pierron G, Troulinaki K, Tavernarakis N, et al. Functional and physical interaction between bcl-x(l) and a bh3-like domain in beclin-1. EMBO J 2007;26:2527-39.   DOI
32 Song Y, Zhao F, Zhang L, Du Y, Wang T, Fu F. Ginsenoside Rg1 exerts synergistic anti-inflammatory effects with low doses of glucocorticoids in vitro. Fitoterapia 2013;91:173-9.   DOI
33 Randall-Demllo S, Chieppa M, ERI R. Intestinal epithelium and autophagy: partners in gut homeostasis. Front Immunol 2013;4.
34 Das G, Shravage BV, Baehrecke EH. Regulation and function of autophagy during cell survival and cell death. Cold Spring Harbor Perspect Biol 2012;4.
35 Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV, Dawson TM, Dawson VL, El-Deiry WS, Fulda S, et al. Molecular definitions of cell death subroutines: recommendations of the nomenclature committee on cell death 2012. Cell Death Differ 2012;19:107-20.   DOI
36 Yu L, Wan F, Dutta S, Welsh S, Liu Z, Freundt E, Baehrecke EH, Lenardo M. Autophagic programmed cell death by selective catalase degradation. Proc Natl Acad Sci U S A 2006;103:4952-7.   DOI
37 Cho C-W, Kim Y-C, Rhee YK, Lee Y-C, Kim K-T, Hong H-D. Chemical composition characteristics of Korean straight ginseng products. J Ethn Foods 2014;1:24-8.   DOI
38 Kim JH, Yi Y-S, Kim M-Y, Cho JY. Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases. J Ginseng Res 2017;41:435-43.   DOI
39 Lee I-S, Uh I, Kim K-S, Kim K-H, Park J, Kim Y, Jung J-H, Jung H-J, Jang H-J. Antiinflammatory effects of ginsenoside Rg3 via $NF-{\kappa}b$ pathway in a549 cells and human asthmatic lung tissue. J Immunol Res 2016;2016. 7521601-7521601.
40 Kim MK, Kang H, Baek CW, Jung YH, Woo YC, Choi GJ, Shin HY, Kim KS. Antinociceptive and anti-inflammatory effects of ginsenoside Rf in a rat model of incisional pain. J Ginseng Res 2018;42:183-91.   DOI
41 Kang J-H, Song K-H, Woo J-K, Park MH, Rhee MH, Choi C, Oh SH. Ginsenoside Rp1 from Panax ginseng exhibits anti-cancer activity by down-regulation of the IGF-1R/Akt pathway in breast cancer cells. Plant Foods Human Nutr 2011;66:298.   DOI
42 Duan Z, Deng J, Dong Y, Zhu C, Li W, Fan D. Anticancer effects of ginsenoside Rk3 on non-small cell lung cancer cells: in vitro and in vivo. Food Funct 2017;8:3723-36.   DOI
43 Cha K-M, Kopalli SR, Han SY, Lee S-H, Jeong M-S, Cho JY, Han C-G, Lee S-H, Kim S-N, Kim J-C, et al. Korean red ginseng attenuates doxorubicin-induced testicular dysfunction in rats by modulating inflammatory, oxidative, and autophagy responses. J Funct Foods 2018;40:736-43.   DOI
44 Park H-H, Choi S-W, Lee GJ, Kim Y-D, Noh H-J, Oh S-J, Yoo I, Ha Y-J, Koo G-B, Hong S-S, et al. A formulated red ginseng extract inhibits autophagic flux and sensitizes to doxorubicin-induced cell death. J Ginseng Res 2017.
45 Takanezawa Y, Nakamura R, Kojima Y, Sone Y, Uraguchi S, Kiyono M. Cytochalasin E increased the sensitivity of human lung cancer a549 cells to bortezomib via inhibition of autophagy. Biochem Biophys Res Commun 2018;498:603-8.   DOI
46 Lim SW, Jin L, Luo K, Jin J, Yang CW. Ginseng extract reduces tacrolimusinduced oxidative stress by modulating autophagy in pancreatic beta cells. Lab Invest 2017;97:1271.   DOI
47 Attele AS, Zhou Y-P, Xie J-T, Wu JA, Zhang L, Dey L, Pugh W, Rue PA, Polonsky KS, Yuan C-S. Antidiabetic effects of Panax ginseng berry extract and the identification of an effective component. Diabetes 2002;51:1851.   DOI
48 Xue P, Yao Y, Yang X-S, Feng J, Ren G-X. Improved antimicrobial effect of ginseng extract by heat transformation. J Ginseng Res 2017;41:180-7.   DOI
49 Choi AMK, Ryter SW, Levine B. Autophagy in human health and disease. N Engl J Med 2013;368:651-62.   DOI
50 Lim SW, Jin L, Jin J, Yang CW. Effect of exendin-4 on autophagy clearance in beta cell of rats with tacrolimus-induced diabetes mellitus. Sci Rep 2016;6:29921.   DOI
51 Kang S, Kim J-E, Song NR, Jung SK, Lee MH, Park JS, Yeom M-H, Bode AM, Dong Z, Lee KW. The ginsenoside 20-O-${\beta}$-d-glucopyranosyl-20(S)-protopanaxadiol induces autophagy and apoptosis in human melanoma via AMPK/JNK phosphorylation. PLoS One 2014;9:e104305.   DOI
52 Wei Y, Pattingre S, Sinha S, Bassik M, Levine B. JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell 2008;30:678-88.   DOI
53 Nikoletopoulou V, Markaki M, Palikaras K, Tavernarakis N. Crosstalk between apoptosis, necrosis and autophagy. Biochim Biophys Acta 2013;1833:3448-59.   DOI
54 Vakana E, Altman JK, Platanias LC. Targeting AMPK in the treatment of malignancies. J Cell Biochem 2012;113:404-9.   DOI
55 Kim AD, Kang KA, Kim HS, Kim DH, Choi YH, Lee SJ, Kim HS, Hyun JW. A ginseng metabolite, compound K, induces autophagy and apoptosis via generation of reactive oxygen species and activation of JNK in human colon cancer cells. Cell Death Dis 2013;4:e750.   DOI
56 Ling LU, Tan KB, Lin H, Chiu GNC. The role of reactive oxygen species and autophagy in safingol-induced cell death. Cell Death Dis 2011;2:e129.   DOI
57 Shao B-z, Han B-z, Zeng Y-x, Su D-f, Liu C. The roles of macrophage autophagy in atherosclerosis. Acta Pharmacol Sin 2016;37:150-6.   DOI
58 Dupont N, Orhon I, Bauvy C, Codogno P. Chapter four e autophagy and autophagic flux in tumor cells. In: Galluzzi L, Kroemer G, editors. Methods in enzymology. Academic Press; 2014. p. 73-88.