Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Author(s): Juling Feng, Haodong Chen, Yangbo Liu, Qidi Ai, Yantao Yang, Wenbin He, Lei Zhao, Shifeng Chu* and Naihong Chen*

DOI: 10.2174/0113895575277359231210145922

DownloadDownload PDF Flyer Cite As
Ferroptosis is Involved in the Pharmacological Effect of Ginsenoside

Page: [1228 - 1237] Pages: 10

  • * (Excluding Mailing and Handling)

Abstract

Ginsenoside is the principal active ingredient in ginseng. Several investigations have found that ginsenosides have anti-inflammatory, antioxidant, anti-apoptotic, anti-cancer, and antiallergic activities. Ferroptosis is an iron-dependent, non-apoptotic form of cell-regulated death caused by lipid peroxidation. Iron, lipid, and amino acid metabolism orchestrate the complex ferroptosis response through direct or indirect regulation of iron accumulation or lipid peroxidation. More and more research has demonstrated that ginsenoside impacts illnesses via ferroptosis, implying that ferroptosis might be employed as a novel target of ginsenoside for disease therapy. This article examines the molecular mechanism of ferroptosis as well as the current advancement of ginsenoside in influencing disorders via ferroptosis.

Graphical Abstract

[1]
Kiefer, D.; Pantuso, T. Panax ginseng. Am. Fam. Physician, 2003, 68(8), 1539-1542.
[PMID: 14596440]
[2]
Arring, N.M.; Millstine, D.; Marks, L.A.; Nail, L.M. Ginseng as a treatment for fatigue: A systematic review. J. Altern. Complement. Med., 2018, 24(7), 624-633.
[http://dx.doi.org/10.1089/acm.2017.0361] [PMID: 29624410]
[3]
Dixon, S.J.; Lemberg, K.M.; Lamprecht, M.R.; Skouta, R.; Zaitsev, E.M.; Gleason, C.E.; Patel, D.N.; Bauer, A.J.; Cantley, A.M.; Yang, W.S.; Morrison, B., III; Stockwell, B.R. Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell, 2012, 149(5), 1060-1072.
[http://dx.doi.org/10.1016/j.cell.2012.03.042] [PMID: 22632970]
[4]
Chen, X.; Li, J.; Kang, R.; Klionsky, D.J. Ferroptosis: Machinery and regulation. Autophagy, 2021, 17(9), 2054-2081.
[5]
Sever, B.; Altıntop, M.D.; Demir, Y.; Akalın Çiftçi, G.; Beydemir, Ş.; Özdemir, A. Design, synthesis, in vitro and in silico investigation of aldose reductase inhibitory effects of new thiazole-based compounds. Bioorg. Chem., 2020, 102, 104110.
[http://dx.doi.org/10.1016/j.bioorg.2020.104110] [PMID: 32739480]
[6]
Demir, Y.; Ceylan, H.; Türkeş, C.; Beydemir, Ş. Molecular docking and inhibition studies of vulpinic, carnosic and usnic acids on polyol pathway enzymes. J. Biomol. Struct. Dyn., 2022, 40(22), 12008-12021.
[http://dx.doi.org/10.1080/07391102.2021.1967195] [PMID: 34424822]
[7]
Stockwell, B.R.; Friedmann Angeli, J.P.; Bayir, H.; Bush, A.I.; Conrad, M.; Dixon, S.J.; Fulda, S.; Gascón, S.; Hatzios, S.K.; Kagan, V.E.; Noel, K.; Jiang, X.; Linkermann, A.; Murphy, M.E.; Overholtzer, M.; Oyagi, A.; Pagnussat, G.C.; Park, J.; Ran, Q.; Rosenfeld, C.S.; Salnikow, K.; Tang, D.; Torti, F.M.; Torti, S.V.; Toyokuni, S.; Woerpel, K.A.; Zhang, D.D. Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease. Cell, 2017, 171(2), 273-285.
[http://dx.doi.org/10.1016/j.cell.2017.09.021] [PMID: 28985560]
[8]
Mao, H.; Zhao, Y.; Li, H.; Lei, L. Ferroptosis as an emerging target in inflammatory diseases. Prog. Biophys. Mol. Biol., 2020, 155, 20-28.
[http://dx.doi.org/10.1016/j.pbiomolbio.2020.04.001] [PMID: 32311424]
[9]
Chen, X.; Kang, R.; Kroemer, G.; Tang, D. Broadening horizons: The role of ferroptosis in cancer. Nat. Rev. Clin. Oncol., 2021, 18(5), 280-296.
[http://dx.doi.org/10.1038/s41571-020-00462-0] [PMID: 33514910]
[10]
Li, Y.; Feng, D.; Wang, Z.; Zhao, Y.; Sun, R.; Tian, D.; Liu, D.; Zhang, F.; Ning, S.; Yao, J.; Tian, X. Ischemia-induced ACSL4 activation contributes to ferroptosis-mediated tissue injury in intestinal ischemia/reperfusion. Cell Death Differ., 2019, 26(11), 2284-2299.
[http://dx.doi.org/10.1038/s41418-019-0299-4] [PMID: 30737476]
[11]
Do Van, B.; Gouel, F.; Jonneaux, A.; Timmerman, K.; Gelé, P.; Pétrault, M.; Bastide, M.; Laloux, C.; Moreau, C.; Bordet, R.; Devos, D.; Devedjian, J.C. Ferroptosis, a newly characterized form of cell death in Parkinson’s disease that is regulated by PKC. Neurobiol. Dis., 2016, 94, 169-178.
[http://dx.doi.org/10.1016/j.nbd.2016.05.011] [PMID: 27189756]
[12]
Abdalkader, M.; Lampinen, R.; Kanninen, K.M.; Malm, T.M.; Liddell, J.R. Targeting Nrf2 to suppress ferroptosis and mitochondrial dysfunction in neurodegeneration. Front. Neurosci., 2018, 12, 466.
[http://dx.doi.org/10.3389/fnins.2018.00466] [PMID: 30042655]
[13]
Anderson, L.J.; Westwood, M.A.; Holden, S.; Davis, B.; Prescott, E.; Wonke, B.; Porter, J.B.; Malcolm Walker, J.; Pennell, D.J. Myocardial iron clearance during reversal of siderotic cardiomyopathy with intravenous desferrioxamine: A prospective study using T2* cardiovascular magnetic resonance. Br. J. Haematol., 2004, 127(3), 348-355.
[http://dx.doi.org/10.1111/j.1365-2141.2004.05202.x] [PMID: 15491298]
[14]
Dexrazoxane, D.; Database, L. Dexrazoxane, Drugs and Lactation Database; (LactMed®);: Bethesda, (MD), 2006.
[15]
Yamaguchi, Y.; Kasukabe, T.; Kumakura, S. Piperlongumine rapidly induces the death of human pancreatic cancer cells mainly through the induction of ferroptosis. Int. J. Oncol., 2018, 52(3), 1011-1022.
[http://dx.doi.org/10.3892/ijo.2018.4259] [PMID: 29393418]
[16]
Ayton, S.; Faux, N.G.; Bush, A.I.; Weiner, M.W.; Aisen, P.; Petersen, R.; Jack, C.R.; Jagust, W.; Trojanowki, J.Q.; Toga, A.W.; Beckett, L.; Green, R.C.; Saykin, A.J.; Morris, J.; Shaw, L.M.; Khachaturian, Z.; Sorensen, G.; Kuller, L.; Raichle, M.; Paul, S.; Davies, P.; Fillit, H.; Hefti, F.; Holtzman, D.; Marcel Mesulam, M.; Potter, W.; Snyder, P.; Schwartz, A.; Montine, T.; Thomas, R.G.; Donohue, M.; Walter, S.; Gessert, D.; Sather, T.; Jiminez, G.; Harvey, D.; Bernstein, M.; Fox, N.; Thompson, P.; Schuff, N.; Borowski, B.; Gunter, J.; Senjem, M.; Vemuri, P.; Jones, D.; Kantarci, K.; Ward, C.; Koeppe, R.A.; Foster, N.; Reiman, E.M.; Chen, K.; Mathis, C.; Landau, S.; Cairns, N.J.; Householder, E.; Taylor-Reinwald, L.; Lee, V.; Korecka, M.; Figurski, M.; Crawford, K.; Neu, S.; Foroud, T.M.; Potkin, S.; Shen, L.; Faber, K.; Kim, S.; Nho, K.; Thal, L.; Buckholtz, N.; Albert, M.; Frank, R.; Hsiao, J.; Kaye, J.; Quinn, J.; Lind, B.; Carter, R.; Dolen, S.; Schneider, L.S.; Pawluczyk, S.; Beccera, M.; Teodoro, L.; Spann, B.M.; Brewer, J.; Vanderswag, H.; Fleisher, A.; Heidebrink, J.L.; Lord, J.L.; Mason, S.S.; Albers, C.S.; Knopman, D.; Johnson, K.; Doody, R.S.; Villanueva-Meyer, J.; Chowdhury, M.; Rountree, S.; Dang, M.; Stern, Y.; Honig, L.S.; Bell, K.L.; Ances, B.; Carroll, M.; Leon, S.; Mintun, M.A.; Schneider, S.; Oliver, A.; Marson, D.; Griffith, R.; Clark, D.; Geldmacher, D.; Brockington, J.; Roberson, E.; Grossman, H.; Mitsis, E.; deToledo-Morrell, L.; Shah, R.C.; Duara, R.; Varon, D.; Greig, M.T.; Roberts, P.; Albert, M.; Onyike, C.; D’Agostino, D., II; Kielb, S.; Galvin, J.E.; Cerbone, B.; Michel, C.A.; Rusinek, H.; de Leon, M.J.; Glodzik, L.; De Santi, S.; Murali Doraiswamy, P.; Petrella, J.R.; Wong, T.Z.; Arnold, S.E.; Karlawish, J.H.; Wolk, D.; Smith, C.D.; Jicha, G.; Hardy, P.; Sinha, P.; Oates, E.; Conrad, G.; Lopez, O.L.; Oakley, M.A.; Simpson, D.M.; Porsteinsson, A.P.; Goldstein, B.S.; Martin, K.; Makino, K.M.; Saleem Ismail, M.; Brand, C.; Mulnard, R.A.; Thai, G.; Mc-Adams-Ortiz, C.; Womack, K.; Mathews, D.; Quiceno, M.; Diaz-Arrastia, R.; King, R.; Weiner, M.; Martin-Cook, K.; DeVous, M.; Levey, A.I.; Lah, J.J.; Cellar, J.S.; Burns, J.M.; Anderson, H.S.; Swerdlow, R.H.; Apostolova, L.; Tingus, K.; Woo, E.; Silverman, D.H.S.; Lu, P.H.; Bartzokis, G.; Graff-Radford, N.R.; Parfitt, F.; Kendall, T.; Johnson, H.; Farlow, M.R.; Hake, A.M.; Matthews, B.R.; Herring, S.; Hunt, C.; van Dyck, C.H.; Carson, R.E.; MacAvoy, M.G.; Chertkow, H.; Bergman, H.; Hosein, C.; Black, S.; Stefanovic, B.; Caldwell, C.; Robin Hsiung, G-Y.; Feldman, H.; Mudge, B.; Assaly, M.; Kertesz, A.; Rogers, J.; Bernick, C.; Munic, D.; Kerwin, D.; Mesulam, M-M.; Lipowski, K.; Wu, C-K.; Johnson, N.; Sadowsky, C.; Martinez, W.; Villena, T.; Scott Turner, R.; Johnson, K.; Reynolds, B.; Sperling, R.A.; Johnson, K.A.; Marshall, G.; Frey, M.; Lane, B.; Rosen, A.; Tinklenberg, J.; Sabbagh, M.N.; Belden, C.M.; Jacobson, S.A.; Sirrel, S.A.; Kowall, N.; Killiany, R.; Budson, A.E.; Norbash, A.; Johnson, P.L.; Allard, J.; Lerner, A.; Ogrocki, P.; Hudson, L.; Fletcher, E.; Carmichael, O.; Olichney, J.; DeCarli, C.; Kittur, S.; Borrie, M.; Lee, T-Y.; Bartha, R.; Johnson, S.; Asthana, S.; Carlsson, C.M.; Potkin, S.G.; Preda, A.; Nguyen, D.; Tariot, P.; Reeder, S.; Bates, V.; Capote, H.; Rainka, M.; Scharre, D.W.; Kataki, M.; Adeli, A.; Zimmerman, E.A.; Celmins, D.; Brown, A.D.; Pearlson, G.D.; Blank, K.; Anderson, K.; Santulli, R.B.; Kitzmiller, T.J.; Schwartz, E.S.; Sink, K.M.; Williamson, J.D.; Garg, P.; Watkins, F.; Ott, B.R.; Querfurth, H.; Tremont, G.; Salloway, S.; Malloy, P.; Correia, S.; Rosen, H.J.; Miller, B.L.; Mintzer, J.; Spicer, K.; Bachman, D.; Finger, E.; Pasternak, S.; Rachinsky, I.; Drost, D.; Pomara, N.; Hernando, R.; Sarrael, A.; Schultz, S.K.; Boles Ponto, L.L.; Shim, H.; Elizabeth Smith, K.; Relkin, N.; Chaing, G.; Raudin, L.; Smith, A.; Fargher, K.; Ashok Raj, B.; Neylan, T.; Grafman, J.; Davis, M.; Morrison, R.; Hayes, J.; Finley, S.; Friedl, K.; Fleischman, D.; Arfanakis, K.; James, O.; Massoglia, D.; Jay Fruehling, J.; Harding, S.; Peskind, E.R.; Petrie, E.C.; Li, G.; Yesavage, J.A.; Taylor, J.L.; Furst, A.J. Ferritin levels in the cerebrospinal fluid predict Alzheimer’s disease outcomes and are regulated by APOE. Nat. Commun., 2015, 6(1), 6760.
[http://dx.doi.org/10.1038/ncomms7760] [PMID: 25988319]
[17]
Bilgic, B.; Pfefferbaum, A.; Rohlfing, T.; Sullivan, E.V.; Adalsteinsson, E. MRI estimates of brain iron concentration in normal aging using quantitative susceptibility mapping. Neuroimage, 2012, 59(3), 2625-2635.
[http://dx.doi.org/10.1016/j.neuroimage.2011.08.077] [PMID: 21925274]
[18]
Devos, D.; Moreau, C.; Devedjian, J.C.; Kluza, J.; Petrault, M.; Laloux, C.; Jonneaux, A.; Ryckewaert, G.; Garçon, G.; Rouaix, N.; Duhamel, A.; Jissendi, P.; Dujardin, K.; Auger, F.; Ravasi, L.; Hopes, L.; Grolez, G.; Firdaus, W.; Sablonnière, B.; Strubi-Vuillaume, I.; Zahr, N.; Destée, A.; Corvol, J.C.; Pöltl, D.; Leist, M.; Rose, C.; Defebvre, L.; Marchetti, P.; Cabantchik, Z.I.; Bordet, R. Targeting chelatable iron as a therapeutic modality in Parkinson’s disease. Antioxid. Redox Signal., 2014, 21(2), 195-210.
[http://dx.doi.org/10.1089/ars.2013.5593] [PMID: 24251381]
[19]
Zille, M.; Karuppagounder, S.S.; Chen, Y.; Gough, P.J.; Bertin, J.; Finger, J.; Milner, T.A.; Jonas, E.A.; Ratan, R.R. Neuronal death after hemorrhagic stroke in vitro and in vivo shares features of ferroptosis and necroptosis. Stroke, 2017, 48(4), 1033-1043.
[http://dx.doi.org/10.1161/STROKEAHA.116.015609] [PMID: 28250197]
[20]
Hambright, W.S.; Fonseca, R.S.; Chen, L.; Na, R.; Ran, Q. Ablation of ferroptosis regulator glutathione peroxidase 4 in forebrain neurons promotes cognitive impairment and neurodegeneration. Redox Biol., 2017, 12, 8-17.
[http://dx.doi.org/10.1016/j.redox.2017.01.021] [PMID: 28212525]
[21]
Coles, L.D.; Tuite, P.J.; Öz, G.; Mishra, U.R.; Kartha, R.V.; Sullivan, K.M.; Cloyd, J.C.; Terpstra, M. Repeated‐dose oral NAcetylcysteine in Parkinson’s Disease: Pharmacokinetics and effect on brain glutathione and oxidative stress. J. Clin. Pharmacol., 2018, 58(2), 158-167.
[http://dx.doi.org/10.1002/jcph.1008] [PMID: 28940353]
[22]
Monti, D.A.; Zabrecky, G.; Kremens, D.; Liang, T.W.; Wintering, N.A.; Cai, J.; Wei, X.; Bazzan, A.J.; Zhong, L.; Bowen, B.; Intenzo, C.M.; Iacovitti, L.; Newberg, A.B. N-acetyl cysteine may support dopamine neurons in Parkinson’s Disease: Preliminary clinical and cell line data. PLoS One, 2016, 11(6), e0157602.
[http://dx.doi.org/10.1371/journal.pone.0157602] [PMID: 27309537]
[23]
Dolma, S.; Lessnick, S.L.; Hahn, W.C.; Stockwell, B.R. Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell, 2003, 3(3), 285-296.
[http://dx.doi.org/10.1016/S1535-6108(03)00050-3] [PMID: 12676586]
[24]
Yu, Y.; Xie, Y.; Cao, L.; Yang, L.; Yang, M.; Lotze, M.T.; Zeh, H.J.; Kang, R.; Tang, D. The ferroptosis inducer erastin enhances sensitivity of acute myeloid leukemia cells to chemotherapeutic agents. Mol. Cell. Oncol., 2015, 2(4), e1054549.
[http://dx.doi.org/10.1080/23723556.2015.1054549] [PMID: 27308510]
[25]
Gao, M.; Monian, P.; Quadri, N.; Ramasamy, R.; Jiang, X. Glutaminolysis and transferrin regulate ferroptosis. Mol. Cell, 2015, 59(2), 298-308.
[http://dx.doi.org/10.1016/j.molcel.2015.06.011] [PMID: 26166707]
[26]
Ma, S.; Henson, E.S.; Chen, Y.; Gibson, S.B. Ferroptosis is induced following siramesine and lapatinib treatment of breast cancer cells. Cell Death Dis., 2016, 7(7), e2307.
[http://dx.doi.org/10.1038/cddis.2016.208] [PMID: 27441659]
[27]
Yang, W.S.; Stockwell, B.R. Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem. Biol., 2008, 15(3), 234-245.
[http://dx.doi.org/10.1016/j.chembiol.2008.02.010] [PMID: 18355723]
[28]
Liu, Q.; Barker, S.; Knutson, M.D. Iron and manganese transport in mammalian systems. Biochim. Biophys. Acta Mol. Cell Res., 2021, 1868(1), 118890.
[http://dx.doi.org/10.1016/j.bbamcr.2020.118890] [PMID: 33091506]
[29]
Sangkhae, V.; Nemeth, E. Placental iron transport: The mechanism and regulatory circuits. Free Radic. Biol. Med., 2019, 133, 254-261.
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.07.001] [PMID: 29981833]
[30]
Song, X.; Zhu, S.; Chen, P.; Hou, W.; Wen, Q.; Liu, J.; Xie, Y.; Liu, J.; Klionsky, D.J.; Kroemer, G.; Lotze, M.T.; Zeh, H.J.; Kang, R.; Tang, D. AMPK-Mediated BECN1 Phosphorylation promotes ferroptosis by directly blocking system Xc– activity. Curr. Biol., 2018, 28(15), 2388-2399.e5.
[http://dx.doi.org/10.1016/j.cub.2018.05.094] [PMID: 30057310]
[31]
Imoto, S.; Kono, M.; Suzuki, T.; Shibuya, Y.; Sawamura, T.; Mizokoshi, Y.; Sawada, H.; Ohbuchi, A.; Saigo, K. Haemin-induced cell death in human monocytic cells is consistent with ferroptosis. Transf. Aphere. Sci., 2018, 57(4), 524-531.
[32]
Li, X.; Chen, J.; Yuan, S.; Zhuang, X.; Qiao, T. Activation of the P62-Keap1-NRF2 pathway protects against ferroptosis in radiationinduced lung injury. Oxid. Med. Cell. Longev., 2022, 2022, 1-16.
[http://dx.doi.org/10.1155/2022/8973509] [PMID: 35847598]
[33]
Sun, X.; Ou, Z.; Chen, R.; Niu, X.; Chen, D.; Kang, R.; Tang, D. Activation of the p62‐Keap1‐NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells. Hepatology, 2016, 63(1), 173-184.
[http://dx.doi.org/10.1002/hep.28251] [PMID: 26403645]
[34]
Alvarez, S.W.; Sviderskiy, V.O.; Terzi, E.M.; Papagiannakopoulos, T.; Moreira, A.L.; Adams, S.; Sabatini, D.M.; Birsoy, K.; Possemato, R. NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis. Nature, 2017, 551(7682), 639-643.
[http://dx.doi.org/10.1038/nature24637] [PMID: 29168506]
[35]
Wang, Y.Q.; Chang, S.Y.; Wu, Q.; Gou, Y.J.; Jia, L.; Cui, Y.M.; Yu, P.; Shi, Z.H.; Wu, W.S.; Gao, G.; Chang, Y.Z. The protective role of mitochondrial ferritin on erastin-induced ferroptosis. Front. Aging Neurosci., 2016, 8, 308.
[http://dx.doi.org/10.3389/fnagi.2016.00308] [PMID: 28066232]
[36]
Mumbauer, S.; Pascual, J.; Kolotuev, I.; Hamaratoglu, F. Ferritin heavy chain protects the developing wing from reactive oxygen species and ferroptosis. PLoS Genet., 2019, 15(9), e1008396.
[http://dx.doi.org/10.1371/journal.pgen.1008396] [PMID: 31568497]
[37]
Ma, S.; Dielschneider, R.F.; Henson, E.S.; Xiao, W.; Choquette, T.R.; Blankstein, A.R.; Chen, Y.; Gibson, S.B. Ferroptosis and autophagy induced cell death occur independently after siramesine and lapatinib treatment in breast cancer cells. PLoS One, 2017, 12(8), e0182921.
[http://dx.doi.org/10.1371/journal.pone.0182921] [PMID: 28827805]
[38]
Li, L.; Hao, Y.; Zhao, Y.; Wang, H.; Zhao, X.; Jiang, Y.; Gao, F. Ferroptosis is associated with oxygen-glucose deprivation/reoxygenation-induced Sertoli cell death. Int. J. Mol. Med., 2018, 41(5), 3051-3062.
[http://dx.doi.org/10.3892/ijmm.2018.3469] [PMID: 29436589]
[39]
Shang, Y.; Luo, M.; Yao, F.; Wang, S.; Yuan, Z.; Yang, Y. Ceruloplasmin suppresses ferroptosis by regulating iron homeostasis in hepatocellular carcinoma cells. Cell. Signal., 2020, 72, 109633.
[http://dx.doi.org/10.1016/j.cellsig.2020.109633] [PMID: 32283255]
[40]
Yi, J.; Zhu, J.; Wu, J.; Thompson, C.B.; Jiang, X. Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis. Proc. Natl. Acad. Sci. USA, 2020, 117(49), 31189-31197.
[http://dx.doi.org/10.1073/pnas.2017152117] [PMID: 33229547]
[41]
Tesfay, L.; Paul, B.T.; Konstorum, A.; Deng, Z.; Cox, A.O.; Lee, J.; Furdui, C.M.; Hegde, P.; Torti, F.M.; Torti, S.V. Stearoyl-CoA desaturase 1 protects ovarian cancer cells from ferroptotic cell death. Cancer Res., 2019, 79(20), 5355-5366.
[http://dx.doi.org/10.1158/0008-5472.CAN-19-0369] [PMID: 31270077]
[42]
Lee, H.; Zandkarimi, F.; Zhang, Y.; Meena, J.K.; Kim, J.; Zhuang, L.; Tyagi, S.; Ma, L.; Westbrook, T.F.; Steinberg, G.R.; Nakada, D.; Stockwell, B.R.; Gan, B. Energy-stress-mediated AMPK activation inhibits ferroptosis. Nat. Cell Biol., 2020, 22(2), 225-234.
[http://dx.doi.org/10.1038/s41556-020-0461-8] [PMID: 32029897]
[43]
Lee, J.Y.; Nam, M.; Son, H.Y.; Hyun, K.; Jang, S.Y.; Kim, J.W.; Kim, M.W.; Jung, Y.; Jang, E.; Yoon, S.J.; Kim, J.; Kim, J.; Seo, J.; Min, J.K.; Oh, K.J.; Han, B.S.; Kim, W.K.; Bae, K.H.; Song, J.; Kim, J.; Huh, Y.M.; Hwang, G.S.; Lee, E.W.; Lee, S.C. Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer. Proc. Natl. Acad. Sci. USA, 2020, 117(51), 32433-32442.
[http://dx.doi.org/10.1073/pnas.2006828117] [PMID: 33288688]
[44]
Muri, J.; Thut, H.; Bornkamm, G.W.; Kopf, M. B1 and marginal zone B Cells but not follicular B2 cells require Gpx4 to prevent lipid peroxidation and ferroptosis. Cell Rep., 2019, 29(9), 2731-2744.e4.
[http://dx.doi.org/10.1016/j.celrep.2019.10.070] [PMID: 31775041]
[45]
Ma, X.; Xiao, L.; Liu, L.; Ye, L.; Su, P.; Bi, E.; Wang, Q.; Yang, M.; Qian, J.; Yi, Q. CD36-mediated ferroptosis dampens intratumoral CD8+ T cell effector function and impairs their antitumor ability. Cell Metab., 2021, 33(5), 1001-1012.e5.
[http://dx.doi.org/10.1016/j.cmet.2021.02.015] [PMID: 33691090]
[46]
Wang, W.; Green, M.; Choi, J.E.; Gijón, M.; Kennedy, P.D.; Johnson, J.K.; Liao, P.; Lang, X.; Kryczek, I.; Sell, A.; Xia, H.; Zhou, J.; Li, G.; Li, J.; Li, W.; Wei, S.; Vatan, L.; Zhang, H.; Szeliga, W.; Gu, W.; Liu, R.; Lawrence, T.S.; Lamb, C.; Tanno, Y.; Cieslik, M.; Stone, E.; Georgiou, G.; Chan, T.A.; Chinnaiyan, A.; Zou, W. CD8+T cells regulate tumour ferroptosis during cancer immunotherapy. Nature, 2019, 569(7755), 270-274.
[http://dx.doi.org/10.1038/s41586-019-1170-y] [PMID: 31043744]
[47]
Kagan, V.E.; Mao, G.; Qu, F.; Angeli, J.P.F.; Doll, S.; Croix, C.S.; Dar, H.H.; Liu, B.; Tyurin, V.A.; Ritov, V.B.; Kapralov, A.A.; Amoscato, A.A.; Jiang, J.; Anthonymuthu, T.; Mohammadyani, D.; Yang, Q.; Proneth, B.; Klein-Seetharaman, J.; Watkins, S.; Bahar, I.; Greenberger, J.; Mallampalli, R.K.; Stockwell, B.R.; Tyurina, Y.Y.; Conrad, M.; Bayır, H. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat. Chem. Biol., 2017, 13(1), 81-90.
[http://dx.doi.org/10.1038/nchembio.2238] [PMID: 27842066]
[48]
Nassar, Z.D.; Mah, C.Y.; Dehairs, J.; Burvenich, I.J.G.; Irani, S.; Centenera, M.M.; Helm, M.; Shrestha, R.K.; Moldovan, M.; Don, A.S.; Holst, J.; Scott, A.M.; Horvath, L.G.; Lynn, D.J.; Selth, L.A.; Hoy, A.J.; Swinnen, J.V.; Butler, L.M. Human DECR1 is an androgen-repressed survival factor that regulates PUFA oxidation to protect prostate tumor cells from ferroptosis. eLife, 2020, 9, e54166.
[http://dx.doi.org/10.7554/eLife.54166] [PMID: 32686647]
[49]
Blomme, A.; Ford, C.A.; Mui, E.; Patel, R.; Ntala, C.; Jamieson, L.E.; Planque, M.; McGregor, G.H.; Peixoto, P.; Hervouet, E.; Nixon, C.; Salji, M.; Gaughan, L.; Markert, E.; Repiscak, P.; Sumpton, D.; Blanco, G.R.; Lilla, S.; Kamphorst, J.J.; Graham, D.; Faulds, K.; MacKay, G.M.; Fendt, S.M.; Zanivan, S.; Leung, H.Y. 2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer. Nat. Commun., 2020, 11(1), 2508.
[http://dx.doi.org/10.1038/s41467-020-16126-7] [PMID: 32427840]
[50]
Chen, P.H.; Wu, J.; Ding, C.K.C.; Lin, C.C.; Pan, S.; Bossa, N.; Xu, Y.; Yang, W.H.; Mathey-Prevot, B.; Chi, J.T. Kinome screen of ferroptosis reveals a novel role of ATM in regulating iron metabolism. Cell Death Differ., 2020, 27(3), 1008-1022.
[http://dx.doi.org/10.1038/s41418-019-0393-7] [PMID: 31320750]
[51]
Bao, W.D.; Pang, P.; Zhou, X.T.; Hu, F.; Xiong, W.; Chen, K.; Wang, J.; Wang, F.; Xie, D.; Hu, Y.Z.; Han, Z.T.; Zhang, H.H.; Wang, W.X.; Nelson, P.T.; Chen, J.G.; Lu, Y.; Man, H.Y.; Liu, D.; Zhu, L.Q. Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer’s disease. Cell Death Differ., 2021, 28(5), 1548-1562.
[http://dx.doi.org/10.1038/s41418-020-00685-9] [PMID: 33398092]
[52]
Wenzel, S.E.; Tyurina, Y.Y.; Zhao, J.; St Croix, C.M.; Dar, H.H.; Mao, G.; Tyurin, V.A.; Anthonymuthu, T.S.; Kapralov, A.A.; Amoscato, A.A.; Mikulska-Ruminska, K.; Shrivastava, I.H.; Kenny, E.M.; Yang, Q.; Rosenbaum, J.C.; Sparvero, L.J.; Emlet, D.R.; Wen, X.; Minami, Y.; Qu, F.; Watkins, S.C.; Holman, T.R.; VanDemark, A.P.; Kellum, J.A.; Bahar, I.; Bayır, H.; Kagan, V.E. PEBP1 wardens ferroptosis by enabling lipoxygenase generation of lipid death signals. Cell, 2017, 171(3), 628-641.e26.
[http://dx.doi.org/10.1016/j.cell.2017.09.044] [PMID: 29053969]
[53]
Yang, W.S.; Kim, K.J.; Gaschler, M.M.; Patel, M.; Shchepinov, M.S.; Stockwell, B.R. Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis. Proc. Natl. Acad. Sci. USA, 2016, 113(34), E4966-E4975.
[http://dx.doi.org/10.1073/pnas.1603244113] [PMID: 27506793]
[54]
Ghandi, M.; Huang, F.W.; Jané-Valbuena, J.; Kryukov, G.V.; Lo, C.C.; McDonald, E.R., III; Barretina, J.; Gelfand, E.T.; Bielski, C.M.; Li, H.; Hu, K.; Andreev-Drakhlin, A.Y.; Kim, J.; Hess, J.M.; Haas, B.J.; Aguet, F.; Weir, B.A.; Rothberg, M.V.; Paolella, B.R.; Lawrence, M.S.; Akbani, R.; Lu, Y.; Tiv, H.L.; Gokhale, P.C.; de Weck, A.; Mansour, A.A.; Oh, C.; Shih, J.; Hadi, K.; Rosen, Y.; Bistline, J.; Venkatesan, K.; Reddy, A.; Sonkin, D.; Liu, M.; Lehar, J.; Korn, J.M.; Porter, D.A.; Jones, M.D.; Golji, J.; Caponigro, G.; Taylor, J.E.; Dunning, C.M.; Creech, A.L.; Warren, A.C.; McFarland, J.M.; Zamanighomi, M.; Kauffmann, A.; Stransky, N.; Imielinski, M.; Maruvka, Y.E.; Cherniack, A.D.; Tsherniak, A.; Vazquez, F.; Jaffe, J.D.; Lane, A.A.; Weinstock, D.M.; Johannessen, C.M.; Morrissey, M.P.; Stegmeier, F.; Schlegel, R.; Hahn, W.C.; Getz, G.; Mills, G.B.; Boehm, J.S.; Golub, T.R.; Garraway, L.A.; Sellers, W.R. Next-generation characterization of the cancer cell line encyclopedia. Nature, 2019, 569(7757), 503-508.
[http://dx.doi.org/10.1038/s41586-019-1186-3] [PMID: 31068700]
[55]
Zou, Y.; Li, H.; Graham, E.T.; Deik, A.A.; Eaton, J.K.; Wang, W.; Sandoval-Gomez, G.; Clish, C.B.; Doench, J.G.; Schreiber, S.L. Cytochrome P450 oxidoreductase contributes to phospholipid peroxidation in ferroptosis. Nat. Chem. Biol., 2020, 16(3), 302-309.
[http://dx.doi.org/10.1038/s41589-020-0472-6] [PMID: 32080622]
[56]
Friedmann Angeli, J.P.; Schneider, M.; Proneth, B.; Tyurina, Y.Y.; Tyurin, V.A.; Hammond, V.J.; Herbach, N.; Aichler, M.; Walch, A.; Eggenhofer, E.; Basavarajappa, D.; Rådmark, O.; Kobayashi, S.; Seibt, T.; Beck, H.; Neff, F.; Esposito, I.; Wanke, R.; Förster, H.; Yefremova, O.; Heinrichmeyer, M.; Bornkamm, G.W.; Geissler, E.K.; Thomas, S.B.; Stockwell, B.R.; O’Donnell, V.B.; Kagan, V.E.; Schick, J.A.; Conrad, M. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat. Cell Biol., 2014, 16(12), 1180-1191.
[http://dx.doi.org/10.1038/ncb3064] [PMID: 25402683]
[57]
Angeli, J.P.F.; Shah, R.; Pratt, D.A.; Conrad, M. Ferroptosis inhibition: Mechanisms and opportunities. Trends Pharmacol. Sci., 2017, 38(5), 489-498.
[http://dx.doi.org/10.1016/j.tips.2017.02.005] [PMID: 28363764]
[58]
Yang, W.S.; SriRamaratnam, R.; Welsch, M.E.; Shimada, K.; Skouta, R.; Viswanathan, V.S.; Cheah, J.H.; Clemons, P.A.; Shamji, A.F.; Clish, C.B.; Brown, L.M.; Girotti, A.W.; Cornish, V.W.; Schreiber, S.L.; Stockwell, B.R. Regulation of ferroptotic cancer cell death by GPX4. Cell, 2014, 156(1-2), 317-331.
[http://dx.doi.org/10.1016/j.cell.2013.12.010] [PMID: 24439385]
[59]
Badgley, M.A.; Kremer, D.M.; Maurer, H.C.; DelGiorno, K.E.; Lee, H.J.; Purohit, V.; Sagalovskiy, I.R.; Ma, A.; Kapilian, J.; Firl, C.E.M.; Decker, A.R.; Sastra, S.A.; Palermo, C.F.; Andrade, L.R.; Sajjakulnukit, P.; Zhang, L.; Tolstyka, Z.P.; Hirschhorn, T.; Lamb, C.; Liu, T.; Gu, W.; Seeley, E.S.; Stone, E.; Georgiou, G.; Manor, U.; Iuga, A.; Wahl, G.M.; Stockwell, B.R.; Lyssiotis, C.A.; Olive, K.P. Cysteine depletion induces pancreatic tumor ferroptosis in mice. Science, 2020, 368(6486), 85-89.
[http://dx.doi.org/10.1126/science.aaw9872] [PMID: 32241947]
[60]
Wang, L.; Cai, H.; Hu, Y.; Liu, F.; Huang, S.; Zhou, Y.; Yu, J.; Xu, J.; Wu, F. A pharmacological probe identifies cystathionine β-synthase as a new negative regulator for ferroptosis. Cell Death Dis., 2018, 9(10), 1005.
[http://dx.doi.org/10.1038/s41419-018-1063-2] [PMID: 30258181]
[61]
Martinez, A.M.; Mirkovic, J.; Stanisz, Z.A.; Patwari, F.S.; Yang, W.S. NSC‐34 motor neuron‐like cells are sensitized to ferroptosis upon differentiation. FEBS Open Bio, 2019, 9(4), 582-593.
[http://dx.doi.org/10.1002/2211-5463.12577] [PMID: 30984534]
[62]
Jeschke, J.; O’Hagan, H.M.; Zhang, W.; Vatapalli, R.; Calmon, M.F.; Danilova, L.; Nelkenbrecher, C.; Van Neste, L.; Bijsmans, I.T.G.W.; Van Engeland, M.; Gabrielson, E.; Schuebel, K.E.; Winterpacht, A.; Baylin, S.B.; Herman, J.G.; Ahuja, N. Frequent inactivation of cysteine dioxygenase type 1 contributes to survival of breast cancer cells and resistance to anthracyclines. Clin. Cancer Res., 2013, 19(12), 3201-3211.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-3751] [PMID: 23630167]
[63]
Hao, S.; Yu, J.; He, W.; Huang, Q.; Zhao, Y.; Liang, B.; Zhang, S.; Wen, Z.; Dong, S.; Rao, J.; Liao, W.; Shi, M. Cysteine dioxygenase 1 mediates erastin-induced ferroptosis in human gastric cancer cells. Neoplasia, 2017, 19(12), 1022-1032.
[http://dx.doi.org/10.1016/j.neo.2017.10.005] [PMID: 29144989]
[64]
Wang, K.; Zhang, Z.; Tsai, H.; Liu, Y.; Gao, J.; Wang, M.; Song, L.; Cao, X.; Xu, Z.; Chen, H.; Gong, A.; Wang, D.; Cheng, F.; Zhu, H. Branched-chain amino acid aminotransferase 2 regulates ferroptotic cell death in cancer cells. Cell Death Differ., 2021, 28(4), 1222-1236.
[http://dx.doi.org/10.1038/s41418-020-00644-4] [PMID: 33097833]
[65]
Zeitler, L.; Fiore, A.; Meyer, C.; Russier, M.; Zanella, G.; Suppmann, S.; Gargaro, M.; Sidhu, S.S.; Seshagiri, S.; Ohnmacht, C.; Köcher, T.; Fallarino, F.; Linkermann, A.; Murray, P.J. Anti-ferroptotic mechanism of IL4i1-mediated amino acid metabolism. eLife, 2021, 10, e64806.
[http://dx.doi.org/10.7554/eLife.64806] [PMID: 33646117]
[66]
Xie, Y.; Zhu, S.; Song, X.; Sun, X.; Fan, Y.; Liu, J.; Zhong, M.; Yuan, H.; Zhang, L.; Billiar, T.R.; Lotze, M.T.; Zeh, H.J., III; Kang, R.; Kroemer, G.; Tang, D. The tumor suppressor p53 limits ferroptosis by blocking DPP4 activity. Cell Rep., 2017, 20(7), 1692-1704.
[http://dx.doi.org/10.1016/j.celrep.2017.07.055] [PMID: 28813679]
[67]
Shimada, K.; Skouta, R.; Kaplan, A.; Yang, W.S.; Hayano, M.; Dixon, S.J.; Brown, L.M.; Valenzuela, C.A.; Wolpaw, A.J.; Stockwell, B.R. Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis. Nat. Chem. Biol., 2016, 12(7), 497-503.
[http://dx.doi.org/10.1038/nchembio.2079] [PMID: 27159577]
[68]
Viswanathan, V.S.; Ryan, M.J.; Dhruv, H.D.; Gill, S.; Eichhoff, O.M.; Seashore-Ludlow, B.; Kaffenberger, S.D.; Eaton, J.K.; Shimada, K.; Aguirre, A.J.; Viswanathan, S.R.; Chattopadhyay, S.; Tamayo, P.; Yang, W.S.; Rees, M.G.; Chen, S.; Boskovic, Z.V.; Javaid, S.; Huang, C.; Wu, X.; Tseng, Y.Y.; Roider, E.M.; Gao, D.; Cleary, J.M.; Wolpin, B.M.; Mesirov, J.P.; Haber, D.A.; Engelman, J.A.; Boehm, J.S.; Kotz, J.D.; Hon, C.S.; Chen, Y.; Hahn, W.C.; Levesque, M.P.; Doench, J.G.; Berens, M.E.; Shamji, A.F.; Clemons, P.A.; Stockwell, B.R.; Schreiber, S.L. Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway. Nature, 2017, 547(7664), 453-457.
[http://dx.doi.org/10.1038/nature23007] [PMID: 28678785]
[69]
Shimada, K.; Hayano, M.; Pagano, N.C.; Stockwell, B.R. Cell-line selectivity improves the predictive power of pharmacogenomic analyses and helps identify NADPH as biomarker for ferroptosis sensitivity. Cell Chem. Biol., 2016, 23(2), 225-235.
[http://dx.doi.org/10.1016/j.chembiol.2015.11.016] [PMID: 26853626]
[70]
Ding, C.K.C.; Rose, J.; Sun, T.; Wu, J.; Chen, P.H.; Lin, C.C.; Yang, W.H.; Chen, K.Y.; Lee, H.; Xu, E.; Tian, S.; Akinwuntan, J.; Zhao, J.; Guan, Z.; Zhou, P.; Chi, J.T. MESH1 is a cytosolic NADPH phosphatase that regulates ferroptosis. Nat. Metab., 2020, 2(3), 270-277.
[http://dx.doi.org/10.1038/s42255-020-0181-1] [PMID: 32462112]
[71]
Cardoso, B.R.; Hare, D.J.; Bush, A.I.; Roberts, B.R. Glutathione peroxidase 4: A new player in neurodegeneration? Mol. Psychiatry, 2017, 22(3), 328-335.
[http://dx.doi.org/10.1038/mp.2016.196] [PMID: 27777421]
[72]
Christensen, L.P. Ginsenosides chemistry, biosynthesis, analysis, and potential health effects. Adv. Food Nutr. Res., 2009, 55, 1-99.
[PMID: 18772102]
[73]
Christensen, L.P.; Jensen, M.; Kidmose, U. Simultaneous determination of ginsenosides and polyacetylenes in American ginseng root (Panax quinquefolium L.) by high-performance liquid chromatography. J. Agric. Food Chem., 2006, 54(24), 8995-9003.
[http://dx.doi.org/10.1021/jf062068p] [PMID: 17117783]
[74]
Tawab, M.A.; Bahr, U.; Karas, M.; Wurglics, M.; Schubert-Zsilavecz, M. Degradation of ginsenosides in humans after oral administration. Drug Metab. Dispos., 2003, 31(8), 1065-1071.
[http://dx.doi.org/10.1124/dmd.31.8.1065] [PMID: 12867496]
[75]
Shibata, S. Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds. J. Korean Med. Sci., 2001, 16(Suppl), S28-S37.
[76]
Bae, E.A.; Han, M.J.; Kim, E.J.; Kim, D.H. Transformation of ginseng saponins to ginsenoside rh2 by acids and human intestinal bacteria and biological activities of their transformants. Arch. Pharm. Res., 2004, 27(1), 61-67.
[http://dx.doi.org/10.1007/BF02980048] [PMID: 14969341]
[77]
Amin, A.; Lotfy, M.; Mahmoud-Ghoneim, D.; Adeghate, E.; Al-Akhras, M.A.; Al-Saadi, M.; Al-Rahmoun, S.; Hameed, R. Pancreas-protective effects of chlorella in STZ-induced diabetic animal model: Insights into the mechanism. J. Diabetes Mellitus, 2011, 1(3), 36-45.
[http://dx.doi.org/10.4236/jdm.2011.13006]
[78]
Abdalla, A.; Murali, C.; Amin, A. Safranal inhibits angiogenesis via targeting HIF-1α/VEGF machinery: In vitro and ex vivo insights. Front. Oncol., 2022, 11, 789172.
[http://dx.doi.org/10.3389/fonc.2021.789172] [PMID: 35211395]
[79]
Dai, C.; Li, H.; Wang, Y.; Tang, S.; Velkov, T.; Shen, J. Inhibition of oxidative stress and ALOX12 and NF-κB pathways contribute to the protective effect of baicalein on carbon tetrachloride-induced acute liver injury. Antioxidants, 2021, 10(6), 976.
[http://dx.doi.org/10.3390/antiox10060976] [PMID: 34207230]
[80]
Li, Y.; Yu, P.; Fu, W.; Wang, S.; Zhao, W.; Ma, Y.; Wu, Y.; Cui, H.; Yu, X.; Fu, L.; Xu, H.; Sui, D. Ginsenoside Rd inhibited ferroptosis to alleviate CCl 4-induced acute liver injury in mice via cGAS/STING pathway. Am. J. Chin. Med., 2023, 51(1), 91-105.
[http://dx.doi.org/10.1142/S0192415X23500064] [PMID: 36437551]
[81]
Shan, Y.; Li, J.; Zhu, A.; Kong, W.; Ying, R.; Zhu, W. Ginsenoside Rg3 ameliorates acute pancreatitis by activating the NRF2/HO-1-mediated ferroptosis pathway. Int. J. Mol. Med., 2022, 50(1), 89.
[http://dx.doi.org/10.3892/ijmm.2022.5144] [PMID: 35582998]
[82]
Zhao, X.; Wu, J.; Guo, D.; Hu, S.; Chen, X.; Hong, L.; Wang, J.; Ma, J.; Jiang, Y.; Niu, T.; Miao, F.; Li, W.; Wang, B.; Chen, X.; Song, Y. Dynamic ginsenoside-sheltered nanocatalysts for safe ferroptosis-apoptosis combined therapy. Acta Biomater., 2022, 151, 549-560.
[http://dx.doi.org/10.1016/j.actbio.2022.08.026] [PMID: 36007778]
[83]
Ye, J.; Lyu, T.J.; Li, L.Y.; Liu, Y.; Zhang, H.; Wang, X.; Xi, X.; Liu, Z.J.; Gao, J.Q. Ginsenoside Re attenuates myocardial ischemia/reperfusion induced ferroptosis via miR-144-3p/SLC7A11. Phytomedicine, 2023, 113, 154681.
[http://dx.doi.org/10.1016/j.phymed.2023.154681] [PMID: 36893674]
[84]
Lee, G.H.; Lee, W.J.; Hur, J.; Kim, E.; Lee, H.G.; Seo, H.G. Ginsenoside Re mitigates 6-Hydroxydopamine-induced oxidative stress through upregulation of GPX4. Molecules, 2020, 25(1), 188.
[http://dx.doi.org/10.3390/molecules25010188] [PMID: 31906464]
[85]
Guo, J.; Wang, R.; Min, F. Ginsenoside Rg1 ameliorates sepsis-induced acute kidney injury by inhibiting ferroptosis in renal tubular epithelial cells. J. Leukoc. Biol., 2022, 112(5), 1065-1077.
[http://dx.doi.org/10.1002/JLB.1A0422-211R] [PMID: 35774015]
[86]
Wu, Y.; Pi, D.; Zhou, S.; Yi, Z.; Dong, Y.; Wang, W.; Ye, H.; Chen, Y.; Zuo, Q.; Ouyang, M. Ginsenoside Rh3 induces pyroptosis and ferroptosis through the Stat3/p53/NRF2 axis in colorectal cancer cells. Acta Biochim. Biophys. Sin., 2023, 55(4), 587-600.
[http://dx.doi.org/10.3724/abbs.2023068] [PMID: 37092860]
[87]
Wu, Y.; Pi, D.; Chen, Y.; Zuo, Q.; Zhou, S.; Ouyang, M. Ginsenoside Rh4 inhibits colorectal cancer cell proliferation by inducing ferroptosis via autophagy activation. Evid.-based Complem. Altern. Med.: eCAM, 2022, 2022(2022), 6177553.
[88]
Bi, S.; Ma, X.; Wang, Y.; Chi, X.; Zhang, Y.; Xu, W.; Hu, S. Protective effect of ginsenoside Rg1 on oxidative damage induced by hydrogen peroxide in chicken splenic lymphocytes. Oxid. Med. Cell. Longev., 2019, 2019, 1-13.
[http://dx.doi.org/10.1155/2019/8465030] [PMID: 31178974]
[89]
Wang, Y.; Liu, Q.; Xu, Y.; Zhang, Y.; Lv, Y.; Tan, Y.; Jiang, N.; Cao, G.; Ma, X.; Wang, J.; Cao, Z.; Yu, B.; Kou, J. Ginsenoside Rg1 protects against oxidative stress-induced neuronal apoptosis through myosin IIA-actin related cytoskeletal reorganization. Int. J. Biol. Sci., 2016, 12(11), 1341-1356.
[http://dx.doi.org/10.7150/ijbs.15992] [PMID: 27877086]
[90]
Dong, X.; Zheng, L.; Lu, S.; Yang, Y. Neuroprotective effects of pretreatment of ginsenoside R b1 on severe cerebral ischemiainduced injuries in aged mice: Involvement of anti‐oxidant signaling. Geriatr. Gerontol. Int., 2017, 17(2), 338-345.
[http://dx.doi.org/10.1111/ggi.12699] [PMID: 26712031]
[91]
Liu, X.; Gu, X.; Yu, M.; Zi, Y.; Yu, H.; Wang, Y.; Xie, Y.; Xiang, L. Effects of ginsenoside Rb1 on oxidative stress injury in rat spinal cords by regulating the eNOS/Nrf2/HO-1 signaling pathway. Exp. Ther. Med., 2018, 16(2), 1079-1086.
[http://dx.doi.org/10.3892/etm.2018.6286] [PMID: 30116359]
[92]
Kim, D.H.; Kim, D.W.; Jung, B.H.; Lee, J.H.; Lee, H.; Hwang, G.S.; Kang, K.S.; Lee, J.W. Ginsenoside Rb2 suppresses the glutamate-mediated oxidative stress and neuronal cell death in HT22 cells. J. Ginseng Res., 2019, 43(2), 326-334.
[http://dx.doi.org/10.1016/j.jgr.2018.12.002] [PMID: 30976171]