Abstract
Dammarane-type ginsenosides are a class of tetracyclic triterpenoids with the same dammarane skeleton. These compounds have a wide range of pharmaceutical applications for neoplasms, diabetes mellitus and other metabolic syndromes, hyperlipidemia, cardiovascular and cerebrovascular diseases, aging, neurodegenerative disease, bone disease, liver disease, kidney disease, gastrointestinal disease and other conditions. In order to develop new antineoplastic drugs, it is necessary to improve the bioactivity, solubility and bioavailability, and illuminate the mechanism of action of these compounds. A large number of ginsenosides and their derivatives have been separated from certain herbs or synthesized, and tested in various experiments, such as anti-proliferation, induction of apoptosis, cell cycle arrest and cancer-involved signaling pathways. In this review, we have summarized the progress in structural modification, shed light on the structure-activity relationship (SAR), and offered insights into biosynthesis-structural association. This review is expected to provide a preliminary guide for the modification and synthesis of ginsenosides.
Keywords: Ginsenosides, dammarane, synthesis, structural modification, neoplasms, structure-activity relationship, 25-OCH3-PPD.
Graphical Abstract
[1]
Vinatoru, M.F.; Chemat, T.J.; Mason, T.J. The extraction of natural products using ultrasound or microwaves. COC, 2011, 15, 237-247.
[4]
Khanna, C.; Rosenberg, M.; Vail, D.M. A review of paclitaxel and novel formulations including those suitable for use in dogs. J. Vet. Intern. Med., 2015, 29, 1006-1012.
[5]
Wall, M.; Wani, M.; Cook, C.; Palmer, K.; McPhail, A.; Sim, G. The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor from Camptotheca acuminata. J. Am. Chem. Soc., 1996, 88, 3888-3890.
[6]
Sriram, D.; Yogeeswari, P.; Thirumurugan, R.; Bal, T.R. Camptothecin and its analogues: A review on their chemotherapeutic potential. Nat. Prod. Res., 2005, 19, 393-412.
[7]
Sun, T.; Zhang, L.; Li, X.; Chen, F.; Li, Y.; Ma, X.Yu.; F., Micro RNA-1 and circulating microvesicles mediate the protective effects of dantonic in acute myocardial infarction rat models. Front. Physiol., 2018, 9.
[8]
Toh, D.F.; Patel, D.N.; Chan, E.C.; Teo, A.; Neo, S.Y.; Koh, H.L. Anti-proliferative effects of raw and steamed extracts of Panax notoginseng and its ginsenoside constituents on human liver cancer cells. Chin. Med. J. , 2011, 6, 1-4.
[9]
Xiong, Y.; Shen, L.; Liu, K.; Tso, P.; Xiong, Y.; Wang, G.; Woods, S.C.; Liu, M. Antiobesity and antihyperglycemic effects of ginsenoside Rb1 in rats. Diabetes, 2010, 59, 2505-2512.
[10]
Wang, X.; Wang, C.; Wang, J.; Zhao, S.; Zhang, K.; Wang, J.; Zhang, W.; Wu, C.; Yang, J. Pseudoginsenoside-F11 (PF11) exerts anti-neuroinflammatory effects on LPS-activated microglial cells by inhibiting TLR4-mediated TAK1/IKK/NF-κB, MAPKs and Akt signaling pathways. Neuropharmacology, 2014, 79, 642-656.
[11]
Xin, X.; Wei, Z.D.; Liu, J. Protection effect of 20(S)-ginsenoside Rg_2 extracted from cultured Panax notoginseng cells on hydrogen peroxide-induced cytotoxity of human umbilical cord vein endothelial cells in vitro. Process Biochem., 2005, 40, 3202-3205.
[12]
Li, J.; Xie, Z.Z.; Tang, Y.B.; Zhou, J.G.; Guan, Y.Y. Ginsenoside-Rd, a purified component from panax notoginseng saponins, prevents atherosclerosis in apoE knockout mice. Eur. J. Pharmacol., 2011, 652, 104-110.
[13]
Sun, B.; Xiao, J.; Sun, X.B.; Wu, Y. Notoginsenoside R1 attenuates cardiac dysfunction in endotoxemic mice: An insight into oestrogen receptor activation and PI3K/Akt signalling. Br. J. Pharmacol., 2013, 168, 1758-1770.
[14]
Pan, C.; Huo, Y.; An, X.; Singh, G.; Chen, M.; Yang, Z.; Pu, J.; Li, J. Panax notoginseng and its components decreased hypertension via stimulation of endothelial-dependent vessel dilatation. Vascul. Pharmacol., 2012, 56, 150-158.
[15]
Lin, M.; Sun, W.; Gong, W.; Ding, Y.; Zhuang, Y.; Hou, Q. Ginsenoside Rg1 protects against transient focal cerebral ischemic injury and suppresses its systemic metabolic changes in cerabral injury rats. Acta Pharm. Sin. B, 2015, 5, 277-284.
[16]
Prasain, J.K.; Kadota, S.; Basnet, P.; Hase, K.; Namba, T. Hepatoprotective effects of Panax notoginseng: Ginsenosides -Re and -Rg(1) as its active constituents in D-galactosamine/lipopolysaccharide-induced liver injury. Phytomedicine, 1996, 2, 297-303.
[17]
Xie, X.S.; Yang, M.; Liu, H.C.; Zuo, C.; Zi, L.I.; Deng, Y.; Fan, J.M. Influence of ginsenoside Rg1, a panaxatriol saponin from Panax notoginseng, on renal fibrosis in rats with unilateral ureteral obstruction. J. Zhejiang Univ. Sci. B, 2008, 9, 885-894.
[18]
Yang, Z.G.; Ye, Y.P.; Sun, H.X. Immunological adjuvant effect of ginsenoside Rh4 from the roots of Panax notoginseng on specific antibody and cellular response to ovalbumin in mice. Chem. Biodivers., 2010, 4, 232-240.
[19]
Cao, J.; Zhang, X.; Qu, F.; Guo, Z.; Zhao, Y. Dammarane triterpenoids for
pharmaceutical use: Expert Opinion on Therapeutic Patents 2015805-817, A
patent review (2005 - 2014).
[20]
Zeng, X.S.; Zhou, X.S.; Luo, F.C.; Jia, J.J.; Qi, L.; Yang, Z.X.; Bai, J. Comparative analysis of the neuroprotective effects of ginsenosides Rg1 and Rb1 extracted from Panax notoginseng against cerebral ischemia. Can. J. Physiol. Pharmacol., 2014, 92, 102-108.
[21]
Wang, T.; Guo, R.; Zhou, G.; Zhou, X.; Kou, Z.; Sui, F.; Li, C.; Tang, L.; Wang, Z. Traditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.H. Chen: A review. J. Ethnopharmacol., 2016, 188, 234-258.
[22]
Wang, J.; Gao, W-Y.; Zhang, J.; Zuo, B-M.; Zhang, L-M.; Huang, L-Q. Advances in study of ginsenoside biosynthesis pathway in Panax ginseng C. A. Meyer. Acta Physiol. Plant., 2011, 34, 397-403.
[23]
Abe, I.; Rohmer, M.; Prestwich, G.D. Enzymatic cyclization of squalene and oxidosqualene to sterols and triterpenes. J. Cheminform., 1994, 2189-2206.
[24]
Wang, W.; Wang, H.; Rayburn, E.R.; Zhao, Y.; Hill, D.L.; Zhang, R. 20(S)-25-methoxyl-dammarane-3beta, 12beta, 20-triol, a novel natural product for prostate cancer therapy: activity in vitro and in vivo and mechanisms of action. Br. J. Cancer, 2008, 98, 792-802.
[28]
Dinda, B.; Debnath, S.; Mohanta, B.C.; Harigaya, Y. Naturally occurring triterpenoid saponins. Chem. Biodivers., 2010, 7, 2327-2580.
[29]
Zhang, Z.; Du, G.J.; Wang, C.Z.; Wen, X.D.; Calway, T.; Li, Z.; He, T.C.; Du, W.; Bissonnette, M.; Musch, M.; Chang, E. Compound K, a ginsenoside metabolite, inhibits colon cancer growth via multiple pathways including p53-p21 interactions. Int. J. Mol. Sci., 2013, 14, 2980-2995.
[30]
Chang, T.L.; Huang, Y.H.; Ou, Y.D. The role of ginsenosides in inhibiting ubiquitin activating enzyme (E1) activity. J. Funct. Foods, 2014, 7, 462-470.
[31]
Gstaiger, M. Jordan, R.; Lim, M.; Catzavelos, C.; Mestan, J.; Slingerland, J.; Krek, W. Skp2 is oncogenic and overexpressed in human cancers. Proc. Natl. Acad. Sci. USA, 2001, 98, 5043-5048.
[32]
Dutto, I.; Tillhon, M.; Cazzalini, O.; Stivala, L.A.; Prosperi, E. Biology of the cell cycle inhibitor p21 CDKN1A: Molecular mechanisms and relevance in chemical toxicology. Arch. Toxicol., 2015, 89, 155-178.
[33]
Wang, J.H.; Nao, J.F.; Zhang, M.; He, P. 20(s)-ginsenoside Rg3 promotes apoptosis in human ovarian cancer HO-8910 cells through PI3K/Akt and XIAP pathways. Tumour Biol., 2014, 35, 11985-11994.
[34]
Kikuchi, Y.; Sasa, H.; Kita, T.; Hirata, J.; Tode, T.; Nagata, I. Inhibition of human ovarian cancer cell proliferation in vitro by ginsenoside Rh2 and adjuvant effects to cisplatin in vivo. Anticancer Drugs, 1991, 2, 63-67.
[35]
Tode, T.; Kikuchi, Y.; Hirata, J.; Kita, T.; Imaizumi, E.; Nagata, I. Inhibitory effects of oral administration of ginsenoside Rh2 on tumor growth in nude mice bearing serous cyst adenocarcinoma of the human ovary. Nippon Shokakibyo Gakkai Zasshi, 1993, 45, 1275-1282.
[36]
Tode, T.; Kikuchi, Y.; Kita, T.; Hirata, J.; Imaizumi, E.; Nagata, I. Inhibitory effects by oral administration of ginsenoside Rh2 on the growth of human ovarian cancer cells in nude mice. J. Cancer Res. Clin. Oncol., 1993, 120, 24-26.
[37]
Nakata, H.; Kikuchi, Y.; Tode, T.; Hirata, J.; Kita, T.; Ishii, K.; Kudoh, K.; Nagata, I. Inhibitory effects of ginsenoside rh2 on tumor growth in nude mice bearing human ovarian cancer cells. Cancer Sci., 1998, 89, 733-740.
[38]
Liul, J.; Shimizu, K.; Yu, H.; Zhang, C.; Jin, F.; Kondo, R. Stereospecificity of hydroxyl group at C-20 in antiproliferative action of ginsenoside Rh2 on prostate cancer cells. Fitoterapia, 2010, 81, 902-905.
[39]
Li, B.; Zhao, J.; Wang, C.Z.; Searle, J.; He, T.C.; Yuan, C.S.; Du, W. Ginsenoside Rh2 induces apoptosis and paraptosis-like cell death in colorectal cancer cells through activation of p53. Cancer Lett., 2011, 301, 185-192.
[40]
Oh, M.E.; Choi, Y.H.; Choi, S.; Chung, H.; Kim, K.; Kim, S.I.; Kim, D.K. Anti-proliferating effects of ginsenoside Rh2 on MCF-7 human breast cancer cells. Int. J. Oncol., 1999, 14, 869-875.
[41]
Choi, S.; Kim, T.W.; Singh, S.V. Ginsenoside Rh2-mediated G1 phase cell
cycle arrest in human breast cancer cells is caused by p15 Ink4B and p27
Kip1-dependent inhibition of cyclin-dependent kinases.. Pharm. Res., 2009, 26, 2280-2288.
[42]
Lasserre, R.; Guo, X.J.; Conchonaud, F.; Hamon, Y.; Hawchar, O.; Bernard, A.M.; Soudja, S.M.; Lenne, P.F.; Rigneault, H.; Olive, D.; Bismuth, G. Raft nanodomains contribute to Akt/PKB plasma membrane recruitment and activation. Nat. Chem. Biol., 2008, 4, 538-5347.
[43]
Park, E.K.; Lee, E.J.; Lee, S.H.; Koo, K.H.; Sung, J.Y.; Hwang, E.H.; Park, J.H.; Kim, C.W.; Jeong, K.C.; Park, B.K.; Kim, Y.N. Induction of apoptosis by the ginsenoside Rh2 by internalization of lipid rafts and caveolae and inactivation of Akt. Br. J. Pharmacol., 2010, 160, 1212-1223.
[44]
Zhao, Y.; Wang, W.; Han, L.; Rayburn, E.R.; Hil, D.L.; Wang, H.; Zhang, R. Isolation, structural determination, and evaluation of the biological activity of 20(S)-25-methoxyl-dammarane-3beta, 12beta, 20-triol[20(S)-25-OCH3-PPD], a novel natural product from Panax notoginseng. Med. Chem., 2007, 3, 51-60.
[45]
Wang, W.; Rayburn, E.R.; Zhao, Y.; Wang, H.; Zhang, R. Novel ginsenosides 25-OH-PPD and 25-OCH3-PPD as experimental therapy for pancreatic cancer: Anticancer activity and mechanisms of action. Cancer Lett., 2009, 278, 241-248.
[46]
Wang, W.; Rayburn, E.R.; Hao, M.; Zhao, Y.; Hill, D.L.; Zhang, R.; Wang, H. Experimental therapy of prostate cancer with novel natural product anti-cancer ginsenosides. The Prostate, 2008, 68, 809-819.
[47]
Bi, X.; Zhao, Y.; Fang, W.; Yang, W. Anticancer activity of Panax notoginseng extract 20(S)-25-OCH3-PPD: Targetting beta-catenin signalling. Clin. Exp. Pharmacol. Physiol., 2009, 36, 1074-1078.
[48]
Zhang, L.H.; Jia, Y.L.; Lin, X.X.; Zhang, H.Q.; Dong, X.W.; Zhao, J.; Shen, J.; Shen, H.J.; Li, F.F.; Yan, X.F.; Li, W. AD-1, a novel ginsenoside derivative, shows anti-lung cancer activity via activation of p38 MAPK pathway and generation of reactive oxygen species. Biochim. Biophys. Acta, 2013, 1830, 4148-4159.
[49]
Yoon, J.H.; Choi, Y.J.; Cha, S.W.; Lee, S.G. Anti-metastatic effects of ginsenoside Rd via inactivation of MAPK signaling and induction of focal adhesion formation. Phytomedicine, 2012, 19, 284-292.
[50]
Osman, N.A.; El-Rehim, D.M.; Kamal, I.M. Defective Beclin-1 and elevated hypoxia-inducible factor (HIF)-1α expression are closely linked to tumorigenesis, differentiation, and progression of hepatocellular carcinoma. Tumour Biol., 2015, 36, 4293-4299.
[51]
Liu, T.; Zhao, L.; Hou, H.; Ding, L.; Chen, W.; Li, X. Ginsenoside 20(S)-Rg3 suppresses ovarian cancer migration via hypoxia-inducible factor 1 alpha and nuclear factor-kappa B signals. Tumour Biol., 2017, 39. [doi.org/10.1177/1010428317692225].
[52]
Gao, Q.; Zheng, J. Ginsenoside Rh2 inhibits prostate cancer cell growth through suppression of microRNA-4295 that activates CDKN1A. Cell Prolif., 2018, 51, e12438.
[53]
Zhang, Q.; Hong, B.; Wu, S.; Niu, T. Inhibition of prostatic cancer growth by ginsenoside Rh2. Tumour Biol., 2015, 36, 2377-2381.
[54]
Li, S.; Guo, W.; Gao, Y.; Liu, Y. Ginsenoside Rh2 inhibits growth of glioblastoma multiforme through mTor. Tumour Biol., 2015, 36, 2607-2612.
[55]
Leung, K.W.; Leung, K.W.; Cheung, L.W.; Pon, Y.L.; Wong, R.N.; Mak, N.K.; Fan, T.P.; Au, S.C.; Tombran‐Tink, J. Wong, A.S. Ginsenoside Rb1 inhibits tube-like structure formation of endothelial cells by regulating pigment epithelium-derived factor through the oestrogen beta receptor. Br. J. Pharmacol., 2007, 152, 207-215.
[56]
Bae, E.A.; Han, M.J.; Kim, E.J.; Kim, D.H. Transformation of ginseng saponins to ginsenoside rh 2 by acids and human intestinal bacteria and biological activities of their transformants. Arch. Pharm. Res., 2004, 27, 61-67.
[57]
Hasegawa, H.; Lee, K.S.; Nagaoka, T.; Tezuka, Y.; Uchiyama, M.; Kadota, S.; Saiki, I. Pharmacokinetics of ginsenoside deglycosylated by intestinal bacteria and its transformation to biologically active fatty acid esters. Biol. Pharm. Bull., 2000, 23, 298-304.
[58]
Wakabayashi, C.; Hasegawa, H.; Murata, J.; Saiki, I. In vivo antimetastatic action of ginseng protopanaxadiol saponins is based on their intestinal bacterial metabolites after oral administration. Oncol. Res., 1997, 9, 411-417.
[59]
Hasegawa, H. Proof of the mysterious efficacy of ginseng: Basic and clinical trials: Metabolic activation of ginsenoside: Deglycosylation by intestinal bacteria and esterification with fatty acid. J. Pharmacol. Sci., 2004, 95, 153-157.
[60]
Wang, P.; Bi, X.L.; Guo, Y.M.; Cao, J.Q.; Zhang, S.J.; Yuan, H.N.; Piao, H.R.; Zhao, Y.Q. Semi-synthesis and anti-tumor evaluation of novel 25-hydroxyprotopanaxadiol derivatives. Eur. J. Med. Chem., 2012, 55, 137-145.
[61]
Liu, Y.F.; Yuan, H.N.; Bi, X.L.; Piao, H.R.; Cao, J.Q.; Li, W.; Wang, P.; Zhao, Y.Q. 25-Methoxylprotopanaxadiol derivatives and their anti-proliferative activities. Steroids, 2013, 78, 1305-1311.
[62]
Liu, X.K.; Ye, B.J.; Wu, Y.; Lin, Z.H.; Zhao, Y.Q.; Piao, H.R. Synthesis and anti-tumor evaluation of panaxadiol derivatives. Eur. J. Med. Chem., 2011, 46, 1997-2002.
[63]
Wang, P.; Bi, X.L.; Xu, J.; Yuan, H.N.; Piao, H.R.; Zhao, Y.Q. Synthesis and anti-tumor evaluation of novel 25-hydroxyprotopanaxadiol analogs incorporating natural amino acids. Steroids, 2013, 78, 203-209.
[64]
Qu, F.; Zhao, C.; Liu, Y.; Cao, J.; Li, W.; Zhao, Y. Semi-synthesis and anti-tumor evaluation of novel 25-hydroxyprotopanaxadiol derivatives as apoptosis inducing agents. MedChemComm, 2015, 6, 2004-2011.
[65]
Yuan, W.; Guo, J.; Wang, X.; Su, G.; Zhao, Y. Non-protein amino acid derivatives of 25-methoxylprotopanaxadiol/25-hydroxyprotopanaxadioland their anti-tumour activity evaluation. Steroids, 2018, 129, 1-8.
[66]
Zhou, W.X.; Cao, J.Q.; Wang, X.D.; Guo, J.H.; Zhao, Y.Q. Sulfamic and succinic acid derivatives of 25-OH-PPD and their activities to MCF-7, A-549, HCT-116, and BGC-823 cell lines. Bioorg. Med. Chem. Lett., 2017, 27, 1076-1080.
[67]
Zhou, W.X.; Sun, Y.Y.; Yuan, W.H.; Zhao, Y.Q. Water-soluble derivatives of 25-OCH3-PPD and their anti-proliferative activities. Steroids, 2017, 121, 32-39.
[68]
Qu, F.Z.; Liu, Y.F.; Cao, J.Q.; Wang, X.D.; Zhang, X.S.; Zhao, C.; Zhao, Y.Q. Novel 25-hydroxyprotopanaxadiol derivatives incorporating chloroacetyl chloride and their anti-tumor evaluation. Bioorg. Med. Chem. Lett., 2014, 24, 5390-5394.
[69]
Qu, F.Z.; Zhao, C.; Cao, J.Q.; Zhang, Y.; Zhao, Y.Q. One-pot synthesis, anti-tumor evaluation and structure-activity relationships of novel 25-OCH3-PPD derivatives. MedChemComm, 2017, 8, 1845-1849.
[70]
Guo, J.; Xu, Z.; Li, Y.; Wang, X.; Zhao, Y. Synthesis of novel 25-hydroxyprotopanaxadiol derivatives by methylation and methoxycarbonylation using dimethyl carbonate as a environment-friendly reagent and their anti-tumor evaluation. Bioorg. Med. Chem. Lett., 2016, 26, 4763-4768.
[71]
De, W. X.; Sun, Y.Y.; Zhao, C.; Qu, F.Z.; Zhao, Y.Q. 12-Chloracetyl-PPD, a novel dammarane derivative, shows anti-cancer activity via delay the progression of cell cycle G2/M phase and reactive oxygen species-mediate cell apoptosis. Eur. J. Pharmacol., 2017, 798, 49-56.
[72]
De Wang, X.; Su, G.Y.; Zhao, C.; Qu, F.Z.; Wang, P.; Zhao, Y.Q. Anticancer activity and potential mechanisms of 1C, a ginseng saponin derivative, on prostate cancer cells. J. Ginseng Res., 2018, 42, 133-143.
[73]
Liao, J.; Sun, J.; Niu, Y.; Yu, B. Synthesis of ginsenoside Rh2 and chikusetsusaponin-LT8 via gold(I)-catalyzed glycosylation with a glycosyl ortho-alkynylbenzoate as donor. Tetrahedron Lett., 2011, 52, 3075-3078.
[74]
Anufriev, V.P.; Malinovskaya, G.V.; Denisenko, V.A.; Uvarova, N.I.; Elyakov, G.B.; Kim, S.I.; Baek, N.I. Synthesis of ginsenoside Rg 3, a minor constituent of Ginseng Radix. Carbohydr. Res., 1997, 304, 179-182.
[75]
Atopkina, L.N.; Denisenko, V.A. Synthesis of 20s-protopanaxadiol beta-d-galactopyranosides. Chem. Nat. Compd., 2011, 47, 79-84.
[76]
Wei, Y.; Ma, C.M.; Hattori, M. Synthesis of dammarane-type triterpene derivatives and their ability to inhibit HIV and HCV proteases. Bioorg. Med. Chem., 2009, 17, 3003-3010.
[77]
Huang, W.; Qi, D. Process for producing dammarane sapogenins and ginsenosides from ginseng and their use as anticancer agents, in US0113316A1.
2005. United States patent application US 10/896,473. May 26. 2005.
[78]
Wang, K.C.; Wang, P.H.; Lee, S.S. Microbial Transformation of Protopanaxadiol and Protopanaxatriol Derivatives with Mycobacterium sp. (NRRL B-3805). J. Nat. Prod., 1997, 60, 1236-1241.
[79]
Yue, C.J.; Zhong, J.J. Purification and characterization of UDPG: Ginsenoside Rd glucosyltransferase from suspended cells of Panax notoginseng. Process Biochem., 2005, 40, 3742-3748.
[80]
Hou, J.; Xue, J.; Wang, C.; Liu, L.; Zhang, D.; Wang, Z.; Li, W.; Zheng, Y.; Sung, C. Microbial transformation of ginsenoside Rg3 to ginsenoside Rh2 by Esteya vermicola CNU 120806. World J. Microbiol. Biotechnol., 2012, 28, 1807-1811.
[81]
Sun, C.; Li, Y.; Wu, Q.; Luo, H.; Sun, Y.; Song, J.; Lui, E.M.; Chen, S. De novo sequencing and analysis of the American ginseng root transcriptome using a GS FLX Titanium platform to discover putative genes involved in ginsenoside biosynthesis. BMC Genomics, 2010, 11, 262.
[82]
Danieli, B.; Falcone, L.; Monti, D.; Riva, S.; Gebhardt, S.; Schubert-Zsilavecz, M. Regioselective enzymatic glycosylation of natural polyhydroxylated compounds: galactosylation and glucosylation of protopanaxatriol ginsenosides. J. Org. Chem., 2001, 66, 262-269.
[83]
Ding, M.; Xu, L.; Zhang, Y.; Zhao, Y. Polymorphic characterization and bioavailability of 20(R)-25-methoxyl-dammarane-3beta,12beta,20-triol, a novel dammarane triterpenoid saponin, as anticancer agents. J. Pharm. Biomed. Anal., 2017, 145, 773-782.
[84]
Allen, J.A.; Halverson-Tamboli, R.A.; Rasenick, M.M. Lipid raft microdomains and neurotransmitter signalling. Nat. Rev. Neurosci., 2007, 8, 128-140.
[85]
Korade, Z.; Kenworthy, A.K. Lipid rafts, cholesterol, and the brain. Neuropharmacology, 2008, 55, 1265-1273.
[87]
Yun, M.; Keshvara, L.; Park, C.G.; Zhang, Y.M.; Dickerson, J.B.; Zheng, J.; Rock, C.O.; Curran, T.; Park, H.W. Crystal structures of the Dab homology domains of mouse disabled 1 and 2. J. Biol. Chem., 2003, 278, 36572-36581.
[88]
Janes, P.W.; Ley, S.C.; Magee, A.I.; Kabouridis, P.S. The role of lipid rafts in T cell antigen receptor (TCR) signalling. Semin. Immunol., 2000, 12, 23-34.
[89]
Adam, R.M.; Mukhopadhyay, N.K.; Kim, J.; Di Vizio, D.; Cinar, B.; Boucher, K.; Solomon, K.R.; Freeman, M.R. Cholesterol sensitivity of endogenous and myristoylated Akt. Cancer Res., 2007, 67, 6238-6246.
[90]
Zhuang, L.; Kim, J.; Adam, R.M.; Solomon, K.R.; Freeman, M.R. Cholesterol targeting alters lipid raft composition and cell survival in prostate cancer cells and xenografts. J. Clin. Invest., 2005, 115, 959-968.
[91]
Anchisi, L.; Dessì, S.; Pani, A.; Mandas, A. Cholesterol homeostasis: A key to prevent or slow down neurodegeneration. Front. Physiol., 2012, 3, 486-486.
[92]
Wang, W.; Zhao, Y.; Rayburn, E.R.; Hill, D.L.; Wang, H.; Zhang, R. In vitro anti-cancer activity and structure-activity relationships of natural products isolated from fruits of Panax ginseng. Cancer Chemother. Pharmacol., 2007, 59, 589-601.
[93]
Odashima, S.; Ohta, T.; Kohno, H.; Matsuda, T.; Kitagawa, I.; Abe, H.; Arichi, S. Control of phenotypic expression of cultured B16 melanoma cells by plant glycosides. Cancer Res., 1985, 45, 2781-2784.
[94]
Hao, M.; Zhao, Y.; Chen, P.; Huang, H.; Liu, H.; Jiang, H.; Zhang, R.; Wang, H. Structure-activity relationship and substrate-dependent phenomena in effects of ginsenosides on activities of drug-metabolizing P450 enzymes. PLoS One, 2008, 3, e2697.
[95]
Chen, Y.; Wang, H.; Xu, S. Study on the chemical constituents of Panax ginseng and their structure–function relationship anti-arrythmia and anti-tumor. Science Foundation China., 1995, 9, 46-48.
[96]
Popovich, D.G.; Kitts, D.D. Structure-function relationship exists for ginsenosides in reducing cell proliferation and inducing apoptosis in the human leukemia (THP-1) cell line. Arch. Biochem. Biophys., 2002, 406, 1-8.
[97]
Jeong, S.M.; Lee, J.H.; Kim, J.H.; Lee, B.H.; Yoon, I.S.; Lee, J.H.; Kim, D.H.; Rhim, H.; Kim, Y.; Nah, S.Y. Stereospecificity of ginsenoside Rg3 action on ion channels. Mol. Cell, 2004, 18, 383-389.
[98]
Fiske, J.L.; Fomin, V.P.; Brown, M.L.; Duncan, R.L.; Sikes, R.A. Voltage-sensitive ion channels and cancer. Cancer Metastasis Rev., 2006, 25, 493-500.
[99]
Wang, W.; Zhang, X.; Qin, J.J.; Voruganti, S.; Nag, S.A.; Wang, M.H.; Wang, H.; Zhang, R. Natural product ginsenoside 25-OCH3-PPD inhibits breast cancer growth and metastasis through down-regulating MDM2. PLoS One, 2012, 7, 1-11.
[100]
Wang, L.; Sun, J.; Horvat, M.; Koutalistras, N.; Johnston, B.; Sheil, A.R. Evaluation of MTS, XTT, MTT and 3HTdR incorporation for assessing hepatocyte density, viability and proliferation. Methods Cell Biol., 1996, 18, 249-255.
[101]
Park, H.; Kwak, T.H.; Bae, J.H.; Moon, D.G.; Kim, J.J.; Cheon, J. Development of the novel anti-cancer immunotherapy for human prostate cancer: In vivo characterization of an immunotropic and anti-cancer activities of the new polysaccharide from the leaves of panax ginseng C.A. Meyer. Eur. Urol., 2004, 3, 94-94.
[102]
Zhang, Y.; Yuan, W.; Wang, X.; Zhang, H.; Sun, Y.; Zhang, X.; Zhao, Y. Synthesis, characterization and cytotoxic activity evaluation of ginsengdiol oxidation and nitrogen hybrid derivatives. MedChemComm, 2018, 9(11), 1910-1919.
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