Antitrypanosomal properties of panax ginseng C. A. Meyer: New possibilities for a remarkable traditional drug

Phytotherapy Research

Volumn 27, Issue 1, 2013, Pages 86-98

  Herrmann, Florian ^a   Sporer, Frank ^a   Tahrani, Ahmad ^a   Wink, Michael ^a  

^a UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

cytotoxicity; Panax ginseng; panaxynol (= falcarinol); polyacetylene; Trypanosoma brucei brucei; trypanothione reductase

Indexed keywords

ANTITRYPANOSOMAL AGENT; DIMINAZENE; EFLORNITHINE; FALCARINDIOL; GINSENG EXTRACT; GINSENOSIDE; GINSENOSIDE RB 1; GINSENOSIDE RC; GINSENOSIDE RD; GINSENOSIDE RE; GINSENOSIDE RG 1; GINSENOSIDE RG 2; GINSENOSIDE RG 3; GINSENOSIDE RH 1; GINSENOSIDE RH 2; HEXANE; METHANOL; PANAX NOTOGINSENG EXTRACT; PANAXYDOL; PANAXYNOL; PANAXYTRIOL; POLYACETYLENE; POLYACETYLENE PANAXYNOL; PROTOPANAXADIOL; PROTOPANAXATRIOL; PSEUDOGINSENOSIDE F; SURAMIN; TRYPANOTHIONE REDUCTASE; UNCLASSIFIED DRUG;

ANTITRYPANOSOMAL ACTIVITY; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG CYTOTOXICITY; DRUG EFFECT; DRUG ISOLATION; DRUG SELECTIVITY; DRUG STRUCTURE; ENZYME INHIBITION; GENETIC IDENTIFICATION; HELA CELL; HUMAN; HUMAN CELL; NONHUMAN; NUCLEOTIDE SEQUENCE; TRADITIONAL MEDICINE; TREATMENT INDICATION; TRYPANOSOMA; TRYPANOSOMA BRUCEI; TRYPANOSOMIASIS;

ANTIPROTOZOAL AGENTS; DIYNES; FATTY ALCOHOLS; GINSENOSIDES; HELA CELLS; HUMANS; PANAX; PLANT EXTRACTS; PLANT ROOTS; TRYPANOSOMA BRUCEI BRUCEI;

PANAX GINSENG; PANAX NOTOGINSENG; TRYPANOSOMA BRUCEI BRUCEI;

EID: 84872073082     PISSN: 0951418X     EISSN: 10991573     Source Type: Journal    
DOI: 10.1002/ptr.4692     Document Type: Article

References (131)

1. Ahn BZ,. 1988. Beziehung zwischen Struktur und cytotoxischer Aktivitat von Panaxydol- Analogen gegen L 12 10 Zellen. Arch Pharm (Weinheim) 321: 6143.
2. Alanko J, Kurahashi Y, Yoshimoto T, Yamamoto S, Baba K,. 1994. Panaxynol, a polyacetylene compound isolated from oriental medicines, inhibits mammalian lipoxygenases. Biochem Pharmacol 48: 1979-1981.
3. Bae EA, Han MJ, Baek NI, Kim DH,. 2001. In vitro anti-Helicobacter pylori activity of panaxytriol isolated from ginseng. Arch Pharm Res 24: 297-299.
4. Baltz T, Baltz D, Giroud C, Crockett J,. 1985. Cultivation in a semi-defined medium of animal infective forms of Trypanosoma brucei, T. equiperdum, T. evansi, T. rhodesiense and T. gambiense. EMBO J 4: 1273-1277.
5. Barrett MP,. 1999. The fall and rise of sleeping sickness. Lancet 353: 1113-1114.
6. Barrett MP, Boykin DW, Brun R, Tidwell RR,. 2007. Human African trypanosomiasis: pharmacological re-engagement with a neglected disease. Br J Pharmacol 152: 1155-1171.
7. Bernart MW, Cardellina JH 2nd, Balaschak MS, Alexander MR, Shoemaker RH, Boyd MR,. 1996. Cytotoxic falcarinol oxylipins from Dendropanax arboreus. J Nat Prod 59: 748-753.
8. Bohlmann F, Niedballa U, Rode KM,. 1966. New polyines with a C17-chain. Chem Ber 99: 3552-3558.
9. Bond CS, Zhang Y, Berriman M, Cunningham ML, Fairlamb AH, Hunter WH,. 1999. Crystal structure of Trypanosoma cruzi trypanothione reductase in complex with trypanothione, and the structure-based discovery of new natural product inhibitors. Structure 7: 81-89.
10. Brandt K, Christensen LP, Hansen-Møller J, et al,. 2004. Health promoting compounds in vegetables and fruits: a systematic approach for identifying plant components with impact on human health. Trends Food Sci Tech 15: 384-393.
11. Brun R, Schumacher R, Schmid C, Kunz C, Burri C,. 2001. The phenomenon of treatment failures in Human African Trypanosomiasis. Trop Med Int Health 6: 906-914.
12. Chen CF, Chiou WF, Zhang JT,. 2008. Comparison of the pharmacological effects of Panax ginseng and Panax quinquefolium. Acta Pharmacol Sin 29: 1103-1108.
13. Cho WC, Yip TT, Chung WS, et al,. 2006. Altered expression of serum protein in ginsenoside Re-treated diabetic rats defected by SELDI-TOF MS. J Ethnopharmacol 108: 272-279.
14. Choi KT,. 2008. Botanical characteristics, pharmacological effects and medicinal components of Korean Panax ginseng C A Meyer. Acta Pharmacol Sin 29: 1109-1118.
15. + currents in rat dorsal root ganglion neurons. Brain Res 1191: 75-83.
16. Christensen LP,. 1992. Acetylenes and related compounds in Anthemideae. Phytochemistry 31: 7-49.
17. Christensen LP, Brandt K,. 2006. Bioactive polyacetylenes in food plants of the apiaceae family: occurrence, bioactivity and analysis. J Pharmaceut Biomed Anal 41: 683-693.
18. Christensen LP, Lam J,. 1990. Acetylenes and related compounds in Cynareae. Phytochemistry 29: 2753-2785.
19. Christensen LP, Lam J,. 1991. Acetylenes and related compounds in Heliantheae. Phytochemistry 30: 11-49.
20. Croft SL,. 1997. The current status of antiparasitic chemotherapy. Parasitology 114 Suppl: 3-15.
21. Cunsolo F, Ruberto G, Amico V, Piattelli M,. 1993. Bioactive metabolites from Sicilian marine fennel, Crithmum maritimum. J Nat Prod 56: 1598-1600.
22. D'Angelo L, Grimaldi R, Caravaggi M, et al,. 1986. A double-blind, placebo-controlled clinical study on the effect of a standardized ginseng extract on psychomotor performance in healthy volunteers. J Ethnopharmacol 16: 15-22.
23. Ebermann R, Alth G, Kreitner M, Kubin A,. 1996. Natural products derived from plants as potential drugs for the photodynamic destruction of tumor cells. J Photochem Photobiol B 36: 95-97.
24. Fairlamb AH,. 2003a. Chemotherapy of human African trypanosomiasis: current status and future prospects. Trends Parasitol 19: 488-494.
25. Fairlamb AH,. 2003b. Target discovery and validation with special reference to trypanothione. In Drugs Against Parasitic Diseases: R&D Methodologies and Issues, Fairlamb AH, Ridley RG, Vial HJ, (eds). WHO TDR: Geneva; 107-118.
26. Fairlamb AH, Blackburn P, Ulrich P, Chait BT, Cerami A,. 1985. Trypanothione: a novel bis (glutathionyl) spermidine cofactor for glutathione reductase in trypanosomatids. Science 227: 1485-1487.
27. Fairlamb AH, Cerami A,. 1985. Identification of a novel, thiol-containing co-factor essential for glutathione reductase enzyme activity in trypanosomatids. Mol Biochem Parasitol 14: 187-198.
28. Fujimoto Y, Sakuma S, Komatsu S, et al,. 1998. Inhibition of 15-hydroxyprostaglandin dehydrogenase activity in rabbit gastric antral mucosa by panaxynol isolated from oriental medicines. J Pharm Pharmacol 50: 1075-1078.
29. Fujimoto Y, Satoh M,. 1988. A new cytotoxic chlorine-containing polyacetylene from the callus of Panax ginseng. Chem Pharm Bull(Tokyo) 36: 4206-4208.
30. Fujimoto Y, Satoh M, Takeuchi N, Kirisawa M,. 1991. Cytotoxic acetylenes from Panax quinquefolium. Chem Pharm Bull(Tokyo) 39: 521-523.
31. Garrod B, Lewis BG,. 1978. Cis-heptadeca-1,9-diene-4,6-diyne-3,8-diol, an antifungal polyacetylene from carrot root tissue. Physiol Mol Plant Pathol 13: 241-246.
32. Gerpe A, Odreman-Nuñez I, Draper P, et al,. 2007. Heteroallyl-containing5-nitrofuranes as new anti-Trypanosoma cruzi agents with a dual mechanism of action. Bioorg Med Chem 16: 569-577.
33. Hai J, Lin Q, Lu Y, Zhang H, Yi J,. 2007. Induction of apoptosis in rat C6 glioma cells by panaxydol. Cell Biol Int 31: 711-715.
34. Halim M, Yee DJ, Sames D,. 2008. Imaging induction of cytoprotective enzymes in intact human cells: coumberone, a metabolic reporter for human AKR1C enzymes reveals activation by panaxytriol, an active component of red ginseng. J Am Chem Soc 130: 14123-14128.
35. Hansen L, Boll PM,. 1986. Polyacetylenes in Araliaceae: their chemistry, biosynthesis and biological significance. Phytochemistry 25: 285-293.
36. Hansen L, Hammershoy O, Boll PM,. 1986. Allergic contact dermatitis from falcarinol isolated from Schefflera arboricola. Contact Dermatitis 14: 91-93.
37. Hansen L, Purup S, Christensen LP,. 2003. Bioactivity of falcarinol and the influence of processing and storage on its content in carrots (Daucus carota L). J Sci Food Agr 83: 1010-1017.
38. 1 cells by panaxynol via cAMP pathway. Neurosci Lett 383: 121-126.
39. Harding VK, Heale JB,. 1980. Isolation and identification of the antifungal compounds accumulating in the induced resistance response of carrot root slices to Botrytis cinerea. Physiol Mol Plant Pathol 17: 277-289.
40. Harding VK, Heale JB,. 1981. The accumulation of inhibitory compounds in the induced resistance response of carrot root slices to Botrytis cinerea. Physiol Mol Plant Pathol 18: 7-15.
41. Harmon MA, Scott TC, Li Y, Boehm MF, Phillips MA, Mangelsdorf DJ,. 1997. Trypanosoma brucei: effects of methoprene and other isoprenoid compounds on procyclic and bloodstream forms in vitro and in mice. Exp Parasitol 87: 229-236.
42. Hausen BM, Bröhan J, König WA, Faasch H, Hahn H, Bruhn G,. 1987. Allergic and irritant contact dermatitis from falcarinol and didehydrofalcarinol in common ivy (Hedera helix L.). Contact Dermatitis 17: 1-9.
43. Hoet S, Opperdoes F, Brun R, Quetin-Leclerq J,. 2004. Natural products active against African trypanosomes: a step towards new drugs. Nat Prod Rep 21: 353-364.
44. Huang HQ, Zhang X, Shen YH, et al,. 2009. Polyacetylenes from Bupleurum longiradiatum. J Nat Prod 72: 2153-2157.
45. Hudson JB,. 1989. Plant photosensitizers with antiviral properties. Antiviral Res 12: 55-74.
46. Ito A, Cui B, Chávez D, et al,. 2001. Cytotoxic polyacetylenes from the twigs of Ochanostachys amentacea. J Nat Prod 64: 246-248.
47. Kang SY, Schini-Kerth VB, Kim ND,. 1995. Ginsenosides of the protopanaxatriol group cause endothelium-dependent relaxation in the rat aorta. Life Sci 56: 1577-1586.
48. Kemp MS,. 1978. Falcarindiol: an antifungal polyacetylene from Agopodium podagraria. Phytochemistry 17: 1002.
49. Kennedy DO, Scholey AB, Wesnes KA,. 2002. Modulation of cognition and mood following administration of single doses of Ginkgo biloba, ginseng, and a ginkgo/ginseng combination to healthy young adults. Physiol Behav 75: 739-751.
50. Kidmose U, Hansen SL, Christensen LP, Edelenbos M, Larsen E, Nørbæk R,. 2004. Effects of genotype, root size, storage, and processing on bioactive compounds in organically grown carrots (Daucus carota L.). J Food Sci 69: 388-394.
51. Kiefer D, Pantuso T,. 2003. Panax ginseng. Am Fam Physician 68: 1539-1542.
52. Kim JS, Lim YJ, Im KS, et al,. 1999. Cytotoxic polyacetylenes from the marine sponge Petrosia sp. J Nat Prod 62: 554-559.
53. Kim JY, Lee KW, Kim SH, Wee JJ, Kim YS, Lee HJ,. 2002. Inhibitory effect of tumor cell proliferation and induction of G2/M cell cycle arrest by panaxytriol. Planta Med 68: 119-122.
54. Kim YS, Jin SH, Kim SI, Hahn DR,. 1989. Studies on the mechanism of cytotoxicities of polyacetylenes against L1210 cells. Arch Pharm Res 12: 207-213.
55. Kitagawa I, Yoshikawa M, Yoshihara M, Hayashi T, Taniyama T,. 1983. Chemical studies of crude drugs (1). Constituents of Ginseng radix rubra. Yakugaku Zasshi 103: 612-622.
56. Kobaek-Larsen M, Christensen LP, Vach W, Ritskes-Hoitinga J, Brandt K,. 2005. Inhibitory effects of feeding with carrots or (-)-falcarinol on development of azoxymethane-induced preneoplastic lesions in the rat colon. J Agric Food Chem 53: 1823-1827.
57. Kobaisy M, Abramowski Z, Lermer L, Saxena G, Hancock REW, Towers GHN,. 1997. Antimycobacterial polyynes of Devil's Club (Oplopanax horridus), a North American native medicinal plant. J Nat Prod 60: 1210-1213.
58. Krauth-Siegel RL, Bauer H, Schirmer RH,. 2005. Dithiol proteins as guardians of the intracellular redox milieu in parasites: old and new targets in trypanosomes and malaria-causing plasmodia. Angew Chem Int Ed Engl 44: 690-715.
59. Kristjanson PM, Swallow BM, Rowlands GJ, Kruska RL, de Leeuw PN,. 1999. Measuring the costs of African animal trypanosomiasis, the potential benefits of control and returns to research. Agr Sys 59: 79-98.
60. Kuo SC, Teng CM, Lee JC, Ko FN, Chen SC, Wu TS,. 1990. Antiplatelet components in Panax ginseng. Planta Med 56: 164-167.
61. Kuo YC, Lin YL, Huang CP, Shu JW, Tsai WJ,. 2002. A tumor cell growth inhibitor from Saposhnikovae divaricata. Cancer Invest 20: 955-964.
62. Kwon BM, Nam JY, Lee SH, Jeong TS, Kim YK, Bok SH,. 1996. Isolation of cholesteryl ester transfer protein inhibitors from Panax ginseng roots. Chem Pharm Bull(Tokyo) 44: 444-445
63. Kwon BM, Ro SH, Kim MK, et al,. 1997. Polyacetylene analogs, isolated from hairy roots of Panax ginseng, inhibit Acyl-CoA: cholesterol acyltransferase. Planta Med 63: 552-553.
64. Lechner D, Stavri M, Oluwatuyi M, Pereda-Miranda R, Gibbons S,. 2004. The anti-staphylococcal activity of Angelica dahurica (Bai Zhi). Phytochemistry 65: 331-335.
65. Lee FC,. 1992. Facts About Ginseng, the Elixir of Life. (1st edn). Hollym International Corp: Elizabeth, NJ.
66. Lee SW, Kim K, Rho MC, et al,. 2004. New polyacetylenes, DGAT inhibitors from the roots of Panax ginseng. Planta Med 70: 197-200.
67. Lee TK, Johnke RM, Allison RR, O'Brien KF, Dobbs LJ Jr., 2005. Radioprotective potential of ginseng. Mutagenesis 20: 237-243.
68. 2 to lower plasma glucose in Wister rats. Clin Exp Pharmacol Physiol 33: 27-32.
69. Legros D, Ollivier G, Gastellu-Etchegorry M, et al,. (2002). Treatment of human African trypanosomiasis - present situation and needs for research and development. Lancet Infect Dis 2: 437-440.
70. Leonti M, Casu L, Raduner S, et al,. 2010. Falcarinol is a covalent cannabinoid CB1 receptor antagonist and induces pro-allergic effects in skin. Biochem Pharmacol 79: 1815-1826.
71. Liu JH, Lee CS, Leung KM, et al,. 2007. Quantification of two polyacetylenes in radix ginseng and roots of related Panax species using a gas chromatography-mass spectrometric method. J Agric Food Chem 55: 8830-8835.
72. Mahady GB, Gyllenhall C, Fong HH, Farnsworth NR,. 2000. Ginseng: a review of safety and efficacy. Nutr Clin Care 3: 90-101.
73. Matsunaga H, Katano M, Saitai T, Yamamoto H, Mori M,. 1994. Potentiation of cytotoxicity of mitomycin C by a polyacetylenic alcohol, panaxytriol. Cancer Chemother Pharmacol 33: 291-297.
74. Matsunaga H, Katano M, Yamamoto H, Fujito H, Mori M, Takata K,. 1990. Cytotoxic activity of polyacetylene compounds in Panax ginseng C. A. Meyer. Chem Pharm Bull(Tokyo) 38: 3480-3482.
75. Matsunaga H, Katano M, Yamamoto H, Mori M, Takata K,. 1989. Studies on the panaxytriol of Panax ginseng C. A. Meyer. Isolation, determination and antitumor activity. Chem Pharm Bull(Tokyo) 37: 1279-1281.
76. Matsunaga H, Saita T, Nagumo F, Moil M, Katano M,. 1995. A possible mechanism for the cytotoxicity of a polyacetylenic alcohol, panaxytriol inhibition of mitochondrial respiration. Cancer Chemother Pharmacol 35: 291-296.
77. McLellan EA, Bird RP,. 1988a. Aberrant crypts: potential preneoplastic lesions in the murine colon. Cancer Res 48: 6187-6192.
78. McLellan EA, Bird RP,. 1988b. Specificity study to evaluate induction of aberrant crypts in murine colons. Cancer Res 48: 6183-6186.
79. Miyazawa M, Shimamura H, Bhuva RC, Nakamura S, Kameoka H,. 1996. Antimutagenic activity of falcarindiol from Peucedanum praeruptorum. Agric Food Chem 44: 3444-3448.
80. KIP1 increase by panaxydol isolated from Panax ginseng. Biochem Pharmacol 59: 1109-1116.
81. Mosmann T,. 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55-63.
82. Muir AD, Cole AL, Walker JR,. 1982. Antibiotic compounds from New Zealand plants. I. Falcarindiol, an anti-dermatophyte agent from Schefflera digitata. Planta Med 44: 129-133.
83. Murdoch SR, Dempster J,. 2000. Allergic contact dermatitis from carrot. Contact Dermatitis 42: 236.
84. Nakajima S, Uchiyama Y, Yoshida K, Mizukawa H, Haruki E,. 1998. The effect of ginseng radix rubra on human vascular endothelial cells. Am J Chin Med 26: 365-373.
85. Nakano Y, Matsunaga H, Saita T, Mori M, Katano M, Okabe H,. 1998. Antiproliferative constituents in Umbelliferae plants II. Screening for polyacetylenes in some Umbelliferae plants, and isolation of panaxynol and falcarindiol from the root of Heracleum moellendorffii. Biol Pharm Bull 21: 257-261.
86. Newman DJ, Cragg GM, Snader KM,. 2003. Natural products as sources of new drugs over the period 1981-2002. J Nat Prod 66: 1022-1037.
87. Nunes IS, Faria JM, Figueiredo AC, Pedro LG, Trinidade H, Barroso JG,. 2009. Menthol and geraniol biotransformation and glycosylation capacity of Levisticum officinale hairy roots. Planta Med 75: 387-391.
88. Oliveira FQ, Andrade-Neto V, Krettli AU, Brandão MG,. 2004. New evidences of antimalarial activity of Bidens pilosa roots extract correlated with polyacetylene and flavonoids. J Ethnopharmacol 93: 39-42.
89. Olsson K, Svensson R,. 1996. The influence of polyacetylenes on the susceptibility of carrots to storage diseases. J Phytopathology 144: 441-447.
90. 2 in human platelet aggregation. J Ethnopharmacol 49: 157-162.
91. Park SE, Park C, Kim SH, et al,. 2009. Korean red ginseng extract induces apoptosis and decreases telomerase activity in human leukemia cells. J Ethnopharmacol 121: 304-312.
92. Pereira RLC, Ibrahim T, Lucchetti L, da Silva AJR, Gonçalves de Moraes VL,. 1999. Immunosuppressive and anti-inflammatory effects of methanolic extract and the polyacetylene isolated from Bidens pilosa L. Immunopharmacology 43: 31-37.
93. Pink R, Hudson A, Mouriès MA, Bending M,. 2005. Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov 4: 727-740.
94. Popzawski J, Wrobel JT, Glinka T,. 1980. Panaxydol, a new polyacetylenic epoxide from Panax ginseng roots. Phytochemistry 19: 1539-1541.
95. Prior RM, Lundgaard NH, Light ME, Stafford GI, van Staden J, Jäger AK,. 2007. The polyacetylene falcarindiol with COX-1 activity isolated from Aegopodium podagraria L. J Ethnopharmacol 113: 176-178.
96. 17-polyacetylenes on intestinal cell proliferation. J Agr Food Chem 57: 8290-8296.
97. Rahman AA, Cho SC, Song J, Mun HT, Moon SS,. 2007. Dendrazawaynes A and B, antifungal polyacetylenes from Dendranthema zawadskii (Asteraceae). Planta Med 73: 1089-1094.
98. Räz B, Iten M, Grether-Bühler Y, Kaminsky R, Brun R,. 1997. The Alamar Blue assay to determine drug sensitivity of African trypanosomes (T.b. rhodesiense and T.b. gambiense) in vitro. Acta Trop 68: 139-147.
99. Resch M, Heilmann J, Steigel A, Bauer R,. 2001. Further phenols and polyacetylenes from the rhizomes of Atractylodes lancea and their anti-inflammatory activity. Planta Med 67: 437-442.
100. Rho MC, Lee HS, Lee SW, et al,. 2005. Polyacetylenic compounds, ACAT inhibitors from the roots of Panax ginseng. J Agric Food Chem 53: 919-922.
101. Rollinger JM, Zidorn C, Dobner MJ, Ellmerer EP, Stuppner H,. 2003. Lignans, phenylpropanoids and polyacetylenes from Chaerophyllum aureum L. (Apiaceae). Z Naturforsch C 58: 553-557.
102. Ross CA, Sutherland DV,. 1997. Drug resistance in trypanosomatids. In Trypanosomiasis and Leishmaniasis: Biology and Control, Hide G, Mottram JC, Coombs GH, Holmes PH, (eds). CAB international: Wallinford, Oxon; 259-269.
103. Scaglione F, Ferrara F, Dugnani S, Falchi M, Santoro G, Fraschini F,. 1990. Immunomodulatory effects of two extracts of Panax ginseng C A Meyer. Drugs Exp Clin Res 16: 537-542.
104. Scaglione F, Weiser K, Alessandria M,. 2001. Effects of the standardized ginseng extract G115® in patients with chronic bronchitis: a nonblind, randomised, comparative pilot study. Clin Drug Investig [New Zealand] 21: 41-45.
105. Schinkovitz A, Stavri M, Gibbons S, Bucar F,. 2008. Antimycobacterial polyacetylenes from Levisticum officinale. Phytother Res 22: 681-684.
106. Schneider I, Bucar F,. 2005a. Lipoxygenase inhibitors from natural plant sources. Part 1: medicinal plants with inhibitory activity on arachidonate 5-lipoxygenase and 5-lipoxygenase/cyclooxygenase. Phytother Res 19: 81-102.
107. Schneider I, Bucar F,. 2005b. Lipoxygenase inhibitors from natural plant sources. Part 2: medicinal plants with inhibitory activity on arachidonate 12-lipoxygenase, 15-lipoxygenase and leukotriene receptor antagonists. Phytother Res 19: 263-272.
108. Senn M, Gunzenhauser S, Brun R, Séquin U,. 2007. Antiprotozoal polyacetylenes from the Tanzanian medicinal plant Cussonia zimmermannii. J Nat Prod 70: 1565-1569.
109. Setzer WN, Green TJ, Whitaker KW, et al,. 1995. A cytotoxic diacetylene from Dendropanax arboreus. Planta Med 61: 470-471.
110. Setzer WN, Gu X, Wells EB, Setzer MC, Moriarity DM,. 2000. Synthesis and cytotoxic activity of a series of diacetylenic compounds related to falcarindiol. Chem Pharm Bull(Tokyo) 48: 1776-1777.
111. Shibata S, Tanaka O, Shoji J, Saito H,. 1985. Chemistry and pharmacology of Panax. In Economic and Medicinal Plant Research, Vol. 1, Wagner H, Hikino H, Farnsworth NR, (eds.). Academic Press: New York; 217-284.
112. Shim SC, Koh HY, Han BH,. 1983. Polyacetylenes from Panax ginseng roots. Phytochemistry 22: 1817-1818.
113. Shin HR, Kim JY, Yun TK, Morgan G, Vainio H,. 2000. The cancer-preventive potential of Panax ginseng: a review of human and experimental evidence. Cancer Cause Control 11: 565-576.
114. Sohn J, Lee CH, Chung DJ, Park SH, Kim I, Hwang WI,. 1998. Effect of petroleum ether extract of Panax ginseng roots on proliferation and cell cycle progression of human renal cell carcinoma cells. Exp Mol Med 30: 47-51.
115. Sorensen H, Sonne J,. 1996. A double-masked study of the effects of ginseng on cognitive functions. Curr Ther Res Clin E 57: 959-968.
116. Sotaniemi EA, Haapakosi E, Rautio A,. 1995. Ginseng therapy in non-insulin-dependent diabetic patients. Diabetes Care 18: 1373-1375.
117. Takashi M, Yoshikura M,. 1964. Studies on the components of Panax ginseng C. A. Meyer. 3. On the ethereal extract of ginseng radix alba. (3). On the structure of a new acetylene derivative "panaxynol". Yakugaku Zasshi 84: 757-759.
118. Teng CM, Kuo SC, Ko FN, et al,. 1989. Antiplatelet actions of panaxynol and ginsenosides isolated from ginseng. Biochim Biophys Acta 990: 315-320.
119. Tobinaga S, Sharma MK, Aalbersberg WG, et al,. 2009. Isolation and identification of a potent antimalarial and antibacterial polyacetylene from Bidens pilosa. Planta Med 75: 624-628.
120. Trouiller P, Olliaro P, Torreele E, Orbinski J, Laing R, Ford N,. 2002. Drug development for neglected diseases: a deficient market and a public-health policy failure. Lancet 359: 2188-2194.
121. Urbina JA,. 2002. Chemotherapy of Chagas disease. Curr Pharm Des 8: 287-295.
122. Wang CN, Shiao YJ, Kuo YH, Chen CC, Lin YL,. 2000. Inducible nitric oxide synthase inhibitors from Saposhnikovia divaricata and Panax quinquefolium. Planta Med 66: 644-647.
123. Wink M,. 2008. Evolutionary advantage and molecular modes of action of multi-component mixtures in phytomedicine. Curr Drug Metab 9: 996-1009.
124. World Health Organisation. 2000. WHO report on global surveillance of epidemic-prone infectious diseases. WHO/CDS/CSR/ISR/2000.1 http://www.who.int/ csr/resources/publications/surveillance/en/a-tryps.pdf Last access: June 2011.
125. Wu JN,. 2005. Panax ginseng. In An illustrated Chinese Materia Medica. Oxford University Press: New York; 460-461.
126. Yang MC, Seo DS, Choi SU, Park YH, Lee KR,. 2008. Polyacetylenes from the roots of cultivated-wild ginseng and their cytotoxicity in vitro. Arch Pharm Res 31: 154-159.
127. Yang ZG, Sun HX, Ye YP,. 2006. Ginsenoside Rd from Panax notoginseng is cytotoxic towards HeLa cancer cells and induces apoptosis. Chem Biodivers 3: 187-197.
128. Young JF, Duthie SJ, Milne L, Christensen LP, Duthie GG, Bestwick CS,. 2007. Biphasic effect of falcarinol on CaCo-2 cell proliferation, DNA damage and apoptosis. J Agric Food Chem 55: 618-623.
129. Yun TK,. 2003. Experimental and epidemiological evidence on non-organ specific cancer preventive effect of Korean ginseng and identification of active compounds. Mutat Res 523-524: 63-74.
130. Yun TK,. 2001. Panax ginseng-a non-organ-specific cancer preventive? Lancet Oncol 2: 49-55.
131. Zidorn C, Jöhrer K, Ganzera M, et al,. 2005. Polyacetylenes from the Apiaceae vegetables carrot, celery, fennel, parsley, and parsnip and their cytotoxic activities. J Agric Food Chem 53: 2518-2523.