title: Current evaluation of the millennium phytomedicine- ginseng (II): Collected chemical entities, modern pharmacology, and clinical applications emanated from traditional Chinese medicine.
abstract: This review, a sequel to part 1 in the series, collects about 107 chemical entities separated from the roots, leaves and flower buds of Panax ginseng, quinquefolius and notoginseng, and categorizes these entities into about 18 groups based on their structural similarity. The bioactivities of these chemical entities are described. The 'Yin and Yang' theory and the fundamentals of the 'five elements' applied to the traditional Chinese medicine (TCM) are concisely introduced to help readers understand how ginseng balances the dynamic equilibrium of human physiological processes from the TCM perspectives. This paper concerns the observation and experimental investigation of biological activities of ginseng used in the TCM of past and present cultures. The current biological findings of ginseng and its medical applications are narrated and critically discussed, including 1) its antihyperglycemic effect that may benefit type II diabetics; in vitro and in vivo studies demonstrated protection of ginseng on beta-cells and obese diabetic mouse models. The related clinical trial results are stated. 2) its aphrodisiac effect and cardiovascular effect that partially attribute to ginseng's bioactivity on nitric oxide (NO); 3) its cognitive effect and neuropharmacological effect that are intensively tested in various rat models using purified ginsenosides and show a hope to treat Parkinson's disease (PD); 4) its uses as an adjuvant or immunotherapeutic agent to enhance immune activity, appetite and life quality of cancer patients during their chemotherapy and radiation. Although the apoptotic effect of ginsenosides, especially Rh2, Rg3 and Compound K, on various tumor cells has been shown via different pathways, their clinical effectiveness remains to be tested. This paper also updates the antioxidant, anti-inflammatory, anti-apoptotic and immune-stimulatory activities of ginseng, its ingredients and commercial products, as well as common side effects of ginseng mainly due to its overdose, and its pharmacokinetics.
authors.affiliation: Developmental Therapeutics Program, National Cancer Institute/ NIH, Rockville, MD 20852, USA. jiale@mail.nih.gov
authors.forename: Lee
authors.initials: L
authors.lastname: Jia
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xing-Jie
authors.initials: XJ
authors.lastname: Liang
mesh_terms: D000818:Animals; D001046:Aphrodisiacs / Q000737:chemistry / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000188:drug therapy; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D009480:Neuropharmacology; D005894:Panax / Q000737:chemistry*; D008517:Phytotherapy; D028321:Plant Preparations / Q000009:adverse effects / Q000737:chemistry* / Q000627:therapeutic use*
chemical_list: D001046:Aphrodisiacs; D028321:Plant Preparations
references.citation: J Asian Nat Prod Res. 2001;3(2):123-30
references.pmid: 11407811
references.citation: Ann N Y Acad Sci. 1999;889:157-92
references.pmid: 10668493
references.citation: Biol Pharm Bull. 1996 Nov;19(11):1434-9
references.pmid: 8951159
references.citation: J Clin Endocrinol Metab. 2002 Aug;87(8):3691-5
references.pmid: 12161497
references.citation: Ann N Y Acad Sci. 2002 May;962:372-7
references.pmid: 12076988
references.citation: J Nat Prod. 2001 Sep;64(9):1127-32
references.pmid: 11575942
references.citation: Breast Cancer Res Treat. 2007 Sep;105(1):17-28
references.pmid: 17111207
references.citation: Cancer Chemother Pharmacol. 2007 Apr;59(5):589-601
references.pmid: 16924497
references.citation: J Nutr. 2007 Jan;137(1 Suppl):183S-185S
references.pmid: 17182823
references.citation: J Korean Med Sci. 2001 Dec;16 Suppl:S28-37
references.pmid: 11748374
references.citation: Cancer Chemother Pharmacol. 2008 Jan;61(1):63-73
references.pmid: 17356822
references.citation: Eur J Pharmacol. 2008 Jan 6;578(1):28-36
references.pmid: 17949708
references.citation: Chem Pharm Bull (Tokyo). 2005 Feb;53(2):177-9
references.pmid: 15684516
references.citation: J Am Coll Nutr. 2006 Apr;25(2):100-7
references.pmid: 16582025
references.citation: Chem Biodivers. 2006 Feb;3(2):187-97
references.pmid: 17193257
references.citation: Biol Pharm Bull. 2007 Nov;30(11):2196-200
references.pmid: 17978500
references.citation: Cancer Chemother Pharmacol. 2005 Jun;55(6):531-40
references.pmid: 15739095
references.citation: J Nat Prod. 2007 Jul;70(7):1203-6
references.pmid: 17629326
references.citation: J Neurosci Res. 1998 Aug 15;53(4):426-32
references.pmid: 9710262
references.citation: Jpn J Pharmacol. 1964 Sep;14:284-94
references.pmid: 14265195
references.citation: Cancer Lett. 1997 Dec 16;121(1):73-81
references.pmid: 9459177
references.citation: Arch Pharm Res. 2005 Mar;28(3):335-42
references.pmid: 15832823
references.citation: Planta Med. 1985 Jun;(3):221-4
references.pmid: 2863834
references.citation: Cancer Causes Control. 2000 Jul;11(6):565-76
references.pmid: 10880039
references.citation: Psychopharmacology (Berl). 2004 Apr;172(4):430-4
references.pmid: 14647971
references.citation: Arch Intern Med. 2000 Apr 10;160(7):1009-13
references.pmid: 10761967
references.citation: J Pharmacol Exp Ther. 1993 Oct;267(1):371-8
references.pmid: 8229764
references.citation: Integr Cancer Ther. 2006 Mar;5(1):9-29
references.pmid: 16484711
references.citation: Arch Pharm Res. 2004 Jan;27(1):61-7
references.pmid: 14969341
references.citation: Br J Clin Pharmacol. 2008 Oct;66(4):444-50
references.pmid: 18754850
references.citation: Chem Pharm Bull (Tokyo). 1997 Jun;45(6):1039-45
references.pmid: 9214709
references.citation: Chin Med. 2007 May 15;2:6
references.pmid: 17502003
references.citation: Evid Based Complement Alternat Med. 2006 Sep;3(3):365-72
references.pmid: 16951721
references.citation: Pharmacol Biochem Behav. 2000 Jul;66(3):595-601
references.pmid: 10899376
references.citation: Circulation. 2004 Sep 7;110(10):1219-25
references.pmid: 15337705
references.citation: Public Health Nutr. 2000 Dec;3(4A):473-85
references.pmid: 11276295
references.citation: Biochem Pharmacol. 2000 Sep 1;60(5):677-85
references.pmid: 10927026
references.citation: Sichuan Da Xue Xue Bao Yi Xue Ban. 2005 Mar;36(2):217-20
references.pmid: 15807271
references.citation: Br J Pharmacol. 1995 May;115(1):15-8
references.pmid: 7647970
references.citation: Biol Pharm Bull. 1998 Jan;21(1):79-80
references.pmid: 9477174
references.citation: Nutr Metab Cardiovasc Dis. 2005 Jun;15(3):149-60
references.pmid: 15955462
references.citation: Zhongguo Yao Li Xue Bao. 1997 Jan;18(1):11-20
references.pmid: 10072887
references.citation: Altern Med Rev. 2004 Sep;9(3):259-74
references.pmid: 15387718
references.citation: J Chromatogr B Biomed Appl. 1996 Dec 13;687(2):443-8
references.pmid: 9017469
references.citation: Chem Pharm Bull (Tokyo). 1982 Jun;30(6):2196-201
references.pmid: 7127606
references.citation: Appl Microbiol Biotechnol. 2008 Jan;77(6):1345-50
references.pmid: 18040682
references.citation: Science. 1992 Dec 18;258(5090):1861
references.pmid: 1470903
references.citation: Planta Med. 1998 Dec;64(8):696-700
references.pmid: 9933987
references.citation: Am J Health Syst Pharm. 1999 Jan 15;56(2):125-38; quiz 139-41
references.pmid: 10030529
references.citation: Acta Neuropathol. 1996;91(1):15-22
references.pmid: 8773141
references.citation: Diabetes Care. 1995 Oct;18(10):1373-5
references.pmid: 8721940
references.citation: Neuroreport. 1998 May 11;9(7):1619-24
references.pmid: 9631476
references.citation: Chin Med J (Engl). 2007 Apr 5;120(7):584-8
references.pmid: 17442207
references.citation: Biochem Pharmacol. 1997 Jul 1;54(1):1-8
references.pmid: 9296344
references.citation: Am J Chin Med. 1999;27(3-4):331-8
references.pmid: 10592841
references.citation: Brain Res. 2002 Sep 20;950(1-2):254-60
references.pmid: 12231251
references.citation: Eur J Gynaecol Oncol. 2001;22(5):339-41
references.pmid: 11766734
references.citation: J Pharm Pharmacol. 1988 Dec;40(12):838-43
references.pmid: 2907575
references.citation: Arch Pharm Res. 1997 Dec;20(6):539-44
references.pmid: 18982256
references.citation: Int J Oncol. 2003 Oct;23(4):1087-93
references.pmid: 12963989
references.citation: Drug Saf. 2002;25(5):323-44
references.pmid: 12020172
references.citation: Br J Pharmacol. 2001 Nov;134(6):1159-65
references.pmid: 11704635
references.citation: Phytomedicine. 1997 Mar;4(1):15-22
references.pmid: 23195240
references.citation: Gen Pharmacol. 1995 May;26(3):483-7
references.pmid: 7789720
references.citation: Arch Biochem Biophys. 2002 Oct 1;406(1):1-8
references.pmid: 12234484
references.citation: J Urol. 2002 Nov;168(5):2070-3
references.pmid: 12394711
references.citation: Am J Chin Med. 1986;14(3-4):145-52
references.pmid: 3799531
references.citation: J Med Invest. 2007 Aug;54(3-4):381-4
references.pmid: 17878692
references.citation: J Neurosci Res. 2001 Mar 15;63(6):509-15
references.pmid: 11241586
references.citation: Chem Pharm Bull (Tokyo). 2007 Sep;55(9):1342-8
references.pmid: 17827759
references.citation: Phytother Res. 2005 Jul;19(7):649-51
references.pmid: 16161030
references.citation: Neuropsychopharmacology. 2006 Jun;31(6):1158-64
references.pmid: 16292329
references.citation: Chem Pharm Bull (Tokyo). 2001 Apr;49(4):442-6
references.pmid: 11310671
references.citation: Carcinogenesis. 2008 Dec;29(12):2351-9
references.pmid: 18802031
references.citation: Chem Pharm Bull (Tokyo). 1989 Feb;37(2):481-4
references.pmid: 2743497
references.citation: Physiol Behav. 2004 Sep 15;82(2-3):345-55
references.pmid: 15276798
references.citation: J Pharmacol Sci. 2006 Mar;100(3):175-86
references.pmid: 16518078
references.citation: Curr Med Chem. 2009;16(19):2475-84
references.pmid: 19601793
references.citation: J Agric Food Chem. 2003 Apr 23;51(9):2555-8
references.pmid: 12696936
references.citation: Gen Pharmacol. 1994 Oct;25(6):1071-7
references.pmid: 7875528
references.citation: Ann N Y Acad Sci. 2002 Nov;973:396-401
references.pmid: 12485900
references.citation: Physiol Behav. 2000 Jun 1-15;69(4-5):511-25
references.pmid: 10913791
references.citation: Biol Pharm Bull. 2007 Sep;30(9):1674-9
references.pmid: 17827719
references.citation: Chem Pharm Bull (Tokyo). 1998 Apr;46(4):647-54
references.pmid: 9579041
references.citation: J Cardiovasc Pharmacol. 2001 Jan;37(1):41-7
references.pmid: 11152372
references.citation: J Asian Nat Prod Res. 2001;3(3):235-40
references.pmid: 11491400
references.citation: Sports Med. 1994 Oct;18(4):229-48
references.pmid: 7817063
references.citation: Am J Health Syst Pharm. 1997 Mar 15;54(6):692-3
references.pmid: 9075501
references.citation: Chem Pharm Bull (Tokyo). 2001 Nov;49(11):1452-6
references.pmid: 11724237
references.citation: Int J Biochem Cell Biol. 1998 Mar;30(3):327-38
references.pmid: 9611775
references.citation: Biol Pharm Bull. 2005 Apr;28(4):652-6
references.pmid: 15802804
references.citation: Brain Res. 2009 Jan 12;1248:184-90
references.pmid: 19026615
references.citation: Am J Chin Med. 2000;28(2):205-16
references.pmid: 10999439
references.citation: J Urol. 1999 Oct;162(4):1508-11
references.pmid: 10492246
references.citation: Adv Neurol. 1999;80:153-9
references.pmid: 10410715
references.citation: Brain Res. 2007 Mar 9;1136(1):190-9
references.pmid: 17239831
references.citation: Arch Pharm Res. 2004 Aug;27(8):834-9
references.pmid: 15460444
references.citation: Biochem Biophys Res Commun. 1998 May 29;246(3):725-30
references.pmid: 9618279
references.citation: Acta Pharmacol Sin. 2002 Dec;23(12):1152-6
references.pmid: 12466053
references.citation: Neurosci Lett. 2003 Jun 19;344(1):1-4
references.pmid: 12781907
references.citation: Zhongguo Zhong Yao Za Zhi. 2007 Aug;32(16):1680-4
references.pmid: 18027667
references.citation: Anticancer Res. 1997 Mar-Apr;17(2A):1067-72
references.pmid: 9137450
references.citation: Life Sci. 2000 Aug 4;67(11):1297-306
references.pmid: 10972198
references.citation: Jpn J Cancer Res. 1998 Jul;89(7):733-40
references.pmid: 9738980
references.citation: J Korean Med Sci. 2001 Dec;16 Suppl:S6-18
references.pmid: 11748383
references.citation: Integr Cancer Ther. 2003 Sep;2(3):247-67
references.pmid: 15035888
references.citation: Neuroreport. 2001 May 25;12(7):1453-6
references.pmid: 11388428
references.citation: J Am Coll Nutr. 2004 Jun;23(3):248-58
references.pmid: 15190050
references.citation: Eur J Pharmacol. 2008 Aug 20;590(1-3):74-9
references.pmid: 18571158
references.citation: Med Chem. 2007 Jan;3(1):51-60
references.pmid: 17266624
references.citation: J Ethnopharmacol. 1986 Apr-May;16(1):15-22
references.pmid: 3528672
references.citation: J Ethnopharmacol. 1988 Feb-Mar;22(2):173-81
references.pmid: 3374151
references.citation: BMC Complement Altern Med. 2008 Aug 19;8:50
references.pmid: 18713456
references.citation: Chem Pharm Bull (Tokyo). 2002 Apr;50(4):538-40
references.pmid: 11964005
references.citation: Int J Impot Res. 1995 Sep;7(3):181-6
references.pmid: 8750052
references.citation: J Asian Nat Prod Res. 1998;1(2):93-7
references.pmid: 11261219
references.citation: Arch Pharm Res. 2003 Jan;26(1):58-63
references.pmid: 12568360
references.citation: Biol Pharm Bull. 2005 Sep;28(9):1621-5
references.pmid: 16141527
references.citation: Urology. 2005 Mar;65(3):611-5
references.pmid: 15780402
references.citation: J Korean Med Sci. 2001 Dec;16 Suppl:S42-53
references.pmid: 11748376
references.citation: Food Chem Toxicol. 1983 Feb;21(1):95-7
references.pmid: 6681799
references.citation: Biochim Biophys Acta. 2002 Aug 15;1572(1):58-66
references.pmid: 12204333
references.citation: Acta Pharmacol Sin. 2002 Apr;23(4):315-22
references.pmid: 11931705
references.citation: Physiol Behav. 1998 Jun 15;64(4):445-50
references.pmid: 9761217
references.citation: Zhongguo Zhong Yao Za Zhi. 1997 Jan;22(1):35-7, 62
references.pmid: 10683909
references.citation: Carcinogenesis. 2005 Feb;26(2):359-67
references.pmid: 15498788
references.citation: Zhongguo Zhong Xi Yi Jie He Za Zhi. 2002 Jun;22(6):450-2
references.pmid: 12585194
references.citation: Chem Pharm Bull (Tokyo). 2007 Apr;55(4):571-6
references.pmid: 17409550
references.citation: Yao Xue Xue Bao. 1989;24(8):593-9
references.pmid: 2618703
references.citation: J Biol Chem. 2000 Sep 29;275(39):30256-63
references.pmid: 10884382
references.citation: Eur J Pharmacol. 1996 Sep 26;312(2):149-51
references.pmid: 8894589
references.citation: Am J Chin Med. 1998;26(3-4):365-73
references.pmid: 9862024
references.citation: Cancer Res. 2005 Mar 1;65(5):1952-60
references.pmid: 15753395
references.citation: Arch Pharm Res. 2000 Oct;23(5):518-24
references.pmid: 11059834
references.citation: Exp Neurol. 2003 Nov;184(1):521-9
references.pmid: 14637121
references.citation: Curr Drug Metab. 2007 Dec;8(8):815-21
references.pmid: 18220562
references.citation: Diabetes. 2002 Jun;51(6):1851-8
references.pmid: 12031973
references.citation: J Sex Med. 2008 Sep;5(9):2079-84
references.pmid: 18638003
references.citation: Mutat Res. 2003 Feb-Mar;523-524:75-85
references.pmid: 12628505
references.citation: Pharmacol Biochem Behav. 2003 Jun;75(3):687-700
references.pmid: 12895687
references.citation: In Vivo. 2001 Mar-Apr;15(2):151-6
references.pmid: 11317520
references.citation: Eur J Cancer. 1999 Mar;35(3):507-11
references.pmid: 10448308
references.citation: Int J Oncol. 1999 May;14(5):869-75
references.pmid: 10200336
references.citation: Toxicol Appl Pharmacol. 2004 Feb 1;194(3):221-9
references.pmid: 14761678
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Oct 15;858(1-2):65-70
references.pmid: 17825630
references.citation: Chem Pharm Bull (Tokyo). 2006 May;54(5):751-3
references.pmid: 16651785
references.citation: J Steroid Biochem Mol Biol. 2003 Mar;84(4):463-8
references.pmid: 12732291
references.citation: Zhongguo Yao Li Xue Bao. 1990 Jan;11(1):29-32
references.pmid: 2119543
references.citation: Br J Cancer. 2008 Feb 26;98(4):792-802
references.pmid: 18253123
references.citation: Jpn J Pharmacol. 2002 Nov;90(3):254-62
references.pmid: 12499580
references.citation: Molecules. 2007 Sep 05;12(9):2140-50
references.pmid: 17962732
references.citation: Exp Neurol. 2002 Feb;173(2):224-34
references.pmid: 11822886
references.citation: Zhongguo Zhong Xi Yi Jie He Za Zhi. 2001 Apr;21(4):260-1
references.pmid: 12577351
references.citation: JAMA. 1979 Apr 13;241(15):1614-5
references.pmid: 430716
references.citation: Planta Med. 1998 Aug;64(6):500-3
references.pmid: 9741293