| REFERENCES [1]Siddiqui U Prevalence and predictors of herbal medication use in veterans with chronic hepatitis C. J Clin Gastroenterol. 2004 Aug;38(7):605-10. [2] Wallace SN Extraction of nutraceuticals from milk thistle: part II. Extraction with organic solvents. Appl Biochem Biotechnol. 2003 Spring;105 -108:891-903. [3] Wallace SN Batch solvent extraction of flavanolignans from milk thistle (Silybum marianum L. Gaertner). Phytochem Anal. 2005 Jan-Feb;16(1):7-16. [4]Duan L Silymarin extraction from milk thistle using hot water. Appl Biochem Biotechnol. 2004 Spring;113-116:559-68.[5] Lee DY, Molecular structure and stereochemistry of silybin A, silybin B, isosilybin A, and isosilybin B, Isolated from Silybum marianum (milk thistle). J Nat Prod. 2003 Dec;66(12):1632. [6] Kim NC Complete isolation and characterization of silybins and isosilybins from milk thistle (Silybum marianum). Org Biomol Chem. 2003 May 21;1(10):1684-9.[7] Manna SK Silymarin [MILK THISTLE] suppresses TNF-induced activation of NF-kappa B, c-Jun N-terminal kinase, and apoptosis. J Immunol. 1999 Dec 15;163(12):6800-9. [8] Lee DG et al Gram-positive bacteria specific properties of silybin derived from Silybum marianum [Milk Thistle]. Arch Pharm Res. 2003 Aug;26(8):597-600.[9] Soliman KF In vitro attenuation of nitric oxide production in C6 astrocyte cell culture by various dietary compounds. Proc Soc Exp Biol Med. 1998 Sep;218(4):390-7.[10] Bialecka M. The effect of bioflavonoids and lecithin on the course of experimental atherosclerosis in rabbits Ann Acad Med Stetin. 1997;43:41-56. [11]Zi X, Novel cancer chemopreventive effects of a flavonoid antioxidant silymarin [MILK THISTLE]: inhibition of mRNA expression of an endogenous tumor promoter TNF alpha. Biochem Biophys Res Commun. 1997 Oct 9;239(1):334-9.[12]Tyagi A Silibinin causes cell cycle arrest and apoptosis in human bladder transitional cell carcinoma cells by regulating CDKI-CDK-cyclin cascade, and caspase 3 and PARP cleavages. Carcinogenesis. 2004 Sep;25(9):1711-20. Epub 2004 Apr *milk thistle [13]Tyagi AK Silibinin down-regulates survivin protein and mRNA expression and causes caspases activation and apoptosis in human bladder transitional-cell papilloma RT4 cells. Biochem Biophys Res Commun. 2003 Dec 26;312(4):1178-84.[14] Vinh PQ et al Chemopreventive effects of a flavonoid antioxidant silymarin [MILK THISTLE] on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in male ICR mice. Jpn J Cancer Res. 2002 Jan;93(1):42-9. [15]Tyagi AK Synergistic anti-cancer effects of silibinin [milk thistle extract] with conventional cytotoxic agents doxorubicin, cisplatin and carboplatin against human breast carcinoma MCF-7 and MDA-MB468 cells. Oncol Rep. 2004 Feb;11(2):493-9.Zi X. Anticarcinogenic effect of a flavonoid antioxidant, silymarin [milk thistle], in human breast cancer cells MDA-MB 468: induction of G1 arrest through an increase in Cip1/p21 concomitant with a decrease in kinase activity of cyclin-dependent kinases and associated cyclins. Clin Cancer Res. 1998 Apr;4(4):1055-64.[17] Kohno H et al, Silymarin [MILK THISTLE], a naturally occurring polyphenolic antioxidant flavonoid, inhibits azoxymethane-induced colon carcinogenesis in male F344 rats. Int J Cancer. 2002 Oct 10;101(5):461-8.[18] Yoo HG Involvement of NF-kappaB and caspases in silibinin-induced apoptosis of endothelial cells. Int J Mol Med. 2004 Jan;13(1):81-6.[19] Qi L, Epidermal growth factor receptor mediates silibinin [milk thistle]-induced cytotoxicity in a rat glioma cell line. Cancer Biol Ther. 2003 Sep-Oct;2(5):526-31.[20] Chu SC Silibinin inhibits the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2. Mol Carcinog. 2004 Jul;40(3):143-9.[21] Ladas EJ Milk thistle: is there a role for its use as an adjunct therapy in patients with cancer? J Altern Complement Med. 2003 Jun;9(3):411-6.[22] [Davis-Searles PR, Milk thistle and prostate cancer: differential effects of pure flavonolignans from Silybum marianum [MILK THISTLE] on antiproliferative end points in human prostate carcinoma cells. Cancer Res. 2005 May 15;65(10):4448-57] [23] Singh RP A cancer chemopreventive agent silibinin [MILK THISTLE], targets mitogenic and survival signaling in prostate cancer. Mutat Res. 2004 Nov 2;555(1-2):21-32.[23] Thelen P Silibinin down-regulates prostate epithelium-derived Ets transcription factor in LNCaP prostate cancer cells. Planta Med. 2004 May;70(5):397-400.[24] Inhibition of telomerase activity and secretion of prostate specific antigen by silibinin [milk thistle] in prostate cancer cells. J Urol. 2004 May;171(5):1934-8. [25] Prostate cancer prevention by silibinin [milk thistle]. Curr Cancer Drug Targets. 2004 Feb;4(1):1-11 [26] A flavonoid antioxidant, silymarin [milk thistle], inhibits activation of erbB1 signaling and induces cyclin-dependent kinase inhibitors, G1 arrest, and anticarcinogenic effects in human prostate carcinoma DU145 cells. Cancer Res. 1998 May 1;58(9):1920-9. 27 Silibinin [Milk Thistle] decreases prostate-specific antigen with cell growth inhibition via G1 arrest, leading to differentiation of prostate carcinoma cells: implications for prostate cancer intervention. Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7490-5. 28 Dhanalakshmi S Silibinin [MILK THISTLE] sensitizes human prostate carcinoma DU145 cells to cisplatin- and carboplatin-induced growth inhibition and apoptotic death. Int J Cancer. 2003 Sep 20;106(5):699-705. 29 Zi X Silibinin [MILK THISTLE] up-regulates insulin-like growth factor-binding protein 3 expression and inhibits proliferation of androgen-independent prostate cancer cells Cancer Res. 2000 Oct 15;60(20):5617-20. [30] Singh RP Dietary feeding of [MILK THISTLE] silibinin inhibits advance human prostate carcinoma growth in athymic mice and increases plasma insulin-like growth factor-binding protein-3 levels. Cancer Res. 2002 Jun 1;62(11):3063-9. [31]Tyagi A et al, Silibinin [MILK THISTLE] strongly synergizes human prostate carcinoma DU145 cells to doxorubicin-induced growth Inhibition, G2-M arrest, and apoptosis. Clin Cancer Res. 2002 Nov;8(11):3512-9. [32] Tyagi A Antiproliferative and apoptotic effects of silibinin [MILK THISTLE] in rat prostate cancer cells. Prostate. 2002 Nov 1;53(3):211-7.[33]Katiyar SK et al, Protective effects of silymarin [milk thistle] against photocarcinogenesis in a mouse skin model. J Natl Cancer Inst. 1997 Apr 16;89(8):556-66][34] Katiyar SK. Silymarin [milk thistle] and skin cancer prevention: anti-inflammatory, antioxidant and immunomodulatory effects (Review). Int J Oncol. 2005 Jan;26(1):169-76.[35] Silibinin prevents ultraviolet radiation-caused skin damages in SKH-1 hairless mice via a decrease in thymine dimer positive cells and an up-regulation of p53-p21/Cip1 in epidermis. Carcinogenesis. 2004 Aug;25(8):1459-65. Epub 2004 Mar 19. [36]A flavonoid antioxidant, silymarin [milk thistle], affords exceptionally high protection against tumor promotion in the SENCAR mouse skin tumorigenesis model. Cancer Res. 1999 Feb 1;59(3):622-32[36] Yanaida Y et al Dietary silymarin [MILK THISTLE] suppresses 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in male F344 rats. Carcinogenesis. 2002 May;23(5):787-94.[37]Silymarin [Milk thistle]: potent inhibitor of cyclic AMP phosphodiesterase. Methods Find Exp Clin Pharmacol. 1985 Aug;7(8):409-13.][38]Crocenzi FA et al, Silibinin [Milk thistle] prevents cholestasis-associated retrieval of the bile salt export pump, Bsep, in isolated rat hepatocyte couplets: possible involvement of cAMP. Biochem Pharmacol. 2005 Apr 1;69(7):1113-20.] [39] von Schonfeld J Silibinin [Milk thistle], a plant extract with antioxidant and membrane stabilizing properties, protects exocrine pancreas from cyclosporin A toxicity. Cell Mol Life Sci. 1997 Dec;53(11-12):917-20.] [40] Maghrani M Study of the hypoglycaemic activity of Fraxinus excelsior and Silybum marianum [Milk thistle] in an animal model of type 1 diabetes mellitus. J Ethnopharmacol. 2004 Apr;91(2-3):309-16. [41] Chlopcikova S Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes. Part I. Silymarin [Milk thistle] and its flavonolignans. Phytother Res. 2004 Feb;18(2):107-10. [42] Katiyar SK. Treatment of silymarin [MILK THISTLE], a plant flavonoid, prevents ultraviolet light-induced immune suppression and oxidative stress in mouse skin. Int J Oncol. 2002 Dec;21(6):1213-22. [43]Wilasrusmee C et al, Immunostimulatory effect of Silybum Marianum (milk thistle) extract. Med Sci Monit. 2002 Nov;8(11):BR439-43.[44] Ferenci P et al, Randomized controlled trial of silymarin [Milk thistle] treatment in patients with cirrhosis of the liver. J Hepatol. 1989 Jul;9(1):105-13. [45] Arteel G Advances in alcoholic liver disease. Best Pract Res Clin Gastroenterol. 2003 Aug;17(4):625-47.[46] Lieber CS Silymarin [Milk thistle] retards the progression of alcohol-induced hepatic fibrosis in baboons. J Clin Gastroenterol. 2003 Oct;37(4):336-9.[47]. Dehmlow C. Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin. Hepatology. 1996 Apr; 23 (4): 749-54. [48]. Wu DF The effects of silymarin [Milk thistle] on hepatic microsomal and mitochondrial membrane fluidity in mice. Zhongguo Zhong Yao Za Zhi. 2003 Sep;28(9):870-2. [49] Tanamly MD et al, Randomised double-blinded trial evaluating silymarin [Milk thistle] for chronic hepatitis C in an Egyptian village: study description and 12-month results. Dig Liver Dis. 2004 Nov;36(11):752-9. [50]Tedesco D Silymarin, a possible hepatoprotector in dairy cows: biochemical and histological observations. J Vet Med A Physiol Pathol Clin Med. 2004 Mar;51(2):85-9.[51] Wang MJ Silymarin [MILK THISTLE] protects dopaminergic neurons against lipopolysaccharide-induced neurotoxicity by inhibiting microglia activation. Eur J Neurosci. 2002 Dec;16(11):2103-12 [52] Kittur S et al, Neurotrophic and neuroprotective effects of milk thistle (Silybum marianum) on neurons in culture. J Mol Neurosci. 2002 Jun;18(3):265-9. [53] Hu Z, Herb-drug interactions: a literature review. Drugs. 2005;65(9):1239-82.][54]DiCenzo R Coadministration of milk thistle and indinavir in healthy subjects. Pharmacotherapy. 2003 Jul;23(7):866-70.[55] Giese LA. Milk thistle and the treatment of hepatitis. Gastroenterol Nurs. 2001 Mar-Apr;24(2):95-7. [56] Saller R et al, The use of silymarin in the treatment of liver diseases Drugs. 2001;61(14):2035-63.[57] Ferenci P. et al, Randomized controlled trial of silymarin (milk thistle) treatment in patients with cirrhosis of the liver. J Hepatol. 1989 Jul;9(1):105-13. [58]Silymarin inhibits T-lymphocyte function at low doses but stimulates inflammatory processes at high doses. Planta Med. 2003 Jan;69(1):44-9.[59] Jacobs BP, Milk thistle for the treatment of liver disease: a systematic review and meta-analysis. Am J Med. 2002 Oct 15;113(6):506-15.[60] Rambaldi A. et al, Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases. Cochrane Database Syst Rev. 2005 Apr 18;(2):CD003620.][61] Physiological responses of a natural antioxidant flavonoid mixture, silymarin, in BALB/c mice: III. Silymarin inhibits T-lymphocyte function at low doses but stimulates inflammatory processes at high doses. Planta Med. 2003 Jan;69(1):44-9. |
| How popular is milk thistle? The most common herbal medications taken by hepatitis C patients were milk thistle (12.2%), ginseng (4.6%), and echinacea (3.0%). [1] RESEARCH ALERT: Milk thistle may help diabetics In a study, researchers treated diabetics with 200 mg of silymarin three times a day. After four months, patients had reductions in blood glucose levels. The reults are very encouraging and the researchers planned to do further large multi-centre studies. [Milk thistle may help diabetics -study, Reuters, October 30, 2006.] |
| Milk Thistle Benefits, Side Effects; Research Finds |


| MILK THISTLE EXTRACTION METHOD The extraction of milk thistle compounds usually involves a two-step: (1) defatting and (2) extraction process using organic solvents. Lipid removal is an important extraction step for milk thistle compounds, because defatted material yields twice the silymarin concentration. [2] Bioling water is an effective method to extract more polar silymarins such as taxifolin and silychristin from milk thistle seed. Severe degradation of milk thistle compounds occurred under hot water extraction at 140 degrees C. [4] The yield of silymarin of milk thistle extraction increases with increasing temperature. While, boling alcohol is an effective way to extract taxifolin, silychristin, silybinin A and silybinin B from defatted milk thistle seed meal. [3] Thus, method of extraction affects the milk thistle extract composition and the benefits it offers. MILK THISTLE INGREDIENTS ISOLATION AND CHARACTERIZATION METHODS Silybin A, silybin B, isosilybin A, and isosilybin B, could be separated from milk thistle by sequential silica gel column chromatography, preparative reversed-phase HPLC, and recrystallization. [5] Milk thistle ingredients include silybins A (1) and B (2), and isosilybins A (3) and B (4) silychristin (5) isosilychristin (6) and silydianin (7), and a flavonoid, taxifolin (8). Methods used are preparative reversed-phase HPLC, 2D NMR and CD spectroscopy. [6] photo by NCCAM |
| NCCAM is currently supporting a phase II research study to better understand the use of milk thistle for chronic hepatitis C. The National Cancer Institute and the National Institute of Nursing Research are also studying milk thistle for cancer prevention and to treat complications in HIV patients. SOURCE Milk Thistle NCCAM Online Publication December 2005. photo by NCCAM |
