Health benefits of Milk thistle and its active constituent Silibinin

Silibinin, a polyphenolic flavonoid also known as silybin [4], is the major biologically active compound of milk thistle [1], a plant that has recently been the subject of many clinical trials and medical studies due to the properties it exerts and the ability of some of the active constituents found in it, as Silibinin, to be used to treat affections and ailments, being an effective chemo-preventive agent in various types of cancer, suppressing cancer cell growth and inhibiting colon cancer stem-like cells [6], being also studied for its inhibitory effects on certain types of breast cancer cells [9,10], and many other anti-neoplastic effects in a variety of in vitro and in vivo cancer models, including skin, breast, lung, colon, bladder, prostate and kidney carcinomas [15]. Image: Eran Finkle under CC license (CC by 2.0).

SYLIBUM MARIANUM

Family: Asteraceae
Genus: Sylibum
Common name: Milk thistle, גדילן מצוי,

In spite Silymarin and its major constituent, Silibinin, have traditionally been used for the treatment of liver diseases [15], It seems that Silibinin, the standardized mixture of flavonolignans from the medical plant Silybum marianum [5], also known as Milk thistle,  has also been the subject of study for its anti-cancer properties, some of them showed that silibinin is able to inhibit up to a certain point the human leukemia cell line K562 [5].  The treatment of the K562 cells with silymarin resulted in a significant inhibition of cell growth and telomerase activity. The anticancer activity of silymarin in human leukemia K562 may lead to the development of new anti-cancer drugs using this property [5].

SILIBININ

---

Molecular Formula: C25H22O10
Molecular Weight: 482.43618
Common names: Silymarin I, silibinin, Silliver, Silybine, Flavobin, Flavobin Spofa, Silymarine I, Silibinine [INN-French], Silibininum [INN-Latin]

SILIBININ AND PROSTATE CANCER

---

Silibinin is obtained from Silybin, an extract from the milk thistle plant seeds that has been shown to exert inhibitory properties against prostate tumor formation in the TRAMP model[8]. It seems however, that this inhibitory properties were limited to inhibition of the growth of established prostate neoplasms late in the process of tumor progression [7], bringing its use to a more therapeutic than chemopreventive purpose [7]. Silibinin is an herbal compound with anti-cancer activity on prostate and colorectal cancers.

SILIBININ AND BREAST CANCER

---

Studies done on the citotoxic effects of Silibinin against T47D breast cancer cells showed how this active constituent found in Milk thistle was able to inhibit the expression and the secretion of leptin, with which it may in future become a drug candidate for breast cancer therapy [13].

Other studies suggest also that may play an important role in the inhibition of metastasis of human breast cancer by preventing the epidermal growth factor [14]. Additionally, silibinin induced MCF-7 cell apoptosis, or natural cell death, on this type of human breast cancer cells [16].

SILIBININ AND COLON / COLO RECTAL CANCER

---

Silibinin is also known to be an herbal compound with anti-cancer activity on prostate and colorectal cancers [13].

In another study on colon tumor cells (SW480) and the metastatic cells (SW620), silibinin showed its potential as promising anti-cancer agent, being able to selectively induce apoptosis (natural programmed cell death) in cancer cells [20]. Another reason to suggest it may well be a new chemopreventive and therapeutic agent.

SILYMARIN FROM MILK THISTLE FOR ALZHEIMER'S DISEASE

---

Last but not least, nature provided us with another active constituent that seems to attenuate cognitive deficits caused by the formation of senile plaques , Silymarin , a flavonoid derived from the herb milk thistle (Silybum marianum).

Silymarin from Milk thistle, used as part of traditional herbal remedies against liver diseases, has been found to be able to suppress senile plaques formation known as amyloid β-protein (Aβ) in mouse models [18]. Silymarin has been shown to have antioxidative properties .

Silibinin (silybin) , the flavonoid derived from the herb Milk thistle, has potent anti-inflammatory and antioxidant properties. Silibinin prevents memory impairment and oxidative damage induced by Abeta(25-35) and may be a potential therapeutic agent for Alzheimer's disease [19].

REFERENCES

[1] Herbal Medicine and Hepatocellular Carcinoma: Applications and Challenges
Yan Li * and Robert C. G. Martin, II
Division of Surgical Oncology, Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40202, USA

[2] Silibinin induces apoptosis via calpain-dependent AIF nuclear translocation in U87MG human glioma cell death
Ji C Jeong,1 Won Y Shin,1 Thae H Kim,2 Chae H Kwon,2 Jae H Kim,2 Yong K Kim,2 and Ki H Kim3
1Department of Oriental Medicine, Dongguk University, Kyung Ju, 780-714, Korea
2Department of Physiology, College of Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, 626-770, Korea
3Department of Obstetrics and Gynecology, College of Medicine, Pusan National University, and Medical Research Institute and Pusan Cancer Center, Pusan National University Hospital, Pusan, 602-739, Korea

[3] Angiopreventive Efficacy of Pure Flavonolignans from Milk Thistle Extract against Prostate Cancer: Targeting VEGF-VEGFR Signaling.
Deep G, Gangar SC, Rajamanickam S, Raina K, Gu M, Agarwal C, Oberlies NH, Agarwal R.
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, Colorado, United States of America.

[4] Wikipedia Silibinin http://en.wikipedia.org/wiki/Silibinin

[5] The Effect of Silymarin on Telomerase Activity in the Human Leukemia Cell Line K562.
Faezizadeh Z, Mesbah-Namin SA, Allameh A.
Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

[6] Silibinin suppresses the maintenance of colorectal cancer stem-like cells by inhibiting PP2A/AKT/mTOR pathways.
Wang JY, Chang CC, Chiang CC, Chen WM, Hung SC.
Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.

[7] Chemoprevention of prostate cancer: Natural compounds, antiandrogens, and antioxidants – In vivo evidence
Nur Özten-Kandaş and Maarten C Bosland*
Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA

[8] Raina K, Blouin MJ, Singh RP, Majeed N, Deep G, Varghese L, et al. Dietary feeding of silibinin inhibits prostate tumor growth and progression in transgenic adenocarcinoma of the mouse prostate model. Cancer Res. 2007;67:11083–91.

[9] Cell adhesion molecule CD44: its functional roles in prostate cancer.
Iczkowski KA.
Department of Pathology, University of Colorado Health Science Center Aurora, CO, USA.

[9] Silibinin-induced apoptosis in MCF7 and T47D human breast carcinoma cells involves caspase-8 activation and mitochondrial pathway.
Tiwari P, Kumar A, Balakrishnan S, Kushwaha HS, Mishra KP.
Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085, India.

[10] Inhibition of human carcinoma cell growth and DNA synthesis by silibinin, an active constituent of milk thistle: comparison with silymarin.
Bhatia N, Zhao J, Wolf DM, Agarwal R.
Center for Cancer Causation and Prevention, AMC Cancer Research Center, Denver, CO 80214, USA.

[11] Inhibition of silibinin on migration and adhesion capacity of human highly metastatic breast cancer cell line, MDA-MB-231, by evaluation of β1-integrin and downstream molecules, Cdc42, Raf-1 and D4GDI.
Dastpeyman M, Motamed N, Azadmanesh K, Mostafavi E, Kia V, Jahanian-Najafabadi A, Shokrgozar MA.
Department of Molecular and Cellular Biology, University of Tehran, Tehran, Iran.

[12] Silibinin enhances ultraviolet B-induced apoptosis in mcf-7 human breast cancer cells.
Noh EM, Yi MS, Youn HJ, Lee BK, Lee YR, Han JH, Yu HN, Kim JS, Jung SH.
Department of Biochemistry, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju, Korea.

[13] Inhibition of leptin gene expression and secretion by silibinin: possible role of estrogen receptors.
Nejati-Koshki K, Zarghami N, Pourhassan-Moghaddam M, Rahmati-Yamchi M, Mollazade M, Nasiri M, Esfahlan RJ, Barkhordari A, Tayefi-Nasrabadi H.
Tuberculosis and Lung Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

[14] Silibinin suppresses EGFR ligand-induced CD44 expression through inhibition of EGFR activity in breast cancer cells.
Kim S, Han J, Kim JS, Kim JH, Choe JH, Yang JH, Nam SJ, Lee JE.
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-Gu, Seoul, 135-710, Korea.

[15] Silibinin--a promising new treatment for cancer.
Cheung CW, Gibbons N, Johnson DW, Nicol DL.
Department of Renal Medicine, University of Queensland at Princess Alexandra Hospital, Brisbane, Queensland, Australia

[16] Silibinin induces protective superoxide generation in human breast cancer MCF-7 cells.
Wang HJ, Jiang YY, Wei XF, Huang H, Tashiro S, Onodera S, Ikejima T.
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, PR China.

[17] Milk thistle other names: Porcher Michel H. et al. 1995 - 2020, Sorting Silybum Names. Multilingual Multiscript Plant Name Database   (M.M.P.N.D)  - A Work in Progress. School of Agriculture and Food Systems. Faculty of Land & Food Resources. The University of Melbourne. Australia. <http://www.plantnames.unimelb.edu.au/Sorting/Silybum.html > (2007).

[18] Silymarin attenuated the amyloid ß plaque burden and improved behavioral abnormalities in an Alzheimer's disease mouse model. Murata N, Murakami K, Ozawa Y, Kinoshita N, Irie K, Shirasawa T, Shimizu T. Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.

[19] Silibinin prevents amyloid beta peptide-induced memory impairment and oxidative stress in mice. Lu P, Mamiya T, Lu LL, Mouri A, Zou L, Nagai T, Hiramatsu M, Ikejima T, Nabeshima T. Department of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, Japan.

[20] The flavonolignan silibinin potentiates TRAIL-induced apoptosis in human colon adenocarcinoma and in derived TRAIL-resistant metastatic cells.
Kauntz H, Bousserouel S, Gossé F, Raul F.
Laboratory of Nutritional Cancer Prevention, Unit EA 4438, IRCAD, University of Strasbourg, 1 Place de l'Hôpital, 67091, Strasbourg-Cedex, France.

[21] Plant names in other languages: Porcher Michel H. et al. 1995 - 2020, Sorting Origanum Names. Multilingual Multiscript Plant Name Database - A Work in Progress. Institute of Land & Food Resources. The University of Melbourne. Australia.   < http://www.plantnames.unimelb.edu.au/Sorting/Origanum.html > (2007).