May help with

• hepatoprotective
• hepatitis B & C
• nephro protective
• anti depressant
• hypoglycemic
• chemo protective

Source : http://www.wikiphyto.org/wiki/Chardon-Marie

Reference on http://www.wikiphyto.org

Translation in English by Google Translate  (go to the page of the source linked | on Chrome cellphones go on the 3 dots on the top right and select translate in your preferred language | on laptop right click your mouse and select option translate when hoovering on the page

plant name

Milk thistle , milk thistle (English), Mariendistel (German)

International Latin denomination

Silybum marianum (L.) Gaertn. (formerly Carduus marianus )

botanical family

Asteraceae

Description and habitat

• Biennial plant growing up to 1.50 m in height
• Leaves with white marbled blades along the veins, the teeth of which end in very sharp yellow tips
• Large purple-mauve flower heads 3 to 8 cm, with spiny bracts
• Wastelands of Southern Europe, Northern Africa, Western Asia

History and tradition

• According to popular belief, the white marks on the leaves come from the milk of the Virgin breastfeeding the child Jesus.

Parts used

• Fruit = rough black achene, 6 to 7 mm by 3, with a remnant of the floral crown in the form of a light yellow cylindrical scale

Dosage forms available

• Carduus marianus fruit tincture
• Fluid extract
• Dry extract
• Légalon® ( Silybum marianum fruit, corresponding to silymarin 70 mg)
• EPS

Usual dosages

• 12-15 grams of herbal drug (fruit or fruit powder)
• Legalon®: 2 tablets, 2 to 3 times a day
  • The effects are more marked for 140mg of silymarin 3 times a day, i.e. 420 mg/day (equivalent to 21 grams of drug if silymarin is present at 2%)

Composition

Main components of the plant

• Flavonolignans responsible for the activity (mixture of flavanonic derivatives called silymarin , 1.5 to 3% of the drug) whose major components are silybin (= silibin = silybinin , formed of two stereoisomers A and B), silydianin and silychristin and their many stereoisomeric derivatives ( isosilybin , dihydrosilybin )
• Flavonoids  : quercetol , taxifolin , dihydrokaempferol , apigenin , naringin , eriodyctiol , chrysoeriol
• Phenolic derivatives
• Tocopherol and sterols  : campesterol , sitosterol , stigmasterol
• Lipids 20 to 30%, proteins, sugars

Main components of buds or young shoots

Main components of essential oil

Properties

Plant properties

• Hepatoprotective by flavonolignans [1] , [2] , [3] , [4] , [5] , activities related to various functions of receptors and transporters located in cell membranes, modulation of TNF-alpha and selectins, antioxidant properties and inhibition of lipoxygenase pathway, inhibition of inducible nitric oxide synthase iNOS, nuclear factor kappa B and reduction of collagen synthesis, DNA and RNA mediated effects [6]
• Silymarin acts by two mechanisms:
  • It is a membrane stabilizer (it inhibits the membrane transport systems of hepatocytes, making the absorption of toxins more difficult, inhibits the peroxidation of lipids [7] and increases the uptake of free radicals produced by hepatotoxic substances); it contributes to the maintenance of the glutathione pool responsible for hepatic detoxification (phase 2 enzymes), reduces the increase in transaminases and alkaline phosphatases, protects against oxidative stress [8]
  • It stimulates the activity of polymerase A, therefore increases the synthesis of ribosomal nucleic acids and the number of ribosomes in hepatocytes, which increases enzyme biosynthesis, protein synthesis and stimulates the capacity for hepatic regeneration
• Prevention and treatment of hepatotoxicity from carbon tetrachloride [9] , galactosamine [10] and phalloidin [11] , [12] , [13]
• Antidote for amanita phalloides poisoning [14] , a meta-analysis of 452 patients with amanita phalloides poisoning show a significant difference in mortality in favor of silibinin (mortality 9.8% vs. 18.3% with standard treatment, p <0.01) [15] , silibinin prevents the absorption of amatoxins from amanita phalloides by hepatocytes, thus protecting liver tissue, it stimulates DNA-dependent RNA polymerases, increasing RNA synthesis [16] , [17] , [18]
• Improved lifespan in cirrhosis [19]
• Antiviral against hepatitis C [20] , [21] , inhibits the RNA polymerase of the virus [22]
• Prevention of hepatocellular carcinoma by synergy Cynara scolymus , Silybum marianum , Cochlospermum angolense [23]
• Nephro-protective [24]
• The plant is also galactogenic [25] , [26] , [27] and anti-depressant
• Anti-cancer properties of silymarin [28] , anti-inflammatory properties and antimetastatic activity by modulation of specific proteins [29]
  • Silymarin exerts anti-cancer activity through multiple mechanisms: initiation of carcinogenesis, promotion and progression. Its antimetastatic effect is notable. Numerous clinical studies show a reduction in the toxicity of chemotherapeutic agents in combination with silymarin [30]
  • Silymarin inhibits the proliferation of tumor cells of various cancers:
    • Of the prostate [31] , [32] , [33] , [34] , with inhibition of angiogenesis and angiogenesis regulatory molecules (VEGF former name of NO, VEGFR1, VEGFR2, phospho-Akt, HIF- 1α) ( flavonolignans  : silybin A , silybin B , isosilybin A , isosilybin B ) [35]
    • From the ovary [36]
    • Breast [37]
    • Lung [38]
    • Skin [39]
    • From the bladder [40] , [41]
• Decreases renal toxicity of cis-platin [42]
• Silymarin ( flavonolignan ) exhibits immunosuppressive effects [43] , [44] , [45]
• The combination with phosphatidyl-choline would increase the absorption and effectiveness of silymarin [46]
• Hypoglycemic effect [47]
• The oil extracted from the seeds, a by-product of the manufacture of silymarin , also has antioxidant properties [48]

Bud properties

Properties of essential oil

Directions

Indications of the whole plant (phytotherapy)

• Hepatitis and latent liver disease, steatosis, cirrhosis
  • In viral hepatitis B or C, silymarin acts favorably on the elevation of transaminases and gamma-GTs, but not on the viral load [49]
• Prophylaxis and treatment of hepatic diseases caused by toxins (prevention of chemotherapy, protection of hepatic cells during cancer chemotherapy) [50]
• Protection against the toxic effects of phalloidin with better effects if the administration is prophylactic (so if the flavonolignans are absorbed before the phalloidin or any other toxicant)
• Cancer:
  • Chemoprotection
  • Silibinin therapy can target inhibition of proliferative pathways of various cancers through molecular mechanisms such as tyrosine kinase receptors, androgen receptors, STATs (signal transducer and activator of transcription), NF-kappaB, cell cycle regulatory pathways and apoptosis signaling pathways [51]
  • Silibinin would have promising antineoplastic properties and would potentiate the effect of anti-cancer drugs (carcinomas of the skin, breast, lung, colon, bladder, prostate and kidney) [52]
  • Some regressions are spectacular (for example of a hepatocarcinoma) [53]
• Nervous breakdown, stimulation of lactation
• Alcoholic infusions and extracts do not deliver enough silymarin to obtain a marked anti-hepatotoxic effect (insufficient effect of TM )
  • Indeed, the usual dose is 12-15 g of drug, and the most marked effects were due to 140 mg of silymarin 3 times a day, i.e. 420 mg/day (if it is present at 2% in this sample would require 21 g of drug). Nevertheless, we can assume that the total extract will have an amplified activity compared to the flavanolignans alone .
• Usefulness in hepatic iron overload and hemochromatosis [54]
• Non-toxic (even at 20 g/kg in mice)
  • In Belgium and Switzerland, silibinin (Legalon Sil®) is used in poisoning by amanita phalloides on experimental data (even if there is no real antidote for phalloides poisoning). Silibinin would act by limiting the intestinal absorption as well as the intra-hepatocyte transport of amatoxins and by stimulating RNA polymerase. A retrospective study of published cases would have found a statistical association between the use of silibinin and a reduction in mortality (as with N-acetylcysteine). Dosage: 5 mg/kg in 5% glucose IV over 2 hours, to be repeated every 6 hours for 6 days. Source: Belgian Poison Centerhttp://www.poisoncentre.be/article.php?id_article=33
  • Silibinin would also be active on the replication of the hepatitis C virus [55].
• Potentialities in autoimmune diseases [43]
• Peak plasma silymarin is reached 2 to 6 hours after oral intake and its elimination half-life is approximately 6 hours [56] , [57]

Indications of the bud (gemmotherapy)

Specific indications of essential oil (aromatherapy)

Known or suspected mode of action

Usual formulations

Regulations

• French Pharmacopoeia list A (leaf, fruit)

Possible side effects and precautions for use

• No acute or chronic toxicity of silymarin (even at 20 g/kg in mice)
• Possibility of allergies to plants of the Asteraceae family
• Pharmacokinetic interactions:
  • Monitor for possible drug interactions, silymarin decreases the activity of cytochrome P-450 (CYP) enzymes, UDP-glucuronosyltransferase (UGT) enzyme and reduces P-glycoprotein (P-gp) transport [58] , [59]
  • Silymarin in particular reduces the activity of the CYP3A4 enzyme and the activity of uridine diphosphoglucuronosyl transferase (UGT1A6/9), it can therefore alter the hepatic metabolism of certain drugs, their pharmacokinetics and thus lead to increased toxicity [60 ] , but other works show that milk thistle extract has no significant influence on the activities of CYP1A2, CYP2C9, CYP2D6 or CYP3A4/5 [61].
  • Avoid combination with chemotherapeutic treatments mainly metabolized by CYP3A4, it is advisable to make therapeutic windows

Bibliographic references

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2. Aller↑ Polyak SJ, Oberlies NH, Sinner EI, Dahari H, Ferenci P, Pawlotsky JM. Silymarin for HCV infection. Antivir Ther. 2013;18(2):141-7. doi: 10.3851/IMP2402. PMID 23011959
3. Aller↑ Polyak SJ, Morishima C, Lohmann V, Pal S, Lee DY, Liu Y, Graf TN, Oberlies NH. Identification of hepatoprotective flavonolignans from silymarin. Proc Natl Acad Sci US A. 2010 Mar 30;107(13):5995-9. doi: 10.1073/pnas.0914009107. PMID 20231449 full text
4. Aller↑ Vargas-Mendoza N, Madrigal-Santillán E, Morales-González Á, et al. Hepatoprotective effect of silymarin. World Journal of Hepatology. 2014;6(3):144-149. doi:10.4254/wjh.v6.i3.144. Full Text
5. Aller↑ Bahmani M, Shirzad H, Rafieian S, Rafieian-Kopaei M. Silybum marianum: Beyond Hepatoprotection. J Evid Based Complementary Altern Med. 2015 Oct;20(4):292-301. doi: 10.1177/2156587215571116. PMID 25686616
6. Aller↑ Saller R, Melzer J, Reichling J, Brignoli R, Meier R. An updated systematic review of the pharmacology of silymarin. Forsch Complementmed. 2007 Apr;14(2):70-80. PMID 17464157
7. Aller↑ Koch HP, Löffler E. Influence of silymarin and some flavonoids on lipid peroxidation in human platelets. Methods Find Exp Clin Pharmacol. 1985 Jan;7(1):13-8. PMID 3990442
8. Aller↑ Asghar Z, Masood Z. Evaluation of antioxidant properties of silymarin and its potential to inhibit peroxyl radicals in vitro. Pak J Pharm Sci. 2008 Jul;21(3):249-54. PMID 18614420
9. Aller↑ Mourelle M, Muriel P, Favari L, Franco T. Prevention of CCL4-induced liver cirrhosis by silymarin. Fundam Clin Pharmacol. 1989;3(3):183-91. PMID 2548940
10. Aller↑ Hikino H, Kiso Y, Wagner H, Fiebig M. Antihepatotoxic actions of flavonolignans from Silybum marianum fruits. PlantaMed. 1984 Jun;50(3):248-50. PMID 6091165
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13. Aller↑ Petzinger VE, Homann J, Frimmer M. Phalloidin antagonists. 2. Protective effect of disilybine in phalloidin poisoning of isolated hepatocytes. Arzneimittelforschung. 1975 Apr;25(4):571-6. PMID 1098677
14. Aller↑ Professional information of the Swiss Compendium of Medicines [ https://compendium.ch/mpro/mnr/26689/html/fr#7850
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17. Aller↑ Carducci R, Armellino MF, Volpe C, Basile G, Caso N, Apicella A, Basile V. Silibinin and acute poisoning with Amanita phalloides. Minerva Anestesiol. 1996 May;62(5):187-93. PMID 8937042
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22. Aller↑ Ahmed-Belkacem A, Ahnou N, Barbotte L, Wychowski C, Pallier C, Brillet R, Pohl RT, et al. Silibinin and Related Compounds Are Direct Inhibitors of Hepatitis C Virus RNA-Dependent RNA Polymerase. Gastroenterology. 2010;138:1112–1122
23. Aller↑ Carla Pereira, Ricardo C. Calhelha, Lillian Barros, Maria João RP Queiroz, Isabel CFR Ferreira. Synergisms in antioxidant and anti-hepatocellular carcinoma activities of artichoke, milk thistle and borututu syrups. Industrial Crops and Products, Volume 52, January 2014, Pages 709–713
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36. Aller↑ Scambia G, De Vincenzo R, Ranelletti FO, Panici PB, Ferrandina G, D'Agostino G, Fattorossi A, Bombardelli E, Mancuso S. Antiproliferative effect of silybin on gynaecological malignancies: synergism with cisplatin and doxorubicin. Eur J Cancer. 1996 May;32A(5):877-82. PMID 9081370
37. Aller↑ Zi X, Feyes DK, Agarwal R. Anticarcinogenic effect of a flavonoid antioxidant, silymarin, 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. PMID 9563902
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40. Aller↑ Alpna Tyagi, Komal Raina, Rana P. Singh, Mallikarjuna Gu, Chapla Agarwal, Gail Harrison, L. Michael Glode, Rajesh Agarwal. Chemopreventive effects of silymarin and silibinin on N-butyl-N-(4-hydroxybutyl) nitrosamine–induced urinary bladder carcinogenesis in male ICR mice. Mol Cancer Ther 2007;6(12). December2007. Full Text
41. Aller↑ Alpana Tyagi, Chapla Agarwal, Gail Harrison, L. Michael Glode, Rajesh Agarwal. 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 vol.25 no.9 pp.1711-1720, 2004 full text
42. Aller↑ Ninsontia C, Pongjit K, Chaotham C, Chanvorachote P. Silymarin selectively protects human renal cells from cisplatin-induced cell death. Pharm Biol. 2011 May 18. PMID 21591838
43. ↑ Aller à :43.0 & 43.1 Gharagozloo, M., Javid, EN, Rezaei, A., & Mousavizadeh, K. (2013). Silymarin inhibits cell cycle progression and mTOR activity in activated human T cells: therapeutic implications for autoimmune diseases. Basic & clinical pharmacology & toxicology, 112(4), 251–256. https://doi.org/10.1111/bcpt.12032 PMID 23121838
44. Aller↑ Esmaeil N, Anaraki SB, Gharagozloo M, Moayedi B. Silymarin impacts on immune system as an immunomodulator: One key for many locks. Int Immunopharmacol. 2017 Sep;50:194-201. doi: 10.1016/j.intimp.2017.06.030. PMID 28672215
45. Aller↑ Gharagozloo M, Jafari S, Esmaeil N, Javid EN, Bagherpour B, Rezaei A. Immunosuppressive effect of silymarin on mitogen-activated protein kinase signaling pathway: the impact on T cell proliferation and cytokine production. Basic Clin Pharmacol Toxicol. 2013 Sep;113(3):209-14. doi: 10.1111/bcpt.12088. PMID 23701595
46. Aller↑ Kidd P, Head K. A review of the bioavailability and clinical efficacy of milk thistle phytosome: a silybin-phosphatidylcholine complex (Siliphos). Altern Med Rev. 2005 Sep;10(3):193-203. PMID 16164374 [2]
47. Aller↑ Maghrani M, Zeggwagh NA, Lemhadri A, El Amraoui M, Michel JB, Eddouks M. Study of the hypoglycaemic activity of Fraxinus excelsior and Silybum marianum in an animal model of type 1 diabetes mellitus. J Ethnopharmacol. 2004 Apr;91(2-3):309-16. PMID 15120454
48. Aller↑ Zhu SY, Dong Y, Tu J, Zhou Y, Zhou XH, Xu B. Silybum marianum oil attenuates oxidative stress and ameliorates mitochondrial dysfunction in mice treated with D-galactose. Pharmacogn Mag. 2014 Jan;10(Suppl 1):S92-9. doi: 10.4103/0973-1296.127353. PMID 24914315
49. Aller↑ Mayer KE, Myers RP, Lee SS. Silymarin treatment of viral hepatitis: a systematic review. J Viral Hepat. 2005 Nov;12(6):559-67. PMID 16255756
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55. Aller↑ Ahmed-Belkacem A, Ahnou N, Barbotte L, Wychowski C, Pallier C, Brillet R, Pohl RT, Pawlotsky JM. Silibinin and Related Compounds are Direct Inhibitors of Hepatitis C Virus RNA-Dependent RNA Polymerase. Gastroenterology. 2009 Dec 3. PMID 19962982
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