Silibinin (INN), also known as silybin (both from Silybum, the generic name of the plant from which it is extracted), is the major active constituent of silymarin, a standardized extract of the milk thistle, containing a mixture of flavonolignans consisting of silibinin, isosilibinin, silychristin, silidianin, and others. Silibinin itself is a mixture of two diastereomers, silybin A and silybin B, in approximately equimolar ratio.[1] Silibinin is used in pure forms as a medication, and more frequently as an active ingredient in milk thistle–derived herbal supplements.
Poor water solubility and bioavailability of silymarin led to the development of enhanced formulations. Silipide (trade name Siliphos, not to be confused with the water treatment compound of the same name, a glass-like polyphosphate containing sodium, calcium magnesium and silicate, formulated for the treatment of water problems), a complex of silymarin and phosphatidylcholine (a phospholipid in lecithin), is about 10 times more bioavailable than silymarin.[16] An earlier study had concluded Siliphos to have 4.6 fold higher bioavailability.[17][non-primary source needed] It has been also reported that silymarin inclusion complex with β-cyclodextrin is much more soluble than silymarin itself.[18] There have also been prepared glycosides of silybin, which show better water solubility and even stronger hepatoprotective effect.[19]
Silymarin, like other flavonoids, has been shown to inhibit P-glycoprotein-mediated cellular efflux.[20] The modulation of P-glycoprotein activity may result in altered absorption and bioavailability of drugs that are P-glycoprotein substrates. It has been reported that silymarin inhibits cytochrome P450 enzymes and an interaction with drugs primarily cleared by P450s cannot be excluded.[21]
Toxicity
Silibinin and all the other compounds found in silymarin, especially silychristin, blocked the MCT8 transporter according to one in vitro study.[22] There is no published clinical information showing silymarin or silibinin cause any thyroid problems. In fact, one clinical trial found that silymarin actually helped prevent thyroid suppression that is often caused by the drug lithium.[23]
There is limited research on milk thistle and silymarin in pregnant humans. However, the one known clinical trial found only benefits, including but not limited to effectively treating intrahepatic cholestasis of pregnancy.[24][25] Silymarin is also devoid of embryotoxic potential in animal models.[26][27]
A phase I clinical trial in humans with prostate cancer designed to study the effects of high dose silibinin found 13 grams daily to be well tolerated in patients with advanced prostate cancer with asymptomatic liver toxicity (hyperbilirubinemia and elevation of alanine aminotransferase) being the most commonly seen adverse event.[28]
↑Balouchi S, Gharagozloo M, Esmaeil N, Mirmoghtadaei M, Moayedi B (August 2014). "Serum levels of TGFβ, IL-10, IL-17, and IL-23 cytokines in β-thalassemia major patients: the impact of silymarin therapy". Immunopharmacology and Immunotoxicology. 36 (4): 271–274. doi:10.3109/08923973.2014.926916. PMID24945737. S2CID21176675.
↑Moayedi Esfahani BA, Reisi N, Mirmoghtadaei M (2015-03-04). "Evaluating the safety and efficacy of silymarin in β-thalassemia patients: a review". Hemoglobin. 39 (2): 75–80. doi:10.3109/03630269.2014.1003224. PMID25643967. S2CID22213963.
↑Barzaghi N, Crema F, Gatti G, Pifferi G, Perucca E (1990). "Pharmacokinetic studies on IdB 1016, a silybin- phosphatidylcholine complex, in healthy human subjects". Eur J Drug Metab Pharmacokinet. 15 (4): 333–8. doi:10.1007/bf03190223. PMID2088770. S2CID26047183.
↑Voinovich D, Perissutti B, Grassi M, Passerini N, Bigotto A (2009). "Solid state mechanochemical activation of Silybum marianum dry extract with betacyclodextrins: Characterization and bioavailability of the coground systems". Journal of Pharmaceutical Sciences. 98 (11): 4119–29. Bibcode:2009JPhmS..98.4119V. doi:10.1002/jps.21704. PMID19226635.
↑Wu JW, Lin LC, Tsai TH (2009). "Drug-drug interactions of silymarin on the perspective of pharmacokinetics". Journal of Ethnopharmacology. 121 (2): 185–93. doi:10.1016/j.jep.2008.10.036. PMID19041708.
↑Ataei S, Mahdian MR, Ghaleiha A, Matinnia N, Nili-Ahmadabadi A (July 2023). "Silymarin Improves Thyroid Function in Lithium-treated Bipolar Patients: A Randomized, Double-blind, Placebo-controlled Pilot Study". Current Drug Therapy. 18 (3): 346–353. doi:10.2174/1574885518666230710122712. S2CID259869834.
↑Soleimani V, Delghandi PS, Moallem SA, Karimi G (June 2019). "Safety and toxicity of silymarin, the major constituent of milk thistle extract: An updated review". Phytotherapy Research. 33 (6): 1627–1638. doi:10.1002/ptr.6361. PMID31069872. S2CID148569634.
↑Hernández R, Nazar E (1982). "Effect of silymarin in intrahepatic cholestasis of pregnancy (preliminary communication)". Revista chilena de obstetricia y ginecología. 47 (1): 22–29. PMID6927150.
↑Hahn G, Lehmann HD, Kürten M, Uebel H, Vogel G (1968). "On the pharmacology and toxicology of silymarin, an antihepatotoxic active principle from Silybum marianum (L.) gaertn". Arzneimittelforschung. 18 (6): 698–704. PMID5755807.
↑Flaig TW, Gustafson DL, Su LJ, Zirrolli JA, Crighton F, Harrison GS, etal. (April 2007). "A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients". Investigational New Drugs. 25 (2): 139–146. doi:10.1007/s10637-006-9019-2. PMID17077998. S2CID20240838.
