- The "giant thistle of the Pampas" reported by Darwin in the Voyage of the Beagle is thought to be Silybum marijuana. (1)
- Originally grown in souther Europe and Asia, it is now found throughout the world. Milk thistle has been used for medicinal purposes for over 2000 year, commonly for treatment of liver diseases or protection of the liver from toxic substances.
Milk thistle is an upright herb with a conical shape that can grow up to 2 meters tall, with a maximum base diameter of 160 cm. Stem is grooved, hollow in large specimens, and may be covered with a light cottony fuzz. Leaves are large and variegated, shiny green, oblong to lanceolate, 15-60 cm long, typically pinnately lobed, with spiny edges like most thistles, hairless, with milk thistle veins. Flower heads are red purple, 4-12 cm long and wide, surrounded by bracts which are hairless, with triangular, spine-edged appendages, tipped with a stout yellow spine. Fruits are black achenes with a single long white pappus—acting as a "parachute", which supports seed dispersal by wind—surround by a yellow basal ring. (1)
- Originally native to southern Europe and Asia, now found throughout the world.
- Reported as a highly invasive weed as far back as the 1800s.
- It invades pastures, and once established eliminates other plant species and hinder movement of livestock and people. (2)
- Seeds yield many compounds such as silibin, silibinin A and B,silicristin, silidianin, apigenin, dehydrosilybin, deoxysilyn cristin, deoxysilyn dianin, among others. (5)
of dried seed yields up to 4% silymarin, which is a combination of flavonoids such as silibinin A and B, silidianin, silicristin, and dihydroxysilibin. Other flavonolignans present in the plant extract include sylandrin, silybinom, silyhermin, and myristic, palmitic, and stearic acids which may have hepatoprotective properties. (5)
- HPLC study revealed marker constituents, namely: taxifolin, silychristin, silydianin, silibinin A, silibinin B, dehydrosilibinin, isosilibinin A, and isosilibinin B.
- Study for seed oil using capillary GLC and HPLC yielded oil rich in linoleic acid (53.3%)
and oleic acid (21.3%). HPLC detected five major triacylglycerols containing linoleic acyls, namely: LLL, LLO, LLP, LOO and LOP. Total tocopherol content was 260 ppm. The oil contained alpha-tocopherol as a major constituent (84.5%), resembling sunflower oil. Sterols included campesterol, 5-stigmasterol, beta-sitosterol, 7-stigmasterol, avenasterol, and spinasterol. (30)
- Considered antioxidant, anti-inflammatory, hepatoprotective, neuroprotective, anticancer, antihypertensive, antihypercholesterolemic, and antiviral.
- Studies have suggested hepatoprotective, antidiabetic, analgesic, antifibrotic,
antibacterial, anti-COVID-19, antioxidant, antidiabetic, tyrosinase-inhibitory, antifungal, antibacterial, anti-echinococcus, anticancer, anti-Candida, anticariogenic properties.
- Young stalks, leaves, roots and flowers can be eaten. Roots and leaves can be eaten raw or cooked, but for leaves, the sharp leaf-spines must first be removed. Flower buds can be cooked. Stems can be eaten raw or cooked. Stems can be eaten raw or cooked, but best when peeled, and soaking recommended to reduce bitterness.
- Cooked leaves
make a good spinach substitute.
- Roasted seeds used as coffee substitute.
In Israel, young fleshy stems traditionally eaten by Arab sector.
- Sprouts are edible. (see study below)
- A medicinal plant that has been used for thousands of years.
- Used in the treatment of jaundice, liver and gall bladder diseases.
- Used for kidney
problems, rheumatism, gastronomic disturbances, and cardiac disorders.
- Used as galactagogue.
- Fuel: Seed oil has potential as new non-edible feedstock for biodiesel. (see study below) (33)
- Fodder: Under cultivation, it is grown as an animal crop.
Toxicity concerns, side effects, interactions
- Milk thistle based supplements have been found to have high mycotoxin concentrations of up to 37 mg/kg compared to plant-based dietary supplements.
- Toxicity to cattle and sheep is attributed to its nitrate content. When potassium nitrate is eaten by ruminants, it is broken down by bacteria in the animal's stomach to produce nitrite ions, which combine with hemoglobin to produce methemoglobin, which blocks the transport of oxygen, resulting in oxygen deprivation. (1)
- It can cause allergic reactions, Risks may be higher with a history of allergy to other plants in the same family, such as: ragweed, chrysanthemums,
marigolds, and daisies. (36)
- Milk thistle may lower blood sugar. If you are diabetic
discuss your use of the supplement with your physician.
- Likewise, women who are pregnant or breastfeeding should discuss supplement use with their healthcare provider.
• Review: Review summarizes high-quality publications related to pharmacologic effects and mechanisms of actions. It has been reported to have antimicrobial, anticancer, hepatoprotective, cardioprotective, neuroprotective, antidiabetic effects among others. It is reported to counter the toxicities of antibiotics, metals, and pesticides. Review discussed potential, perspectives and insights for its application for the development of new drugs. (5)
• Silymarin: Seeds and fruits of Silybum marianum contain a flavonolignsn complex called silymarin, with active compounds including silybin, isosilybin, silychristin, dihydrosilybin, silydianin, among others. Silymarin is rapidly absorbed from the gastrointestinal tract reaching maximum blood concentration after 2 to 4 hours, with a half-life excretion of 6 hours. Eighty percent of the drug is excreted in the bile. Bioavailability depends on the type of formulation. (5)
• Hepatoprotection: Its use as hepatoprotective dates back to 2000 years ago. Studies have shown the plant to protect the liver from toxicities resulting from toxins such as carbon tetrachloride, acetaminophen, and tetrachloromethane. (5)
• Beyond Hepatoprotection / Review: The plant has long been used as a hepatoprotective remedy for liver conditions characterized by functional impairment or degenerative necrosis. Its mechanisms of activity is varied,: antioxidant,, anti-inflammatory, cell permeability regulator and membrane stabilizer, stimulation of liver regeneration and inhibition of deposition of collagen fibers, which may lead to cirrhosis. Recent studies have suggested renal protective, hypolipidemic, antiatherosclerotic and cardioprotective properties. (5)
• Antidiabetic / Clinical Trial: A 4-month randomized, double-blind, placebo-controlled clinical trial was conducted in 51 patients with type-II diabetes. One group received silymarin (200 mg) tablets 3 times daily plus conventional therapy while the other group received placebo tablets. Results showed a significant decrease in HbA1c, FBS, total cholesterol, LDL, triglycerides, SGOT and SGPT levels in silymarin-treated patients. (6)
• Hypoglycemic / Type 1 Diabetes Model / Aerial Parts: Study evaluated the hypoglycemic effect of aqueous extracts of Fraxinus excelsior and Silybum marianum in normal and STZ-induced diabetic rats. Results showed the extracts exhibited potent hypoglycemic and anti-hypoglycemic activities without affecting basal plasma insulin concentrations. (7)
• Obsessive Compulsive Disorder / VS Fluoxetine / Aerial Parts: Study compared the efficacy of the extract of S. marianum with fluoxetine in the treatment of OCD in an 8-week pilot double-blind randomized trial. The minimum score of Yale-Brown Scale for OCD was 21 for all patients. Results showed no significant difference between the extract and fluoxetine. There was also no observed difference in side effects. (8)
• ZnO Nanoparticles / Antidiabetic / Antibacterial / Seeds: Study reports on the green eco-friendly microwave-assisted synthesis of ZnO nanoparticles using S. marianum seed extract. The ZnONP showed good antidiabetic activity with a major fall in fasting blood sugar and rise in HDL levels in diabetic rats and good antibacterial activity against E. coli. (9)
• Silymarin in CCl4-Induced Liver Damage: Study evaluated ethyl acetate and ethanol seed extracts of S. marianum were tested against injections of carbon tetrachloride induced liver damage. Activity was compared with standard hepatic drug hepaticum. The ethanolic extract showed the most significant decrease in liver enzymes. For oxidative experiments, the ethyl acetate extract showed the most increase in glutathione level and risk factor HDL/LDL significantly. Hepaticum showed most significant decrease for malondialdehyde and fucosidase activity. (10)
• Antioxidant / Antibacterial / Antifungal / Fruit: Study evaluated ethanol, methanol, and dichlormethane extracts of fruits fro antioxidant, antibacterial and antifungal activities. Results showed high antioxidant activity Extracts showed more activity against gram negative bacteria, and showed activity against Candida species. (11)
• Tyrosinase Inhibitory Activity / Antimelanogenesis / Flavonolignans / Seeds: Studies have reported the anti-melanogenesis effects of silimaryin from milk thistle evaluated the tyrosinase inhibitory activity of flavonolignans of S. marianum. Study substantiated tyrosinase inhibition and its mechanism. The responsible components for tyrosinase inhibition were flavonolignans, namely: isosilybin A (1), isosilybin B (2), silydianin (3), 2,3-dihydrosilychristin (4), silvchristin A (5), silvchristin B (6) and silybin (7). The isolated flavonolignans (1-7) significantly inhibited both monophenolase and diphenolase of tyrosinase. Inhibitions were 10-fold more effective compared to mother skeletons (8-10). The isolated inhibitory compounds were found to be the most abundant metabolites in the target plant. (12)
• Effect on Pharmacokinetics/ of Irinotecan: Silybin, a principle constituent of milk thistle, significantly inhibits cytochrome P450 isoform 3A5 (CYP3A4) and UDP glucuronosyltransferase isoform 1A1 (UGT1A1) in vitro. Study evaluated whether S. marianum affects the pharmacokinetics of irinotecan, a substrate for CYP3A4 and UGT1A1 in humans. Results showed silybin concentrations after intake of milk thistle are too low to significantly affect the function of the enzymes, indicating milk thistle is unlikely to alter the deposition of anticancer drugs metabolized by these enzymes. (13)
• Anti-COVID-10 Infection / Silybin: In a study of 30 plants screen for phytochemicals, Silybin, an active constituent found Silybum marianum exhibited higher binding capacity with targets SARS-Cov-2 in comparison to currently used repurposed drugs against SARS-Cov-2. Other plant compounds viz. Withania somnifera (Withaferin A), Tinospora cordifolia (Cordioside), and Aloe barbadensis (Catechin and Quercetin) also exhibited higher binding energetics than widely used hydroxychloroquine and other repurposed drugs used for the treatment of COVID-19. (15)
• Gastrointestinal Absorption of Flavonolignans / Membrane Permeability: Study evaluated the gastrointestinal absorption of natural flavonolignans from Silybum marianum by combine in vitro and in silico methods. A parallel artificial membrane permeability assay (PAMPA) was used to evaluate the transcellular permeability of the plant main compounds. Results showed most flavonolignans were highly permeable in the gastrointestinal tract, which is a prerequisite for sufficient bioavailability and use as lead structures in drug development. (16)
• Antidiabetic Effects Before Insulin Therapy / Seed: / Clinical Trial: Most uncontrolled type-II diabetic patients prefer to continue oral therapy or alternative treatments such as herbal therapy instead of insulin therapy. Study evaluated the effects of Silybum marianum seed extract on glycemic control in type II diabetic patients who are candidates for insulin therapy. A 2-month clinical trial was done on two groups of patients: one group received silymarin tablets 200 mg 3x daily plus standard therapy, while a control group received placebo plus standard therapy. Results showed a significant decrease in HbA1c from 9.81 to 8.25 in the silymarin group, while the control group showed an increase from 9.83 to 10.21. There was also a drop i FBS, 2hr-ppbs, total cholesterol and LDL, and no significant change in the control group. Results suggest positive glycemic control effects as well as hypolipidemic effects in patients who need to be on insulin therapy. (17)
• Silybin / Fruit: The main component of a fruit extract (silymarin) is a flavonolignan, silybin, It is also the most active ingredient of the extract. Since the 1970s, silybin has been considered a substance with hepatoprotective properties. Research has imbued it with many other healthy properties. This study focuses on the silybin molecule—its structure, chemistry, bioavailability, and metabolism. (18)
• Anti-Echinococcosis / Scolicidal: Cystic echinococcosis (CE) is a parasitic zoonosis caused by Echinococcus granulosus larvae in liver and lungs of both humans and animals. Surgical intervention has been the mainstay of treatment. This in-vitro study evaluated the scolicidal effects of Silybum marianum ethanolic extracts and its combination with albendazole. HPLC analysis showed the main constituents of the ethanolic extract of S. marianum were silydianin (14.41%), isosilybin A (10.50&), and silychristin (10.46%). Results showed scolicidal activity in vitro. The highest scolicidal effects were obtained with a combination of S. marianum and albendazole (79%), the extract alone (77%), and albendazole (69%). (19)
• Supportive Phototherapeutic Use in Oncology: The potential therapeutic use of Silymarin in cancer patients has drawn attention recently. Study reviews available information on the therapeutic effects of milk thistle in oncology patients and its potential as a supportive therapy either as an anticarcinogenic agent or as an agent that attenuates the side effects of oncological treatments. Evidence from clinical studies suggest it has mainly beneficial effects in hepatotoxicity and radiotherapy-induced skin and mucosa damage, especially for treatment of side effects of anticancer chemotherapeutics at dosages of 160-600 mg daily. (20) Silymarin (140 mg three times daily) has been found significantly effective in reducing pain and inflammation, enhancing antioxidant capacity and accelerating healing of ulcers in chemotherapy induced oral mucositis. (22)
• Efficacy on Liver Cirrhosis in Chronic Hepatitis B / : Cirrhosis is the irreversible sequel of various disorders that damage liver cells. Study evaluated the efficacy of herbal medicine Khar maryam or silymarin on liver cirrhosis in chronic hepatitis B patients. Results showed a hepatoprotective effect. Patients treated with silymarin for 12 months had significantly better child-pugh score, decreased ascites, decreased AST and ALT. (21)
• Antioxidant / Hepatoprotective: Studies have suggested the positive roles of milk thistle in hepatoprotection and regeneration. Administration of 250 mg/kg of silybin was found to restore oxidant-antioxidant balance and reduce biomarkers of inflammation and immunomodulation in induced liver oxidative stress in rats. Silymarin promoted the hepatic generation of glutathione, which enhanced the antioxidant defense in the liver of mice models.. In humans, studies revealed a significant reduction of lipid peroxidation in patients with alcoholic liver disease after administration of 450 mg/day of silymarin from dry fruit extract of the plant. (22)
• Anticariogenic: Following biofilm formation, gram negative bacteria were found to upregulate the inflammatory immune response thorough production of proinflammatory cytokines such as TNF-α, IL-6, IL-8, COX-2. Silymarin can exert anti-inflammatory effect through alteration of the pathways of transcription factor NF-kB activation and translocation. Silymarin and silibinin (silybin A and B) were found to both exert antimicrobial actions against some cariogenic pathogens like C. albicans, E. faecalis, L. acidophilus, S. aureus, and S. mutans with silymarin showing higher efficacy at lower concentrations than silibinin. (22)
• Effect on Oral Candidiasis: An invitro study has noted that silymarin at concentrations from 30 to 300 mg/ml can inhibit C. albicans cellular growth. It was found to have anti-virulence properties through downregulation of the involved gene in virulence, biofilm destabilization and inhibition of hydrolases secretion. Another study has shown inhibitory effects of milk thistle extract silibinin on C. albicans membrane damage and biofilm formation. (22)
• Oral Cancer: Oral cancer is the sixth most common neoplasm worldwide. Milk thistle has proven chemopreventive and anticancer effects in various cancers i.e., liver, lung, prostate, breast, cervical and colorectal cancers. In invivo and invitro studies, silymarin (silybin A and B, isosylibin A and B, silychristin, silydianin, taxifolin and apigenin 7-glucoside, equivalent to 45% silybin by weight) significantly inhibited cellular proliferation and promoted apoptosis in different oral cancer cell lines in a dose dependent manner Caspase 8 and death receptor 5 were possible mechanisms for apoptosis. Silymarin also had effect on tumor size and growth suppression in mice without toxicity. (22)
• Preventive Effect on Galactose-Induced Cataract / Seeds: In diabetes, the oxygen free radical and reduced glutathione level are important risk factors for cataract formation. In the study,, Silybum marianum seed extract (silymarin) with its antioxidant property, increased cellular glutathione level and cellular membrane stabilizing properties was tested against development of galactose-induced cataract in male rats. In the silymarin treated group, all stages of cataract development were significantly delayed. The preventive effect may be due to antioxidant, anti-inflammatory, increased glutathione level and membrane stabilizing properties of the herbal medicine. (23)
• Neurotrophic and Neuroprotective Effects: Study evaluated the effects of milk thistle extract on differentiation and survival of cultured neural cells. Milk thistle enhanced nerve growth factor (NGF)-induced neurite outgrowth in PC-12 neural cells and prolonged their survival in culture. The extract also protected cultured rat hippocampal neurons against oxidative stress-induced cell death. Results demonstrated milk thistle can promote neuronal differentiation and survival. (24)
• Variable Silymarin Content in Commercial Tinctures: Silymarin, the active fraction of Silybum marianum tinctures, accounts for 70-80% of the plant's hydroalcoholic extract and extracts of a mixture of flavonolignans and a flavonoid. Studies have shown inconsistency in the therapeutic efficacy of Silybum marianum tinctures, which has been attributed to content variability of silymarin, resulting from lack of standardized and regulated manufacturing processes. Study quantified the silymarin content in commercial Silybum marianum tinctures and reported on the total silymarin content in 11 different commercial tinctures in the UK using commercial and accurate HPLC-UV method. There was significant variability between herb and liquid as well as percentage of ethanol used during the extraction process. Results showed a direct correlation between silymarin content in tinctures and alcohol strength. Silymarin could not be detected in tinctures extracted with 25% ethanol. Effective therapeutic doses were found in tinctures with concentration ratio of 1:1 herb to liquid and an alcohol content of 70%. To guarantee quality and safety of herbal medicinal products, legal requirements to produce plant-based products under regulatory frameworks are needed. (25)
• Vitiligo / Phototherapy Plus Silymarin / Clinical Trial: A double-blind, controlled randomized clinical trial evaluated the effect of phototherapy plus oral Silybum marianum on the treatment of, skin lesions of vitiligo. Results in the mean VASI score showed a statistically significant decrease in both group—phototherapy plus Narrow-band UVB plus oral silymarin vs P+NBUVB + placebo—with more decrease in the silymarin group. Study suggest silymarin is probably a good choice for patients vitiligo, and recommends further studies. (26)
• Hepatoprotective / Probable Synergism with Glycyrrhizin: Study evaluated the ability of silymarin (SLN) and glycyrrhizin (GLN) to lessen oxidative stress in rats with hepatic injury caused by carbon tetrachloride. Both significantly reduced ALT, AST, ALP, and TBARS levels and increased GSH, SOD, and CAT levels. Results showed both plants have hepatoprotective effects. Study also showed that SLN and GLN have marked hepatoprotective effects when used in combination at 200 mg/kg and 50 mg/kg, respectively. (27)
• Effect on Morphine Addiction / Compared to Naloxone: Study evaluated the effects of Silybum marianum in animals treated for morphine addiction compared to chemical drug Naloxone. Results showed treatment of addicted rats at dose of 400 mg/kg led to a major reduction in serum morphine compared to Naloxone. The extract also caused a significant reduction in MDA levels compared to control. The silymarin in milk thistle was more selective toward u-opioid receptor than morphine or Naloxone as a narcotic receptor antagonist. (28)
• Analgesic Effect / Possible Mechanisms: Study evaluated the analgesic effects of single and multiple-dose of IP administration of silymarin and the probable role of nitric oxide or opioid receptors using tail flick assay. Results showed only silymarin 100 mg/kg exhibited analgesic properties. Since naloxone did not change silymarin;s analgesic effect, study concludes that opioid receptors are not involved. In the presence of L-arginine, the analgesic effect of silymarin remained intact, but the involvement of the nitric oxide pathway is unclear. Results suggest an analgesic effect via other mechanisms, Possibly, it could be via inhibition of 5-lipoxygenase and neutrophil chemotaxis to inflammation location. (29)
• Flavonolignans Study on Dermal Delivery: Study evaluated flavonolignans interactions with human skin and potential for dermal delivery. HPLC determined the partition coefficients log of main constitutive flavonolignans, taxifolin and their derivatives. During transdermal transport, all the studied compounds permeated the human skin ex vivo; none reached the acceptor liquid. The polyphenols were divided into two groups: low (taxifolin, silychristin, silydianin) vs high (silybin, dehydrosilybin, isosilybin) lipophilicity and skin intake. No dermal delivery differences could be provided for the compounds with very similar physico-chemical properties. (31)
• Silymarin Inhibition of Collagen Deposition in Biliary Fibrosis: Silymarin (SIL), a standardized extract containing about 60% polyphenol silibin, was evaluated in Wistar rats subjected to complete bile duct obstruction (BDO) by injection of sodium amidotrizoate (Ethibloc), which induces progressive portal fibrosis without significant inflammation. Untreated rats showed an almost 9-fold increase in total liver collagen, reduced total HYP (hydroxyproline). Study concludes SIL can ameliorate collagen accumulation even in advanced biliary fibrosis. PIIINP appears to be a suitable serum marker to monitor the inhibition of hepatic fibrogenesis in this model of biliary fibrosis. (32)
• Potential for Biodiesel: Study evaluated the alkaline transesterification of S. marianum seed oil to biodiesel using methanol and ethanol. Oil was extracted from the seeds, which contained 46% oil with low fatty acids (0.68%). Linoleic acid (65.68%) was the main component of the oil. Ultrasonification transesterification with methanol gave the highest yield (95.75%). Findings of the study complement the abundance of S. marianum oil at cultivation and silymarin industrial production as by-product suggests a potentially new non-edible feedstock for biodiesel. (33)
• Nutritional Potential of Sprouts: Study in Israel evaluated the potential of milk thistle as a source of edible sprouts rich in antioxidants. Seed germination within 3-4 days was high (96%) except for striated seeds. Exposure to light significantly reduced sprout growth and significantly increased polyphenol content and antioxidant capacity. The polyphenol content was 30% higher in seeds originating from purple inflorescences than from white ones. Results suggest milk thistle as a good source of healthy edible sprouts. (34)
• Potential for Marginal Agricultural Environments . Review: Silybum marianum is a versatile crop that has adopted
to different soils and environmental conditions throughout all contents. The fruit (seeds) of the plant are the only reliable source of silymarin. which has been studied extensively and recognized for its potential and many therapeutic uses. Its potential for livestock feed can be a significant boon for enhancing and stabilizing farm income. It presents as a most interesting alternative crop, even for marginal environments. The review discusses issues on constraints and agronomic challenges, lack of field data on suitable cropping protocols. The review focused on updating information on morphological and phytochemical traits of the crop and agronomic characteristics and novel uses, and guidelines for farmers eager to cope with the cultivation of a challenging and resource-rich crop.(38)
- Capsules, tablets, powders and extracts in the cybermarket.