Milk thistle extracts:Pharmacological effects,Safety and toxicity

Introduction

Milk thistle extracts (Figure 1) have been used as medicinal herbs in the treatment of liver cirrhosis, chronic hepatitis (liver inflammation), and gallbladder disorders.Treatment claims also include lowering cholesterol levels; reducing insulin resistance; reducing the growth of cancer cells in breast, cervical, and prostate gland cancers; and antiviral activity. Other reported uses of milk thistle in folk medicine include as a treatment for malarial fever, bronchitis, gallstones, jaundice, peritonitis, uterine congestion, varicose veins, and as a milk production stimulant for nursing mothers. The roots soaked in water overnight are used in food, and the despined leaves are added to salads. Roasted milk thistle fruit has been used as a coffee substitute. Milk thistle extract was nominated for study by the National Institute of Environmental Health Sciences because it is one of the most widely used herbs in the United States.Male and female F344/N rats and B6C3F1 mice were exposed to an ethanol/water extract of milk thistle fruit (milk thistle extract) containing approximately 65% silymarin in feed for 3 months or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Escherichia coli and mouse peripheralblood erythrocytes.[1]

Pharmacological effects of silymarin (milk thistle extract)

In some studies, milk thistle extract usually refers specifically to silymarin. Silymarin is the major constituent of milk thistle extract. Silymarin contains a group of closely-related flavonolignan compounds including silibinin, and is extracted from Silybum marianum species, also called milk thistle. Silymarin has been shown to protect the liver in both experimental models and clinical studies. The chemopreventive activity of silymarin has shown some efficacy against cancer both in vitro and in vivo. Silymarin can modulate apoptosis in vitro and survival in vivo, by interfering with the expression of cell cycle regulators and apoptosis-associated proteins. In addition to its antimetastatic activity, silymarin has also been reported to exhibit anti-inflammatory activity. The chemoprotective effects of silymarin and silibinin (its major constituent) suggest they could be applied to reduce the side effects and increase the anti-cancer effects of chemotherapy and radiotherapy in various cancer types, especially in gastrointestinal cancers.[2]

Milk thistle extract in STAM™ model of nonalcoholic steatohepatitis

A subcategory of nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) is characterized by accumulation of fat accompanied by inflammatory infiltration and hepatocellular damage. The active complex of milk thistle is a lipophilic extract from its seeds, comprising three isomers, collectively known as silymarin. Silymarin (Milk thistle extract) has demonstrated antioxidant, anti-inflammatory, and antifibrotic properties, and has been extensively studied in the treatment of liver diseases. The majority of published clinical research on silymarin has used Legalon(®) (Rottapharm/Madaus), containing the patented extract of milk thistle ETHIS-094™ (Euromed). The current study was undertaken to examine the effects of ETHIS-094™ in the Stelic Animal Model (STAM™), a validated and widely used animal model for NASH.

After 4 h fasting from 4 to 8 weeks of age, 15 male mice in whom NASH had been induced were orally administered, once daily, either (1) vehicle (saline) at a volume of 10 mL/kg, (2) vehicle supplemented with milk thistle at a dose of 500 mg/kg, or (3) vehicle supplemented with milk thistle at a dose of 1,000 mg/kg. Mean liver weight and the liver-to-body weight ratio were significantly (P<0.01) decreased in the milk thistle high-dose group compared with the vehicle group. NAFLD activity score (NAS) tended to decrease in the milk thistle treatment groups compared with vehicle group, as did steatosis scores. Milk thistle extract administration induced a decreasing trend in NAS compared with the vehicle group. Milk thistle induced a numerical decrease of the steatosis score compared with vehicle, and this was accompanied by a statistically significant decrease in liver weight and the liver-to-body weight ratio, implying a potential anti-steatosis effect of milk thistle.[3]

Improve the Welfare, Growth Performance and Meat Quality of Broiler Chicken

Modern poultry production looks for feed and water additives that improve the welfare of chickens. The utilization of herbs as additives in feed or drinking water is becoming increasingly well known. The aim of this study was to determine the effect of milk thistle extract (Silybum marianum), administered in drinking water, on chickens' welfare, production results, selected physicochemical properties of the breast muscles, the activity of selected enzymes, and the antioxidant potential of blood serum and breast muscles. A total of 102 one-day-old male ROSS 308 chicks were allocated into three treatment groups. The material was an infusion of dried milk thistle seeds in two doses, administered in drinking water for chickens (group: C=0; E1=0.24; E2=0.36 g/day/animal) under standard rearing conditions. As a result of adding the milk thistle to the drinking water, there was an improvement in the welfare of the chickens and in the production results, enzymatic capacity of selected enzymes, and antioxidant capacity in the blood serum and in pectoral muscle (p≤0.05). The addition of a milk thistle seed infusion for chickens can be used in poultry production to improve the rearing performance antioxidant capacity and welfare of chickens.[4]

Safety and toxicity of silymarin (milk thistle extract)

Also, studies have shown other therapeutic effects such as anticancer, anti-Alzheimer, anti-Parkinson, and anti-diabetic, so its safety is very important. It has no major toxicity in animals. Silymarin (milk thistle extract) was mutagen in Salmonella typhimurium strains in the presence of metabolic enzymes. Silybin, silydianin, and silychristin were not cytotoxic and genotoxic at concentration of 100μM. Silymarin (milk thistle extract) is safe in humans at therapeutic doses and is well tolerated even at a high dose of 700 mg three times a day for 24 weeks. Some gastrointestinal discomforts occurred like nausea and diarrhea. One clinical trial showed milk thistle extract is safe in pregnancy, and there were no anomalies. Consequently,caution should be exercised during pregnancy, and more studies are needed especially in humans. Silymarin has low-drug interactions, and it does not have major effects on cytochromes P-450. Some studies demonstrated that the use of silymarin must be with caution when co-administered with narrow therapeutic window drugs.[5]

References

1.National Toxicology Program. Toxicology and carcinogenesis studies of milk thistle extract (CAS No. 84604-20-6) in F344/N rats and B6C3F1 mice (Feed Studies). Natl Toxicol Program Tech Rep Ser. 2011;(565):1-177.

2.Fallah M, Davoodvandi A, Nikmanzar S, et al. Silymarin (milk thistle extract) as a therapeutic agent in gastrointestinal cancer. Biomed Pharmacother. 2021;142:112024. doi:10.1016/j.biopha.2021.112024

3.Pais P, D'Amato M. In vivo efficacy study of milk thistle extract (ETHIS-094™) in STAM™ model of nonalcoholic steatohepatitis. Drugs R D. 2014;14(4):291-299. doi:10.1007/s40268-014-0068-2

4.Bendowski W, Michalczuk M, Jóźwik A, et al. Using Milk Thistle (Silybum marianum) Extract to Improve the Welfare, Growth Performance and Meat Quality of Broiler Chicken. Animals (Basel). 2022;12(9):1085. Published 2022 Apr 22. doi:10.3390/ani12091085

5.Soleimani V, Delghandi PS, Moallem SA, Karimi G. Safety and toxicity of silymarin, the major constituent of milk thistle extract: An updated review. Phytother Res. 2019;33(6):1627-1638. doi:10.1002/ptr.6361

You may like