Milk Thistle (Silybum marianum) as a tool for helping with Liver support

Background Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease characterized by excess accumulation of fat in hepatocytes. Because no drug has been approved for NAFLD treatment, this work analyzed the effects of agents resulting from 2 research hotspots, metabolic target agents, and natural plant drugs, on NAFLD with network meta-analysis. Methods Public databases were searched through August 14, 2020. Randomized controlled trials that compared obeticholic acid, elafibranor, cenicriviroc, selonsertib, curcumin, silymarin, and resveratrol to placebo were included. Liver pathology improvement, hepatic biochemical indicators, and lipid metabolism indicators were analyzed. Results Thirty-five studies were included in the meta-analysis. Obeticholic acid was found to significantly increase the frequency of liver biopsy improvement compared to placebo (OR: 2.10; 95% CI: 1.60, 2.77). The ranking results among the hepatic biochemical indicators showed that obeticholic acid (94.9%) and elafibranor (86.3%) have a relative advantage in reducing alanine aminotransferase (ALT) levels, and obeticholic acid also had an advantage (95.4%) in reducing aspartate aminotransferase (AST) levels. Considering lipid metabolic indicators, elafibranor (expSMD: 0.01; 95% CI: 0.00, 0.05; SUCRA: 100%), and obeticholic acid (expSMD: 0.48; 95% CI: 0.28,0.84; SUCRA: 75.6%) significantly reduced triglyceride (TG) levels compared with placebo; moreover, obeticholic acid, but not elafibranor, caused a serious increase in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and a decrease in high-density lipoprotein cholesterol (HDL-C) levels. Conclusions Novel metabolic targeted agents generally have better effects than natural plant drugs, especially obeticholic acid, and elafibranor. However, obeticholic acid showed serious adverse effects such as increasing LDL-C levels and decreasing HDL-C levels. Curcumin showed potential advantages for NAFLD but lacked statistical significance.

Milk thistle (Silybum marianum) is a medicinal plant from the Asteraceae family. Silymarin is the major constituent of milk thistle extract and is a mixture of some flavonolignans such as silybin, which is the most active component of silymarin. It is most commonly known for its hepatoprotective effect. 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 was mutagen in Salmonella typhimurium strains in the presence of metabolic enzymes. Silybin, silydianin, and silychristin were not cytotoxic and genotoxic at concentration of 100 μM. Silymarin 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 silymarin 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.

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 anti-metastatic 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. This review examines the recent studies and summarizes the mechanistic pathways and down-stream targets of silymarin in the therapy of gastrointestinal cancer.