Metabolism, Transport and Drug–Drug Interactions of Silymarin

Abstract

Silymarin, the extract of milk thistle, and its major active flavonolignan silybin, are common products widely used in the phytotherapy of liver diseases. They also have promising effects in protecting the pancreas, kidney, myocardium, and the central nervous system. However, inconsistent results are noted in the different clinical studies due to the low bioavailability of silymarin. Extensive studies were conducted to explore the metabolism and transport of silymarin/silybin as well as the impact of its consumption on the pharmacokinetics of other clinical drugs. Here, we aimed to summarize and highlight the current knowledge of the metabolism and transport of silymarin. It was concluded that the major efflux transporters of silybin are multidrug resistance-associated protein (MRP2) and breast cancer resistance protein (BCRP) based on results from the transporter-overexpressing cell lines and MRP2-deficient (TR−) rats. Nevertheless, compounds that inhibit the efflux transporters MRP2 and BCRP can enhance the absorption and activity of silybin. Although silymarin does inhibit certain drug-metabolizing enzymes and drug transporters, such effects are unlikely to manifest in clinical settings. Overall, silymarin is a safe and well-tolerated phytomedicine.

Identification of a repurposed drug as an inhibitor of Spike protein of human coronavirus SARS-CoV-2 by computational methods

“…Silymarin is a phytomedicine extracted from milk thistle seeds. Along with its hepatoprotective effects, it is also known for anti-oxidant, antiviral, anti-inflammatory, and anti-fibrotic activities (Soleimani et al 2019 ; Xie et al 2019 ). It exhibits interactions with both ‘Site 1’ and ‘Site 2’ residues, thereby inhibiting His34 and Lys343 of ACE2 (figure 4 G).…”

Effects of silymarin supplementation during transition and lactation on reproductive performance, milk composition and haematological parameters in sows

“…However, in other two studies in sows, the serum concentrations of PRL were unaffected in response to dietary inclusion of silymarin, which was believed to be associated with inadequate inclusion of silymarin in diets (Farmer, Lapointe, & Cormier, 2017; Loisel, Quesnel, & Farmer, 2013). Only 23%–47% of oral silymarin can be finally absorbed, and its bioavailability is very low (Xie, Zhang, Zhang, & Yuan, 2019). Consequently, it is worth investigating whether increasing the dose of silymarin in diets leads to improved outcomes.…”

Identification of a Potent Inhibitor Targeting the Spike Protein of Pandemic Human Coronavirus, SARS-CoV-2 by Computational Methods

“…Silymarin is a phytomedicine extracted from milk thistle seeds. Along with its hepatoprotective effects, it is also known for anti-oxidant, anti-viral, anti-inflammatory and anti-fibrotic activities (40,41). It exhibits interactions with both 'Site 1' and 'Site 2' residues thereby inhibiting His34 and Lys343 of ACE2 ( Figure 4G).…”