Silymarin, a standardized extract of milk thistle fruits and seeds, contains at least 7 flavonolignans; silibin is considered the primary active ingredient. The primary phase metabolite, silibinin glucuronide, is metabolized and secreted in bile wherein concentrations are 100¥ concentrations in serum. Silibinin is water insoluble and not readily absorbed by intestines; however, milk thistle extracts can be combined with solubilizing substances to improve oral bioavailability. The mechanism of action is understood as an antioxidant free radical scavenging and an inhibition of lipid peroxidation in hepatocytes, peripheral blood, and several other body tissues, making it useful as a protectant for the liver. The multiple cellular effects of silibinin include various inhibitions of inflammatory mediators. In humans with nonalcoholic fatty liver disease, silibinin can decrease C-reactive protein, inflammatory cytokines, and indices of hepatic fibrosis.

Silibinin is considered a safe drug, with no deaths or life-threatening symptoms reported in humans. In veterinary medicine, applications include administration in toxicity cases, hepatic disease (eg, hepatitis, cirrhosis), or fatty liver disease. Not to be considered a sole treatment, silibinin is a useful adjunct to acute and chronic disease affecting liver function. There is limited evidence regarding silibinin pharmacokinetics in domestic small animals and large animal herbivores, so its use warrants further investigation.

Commentary
Silymarin and its major constituent silibinin have been used for the treatment of liver disease for thousands of years. In addition, it is undergoing research as a promising anticancer agent in various in vitro and in vivo cancer models (eg, skin, breast, lung, colon, bladder, prostate, kidney). Studies have also shown that silibinin may help lower cholesterol and increase good cholesterol in humans. Silibinin is an interesting example of how an ancient herb can translate into modern Western medicine.—Heather Troyer, DVM, DABVP, CVA

Global Commentary
Treatment of inflammatory liver disease can be a challenge. The basis of therapy lies in immunomodulation, usually with corticosteroids; however, recent evidence suggests that cyclosporine may be more effective. Ursodeoxycholic acid, a synthetic bile salt, is also useful in treating many liver diseases. Because most liver damage is associated with oxidative damage within the hepatocyte, adjunctive use of antioxidants has long been recommended. This includes S-adenosylmethionine (SAMe) and vitamin E. This research suggested that the silibinin in milk thistle, a folk remedy to treat liver disease in humans, has strong antioxidant properties. As the authors suggested, however, controlled studies of its efficacy in veterinary medicine are lacking and sorely needed.—Colin F. Burrows, BVetMed, PhD, Hon FRCVS, DACVIM

Source
Milk thistle and its derivative compounds: A review of opportunities for treatment of liver disease. Hackett ES, Twedt DC, Gustafson DL. JVIM 27:10-16, 2013.