Silymarin consists of a family of flavonoids (silybin, isosilybin, silychristin, silydianin and taxifoline) commonly found in the dried fruit of the milk thistle plant Silybum marianum. Although silymarin's role as an antioxidant and hepatoprotective agent is well known, its role as an anticancer agent has begun to emerge. Extensive research within the last decade has shown that silymarin can suppress the proliferation of a variety of tumor cells (e.g., prostate, breast, ovary, colon, lung, bladder); this is accomplished through cell cycle arrest at the G1/S-phase, induction of cyclin-dependent kinase inhibitors (such as p15, p21 and p27), down-regulation of anti-apoptotic gene products (e.g., Bcl-2 and Bcl-xL), inhibition of cell-survival kinases (AKT, PKC and MAPK) and inhibition of inflammatory transcription factors (e.g., NF-kappaB). Silymarin can also down-regulate gene products involved in the proliferation of tumor cells (cyclin D1, EGFR, COX-2, TGF-beta, IGF-IR), invasion (MMP-9), angiogenesis (VEGF) and metastasis (adhesion molecules). The antiinflammatory effects of silymarin are mediated through suppression of NF-kappaB-regulated gene products, including COX-2, LOX, inducible iNOS, TNF and IL-1. Numerous studies have indicated that silymarin is a chemopreventive agent in vivo against a variety of carcinogens/tumor promoters, including UV light, 7,12-dimethylbenz(a)anthracene (DMBA), phorbol 12-myristate 13-acetate (PMA) and others. Silymarin has also been shown to sensitize tumors to chemotherapeutic agents through down-regulation of the MDR protein and other mechanisms. It binds to both estrogen and androgen receptors, and down-regulates PSA. In addition to its chemopreventive effects, silymarin exhibits antitumor activity against human tumors (e.g., prostate and ovary) in rodents. Various clinical trials have indicated that silymarin is bioavailable and pharmacologically safe. Studies are now in progress to demonstrate the clinical efficacy of silymarin against various cancers.

Anticancer potential of silymarin: from bench to bed side.

Extracts of milk thistle have been recognized for centuries as "liver tonics" and are well-known to prevent or reverse hepatotoxicity of reactive drug metabolites or naturally occurring toxins. Milk thistle extracts are now under intense study in the experimental therapeutics of cancer for chemoprevention, treatment, and amelioration of chemotherapy side effects. Precision in nomenclature, however, has lagged behind this progress. The crude commercial product of milk thistle is termed silymarin, a complex of at least 7 flavonolignans and 1 flavonoid that comprises 65% to 80% of milk thistle extract. From silymarin is derived silibinin, a semipurified fraction once thought to be a single compound but now recognized as a 1:1 mixture of 2 diastereoisomers, silybin A and silybin B. The distinction between silymarin and silibinin is not only important to understanding the historical literature, but thorough characterization and use of chemically defined mixtures in preclinical and clinical studies are essential to the progress of these botanical compounds as human therapeutics. As a result, we urge clinicians and preclinical investigators alike to exercise rigor in nomenclature and use pure compounds or precisely defined chemical mixtures in subsequent studies. Herein, we provide a guide to the proper nomenclature and composition of milk thistle extracts and discuss the known pharmacokinetic studies of these botanical medicines. The drug-interaction potential of these extracts appears to be quite low, and in fact, silibinin appears to synergize with the antitumor effects of some commonly used chemotherapeutics. However, some precautions are advised as high-dose, phase II studies are conducted.

https://journals.sagepub.com/doi/pdf/10.1177/1534735407301825

Milk Thistle Nomenclature: Why It Matters in Cancer Research and Pharmacokinetic Studies

Inhibition of T-Cell Inflammatory Cytokines, Hepatocyte NF-κB Signaling, and HCV Infection by Standardized Silymarin

Solubility and solution thermodynamic properties of quercetin and quercetin dihydrate in subcritical water

Medicinal plants have been traditionally used for treating liver diseases since centuries. Several leads from plant sources have been found as potential hepatoprotective agents with diverse chemical structures. Although, a big list of hepatoprotective phytomolecules was reported in the scientific literature, only a few were potent against various types of liver damages. Of which, silymarin, andrographolide, neoandrographolide, curcumin, picroside, kutkoside, phyllanthin, hypophyllanthin, and glycyrrhizin have largely attracted the scientific community. This review focuses discussion on the chemistry, biological activity, mode of action, toxicity, and future prospects of these leads.

http://staff.cimap.res.in/PublicationFiles/Medicinal_Research_Reviews.pdf

Recent advances in plant hepatoprotectives: A chemical and biological profile of some important leads

Herbal medicine is used worldwide either as a sole treatment method or as part of a comprehensive treatment plan alongside orthodox methods of diagnosis and treatment. A survey reported that, in the USA, nearly one-sixth of women took at least one herbal product in 2000. Despite their widespread use, numerous reports show that the herbal products available to consumers are of variable quality. This disparity in quality of herbal preparations can be attributed to the fact that their production is complicated. To produce high-quality herbal products, attention must be paid to, among others, phytochemical variations due to plant breed, organ specificity, stages of growth, cultivation parameters, contamination by microbial and chemical agents, substitution, adulteration with synthetic drugs, heavy metal contamination, storage and extraction. This review focuses on organ specificity, seasonal variations, the effect of drying and storage, and the extraction of phytochemical constituents. Special emphasis is placed on the four most frequently used herbal products in the USA: echinacea, Ginkgo biloba , ginseng and St John's Wort.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S1479262105000341

Pre- and post-harvest processing of medicinal plants

Hot water is attracting attention as an extraction solvent in the recovery of compounds from plant material as the search for milder and "greener" solvents intensifies. The use of hot water as an extraction solvent for milk thistle at temperatures above 100 degrees C was explored. The maximum extraction yield of each of the silymarin compounds and taxifolin did not increase with temperature, most likely because significant compound degradation occurred. However, the time required for the yields of the compounds to reach their maxima was reduced from 200 to 55 min when the extraction temperature was increased from 100 to 140 degrees C. Severe degradation of unprotected (plant matrix not present) silymarin compounds was observed and first-order degradation kinetics were obtained at 140 degrees C.

Silymarin extraction from milk thistle using hot water.

In an effort to increase revenues from a given feedstock, valuable co-products could be extracted prior to biochemical or thermochemical conversion with subcritical water. Although subcritical water shows significant promise in replacing organic solvents as an extraction solvent, compound degradation has been observed at elevated extraction temperatures. First order thermal degradation kinetics from a model system, silymarin extracted from Silybum marianum, in water at pH 5.1 and 100, 120, 140, and 160 °C were investigated. Water pressure was maintained slightly above its vapor pressure. Silymarin is a mixture of taxifolin, silichristin, silidianin, silibinin, and isosilibinin. The degradation rate constants ranged from 0.0104 min−1 at 100 °C for silichristin to a maximum of 0.0840 min−1 at 160 °C for silybin B. Half-lives, calculated from the rate constants, ranged from a low of 6.2 min at 160 °C to a high of 58.3 min at 100 °C, both for silichristin. The respective activation energies for the compounds ranged from 37.2 kJ/gmole for silidianin to 45.2 kJ/gmole for silichristin. In extracting the silymarin with pure ethanol at 140 °C, no degradation was observed. However, when extracting with ethanol/water mixtures at and 140 °C, degradation increased exponentially as the concentration of water increased.

/pdf/extraction-of-co-products-from-biomass-example-of-thermal-4mmo98kgyb.pdf

Lijun Duan

Papers

Pre- and post-harvest processing of medicinal plants

Silymarin extraction from milk thistle using hot water.

Extraction of Co-Products from Biomass: Example of Thermal Degradation of Silymarin Compounds in Subcritical Water