Mechanism of the Antioxidant Action of Silybin and 2,3-Dehydrosilybin Flavonolignans: A Joint Experimental and Theoretical Study

Abstract

Flavonolignans from silymarin, the standardized plant extract obtained from thistle, exhibit various antioxidant activities, which correlate with the other biological and therapeutic properties of that extract. To highlight the mode of action of flavonolignans as free radical scavengers and antioxidants, 10 flavonolignans, selectively methylated at different positions, were tested in vitro for their capacity to scavenge radicals (DPPH and superoxide) and to inhibit the lipid peroxidation induced on microsome membranes. The results are rationalized on the basis of (i) the oxidation potentials experimentally obtained by cyclic voltammetry and (ii) the theoretical redox properties obtained by quantum-chemical calculations (using a polarizable continuum model (PCM)-density functional theory (DFT) approach) of the ionization potentials and the O-H bond dissociation enthalpies (BDEs) of each OH group of the 10 compounds. We clearly establish the importance of the 3-OH and 20-OH groups as H donors, in the presence of the 2,3 double bond and the catechol moiety in the E-ring, respectively. For silybin derivatives (i.e., in the absence of the 2,3 double bond), secondary mechanisms (i.e., electron transfer (ET) mechanism and adduct formation with radicals) could become more important (or predominant) as the active sites for H atom transfer (HAT) mechanism are much less effective (high BDEs).

Hepatoprotective effect of silymarin

“…In previous studies, the inherent hepatoprotective and antioxidant activity of silymarin was shown to be caused by its control of free radicals (FR), which are produced by the hepatic metabolism of toxic substances such as Et-OH, acetaminophen (Paracetamol), or carbon tetrachloride. The FR damage cellular membranes and cause lipoperoxidation (LPO) [19] . The cytoprotective effect in liver is also caused by the inhibition of the cyclooxygenase cycle, leukotrienes, and the production of FR in Kupffer cells in mice.…”

Oxidative stress modulation in hepatitis C virus infected cells

“…The antioxidant effects of silibinin have been showed in several cell studies. Silibinin is classified as an antioxidant compound because it blocks radical formation, binds many radical species (scavenger), interferes with lipid peroxidation mechanisms of membranes, and then increases the intracellular content of scavengers [60] . Gomez et al [61] in 2010 investigated the role of Viusid as an antioxidant and an immunomodulator in nonresponder HCV infected patients.…”

Importance of Proton-Coupled Electron Transfer from Natural Phenolic Compounds in Superoxide Scavenging

“…[20][21][22] However, the theoretical aspects of the free radical scavenging mechanism of phenolic antioxidants remains an important subject for the accurate prediction of free radical scavenging activity in physiological environments. [23][24][25][26][27] As a free radical, O 2 ·− is an important biological intermediate in living cells, 28) and is overproduced in tissues subjected to chronic infection and inflammation. 29) O 2 ·− causes oxidative DNA damage in living tissues under inflammatory conditions.…”