Inhibition of cyclooxygenase-2 and inducible nitric oxide synthase by silymarin in proliferating mesenchymal stem cells: comparison with glutathione modifiers

Abstract

Silymarin, a mixture of flavonolignans, is extracted from milk thistle (Silybum marianum) and has a strong antioxidant activity and exhibits anticarcinogenic, anti-inflammatory, and cytoprotective effects. In this study we attempted to determine whether silymarin and the glutathione modifiers, buthionine sulfoxamine (BSO) and N-acetylcysteine (NAC), are involved in regulation of cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) in proliferating mesenchymal stem cells (MSCs). Cellular glutathione was manipulated during a 14-day culture using BSO, NAC and silymarin. At intervals of 2, 7 and 14 days, cells were collected and COX-2 and iNOS levels were measured. In parallel, generation of cellular H(2)O(2) and glutathione were measured. Supplementation of the culture media with BSO caused a dose-dependent decrease in MSC proliferation, whereas NAC or silymarin elevated the proliferation (p < 0.05). Treatment of MSC with NAC or silymarin caused a significant decrease in COX-2 levels. However, COX-2 levels in cells treated with high levels of NAC (1.0 mM) were significantly lower than those in MSCs treated with high levels of silymarin (100 μM). BSO (1.0 and 5.0 μM) caused a significant increase in COX-2 on days 2, 7 and 14. BSO caused a significant increase in iNOS, whereas NAC or silymarin decreased cellular iNOS. Overall result show that glutathione, iNOS and COX-2 in proliferating MSCs are affected by silymarin treatment. It appears that glutathione is the main target of silymarin, and in consequence iNOS and COX-2 are affected in response to silymarin treatment.

Study the Effect of Silymarin and Vitamin C in Skin Aging Induced by UVB Rays on the Mice Skin Redox System

“…Silymarin can grow there easily to use in skin protecting products. The photo aging and reduce wrinkles, dryness; it can also stimulate the proliferation of human keratinocytes, induce skin moisture [33][34][35]. Silymarin has a protective effect on cells against H2O2 as an antiaging effect [48] and increases total antioxidant capacity of cell extract [49].…”

“…Silymarin is a safe plant for treatment of diseases that isn't toxic even at higher physiological doses [32]. It also decreases the level of COX-2 that relates to carcinogenesis [33]. minimum effective dose of this plant can be used for maximum protective effect [34].…”

Candesartan modulates the antioxidant effect of silymarin against CCl4-induced liver injury in rats

“…This effect is explained by the ability of SIL to inhibit expression of NOS and cause elevation of GSH level. 26 Of interest, CAN administration corrected the levels of serum aminotransferases (ALT & AST) and GGT as compared to that of fibrotic rats. Simultaneously, CAN attenuated the hepatic fibrosis in treated rats.…”

Silymarin Improves Vascular Function of Aged Ovariectomized Rats

“…Increased cardiovascular mortality of aging can also be explained by vascular inflammation and oxidative stress (Gencel et al ., ). Cyclooxygenase‐2 and the inducible form of NOS are inducible in inflammation, modulated by SM in proliferating mesenchymal stem cells (Ahmadi‐Ashtiani et al ., ) and by silibinin in tumorigenic mouse lung epithelial cells together with proinflammatory cytokine tumor necrosis factor‐α (Tyagi et al ., ). These authors demonstrated that anti‐inflammatory activity of silibinin is the result of a possible inhibition of the signal transducers and activators (STATs) and nuclear factor‐κB inflammatory pathways in the cells.…”