Treatment of silymarin, a plant flavonoid, prevents ultraviolet light-induced immune suppression and oxidative stress in mouse skin.
It is well documented that ultraviolet (UV) light-induced immune suppression and oxidative stress play an important role in the induction of skin cancers. Earlier, we have shown that topical treatment of silymarin, a plant flavonoid from milk thistle (Silybum marianum L. Gaertn.), to mouse skin prevents photocarcinogenesis, but the preventive mechanism of photocarcinogenesis in vivo animal system by silymarin is not well defined and understood. To define the mechanism of prevention, we employed immunostaining, analytical assays and ELISA which revealed that topical treatment of silymarin (1 mg/cm2 skin area) to C3H/HeN mice inhibits UVB (90 mJ/cm2)-induced suppression of contact hypersensitivity (CHS) response to contact sensitizer dinitrofluorobenzene. Prevention of UVB-induced suppression of CHS by silymarin was found to be associated with the inhibition of infiltrating leukocytes, particularly CD11b+ cell type, and myeloperoxidase activity (50-71%). Silymarin treatment also resulted in significant reduction of UVB-induced immunosuppressive cytokine interleukin-10 producing cells and its production (58-72%, p<0.001). Topical treatment of silymarin also resulted in significant reduction of the number of UVB-induced H2O2 producing cells and inducible nitric oxide synthase expressing cells concomitant with decrease in H2O2 (58-65%, p<0.001) and nitric oxide (65-68%, p<0.001) production. Together, these data suggest that prevention of UVB-induced immuno-suppression and oxidative stress by silymarin may be associated with the prevention of photocarcinogenesis in mice. The data obtained from this study also suggest: i) phase-I clinical trial of silymarin in high skin cancer risk human population and ii) development of sunscreen containing silymarin as an antioxidant (chemopreventive agent) or silymarin can be supplemented in skin care products.
Katiyar
Santosh K
SK
Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294-0019, USA. skatiyar@uab.edu
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D039481:CD11b Antigen / Q000378:metabolism; D003877:Dermatitis, Contact / Q000188:drug therapy* / Q000276:immunology; D004139:Dinitrofluorobenzene / Q000633:toxicity; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D044950:Flavanones; D005419:Flavonoids / Q000627:therapeutic use; D006861:Hydrogen Peroxide / Q000378:metabolism; D007108:Immune Tolerance / Q000187:drug effects* / Q000528:radiation effects; D007124:Immunoenzyme Techniques; D016753:Interleukin-10 / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000528:radiation effects; D051379:Mice; D008809:Mice, Inbred C3H; D020944:Silybum marianum / Q000737:chemistry; D020556:Neutrophil Infiltration; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects; D009195:Peroxidase / Q000378:metabolism; D010946:Plants, Medicinal; D020011:Protective Agents / Q000627:therapeutic use*; D012838:Silymarin / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects* / Q000528:radiation effects; D013473:Sunscreening Agents; D014466:Ultraviolet Rays
D000975:Antioxidants; D039481:CD11b Antigen; D044950:Flavanones; D005419:Flavonoids; D020011:Protective Agents; D012838:Silymarin; D013473:Sunscreening Agents; D016753:Interleukin-10; D006861:Hydrogen Peroxide; D004139:Dinitrofluorobenzene; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C028610:flavanone