Calluna vulgaris extract modulates NF-κB/ERK signaling pathway and matrix metalloproteinase expression in SKH-1 hairless mice skin exposed to ultraviolet B irradiation.
Photochemoprevention with natural products represents a new concept in the attempt to reduce the occurrence of skin cancer. However, the molecular mechanisms caused by ultraviolet light exposure remain still unclear. The aim of the study was to assess the mechanisms involved in the action of a Calluna vulgaris (Cv) extract, administered in single or multiple doses (10 consecutive days), on UVB-induced skin damage in SKH-1 hairless mice. The extract was topically applied 30 min before each UVB exposure in two doses (2.5 and 4 mg total polyphenolic content/40 μl/cm(2)). At 24 hours after the last treatment, total mitogen-activated protein kinase (p44/42MAPkinase, ERK 1/2), nuclear factor-κB (phospho-NF-κB p65), matrix metalloproteinases (MMP-2, MMP-9) and metalloproteinase inhibitor 1 (TIMP-1) levels were measured in skin using enzyme-linked immunosorbent assay (ELISA). MMP-2 and -9 activities were additionally evaluated by zymography. One topical application of Cv extract reduced the secretion (p<0.004) and inhibited MMP-9 activity UVB-mediated (54% inhibition) via inhibition of NF-κB activation (68% inhibition). In multiple UVB exposures, both doses of Cv extract induced the increase of ERK 1/2 level in correlation with activation of NF-κB and reduced the secretion (p<0.04) and activation of MMP-9 (62% inhibition). Pretreatment with Cv diminished the MMP-2 protein secretion only in one dose UVB-irradiated group (p<0.0001) and decreased TIMP-1 level (p<0.001). These results demonstrated the dual behavior of Cv extract in skin protection against single versus multiple doses of UVB irradiation.
Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania. adrianafilip33@yahoo.com
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D000287:Administration, Topical; D000818:Animals; D029795:Calluna; D004890:Erythema / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006965:Hyperplasia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D016328:NF-kappa B / Q000378:metabolism; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000008:administration & dosage*; D020011:Protective Agents / Q000008:administration & dosage*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
D016328:NF-kappa B; D010936:Plant Extracts; D020011:Protective Agents; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse