Beneficial regulation of matrixmetalloproteinases and their inhibitors, fibrillar collagens and transforming growth factor-beta by Polypodium leucotomos, directly or in dermal fibroblasts, ultraviolet radiated fibroblasts, and melanoma cells.
The extracellular matrix (ECM) that gives tissue its structural integrity is remodeled in skin aging/photoaging and cancer via the increased expression/activities of matrixmetalloproteinases (MMP), inhibition of the tissue inhibitors of matrix metalloproteinases (TIMP), or inhibition of collagen synthesis. Transforming growth factor-beta (TGF-beta), a predominant regulator of the ECM, is inhibited in aging/photoaging and stimulated in carcinogenesis. P. leucotomos (fern) extract has potential to counteract these alterations via its antioxidant, anti-inflammatory and photoprotective properties. The goal of this research was to determine the efficacy of P. leucotomos to (a) directly inhibit MMP-1, 2, 3, and 9 activities, (b) inhibit MMP-2, and stimulate TIMPs, fibrillar collagens and TGF-beta in non-irradiated or ultraviolet (UV) radiated fibroblasts, and (c) inhibit MMPs and TGF-beta, and stimulate TIMPs in melanoma cells. To this purpose, we examined the direct effect of P. leucotomos (0-1%) on MMPs' activities, and its effects on the expression (protein and/or transcription levels) of (1) MMPs and TIMPs in dermal fibroblasts, and melanoma cells, (2) TGF-beta in non-irradiated, UVA (2.5 J/cm2) or UVB (2.5 mJ/cm2) irradiated fibroblasts, and melanoma cells, and (3) types I, III, and V collagen in non-irradiated or UV irradiated fibroblasts. P. leucotomos directly inhibited the activities of MMPs as well as the expression of MMPs in fibroblasts, and melanoma cells while stimulating the expression of TIMPs in these cells. P. leucotomos stimulated types I, III, and V collagen in non-irradiated fibroblasts, and types I and V collagen in UV radiated fibroblasts. P. leucotomos had predominant stimulatory effects on TGF-beta expression in non-irradiated or UV radiated fibroblasts, and inhibited TGF-beta expression in melanoma cells. The effects of P. leucotomos were largely similar to that of ascorbic acid. P. leucotomos demonstrated dual protective effects on the ECM via its inhibition of the ECM proteolytic enzymes and the stimulation of the structural ECM collagens. The effects of P. leucotomos on fibroblasts and melanoma cells may be partly via its cell-specific regulation of TGF-beta expression and partly via its antioxidant property. The intake or topical application of P. leucotomos may be beneficial to skin health, in aging and cancer prevention or treatment.
School of Natural Sciences, University College, Fairleigh Dickinson University, H-DH4-03, 1000 River Road, Teaneck, NJ 07666, USA. nphilips@fdu.edu
Neena
N
Philips
Jennifer
J
Conte
Yu-Jun
YJ
Chen
Prashanti
P
Natrajan
May
M
Taw
Thomas
T
Keller
Joshua
J
Givant
Marvin
M
Tuason
Luiji
L
Dulaj
Donna
D
Leonardi
Salvador
S
Gonzalez
D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid; D002478:Cells, Cultured; D019610:Cytoprotection; D005109:Extracellular Matrix / Q000378:metabolism; D024022:Fibrillar Collagens / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D007231:Infant, Newborn; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D032494:Polypodium; D015595:Skin Aging / Q000187:drug effects; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
D000975:Antioxidants; D024022:Fibrillar Collagens; D010936:Plant Extracts; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D020782:Matrix Metalloproteinases; D001205:Ascorbic Acid