Philips Neena, Conte Jennifer, Chen Yu-Jun, Natrajan Prashanti, Taw May, Keller Thomas, Givant Joshua, Tuason Marvin, Dulaj Luiji, Leonardi Donna, Gonzalez Salvador
School of Natural Sciences, University College, Fairleigh Dickinson University, H-DH4-03, 1000 River Road, Teaneck, NJ 07666, USA.
Arch Dermatol Res. 2009 Aug;301(7):487-95. doi: 10.1007/s00403-009-0950-x. Epub 2009 Apr 17.
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.
赋予组织结构完整性的细胞外基质（ECM）在皮肤老化/光老化和癌症过程中会通过基质金属蛋白酶（MMP）表达/活性增加、基质金属蛋白酶组织抑制剂（TIMP）受抑制或胶原蛋白合成受抑制而发生重塑。转化生长因子-β（TGF-β）是ECM的主要调节因子，在老化/光老化过程中受到抑制，而在致癌过程中受到刺激。白藓提取物具有通过其抗氧化、抗炎和光保护特性来抵消这些改变的潜力。本研究的目的是确定白藓对（a）直接抑制MMP-1、2、3和9的活性，（b）在未照射或紫外线（UV）照射的成纤维细胞中抑制MMP-2并刺激TIMP、纤维状胶原蛋白和TGF-β，以及（c）在黑色素瘤细胞中抑制MMP和TGF-β并刺激TIMP的功效。为此，我们研究了白藓（0-1%）对MMP活性的直接影响，以及它对（1）真皮成纤维细胞和黑色素瘤细胞中MMP和TIMP的表达（蛋白质和/或转录水平）、（2）未照射、UVA（2.5 J/cm2）或UVB（2.5 mJ/cm2）照射的成纤维细胞和黑色素瘤细胞中TGF-β的表达，以及（3）未照射或UV照射的成纤维细胞中I型、III型和V型胶原蛋白表达的影响。白藓直接抑制成纤维细胞和黑色素瘤细胞中MMP的活性以及MMP的表达，同时刺激这些细胞中TIMP的表达。白藓刺激未照射的成纤维细胞中I型、III型和V型胶原蛋白的表达，以及UV照射的成纤维细胞中I型和V型胶原蛋白的表达。白藓对未照射或UV照射的成纤维细胞中TGF-β的表达具有主要的刺激作用，而在黑色素瘤细胞中抑制TGF-β的表达。白藓的作用在很大程度上与抗坏血酸相似。白藓通过抑制ECM蛋白水解酶和刺激结构性ECM胶原蛋白，对ECM表现出双重保护作用。白藓对成纤维细胞和黑色素瘤细胞的作用可能部分是通过其对TGF-β表达的细胞特异性调节，部分是通过其抗氧化特性。口服或局部应用白藓可能对皮肤健康有益，有助于预防或治疗皮肤老化和癌症。
