Treatment Of Photoaged Skin Research Articles

The flavonoids apigenin and luteolin suppress ultraviolet A-induced matrix metalloproteinase-1 expression via MAPKs and AP-1-dependent signaling in HaCaT cells

Ultraviolet (UV) irradiation causes major changes in skin connective tissues as a result of the degradation of collagen, a major structural component of the extracellular matrix. This process is likely mediated by matrix metalloproteinases (MMPs). Such changes in collagenous skin tissues have been suggested to be causes of cutaneous aging and skin cancer. We investigated the protective effects of apigenin and luteolin on immortalized human keratinocytes (HaCaT) against UVA damage. We then explored the inhibitory effects of apigenin and luteolin on UVA-induced MMP-1 and investigated the molecular mechanism underlying those effects. HaCaT cells were treated with apigenin and luteolin for the indicated times followed by irradiation with UVA. Those effects were assessed by semi-quantitative PCR, Western blotting and enzymic activity assays. These two compounds, at concentrations of 1-5μM, increased the viability of, and inhibited ROS production in HaCaT cells exposed to UVA irradiation. Pre-treatment of HaCaT cells with apigenin and luteolin also inhibited UVA-induced production of the collagenases MMP-1. They also suppressed UVA-induced expression of c-Jun and c-Fos and the phosphorylation of three MAP kinases, upstream modulators of AP-1. Furthermore, the same two flavonoids decreased the UVA-induced influx of Ca(2+) into HaCaT cells and the phosphorylation of Ca(2+)/calmodulin-dependent kinases (CaMKs). The results indicate that apigenin and luteolin inhibited UVA-induced collagenolytic MMP-1 production by interfering with Ca(2+)-dependent MAPKs and AP-1 signaling. They may thus be potentially useful in the prevention and treatment of skin photoaging.

Glycolic acid peels and effective home care products rejuvenate skin and complement the benefits of injectable fillers and botulinum toxin type A in the treatment of photoaged skin

Glycolic acid peels and effective home care products rejuvenate skin and complement the benefits of injectable fillers and botulinum toxin type A in the treatment of photoaged skin

Radix clematidis extract inhibits UVB-induced MMP expression by suppressing the NF-κB pathway in human dermal fibroblasts

Ultraviolet (UV)B irradiation induces the production of matrix metalloproteinases (MMPs), which are responsible for the degradation of collagenous extracellular matrix in connective tissues, causing skin photoaging. Although Radix clematidis is commonly used in Chinese medicine for the treatment of arthralgia, the anti-skin photoaging effects of Radix clematidis have not yet been reported. In the present study, we investigated the inhibitory effects of Radix clematidis extract (RCE) on MMP-1 and -3 expression of human dermal fibroblast cells via various in vitro experiments and elucidated the pathways of inhibition. Western blot analysis and real-time PCR revealed RCE inhibited UVB-induced MMP-1 and -3 expressions in a dose-dependent manner. UVB strongly activated nuclear factor-kappaB (NF-kappaB) activity, which was determined by IkappaBalpha degradation, nuclear localization of p50 and p65 subunit, and NF-kappaB binding activity. However, UVB-induced NF-kappaB activation was completely blocked by RCE pretreatment. These findings suggest that RCE prevents UVB-induced MMP expression through inhibition of NF-kappaB activation. In conclusion, RCE is a potential agent for the prevention and treatment of skin photoaging.

Cordycepin inhibits UVB-induced matrix metalloproteinase expression by suppressing the NF--κB pathway in human dermal fibroblasts

Cordycepin (3-deoxyadenosine) has been shown to exhibit many pharmacological activities, including anti-cancer, anti-inflammatory, and anti-infection activities. However, the anti-skin photoaging effects of cordycepin have not yet been reported. In the present study, we investigated the inhibitory effects of cordycepin on matrix metalloproteinase-1 (MMP-1) and -3 expressions of the human dermal fibroblast cells. Western blot analysis and real-time PCR revealed cordycepin inhibited UVB-induced MMP-1 and -3 expressions in a dose-dependent manner. UVB strongly activated NF-kappaB activity, which was determined by IkappaBalpha degradation, nuclear localization of p50 and p65 subunit, and NF-kappaB binding activity. However, UVB-induced NF-kappaB activation and MMP expression were completely blocked by cordycepin pretreatment. These findings suggest that cordycepin could prevent UVB-induced MMPs expressions through inhibition of NF-kappaB activation. In conclusion, cordycepin might be used as a potential agent for the prevention and treatment of skin photoaging.

A study to determine the efficacy of a novel handheld light‐emitting diode device in the treatment of photoaged skin

The use of visible or near-infrared spectral light alone for the purpose of skin rejuvenation has been previously reported in the literature. These devices use large arrays of diodes to deliver light to the skin. In this study, a novel method of light-emitting diode (LED) photo rejuvenation incorporating a combination of these wavelengths delivered from a small handheld unit is proposed. Twenty-two subjects with facial rhytides received eight light therapy treatments over a course of 4 weeks, using the Omnilux handheld LED system. Assessment of global skin grading was evaluated at weeks 6, 9, and 12 by a dermatologist. Additional outcome measures included assessments of clinical photography and patient satisfaction scores. Seventy-four percent of the subjects reported a visible improvement in fine lines and wrinkles at 8 weeks posttreatment. Combination red and near-infrared LED therapy delivered from a small portable handheld unit represents an effective and acceptable method of photo rejuvenation. Further studies to optimize the parameters of treatment are required.

Application of a New Intense Pulsed Light Device in the Treatment of Photoaging Skin in Asian Patients

BACKGROUND Intense pulsed light (IPL) technology has long been used in the treatment of photoaging skin. OBJECTIVE To evaluate the efficacy and safety of a new IPL device in the treatment of photoaging skin in Asian patients. METHODS One hundred fifty-two Chinese women with photoaging skin were enrolled in this open-labeled study. Subjects received four IPL treatments at 3- to 4-week intervals. Changes of photoaging were evaluated using a global evaluation, an overall self-assessment, a Mexameter, and a Corneometer. RESULTS One hundred thirty-nine of 152 patients (91.44%) experienced a score decrease of 3 or 2 grades, according to the dermatologist. One hundred thirty-six of 152 patients (89.47%) rated their overall improvement as excellent or good. The mean skin melanin index (MI) and erythema index values deceased with each session. MI on forehead and EI on cheilion decreased most significantly. Adverse effects were limited to mild pain and transient erythema. CONCLUSION IPL treatment is a safe and effective method for photoaging skin in Asian patients. Adverse effects were minimal and acceptable.

Application of a New Intense Pulsed Light Device in the Treatment of Photoaging Skin in Asian Patients

Intense pulsed light (IPL) technology has long been used in the treatment of photoaging skin. To evaluate the efficacy and safety of a new IPL device in the treatment of photoaging skin in Asian patients. One hundred fifty-two Chinese women with photoaging skin were enrolled in this open-labeled study. Subjects received four IPL treatments at 3- to 4-week intervals. Changes of photoaging were evaluated using a global evaluation, an overall self-assessment, a Mexameter, and a Corneometer. One hundred thirty-nine of 152 patients (91.44%) experienced a score decrease of 3 or 2 grades, according to the dermatologist. One hundred thirty-six of 152 patients (89.47%) rated their overall improvement as excellent or good. The mean skin melanin index (MI) and erythema index values deceased with each session. MI on forehead and EI on cheilion decreased most significantly. Adverse effects were limited to mild pain and transient erythema. IPL treatment is a safe and effective method for photoaging skin in Asian patients. Adverse effects were minimal and acceptable.

Fucoidan Inhibits UVB-Induced MMP-1 Expression in Human Skin Fibroblasts

Ultraviolet (UV)B irradiation induces the production of matrix metalloproteinases (MMPs) by activating cellular signaling transduction pathways, which are responsible for the degradation or synthesis inhibition of collagenous extracellular matrix in connective tissues, causing skin photoaging. Using the human skin fibroblast (HS68) cell line in the present study, we investigated the inhibitory effects of fucoidan on MMP-1 expression by various in vitro experiments and elucidated the pathways of inhibition. Pretreatment with fucoidan inhibited UVB-induced MMP-1 expression in a dose-dependent manner. Extracellular signal regulated kinase (ERK) activation was markedly inhibited by treatment with fucoidan, though JNK activation was very slightly affected by fucoidan. We also found that fucoidan pretreatment significantly reduced MMP-1 mRNA expression in comparison with UVB irradiation only. In conclusion, our results demonstrate that fucoidan can mainly inhibit UVB-induced MMP-1 expression by inhibiting the ERK pathways. Therefore, fucoidan might be used as a potential agent for the prevention and treatment of skin photoaging.

(−)Epigallocatechin gallate hampers collagen destruction and collagenase activation in ultraviolet-B-irradiated human dermal fibroblasts: Involvement of mitogen-activated protein kinase

Ultraviolet (UV) irradiation leads to distinct changes in skin connective tissues by degradation of collagen, which is a major structural component in the extracellular matrix most likely mediated by matrix metalloproteinases (MMP), collagenases. These changes in collagenous skin tissues have been suggested to be causes of the skin wrinkling observed in premature aging of the skin. This study mimicked the action of environmental ultraviolet on skin and investigated whether (−)epigallocatechin gallate (EGCG), a bioactive catechin component of green tea, mechanistically inhibited activation of MMP-1, MMP-8, and MMP-13 and destruction of collagen in UV-B irradiated human dermal fibroblasts by modulating cellular signaling pathways. Cell viability was moderately decreased by ⩾30% in human dermal fibroblasts treated with 100 mJ/cm 2 UV-B, accompanying a substantial generation of reactive oxygen species evidenced by DCF staining. Western blot analysis and immunocytochemical staining revealed that EGCG markedly suppressed collagen degradation enhanced in UV-B-exposed human dermal fibroblast. Pre-treatment of fibroblasts with EGCG also inhibited UV-B-induced production of collagenases, MMP-1, MMP-8 and MMP-13, in a dose-dependent manner. In addition, EGCG rapidly and substantially hampered UV-B irradiation-induced activation of ASK-1 and phosphorylation of MAPK, JNK, p38 MAPK, and ERK1/2, in dermal fibroblasts. These results demonstrate that EGCG has abilities to hamper UV-B-induced collagenolytic MMP production via interfering with the MAPK-responsive pathways. Therefore, EGCG may be a potential agent for the prevention and treatment of skin photoaging.

Photodynamic therapy in the treatment of skin photoaging

皮肤光老化中皱纹和皮肤粗糙常困扰患者,光动力疗法治疗皮肤光老化逐渐受到重视,近年来临床研究证实其疗效确切,尤其对改善细纹和肤质方面特别显著,优于目前单用强脉冲光或激光的治疗方法.电子显微镜分析治疗前后的活检组织.发现光动力治疗侧的面部I型胶原合成多于单用强脉冲光的一侧.综述光动力临床研究中光敏剂的封包时间和光源选择,探讨导致疗效差异的因素.阐明紫外线导致皱纹形成的主要途径,以及热休克蛋白和基质金属蛋白酶在光动力治疗皱纹方面的作用。

The use of light‐emitting diode therapy in the treatment of photoaged skin

Light-emitting diode (LED) therapy is an increasingly popular methodology for the treatment of sun damage. Combination use of light wavelengths reported to stimulate collagen synthesis and accelerate fibroblast-myofibroblast transformation may display a composite rejuvenative effect. To clinically assess reduction in sun damage signs following a 5-week course of LED therapy and to assess subject's perception of the treatment. Thirteen subjects with wrinkles or fine lines in the periorbital and nasolabial region and those presenting Glogau scale photodamage grade II-III received nine 20-min duration light treatments using the Omnilux LED system. The treatments combined wavelengths of 633 and 830 nm at fluences of 126 and 66 J/cm(2), respectively. Sun-damage reduction was assessed at 6, 9, and 12 weeks by clinical photography and patient satisfaction scores. The majority of subjects displayed "moderate" (50%) or "slight" (25%) response to treatment at investigator assessment. Treatment of the periorbital region was reported more effective than the nasolabial region. At 12-week follow-up, 91% of subjects reported improved skin tone, and 82% reported enhanced smoothness of skin in the treatment area. Good response to LED therapy has been shown in this modest sample. Larger trials are needed to assess optimum frequency of light treatments and overall treatment time.

The use of hydroxy acids on the skin: characteristics of C8‐lipohydroxy acid

The hydroxy acids are widely used in skin creams because of their exfoliating and rejuvenating effect on photoaged skin. As a member of this family, the salicylic acid derivative known in the literature as 2-hydroxy-5-octanoyl benzoic acid or beta-lipohydroxy acid has also been proposed as an exfoliant and as a treatment of photoaged skin and acne. This article reviews the effects of the hydroxy acids and compares them to those of the salicylic acid derivative. We propose the name C(8)-lipohydroxy acid (C8-LHA) for this derivative to differentiate it from other related compounds. The lipophilic nature of C8-LHA and its relatively slow penetration in the skin afford it an exfoliating effect that is efficient at low concentrations. It appears to have antimicrobial, anti-inflammatory, and anticomedogenic properties, which make it effective against acne. Its antifungal and exfoliating properties are also likely to prove useful in combating dandruff.

Reconstructed human skin: From photodamage to sunscreen photoprotection and anti-aging molecules

Acute or repetitive sun exposure has been shown to be responsible for various deletorious consequences such as sunburn reaction, photoaging and photocancers. Determination of early biological events occurring after UV exposure is essential for photoprotection. Using a human reconstructed skin in vitro, comprising both a fully differentiated epidermis and a living dermal equivalent, the effects of UVB and UVA were analysed in keratinocytes and fibroblasts. The efficiency of sunscreen protection was afforded after topical application. The effect of Vitamin C was analyzed. Reconstructed skin was exposed to UVB, UVA or SSR. Morphological aspect, DNA lesions, sunburn cells, MMP-1 were evaluated. Sunscreen photoprotection was assessed with formulations having different profile of absorption or photostability. Vitamin C was added to the culture medium during reconstruction of the skin. While UVB essentially induced direct epidermal damage such as DNA lesions or sunburn cells, UVA reached the dermis and led to alterations in fibroblasts and dermal extracellular matrix. Both UVB and UVA, alone or combined using solar simulated radiation (SSR), induced MMP-1 production, directly in dermal fibroblasts after UVA exposure, or through release of soluble epidermal factors after UVB. Based on the identification of these biological end-points, evaluation of sunscreeen photoprotection was performed after topical application of formulations. The data showed that broad UVB + UVA spectrum profile together with photostability are required for a real efficient protection. Finally, we found that Vitamin C could improve the morphogenesis of dermal epidermal junction, through its ability to promote synthesis of extracellular matrix and basement membrane proteins. These results may help in understanding the beneficial effects of such molecule in the treatment of photoaged skin. Altogether, these data emphazied the fact that human skin reconstructed in vitro is a valuable tool for research studies as well as for evaluation of compounds designed to prevent or correct photodamage.

Prevention and Treatment of Skin Photoaging With Topical Drugs

光老化是指皮肤衰老过程中由光线特别是紫外线辐射所造成的损伤.皮肤光老化可并发多种皮肤病甚至与皮肤肿瘤的发生有病因学的联系.因此,预防和治疗皮肤光老化很有必要.随着对光老化认识的加深,对其预防与治疗的方法也取得了相应进展.为此,综述了近年来皮肤光老化预防和治疗中应用的包括防晒剂、维A酸类、绿茶等多种外用药物,并从作用机制、临床应用及疗效等方面逐一介绍。

Effects of Infrared Radiation on Skin Photo-Aging and Pigmentation

Infrared radiation is increasingly and uncritically used for cosmetic and wellness purposes, despite the poorly understood biologic effects of such treatments on humans. In the present study, we investigated the effects of infrared radiation on collagen and elastin production in dermal fibroblasts, as well as the clinical and histopathologic effects of infrared radiation on photo-aged facial skin lesions. In order to determine the effects of infrared radiation on collagen and elastin production, dermal fibroblasts were exposed to infrared radiation for varying lengths of time and collagen and elastin contents were subsequently determined. Additionally, 20 patients with mild to moderate facial wrinkles and hyperpigmented lesions received daily treatments of far infrared radiation (900 to 1000 µm) for six-months. During the treatment, patients and a medical observer conducted independent photographic and clinical evaluations every 4 weeks, and skin biopsies were obtained for histological analysis at baseline and one month post-treatment. We found that the content of collagen and elastin produced by the fibroblasts increased after infrared radiation, and that this increase was proportional to the duration of irradiation exposure. Following 6 months of treatment, all patients reported good (51-75%) improvements in skin texture and roughness. Additionally, patients noted fair (25-50%) improvement in color tone of the skin; however, improvements in hyperpigmented lesions were not observed. Objective medical evaluation of the patients indicated that roughness and laxity were fairly improved, but there was no significant improvement in hyperpigmented lesions. Histological examination failed to reveal any differences as well. These results suggest that infrared radiation may have beneficial effects on skin texture and wrinkles by increasing collagen and elastin contents from the stimulated fibroblasts. Therefore, skin treatment with infrared radiation may be an effective and safe non-ablative remodeling method, and may also be useful in the treatment of photo-aged skin.

Treatment of photoaged skin with a cream containing 0.05% isotretinoin and sunscreens

Aims: To determine the safety and efficacy of a cream formulation of 0.05% isotretinoin with sunscreens (SPF 15) (I+S) in the treatment of photoaged skin. Design and subjects: A 6‐month, multicentre, randomized, double‐blind, parallel‐group, vehicle‐controlled study of 346 subjects with photoaged skin, as defined by the presence of fine lines in the periorbital region. The main outcome measure was profilometry measurements of replicas of the periorbital region, taken at 0 and 6 months. Subsidiary outcome measures were clinical scoring of wrinkles/fine lines at 0, 1, 3, 6 and 9 months and histopathology at 0 and 6 months. Methods and results: A total of 172 subjects were randomized to 0.05% I+S and 174 subjects to vehicle. Subjects used the study medication topically, once‐daily for 6 months, followed by a 3‐month washout period. Profilometry measurements of the distance between the highest peak and lowest valley (Rz) and the distance between all valleys and peaks from mid‐line (Ra) showed that subjects using I+S had statistically significant improvement (p<0.05) compared with the vehicle group. Additionally, at all visits, VAS clinical scoring of wrinkles/fine lines showed a statistically significant difference between the groups in favour of I+S. Tolerance assessments showed that more subjects in the I+S group experienced local side effects at the start of the study; however, reports of side effects decreased over time in both groups. Conclusion: This study confirms that I+S improves the appearance of fine wrinkles associated with photoaged skin.

A Prospective Study of Anti-Aging Topical Therapies Using a Quantitative Method of Assessment

In the treatment of photoaged skin, glycolic acid works by removing superficial portions of the epidermis and stimulating dermis regeneration. Vitamins A, C, and E should stimulate collagen production and antioxidants should prevent free radical damage and skin aging. However, the effectiveness of different therapies has often relied on subjective methods of assessment. Histologic analysis has seldom been used because of the drawback of permanent scarring. In the literature, the use of a quantitative method for the assessment of facial rejuvenation has been described: the silicone replica technique. The authors' aim was to promote and recommend the use of this technique and, in particular, to test the effect of glycolic acid and multivitamin- and antioxidant-based products on skin texture. The authors performed a prospective, randomized, double-blind, controlled study on 30 women treated topically in the outer canthal region (crow's-feet area). Patients were divided into three groups (groups A, B, and C); each group consisted of five patients between the ages of 31 and 40 years and five patients between the ages of 41 and 50 years. Group A was treated by glycolic acid application, initially at home for 2 weeks, followed by a higher concentration administered in the office weekly for six applications. Group B was treated by topical application at home of a multivitamin product daily for 3 months. Group C was treated with a cream base (placebo) for 3 months and represented the control group. Skin areas under treatment were photographed and reproduced by the silicone replica technique at baseline and at the end of treatment. This technique reproduces exactly the skin's texture. Digital images were obtained from skin replicas and analyzed by specific software for different parameters: roughness, microsulcus number, and width. Pretreatment and posttreatment values were compared using the Wilcoxon signed-rank test. In group A, microsulcus number and width were statistically decreased, but roughness was not. In groups B and C, parameters were not statistically modified. The silicone replica technique allowed a quantitative analysis of results obtained with different topical therapies. In particular, it confirmed the efficacy of glycolic acid in skin rejuvenation.

Tretinoin reverses upregulation of matrix metalloproteinase-13 in human keloid-derived fibroblasts.

Keloids are skin abnormalities that are characterized by excessive deposition of collagen bundles in the dermis. Patients with keloids complain not only about their cosmetic appearance, but also about continuous itching and/or tenderness associated with chronic inflammation. Degradation of extracellular matrix (ECM) may be upregulated, associated with the expansion of keloids into circumferential skin, and high metabolic activity of keloid tissues may be due to increased matrix metalloproteinase (MMP) activity. Based on these hypotheses, we examined differences in expression of MMP-1, MMP-8, and MMP-13 between keloid-derived and normal dermal fibroblasts. Since retinoids are potent inhibitors of MMPs in the treatment of photoaged skin and cancers, we also examined whether or not tretinoin affects MMP expression of keloid-derived fibroblasts. The results of real-time polymerase chain reaction and ELISA demonstrated significant upregulation of MMP-13 and significant downregulation of MMP-1 and MMP-8 in keloid-derived fibroblasts, at both mRNA and protein levels. MMP-1 mRNA expression in the control group was significantly upregulated after the addition of tretinoin, whereas no significant change was observed in the keloid group. MMP-8 mRNA expression in the control group was significantly upregulated by tretinoin, with the peak at 12 h, while no significant change was observed in the keloid-derived fibroblasts. In contrast, the remarkably elevated MMP-13 mRNA expression in the keloid group was significantly suppressed, with the peak suppression at 12 h after addition of tretinoin, while MMP-13 mRNA expression in the control group was not significantly changed. The decrease in MMP-1 and MMP-8 may contribute to accumulation of type I and type III collagen in keloid tissues, and this mechanism may be modulated by molecular interaction with MMP-13. Tretinoin appeared to reverse the abnormal expression profile of MMPs in keloid-derived fibroblasts, such as markedly elevated expression of MMP-13, partly through inactivation of AP-1 pathway. The present results suggest that tretinoin may be clinically useful to improve the chronic inflammation seen in keloids and prevent expansion of keloid tissues into circumferential normal skin.

Review of nonablative photorejuvenation: reversal of the aging effects of the sun and environmental damage using laser and light sources.

This review article outlines all the latest light or electromagnetic radiation based technologies used for nonablative skin rejuvenation. While many technologies have been available for a number of years, emerging technologies are also discussed, which may play a role in treatment of photoaged skin in the very near future. The principles behind these technologies are discussed in detail.

Nonablative laser resurfacing: a systematic review of the literature.

'Nonablative laser resurfacing' is a new treatment for photoaged skin, the aim of which is to wound the upper dermis in order to induce dermal fibrosis and improve the clinical appearance. Unlike conventional laser resurfacing or dermabrasion, the epidermis is protected and retained to avoid the problems associated with open wounds and reepithelialization. A number of lasers and light sources have been developed or adapted for this purpose.