Radiation-induced Skin Damage Research Articles

Prevention and Treatment of Radiation Induced Skin Damage in Breast Cancer

Introduction: Skin toxicity is a frequent side effect of radio and chemo-treatments in patients treated for breast cancer after conservative surgery. The aim of this paper is to report our experience in the management of skin toxicity evaluating radiotherapy planning and using preventive local aids. Materials and Methods: We have observed 300 patients undergoing radiotherapy. All received the prescription of a prophylactic moisturizing cream. Skin toxicity was valuated according to Acute Radiation Morbidity Scoring Criteria of the RTOG. Moreover, in a subgroup of 100 patients, we correlated the study of breast volume and features of treatment plans, with the addition of topic prophylactic treatment, using an oral therapy based on Resveratrol, Lycopene, Vitamin C and Anthocyanins (Ixor?). In another subgroup, 100 patients were subjected to corneometry assessing numerically skin hydration before, during and after radiotherapy. Results: In all patients, we related skin toxicity and the type of cream used. All patients completed the radiotherapy treatment, and G4 cutaneous toxicity was not observed in any of them. In patients treated with topic treatment and therapy based on Resveratrol, Lycopene, Vitamin C and Anthocyanins (Ixor?), the protective effect of (Ixor?) is more detected in patients with PTV (Planning Target Volume)

Amelioration of Radiation-induced Skin Injury by HIV-TAT-Mediated Protein Transduction of RP-1 from Rana pleurade

Radiation-induced reactive oxygen species (ROS) can damage DNA and most other biological macromolecules in skin and radiation-induced skin injury is a serious concern for radiation therapy. Skin possesses an extremely efficient antioxidant system, which is conferred by two systems: antioxidant enzymes and small molecules that can scavenge ROS by donating electrons. Amphibian skin is a multifunctional organ, which protects against dangers of various oxidative stresses. Recently, a small peptide called RP-1 was isolated from the skin secretions of Rana pleurade, which shows strong antioxidant activity. However, this RP-1 peptide is limited because its inability to across the cell membrane. Protein transduction domains (PTDs) have demonstrated high efficiency for facilitating the internalization of both homologous and heterogeneous proteins into cells. This study aims to elucidate the protective effects of a HIV-TAT (TAT) PTD-coupled RP-1 fusion protein (TAT-RP1) on radiation-induced skin injury in vitro and in vivo. The synthesized fusion TAT-RP1 peptide can be incorporated into human keratinocyte HaCaT cells in a dose- and time-dependent manner without cytotoxicity. We then evaluated the protective role of TAT-RP1 against ionizing radiation. TAT-RP1 supplementation increased anti-superoxide anion ability of HaCaT cells and decreased HaCaT cell radiosensitivity to irradiation. Moreover, TAT-RP1 was able to penetrate the skin of rats, entering epidermis as well as the dermis of the subcutaneous layer in skin tissue. Topical spread of TAT-RP1 promoted the amelioration of radiation-induced skin damage in rats. These results suggest that TAT-RP1 has potential as a protein therapy for radiation-induced skin injury.

Topical Formulations Containing Pimenta pseudocaryophyllus Extract: In Vitro Antioxidant Activity and In Vivo Efficacy Against UV-B-Induced Oxidative Stress

Pimenta pseudocaryophyllus is a Brazilian native plant that presents high concentrations of flavonoids and other polyphenolic compounds. Herein, we evaluated: (1) the chemical properties of P. pseudocaryophyllus ethanolic extract (PPE), (2) the in vitro antioxidant activity (AA) of PPE and of two different topical formulations (F1 and F2) containing PPE, (3) physico-chemical and functional stability, (4) in vitro release of PPE, and (5) in vivo capacity of formulations to prevent UV-B irradiation-induced skin damage. Results show that the polyphenol and flavonoid contents in PPE were 199.33 and 28.32 mg/g, respectively, and HPLC results show the presence of eugenol, tannic acid, and rutin. Evaluation of the in vitro AA of PPE demonstrated a dose-dependent effect and an IC50 of 4.75 μg/mL in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 3.0 μg/mL in 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. The ferric-reducing antioxidant power (FRAP assay) was 0.046 μmol/L trolox equivalent/μg/mL of extract. Among the AA, only the capacity to scavenge DPPH radical of PPE was maintained in F1 and F2. In addition, both formulations satisfactorily released the extract. The evaluation of the functional stability of F1 and F2 did not demonstrate loss of activity by storage at room temperature and at 4°C/6 months. In irradiated mice, treatment with F1 and F2 added with PPE significantly increased the capacity to scavenge ABTS radical and the FRAP of skin compared to vehicle-treated mice. In conclusion, the present results suggest that formulations containing PPE may be a topical source of antioxidant compounds to decrease oxidative damages of the skin.

Antioxidant effect of 4-nerolidylcatechol and α-tocopherol in erythrocyte ghost membranes and phospholipid bilayers

4-Nerolidylcatechol (4-NC) is found in Pothomorphe umbellata root extracts and is reported to have a topical protective effect against UVB radiation-induced skin damage, toxicity in melanoma cell lines, and antimalarial activity. We report a comparative study of the antioxidant activity of 4-NC and α-tocopherol against lipid peroxidation initiated by two free radical-generating systems: 2,2′-azobis(2-aminopropane) hydrochloride (AAPH) and FeSO4/H2O2, in red blood cell ghost membranes and in egg phosphatidylcholine (PC) vesicles. Lipid peroxidation was monitored by membrane fluidity changes assessed by electron paramagnetic resonance spectroscopy of a spin-labeled lipid and by the formation of thiobarbituric acid-reactive substances. When lipoperoxidation was initiated by the hydroxyl radical in erythrocyte ghost membranes, both 4-NC and α-tocopherol acted in a very efficient manner. However, lower activities were observed when lipoperoxidation was initiated by the peroxyl radical; and, in this case, the protective effect of α-tocopherol was lower than that of 4-NC. In egg PC vesicles, malondialdehyde formation indicated that 4-NC was effective against lipoperoxidation initiated by both AAPH and FeSO4/H2O2, whereas α-tocopherol was less efficient in protecting against lipoperoxidation by AAPH, and behaved as a pro-oxidant for FeSO4/H2O2. The DPPH (2,2-diphenyl-1-picrylhydrazyl) free-radical assay indicated that two free radicals were scavenged per 4-NC molecule, and one free radical was scavenged per α-tocopherol molecule. These data provide new insights into the antioxidant capacity of 4-NC, which may have therapeutic applications for formulations designed to protect the skin from sunlight irradiation.

The Use of Antioxidants in Radiotherapy-Induced Skin Toxicity

Radiation-induced skin damage is one of the most common complications of radiotherapy. In order to combat these side effects, patients often turn to alternative therapies, which often include antioxidants. Antioxidants such as those in the polyphenol chemical class, xanthine derivatives, tocepherol, sucralfate, and ascorbate have been studied for their use in either preventing or treating radiotherapy-induced skin damage. Apart from their known role as free radical scavengers, some of these antioxidants appear to alter cytokine release affecting cutaneous and systemic changes. We review the role of antioxidants in treating and preventing radiation-induced skin damage as well as the possible complications of using such therapy.

The effect of RHIZOMA COPTIDIS and COPTIS CHINENSIS aqueous extract on radiation-induced skin injury in a rat model

BackgroundRadiation-induced skin injury is a common complication of radiotherapy. The RHIZOMA COPTIDIS and COPTIS CHINENSIS aqueous extract (RCE) can ameliorate radiation-induced skin injury in our clinical observation. But, the protective mechanism of RHIZOMA COPTIDIS and COPTIS CHINENSIS in radiation-induced skin injury remains unclear.MethodsIn this experiment, we developed a radiation-induced skin injury rat model to study the mechanism. The animals were randomly divided into control group, treatment group, radiation group, and treatment and radiation group. 5 rats in each group were separately executed on 2 d and 49 d post-radiation. The semi-quantitative skin injury score was used to measure skin reactions by unblinded observers, and hematoxylin and eosin staining was used to evaluate the damage areas by irradiation. The MDA content, SOD activity of skin and serum were measured to detect the oxidative stress.ResultsAcute skin reactions were caused by a single dose of 45 Gy of β-ray irradiation, and the skin injury could be found in all rats receiving irradiation based on the observation of HE staining of skin at different time-points, while RCE could significantly ameliorate those changes. The MDA content in serum and skin of control rats was 4.13 ± 0.12 mmol/ml and 4.95 ± 0.35 mmol/mgprot on 2 d post-radiation. The rats receiving radiation showed an increased content of MDA (5.54 ± 0.21 mmol/ml and 7.10 ± 0.32 mmol/mgprot), while it was 4.57 ± 0.21 mmol/ml and 5.95 ± 0.24 mmol/mgprot after treated with RCE (p < 0.05). Similar changes of the MDA content could be seen on 49 d post-radiation. However, the SOD activity of rats receiving radiation decreased compared with control group on both time-points, which was inhibited by RCE (p < 0.05). Meanwhile, no valuable changes could be found between control group and treatment group on 2 d and 49 d.ConclusionsOur study provides evidences for the radioprotective role of RCE against radiation-induced skin damage in rats by modulating oxidative stress in skin, which may be a useful therapy for radiation-induced skin injury.

The balneotherapy effect of hydrogen reduced water on UVB-mediated skin injury in hairless mice

Exposure to UVB radiation induced skin damage that results to increase risk of skin cancer. Despite the clinical importance of skin-induced damage, antioxidants imposed limited therapeutic success. Hydrogen molecule (H2) has been known as a safe antioxidant in the prevention and therapeutic approach towards several diseases. Drinking hydrogen reduced water (HRW), inhalation of hydrogen gas, and injecting H2-dissolved saline are widely accepted to incorporate H2 in the body. However, there is no document about the beneficial effect of hydrogen water bath. Here, we investigated the effect of hydrogen bathing on the UVB-induced skin damage in hairless mice. For this, mice of the bathing group are allowed to freely swim on HRW, and let the HRW penetrate for 60 mins. Scoring of skin injury, reactive oxygen species (ROS) enzyme activity quantification, cytokine analysis, and ultrastructural change of corneocytes were measured after exposure to UVB radiation of 360–540 mJ/cm2. In summary, the bathing with HRW significantly reduced the levels of skin damage, as well as increased activity of glutathione peroxidase. Further, the effect of HRW on cytokine network in the skin after UVB exposure revealed that HRW significantly decreased the level of inflammatory cytokines such as IL-1β, IL-6, TNF-α and IFN-γ. Finally, scanning electron microscopy data revealed low number of defected corneocytes and ultrastructural changes, suggesting that HRW bathing would protect UV-induced cell damage.

Effect of Artocarpus communis Extract on UVB Irradiation-Induced Oxidative Stress and Inflammation in Hairless Mice

Administration of antioxidants and anti-inflammatory agents is an effective strategy for preventing ultraviolet (UV) irradiation-induced skin damage. Artocarpus communis possesses several pharmacological activities, such as antioxidant, anticancer and anti-inflammation. However, the photoprotective activity of methanol extract of A. communis heartwood (ACM) in ultraviolet irradiation-induced skin damage has not yet been investigated. The present study was performed using ultraviolet absorption, histopathological observation, antioxidant and anti-inflammation assays to elucidate the mechanism of the photoprotective activity of ACM. Our results indicated that ACM displayed a UVA and UVB absorption effect and then effectively decreased scaly skin, epidermis thickness and sunburn cells during ultraviolet irradiation in hairless mice. ACM not only decreased ultraviolet irradiation-mediated oxidative stress, including lowering the overproduction of reactive oxygen species and lipid peroxidation (p < 0.05), but also reduced the levels of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin 1β. Additionally, ACM can decrease the synthesis of cytosolic phospholipase A2, cyclooxygenase, inducible nitric oxide synthase and vascular cell adhesion molecular-1 via inhibiting TNF-α-independent pathways (p < 0.05) in UVB-mediated inflammation and formation of sunburn cells. Consequently, we concluded that ACM extract has a photoprotective effect against UVB-induced oxidative stress and inflammation due to its sunscreen property, and its topical formulations may be developed as therapeutic and/or cosmetic products in further studies.

Toll-like receptors in ultraviolet radiation-induced skin damage and cancer

Ultraviolet (UV) irradiation can cause immune suppression,DNA damage and skin tumors.Toll-like receptors (TLRs),as important pattern recognition receptors,play essential roles in both innate and adaptive immune responses,and are expressed on a variety of cell types in skin,including keratinocytes,Langerhans cells,dendritic cells,mast cells,fibroblasts and melanocytes.TLR activation can upregulate the expression of cytokines,chemokines,and costimulatory and adhesion molecules involved in innate and adaptive immune responses.Mounting evidences have suggested that TLRs are associated with cellular responses to UV exposure.In addition,there has been a growing interest in the targeting of TLRs for the prevention and treatment of skin cancer. Key words: Toll like receptors; Immunity; Ultraviolet rays; Skin neoplasms

Raman spectroscopic mapping for the analysis of solar radiation induced skin damage

The effects of simulated solar irradiation of an artificial skin model have been examined using Raman spectroscopy and the results are compared with cytotoxicological and histological profiling. Samples exposed for times varying between 30 minutes and 240 minutes were incubated post exposure for a period of 96 hours. The cytotoxicological response as measured by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay demonstrated a ~50% loss of viability of the artificial tissue after 120 minutes exposure. Histological staining of tissue sections showed considerable loss of cellular content in the epidermal layer at this endpoint. Raman spectroscopic mapping of tissue sections, coupled with K-means cluster analysis (KMCA) clearly identified the dermal and stratum corneum layers and differentiated further substructures of the epidermis. Post irradiation, a significant loss of DNA features in the basal layer was apparent in the results of the KMCA. Principal Components Analysis (PCA) of layers identified by the KMCA post exposure compared with controls indicated a significant increase in the lipidic signatures of the stratum corneum. In the dermal layer, little photodamage was observed, but a similar increase in lipidic signatures in the basal layer was accompanied by a decrease in DNA and protein contributions. The spectral profiles of the photodamage to the basal layer as identified by PCA are consistent over the exposure periods of 30-240 minutes, but an examination of the evolution of features associated with specific biochemical components indicated DNA damage and loss of lipidic signatures at the early exposure times, whereas changes in protein signatures appeared to evolve over longer periods. In comparison to the cytotoxicological responses, the study demonstrates that Raman spectroscopy can identify biochemical changes as a result of solar exposure at time points significantly earlier than changes in tissue viability are observed.

English

In this report, the chemical composition and pharmacological properties of&nbsp;Punica granatum&nbsp;L. (Punicaceae) have been reviewed. In the past decade, numerous studies on the antioxidant, anticarcinogenic, and anti-inflammatory properties of pomegranate constituents have been published, focusing on treatment and prevention of cancer, cardiovascular disease, diabetes, dental conditions, erectile dysfunction, bacterial infections and antibiotic resistance, and ultraviolet radiation-induced skin damage. Other potential applications include infant brain ischemia, male infertility, Alzheimer&rsquo;s disease, arthritis and obesity. &nbsp; Key words:&nbsp;Punica granatum&nbsp;L., pomegranate, chemical composition, pharmacological activities.

Amelioration of radiation-induced skin injury by adenovirus-mediated heme oxygenase-1 (HO-1) overexpression in rats

ObjectiveRadiation-induced skin injury remains a serious concern for radiation therapy. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, has been reported to have potential antioxidant and anti-apoptotic properties. However, the role of HO-1 in radiation-induced skin damage remains unclear. This study aims to elucidate the effects of HO-1 on radiation-induced skin injury in rats.MethodsA control adenovirus (Ad-EGFP) and a recombinant adenovirus (Ad-HO1-EGFP) were constructed. Rats were irradiated to the buttock skin with a single dose of 45 Gy followed by a subcutaneous injection of PBS, 5 × 109 genomic copies of Ad-EGFP or Ad-HO1-EGFP (n = 8). After treatment, the skin MDA concentration, SOD activity and apoptosis were measured. The expression of antioxidant and pro-apoptotic genes was determined by RT-PCR and real-time PCR. Skin reactions were measured at regular intervals using the semi-quantitative skin injury score.ResultsSubcutaneous injection of Ad-HO1-EGFP infected both epidermal and dermal cells and could spread to the surrounding regions. Radiation exposure upregulated the transcription of the antioxidant enzyme genes, including SOD-1, GPx2 and endogenous HO-1. HO-1 overexpression decreased lipid peroxidation and inhibited the induction of ROS scavenging proteins. Moreover, HO-1 exerted an anti-apoptotic effect by suppressing FAS and FASL expression. Subcutaneous injection of Ad-HO1-EGFP demonstrated significant improvement in radiation-induced skin injury.ConclusionsThe present study provides evidences for the protective role of HO-1 in alleviating radiation-induced skin damage in rats, which is helpful for the development of therapy for radiation-induced skin injury.

Protective Mechanisms of a Grape Seed Extract (Burgund Mare Variety) on Chronic Ultraviolet B Irradiation-induced Skin Damage in SKH-1 Hairless MICE

Protective Mechanisms of a Grape Seed Extract (Burgund Mare Variety) on Chronic Ultraviolet B Irradiation-induced Skin Damage in SKH-1 Hairless MICE

Pomegranate (Punica granatum L). Ancient seeds for modern cure? Review of potential therapeutic applications

Pomegranate (Punica granatum L), in addition to its ancient historical uses, has been used in several systems of medicine for a variety of ailments. Pomegranate juice is a polyphenol-rich juice with high antioxidant capacity. In studies of human and murine models, pomegranate juice has been shown to exert significant antiatherogenic, antioxidant, anti-carcinogenic, and anti-inflammatory effects. In the past decade, numerous studies on the antioxidant, anti-carcinogenic, and anti-inflammatory properties of pomegranate constituents have been published, focusing on the treatment and prevention of cancer, cardiovascular disease, diabetes, dental conditions, and ultraviolet radiation-induced skin damage. Other potential applications include infant brain ischemia, male infertility, Alzheimer's disease, arthritis, and obesity. The aim of the present review is to discuss the cumulative evidence, which suggests that pomegranate consumption possesses a diverse array of biological actions and may be helpful in the prevention of some inflammatory-mediated diseases, including cancer. The search strategy included Pubmed, using terms 'pomegranate' or 'Punica granatum'. Citations relevant to the topic were screened.

Effects of various flavonoids isolated from Scutellaria baicalensis roots on skin damage in acute UVB-irradiated hairless mice

Solar ultraviolet (UV) radiation causes skin damage including increasing skin thickness, edema and flush. Scutellaria baicalensis roots have been traditionally used as a remedy for allergic inflammatory diseases in China and Japan. In this study, we examined the effects of four flavonoids isolated from these roots, namely 2',5, 5',7-tetrahydroxy-6',8-dimethoxyflavone (1), skullcapflavone II (2), 2(S)-2',5,6',7-tetrahydroxyflavanone (3) and 2(R), 3(R)-2',3,5,6',7-pentahydroxyflavanone (4), on acute UVB irradiation-induced skin damage in hairless mice. The four flavonoids were orally administered twice daily, at doses of 10 and 50 mg/kg, for 14 consecutive days. The UVB irradiation was performed at a dose of 200 mJ cm(-2) on days 7 and 8 after beginning oral administration of the four flavonoids. Compounds 1 and 4 prevented increases in skin thickness, levels of matrix metalloproteinases (MMP)-2 and MMP-9, and vascular endothelial growth factor (VEGF) induced by UVB irradiation. The other two flavonoids 2 and 3 had no effect. Compounds 1 and 4 isolated from Scutellaria baicalensis roots may be useful for preventing skin inflammation induced by acute UVB irradiation.

Postradiation Chronic Scalp Ulcer

For example, ionizing radiation, although beneficial for treating cancer, has negative effects on surrounding uninvolved tissues. Fragile and friable areas of damaged skin after radiation may lead to chronic, painful, and recalcitrant ulcers and, at times, bony changes. It may also result in more difficult healing after surgery and recurrence of the wound even with minor trauma. Despite improvements in radiation therapy techniques and equipment, chronic radiation ulcers are often resistant to conventional treatment modalities or advanced surgical options such as flap coverage or skin grafting and continue to be a therapeutic challenge. We present a case of a radiation ulcer treated using tissue engineered skin, discuss the pathophysiology of radiation-induced skin damage, and review the current management strategies.

SU‐E‐I‐10: Skin Dose in Routine CT Brain Perfusion Studies Using Siemens 64 Slice, Definition Dual Source, and Flash CT Scanners

Purpose: To determine and compare the entrance skin doses from the routine CT brain perfusion protocols on various Siemens CT scanners. Methods: Four Siemens CT scanners were surveyed using their brain perfusion protocol (see supporting document): two Sensation 64‐slice scanners (EC‐CT‐2 and IP‐CT‐2), one Definition Dual Source (64‐slice), and one Definition Flash (128‐slice). The skin dose was measured using a RANDO® anthropomorphic phantom and Landauer optically stimulated luminescent (OSL) nanoDot dosimeters. We performed the scan three times on each scanner with the OSL nanoDots on the surface of the head at the 0, 90, 180, and 270 degree positions. We then averaged the skin doses from the three scans at each of the four positions to calculate an average skin dose for each CT scanner and an average skin dose per scan, independent of position. Results: The mean skin doses obtained were 341.7 mGy ± 44.5 for the Definition Dual Source, 326.7 mGy ± 37.3 for EC‐CT‐2 (64 slice), 326.6 mGy ± 55.6 for IP‐CT‐2 (64 slice), and 435.6 mGy ± 29.7 mGy for the Flash CT. The skin doses of the two 64‐slice scanners and the Definition dual source CT were similar, as expected, since they employed the same beam width. The skin dose of the Flash CT was 32.8% higher, which as expected, since its beam width is ∼33% larger (38.4 mm for the Flash vs. 28.8 mm for the others). Conclusions: Based on the phantom study, the skin doses for routine CT brain perfusion protocols on the mentioned scanners are 325–435 mGy, which is far below the dose threshold for possible radiation induced skin damage (2000 mGy)

Efficacy of Marigold Extract-Loaded Formulations Against UV-induced Oxidative Stress

The present study investigated the potential use of topical formulations containing marigold extract (ME) (Calendula officinalis extract) against ultraviolet (UV)B irradiation-induced skin damage. The physical and functional stabilities, as well as the skin penetration capacity, of the different topical formulations developed were evaluated. In addition, the in vivo capacity to prevent/treat the UVB irradiation-induced skin damage, in hairless mice, of the formulation with better skin penetration capacity was investigated. All of the formulations were physically and functionally stable. The gel formulation [Formulation 3 (F3)] was the most effective for the topical delivery of ME, which was detected as 0.21 μg/cm(2) of narcissin and as 0.07 μg/cm(2) of the rutin in the viable epidermis. This formulation was able to maintain glutathione reduced levels close to those of nonirradiated animals, but did not affect the gelatinase-9 and myeloperoxidase activities increased by exposure to UVB irradiation. In addition, F3 reduced the histological skin changes induced by UVB irradiation that appear as modifications of collagen fibrils. Therefore, the photoprotective effect in hairless mice achieved with the topical application of ME in gel formulation is most likely associated with a possible improvement in the collagen synthesis in the subepidermal connective tissue.

Effects of baicalein and wogonin isolated from Scutellaria baicalensis roots on skin damage in acute UVB-irradiated hairless mice

Solar ultraviolet (UV) radiation causes skin damage including increases in skin thickness, edema, and flush. In this study, we examined the effects of two main flavonoids (wogonin and baicalein) isolated from the roots of Scutellaria baicalensis, a traditional remedy for allergic inflammatory diseases long used in China and Japan, on acute UVB irradiation-induced skin damage in hairless mice. Baicalein and wogonin (10 or 50 mg/kg) were administered orally twice daily for 14 consecutive days. The UVB irradiation was performed at a dose of 200 mJ/cm 2 on days 7 and 8 of the treatment with the two main flavonoids. Baicalein, and wogonin prevented the increases in skin thickness and the levels of matrix metalloproteinase (MMP)-9, and vascular endothelial growth factor (VEGF) induced by the irradiation. Wogonin reduced the levels of cyclooxygenase (COX)-2 and hypoxia inducible factor (HIF)-1α in UVB-treated HaCaT cells. These findings suggest that wogonin inhibits irradiation-induced skin damage by suppressing increases in the levels of MMP-9, and VEGF through the inhibition of COX-2 and HIF-1α expression. Baicalein inhibited COX-2 and NF-κB/p65 expression, but stimulated HIF-1α expression. Therefore, its inhibitory action is likely due to the expression of MMP-9 and VEGF through the suppression of COX-2 and NF-κB/p65 expression. Furthermore, the inhibitory effects of baicalein on UVB-irradiated hyperplasia of skin epidermis may be due to the stimulation of HIF-1α expression.

Quercetin inhibits UV irradiation-induced inflammatory cytokine production in primary human keratinocytes by suppressing NF-κB pathway

Topical flavonoids, such as quercetin, have been shown to reduce ultraviolet (UV) irradiation-mediated skin damage. However, the mechanisms and signaling pathways involved in this protective effect are not clear. UV irradiation leads to activation of two major signaling pathways, namely nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1) pathways. Activation of NF-κB pathway by UV irradiation stimulates inflammatory cytokine expression, whereas activation of AP-1 pathway by UV irradiation promotes matrix metalloproteinase (MMP) production. Both pathways contribute to UV irradiation-induced skin damage, such as photoaging and skin tumor formation. To elucidate the underlying mechanism, we examined the effect of quercetin on UV irradiation induced activation of NF-κB and AP-1 pathways. Primary human keratinocytes, the major skin cell type subjected to physiological solar UV irradiation, were used to study the effects of quercetin on UV irradiation-induced signal transduction pathways. Quercetin decreased UV irradiation-induced NF-κB DNA-binding by 80%. Consequently, quercetin suppressed UV irradiation-induced expression of inflammatory cytokines IL-1β (∼60%), IL-6 (∼80%), IL-8 (∼76%) and TNF-α (∼69%). In contrast, quercetin had no effect on UV irradiation activation of three MAP kinases, ERK, JNK, or p38. Accordingly, induction of AP-1 target genes such as MMP-1 and MMP-3 by UV irradiation was not suppressed by quercetin. Our data indicate that the ability of quercetin to block UV irradiation-induced skin inflammation is mediated, at least in part, by its inhibitory effect on NF-κB activation and inflammatory cytokine production.