Solamargine Alleviated UVB-Induced Inflammation and Melanogenesis in Human Keratinocytes and Melanocytes via the p38 MAPK Signaling Pathway, a Promising Agent for Post-inflammatory Hyperpigmentation.

Post-inflammatory hyperpigmentation (PIH) is a common acquired pigmentary disorder occurring after skin inflammation or injury. Ultraviolet B irradiation could exaggerate PIH clinically due to its effect on promoting cutaneous inflammation and melanogenesis in keratinocytes and melanocytes, respectively. Solamargine (SM), a steroidal alkaloid glycoside extracted from Solanum undatum, significantly inhibits Ultraviolet B (UVB)-induced pro-inflammatory cytokines IL-1α, IL-1ß, IL-8, and IFN-γ, as well as paracrine melanogenic factors ET-1, α-MSH, and bFGF in human keratinocytes. Additionally, SM significantly attenuated UVB-induced melanin synthesis in human epidermal melanocytes through down-regulation of tyrosinase activity and expression of MITF, TRP-1, TRP-2, and tyrosinase. SM exerted an anti-inflammatory effect in UVB-irradiated keratinocytes through the p38 MAPK/Nrf2/HO-1 signaling pathway. With its anti-inflammatory and whitening effect, SM may improve PIH through paracrine regulations of keratinocytes and direct action on melanocytes, making it a promising agent for PIH.

Urolithin A protects human dermal fibroblasts from UVA-induced photoaging through NRF2 activation and mitophagy.

Photoaging, caused by exposure to sunlight and especially UVA, has been identified as one of the culprits for age-related skin deterioration. Here, we initially demonstrated that urolithin A (UroA), a metabolite derived from intestine microflora, possessed sufficient photoprotective capacity and attenuated UVA-induced senescent phenotypes in human fibroblasts, such as growth inhibition, senescence-associated ß-galactosidase activity, breakdown of extracellular matrix, synthesis of senescence-associated secretory phenotypes and cell cycle arrest. Furthermore, UroA lessened the accumulation of intracellular reactive oxygen species, which promoted the phosphorylation and afterwards nuclear translocation of NRF2, subsequently driving the activation of downstream antioxidative enzymes. In parallel, we proved that UroA restored mitochondrial function by induction of mitophagy, which was regulated by the SIRT3-FOXO3-PINK1-PARKIN network. Taken together, our results showed that UroA protected dermal fibroblast from UVA damage through NRF2/ARE activation and mitophagy process, thus supporting UroA as a potential therapeutic agent for photoaging.

Effects of Solanum undatum extract (SR-T100) on photocarcinogenesis and photoaging of actinic keratosis.

SR-T100 gel, containing solamargine extracted from Solanum undatum (synonym: Solanum incanum), had good therapeutic effects on actinic keratosis (AK) in human and ultraviolet B-induced papilloma in mice. This study aimed to investigate the immunohistochemical changes in the human skin after SR-T100 treatment. An immunohistochemical study was performed and the changes in photocarcinogenesis and photoaging markers after 16-week SR-T100 gel treatment were documented. SR-T100 gel treatment for 16 weeks resulted in complete remission in nine AK lesions and partial remission in four AK lesions. SR-T100 gel abolished the expression of mutant p53 and SOX2 and restored the expression of NOTCH1. Additionally, SR-T100 gel improved wrinkling in human skin, while restoring the expression of lamin B1 and increasing synthesis of new elastic fibers. SR-T100 gel had therapeutic effects on photocarcinogenesis and photoaging of photodamaged skin with AK.

Dynamic evaluation of an in vivo postinflammatory hyperpigmentation model using reflectance confocal microscopy and spectrophotometry.

BACKGROUND: Postinflammatory hyperpigmentation (PIH) reflects a dynamic process from primary injury and cutaneous inflammation to subsequent melanogenesis and hyperpigmentation, of which pathogenesis remains unclear, hindering the development of targeted therapies. AIMS: To observe the dynamic development of PIH; determine the starting point and peak point of the inflammatory phase and pigmentary phase; and clarify the timing of anti-inflammatory and anti-pigmentary treatment. METHODS: Thirty healthy volunteers with Fitzpatrick skin types III-IV were enrolled and underwent suction blisters. The noninvasive evaluation of inflammation and hyperpigmentation on suction blister sites were performed via spectrophotometry (CM2600d and SIAscope) and RCM for the following 24 weeks. RESULTS: We successfully observed suction blister-induced PIH lasting over 24 weeks. The inflammatory phase started soon after the procedure and lasted for 8-12 weeks, manifested by significantly elevated a* values and erythema index detected by spectrophotometry, as well as inflammatory infiltration and angiogenesis shown in RCM images. Meanwhile, melanogenesis was accelerated after week 3 and reached peak on week 8, manifested by significantly accumulated melanin granules and bright pigment rings in different depths under RCM, which was in parallel with elevated melanin index. The darkening skin tone in PIH actually presented a mixture of inflammatory erythema, angiogenesis, and hyperpigmentation. The inflammation and pigmentation phases of PIH were not sequential but partially overlap. CONCLUSION: The duration of suction blister-induced PIH is more than 24 weeks. The inflammatory phase partially overlaps with the pigmentary phase, and those drugs with anti-inflammatory and anti-pigmentary dual effects are potential choices.

Efficacy of a wound-dressing biomaterial on prevention of postinflammatory hyperpigmentation after suction blister epidermal grafting in stable vitiligo patients: a controlled assessor-blinded clinical study with in vitro bioactivity investigation.

Postinflammatory hyperpigmentation (PIH) is a common disfiguring complication following inflammatory dermatoses and cosmetic procedures in dark-skinned individuals. Anti-inflammatory and repairing agents targeting primary inflammation and injury are becoming promising choices for preventing PIH. The aim of this active-controlled, assessor-blinded, intra-individual monocentric study was to evaluate the preventive effect of a wound-dressing biomaterial, mussel adhesive protein (MAP) in the suction blister-induced PIH model. Twenty Chinese patients underwent suction blister epidermal grafting had defined wound areas to receive a topical MAP spray or a potent corticosteroid cream once daily for seven consecutive days after operation. In situ semi-quantitative evaluations of inflammation and pigmentation were achieved by Mexameter, reflectance confocal microscopy and dermoscopy on week 1, week 4, and week 12. Topical application of MAP exerted remarkably inhibitory effect on PIH comparable to fluticasone propionate, manifested as significantly lower melanin index and papillary contrast measured by Mexameter and confocal microscopy on week 12 compared to untreated sites. Although MAP exhibited moderate anti-inflammatory effect weaker than fluticasone propionate, MAP-treated sites healed faster than steroid-treated and untreated sites. The biological activity of MAP was further studied in UVB-irradiated HaCaT cell model, which revealed MAP decreased the expression of UVB-induced α-melanocyte stimulating hormone (α-MSH) and pro-inflammatory cytokines (IL-1α, IL-6, COX-2). It also protected HaCaT cells from UVB-induced cell death and apoptosis. In conclusion, MAP could be a novel postoperational wound dressing preventing PIH associated with skin inflammation and injury.

Comparison of efficacy and safety profile for home NB-UVB vs. outpatient NB-UVB in the treatment of non-segmental vitiligo: A prospective cohort study.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of home and outpatient narrowband ultraviolet B light (NB-UVB) for the treatment of non-segmental vitiligo. METHODS: A total of 94 patients with non-segmental vitiligo were enrolled. Forty-eight patients were treated with home NB-UVB, and the other 46 patients were treated with outpatient NB-UVB over a period of 6 months. The efficacy, patient quality of life, and adverse events were assessed at month 3 and month 6 after treatment. RESULTS: There was no significant difference in repigmentation and VASI-reverse (VR) rates between outpatient NB-UVB and home NB-UVB groups. VR was higher in outpatient NB-UVB group at month 3, and similar at month 6. For long-standing vitiligo, VR was higher in the outpatient NB-UVB group compared with home NB-UVB group after 6 months of treatment. In recent vitiligo, the VR was similar between the two groups. Additionally, vitiligo-specific health-related quality-of-life instrument (VitiQoL) score was similar, and the adverse effects were minimal among the two groups. CONCLUSIONS: The efficacy and safety of home NB-UVB and outpatient NB-UVB phototherapy for non-segmental vitiligo were comparable. According to our results, those with long-standing vitiligo may be recommended to receive outpatient NB-UVB phototherapy.

Comparison of Moderate and High Energy of a Nano-Fractional Radiofrequency Treatment on a Photoaging Hairless Mice Model.

BACKGROUND: Fractional radiofrequency (FRF) has been widely used in skin rejuvenation. To explore optimal settings, it is important to compare different treatment parameters. OBJECTIVE: This study was designed to compare the effect of moderate-energy and high-energy FRF treatment on a hairless mice model. METHODS: Fifteen photoaged hairless mice were assigned to 3 groups: control, moderate energy, and high energy. Two treatment sessions (T × 1 and T × 2) were performed at 1-month interval. Transepidermal water loss was measured at baseline, immediately, 1, 2, and 4 weeks after T × 1. Skin samples were harvested before each treatment, 1 and 2 months after T × 2. Neocollagenesis was evaluated by hematoxylin and eosin staining, Masson staining, and immunohistochemistry analysis. RESULTS: Transepidermal water loss of high-energy group was significantly higher than the moderate-energy group (p = .008) immediately after T × 1. Remarkable fibroblast proliferation was observed at 1 month after T × 1, followed by significant dermal thickening, and increase of Type I collagen and Type III collagen. There was no significant difference between 2 energy groups in fibroblast proliferation, dermal thickness, and collagen density. CONCLUSION: The effect of moderate-energy treatment was comparable with that of high energy in neocollagenesis, whereas moderate energy yielded less damage to skin barrier function.

Objective evaluation of the effects of intense pulsed light treatment on Asian skin by reflectance confocal microscopy analysis.

This study aimed to evaluate the effect of IPL treatment on Asian skin by reflectance confocal microscopy (RCM) analysis. Ten Asian female volunteers (39~54 years old, Fitzpatrick skin type III~IV) received five monthly IPL treatments. RCM skin images were evaluated, and several skin physiological parameters including thickness of stratum corneum, minimal thickness of epidermis, thickness of basal layer, density of dermal papillae, and mean diameter of papillae capillaries were measured both at baseline and 1 month after the last treatment. Transepidermal water loss (TEWL) was evaluated, as well. Thickness of stratum corneum was 4.80 ± 1.48 µm before IPL treatment and 5.50 ± 1.35 µm after treatment (p = 0.322). Both minimal thickness of epidermis and thickness of basal layer were significantly increased (p = 0.002 and 0.018, respectively) after IPL treatment. Dermal papillae density was significantly increased (p = 0.035), whereas mean capillary diameter was reduced significantly (p = 0.035). TEWL was slightly increased after treatment, while the difference was not significant on either T-zone or U-zone (p = 0.085 on T-zone and p = 0.114 on U-zone). RCM imaging is a feasible method to evaluate the effect of IPL effect on human skin. Moreover, IPL treatment serves to be highly safe in skin rejuvenation.

Comparison of different regimens of pimecrolimus 1% cream in the treatment of facial seborrheic dermatitis.

BACKGROUND: Pimecrolimus 1% cream has already been proved to be an effective and safe alternative to treat seborrheic dermatitis. However, the treatment periods were inconstant in previous studies. OBJECTIVE: To evaluate the comparative efficacy of pimecrolimus 1% cream with different regimens for the treatment of facial seborrheic dermatitis. METHOD: Thirty patients with facial seborrheic dermatitis were enrolled and randomly distributed to three groups. Patients of Group 1 were treated with topical pimecrolimus cream 1% twice daily for 2 weeks and then a moisturizer cream twice daily for 2 weeks. Patients of Group 2 were treated with pimecrolimus cream 1% twice daily for 2 weeks and then once daily for another 2 weeks. Patients of Group 3 had a consecutive course of pimecrolimus cream 1% twice daily for 4 weeks. Objective symptoms, subjective symptoms, and dermatology life quality index (DLQI) were measured at weeks 0, 2, 4, and 6. RESULTS: At week 4, the clinical severity scores of all three regimens significantly decreased (P<.01). The improvement of total severity score in Group 3 was more remarkable than groups 1 and 2 (both P<.05). This effect was maintained until the end of the study in Group 3. Life quality of all three groups was significantly improved at week 4 (P<.001), while there was no statistical difference on the improvement of life quality among three groups. CONCLUSION: We recommend pimecrolimus 1% cream could be applied twice a day for 4 weeks to treat seborrheic dermatitis.