Phycocyanin (Pc) is one of the active pigment constituents of Spirulina microalgae. It has been used for its potent antioxidant and anti-inflammatory properties. However, the protective effects of Pc against ultraviolet-B (UVB)-induced primary skin cells damage are still undefined. In the present study, we investigated whether Pc prevented UVB-induced apoptotic cell death in human dermal fibroblasts (HDF) and human epidermal keratinocytes (HEK). Pc induced the transcription of heme oxygenase-1 (HO-1). Furthermore, Pc treatments resulted in a marked increase in nuclear factor erythroid-derived 2 (NF-E2)-like 2 (Nrf-2) nuclear translocation. Also, Pc protected UVB induced apoptosis and reduced the p53 and Bax levels, as well as caspase-3 activation. Pc treatment showed a significantly enhanced effect on the phosphorylation of protein kinase C (PKC) α/β II, but not that of p38 mitogen-activated protein kinase (MAPK) or Akt. Induction of HO-1 induced by Pc was suppressed by Go6976, a selective inhibitor of PKC α/β II. In addition, knockdown of HO-1 by small interfering (siRNA) caused a significant increase in poly (ADP-ribose) polymerase 1 (PARP-1) cleavage and caspase-3 activation after Pc pretreatment. Taken together, our results demonstrate that Pc-induced expression of HO-1 is mediated by the PKC α/β II-Nrf-2/HO-1 pathway, and inhibits UVB-induced apoptotic cell death in primary skin cells.

Insects are some of the most diverse organisms on the planet, and have potential value as food or medicine. Here, we investigated the photoprotective properties of insect extracts using hairless mice. The alleviating wrinkle formation effects of insect extracts were evaluated by histological skin analysis to determine epidermal thickness and identify collagen fiber damage. Moreover, we investigated the ability of the insect extracts to alleviate UVB-induced changes to matrix metalloproteinases (MMPs), oxidative damage, the mitogen-activated protein kinases (MAPKs) signaling pathway, and the expression of pro-inflammatory cytokines. Insect extracts reduced UVB-induced skin winkles, epidermal thickening, and collagen breakdown, and alleviated the epidermal barrier dysfunction induced by UVB, including the increased loss of transepidermal water. Moreover, the expression of skin hydration-related markers such as hyaluronic acid, transforming growth factor-beta (TGF-β), and procollagen was upregulated in the group treated with insect extracts compared to the vehicle-treated group after ultraviolet B (UVB) exposure. UVB irradiation also upregulated the expression of MMPs, the phosphorylation of MAPKs, and pro-inflammatory cytokines, which were all attenuated by the oral administration of insect extracts. These results indicate the photoaging protection effect of insect extracts and the underlying mechanism, demonstrating the potential for clinical development.

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. AD pathogenesis is associated with increased oxidative stress, impairment of the skin barrier, and activation of the immune response. Rosmarinic acid (RA), a caffeic acid ester, is known for its anti-inflammatory and antioxidant properties. However, the effects of RA on Dermatophagoides farinae extract (DfE)-induced AD-like skin inflammation, as well as its ability to regulate oxidative stress through the Nrf2/HO-1 pathway in TNF-α/IFN-γ-treated keratinocytes, remain unclear. We investigated RA activity in a DfE-induced AD-like skin inflammation mouse model and IFN-γ/TNF-α-stimulated keratinocytes. We found that RA attenuates DfE-induced inflammation by decreasing dermatitis scores and serum inflammatory marker levels and mast cell infiltration. Additionally, RA significantly suppressed IFN-γ/TNF-α-induced chemokine production in keratinocytes and reduced Th cytokine levels in concanavalin A-stimulated splenocytes. Importantly, RA also increased Nrf2/HO-1 expression in TNF-α/IFN-γ-treated keratinocytes. In conclusion, this study demonstrated that RA effectively alleviates DfE-induced AD-like skin lesions by reducing the levels of inflammatory cytokines and chemokines. Furthermore, RA promotes Nrf2/HO-1 signaling in keratinocytes, which may help mitigate DfE-induced oxidative stress, thereby alleviating AD-like skin inflammation. These findings highlight the potential of RA as a therapeutic agent for treating AD and other skin inflammation.

Atopic dermatitis (AD) is chronic allergic contact dermatitis with immune dysregulation. Veronica persica has pharmacological activity that prevents asthmatic inflammation by ameliorating inflammatory cell activation. However, the potential effects of the ethanol extract of V. persica (EEVP) on AD remain elusive. This study evaluated the activity and underlying molecular pathway of EEVP in two AD models: dinitrochlorobenzene (DNCB)-induced mice and interferon (IFN)-γ/tumor necrosis factor (TNF)-α-stimulated human HaCaT keratinocytes. EEVP attenuated the DNCB-induced increase in serum immunoglobulin E and histamine levels, mast cell counts in toluidine-blue-stained dorsal skin, inflammatory cytokine (IFN-γ, interleukin [IL]-4, IL-5, and IL-13) levels in cultured splenocytes, and the mRNA expression of IL6, IL13, IL31 receptor, CCR-3, and TNFα in dorsal tissue. Additionally, EEVP inhibited the IFN-γ/TNF-α-induced mRNA expression of IL6, IL13, and CXCL10 in HaCaT cells. Furthermore, EEVP restored the IFN-γ/TNF-α-induced downregulation of heme oxygenase (HO)-1 in HaCaT cells by inducing nuclear factor erythroid 2-related factor 2 (Nrf2) expression. A molecular docking analysis demonstrated that EEVP components have a strong affinity to the Kelch-like ECH-associated protein 1 Kelch domain. In summary, EEVP inhibits inflammatory AD by attenuating immune cell activation and inducing the Nrf2/HO-1 signaling pathway in skin keratinocytes.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin barrier dysfunction and chronic inflammatory responses. Reynoutria japonica, known as Huzhang in traditional Chinese Medicine, can enhance blood circulation to eliminate wind pathogens and terminate coughing. Despite pharmacological evidence supporting the efficacy of R. japonica in suppressing edema-induced skin inflammation or connective tissue diseases, its pharmaceutical potential for treating AD-like skin inflammation remains unexplored. This study investigated the possible effects of R. japonica ethanol extract (RJE) on Dermatophagoides farinae extract (DfE)-induced AD-like skin inflammation in NC/Nga mice. To elucidate the underlying mechanisms by which RJE inhibits skin inflammation, we examined the effect of RJE on IFN-γ/TNF-α-induced signal transducer and activator of transcription (STAT) signaling in human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs). Our findings revealed that RJE mitigates DfE-induced AD-like symptoms and skin barrier disruptions in mouse skin lesions. Moreover, RJE attenuated DfE-induced mast cell infiltration and serum levels of inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-23, IFN-γ, TNF-α, and GM-CSF). RJE also inhibited IFN-γ/TNF-α-induced chemokine levels and STAT3 phosphorylation in HEKs and HDFs. Virtual binding analysis of the RJE components suggested that emodin-8-β-D-glucoside binds to Janus kinase (JAK) 1/2, thereby suppressing STAT signaling, which was confirmed by Western blot analysis. In conclusion, our results suggest that RJE may alleviate DfE-induced skin barrier dysfunction by inhibiting JAK/STAT signaling and the proinflammatory immune response through the suppression of inflammatory mediators in AD-like skin disease. These findings suggest that RJE has potential as an effective therapy for AD management.

Ultraviolet-B (UVB) radiation-induced photoaging of the skin is characterized by amplified expression of matrix metalloproteinase-1 (MMP-1) and reduced collagen fibers, both of which contribute to skin wrinkle formation. Edible natural products can protect against skin photoaging. Here, we investigate the protective effect of Dolichos lablab Linne (DLL) water extract against UVB radiation-prompted skin damage and attempt to uncover its fundamental mechanisms in human keratinocytes (HaCaT) and HR-1 hairless mouse. We found DLL extract rescued the reduction in cell viability associated with UVB exposure without any associated cytotoxic effects. It also protected against skin photoaging by inhibiting mitogen-activating protein kinase (MAPK) signaling, thereby preventing the UVB-associated increase in MMP-1 and -9 expression. DLL extract also increased the expression of both superoxide dismutase 1 (SOD1) and catalase (CAT). We identified chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A as bioactive components of DLL. Although we have not yet identified the mechanisms by which these compounds reduce the effects of photoaging, we have demonstrated that chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A reduce MMP-1, MMP-9, p–c-Fos, and p–c-Jun expression, while also avoiding any cytotoxicity. We found oral administration of DLL extract effectively alleviated dorsal epidermal thickening and skin dehydration in HR-1 hairless mouse visible to UVB. DLL extract also prevents UVB-induced activation of the MAPK/AP-1 signaling pathway, thereby reducing the expression of MMPs in dorsal mouse skin. Our results indicate that chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A are bioavailable components of DLL extract that can reduce UVB-induced skin damage via MMPs by deactivating the MAPK/AP-1 signaling pathway. These findings suggest DLL extract can be used as a skin anti-photoaging agent.