Porcine Placenta Extract Reduced Wrinkle Formation by Potentiating Epidermal Hydration

Background: Placenta extract is used as an alternative medicine especially in Asian countries as it is a rich reservoir of diverse bioactive molecules. The effects of placenta extract on skin conditions have been previously reported, however, the mechanism underlying for reduced wrinkle formation remains unclear. Objective: The primary objective of this study was to determine whether the continuous application of porcine placenta extract (PPE) alleviates wrinkle formation in humans and explore the underlying mechanism. Methods: Wrinkle formation, skin hydration, and skin elasticity were measured in 15 volunteers at weeks 0 and 6 after continuous application of a gel containing PPE. The production of type I collagen and hyaluronic acid from fibroblasts and keratinocytes, respectively, were measured using ELISA. Expression levels of ceramide synthase 3 (CERS3), filaggrin (FLG), transglutaminase 1 (TGM1), and kallikrein-7 (KLK7) were evaluated by quantitative real-time PCR. Results: The wrinkle index was significantly reduced to 72.1% after a 6-week of applying the PPE gel, along with a significant increase in skin hydration to 126.5%. Type I collagen production from fibroblasts was enhanced slightly but significantly following treatment with PPE. PPE accelerated the expression of CERS3 (1.85-fold), FLG (1.35-fold), TGM1 (1.76-fold), and KLK7 (1.62-fold). Conclusion: Treatment with PPE alleviates wrinkle formation and simultaneously enhances skin hydration, which is induced via the accelerated expression of moisturizing-related proteins. These findings suggest that PPE is effective for combating dryness-induced wrinkle formation.

Porcine Placenta Extract Enhances Ceramide Synthase 3 Expression through the PPARδ/ILK/Akt/mTOR/STAT3 Pathway

Porcine placenta extract (PPE) is widely accepted as an ingredient in complementary and alternative medicine and previous studies have reported its availability, however, its underlying action mechanism remains unclear. In this study, we investigated the underlying mechanism of PPE-induced ceramide synthase 3 upregulation. PPE enhanced the expression of ceramide synthase 3 at both the mRNA and protein levels in HaCaT cells. Moreover, PPE-induced ceramide synthase3 upregulation was suppressed by the Akt inhibitor, suggesting the involvement of Akt in the underlying mechanism. As the PI3K inhibitor did not affect PPE-induced ceramide synthase 3 upregulation, the factors upstream of Akt were estimated. Inhibition and small interfering RNA experiments demonstrated that the peroxisome proliferator-activated receptors δ (PPARδ) and integrin-linked kinase (ILK) are involved in the phosphorylation of Akt. Next, we explored the factors downstream of Akt and found that PPE induced phosphorylation of the STAT3 while PPE-induced upregulation of ceramide synthase 3 was significantly suppressed by the inhibitor of the mTOR, suggesting that the mTOR/STAT3 pathway is involved in the downstream of Akt. These results demonstrate that PPE upregulates CerS3 expression via the PPARδ/ILK/Akt/mTOR/STAT3 pathway.

Baicalein and Salvia officinalis Extract Upregulate Transglutaminase 1 mRNA Expression via the Activation of Transient Receptor Potential Channel V4

Background: It is important to maintain skin homeostasis for cosmetic and medical reasons. Many ceramide-related ingredients and cosmetics have been developed to improve the skin barrier function and skin hydration. Similar to extracellular lipids, the cornified envelope, which is a structure formed beneath the plasma membrane, contributes to the skin barrier function as a scaffold for extracellular lipids. Therefore, in this study, we focused on transglutaminase 1 (TGM1) which is the key enzyme for formation of the cornified envelope Objective: The objectives of this study were to identify compounds that could upregulate the expression of TGM1 and evaluate their underlying action mechanisms. Methods: Expression of the transient receptor potential channel vanilloid subfamily member 4 (TRPV4) at the mRNA and protein levels was estimated by PCR and western blotting. Effects of baicalein and Salvia officinalis (SO) extract on TGM1 mRNA expression were measured by PCR. The involvement of TRPV4 in TGM1 mRNA expression was evaluated by the inhibition and silencing of TRPV4. Results: TRPV4 was expressed in both basal cell-like HaCaT cells and suprabasal cell-like HaCaT cells. Baicalein and SO extract upregulated TGM1 mRNA expression in basal cell-like HaCaT cells. However, inhibition and silencing of TRPV4 abrogated the effects of baicalein and SO extract. Conclusion: Baicalein and SO extract upregulated the expression of TGM1 mRNA via the activation of TRPV4, suggesting that it may improve the skin barrier function by enhancing cornified envelope formation.

Royal Jelly Extract Accelerates Keratinocyte Proliferation, and Upregulates Laminin α3 and Integrin β1 mRNA Expression, via Akt/mTOR/HIF-1α Pathway

Background: In the previous decade, various benefits and biological activities of royal jelly, applied in alternative and modern medicine, and cosmetics, have been reported. However, the effects of royal jelly extract (RJ) on keratinocytes have not been fully elucidated. Objective: The primary objectives of this study were to reveal the effects of RJ on keratinocytes and explore the underlying mechanism. Methods: HaCaT cells, an immortal human epidermis-derived keratinocyte cell line, were used in this study. Laminin α3 (LAMA3), integrin β1 (ITGB1), and hypoxia-inducible factor-1α (HIF-1α) mRNA expression levels were determined using real-time PCR. Cell proliferation rate was measured using a bromodeoxyuridine uptake assay. Results: RJ treatment upregulated LAMA3, ITGB1 and HIF-1α mRNA expression, and accelerated HaCaT cell proliferation. Akt and mTOR inhibitors suppressed the RJ-induced HIF-1α expression and cell proliferation. HIF-1α silencing abrogated RJ-induced LAMA3 and ITGB1 mRNA expression and cell proliferation, whereas LAMA3 silencing and antibody-mediated ITGB1 blockade did not affect the effects of RJ. Conclusion: RJ upregulates LAMA3 and ITGB1 mRNA expression levels by HIF-1α expression enhancement. In addition, RJ accelerates keratinocyte proliferation via Akt/mTOR/HIF-1α/NF-κB signaling pathway. These suggest that RJ is beneficial for anti-aging, as a skin care product ingredient.