Royal Jelly Extract Accelerates Keratinocyte Proliferation, and Upregulates Laminin <i>α</i>3 and Integrin <i>β</i>1 mRNA Expression, via Akt/mTOR/HIF-1<i>α</i> Pathway

Abstract

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 α 3 (LAMA3), integrin β 1 (ITGB1), and hypoxia-inducible factor-1 α (HIF-1 α ) 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-1 α mRNA expression, and accelerated HaCaT cell proliferation. Akt and mTOR inhibitors suppressed the RJ-induced HIF-1 α expression and cell proliferation. HIF-1 α 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-1 α expression enhancement. In addition, RJ accelerates keratinocyte proliferation via Akt/mTOR/HIF-1 α /NF- κ B signaling pathway. These suggest that RJ is beneficial for anti-aging, as a skin care product ingredient.