Ligustroside derived from Ligustrum japonicum inhibits melanogenesis via blocking the MAPK and PKA/CREB signaling pathways

Abstract

Objective: To investigate the anti-melanogenic potential of ligustroside isolated from Ligustrum japonicum.

Methods: The cytotoxicity of ligustroside was tested via MTT assay. Furthermore, the effects of ligustroside on the expression of critical melanogenic markers such as tyrosinase, tyrosinase related proteins (TRPs), and microphthalmia-associated transcription factor (MITF) were analyzed at both mRNA and protein levels via RT-qPCR and Western blot, respectively, in α-melanocyte stimulating hormone-induced B16F10 cells. In addition, phosphorylation of p38, ERK and JNK proteins was investigated. Immunofluorescence analysis of MITF was also conducted.

Results: Ligustroside significantly reduced intracellular tyrosinase activity and melanin content by 37.11% and 29.12%, respectively, compared to untreated cells. Moreover, it downregulated the expression of MITF, tyrosinase, TRP-1, and TRP-2 at the mRNA and protein levels by regulating both the mitogen-activated protein kinase (MAPK) and protein kinase A (PKA)/cAMP response element-binding protein (CREB) signaling pathways. Ligustroside also suppressed the nuclear protein expression of MITF, β-catenin, and p-CREB, and decreased immunofluorescence intensity of nuclear MITF.

Conclusions: Ligustroside derived from Ligustrum japonicum shows a significant anti-melanogenesis effect via suppression of the MAPK and PKA/CREB signaling pathways.

Keywords

Ligustrum japonicum / Ligustroside / MAPK / Melanogenesis / CREB / PKA

Conflict of interest statement

The authors declare that they have no conflict of interest.

Funding

This research was supported by the BB21plus funded by Busan Metropolitan City and Busan Techno Park, and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. NRF-2023R1A2C1006268 and RS-2023-00212560).

Data availability statement

The data supporting the findings of this study are available from the corresponding authors upon request.

Authors’ contributions

XRZ and CSK conceived the idea and designed the study. XRZ, and JHO performed the experiments, acquired the data and validated the results. XRZ and FK drafted the original manuscript and XRZ, FK and YS contributed to the revisions. JHO and YS performed the extraction and fractionation. JHO, FK, and CSK performed the statistical analysis, data curation, and validation and visualization of the results. YS and CSK supervised the project.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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