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

31/03/2025 Frontiers Journals
Mitogen-activated protein kinase (MAPK) and Wnt signaling pathways are critical for melanocyte development and melanogenesis and could be novel therapeutic targets for modulating melanin synthesis. Ligustroside is a derivative of secoiridoid compounds and has antiviral, mitochondrial dysfunction improving, and antioxidant effects. The present study aimed to evaluate the anti-melanogenesis effect of ligustroside on α-MSH-induced B16F10 murine melanoma cells.
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.
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 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.
Ligustroside derived from Ligustrum japonicum shows a significant anti-melanogenesis effect via suppression of the MAPK and PKA/CREB signaling pathways.

The work entitled “Ligustroside derived from Ligustrum japonicum inhibits melanogenesis via blocking the MAPK and PKA/CREB signaling pathways” was published on Asian Pacific Journal of Tropical Biomedicine (published on Jan. 17, 2025).

DOI: 10.4103/apjtb.apjtb_568_24
https://doi.org/10.4103/apjtb.apjtb_568_24
Reference: Zhou XR, Karadeniz F, Oh JH, Seo Y, Kong CS. Ligustroside derived from Ligustrum japonicum inhibits melanogenesis via blocking the MAPK and PKA/CREB signaling pathways. Asian Pac J Trop Biomed 2025; 15(2): 65-74.
https://doi.org/10.4103/apjtb.apjtb_568_24
Attached files
  • Image 1: Effect of ligustroside on mRNA and protein expression levels of tyrosinase, MITF, TRP-1, and TRP-2 in α-MSH-stimulated B16F10 cells. Cells were treated with ligustroside for 24 h and the changes in mRNA and protein expressions were quantified by RT-qPCR and Western blot, respectively. Values were given as relative changes compared to the control group. β-actin was used as a housekeeping gene. KA: kojic acid. *P<0.05, **P<0.001 vs. control cells, #P<0.05 vs. the blank group.
  • Image 2: Effect of ligustroside on (A-B) the MAPK and PKA/CREB signaling pathways as well as (C) nuclear protein levels of MITF, β-catenin, and p-CREB/CREB in α-MSH-stimulated B16F10 murine melanoma cells. Cells were treated with ligustroside for 24 h and the changes in protein expression were quantified by Western blot. Values were given as relative percentage of the control group. β-actin or Lamin B1 was used as a housekeeping protein. *P<0.05, **P<0.001 vs. control cells, #P<0.05 vs. the blank group.
  • Image 3: Representative images of immunofluorescence staining of MITF in α-MSH-induced B16F10 cells. Cells were stained with DAPI for viability and MITF was stained with green Alexa Fluor 488-conjugated antibody.
31/03/2025 Frontiers Journals
Regions: Asia, China
Keywords: Health, People in health research, Well being

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