Therapeutic Potentials of Secoiridoids from the Fruits of Ligustrum lucidum Aiton against Inflammation-Related Skin Diseases

Ligustrum lucidum Aiton is a flowering plant of the Oleaceae family, and its fruits have been traditionally used for skin nourishment and the treatment of skin diseases. However, the anti-inflammatory constituents for skin disease are not well-characterized. Phytochemical investigation of L. lucidum fruits resulted in the isolation of a new secoiridoid, secoligulene (1), together with (E)-3-(1-oxobut-2-en-2-yl)pentanedioic acid (2) and trans-(E)-3-(1-oxobut-2-en-2-yl)glutaric acid (3). Secoligulene (1) displayed the potent inhibitory effect on NO production with an IC(50) value of 12.0 μg/mL. Secoligulene (1) also downregulated mRNA transcriptional levels of pro-inflammatory cytokines such as IL-1 α, IL-1β, IL-6 and COX-2 in LPS-stimulated RAW264.7 cells. Further investigation showed that secoligulene (1) inhibited the phosphorylation of IκB and JNK activated by LPS. In addition, secoligulene (1) downregulated the expression of chemokines such as CXCL8 and CCL20 in the TNF-α/IL-17/IFN-γ induced HaCaT psoriasis model. Taken together, these findings support the beneficial effects of L. lucidum and its constituents on inflammation-related skin diseases and can be further developed as therapeutic treatments for related diseases.