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 IC50 value of 12.0 mu g/mL. Secoligulene (1) also downregulated mRNA transcriptional levels of pro-inflammatory cytokines such as IL-1 alpha, IL-1 beta, IL-6 and COX-2 in LPS-stimulated RAW264.7 cells. Further investigation showed that secoligulene (1) inhibited the phosphorylation of I kappa B and JNK activated by LPS. In addition, secoligulene (1) downregulated the expression of chemokines such as CXCL8 and CCL20 in the TNF-alpha/IL-17/IFN-gamma 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.