Anti-inflammatory activity of iridoid and catechol derivatives from Eucommia ulmoides Oliver

Neuroinflammation and pro-inflammatory mediators play key roles in the pathogenesis of neurodegenerative diseases including stroke, which account for a significant burden of morbidity and mortality worldwide. Recently, the unsatisfactory pharmacotherapy and side effects of the drugs led to the development of alternative medicine for treating these diseases. Du Zhong (DZ), Eucommia ulmoides Oliver leaves, is a commonly used herb in the therapy of stroke in China. We hypothesize that the components from DZ inhibit neuroinflammation. In this study, DZ was extracted and the bioactive fractions with inhibitory effect on lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in BV-2 microglial cells were further separated using chromatography. Two purified bioactive compounds, genipin (compound C) and 4-(1,2-dimethoxyethyl)benzene-1,2-diol (compound F), were isolated and identified after spectroscopic analysis. The results showed that they inhibited LPS-stimulated NO and tumor necrosis factor-alpha (TNF-α) production. Genipin exerted its anti-inflammatory effects through PI3K/Akt signaling pathway, whereas compound F inhibited phosphorylation of p38 mitogen-activated protein kinase (MAPK). In conclusion, genipin and compound F have potential for developing into new drugs for treating neurodegenerative diseases.