Immunomodulatory evaluation of caffeic acid and its quinic acid derivatives using Th1/Th2 cytokine secretion profiles and principal component analysis.

Eleven Caffeic acid and its Quinic acid derivatives, including Caffeic acid, 1-O-Caffeoylquinic acid, 3-O-Caffeoylquinic acid, 4-O-Caffeoylquinic acid, 5-O-Caffeoylquinic acid, 1,3-Dicaffeoylquinic acid, 1,4-Dicaffeoylquinic acid, 1,5-Dicaffeoylquinic acid, 3,4-Dicaffeoylquinic acid, 3,5-Dicaffeoylquinic acid, and 4,5-Dicaffeoylquinic acid, were selected to evaluate their Th1/Th2 immune balance using mouse primary splenocytes. The optimal non-cytotoxic concentrations of each test compound were determined using the 3-(4,5-dimethylthiazol-2-diphenyl)-2,5-tetrazolium bromide assay. Th1 (IL-2, TNF-α) and Th2 (IL-4, IL-10) cytokine secretion levels by treated splenocytes were measured using an enzyme-linked immunosorbent assay. The tendency of each test sample towards the Th1/Th2 immune balance was further analyzed by Principal Component Analysis. The results showed that the half-maximal inhibitory concentration of Dicaffeoylquinic acids (18.0-37.8 μM) had higher cytotoxicity to splenocytes than that of Caffeic acid (49.4 μM) and Caffeoylquinic acids (45.6-52.3 μM). Caffeic acid, 3-O-Caffeoylquinic acid, and 5-O-Caffeoylquinic acid among eleven selected compounds exhibited a much higher Th1-inclined immune response, suggesting their potent Th1-inclined immunomodulatory and anti-allergic potential, but they might slightly enhance inflammation. In contrast, 1,4-Dicaffeoylquinic acid, 1,5-Dicaffeoylquinic acid, and 3,4-Dicaffeoylquinic acid tended to have a relative Th2-inclined immunomodulatory property but were speculated to have anti-inflammatory potential.