Dendropanax dentiger (Harms) Merr. root and its major constituents exert therapeutic effect on adjuvant-induced arthritis in rats

Abstract

Ethnopharmacological relevanceThe root of Dendropanax dentiger (Harms) Merr. is a pivotal folk Chinese medicine against rheumatoid arthritis (RA) with no scientific validation. Aim of the studyThis study was conducted to explore the anti-RA effect of the D. dentiger extract on complete Freund's adjuvant-induced arthritis (AIA) in rats and identified its major bio-constituents. Materials and methodsDendropanax dentiger roots extracts (127.5, 255.0 and 510.0 mg/kg, once daily) were orally at day 7 post-administration adjuvant and lasting for 22 days. The therapeutic effects of D. dentiger roots extract on AIA rats were investigated by body weight growth, arthritis score, thymus and spleen indices, and histopathological analysis. Moreover, the levels of rheumatoid factor (RF), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-4, IL-6, IL-10, IL-17, cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and matrix metalloproteinase-2 (MMP-2) were also evaluated. Finally, the major constituents were isolated and identified from D. dentiger roots extract with COX-2 inhibitory and antioxidant activities. ResultsDendropanax dentiger roots extract remarkably alleviated the histological lesions of knee joint, increased body weight growth, decreased arthritis score, and reduced thymus and spleen indices in model rats. In parallel, the levels of RF, CRP, TNF-α, IL-1β, IL-6, IL-17, COX-2, 5-LOX and MMP-2 were observably downregulated, while the levels of IL-4 and IL-10 were prominently upregulated in D. dentiger roots extract-treated rats. Meanwhile, 14 compounds were isolated and identified from D. dentiger roots extract, and four phenol derivatives (1, 4, 6 and 7) exhibited remarkable COX-2 inhibitory and antioxidant activities. ConclusionsDendropanax dentiger roots extract possessed persuasive anti-RA effect may be partly responsible for phenol derivatives via modulation of inflammatory biomarkers, and supports the traditional folk use of D. dentiger in China.