The diterpenoid fraction (DF) prepared from fruit of Rhododendron molle was shown to have potential therapeutic effects on collagen-induced arthritis (CIA) rats based on our previous studies. As a continuation of those studies, herein, a lipopolysaccharide-induced endotoxin shock mouse model was used. The results showed that 0.2 mg/ml of DF significantly increased the mouse survival rate and had an anti-inflammatory effect. Further studies showed that DF could decrease the proportion of T helper cells (Th1 and Th17), and increase the proportion of Th2 and regulatory T cells (Tregs). Enzyme-linked immunosorbent assays indicated that DF inhibited the secretion of inflammatory cytokines such as TNF-α, IL-1β, and IL-6; western blotting showed that DF significantly reduced the levels of phosphorylated STAT1 and STAT3. In vitro, DF could dose-dependently inhibit the polarization of naive CD4+ T cells to Th1 or Th17 cells. DF at 10 μg/ml could markedly decrease the expression of mRNA encoding IFN-γ and T-bet, and suppress Th1 differentiation by downregulation of the activity of STAT1 and STAT4. Meanwhile, DF at 10 μg/ml remarkably reduced the expression of mRNA encoding IL-17a, IL-17f, and RORγt, and downregulated STAT3 phosphorylation, suggesting that DF could inhibit Th17 differentiation by reducing STAT3 activation. Taken together, DF blocked the JAK/STAT signaling pathway by inhibiting STAT1 and STAT3 phosphorylation, which clarified the important role of JAK/STAT signaling pathway in anti-rheumatoid arthritis.
Rhododendron Molle G. Don belongs to Ericaceae family. As a toxic traditional Chinese medicine, its roots, flowers, and fruit are often mixed and substituted arbitrarily to treat rheumatoid arthritis in clinic. To clarify the main chemical basis of each medicinal part, and provide sufficient scientific basis for clinical application, analysis using HPLC-ELSD of the roots, flowers, and fruit from R. molle was established, and characteristic chemical constituents of them were separated by tracking. The structures were determined by NMR methods.Finally, 16, 21, and 18 compounds were obtained from the roots, flowers, and fruit, respectively. Overall, 49 compounds were obtained, of which 25 were identified for the first time in R. molle. Meanwhile, among the obtained compounds, 12, 11, and 6 characteristic peaks were identified from the roots, flowers, and fruit, respectively. Thus, the basic chemical substances of the medicinal parts of R. molle were determined initially.
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