Immunosuppressive Sesquiterpene Pyridine Alkaloids from Tripterygium wilfordii Hook. f.

Abstract

Tripterygium wilfordii Hook. f. is a well-known traditional Chinese medicine used to treat autoimmune diseases. Sesquiterpene pyridine alkaloids (SPAs) are a major class of components found in this herb that have piqued the interest of researchers due to their complex and diverse structures as well as significant biological activities. In this study, ten new SPAs, wilfordatine A–J (1–10), were isolated from the roots of T. wilfordii, along with ten known analogues (11–20). Their structures were primarily elucidated by extensive 1D and 2D NMR spectroscopic analysis. To search for more immunosuppressive ingredients related to the clinical efficacy of T. wilfordii, the total alkaloids (TA) and compounds 4, 5, and 9–16 were tested for their inhibitory effects on nuclear factor-kappa B (NF-κB) pathway in Lipopolysaccharide (LPS) induced HEK293/NF-κB-Luc cells. Among them, TA, compounds 5, 11, and 16 showed potent immunosuppressive activity, with IC50 values of 7.25 μg/mL, 8.75 μM, 0.74 μM, and 15.66 μM, respectively, and no influence on the cell viability at a concentration of 100 μg/mL (TA) or 100 μM (5, 11, and 16). Accordingly, TA, 5, 11, and 16, especially 11, were identified as promising candidates for further investigation into their potential use as immunosuppressive agents.

Research Progress of Natural Active Substances with Immunosuppressive Activity

“…The inhibitory effects of compounds 150-152 on the nuclear factor-kappa B pathway were assessed in HEK293 cells induced with LPS. The IC 50 values obtained for these compounds were 8.75 µM, 0.74 µM, and 15.66 µM, respectively [60]. Alopecines A-E (153-157) were isolated from the seeds of Sophora alopecuroides, which showed moderate to significant immunosuppressive activity against T-cell and B-cell proliferation, with the IC 50 values ranging from 3.9 to 100 µM and from 3.7 to 96.8 µM, respectively [61].…”

“…Tables S1-S9: Compounds 1-324 with Immunosuppressive Effects. References [60][61][62][63][64][65][66][67][68] are cited in the Supplementary Materials.…”