Scrodentoids H and I, a Pair of Natural Epimerides from Scrophularia dentata, Inhibit Inflammation through JNK-STAT3 Axis in THP-1 Cells

Abstract

Background. Scrophularia dentata is an important medicinal plant and used for the treatment of exanthema and fever in Traditional Tibetan Medicine. Scrodentoids H and I (SHI), a pair of epimerides of C19-norditerpenoids isolated from Scrophularia dentata, could transfer to each other in room temperature and were firstly reported in our previous work. Here, we first reported the anti-inflammatory effects of SHI on LPS-induced inflammation. Purpose. To evaluate the anti-inflammatory property of SHI, we investigated the effects of SHI on LPS-activated THP-1 cells. Methods. THP-1 human macrophages were pretreated with SHI and stimulated with LPS. Proinflammatory cytokines IL-1β and IL-6 were measured by RT-PCR and enzyme-linked immunosorbent assays (ELISA). The mechanism of action involving phosphorylation of ERK, JNK, P38, and STAT3 was measured by western Blot. The NF-κB promoter activity was evaluated by Dual-Luciferase Reporter Assay System in TNF-α stimulated 293T cells. Results. SHI dose-dependently reduced the production of proinflammatory cytokines IL-1β and IL-6. The ability of SHI to reduce production of cytokines is associated with phosphorylation depress of JNK and STAT3 rather than p38, ERK, and NF-κB promoter. Conclusions. Our experimental results indicated that anti-inflammatory effects of SHI exhibit attenuation of LPS-induced inflammation and inhibit activation through JNK/STAT3 pathway in macrophages. These results suggest that SHI might have a potential in treating inflammatory disease.

A Comprehensive Review of the Classification, Sources, Phytochemistry, and Pharmacology of Norditerpenes

“…In response to inflammatory stimuli, STAT3 acts as a transcription factor that directly governs the expression of pro-inflammatory cytokines. Scrodentoids H and I might be beneficial in the treatment of inflammatory diseases, like ulcerative colitis and atherosclerotic diseases [ 105 ].…”