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

Abstract EN

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.