Spirohypertones A and B as potent antipsoriatics: Tumor necrosis factor- inhibitors with unprecedented chemical architectures.

Tumor necrosis factor- (TNF-) is a promising target for inflammatory and autoimmune diseases. Spirohypertones A () and B (), two unprecedented polycyclic polyprenylated acylphloroglucinols with highly rearranged skeletons, were isolated from . The structures of and were confirmed through comprehensive spectroscopic analysis, single-crystal X-ray diffraction and electronic circular dichroism calculations. Importantly, showed remarkable TNF- inhibitory activity, which could protect L929 cells from death induced by co-incubation with TNF- and actinomycin D. It also demonstrated the ability to suppress the inflammatory response in HaCaT cells stimulated with TNF-. Notably, in an imiquimod-induced psoriasis murine model, restrained symptoms of epidermal hyperplasia associated with psoriasis, presenting anti-inflammatory and antiproliferative effects. This discovery positions as a potent TNF- inhibitor, providing a promising lead compound for developing an antipsoriatic agent.