Monocyclic and polycyclic polyprenylated acylphloroglucinols with anti-steatohepatitis effect from the pericarps of Garcinia multiflora.

Natural products are an important source of drug candidates against fatty liver. Herein, two previously undescribed monocyclic polyprenylated acylphloroglucinols (MPAPs, 1 and 2) and three new polycyclic polyprenylated acylphloroglucinols (PPAPs, 3-5) were isolated from the pericarps of Garcinia multiflora, and structurally elucidated by comprehensive spectroscopic analyses and electronic circular dichroism (ECD) calculations, together with five known PPAPs. Compounds 1 and 2 are rare dinor-MPAPs. In lipopolysaccharide (LPS)-induced RAW264.7 macrophages, compounds 1, 3 and 4 significantly suppressed nitric oxide production. Among them, compound 3 showed the best inhibitory effect with an IC50 value of 4.12 ± 0.94 μМ. Furthermore, compound 3 effectively reduced interleukin-1β secretion in LPS plus nigericin-induced THP-1 macrophages by inhibiting NLRP3 inflammasome activation. Interestingly, the conditioned medium from LPS plus nigericin-stimulated THP-1 macrophages pre-treated with compound 3 attenuated lipid accumulation in oleic acid plus palmitic acid (2/1)-induced HepG2 hepatocytes. Taken together, these findings expand the chemical diversity of G. multiflora, and further demonstrate the potential of PPAPs as candidates for treating steatohepatitis.