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

Abstract

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.