Hyparillums A and B: polycyclic polyprenylated acylphloroglucinols from Hypericum patulum.

Hyparillums A (1) and B (2), two previously unidentified polycyclic polyprenylated acylphloroglucinols (PPAPs) with intricate architectures, were isolated from Hypericum patulum Thunb. Hyparillum A was the first PPAP with eight-carbon rings based on an unprecedented 6/6/5/6/6/5/6/4 octocyclic system featuring a rare heptacyclo[10.8.1.11,10.03,8.08,21.012,19.014,17]docosane core. In contrast, hyparillum B featured a novel heptacyclic architecture (6/6/5/6/6/5/5) based on a hexacyclo[9.6.1.11,9.03,7.07,18.011,16]nonadecane motif. Furthermore, hyparillums A and B demonstrated promising inhibitory effects on the proliferation of murine splenocytes stimulated by anti-CD3/anti-CD28 monoclonal antibodies and lipopolysaccharide, exhibiting half-maximal inhibitory concentration (IC50) values ranging from 6.13 ± 0.86 to 12.69 ± 1.31 µmol·L-1.

Maydistacins A-G, Terpestacin-type Sesterterpenoids with Anti-inflammatory Activity from the Phytopathogenic Fungus Bipolaris maydis.

Seven undescribed terpestacin-type sesterterpenoids, maydistacins A-G (1-7), along with two known congeners (8 and 9), were isolated from the phytopathogenic fungus Bipolaris maydis collected from the leaves of Hypericum longistylum. The structures of 1-7 were elucidated based on extensive spectroscopic analysis, chemical methods, NMR calculations with DP4+ probability analysis, and comparison of experimental and calculated electronic circular dichroism (ECD) calculations. In vitro anti-inflammatory effects of these compounds were tested in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Compound 1 exhibited inhibition of the production of nitric oxide in LPS-induced macrophages, with an IC50 value of 19 ± 2 µM. A dexamethasone control displayed an IC50 value of 6.7 ± 0.6 µM. Compound 1 is the first terpestacin-type sesterterpenoid reported to display anti-inflammatory activity and may provide a novel chemical scaffold for the discovery of new anti-inflammatory drugs.

Prenyllongnols A-D, New Prenylated Acylphloroglucinols that Fight Concanavalin A-Induced Autoimmune Hepatitis.

Autoimmune hepatitis is a serious hepatic disorder with unknown nosogenesis, and natural products have been deemed to be one of the most significant sources of new drugs against this disease. Prenyllongnols A-D (1-4), four undescribed prenylated acylphloroglucinols, were isolated from Hypericum longistylum. Compounds 1-4 exhibited remarkable immunosuppressive activities in murine splenocyte proliferation under the induction of concanavalin A (Con A), and IC50 values ranged from 2.98 ± 0.21 to 6.34 ± 0.72 µM. Furthermore, in a Con A-challenged autoimmune hepatitis mouse model, the mice in the group that were pretreated with isolate 2 significantly ameliorated liver injury and decreased proinflammatory cytokine production. Notably, natural product 2 was the first prenylated acylphloroglucinol to protect against concanavalin A-induced autoimmune hepatitis. This finding underscores the potential of prenylated acylphloroglucinol-type metabolites as promising candidates for designing novel immunosuppressors in the quest for new antiautoimmune hepatitis drugs.