Seven new meroterpenoids from the fungus Penicillium sclerotiorum GZU-XW03-2.

Seven previously undescribed meroterpenoids, peniscmeroterpenoids H - N (1-7), were isolated from the marine-derived fungus Penicillium sclerotiorum GZU-XW03-2. Their structures were established by the spectroscopic methods and the electronic circular dichroism (ECD) calculations. Peniscmeroterpenoid H was a 6/6/6/5/6 rearranged pentacyclic meroterpenoid, featuring a unique 2-oxaspiro[5.5] undeca-4,7-dien-3-one motif. Peniscmeroterpenoids I and J (2 and 3) owned rare 6(D)/5(E) fused rings were not common in natural products, and compound 2 was the second example of a berkeleyone analogue stripped of the methyl ester fragment. Peniscmeroterpenoid K (4) was the first case where the C-24 was oxidized. In bioassay, compound 5 showed moderate anti-inflammatory activity.

Triterpenoids from the genus Ilex attenuate free fatty acid-induced lipid accumulation in HepG2 cells by regulating lipid metabolism disorder and the AMPK signalling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Various traditional Chinese medicines from the genus Ilex (Aquifoliaceae) have been reported to have excellent hypolipidaemic effects. Although triterpenoids have been found to be the main active components, the underlying mechanisms have not been clarified. AIM OF THE STUDY: This study aimed to investigate the lipid-lowering effect, structure-activity relationship and action mechanism of triterpenoids from the genus Ilex. MATERIALS AND METHODS: FFA was used to induce HepG2 cells to establish a classical lipid-lowering activity screening model for the activities of 31 triterpenoids, and the contents of intracellular lipids, TC, and TG were measured. Furthermore, the structure-activity relationship was discussed. Mechanistically, UPLC-Q/TOF-MS-based metabolomics and lipidomics studies were performed, and metabolic pathways were analysed to investigate the lipid-lowering mechanism. Moreover, western blotting was performed to analyse the expression of key proteins of lipid metabolism and predict the targets of action. RESULTS: Thirteen triterpenoids significantly reduced intracellular lipid accumulation and decreased the levels of TG and TC. Among them, rotundic acid (RA) showed stronger lipid-lowering activity than the simvastatin-positive group, and structure-activity relationship analysis indicated that the hydroxyl groups at C-3 and C-19, hydroxymethyl groups at C-23, and carboxyl groups at C-28 may be the key groups for biological activity. Twenty-two metabolites in the metabolomics study and 19 metabolites in the lipidomics study were identified. The identified biomarkers were primarily glycerophosphocholine, LysoPCs, PCs, TAGs, LysoPEs, LysoPIs and sphingolipids, which are involved in glycerophospholipid and sphingolipid metabolism. Moreover, western blotting analysis showed that the expression of SREBP-1 and HMGCR decreased, while AMPK and ACC phosphorylation and the expression of CPT1A and CYP7A1 increased in the RA-treated group. CONCLUSION: The results suggested that triterpenoids from the genus Ilex showed significant lipid-lowering effects and that RA may be a novel hypolipidaemic drug candidate. Moreover, the underlying mechanism indicated that RA showed a lipid-lowering effect by regulating glycerophospholipid and sphingolipid metabolism and activating the AMPK pathway.

Meroterpenoids from the fungus Penicillium sclerotiorum GZU-XW03-2 and their anti-inflammatory activity.

Seven undescribed meroterpenoids, peniscmeroterpenoids A - G, were isolated from the marine-derived fungus Penicillium sclerotiorum GZU-XW03-2. Their structures were established by the spectroscopic methods and the electronic circular dichroism (ECD) calculations. Peniscmeroterpenoid A possessed an unprecedented and highly oxidized 6/7/6/5/5 pentacyclic system, featuring a unique tetrahydrofuro [2,3-b]furan-2(3H)-one motif. Peniscmeroterpenoids B - E owned rare 6(D)/5(E) fused rings were not common in natural products, and peniscmeroterpenoid E is the first example of a berkeleyone analogue stripped of the methyl ester fragment. In bioassays, peniscmeroterpenoids A and D inhibited the production of nitric oxide (NO) in RAW264.7 cells with IC50 values of 26.60 ± 1.15 and 8.79 ± 1.22 µM. Moreover, peniscmeroterpenoid D significantly suppressed the production of pro-inflammatory mediators (COX-2, IL-1ß and IL-6) and the protein expression of the enzyme iNOS.