RESUMEN
Cembranolides are characteristic metabolites in marine soft corals, with complex structures and widespread biological activities. However, seldom has an intensive pharmacological study been done for these intriguing marine natural products. In this work, systematic chemical investigation was performed on Sinularia pedunculata by HSQC-based small molecule accurate recognition technology (SMART), resulting in the isolation and identification of 31 cembrane-type diterpenoids, including six new ones. In the bioassay, several compounds showed significant anti-inflammatory activities on the inhibition of NO production. The structure-activity relationship (SAR) was comprehensively analyzed, and two most bioactive and less toxic compounds 8 and 9 could inhibit inflammation through suppressing NF-κB and MAPK signaling pathways, and reduce the secretion of inflammatory cytokines. In a mouse model of dextran sodium sulfate (DSS)-induced acute colitis, 8 and 9 exhibited good anti-inflammatory effects and the ability to repair the colon epithelium, giving insight into the application of cembranolides as potential ulcerative colitis (UC) agents.
Asunto(s)
Antozoos , Colitis Ulcerosa , Sulfato de Dextran , Diterpenos , Animales , Colitis Ulcerosa/tratamiento farmacológico , Diterpenos/farmacología , Diterpenos/química , Diterpenos/uso terapéutico , Diterpenos/aislamiento & purificación , Ratones , Relación Estructura-Actividad , Antozoos/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Antiinflamatorios/aislamiento & purificación , Células RAW 264.7 , FN-kappa B/metabolismo , FN-kappa B/antagonistas & inhibidores , Descubrimiento de Drogas , Ratones Endogámicos C57BL , Humanos , Masculino , Óxido Nítrico/metabolismoRESUMEN
Alpinia hainanensis is an important food spice and ethnic medicine in Southwest China. In this study, we found that the EtOAc-soluble fraction (AHE) of the A. hainanensis rhizome ethanol extract could ameliorate dextran sulfate sodium-induced ulcerative colitis (UC). To explore active constituents, five pairs of previously unreported enantiomers (1-5), together with nine known ones (6-14), were obtained. Structural characterization was achieved by comprehensive spectroscopic methods. Compounds 1 and 2 were new curcumin-butyrovanillone hybrids featuring a rare structural fragment of 2,3-dihyrofuran. The anti-inflammatory activities of isolates were evaluated, and the results indicated that compounds (-)-1, (-)-3, 6, 9, 11, and 12 significantly inhibited the nuclear factor-κB signaling pathway. These findings indicate the major active fraction of the A. hainanensis rhizome ethanol extract enriched with diarylheptanoids, flavonoids, phenolics, and their hybrid mixtures, which could be developed as a nutritional and dietary supplement for treating UC.
Asunto(s)
Alpinia , Colitis Ulcerosa , Animales , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Humanos , FN-kappa B/metabolismo , Extractos Vegetales/química , RizomaRESUMEN
Hedyorienoids A (1) and B (2), two sesquiterpenoid dimers, were isolated and characterized from Hedyosmum orientale. Compound 1 was an unprecedented heterodimer of two different classes of sesquiterpenoids furnished by forming an unusual 1,3-dioxolane ring, while compound 2 possessed a new dimerization pattern of two guaiane-type sesquiterpenoids. Biosynthetic pathways for 1 and 2 were proposed with the coexisting monomers chloranthalactone A (3) and hedyosumin A (4) as the precursors. Compounds 2 and 3 showed significant NF-κB inhibitory activity.
