Hinokione: an abietene diterpene with pancreatic ß cells regeneration and hypoglycemic activity, and other derivatives with novel structures from the woods of Agathis dammara.

In this study, 14 abietene and pimarene diterpenoids were isolated from the woods of Agathis dammara. Among them, 4 new compounds, dammarone A-C and dammaric acid A (1-4), were firstly reported, respectively. The structure of the new compounds was determined by HR ESI-MS and 1D/2D NMR spectroscopy, and their absolute configuration was determined by electronic circular dichroism (ECD) exciton chirality method. The hypoglycemic effect of all compounds was evaluated by transgenic zebrafish model, and the structure-activity relationship was discussed. Hinokione (7, HO) has low toxicity and significant hypoglycemic effects on zebrafish, the mechanism is mainly by promoting the differentiation of zebrafish pancreatic endocrine precursor cells (PEP cells) into ß cells, thereby promoting the regeneration of pancreatic ß cells.

Compounds from Agathis dammara exert hypoglycaemic activity by enhancing glucose uptake: lignans, terpenes and others.

In this study, two new kaurane diterpenes (16, 17), together with 12 lignans (1-12), a triterpene (15), and two other compounds (13, 14) were isolated from the woods of Agathis dammara. The structure of the new compound was determined by HR ESIMS and 1D/2D NMR spectroscopy, and its absolute configuration was determined by electronic circular dichroism (ECD) exciton chirality method. Compounds 5, 11, 14 exhibit significant hypoglycaemic activity in zebrafish, and their mechanism of action is to enhance glucose uptake in zebrafish.

Three new compounds from Anoectochilus roxburghii (Wall.) Lindl.

In this study, three new compounds, roxburic acid A (1) and two flavone glycosides isorhamnetin-3-O-α-L-rhamnosyl-(1→6)-ß-D-glucopyranose-(1→3)-ß-D-glucopyranoside (2), and kaempferol-7-O-ß-D-glucopyranosyl-(1→3)-ß-D-glucopyranoside (3) were isolated from an ethanol extract of the fresh Anoectochilus roxburghii (Wall.) Lindl., together with 10 known compounds (4-13). The structures of these compounds were comprehensively characterized by HR-ESI-MS, 1H NMR, 13C NMR, and 2 D-NMR. The DPPH free radical scavenging activity of the isolated compounds was evaluated, and the results showed that kaempferol-7-O-ß-D-glucopyranosyl- (1→3) -ß-D-glucopyranoside (3) and rutin (11) has the potential antioxidant activity with IC50 values of 139 µg/mL and 22.5 µg/mL respectively.

Anti-inflammatory sesquiterpenoids from the heartwood of Juniperus formosana Hayata.

Juniperus formosana Hayata (J. formosana) is a commom needlebush cultivar growing in China. Six new compounds (1-6), including four cadinene sesquiterpenoids (1-4), one abietane diterpenoid (5), and one ß-naphthol derivative (6), along with 18 known compounds (7-24) were isolated and identified through phytochemical investigation on the heartwood of J. formosana. The structures of these compounds were fully elucidated by their 1D and 2D NMR, HR-ESI-MS, UV, and IR spectral data analyses. The absolute configurations of compounds 1, 3, and 5 were confirmed by experimental and calculated electronic circular dichroism (ECD) data. Moreover, X-ray crystallographic analysis was carried out to characterize the structure of compound 4. The inhibitory effects on the nitric oxide (NO) production of all the isolated compounds were initially examined in RAW264.7 macrophages induced by lipopolysaccharide (LPS). The results showed that compounds 3 and 12 possessed significant inhibitory potency on NO generation with IC50 values of 3.41 µM and 6.15 µM among the new and known compounds, respectively. The expressions of IL-1ß, IL-6, and TNF-α were measured in LPS-stimulated RAW264.7 cells to evaluate the anti-inflammatory effects of compounds 1-24. Compounds 1-6 and 9-12 exhibited potent anti-inflammatory effects. Additionally, the expressions of p38, Erk, and IκBα proteins were further determined to explore the anti-inflammatory mechanism of the most potent compounds 3 and 12. Overall, our findings indicate the potential of J. formosana for developing medicine candidates as the treatments of inflammation.

Bioactive compounds derived from the marine-derived fungus MCCC3A00951 and their influenza neuraminidase inhibition activity in vitro and in silico.

Penicillium polonicum MCCC3A00951 is a fungus with influenza neuraminidase (NA) inhibition activity derived from a sediment of the mangrove forest of Zhangjiangkou in Fujian province, China. Chemical investigation on an ethyl acetate extract of its fermentation led to the isolation of a new compound, 7-hydroxy-3,10-dehydrocyclopeptine (1), and 13 known compounds (2-14). The new compound was comprehensively characterised by high-resolution electrospray ionisation-mass spectrometry, and 1D, 2D nuclear magnetic resonance (NMR) spectra. The anti-influenza NA assay was performed to evaluate the potential biological activity. Surprisingly, Cyclopenin (2) showed potent influenza NA inhibition with an IC50 value of 5.02 µM. Besides, molecular docking simulation was performed to investigate the binding model of cyclopenin (2) with influenza NA. Consequently, cyclopenin (2) could be further optimised to be a potential anti-influenza NA candidate.