A new canthinone glycoside isolated from the root barks of Ailanthus altissima with NO inhibitory activity.

One new canthinone glycoside (1), together with six known compounds (2-7) including three lignans (2-4), two coumarins (5-6) and one phenol (7) was isolated from the root barks of Ailanthus altissima. The structure of new compound 1 was established by the interpretation of UV, IR, MS and NMR data, while its absolute configuration was determined by acid hydrolysis and GIAO NMR calculations with DP4+ probability analysis. The inhibitory effects of all compounds on Nitric oxide (NO) production were investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Results showed that compounds 2 and 5 displayed NO production inhibitory activity with IC50 values of 30.1 and 15.3 µM, respectively.

2,3-Seco and 3-nor guaianolides fromAchillea alpina with antidiabetic activity.

In this study, we presented the isolation and characterization of eight novel seco-guaianolide sesquiterpenoids (1-8) and two known guaianolide derivatives (9 and 10), from the aerial part of Achillea alpina L.. Compounds 1-3 were identified as guaianolides bearing an oxygen insertion at the 2, 3 position, while compounds 4-8 belonged to a group of special 3-nor guaianolide sesquiterpenoids. The structural elucidation of 1-8, including their absolute configurations, were accomplished by a combination of spectroscopic data analysis and quantum electronic circular dichroism (ECD) calculations. To evaluate the potential antidiabetic activity of compounds 1-10, we investigated their effects on glucose consumption in palmitic acid (PA)-mediated HepG2-insulin resistance (IR) cells. Among the tested compounds, compound 7 demonstrated the most pronounced ability to reverse IR. Moreover, a mechanistic investigation revealed that compound 7 exerted its antidiabetic effect by reducing the production of the pro-inflammatory cytokine IL-1ß, which was achieved through the suppression of the NLRP3 pathway.

Monomeric and dimeric guaianolide sesquiterpenoids with hypoglycemic activity from Achillea alpina.

Three new monomeric (1-3) and two newdimeric guaianolides (4 and 5), along with three known analogues (6-8) were isolated from the aerial part of Achillea alpina L. Compounds 1-3 were three novel 1,10-seco-guaianolides, while 4 and 5 were two novel 1,10-seco-guaianolides involved heterodimeric [4 + 2] adducts. The new structures were elucidated by analysis of spectroscopic data and quantum chemical calculations. All isolates were evaluated for their hypoglycemic activity with a glucose consumption model in palmitic acid (PA)-induced HepG2-insulin resistance (IR) cells, and compound 1 showed the most promising activity. A mechanistic study revealed that compound 1 appeared to mediate hypoglycemic activity via inhibition of the ROS/TXNIP/NLRP3/caspase-1 pathway.

Two new guaianolide-type sesquiterpenoids with NO inhibitory activity from Chrysanthemum indicum.

Two new guaianolide-type sesquiterpenoids chrysanthemulides K and L (1 and 2), together with six known analogues (3-8), were isolated from an CH2Cl2 extract of the aerial parts of Chrysanthemum indicum. The structures of new compounds 1 and 2 were established by extensive spectroscopic analysis, including UV, IR, MS, NMR and computational electronic circular dichroism (ECD) methods. Inhibitory effects of all compounds on nitric oxide production were investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Results showed that compounds 1-8 displayed NO production inhibitory activity with IC50 values ranged from 3.5 to 34.3 µM.

Germacranolide- and guaianolide-type sesquiterpenoids from Achillea alpina L. reduce insulin resistance in palmitic acid-treated HepG2 cells via inhibition of the NLRP3 inflammasome pathway.

Chemical investigation on the aerial part of Achillea alpina L. led to the isolation of twenty sesquiterpenoids. The structures of the undescribed achigermalides A-H were determined by extensive spectroscopic analysis, including NMR, HRESIMS, UV and IR, and their absolute configurations were established by computational electronic circular dichroism (ECD) method. The X-ray crystal structure for 8α-angeloxy-1ß,2ß:4ß,5ß-diepoxy-10ß-hydroxy-6ßH,7αH,11ßH-12,6α-guaianolide was reported for the first time. Glucose consumption was analyzed to investigate the effect of all compounds on palmitic acid (PA)-mediated insulin resistance (IR) in HepG2 cells, and achigermalides D-F, desacetylherbohde A, and 4E,10E-3-(2-methylbutyroyloxy)-germacra-4,10(1)-diene-12,6α-olide appreciably enhanced the glucose consumption at low concentrations of 1.56-6.25 µM. Moreover, achigermalide D decreased the expression of IL-1ß and the generation of reactive oxygen species (ROS), and also down-regulated the protein levels of TXNIP, NLRP3, caspase-1 and NF-κB in the Western blot analysis, suggesting achigermalide D mediated IR via the suppression of NLRP3 inflammasome pathway.