Highly Oxygenated Labdane Diterpenoids from Stevia rebaudiana and Their Anti-Atherosclerosis Activities.

Five unknown labdane diterpenoids Stevelins A-E (1-5), three known labdane diterpenoids (6-8) and three labdane norditerpenoids (9-11) were isolated from the Stevia rebaudiana. The structures were determined primarily via NMR spectroscopic data and HR-ESI-MS experiments. X-ray crystallography using CuKα radiation was used to determine the absolute configurations of 1, and the absolute configurations of 2-5 were deduced by electronic circular dichroism (ECD) calculations. The potential anti-atherosclerosis activities of all compounds were evaluated by measuring their inhibitory effects on the macrophage foam cell formation. As a result, most isolated compounds could significantly inhibit oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation, which suggests that these compounds may be promising candidates in the treatment for atherosclerosis.

Callicarpanes A-L, Twelve New Clerodane Diterpenoids with NLRP3 Inflammasome Inhibitory Activity from Callicarpa integerrima.

Twelve new clerodane diterpenoids named callicarpanes A-L (1-12), together with eight known compounds (13-20), were isolated from Callicarpa integerrima. Their structures were determined by comprehensive spectroscopic data. The calculated chemical shifts were used to identify relative configurations using DP4+ analysis. The absolute configurations (AC) were assigned based on quantum chemical calculations and X-ray single-crystal diffraction methods. Compounds 1, 3, 5, 9, 10, 12, 15, 16, and 19 showed significant inhibitory activity for NLRP3 inflammasome activation, with the IC50 against lactate dehydrogenase (LDH) release ranging from 0.08 to 4.78 µM. Further study revealed that compound 10 repressed IL-1ß secretion and caspase-1 maturation in J774A.1 cell as well as blocked macrophage pyroptosis.

Chemical constituents from the twigs and leaves of Picrasma quassioides.

Two new compounds, including a norsesquiterpenoid, annuionone H (1), and a quassinoid, picraqualide G (2), along with eleven known compounds (3-13), were isolated from the twigs and leaves of Picrasma quassioides. Comprehensive spectroscopic analyses and NMR calculation with DP4+ analysis were used to identify their structures. Moreover, of all these compounds, compound 4 showed a week inhibition rate in the anti-inflammatory screening results against mouse macrophage J774A.1 cell.

Two new compounds from Verbena bonariensis.

Two new compounds verboncin A (1) and verboncin B (4) and 14 known compounds (2-3 and 5-16) were isolated from Verbena bonariensis, and these 14 compounds were first obtained from this plant. Their chemical structures were established by one and two-dimensional NMR and HRESIMS analysis and the results were compared with literature values. The absolute configuration of 1 was determined by calculating electronic circular dichroism (ECD). The cytotoxicity of some of the compounds against MCF-7, HCT-116, MDA-MB-231, and SW620 human cancer cell lines were evaluated, in which compound 4 showed negligible cytotoxic activity with an IC50 value of 68.08 ± 0.35 µM against the MCF-7 cell line.

Callintegers A and B, Unusual Tricyclo[4.4.0.09,10]tetradecane Clerodane Diterpenoids from Callicarpa integerrima with Inhibitory Effects on NLRP3 Inflammasome Activation.

Callintegers A (1) and B (2), unprecedented clerodane norditerpenoids based on a novel carbon skeleton, were isolated from Callicarpa integerrima. Compounds 1 and 2 possess a novel 6/6/6-fused tricyclic ring system. Their structures and absolute configurations were determined by quantum chemical calculations, spectroscopic analysis, and single-crystal X-ray diffraction methods. Biological evaluation showed that compound 2 inhibited IL-1ß secretion in a dose-dependent manner with an IC50 value of 5.5 ± 3.2 µM. Caspase-1 maturation and IL-1ß secretion were also reduced, indicating that compound 2 impaired NLRP3 inflammasome activation.

Callicarpnoids A-C, structurally intriguing ent-Clerodane diterpenoid dimers with cytotoxicity against MCF-7 and HCT-116 cell lines from Callicarpa arborea Roxb.

Callicarpnoids A-C (1-3), three new ent-clerodane diterpenoid dimers formed via a [4 + 2] hetero Diels-Alder cycloaddition, appeared as a third example of this type of dimers, were isolated from the stems of Callicarpa arborea Roxb.. Their structures were elucidated by comprehensive spectroscopic analysis, and the absolute configurations were confirmed by single-crystal X-ray diffraction and electronic circular dichroism (ECD) calculations, as well as DP4 + analysis. Cytotoxicity test in two cell lines indicated that compounds 2 and 3 had significant cytotoxic effect against breast cancer cell (MCF-7) and colorectal cancer cell (HCT-116) with IC50 ranging from 5.2 to 7.2 µM, comparable to those of the positive control. Furthermore, the western blot analysis revealed that the protein expression levels of Bax were increased following compounds 2 and 3 treatment, whereas the expression levels of caspase 8, caspase 3, caspase 9 and Bcl2 were decreased in a dose-dependent manner, indicating that compounds 2 and 3 may induce apoptosis via both intrinsic and extrinsic pathways in MCF-7 and HCT-116 cells.

Ainslides A-F, Six Sesquiterpenoids Isolated from Ainsliaea pertyoides and Their NLRP3-Inflammasome Inhibitory Activity.

Six new sesquiterpenoids, named as ainslides A-F (1-6), including one carotene-type sesquiterpene (1), one eudesmane (2), four guaianolides (3-6), together with eight known sesquiterpenoids (7-14), were purified from the whole plants of Ainsliaea pertyoides. The structures of these sesquiterpenoids were characterized based on spectroscopic methods including 1D and 2D NMR, HR-ESI-MS, UV, and IR spectra, together with ECD calculations and X-ray diffraction experiments. The anti-inflammatory activity of all the isolated compounds was screened and compounds 3 and 7-13 exhibited NLRP3-inflammasome inhibitory activity with IC50 values of 1.80-4.33 µM.

Callicarpins, Two Classes of Rearranged ent-Clerodane Diterpenoids from Callicarpa Plants Blocking NLRP3 Inflammasome-Induced Pyroptosis.

Callicarpins A-D (1-4), possessing an unprecedented A-homoent-clerodane scaffold with a bicyclo[5.4.0]undecane ring system, and callicarpins E-G (5-7), with 5/6-fused ent-clerodane diterpenoid skeletons, were isolated from Callicarpaarborea and C. integerrim. Their structures were elucidated by comprehensive spectroscopic data, X-ray crystal diffraction, chemical derivatization, and electronic circular dichroism (ECD) data. Putative biosynthetic pathways for these callicarpins are proposed. Compounds 2, 3b, and 6-8 showed potent inhibitory effects against the NLRP3 inflammasome with IC50 values from 1.4 to 5.3 µM, and 2 significantly blocked NLRP3 inflammasome-induced pyroptosis by inhibiting Casp-1 activation and IL-1ß secretion in J774A.1 cells.

Rubellawus A-D, Four New Diterpenoids Isolated from Callicarpa rubella and Their Anti-NLRP3 Inflammasome Effects.

Four new diterpenoids, rubellawus A-D (1-4), along with three known compounds, were isolated and identified from the flowers of Callicarpa rubella. Their structures were elucidated by various spectroscopic analysis. All the compounds were screened for their anti-inflammatory activity and 14α-hydroxyisopimaric acid and isopimaric acid showed significant NLRP3 inflammasome inhibitory activity with IC50 values of 7.02 and 3.99 µM.

Euphopias G - J, macrocyclic diterpenes with anti-zika virus activity from Euphorbia helioscopia L.

Four new diterpenoids (1-4) and sixteen known diterpenoids (5-20) were purified from the whole plant of Euphorbia helioscopia L. Compounds 1 and 2 were rhamofolane diterpenoids with a 5/7/6 tricyclic systems, compound 3 was a lathyranes diterpenoid, and compound 4 was a jathophanes diterpenoid. The isolated compounds were tested for their cytotoxicity and anti-Zika virus properties, and compounds 9 and 15 showed low cytotoxicity and strong anti-Zika virus properties with EC50 2.63 and 5.94 µM, respectively. Further, the inhibitory effects of compounds on protein levels were determined using Western blotting and immunofluorescence assays.

Three new lanostane triterpenoids and two new amides from Alternaria sp. with NLRP3 inflammasome inhibitory activity.

Three new lanostane triterpenoids (1-3) along with two new amides fatty compounds (4-5) were isolated from the ethyl acetate extract of a culture of the endophytic fungus Alternaria sp. gx-2. Their structures were identified by 1D and 2D NMR spectral data and HRESIMS. Compounds 1-12 were evaluated for their anti-inflammatory and tyrosinase inhibition activities. The isolated compounds did not show inhibitory activities at a concentration of 100 µM against tyrosinase, while under the concentration of 10 µM, the release of lactate dehydrogenase (LDH) inhibition rate of compound 1 was 54.45%, indicating that compound 1 had moderate anti-inflammatory activity on the activation of NLRP3 inflammasome.

Caseatardies A-K, eleven undescribed clerodane diterpenoids isolated from Casearia tardieuae and their anti-inflammatory activity.

A phytochemical investigation to obtain bioactive substances as lead compounds or agents for anti-inflammatory led to the obtainment of eleven previously undescribed clerodane diterpenoids, named caseatardies A-K (1-11), and four known clerodane diterpenoids (12-15) from the twigs and leaves of Casearia tardieuae. The structural elucidation of these clerodane diterpenoids was based on 1D and 2D-NMR spectroscopy (COSY, HSQC, HMBC and ROESY) as well as high resolution mass spectrometry (HR-ESI-MS). The relative configurations were defined by ROESY correlations. The anti-inflammatory activity of all the isolated compounds was screened and compound 15 decreased LDH level in a dose-dependent manner, showing IC50 value of 2.89 µM.

Euphzycopias A-I, macrocyclic diterpenes with NLRP3 inflammasome inhibitory activity from Euphorbia helioscopia L.

A phytochemical investigation was conducted on Euphorbia helioscopia, resulting in the isolation of thirteen compounds, including nine undescribed diterpenoids, Euphzycopias A - I (1-9), of which the skeletons of compounds 1-4 were found in E. helioscopia L. Compounds 1-3 had 5/7/6 cyclic systems, while compound 4 had a 4/11 polycyclic system with a 4,7-cyclic ether between C-4 and C-7. The anti-inflammasome test using the isolated compounds (1-6, 8-13) showed that the diterpenes from E. helioscopia L. had a strong inhibitory effect on NLRP3 inflammasomes with IC50 values of 3.34-14.92 µM.

Four Hybrid Flavan-Chalcones, Caesalpinnone A Possessing a 10,11-Dioxatricyclic [5.3.3.01,6]Tridecane-Bridged System and Caesalpinflavans A-C from Caesalpinia enneaphylla.

Caesalpinnone A (1), an unprecedented hybrid of flavan and chalcone, possessing a 10,11-dioxatricyclic [5.3.3.01,6]tridecane-bridged system, and caesalpinflavans A-C (2-4), three new hybrid flavan-chalcones, were isolated from the twigs and leaves of Caesalpinia enneaphylla. Their structures were elucidated by a combination of spectroscopic analyses and single-crystal X-ray diffraction. Caesalpinnone A showed the highest cytotoxicity against the HL-60, SMMC-7721, A-549, MCF-7, and SW-480 human tumor cell lines with an IC50 in the range of 0.54-0.87 µM.