Constituents from leaves of Macaranga hemsleyana.

Objective: To study constituents of the leaves of Macaranga hemsleyana, and evaluate their inhibitory effects against NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation, and antiproliferative activity. Methods: The constituents were isolated and purified by column chromatography on MCI gel CHP20P/P120, silica gel, Sephadex LH-20, and HPLC. The structures of compounds were determined by 1D, 2D NMR, and HR-ESI-MS data. The inhibitory effect of compounds on inflammasome activation was determined by lactate dehydrogenase (LDH) procedure. The antiproliferative activity was evaluated using MTT assay. Results: The study led to the isolation of 23 compounds, including one new compound, identified as (2Z)-3-[4-(ß-D-glucopyranosyloxy)-2'-hydroxy-5'-methoxyphenyl]-2-propenoic acid (1), together with 22 known compounds recognized as 1,4-dihydro-4-oxo-3-pyridinecarbonitrile (2), methyl 4-methoxynicotinate (3), 4-methoxynicotinonitrile (4), 1-(3-O-ß-D-glucopyranosyl-4,5-dihydroxyphenyl)-ethanone (5), neoisoastilbin (6), isoastilbin (7), aromadendrin (8), neoastilbin (9), astilbin (10), quercitrin (11), neoschaftoside (12), apigenin 6,8-bis-C-α-L-arabinoside (13), vitexin (14), bergenin (15), scopoletin (16), glucopyranoside salicyl (17), koaburside (18), benzyl ß-D-glucoside (19), icariside B5 (20), roseoside (21), loliolide (22), and adenosine (23). The tested compounds did not show LDH inhibition nor antiproliferative activity. Conclusion: Compound 1 was a new glycoside. Compounds 2 and 3 were obtained for the first time from natural source. The 22 known compounds constituted of alkaloids (2-4, 23), phenolics (5, 15, 17, 18), flavonoids (6-14), coumarin (16), benzyl glycoside (19), and norsesquiterpenes (20-22). All the compounds, 1-23, were revealed from M. hemsleyana for the first time. This is the initial uncovering of molecules 1-10, 12, 13, 17-19, and 23 from the genus Macaranga. The isolated compounds, 11, 14-16, and 20-22 established taxonomic classification of M. hemsleyana in Euphorbiaceae family. Flavonoids were outstanding as chemosystematic markers of Macaranga genus.

Euphzycopins A - D, macrocyclic diterpenoids with potential anti-inflammatory activity from Euphorbia Helioscopia.

Four new diterpenoids (1-4) and four known diterpenoids (5-8) were purified from the whole plant of Euphorbia helioscopia L. Compounds 1 and 2 were jathophanes diterpenoids with a 5/12 polycyclic systems, compound 3 was rhamofolane diterpenoid with a 5/10 bicyclic skeleton and compound 4 was a rare class of euphorbia diterpenes featuring an unusual 5/10 fused ring system. Anti-inflammatory activity tests were conducted on the separated compounds, indicating that compound 4 had significant inhibitory effect on NLRP3 inflammasome with an IC50 value of 7.75 µM. Further, the inhibitory effect of 4 was determined using immunofluorescence assays.

Bioactive diterpenoids isolated from the twigs and leaves of Casearia velutina.

Nine previously undescribed clerodane-type diterpenoids (1-9), named caseabalanspenes A-I, along with six know compounds (10-15), were isolated from the twigs and leaves of Casearia velutina. Spectroscopic data (1D and 2D NMR) analysis permitted the definition of their structures and then determination of the molecular formula of the compound by high resolution mass spectrometry (HR-ESI-MS). It is worth noting that compound 7 contains N- heterocycle. Compounds 1-8 were tested the anti-inflammasome activity, and compound 3 exhibited potent activity and decreased LDH level in a dose-dependent manner, with IC50 values of 2.90 µM.

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.

Diterpenoids from Strophioblachia glandulosa and Their NLRP3 Inflammasome Inhibitory Effects.

Our study on the roots and leaves of the never-hitherto-chemically studied S. glandulosa led to the isolation of five new diterpenes, referred to as stroglandulons A-E (1-5), alongside 18 known constituents (6-23). The structures of the new compounds were elucidated on the basis of their spectroscopic data, while the known ones were determined based on the comparison of their data with the literature values. Compounds 1-5 were evaluated for their inhibitory effects against NLRP3 inflammasome activation; compound 5 showed inhibition by an IC50 value of 6.12±0.03 µM.

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.

Leojaponin inhibits NLRP3 inflammasome activation through restoration of autophagy via upregulating RAPTOR phosphorylation.

ETHNOPHARMACOLOGICAL RELEVANCE: Duan Teng Yimu decoction is a Chinese herbal medicine compound with proven therapeutic effects on inflammasome-related diseases, such as rheumatoid arthritis. This decoction consists of three Chinese herbal medicines, including Leonurus japonicus (L. japonicus), which promotes the blood circulation and exhibits detumescence activity, traditionally curing gynecologic and inflammasome diseases. AIM OF THE STUDY: To explore the anti-inflammasome activity and the underlying mechanisms of action of the compounds from L. japonicus. MATERIALS AND METHODS: A series of compounds were isolated from L. japonicus. Their anti-inflammasome activities were evaluated in macrophages that were co-stimulated by lipopolysaccharide (LPS) and NLRP3 inflammasome inducers. NLRP3 inflammasome formation and apoptosis speck like containing a CARD (ASC) oligomerization were evaluated by immunofluorescent microscopy and Western blot analysis. The regulation of autophagy after treatment of this compound was also evaluated. Lastly, in vivo activity of Leojaponin was analyzed in a mouse acute gouty arthritis model. RESULTS: Here we show that Leojaponin, a diterpenoid compound from L. japonicus, suppressed lactate dehydrogenase and IL-1ß release in Nigericin-stimulated macrophages in a pyroptosis model. Leojaponin inhibits NLRP3 inflammasome activation in both J774A.1 cells and bone marrow-derived macrophages in a dose dependent manner. Moreover, Leojaponin suppressed NLRP3-mediated ASC specks formation and ASC oligomerization. These activities of Leojaponin depend on restoration of autophagy via promoting RAPTOR phosphorylation. Furthermore, Leojaponin ameliorated monosodium urate (MSU)-induced acute gouty arthritis in vivo. CONCLUSION: Our findings suggest that Leojaponin inhibits NLRP3 inflammasome activation through enhancing autophagy via RAPTOR phosphorylation, thereby highlighting Leojaponin as a potent drug for inflammasome-related diseases.