Flavonoid glycosides from Barringtonia acutangula

Using various chromatographic separation techniques, ten flavonoid glycosides, including six new compounds namely barringosides A?F (1–6), were isolated from a methanol extract of the Barringtonia acutangula leaves. The structure elucidation was confirmed by spectroscopic analyses, including 1D and 2D NMR, and HR ESI MS. Their inhibitory effects on LPS-induced NO production in RAW264.7 cells were also evaluated. Among the isolated compounds, quercetin 3-O-β-d-(6-p-hydroxybenzoyl)galactopyranoside (9) showed significant effect with an IC₅₀ of 20.00 ± 1.68 µM. This is the first report of these flavonoid glycosides from Barringtonia genus and their inhibition on LPS-induced NO production in RAW264.7 cells was reported here for the first time.     

New lignan glycosides from the root barks of Litsea glutinosa

An investigation on the chemical constituents in the root barks of Litsea glutinosa was performed for the first time. Three new lignan glycosides named Litseasins A–C (1–3), together with a known one (4), were obtained. The structures of the new compounds were established through extensive spectroscopic analyses including HR-ESI–MS, NMR, and circluar dichroism (CD). The new compounds were evaluated for their anti-inflammatory activities on lipopolysaccharide (LPS)-induce nitric oxide (NO) production in RAW264.7 murine macrophage cells. However, these compounds showed no inhibition on LPS-induced NO productions.     

Anti-inflammatory activity of halogenated secondary metabolites of Laurencia snackeyi (Weber-van Bosse) Masuda in LPS-stimulated RAW 264.7 macrophages

Secondary metabolites of tropical seaweed are proven to exhibit variety of biological activities. Six species of seaweed (Caulerpa racemosa var. laete-virens, Caulerpa sertularioides f. longipes, Halymenia dilatata, Laurencia snackeyi, Padina boryana, and Sargassum swartzii) were tested for anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Crude L. snackeyi extract exhibit potent activity, and upon bioassay-guided isolation, it contained four halogenated compounds that exert profound inhibitory effects against nitric oxide (NO) production in LPS-stimulated RAW 264.7 cells. These compounds were subjected to spectroscopic measurements and were identified as palisadin A (1), aplysistatin (2), 5-acetoxypalisadin B (3), and palisol (4). Further experiments showed aplysistatin (2) to significantly inhibit NO production and prostaglandin-E2 (PGE2) production, and suppress inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in LPS-stimulated RAW 264.7 cells. Therefore, aplysistatin (2) is suggested to inhibit NO and PGE2 production via the inhibition of iNOS and COX-2, indicating that its activity may be attributed to the modulation of anti-inflammatory agents.     

Three Neolignan Glycosides from the Root of Nothopanax davidii

Three neolignan glycosides, including a new compound (7S,8R)-dihydro-3′-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1′-benzofuranpropanol-9-O-β-D-xylopyranoside ( 1 ), were isolated from the root of Nothopanax davidii. Their structures were determined by extensive spectroscopic analyses, particularly NMR, HR-ESI-MS, and ECD experiments, and the absolute configuration of 2 was first definitively determined. The anti-tumor activity was assessed on four tumor cells by MTT assay, the anti-inflammatory activity was determined by inhibition of NO production in LPS reduced RAW264.7 cells, and the interaction with iNOS was predicted by molecular docking. At the dose of 100 μM, the three neolignan glycosides showed no cytotoxic activity against HepG2, HCT116, HeLa and A549 human tumor cells, but significantly inhibited LPS induced NO generation in RAW264.7 cells with inhibition rates of 31.53 %, 23.95 %, and 20.79 %, respectively, showing weak anti-inflammatory activity, possibly due to their binding to key residues of iNOs involved in inhibitor binding.     

Phenolic glycosides from Alangium salviifolium leaves with inhibitory activity on LPS-induced NO,PGE2, and TNF-α production

Three new phenolic glycosides, salviifosides A?C (13), and three known compounds salicin (4), kaempferol (5), and kaempferol 3-O-β-d-glucopyranoside (6) were isolated from the leaves of Alangium salviifolium (L.f.) Wangerin (Alangiaceae). The structures of the new metabolites were determined on the basic of spectroscopic analyses including two dimensional NMR. The anti-inflammatory activities of new compounds (1?3) were investigated on lipopolysaccharide (LPS)-induced murine macrophage cells line, RAW 264.7. Salviifoside B (2) potentially inhibits the productions of nitric oxide (NO), prostaglandin E₂ (PGE₂), and tumor necrosis factor-α (TNF-α).     

Triterpene glycosides from red ginseng marc and their anti-inflammatory activities

Three new triterpene glycosides ursan-3β,19α,22β-triol-3-O-β-d-glucopyranosyl (2′→1″)-β-d-glucopyranoside (1), ursan-3α,11β-diol-3-O-α-d-glucopyranosyl-(6′→1″)-α-d-glucopyranosyl-(6″→1‴)-α-d-glucopyranosyl-(6‴→1‴′)-α-d-glucopyranoside (2) and lanost-5,24-dien-3β-ol-3-O-β-d-glucopyranosyl-(6′→1″)-β-d-glucopyranosyl-(6″→1‴)-β-d-glucopyranoside (3), together with one known compound were isolated and identified from the marc of red ginseng. Their structures were elucidated by spectroscopic data analysis. Compounds (1–3) were investigated for anti-inflammatory effects using the RAW 264.7 macrophage cell line. In the cell proliferation assay, lipopolysaccharide stimulation decreased cell proliferation of RAW 264.7 macrophage cells, but the suppression of cell proliferation was significantly protected by treatment with compounds 2 and 3. Compounds 2 and 3 had a suppressive effect on the production of nitric oxide (NO), and they inhibited mRNA expression of proinflammatory mediators such as inducible nitric oxide synthase, and cyclooxygenase-2, and proinflammatory cytokines such as two interleukins and tumor necrosis factor-α. These findings suggest that compounds 2 and 3 have potential anti-inflammatory activities.     

Synergistic anti-inflammatory effects of silibinin and thymol combination on LPS-induced RAW264.7 cells by inhibition of NF-κB and MAPK activation

BackgroundCombination drug therapy has become an effective strategy for inflammation control. The anti‑inflammatory capacities of silibinin and thymol have each been investigated on its own, but little is known about the synergistic anti-inflammatory effects of these two compounds.PurposeThis study aims to investigate the synergistic anti-inflammatory effects of silibinin and thymol when administered in combination to lipopolysaccharide (LPS)-induced RAW264.7 cells.MethodsRAW264.7 cells were pre-treated with silibinin and thymol individually or in combination for 2 h before LPS stimulation. Cell viability was detected by the MTT assay. Nitric oxide (NO) production was measured by Griess reagent. Reactive oxygen species (ROS) was evaluated by 2’,7’-dichlorofluorescein-diacetate. ELISA was used to detect tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Western blot was performed to analyse the protein expression of LPS-induced RAW264.7 cells.ResultsWe observed a synergistic anti-inflammatory effect of silibinin and thymol when administered in combination to LPS-induced RAW264.7 cells. Silibinin combined with thymol (40 μM and 120 μM respectively, with the molar ratio 1:3) had more potent effects on the inhibition of NO, TNF-α, and IL-6 than those exerted by individual administration of these compounds in LPS-induced RAW264.7 cells. The combination of silibinin and thymol (40 μM and 120 μM respectively, with the molar ratio 1:3) strongly inhibited ROS and cyclooxygenase-2 (COX-2). More importantly, the combination of silibinin and thymol (40 μM and 120 μM respectively, with the molar ratio 1:3) was also successful in inhibiting nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) activities. Our results suggest that the synergistic anti-inflammatory effects of silibinin with thymol were associated with the inhibition of NF-κB and MAPK signalling pathways.ConclusionThe combination of silibinin and thymol (40 μM and 120 μM, respectively, with the molar ratio 1:3) could inhibit inflammation by suppressing NF-κB and MAPK signalling pathways in LPS-induced RAW264.7 cells.     

Polygonflavanol A,a novel flavonostilbene glycoside from the roots of Polygonum multiflorum

Polygonflavanol A (1), a novel flavonostilbene glycoside with an unusual coupling pattern, together with five known stilbene glycosides (2–6), was isolated from the roots of Polygonum multiflorum. The structures were elucidated on the basis of extensive spectroscopic analysis and chemical evidence. The absolute configuration of 1 was further determined by CD analysis. Most of the compounds could inhibit nitric oxide (NO) secretion of RAW264.7 cells in respond to lipopolysaccharide (LPS) in a dose dependent manner. Among them, compound 2 displayed the highest inhibitory activity.     

Corrigendum to “A new phenylethyl glycoside and a new dibenzocyclooctadiene lignan from the leaves of Kadsura coccinea (Lem.) A. C. Smith” [Phytochem. Lett. 45 (2021) 57–62]

A new phenylethyl glycoside (1), (S)-1-phenylethyl-6-α-L-arabinopyranosyl-β-D-glucopyranoside), and a new dibenzocyclooctadiene lignan (7), Kasuracin A, together with seven known compounds, were isolated and identified from the leaves of Kadsura coccinea. Their structures were determined by analysis of multinuclear and multidimensional nuclear magnetic resonance (NMR), circular dichroism (CD), mass spectrometry, hydrolysis analysis, or comparison to those reported in the literature. Then, all the isolates 1‒9 were evaluated for their inhibitory eff ;ects against nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Among them, compounds 2 and 3 were isolated for the first time from this plant and compounds 3, 7, 8, and 9 significantly inhibited NO production with IC₅₀ values of 36.4, 10.2, 12.3, and 21.7 μM, respectively.     

Five New Glycoside Constituents from the Roots of Gentiana crassicaulis Duthie ex Burk.

Three undescribed glycoside constituents, macrophyllosides E-G and a pair of iridoid glycosides genticrasides A/B, together with eleven known glycoside compounds were isolated from the roots of Gentiana crassicaulis Duthie ex Burk. Their structures were identified by means of spectra analysis and data comparison with previous literatures. Interestingly, the glucose moieties in macrophylloside E and F possess free anomeric hydroxy groups. Genticrasides A/B, identified as a pair of iridoid originated lactones, have not been reported from Gentianaceae family up to now. The anti-inflammatory effects of selected compounds were also evaluated through the nitric oxide (NO) production inhibition in lipopolysaccharides (LPS)-induced RAW264.7 macrophage cells. In which, macrophyllosides G and D showed NO inhibitory activities with rates of 76.14±4.02 % and 52.44±8.29 % at 100 μg/mL.     

Two pairs of new diastereoisomeric flavonolignans from the seeds of Hovenia acerba

Two pairs of new diastereomeric flavonolignans, hovenins A–D (1–4), were isolated from the seeds of Hovenia acerba. Their structures were established on the basis of spectroscopic methods and circular dichroism experiments. All compounds significantly inhibited NO and IL-6 generation in lipopolysaccharide (LPS)-stimulated macrophages (RAW264.7 cells) in a dose-dependent manner.     

Structures and biological evaluation of phenylpropanoid derivatives from Murraya koenigii

Four new phenylpropanoid derivatives (1–4), together with eleven known analogues (5–15) were isolated and identified by comparison with their references and extensive spectroscopic methods from Murraya koenigii for the first time. Compounds (1–15) were assayed for their inhibitory activities by measuring IL-6-induced STAT3 promoter activities in HepG2 cells, and found compounds 1, 2, 6, and 15 showed inhibitory effects with IC₅₀ values of 11.5, 18.7, 8.9, and 22.7 μM, respectively. The inhibitory activities of compounds (1–15) were screened against NO production in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells, and found compounds 3, 4, 9, 11, and 14 exhibited inhibitions against LPS-induced NO production in RAW264.7 macrophages, with IC₅₀ values of 32.7, 7.9, 42.1, 58.9, and 62.4 μM, respectively.     

Sentulic acid isolated from Sandoricum koetjape Merr attenuates lipopolysaccharide and interferon gamma co-stimulated nitric oxide production in murine macrophage RAW264 cells

A seco-triterpenoid, sentulic acid (SA) isolated from Sandoricum koetjape Merr attenuated nitric oxide (NO) production following co-stimulation with lipopolysaccharide (LPS) and interferon-gamma (IFNγ) in RAW264.7 macrophage cells. The mRNA expression levels of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), IFNγ, interleukin (IL)-6, and IL-12 in LPS/IFNγ co-stimulated RAW264.7 cells also decreased upon SA treatment. To determine the molecular mechanisms underlying the inhibitory effect of SA on LPS/IFNγ-induced NO production in RAW264.7 cells, we further analyzed Toll-like receptor (TLR) signaling by western blotting. The expression of TLR4 and IFN signaling molecules in cells treated with SA was significantly suppressed compared to that in cells not treated with SA. Additionally, SA inhibited the binding of LPS to the TLR4 receptor in RAW264.7 cells stimulated with Alexa Fluor 488-conjugated LPS. These results demonstrate that SA attenuates NO production after LPS/IFNγ co-stimulation in RAW264.7 cells by inhibiting the binding of LPS to TLR4. Our findings suggest that SA is beneficial for the treatment of inflammatory diseases.     

Anti-inflammatory effects of two new stilbene-phenylpropanoid derivatives from Chamaecrista pumila

Two new stilbeno-phenylpropanoid compounds, given the trivial names chamaecristanols A and B (1 and 2), were isolated from the ethyl acetate-soluble partitions of separate methanol extracts of the aerial parts of Chamaecrista pumila (Lam.) K. Larsen. The structures of these compounds were determined on the basis of interpretation of their spectroscopic data and comparison with reported literature data. Their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells were evaluated. Results showed that compounds 1 and 2 significantly inhibited NO production with IC₅₀ values of 41.69 ± 1.34 and 32.14 ± 0.15 µM, respectively.     

Isolation and Characterization of Anti-Inflammatory Sorbicillinoids from the Mangrove-Derived Fungus Penicillium sp. DM815

Marine derived fungus has gained increasing ground in the discovery of novel lead compounds with potent biological activities including anti-inflammation. Here, we first report the characterization of one new sorbicillinoid ( 1 ) and fourteen known compounds ( 2 – 15 ) from the ethyl acetate (AcOEt) extract of a cultured mangrove derived fungus Penicillium sp. DM815 by UV, IR, HR ESI-Q-TOF MS, and NMR spectra. We then evaluated the anti-inflammatory effects of eleven sorbicillinoids ( 1 – 11 ) using cultured macrophage RAW264.7 cells. The results show that compound 9 , and to a lesser degree compound 5 , significantly inhibited the Gram-negative bacteria lipopolysaccharide (LPS)-induced upregulation of the inducible nitric oxide synthase (iNOS). Consistently, compounds 5 and 9 significantly reduced the level of nitric oxide (NO), the product of iNOS, induced by LPS. We further show that these two compounds dose-dependently inhibited LPS-triggered iNOS expression and NO production, but had no effect on proliferation of RAW264.7 cells in the presence of LPS. In conclusion, our study identifies novel and known sorbicillinoids as potent anti-inflammatory agents, holding the promise of developing novel anti-inflammation treatment in the future.     

Tanzawaic acid derivatives from a marine isolate of Penicillium sp. (SF-6013) with anti-inflammatory and PTP1B inhibitory activities

Chemical investigation of a marine-derived fungus Penicillium sp. SF-6013 resulted in the discovery of a new tanzawaic acid derivative, 2E,4Z-tanzawaic acid D (1), together with four known analogues, tanzawaic acids A (2) and D (3), a salt form of tanzawaic acid E (4), and tanzawaic acid B (5). Their structures were mainly determined by analysis of NMR and MS data, along with chemical methods. Preliminary screening for anti-inflammatory effects in lipopolysaccharide (LPS)-activated microglial BV-2 cells showed that compounds 1, 2, and 5 inhibited the production of nitric oxide (NO) with IC₅₀ values of 37.8, 7.1, and 42.5 μM, respectively. Compound 2 also inhibited NO production in LPS-stimulated RAW264.7 murine macrophages with an IC₅₀ value of 27.0 μM. Moreover, these inhibitory effects correlated with the suppressive effect of compound 2 on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in LPS-stimulated RAW264.7 and BV2 cells. In addition, compounds 2 and 5 significantly inhibited the activity of protein tyrosine phosphatase 1B (PTP1B) with the same IC₅₀ value (8.2 μM).     

New C-2 diastereomers of flavanone glycosides conjugated with 3-hydroxy-3-methylglutaric acid from the pericarp of Citrus grandis (L.) Osbeck

Two new 3-hydroxy-3-methylglutaryl (HMG) flavanone 7-O-diglycosides, cigranosides A and B (1 and 2), the known naringenin 7-(2′′-α-rhamnosyl-6′′-(3′′′′-hydroxy-3′′′′-methylglutaryl)-glucoside (melitidin, 3), their common biosynthetic precursor flavanone 7-O-diglycoside (naringin, 4), and one known flavone 7-O-diglycoside (rhoifolin, 5) were isolated from the pericarp of Citrus grandis (L.) Osbeck. The structures of these compounds were elucidated by spectroscopic and chemical techniques. The relative ratios and absolute configurations of the C-2 diastereomers of compounds 1, 2 and 4 were determined by online normal-phase HPLC-CD using a Chiralcel column. The absolute configuration of the HMG fragment in compounds 1–3 was assigned to be S through spectroscopic analysis of the mevalonamide obtained by amidation and reduction of the HMG moiety. The NO inhibitory activities of compounds 1–5 were evaluated using lipopolysaccharide-induced RAW264.7 cells. Compounds 1–5 were not cytotoxic to RAW264.7 cells at 10 μM.     

Pelliolatifolias A-D,Four Undescribed Compounds from Pellionia latifolia Boerl. and Their Nitric Oxide Production Inhibitory Activity

Four undescribed compounds ( 1 – 4 ) named pelliolatifolias A−D together with seven known compounds trans-clovamide ( 5 ), N-trans-caffeoyl-4-hydroxyphenylalanine methyl ester ( 6 ), N-trans-caffeoyl-3,4-dihydroxyphenylalanine methyl ester ( 7 ), luteolin 4’-O-β-D-glucopyrannoside ( 8 ), cis-syringin ( 9 ), trans-syringin ( 10 ), and citroside A ( 11 ) have been isolated from the methanol extract of the Pellionia latifolia leaves. Their chemical structures were elucidated based on extensive analyses of HR-ESI-MS, 1D and 2D NMR, and CD spectra. Compounds 1 – 7 , 9 and 10 showed moderate inhibition of NO production in LPS-activated RAW264.7 cells with their IC₅₀ values ranging from 39.27 to 75.42 μM, compared to that of the positive control compound, dexamethasone, IC₅₀ value of 14.20 μM.