Chemical constituents of the Vietnamese liverwort Porella densifolia

From the ether extract of Porella densifolia, the first liverwort collected and chemically investigated in Vietnam, a kaurane diterpenoid, ent-kauren-15-one (1) and two sesquiterpene norpinguisone (2) and norpinguisone methyl ester (3) have been purified. Their structures were elucidated by spectroscopic analysis. In addition, an X-ray crystal structure of norpinguisone was obtained, allowing to determine its stereochemistry. Furthermore, the inhibitory activity of nitric oxide (NO) production in RAW 264.7 cells stimulated by lipopolysaccharide (LPS) of compounds 1–3 was examined with their IC₅₀ values of 69.4, 45.5 and 1.68 μM, respectively.     

3, 4-seco-Labdane diterpenoids from the leaves of Callicarpa nudiflora and their inhibitory effects on nitric oxide production

As a part of our ongoing search for bioactive compounds from the leaves of Callicarpa nudiflora that inhibit nitric oxide (NO) production, the 90% EtOH fraction eluted by macroporous resin adsorption was found to show significant inhibitory activity against the production of NO in RAW 264.7 stimulated by lipopolysaccharide (LPS). Bioactivity-guided isolation of the fraction yielded three new bioactive diterpenoids, named ent-3, 4-seco-14-carbonyl-15, 16-epoxy-4(18), 8(17), 13(14)-labdatrien-3-oic acid (1), syn-3, 4-seco-12R-hydroxy-15, 16-epoxy-4(18), 8(17), 13(16), 14(15)-labdatetraen-3-oic acid (2) and syn-3, 4-seco-12S-hydroxy-15, 16-epoxy-4(18), 8(17), 13(16), 14(15)-labdatetraen-3-oic acid (3). Their structures and configurations were elucidated by comprehensive spectroscopic analysis. All the three compounds exhibited potent inhibitory activity on NO production in LPS-activated RAW 264.7 macrophage cells.     

Screening of Indonesian medicinal plants for inhibitor activity on nitric oxide production of RAW264.7 cells and antioxidant activity

Traditional Indonesian medicinal plants were screened for their inhibitory effects on the nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and for the antioxidant activity through the evaluation of free radical scavenging effect and reducing power. The results of screening indicated that 50 methanolic extracts inhibited (>50%) lipopolysaccharides (LPS)-induced NO release from RAW264.7 cells at 50 microg/ml, with 18 having greater than 100% inhibition. At 200 microg/ml, 61 methanol extracts exhibited inhibitory activity (>50%), with 45 showing greater than 100% inhibition. In addition, the free radical scavenging effects of 6 methanolic extracts were found to be more than 50% for extract concentration of 0.5 mug/ml. The results indicate that the extracts contain active compounds that inhibit NO release and scavenge free radical.     

Japonicones Q–T,four new dimeric sesquiterpene lactones from Inula japonica Thunb.

Four new dimeric sesquiterpene lactones (japonicones Q–T, 1–4) were isolated from the aerial part of Inula japonica Thunb., together with two known ones. Their structures were determined mainly by 1D and 2D NMR spectroscopic techniques including HSQC, ¹H–H COSY, HMBC, and NOESY. Herein, the inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 macrophages of 1–6 were evaluated; IC₅₀ values were tested as 8.5, 8.9, 4.3, 4.3, 4.2, and 9.2 μM, respectively.     

Labdane diterpenes from Chloranthus serratus

Five new labdane diterpenes (1–5), serralabdanes A–E, were isolated from the whole plant of Chloranthus serratus. Their structures were elucidated by spectroscopic methods, and the absolute configuration of the 12,13-diol moiety in serralabdane C (3) was determined by observing the induced circular dichroism (ICD) after addition of dimolybdenum teracetate in DMSO solution. Serralabdanes A–E (1–5) showed inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells.     

New ursane-type triterpenoid saponins from the stem bark of Schefflera heptaphylla

Phytochemical investigation on the stem bark of Schefflera heptaphylla led to the isolation of five new ursane-type triterpenoid saponins (1–5). Their structures were determined on the basis of spectroscopic and chemical methods. It is noteworthy in this study that the genins of all compounds are reported for the first time. All compounds isolated from this plant were evaluated for their inhibitory activities on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells, and compounds 2 and 5 showed weak anti-inflammatory activities under their non-cytotoxic concentrations.     

Indole alkaloids from the roots of Isatis indigotica and their inhibitory effects on nitric oxide production

Three rare indole-2-S-glycosides, indole-3-acetonitrile-2-S-β-D-glucopyranoside (1), indole-3-acetonitrile-4-methoxy-2-S-β-D-glucopyranoside (2) and N-methoxy-indole-3-acetonitrile-2-S-β-D-glucopyranoside (3), together with 11 known indole alkaloids were isolated from the roots of Isatis indigotica Fort. (Cruciferae). The structures of 1–3 were elucidated on the basis of mass spectrometry and extensive 1D and 2D NMR spectroscopy. All of the isolated compounds were tested for inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages. A plausible biosynthesis pathway of 1–3 is also proposed.     

Anti-inflammatory and anti-osteoporotic lignans from Vitex negundo seeds

Chemical investigation of Vitex negundo seeds afforded four new lignans, including a phenylindene-type lignan, vitexdoin F (1), and three phenylnaphthalene-type lignans, vitexdoins G, H and I (2–4). Their structures were elucidated by detailed spectroscopic analyses on the basis of NMR, IR, and MS data. All compounds were evaluated for their anti-inflammatory and anti-osteoporotic activities, employing RAW264.7 macrophages, osteoblast-like UMR106 and osteoclastic cells, respectively. Compound 1 showed significant inhibition on the nitric oxide (NO) production (IC₅₀ 4.17 μg/mL) due to its down-regulation of the inducible nitric oxide synthase (iNOS) protein expression in LPS-stimulated RAW264.7 cells, which also exhibited potent stimulatory effects on the proliferation and ALP (alkaline phosphatase) activity of UMR106 cells, and significantly up-regulated the OPG/RANKL protein ratio.     

Protection against neurodegenerative diseases of Iris pseudopumila extracts and their constituents

The present study describes for the first time the in vitro properties of Iris pseudopumila flowers and rhizomes extracts and their constituents. The methanolic extract of rhizomes showed significant anti-inflammatory activity through inhibition of NO production in the murine monocytic macrophage cell line RAW 264.7. Among the isolated compounds, those which most effectively inhibited LPS-induced NO production were irisolidone and 7-methyl-tectorigenin-4′-O-[β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside], with IC₅₀ values of 23.6 μM and 29.4 μM respectively. Isoorientin and isovitexin exhibited the most promising activity against AChE with IC₅₀ of 26.8 μM and 36.4 μM, respectively. The same compounds exhibited also the higher activity against BChE.     

New sesquiterpenic acids from Inula wissmanniana

Eight new (1−8) and two known (9 and 10) sesquiterpenic acids featuring α-methylene-γ-carboxyl units were isolated from the whole plants of Inula wissmanniana, along with two new germacranolides (11 and 12). Their structures were elucidated based on detailed spectroscopic analysis, including HRESIMS, 1D and 2D NMR, and X-ray crystallography. Notably, the skeleton of 1 was firstly discovered from nature, while that of 2 was discovered for the second time. All the compounds were evaluated for their inhibition against LPS-induced nitric oxide (NO) production in RAW264.7 macrophages. Compound 11 exhibited the strongest activity with the IC₅₀ value of 1.04 μM.     

New sesquiterpenoids from the dried flower buds of Tussilago farfara and their inhibition on NO production in LPS-induced RAW264.7 cells

Three new sesquiterpenoids, 1α-(3″-ethyl-cis-crotonoyloxy)-8-angeloyloxy-3β,4β-epoxy-bisabola-7(14),10-diene (1), 7β-angeloyloxy-14-hydroxy-notonipetranone (2) and 1α-hydroxy-7β-(4-methylsenecioyloxy)-oplopa-3(14)Z,8(10)-dien-2-one (3) were isolated from ethanolic extract of the dried flower buds of Tussilago farfara L., along with nine known sesquiterpenoids (4-12). All of these compounds were evaluated for their effect on the inhibition of nitric oxide (NO) production induced by lipopolysaccharide in macrophage cell line RAW 264.7 and exhibited inhibitory activity on NO production in a dose-dependent manner. 7β-(4-Methylsenecioyloxy)-oplopa-3(14)E,8(10)-dien-2-one (8) was proved to be the best among these tested sesquiterpenoids with an IC(50) value of 10.80 μM.     

Dihydrochalcones and homoisoflavanes from the red resin of Dracaena cochinchinensis (Chinese dragon's blood)

Two new dihydrochalcones, 4-hydroxy-2,4′-dimethoxydihydrochalcone (1) and 3,4′-dihydroxy-2,4,6-trimethoxydihydrochalcone (2), and a new homoisoflavane, 7,3′-dihydroxy-8,4′-dimethoxyhomoisoflavane (3), along with 12 known compounds (4–15), were isolated from the red resin of Dracaena cochinchinensis (Chinese dragon's blood). Their structures were assigned by a variety of spectroscopic techniques. Diversity of cleavage pathways were proposed for dihydrochalcones and homoisoflavanes based on the mass spectroscopic behaviors of those identified compounds using hybrid ion trap-time of flight mass spectrometry. All the compounds were evaluated for their inhibitory effects on nitric oxide production in lipopolysaccharide-induced RAW 264.7 macrophages, and compound 9 exhibited mild inhibition of NO production in this assay with IC₅₀ value of 50.3 μM.     

Phenolics from Leontopodium leontopodioides inhibiting nitric oxide production

Two new compounds, a neolignan (1), and a benzofuran derivative (2), along with 6 known compounds (3-8), were isolated from the aerial parts of Leontopodium leontopodioides. The structures of the new compounds were elucidated as (7R,8S)-3,5'-dimethoxy-4',7-epoxy-8,3'-neolignane-5,9,9'-triol (1) and (2R)-12-hydoxy-4-methoxy-tremeton (2) on the basis of their spectroscopic data, respectively. All of the isolates were evaluated for their effects on the inhibition of nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 macrophages and compounds 1 and 8 exhibited inhibitory activity with IC(50) values of 35.80 and 24.41 μM, respectively.     

Cytotoxic and anti-inflammatory ent-kaurane diterpenoids from Isodon wikstroemioides

Seven new ent-kaurane diterpenoids, isowikstroemins A–G (1–7), were isolated from EtOAc extracts of the aerial parts of Isodon wikstroemioides. Their structures were elucidated by extensive spectroscopic analysis. The isolates were evaluated for their cytotoxicity against five human tumor cell lines, and compounds 1–4 exhibited significant activity with IC₅₀ values ranging from 0.9 to 7.0 μM. In addition, compounds 1, 2, 3, 4, and 7 exhibited inhibitory activity against nitric oxide (NO) production in LPS-activated RAW264.7 macrophages.     

Four new eudesmane-type sesquiterpenes from the basal leaves of Salvia plebeia R. Br.

Four new eudesmane-type sesquiterpenes, named plebeiolide A–C (1–3) and plebeiafuran (4), together with a known eudesmanolide (5), were isolated from the basal leaves of Salvia plebeia R. Br. Their structures were elucidated by extensive spectroscopic analysis including 1D and 2D NMR, HR-ESI-MS spectra. The absolute configuration of compound 1 was confirmed by single-crystal X-ray analysis and CD spectra. The inhibitory activity of isolated compounds toward NO production in lipopolysaccharide-induced RAW264.7 cells was evaluated and compounds 3 and 4 showed moderate inhibitory activity. In addition, the sesquiterpene lactones in Lamiaceae plants may possess some chemosystematic implications at intergeneric and intrageneric levels.     

Anti-inflammatory lignanamides from the roots of Solanum melongena L.

Four new lignanamides, melongenamides A–D (1–4), together with six known ones (5–10), were isolated from the roots of Solanum melongena L. Their structures were elucidated on the basis of 1D and 2D NMR experiments and by comparison of their spectroscopic and physical data with the literature values. Compounds 2–8 exhibited inhibitions of nitric oxide production in lipopolysaccharide-induced RAW 264.7 macrophages with IC₅₀ values ranging from 16.2 to 58.5 μM.     

Induction of heme oxygenase-1 by Macleaya cordata extract and its constituent sanguinarine in RAW264.7 cells

Macleaya cordata (plume poppy) is used in traditional Chinese medicine for its anti-inflammatory and antibacterial activities. In this study, we examined whether M. cordata extract and/or its major alkaloid constituents, protopine, allocryptopine, sanguinarine and chelerythrine activate the Nrf2 signalling pathway which regulates the expression of cytoprotective enzymes including heme oxygenase-1 (HO-1) and thioredoxin 1. In murine macrophage RAW264.7 cells, M. cordata extract increased both mRNA and protein levels of HO-1. Of the alkaloids examined, only sanguinarine appeared to be responsible for these effects. At the concentration of 2 μM, sanguinarine induced nuclear accumulation of Nrf2, increased the expression of Hmox1 gene encoding HO-1 and elevated HO-1 protein levels. Sanguinarine-induced Hmox1 mRNA expression was suppressed by SB203580, a pharmacologic inhibitor of p38 mitogen-activated protein kinases (p38 MAPKs). The upregulation of HO-1 in RAW264.7 cells by sanguinarine was, however, accompanied by decrease in cell viability. Nonetheless, sanguinarine at micromolar, non-cytotoxic concentrations elevated protein levels of HO-1 and thioredoxin 1 in primary cultures of human hepatocytes. We conclude that sanguinarine may, under appropriate conditions, increase the capacity of the enzymatic antioxidant defence system via activation of the p38 MAPK/Nrf2 pathway.     

Anti-inflammatory activity of sulfate-containing phenolic compounds isolated from the leaves of Myrica rubra

Three sulfated phenolic compounds, juglanin B (11R)-O-sulfate (1), myricetin 3´-O-sulfate (2), and ampelopsin 3´-O-sulfate (3), were isolated from the leaves of Myrica rubra. Compound 1 was a new sulfated lignan, 2 was a new sulfated flavone, and 3 was a known sulfated flavone. The structures of the new compounds (1 and 2) were determined by acid hydrolysis and spectroscopic methods, including IR, FAB-MS, 1D and 2D NMR. The inhibitory activities of compounds 1–3 and their hydrolysates (1a–3a) against LPS-induced cytokine (TNF-α, IL-1β, and IL-6) production in macrophage RAW 264.7 cells were evaluated. The 2 new compounds (1 and 2) and their aglycones (1a and 2a) significantly reduced LPS-induced expression of iNOS and COX-2 proteins.     

Sesquiterpenes inhibiting NO production from Celastrus orbiculatus

Two new (1 and 2) and one known (3) β-dihydroagarofuran sesquiterpenes were isolated from the fruits of Celastrus orbicultus Thunb. Their structures were elucidated as 1β,13-diacetoxy-8β,9β-dibenzoyloxy-β-dihydroagarofuran (1), 1β,13-diacetoxy-8α-hydroxy-9β-benzoyloxy-β-dihydroagarofuran (2), and 1β,6α,13-triacetoxy-9α-benzoyloxy-β-dihydroagarofuran (3), on the basis of spectroscopic data analyses. All the compounds exhibited inhibitory effects on LPS-induced nitric oxide production in murine microglial BV-2 cells.