Anti-inflammatory effects of phenolic compounds isolated from the flowers of Nymphaea mexicana Zucc.

Nymphaea mexicana Zucc. is an aquatic plant species which belongs to the family Nymphaea and is commonly known as the yellow water lily. The aim of this work was to study the in vitro antiinflammatory effects of phenolic compounds isolated from the flowers of Nymphaea mexicana Zucc. Seven phenolic compounds including vanillic acid, 4-methoxy-3,5-dihydroxybenzoic acid, (2R,3R)-3,7-dihydroxyflavanone, naringenin (4), kaempferol 3-O-(3-O-acetyl-a-L-rhamnopyranoside), kaempferol 3-O-(2-O-acetyl-a-L-rhamnopyranoside), and quercetin 3-(30 0-acetylrhamnoside) (7) were isolated from the flowers of Nymphaea mexicana Zucc. These results revealed that compound 4 has the most prominent inhibitory effect on the LPS-stimulated nitric oxide (NO), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF-a) production in RAW 264.7 macrophages. In addition, compound 4 also inhibited LPS-mediated induction of protein expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and phospho-ERK in RAW 264.7 macrophages. Thus, compound 4 from the flowers of Nymphaea mexicana Zucc. may provide a potential therapeutic approach for inflammation-associated disorders.

Geranyl flavonoid derivatives from the fresh leaves of Artocarpus communis and their anti-inflammatory activity.

Breadfruit (Artocarpus communis) is a widely distributed crop in tropical and subtropical regions of the world. It is used in Southeast Asia and India to treat several inflammatory disorders. The aim of this study was to investigate the presence of anti-inflammatory flavonoids in A. communis leaves. Three new geranyl flavonoids, arcommunol C (1), arcommunol D (3), and 5'-geranyl-3,4,2',4'-tetrahydroxychalcone (5), together with four known compounds, prostratol (2), arcommunol E (4), 3'-geranyl-3,4,2',4'-tetrahydroxydihydrochalcone (6), and 3'-geranyl-3,4,2',4'-tetrahydroxychalcone (7), were isolated from the leaves of A. communis. Compound 4 was isolated for the first time from natural sources. The anti-inflammatory activity of the isolated compounds (1-7) was evaluated by determining their inhibitory activity on the production of proinflammatory mediators in lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophage cells. Compounds 2, 3, and 4 suppressed the LPS-induced production of nitric oxide (NO) in RAW 264.7 cells with IC50 values of 8.13 ± 0.17, 18.45 ± 2.15, and 22.74 ± 1.74 µM, respectively. Furthermore, 2 decreased lipopolysaccharide (LPS)-mediated induction of protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW 264.7 cells. It was also found that 2 suppressed LPS-induced phosphorylation of JNK and p38 mitogen-activated protein kinase (MAPK) signaling.

Anti-inflammatory effect of the 5,7,4'-trihydroxy-6-geranylflavanone isolated from the fruit of Artocarpus communis in S100B-induced human monocytes.

The fruit of Artocarpus communis Moraceae, a traditional starch crop, is a rich source of phytochemicals, such as flavonoids and their derivatives. The aim of this study was to investigate whether 5,7,4'-trihydroxy-6-geranylflavanone (AC-GF), a geranyl flavonoid derivative isolated from the fruits of A. communis, could decrease the activation of inflammatory mediators induced by S100B (ligand of receptor for advanced glycation end products, RAGE) in THP-1 monocytes. According to the results, low levels of AC-GF (≤2.5 µM) showed a great inhibitory effect on gene expression of RAGE and down-regulated both TNF-α and IL-1ß secretion and gene expression (p < 0.05). AC-GF also decreased reactive oxygen species (ROS) production in response to S100B (p < 0.05). Additionally, Western blotting revealed that AC-GF could effectively attenuate RAGE-dependent signaling, including expression of protein kinase C (PKC) and p47phox, phosphorylation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK), and particularly NF-κB activation (p < 0.05). In conclusion, this is the first report that AC-GF possesses great antioxidant and anti-inflammatory properties in vitro. This finding may contribute to increased implication and utilization of the fruit of A. communis Moraceae in functional foods.

Anticancer effects of flavonoid derivatives isolated from Millettia reticulata Benth in SK-Hep-1 human hepatocellular carcinoma cells.

Millettia reticulata Benth is cultivated in Asian countries. M. reticulata Benth has multiple biological functions and is one of the oldest tonic herbs in traditional Chinese medicine. It has been elevated to one of the most commonly used herbs in modern Chinese medicine. The aims of this work were to study the in vitro anticancer activity of flavonoid derivatives isolated from the stems of M. reticulata Benth. Six flavonoid derivatives including (-)-epicatechin (1), naringenin (2), 5,7,3',5'-tetrahydroxyflavanone (3), formononetin (4), isoliquiritigenin (5), and genistein (6) were isolated from the stems of M. reticulata Benth. The structures of 1-6 were determined by spectroscopic methods. The effects of flavonoid derivatives (1-6) on the viability of human cancer cells (including HepG2, SK-Hep-1, Huh7, PLC5, COLO 205, HT-29, and SW 872 cells) were investigated. The results indicated that genistein (6) had the strongest inhibitory activity with an IC(50) value of 16.23 microM in SK-Hep-1 human hepatocellular carcinoma cells. Treatment of SK-Hep-1 cells with genistein (6) caused loss of mitochondrial membrane potential. Western blot data revealed that genistein (6) stimulated an increase in the protein expression of Fas, FasL, and p53. Additionally, treatment with genistein (6) changed the ratio of expression levels of pro- and anti-apoptotic Bcl-2 family members and subsequently induced the activation of caspase-9 and caspase-3, which was followed by cleavage of poly(ADP-ribose) polymerase (PARP). These results demonstrate that genistein (6) induces apoptosis in SK-Hep-1 cells via both Fas- and mitochondria-mediated pathways.

Synthesis, antiplatelet and vasorelaxing activities of xanthone derivatives.

A series of omega-aminoalkoxylxanthones was synthesized and tested in vitro for their ability to inhibit platelet aggregation and cause vasorelaxing action. Compounds 4, 5, 12, 17, and 18 showed significant antiplatelet effects on thrombin-, arachidonic acid (AA)-, collagen-, and platelet activating factor (PAF)-induced washed rabbit platelet aggregation and exhibited inhibition of primary and secondary aggregation induced by adenosine-5'-diphosphate (ADP) in human platelet-rich-plasma (PRP). Compounds 4, 17, and 18 revealed vasorelaxing activities in rat thoracic aorta. We concluded that these compounds may be developed as new antithrombotic agents.

Cytotoxic effects of new geranyl chalcone derivatives isolated from the leaves of Artocarpus communis in SW 872 human liposarcoma cells.

Breadfruit (Artocarpus communis Moraceae) is cultivated in tropical and subtropical regions as a traditional starch crop and also has potential medicinal properties. The aim of this work was to study the in vitro anticancer activity of compounds isolated from the leaves of Artocarpus communis. Three new geranyl chalcone derivatives including isolespeol (1), 5'-geranyl-2',4',4-trihydroxychalcone (2), and 3,4,2',4'-tetrahydroxy-3'-geranyldihydrochalcone (3), together with two known compounds lespeol (4) and xanthoangelol (5), were isolated from the leaves of Artocarpus communis. The structures of 1- 5 were elucidated by spectroscopy and through comparison with data reported in the literature. The effects of geranyl chalcone derivatives (1- 5) on the viability of human cancer cells (including SW 872, HT-29, COLO 205, Hep3B, PLC5, Huh7, and HepG2 cells) were investigated. The results indicate that isolespeol (1) showed the highest inhibitory activity with an IC 50 value of 3.8 muM in SW 872 human liposarcoma cells. Treatment of SW 872 human liposarcoma cells with isolespeol (1) caused the loss of mitochondrial membrane potential (DeltaPsim). Western blotting revealed that isolespeol (1) stimulated increased protein expression of Fas, FasL, and p53. The expression ratios of pro- and antiapoptotic Bcl-2 family members were also changed by isolespeol (1) treatment to subsequently induce the activation of caspase-9 and caspase-3, which was followed by cleavage of poly (ADP-ribose) polymerase (PARP). These results demonstrate that isolespeol (1) induces apoptosis in SW 872 cells through Fas- and mitochondria-mediated pathways.

Anti-inflammatory effects of phenolic compounds isolated from the fruits of Artocarpus heterophyllus.

Artocarpus heterophyllus Lam is a large evergreen tree cultivated throughout Southeast Asia for its fruits. Its leaves and roots have been used for medicinal purposes. The aim of this work was to study the in vitro anti-inflammatory effects of phenolic compounds isolated from the ethyl acetate extracts of the fruits of Artocarpus heterophyllus. Three phenolic compounds were characterized as artocarpesin [5,7,2',4'-tetrahydroxy-6-(3-methylbut-3-enyl) flavone] ( 1), norartocarpetin (5,7,2',4'-tetrahydroxyflavone) ( 2), and oxyresveratrol [ trans-2,4,3',5'-tetrahydroxystilbene] ( 3) by spectroscopic methods and through comparison with data reported in the literatures. The anti-inflammatory effects of the isolated compounds ( 1- 3) were evaluated by determining their inhibitory effects on the production of proinflammatory mediators in lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophage cells. These three compounds exhibited potent anti-inflammatory activity. The results indicated that artocarpesin ( 1) suppressed the LPS-induced production of nitric oxide (NO) and prostaglandin E 2 (PGE 2) through the down-regulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein expressions. Thus, artocarpesin ( 1) may provide a potential therapeutic approach for inflammation-associated disorders.