Nitric Oxide Inhibitory Activity Research Articles

Anti-inflammatory effects of compounds from Kaempferia parviflora and Boesenbergia pandurata

Abstract Kaempferia parviflora and Boesenbergia pandurata are perennial herbs in the Zingiberaceae family. The rhizomes of these two plants have been used as food ingredients and in Thai traditional medicine for treatment of several inflammatory-related diseases, such as gout, allergy, apthous ulcer and peptic ulcer. The compounds isolated from the rhizomes of K. parviflora and B. pandurata were, therefore, examined for their inhibitory activities against nitric oxide (NO) production. For K. parviflora, compound 5 (5-hydroxy-3,7,3′,4′-tetramethoxyflavone) exhibited the highest activity against the NO inhibitory effect, with an IC50 value of 16.1 μM, followed by 4 (IC50 = 24.5 μM) and 3 (IC50 = 30.6 μM). Regarding the NO inhibitory activity of B. pandurata, compound 2 (panduratin A) displayed the most potent effect with an IC50 value of 5.3 μM, followed by 3 (hydroxypanduratin A, IC50 = 13.3 μM) and 7 (cardamonin, IC50 = 24.7 μM), respectively. The 5-hydroxy-3,7,3′,4′-tetramethoxyflavone (5), panduratin A (2) and hydroxypanduratin A (3), were also tested on prostaglandin E2 (PGE2) and tumour necrosis factor-alpha (TNF-α) production. 5-Hydroxy-3,7,3′,4′-tetramethoxyflavone (5) exhibited a potent inhibitory effect on PGE2 production (IC50 = 16.3 μM), but a mild effect on TNF-α (IC50 > 100 μM). Panduratin A and hydroxypanduratin A showed strong activity against PGE2 with IC50 values of 10.5 and 12.3 μM, respectively, and a moderate effect on TNF-α (IC50 = 60.3 and 57.3 μM, respectively). This study indicated that compound 5 (5-hydroxy-3,7,3′,4′-tetramethoxyflavone) is responsible for anti-inflammatory activity of K. parviflora, while 2 (panduratin A) and 3 (hydroxypanduratin A), the prenylated chalcones, are responsible for that of B. pandurata. The present study, therefore, supports the traditional use of K. parviflora and B. pandurata rhizomes for treatment of inflammatory-related diseases through the inhibition of NO, PGE2 and TNF-α release.

Effects of compounds from Kaempferia parviflora on nitric oxide, prostaglandin E 2 and tumor necrosis factor-alpha productions in RAW264.7 macrophage cells

Kaempferia parviflora Wall. ex Baker, is one of the plants in the Zingiberaceae family, locally known in Thai as kra-chai-dam. The rhizome of this plant has been used for treatment of gout, apthous ulcer and abscesses. Since K. parviflora rhizomes have long been used for treatment of inflammation and possessed marked nitric oxide (NO) inhibitory activity (IC 50 = 7.8 μg/ml), we thus investigated the inhibitory activity of compounds isolated from this plant against lipopolysaccharide (LPS)-induced NO release in RAW264.7 cells. From bioassay-guided fractionation of K. parviflora, seven methoxyflavones were isolated from the hexane fraction and were tested for their anti-inflammatory effects. Among the isolated compounds, compound 5 (5-hydroxy-3,7,3′,4′-tetramethoxyflavone) exhibited the highest activity against NO release with an IC 50 value of 16.1 μM, followed by 4 (IC 50 = 24.5 μM) and 3 (IC 50 = 30.6 μM). Compound 5 was also tested on LPS-induced prostaglandin E 2 (PGE 2) and tumor necrosis factor-alpha (TNF-α) releases from RAW264.7 cells. It was revealed that 5 showed appreciable inhibitory effect on PGE 2 release (IC 50 = 16.3 μM), but inactive on TNF-α (IC 50 > 100 μM). These findings may support the use in Thai traditional medicine of K. parviflora for treatment of inflammatory-related diseases through the inhibition of NO and PGE 2 releases but partly due to that of TNF-α.

Maleimide and Maleic Anhydride Derivatives from the Mycelia of Antrodia cinnamomea and Their Nitric Oxide Inhibitory Activities in Macrophages

On cultivation of the fungus Antrodia cinnamomea (BCRC 36799) on a medium, the mycelium was extracted and evaluated for nitric oxide (NO) inhibitory activity. Bioactivity-directed fractionation led to the isolation of two new maleimide derivatives, antrocinnamomins A (1) and B (2), and two new maleic anhydride derivatives, antrocinnamomins C (3) and D (4), along with three known compounds, 3-isobutyl-4-[4-(3-methyl-2-butenyloxy)phenyl]furan-2,5-dione (5), 3-isobutyl-4-[4-(3-methyl-2-butenyloxy)phenyl]-1H-pyrrole-2,5-dione (6), and 3-isobutyl-4-[4-(3-methyl-2-butenyloxy)phenyl]-1H-pyrrol-1-ol-2,5-dione (7). Structural elucidation of compounds 1-4 was carried out by spectroscopic data. Compound 1 displayed significant inhibitory effect on nitric oxide (NO) production.

Anti-inflammation activity of fruit essential oil from Cinnamomum insularimontanum Hayata

In this study, the fruit essential oil of Cinnamomum insularimontanum was prepared by using water distillation. Followed by GC–MS analysis, the composition of fruit essential oil was characterized. The main constituents of essential oil were α-pinene (9.45%), camphene (1.70%), β-pinene (4.30%), limonene (1.76%), citronellal (24.64%), citronellol (16.78%), and citral (35.89%). According to the results obtained from nitric oxide (NO) inhibitory activity assay, crude essential oil and its dominant compound (citral) presented the significant NO production inhibitory activity, IC 50 of crude essential oil and citral were 18.68 and 13.18 μg/mL, respectively. Moreover, based on the results obtained from the protein expression assay, the expression of IKK, iNOS, and nuclear NF-κB was decreased and IκBα was increased in dose-dependent manners, it proved that the anti-inflammatory mechanism of citral was blocked via the NF-κB pathway, but it could not efficiently suppress the activity on COX-2. In addition, citral exhibited a potent anti-inflammatory activity in the assay of croton oil-induced mice ear edema, when the dosage was 0.1 and 0.3 mg per ear, the inflammation would reduce to 22% and 83%, respectively. The results presented that the fruit essential oil of C. insularimontanum and/or citral may have a great potential to develop the anti-inflammatory medicine in the future.

Triterpenoidal Saponins from the Barks of Zygophyllum fabago L.

Two new triterpenoid saponins, zygophylosides O (1) and P (2), have been isolated from the barks of Zygophyllum fabago L. Their structures were elucidated as 3beta-[(2-O-sulfo-beta-D-xylopyranosyl)oxy]urs-12-ene-27,28-dioic acid and 3beta-[(2-O-sulfo-beta-D-xylopyranosyl)oxy]urs-12-ene-27,28-dioic acid 28-beta-D-glucopyranoside, respectively, by spectral and chemical evidence. Compound 1 showed weaker Nitric Oxide (NO) inhibitory activity.

Anti-oxidant and anti-inflammatory activities of leaves of Barringtonia racemosa

The medicinal plant of Barringtonia racemosa (lecythidaceae family) has been used widely in traditional medicine for anti-inflammation and anticancer in Malaysia. The present investigation was carried out to study of the anti-oxidant and anti-inflammatory effects of fully expanded leaf extracts of B. racemosa. Antioxidant activity was measured by using FTC, TBA and DPPH free radical scavenging methods and Griess assay was also used for the measurement of nitric oxide inhibition in lipopolysaccharide (LPS) and interferon- ×¢ (IFN- ×¢)-treated RAW 264.7 cells. Different crude extracts of fully expanded leaf extracts of B. racemosa have exhibited a very good level of nitric oxide (NO) inhibitory and antioxidant activities. In the Griess assay, non polar extracts such as chloroform and hexane extracts were found to be strong inhibitors of NO at different concentrations (25, 50, 100 and 200 µg/ml) in comparison with polar extract (ethanol extract). Chloroform extract didn’t show cytotoxicity against RAW 264.7 cells at different concentrations contrary to hexane and ethanol extracts. The chloroform and hexane extracts exhibited very strong antioxidant properties when compared to Vitamin E (a-tocopherol) in the FTC and TBA methods, the chloroform and hexane extracts exhibited the radical scavenging activity with an IC50 value of 54.29 and 63 µg/ml respectively. Results demonstrated that chloroform extract of B. racemosa leaf may have the potential to be used as anti-inflammation and anti-oxidant agents and it was revealed that the active compound in B. racemosa is lycopene. Key words: Barringtonia racemosa, anti-oxidant, anti-inflammatory.

Antiinflammatory activity of Lindera erythrocarpa fruits

In this study, in vitro and in vivo antiinflammatory activities of fruits from Lindera erythrocarpa Makino were evaluated. The ethyl acetate soluble fraction derived from the ethanol extract of L. erythrocarpa fruits inhibited significantly nitric oxide (NO) production in lipopolysaccharide (LPS) induced NO in the murine macrophage cell line (RAW264.7) assay, the EC(50) being 16.35 microg/mL. Four compounds, including lucidone (1), cis/trans-methylludicone (2), methyl linderone (3) and linderone (4) were identified from the active fraction based on the bioactivity-guided fractionation procedure. Of these lucidone possessed the strongest NO inhibitory activity with an EC(50) value of 4.22 microg/mL. Furthermore, results from the protein expression assay demonstrated that lucidone suppressed iNOS and COX-2 protein expression in a dose-dependent manner. Lucidone also provided antiinflammatory activity in the croton oil-induced ear edema assay. When it was applied topically at a dosage of 0.5 and 1 mg per ear, the percent edema reduction in treated mice was 44% and 25%, respectively. The results obtained in this study indicated that lucidone has a good potential to be developed as an antiinflammation agent.

Stilbene and dihydrophenanthrene derivatives from Pholidota chinensis and their nitric oxide inhibitory and radical-scavenging activities

Two new stilbene derivatives, (E)-2′,3,3′-trihydroxy-5-methoxystilbene (1, Pholidotol C) and (Z)-3,3′-hydroxy-5-methoxystilbene (2, Pholidotol D), were isolated from the air-dried whole plant of Pholidota chinensis Lindl., together with eight known dihydrophenanthrene derivatives, lusianthridin (3), cannabidihydrophenanthrene (4), coelonin (5), hircinol (6), erianthridin (7), 4,5-dihydroxy-2-methoxy-9,10-dihydrophenanthrene (8), eulophiol (9), and 2,4,7-trihydroxy-9,10-dihydrophenanthrene (10), and a benzoxepin derivative bulbophylol B (11). Their inhibitory effects on nitric oxide (NO) production activity and 1,1-diphenyl-2-picrylhydrazil radical-scavenging activity were examined. Among these compounds, 11 exhibited the most potent activity toward NO production inhibition activity and radical-scavenging activity; moreover, 11 reduced inducible nitric oxide synthase mRNA expression.

Anti-inflammatory Effects of a Sesquiterpene Lactone Extract from Chicory (Cichorium intybus L.) Roots

A chicory root extract rich in sesquiterpene lactones significantly reduced inflammation in two animal models. In a rat paw edema model, chicory extract at 50 and 100 mg/kg significantly reduced inflammation by 58 and 76%, respectively, 24 h after carrageenan injection. In a mouse collagen induced arthritis model, chicory extract (200 mg/kg) reduced paw edema by 71% while the extract was being administered, and 31% 48 h after extract administration was discontinued. Two possible modes of action were investigated, pro-inflammatory gene expression and nitric oxide production by LPS-elicited macrophages. Chicory root extract down-regulated COX-2, TNF-α, IL1β, and iNOS expression and reduced nitric oxide production in a dose dependant manner. Several compounds were isolated from the chicory extract and tested in vitro to confirm activity. Dihydrolactucopicrin and 8-deoxylactucin showed particularly high nitric oxide inhibitory activity (IC50 = 13 μM for both). Dihydrolactucopicrin also was shown to down-regulate pro-inflammatory gene expression. These data demonstrate that chicory extracts rich in sesquiterpene lactones have potent anti-inflammatory activity with potential therapeutic use.

Chemical Constituents of Malagasy Liverworts. 6. A Myltaylane Caffeate with Nitric Oxide Inhibitory Activity from Bazzania nitida

The phytochemical investigation of the Malagasy liverwort, Bazzania nitida, led to the isolation of (+)-(lS,4R)-7-hydroxycalamenene (1), together with a new myltayl-4(12)-ene-2-caffeate (2). Although cyclomyltaylane sesquiterpenoids have been known to be present in Bazzania species, this is the second isolation of myltaylane-type sesuiterpenoids from the genus. Biosynthetically, myltaylane sesquiterpenoids are proposed to be derived from chamigrene with a route different from those of cyclomyltaylanoids. The chemosystematics of Bazzania species is also discussed. Compound 2 showed potent inhibition of nitric oxide in LPS-induced RAW 264.7 cells (IC50 = 6.3 microM).

Protopanaxadiol modulates LPS-induced inflammatory activity in murine macrophage RAW264.7 cells

Protopanaxadiol (PPD) is a mixture of protopanaxadiol type saponins with a dammarane skeleton, from Korean red ginseng (Panax ginseng C.A. Meyer; Araliaceae). Korean ginseng is well-known herb to treat almost all kinds of diseases in Oriental medicine. This herb was particularly prescribed for treatment various inflammatory diseases, including rheumatoid arthritis, atherosclerosis, and diabetes mellitus, for centuries. To understand the efficacy of ginseng against inflammatory diseases, we aimed to show anti-inflammatory activities of the PPD in murine macrophage cell line, RAW264.7 cells using nitric oxide (NO) production assay and the expressions of pro-inflammatory cytokines, such as tumor necrosis <TEX>$factor-{\alpha}$</TEX> (<TEX>$TNF-{\alpha}$</TEX>), interleukin-<TEX>$1{\beta}$</TEX> (IL-<TEX>$1{\beta}$</TEX>), and IL-6, and monocyte chemotactic protein-1 (MCP-1). We found that PPD saponin significantly blocked LPS (<TEX>$1{\mu}g/ml$</TEX>)-induced NO production in a dose-dependent manner. In addition, PPD abrogated the expressions of LPS-induced pro-inflammatory cytokines, such as IL-<TEX>$1{\beta}$</TEX> and MCP-1. Moreover, cyclooxygenase (COX)-2, a critical enzyme to produce prostaglandin E2 (PGE2), was significantly inhibited by PPD in LPS-activated RAW264.7 cells. Taken together, these results suggested that anti-inflammatory efficacy of Korean red ginseng on inflammatory diseases is, at least, due to the NO inhibitory activity and the inhibition of the expressional level of inflammatory cytokines and/or mediators.

Antiallergic Agents from Natural Sources. Part 16. New Lignans from Kadsura coccinea and Their Nitric Oxide Inhibitory Activities.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Chemical Constituents of Malagasy Liverworts. Part 5. Prenyl Bibenzyls and Clerodane Diterpenoids with Nitric Oxide Inhibitory Activity from Radula appressa and Thysananthus spathulistipus.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Antiallergic Agents from Natural Sources. Part 15. New Lignans from Kadsura coccinea and Their Nitric Oxide Inhibitory Activities.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Biological Evaluation of Curcumin and Related Diarylheptanoids

Nine derivatives of three natural diarylheptanoids, curcumin, demethoxycurcumin and bisdemethoxycurcumin, were prepared. Their antioxidant, free radical scavenging, nitric oxide (NO) inhibitory and cytotoxic activities were evaluated and compared with those of the respective natural compounds. Curcumin (1), demethoxycurcumin (2), demethyldemethoxy-curcumin (C3), diacetyldemethoxycurcumin (AC2) and triacetyldemethylcurcumin (AC5) exhibited higher antioxidant activity than quercetin while products from demethylation of 1 and 2 exhibited higher free radical scavenging activity. Compounds AC2 and AC5 were found to be most active in inhibiting breast cancer cells (MCF-7) proliferation with IC50 values of 6.7 and 3.6 microM, respectively. The activity of AC2 is almost doubled and of AC5 almost tripled as compared to curcumin. Their selectivity towards different cell lines is also more noticeable. Compounds AC2 and AC5 also showed increased activity against a human prostate cancer cell line (DU-145) and non-small lung cancer cell line (NCI-H460) with IC50 values of 20.4, 16.3 and 18.3, 10.7 microM, respectively.

Nitric oxide inhibitory substances from the rhizomes of Dioscorea membranacea

Thai medicinal plants locally known as Hua-Khao-Yen were examined for their inhibitory activities against lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW 264.7 cell lines. Among the plant species studied, an ethanolic extract of Dioscorea membranacea exhibited the most potent inhibitory activity, with an IC 50 value of 23.6 μg/ml. From this extract, eight compounds [two naphthofuranoxepins ( 1, 2), one phenanthraquinone ( 3), three steroids ( 4– 6) and two steroidal saponins ( 7, 8)] were isolated and further investigated for their inhibitory properties of NO production. It was found that diosgenin-3- O-α- l-rhamnosyl (1 → 2)-β- d-glucopyranoside ( 7) possessed the highest activity (IC 50 = 3.5 μM), followed by dioscoreanone ( 3, IC 50 = 9.8 μM) and dioscorealide B ( 2, IC 50 = 24.9 μM). Regarding structural requirements of diosgenin derivatives for NO production inhibitory activity, compound 7 which has a rhamnoglucosyl moiety at C-3 exhibited much higher activity than compounds that have either a diglucosyl substitution ( 8) or its aglycone ( 9); whereas, hydroxyl substitution at position 8 of naphthofuranoxepin derivatives conferred higher activity than the methoxyl group. It is concluded that diosgenin-3- O-α- l-rhamnosyl (1 → 2)-β- d-glucopyranoside ( 7), dioscoreanone ( 3) and dioscorealide B ( 2) are active principles for NO inhibitory activity of Dioscorea membranacea. Compounds 1– 3 were also tested for the inhibitory effect on LPS-induced TNF-α release in RAW 264.7 cells. The result revealed that 3 possessed potent activity against TNF-α release with an IC 50 value of 17.6 μM, whereas, 1 and 2 exhibited mild activity. The present study may support the use of Dioscorea membranacea by Thai traditional doctors for treatment of the inflammatory diseases.

Anti‐Allergic Agents from Natural Sources. Part 13. Lignans from the Roots of Wikstroemia indica and Their DPPH Radical Scavenging and Nitric Oxide Inhibitory Activities.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Chemical Constituents of Malagasy Liverworts, Part V: Prenyl Bibenzyls and Clerodane Diterpenoids with Nitric Oxide Inhibitory Activity from Radula appressa and Thysananthus spathulistipus

3Beta,4beta:15,16-diepoxy-13(16),14-clerodadiene (1) and a new clerodane diterpenoid designated thysaspathone (2) were isolated from the liverwort Thysananthus spathulistipus, while Radula appressa produced radulannin A (3), radulannin L (4), 2-geranyl-3,5-dihydroxybibenzyl (5), 2(S)-2-methyl-2-(4-methyl-3-pentenyl)-7-hydroxy-5-(2-phenylethyl) chromene (o-cannabichromene) (6), 6-hydroxy-4-(2-phenylethyl) benzofuran (7), and o-cannabicyclol (8). All of the isolated compounds inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the greatest inhibition was attributed to compound 5, with an IC50 value of 4.5 microM.

New Lignans from Kadsura coccinea and Their Nitric Oxide Inhibitory Activities

In vitro anti-allergic screening of medicinal herbal extracts revealed that the chloroform extract of the rhizoma of Kadsura coccinea inhibited nitric oxide (NO) production in a lipopolysaccharide (LPS) and recombinant mouse interferon-gamma (IFN-gamma) activated murine macrophage like cell line RAW 264.7. Further fractionation of the chloroform extract led to the isolation of three new lignans, including two dibenzocyclooctadiene lignans and one arylnaphthalene lignan, together with other three known dibenzocyclooctadiene lignans. This is the first report of NO production inhibitory activity of Kadsura coccinea and first report about the isolation of arylnaphthalene lignan from K. coccinea.

New Lignans from Kadsura coccinea and Their Nitric Oxide Inhibitory Activities

In vitro anti-allergic screening of medicinal herbal extracts revealed that the chloroform extract of the rhizoma of Kadsura coccinea inhibited nitric oxide (NO) production in a lipopolysaccharide (LPS) and recombinant mouse interferon-y (IFN-y) activated murine macrophage like cell line, RAW264.7. Further fractionation of the chloroform extract led to the isolation of two new lignans kadsuralignans D (1) and E (2) with other two known dibenzocyclooctadiene lignans kadsulignan N (3) and neokadsuranin (4).