Lipopolysaccharide-activated Mouse Peritoneal Macrophages Research Articles

A Review of Anti-inflammatory Terpenoids from the Incense Gum Resins Frankincense and Myrrh.

Frankincense and myrrh have been used as incense in religious and cultural ceremonies since the beginning of written history. Their common medicinal properties are used in the treatment for inflammatory conditions, some cancerous diseases, and wound healing. In the course of our characterization of the anti-inflammatory constituents from frankincense and myrrh, several terpenoid constituents were found to inhibit nitric oxide production in lipopolysaccharide-activated mouse peritoneal macrophages. Here we review the structure of those terpenoid constituents from the gum resins of frankincense and myrrh and evaluate their anti-inflammatory effects by their nitric oxide production inhibitory activity.

New terpenoids, olibanumols D–G, from traditional Egyptian medicine olibanum, the gum-resin of Boswellia carterii

A new prenylaromadendrane-type diterpene, olibanumol D (1), and three new oleanane- and lupane-type triterpenes, olibanumols E (2), F (3), and G (4), were isolated from the traditional Egyptian medicine olibanum, the exuded gum-resin from Boswellia carterii Birdw. Their structures were established mainly on the basis of 1D and 2D NMR spectral data. Compounds 1 and 2 exhibited nitric oxide production inhibitory activity in lipopolysaccharide-activated mouse peritoneal macrophages.

Bioactive Constituents from Chinese Natural Medicines. XXXIII. Inhibitors from the Seeds of Psoralea corylifolia on Production of Nitric Oxide in Lipopolysaccharide-Activated Macrophages

The methanolic extract from the seeds of Psoralea corylifolia was found to inhibit production of nitric oxide (NO) in lipopolysaccharide-activated mouse peritoneal macrophages. Among the isolated compounds, bavachinin (IC(50)=26 microM), isobavachalcone (17 microM), neobavaisoflavone (ca. 29 microM), corylifol A (ca. 21 microM), and psoralidin (ca. 23 microM) significantly inhibited the accumulation of nitrite (NO(2)(-)) as a marker of production of NO. Bakuchiol, which is mainly contained in the extract, also showed weak activity at 10 microM, but cytotoxic effects were observed more than 30 microM.

Absolute Stereostructures of Olibanumols A, B, C, H, I, and J from Olibanum, Gum-Resin of Boswellia carterii, and Inhibitors of Nitric Oxide Production in Lipopolysaccharide-Activated Mouse Peritoneal Macrophages

Three new monoterpenes, olibanumols A (1), B (2), and C (3), and three new triterpenes, olibanumols H (4), I (5), and J (6), were isolated from olibanum, the exuded gum-resin from Boswellia carterii BIRDW. Their structures including the absolute configuration were determined by chemical and physicochemical evidence. Among the constituents, olibanumols A (1), H (4), and I (5), and isofouquierol (12) exhibited nitric oxide production inhibitory activity in lipopolysaccharide-activated mouse peritoneal macrophages.

Activin A down-regulates the phagocytosis of lipopolysaccharide-activated mouse peritoneal macrophages in vitro and in vivo

Activin A is a multifunctional factor of the transforming growth factor-beta (TGF-β) superfamily and acts as an anti-inflammatory cytokine produced by microglia and macrophages. In this study, we investigated the regulatory effect and possible mechanism of activin A on activation of lipopolysaccharide (LPS)-induced mouse peritoneal macrophages. The results showed that activin A could decrease NO release in LPS-activated mouse peritoneal macrophages, and suppressed phagocytosis and pinocytosis of mouse peritoneal macrophages stimulated by LPS in vitro and in vivo. Furthermore, activin A remarkably inhibited the expressions of CD14 and MHC II on LPS-induced mouse peritoneal macrophages, but had no significant effect on the expression of MHC I and the proliferation of mouse peritoneal macrophages. These findings suggest that activin A can down-regulate inflammatory mediator production and phagocytosis of LPS-activated macrophages via suppressing CD14 expression, and may influence the presentation of exogenous antigens via inhibiting MHC II expression. Thus, activin A might have the potential for treatment of macrophage-mediated inflammatory diseases through modulating both innate and adaptive immune responses.

Inhibitory effects of coumarin and acetylene constituents from the roots of Angelica furcijuga on d-galactosamine/lipopolysaccharide-induced liver injury in mice and on nitric oxide production in lipopolysaccharide-activated mouse peritoneal macrophages

The methanolic extract (200 mg/kg, p.o. and i.p.), principal coumarin constituents (isoepoxypteryxin, anomalin, and praeroside IV), and a polyacetylene constituent (falcarindiol) (25 mg/kg, i.p.) from the roots of Angelica furcijuga protected the liver injury induced by d-galactosamine ( d-GalN)/lipopolysaccharide (LPS) in mice. In in vitro experiments, coumarin constituents (hyuganins A–D, anomalin, pteryxin, isopteryxin, and suksdorfin) and polyacetylene constituents [(−)-falcarinol and falcarindiol] substantially inhibited LPS-induced NO and/or TNF-α production in mouse peritoneal macrophages, and isoepoxypteryxin inhibited d-GalN-induced cytotoxicity in primary cultured rat hepatocytes. Furthermore, hyuganin A, anomalin, and isopteryxin inhibited the decrease in cell viability by TNF-α in L929 cells.

Inhibitors of Nitric Oxide Production from the Flowers of Angelica furcijuga: Structures of Hyuganosides IV and V.

AbstractFor Abstract see ChemInform Abstract in Full Text.

1′ S-1′-Acetoxychavicol acetate as a new type inhibitor of interferon-β production in lipopolysaccharide-activated mouse peritoneal macrophages

1′ S-1′-Acetoxychavicol acetate from the rhizomes of Alpinia galanga was known to show potent inhibitory effect on the production of nitric oxide (NO) in lipopolysaccharide-activated mouse peritoneal macrophages. To clarify its mechanism of action, the effects of 1′ S-1′-acetoxychavicol acetate on the expression of interferon-β (IFN-β) mRNA and activation of nuclear factor-κB (NF-κB), both of which participate in the induction of inducible NO synthase, were examined in lipopolysaccharide-activated macrophages. The results were compared with those of two inhibitors of the NF-κB activation, costunolide and caffeic acid phenethyl ester. 1′ S-1′-Acetoxychavicol acetate inhibited IFN-β mRNA expression as well as NF-κB activation, and two related compounds, (±)-1-acetoxy-1-(2-acetoxyphenyl)-2-propene and (±)-1-acetoxy-1-(4-acetoxyphenol)-3-butene, also inhibited IFN-β mRNA expression. In addition, 1′ S-1′-acetoxychavicol acetate inhibited the production of NO stimulated by poly(I:C) via Toll-like receptor 3.

Structure–activity relationships of 1′ S-1′-acetoxychavicol acetate for inhibitory effect on NO production in lipopolysaccharide-activated mouse peritoneal macrophages

1′ S-1′-Acetoxychavicol acetate from the rhizomes of Alpinia galanga inhibited nitric oxide (NO) production in lipopolysaccharide-activated mouse peritoneal macrophages with an IC 50 value of 2.3 μM. To clarify the structure–activity relationship of 1′ S-1′-acetoxychavicol acetate, various natural and synthetic phenylpropanoids and synthetic phenylbutanoids were examined, and the following structural requirements were clarified. (1) The para or ortho substitution of the acetoxyl and 1-acetoxypropenyl groups at the benzene ring was essential. (2) The S configuration of the 1′-acetoxyl group was preferable. (3) The presence of the 3-methoxyl group and disappearance of the 2′–3′ double bond by hydrogenation reduced the activity. (4) The substitution of acetyl groups with propionyl or methyl groups reduced the activity. (5) Lengthening of the carbon chain between the 1′- and 2′-positions reduced the activity.

Inhibitors of Nitric Oxide Production from the Flowers of Angelica furcijuga: Structures of Hyuganosides IV and V

The methanolic extract from the flowers of Angelica furcijuga KITAGAWA was found to inhibit nitric oxide production in lipopolysaccharide-activated mouse peritoneal macrophages. From the methanolic extract, two new glycosides, hyuganosides IV and V, were isolated together with 28 known constituents. The structures of the new constituents were determined on the basis of chemical and physicochemical evidence. Furthermore, the inhibitory effects of 11 coumarin constituents on nitric oxide production were examined. Among them, 3'-angeloyl-cis-khellactone (IC(50)=82 microM), (S)-(-)-oxypeucedanin (57 microM), imperatorin (60 microM), isoepoxypteryxin (53 microM), and isopteryxin (8.8 microM) showed inhibitory activity.

Absolute Stereostructures of Polypodane‐ and Octanordammarane‐Type Triterpenes with Nitric Oxide Production Inhibitory Activity from Guggul‐Gum Resins.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Absolute stereostructures of polypodane- and octanordammarane-type triterpenes with nitric oxide production inhibitory activity from guggul-gum resins

The methanolic extract from guggul-gum resin, the resin of Balsamodendron mukul, was found to inhibit nitric oxide production in lipopolysaccharide-activated mouse peritoneal macrophages (IC 50 = 13 μg/mL). From the methanolic extract, three new polypodane-type triterpenes, myrrhanol B and myrrhanones B and A acetate, and a new octanordammarane-type triterpene, epimansumbinol, were isolated together with 17 known compounds including progesterone and the related steroids. The absolute stereostructures of new triterpenes were elucidated on the basis of chemical and physicochemical evidence. The several constituents showed inhibitory effects on nitric oxide production and induction of inducible nitric oxide synthase.

Structural Requirements of Flavonoids for Nitric Oxide Production Inhibitory Activity and Mechanism of Action

To clarify the structure–activity relationships of flavonoids for nitric oxide (NO) production inhibitory activity, we examined the inhibitory effects of 73 flavonoids on NO production in lipopolysaccharide-activated mouse peritoneal macrophages. Among those flavonoids, apigenin (IC 50=7.7 μM), diosmetin (8.9 μM), and tetra- O-methylluteolin (2.4 μM), and hexa- O-methylmyricetin (7.4 μM) were found to show potent inhibitory activity, and the results suggested the following structural requirements of flavonoids: (1) the activities of flavones were stronger than those of corresponding flavonols; (2) the glycoside moiety reduced the activity; (3) the activities of flavones were stronger than those of corresponding flavanones; (4) the flavones and flavonols having the 4′-hydroxyl group showed stronger activities than those lacking the hydroxyl group at the B ring and having the 3′,4′-dihydroxyl group; (5) the flavonols having the 3′,4′-dihydroxyl group (catechol type) showed stronger activities than those having the 3′,4′,5′-trihydroxyl group (pyrogallol type); (6) the 5-hydroxyl group tended to enhance the activity; (7) methylation of the 3-, 5-, or 4′-hydroxyl group enhanced the activity; (8) the activities of isoflavones were weaker than those of corresponding flavones; (9) methylation of the 3-hydroxyl group reduced the cytotoxicity. In addition, potent NO production inhibitors were found to inhibit induction of inducible nitric oxide synthase (iNOS) without iNOS enzymatic inhibitory activity.

Labdane-type Diterpenes with Inhibitory Effects on Increase in Vascular Permeability and Nitric Oxide Production from Hedychium coronarium

The methanolic extract from the rhizome of Hedychium coronarium was found to inhibit the increase in vascular permeability induced by acetic acid in mice and nitric oxide production in lipopolysaccharide-activated mouse peritoneal macrophages. From the methanolic extract, three new labdane-type diterpenes, hedychilactones A, B, and C, were isolated together with six known diterpenes. The structures of hedychilactones were elucidated on the basis of chemical and physicochemical evidence. The diterpene constituents showed inhibitory effects on the increase in vascular permeability, nitric oxide production, and inducible nitric oxide synthase induction.

Antiinflammatory Principles and Three New Labdane-Type Diterpenes, Hedychilactones A, B, and C, from the Rhizome of Hedychium coronarium Koeng

Three new labdane-type diterpenes named hedychilactones A, B, and C were isolated from the methanolic extract of the fresh rhizome of Hedychium coronarium KOENG. Their structures were elucidated on the basis of chemical and physicochemical evidence, which included the application of the allylic benzoate rule. The methanolic extract and diterpene constituents were found to inhibit the increase of vascular permeability induced by acetic acid in mice and nitric oxide production in lipopolysaccharide-activated mouse peritoneal macrophages.

Medicinal foodstuffs. XXVIII. Inhibitors of nitric oxide production and new sesquiterpenes, zedoarofuran, 4-epicurcumenol, neocurcumenol, gajutsulactones A and B, and zedoarolides A and B, from Zedoariae Rhizoma.

A new eudesmane-type sesquiterpene, zedoarofuran, and six new guaiane- or seco-guaiane-type sesquiterpenes, 4-epicurcumenol, neocurcumenol, gajutsulactones A and B, and zedoarolides A and B, were isolated from aqueous acetone extract of Zedoariae Rhizoma together with 36 known sesquiterpenes and two diarylheptanoids. Their stereostructures were elucidated on the basis of chemical and physicochemical evidence. The effects of isolated components on nitric oxide production in lipopolysaccharide-activated mouse peritoneal macrophages were examined and 16 sesquiterpenes including gajutsulactones A and B, and bis(4-hydroxycinnamoyl)methane were found to show inhibitory activity.

Stable prostaglandin I1 analog SM-10906 modulates productions of tumor necrosis factor-alpha, interleukin-1 and interleukin-6 in mouse macrophages.

The present study investigated the effects of stable agonist for prostaglandin (PG) I2 receptor with PGI1 skeleton, SM-10906, on pro-inflammatory cytokine production by mouse peritoneal macrophages (PEMs) in comparison with PGE1 and PGI2. In mouse PEMs, SM-10906 and PGE1 slightly enhanced interleukin (IL)-6 secretion, but had no effects on tumor necrosis factor-alpha (TNF-alpha) or IL-1 production. SM-10906 concentration-dependently inhibited TNF-alpha, IL-1 and IL-6 releases from lipopolysaccharide-activated mouse PEMs, as with PGE1, PGI2 and cAMP analog. Additionally, SM-10906, PGE1 and PGI2 caused concentration-dependent accumulation of cAMP contents in mouse PEMs. It is concluded that PGI1 analog SM-10906 exerts anti-inflammatory effects on stimulated mouse PEMs by increasing in cAMP levels, as with E-series of PG.