Lipopolysaccharide-treated RAW Research Articles

Inhibitory activity of prostaglandin E 2 production by the synthetic 2′-hydroxychalcone analogues: Synthesis and SAR study

A series of 2′-hydroxychalcones has been synthesized and screened for their in vitro inhibitory activities of cyclooxygenase-2 catalyzed prostaglandin production from lipopolysaccharide-treated RAW 264.7 cells. Structure–activity relationship study suggested that inhibitory activity against prostaglandin E 2 production was governed to a greater extent by the substituent on B ring of the chalcone, and most of the active compounds have at least two methoxy or benzyloxy groups on B ring. The relationship between chalcone structures and their PGE 2 inhibitory activities was also interpreted by docking study on cyclooxygenase-2.

Liquid Perfluorochemical Inhibits Inducible Nitric Oxide Synthase Expression and Nitric Oxide Formation in Lipopolysaccharide-Treated RAW 264.7 Macrophages

Partial liquid ventilation with various types of perfluorocarbon (PFC) has been shown to be beneficial in treating acute lung injury, a clinical outcome that may involve the anti-inflammatory activity of PFC. FC-77 is a type of PFC with relatively higher vapor pressure and evaporative loss than other PFCs during partial liquid ventilation. Overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been proposed to play a crucial role in the pathogenesis of inflammatory diseases. However, whether the iNOS/NO pathway is affected by FC-77 is unknown. Thus, the aim of this study was to investigate whether FC-77 inhibits iNOS expression and NO production in lipopolysaccharide (LPS)–treated RAW 264.7 macrophages. We found that treatment with FC-77 significantly attenuated LPS-induced iNOS expression/activity and production of NO and reactive oxygen species (ROS). FC-77 also attenuated LPS-induced pro-inflammatory cytokine formation, but enhanced interleukin-10 production. Furthermore, the LPS-induced degradation of cytosolic IκB-α and activation of nuclear transcription factor-κB (NF-κB) were also inhibited by FC-77. In conclusion, the present study is the first to demonstrate that FC-77 decreases LPS-induced NO production in macrophages, which may be associated with the suppression of pro-inflammatory cytokines, and ROS production, as well as NF-κB activation. These results also provide a novel explanation for its anti-inflammatory activity.

Synthesis of biflavones having a 6-O-7’’ linkage and effects on cyclooxygenase-2 and inducible nitric oxide synthase

In order to establish anti-inflammatory potential of biflavonoids, 17 biflavone derivatives having a 6-O-7″ linkage were synthesized and their effects on cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were evaluated. The basic molecule (6-O-7″ biflavone) potently inhibited COX-2-mediated PGE 2 production (IC 50: < 2 μM), being less active on iNOS-mediated NO production (IC 50: > 50 μM) from lipopolysaccharide-treated RAW 264.7 cells, a mouse macrophage cell line. Generally, the hydroxyl/methoxyl substitution(s) on the basic biflavone (6-O-7″) reduced the inhibitory activity of PGE 2 production, while the effects on NO production were varied. It is suggested that the basic biflavone (6-O-7″) may have a potential for new anti-inflammatory agent.

Anti-Inflammatory Activity of the Ethanol Extract of Chungkukjang, Korean Fermented Bean: 5-Lipoxygenase Inhibition

The anti-inflammatory activity of Chungkukjang, a Korean traditional fermented soybean food (Korean-style Natto), was examined for the first time. From the results, it was found that the ethanol extract of Chungkukjang inhibited 5-lipoxygenase from A23187-treated RBL-1 cells, reducing leukoriene production (50% inhibitory concentration = 54.1 microg/mL). However, it did not greatly affect cyclooxygenase-2-catalyzed prostaglandin E(2) and inducible nitric oxide synthase-catalyzed nitric oxide production from lipopolysaccharide-treated RAW 264.7 cells at the same concentration ranges. Since leukotrienes are intimately involved in some allergic disorders, the anti-allergic activity of Chungkukjang was further examined in animal models of passive cutaneous anaphylaxis (type I hypersensitivity) and arachidonic acid-induced ear edema, two well-known in vivo models sensitive to 5-lipoxygenase inhibitors. After oral administration for 5 consecutive days, Chungkukjang significantly reduced (27.3%) passive cutaneous anaphylaxis in rats at 400 mg/kg/day. It also showed in vivo anti-inflammatory activity against arachidonic acid-induced mouse ear edema. Therefore, it is suggested that Chungkukjang may be beneficial for several allergic conditions such as asthma and atopic dermatitis.

Effects of the Constituents of Gardenia Fructus on Prostaglandin and NO Production

The fruits of Gardenia jasminoides Ellis have been previously reported to possess anti-inflammatory activity. In this study, the constituents including geniposide, geniposidic acid, genipin and crocin were evaluated for their effects on prostaglandin and NO production in an attempt to establish anti-inflammatory cellular mechanisms. Among the constituents tested, only genipin significantly inhibited cyclooxygenase-2-mediated <TEX>$PGE_2$</TEX> and inducible nitric oxide synthase-mediated NO production from lipopolysaccharide-treated RAW 264.7 cells at 10-100 <TEX>${\mu}$</TEX>M. Genipin also inhibited nuclear transcription factor-<TEX>${\kappa}B$</TEX> activation. Moreover, genipin showed in vivo antiinflammatory activity on <TEX>${\lambda}$</TEX>-carrageenan-induced paw edema in mice (10.4-29.9% inhibition at 20-100 mg/kg, i.p.). All of these results suggest that genipin may contribute to anti-inflammatory activity of the fruits of G. jasminoides and an inhibitory action on prostaglandin and NO production is, at least, the part of anti-inflammatory mechanism of genipin.

Inhibition of prostaglandin and nitric oxide production in lipopolysaccharide-treated RAW 264.7 cells by tanshinones from the roots of Salvia miltiorrhiza bunge

This study examined the effects of tanshinone derivatives (tanshinone I, cryptotanshinone, 15,16-dihydrotanshinone I) on prostaglandin (PG) and nitric oxide (NO) metabolism in an attempt to establish their anti-inflammatory mechanisms and to present a scientific rationale for the use of Salvia miltiorrhiza (danshen) in inflammatory conditions. From lipopolysaccharide-treated RAW 264.7 cells, cyclooxygenase-2 (COX-2)-mediated PGE2 production was inhibited by tanshinone I, cryptotanshinone and 15,16-dihydrotanshinone I, while only cryptotanshinone and 15,16-dihydrotanshinone I inhibited inducible NO synthase (iNOS)-mediated NO synthesis at 1-50 microM. Particularly, cryptotanshinone was found to be a down-regulator of proinflammatory molecule expression, including COX-2 and iNOS. The electrophoretic mobility shift assay showed that cryptotanshinone and 15,16-dihydrotanshinone I also inhibited the activation of the transcription factors, such as nuclear transcription factor-kappaB and activator protein-1. Moreover, cryptotanshinone exhibited in vivo anti-inflammatory activity against carrageenan-induced paw edema in rats. Overall, these results provide additional scientific rationale for the anti-inflammatory use of danshen in Chinese medicine. Especially, cryptotanshinone and 15,16-dihydrotanshinone I are important constituents.

Anti-inflammatory activity of phylligenin, a lignan from the fruits of Forsythia koreana, and its cellular mechanism of action

Aim of the study The fruits of Forsythia koreana have long been used in Chinese medicine to treat inflammatory disorders. However, the pharmacological data is not sufficient to clearly establish a scientific rationale for the anti-inflammatory medicinal use of this plant material, and the search for its active principles has been limited so far. Materials and methods Phylligenin (lignan) was isolated from the fruits of Forsythia koreana and its anti-inflammatory activity was examined. Results and conclusion Phylligenin (1–100 μM) and the methanol extract of Forsythia koreana fruits inhibited cyclooxygenase-2 (COX-2)-mediated prostaglandin E 2 and inducible nitric oxide synthase (iNOS)-mediated nitric oxide (NO) synthesis from lipopolysaccharide-treated RAW 264.7 cells. In the mechanism study, phylligenin inhibited iNOS expression and nuclear factor-κB (NF-κB) activation but had no effect on COX-2 expression. Moreover, phylligenin significantly inhibited mouse carrageenan-induced paw edema by intraperitoneal administration (22.1–34.7% inhibition at 12.5–100 mg/kg). These pharmacological properties indicate that phylligenin possesses significant anti-inflammatory activity in vitro and in vivo, and may provide the scientific rationale for anti-inflammatory use of the fruits of Forsythia koreana.

Anti-inflammatory Activity of Pectolinarigenin and Pectolinarin Isolated from Cirsium chanroenicum

In order to identify the active anti-inflammatory ingredient(s) in Cirsium chanroenicum (Compositae), its methanol extract and several solvent fractions were prepared; the methanol extract and the ethylacetate fraction inhibited cyclooxygenase-2 (COX-2)-mediated prostaglandin E2 (PGE2) and 5-lipoxygenase (5-LOX)-mediated leukotriene (LT) production in lipopolysaccharide-treated RAW 264.7 cells and A23187-treated rat basophilic leukemia (RBL-1) cells, respectively. Further bioactivity-guided fractionation of the ethylacetate fraction using column chromatography led to the isolation of pectolinarigenin (5,7-dihydroxy-4',6-dimethoxyflavone), along with pectolinarin [pectolinarigenin 7-rhamnosyl-(1-->6)-glucoside]. Pectolinarigenin strongly inhibited COX-2-mediated PGE2 and 5-LOX-mediated LT production at >1 microM, indicating that it is a dual inhibitor of COX-2/5-LOX. However, pectolinarigenin did not affect COX-2 expression or nuclear transcription factor (NF-kappaB) activation. In addition, in vivo studies demonstrated that oral administration of these two compounds at 20-100 mg/kg resulted in similar inhibitory activities against several animal models of inflammation/allergy: arachidonic acid-induced mouse ear edema, carrageenan-induced mouse paw edema and passive cutaneous anaphylaxis. All of these results suggest that pectolinarigenin and pectolinarin possess anti-inflammatory activity and that they may inhibit eicosanoid formation in inflammatory lesions. These activities certainly contribute to the anti-inflammatory mechanism of C. chanroenicum.

Anti-inflammatory Activity of the Synthetic Chalcone Derivatives: Inhibition of Inducible Nitric Oxide Synthase-Catalyzed Nitric Oxide Production from Lipopolysaccharide-Treated RAW 264.7 Cells

Chalcones belong to the flavonoid family from plant origin and some of them possess anti-inflammatory activity. Recently, several natural and synthetic chalcone derivatives were reported to inhibit inducible nitric oxide synthase (iNOS)-catalyzed NO production in cell cultures. In the present study, to find the optimal chemical structures and to elucidate their action mechanisms, 41 synthetic chalcones having the substituent(s) on A- and B-rings were prepared and their effects on iNOS-catalyzed NO production were evaluated using lipopolysaccharide (LPS)-treated RAW 264.7 cells. When simultaneously added with LPS, 2'-methoxy-3,4-dichlorochalcone (Ch15), 2'-hydroxy-6'-methoxychalcone (Ch29), 2'-hydroxy-3-bromo-6'-methoxychalcone (Ch31) and 2'-hydroxy-4',6'-dimethoxychalcone (Ch35) among the tested compounds potently inhibited NO production (IC(50)s, 7.1-9.6 muM). The favorable chemical structures were found to be a methoxyl substitution in A-ring at an adjacent position (2' or 6') to carbonyl moiety with/without 2'-(or 6'-)hydroxyl group and 3-halogen substitution in B-ring. When the cellular action mechanisms of Ch15, Ch31 and Ch35 were further examined using Western blotting and electrophoretic mobility shift assay, it was revealed that Ch15 and Ch31 clearly down-regulated iNOS expression while Ch35 did not. Moreover, Ch15 and Ch31 were proved to suppress the nuclear transcription factor-kappaB activation. From the results, it is suggested that certain chalcone derivatives potently inhibit iNOS-catalyzed NO production by the different cellular mechanisms, iNOS down-regulation and/or iNOS inhibition, depending on their chemical structures. These chalcone derivatives may possibly be used as lead compounds for developing new anti-inflammatory agents.

Inhibitory effect of obovatol on nitric oxide production and activation of NF-κB/MAP kinases in lipopolysaccharide-treated RAW 264.7cells

The components of Magnolia obovata are known to have many pharmacological activities. In this study, we investigated the effects of obovatol, a neolignan compound isolated from the leaves of M. obovata, on nitric oxide (NO) production and NF-κB activity in lipopolysaccharide (LPS)-activated RAW 264.7 cells. The results show that obovatol (1–5 μM) significantly inhibited LPS-induced NO production in a concentration-dependent manner (IC 50: 0.91 μM). Consistent with the inhibitory effect on NO production, obovatol inhibits the expression of inducible nitric oxide synthase and cyclooxygenase-2 expression. Furthermore, obovatol suppressed NF-κB (p50 and p65) translocation to the nucleus as well as IκB release resulting in the inhibition of the DNA binding activity of the NF-κB. Obovatol also inhibited c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) signal, which are the most significantly involved signal in NO production and NF-κB activation. When the cells were treated with the combination of obovatol with U0126 (an ERK inhibitor) or SP600125 (a JNK inhibitor) as well as with SC-514 (an IKK2 inhibitor), much more inhibition of NO production was observed than that by obovatol alone. The present results suggest that obovatol has an inhibitory effect on NO production through the inhibition of NF-κB/MAPK activity, and thus can be used as an anti-inflammatory agent.

Anti-inflammatory principles from the fruits ofEvodia rutaecarpa and their cellular action mechanisms

The fruits of Evodia rutaecarpa Benth (Rutaceae) has long been used for inflammatory disorders and some anti-inflammatory actions of its constituents such as dehydroevodiamine, evodiamine and rutaecarpine were previously reported. Since the pharmacological data is not sufficient to clearly establish the scientific rationale of anti-inflammatory medicinal use of this plant material and the search for its active principles is limited so far, three major constituents (evodiamine, rutaecarpine, goshuyuamide II) were evaluated for their anti-inflammatory cellular action mechanisms in the present study. From the results, evodiamine and rutaecarpine were found to strongly inhibit prostaglandin E2 synthesis from lipopolysaccharide-treated RAW 264.7 cells at 1-10 microM. Evodiamine inhibited cyclooxygenase-2 induction and NF-kappaB activation, while rutaecarpine did not. On the other hand, goshuyuamide II inhibited 5-lipoxygenase from RBL-1 cells (IC50 = 6.6 microM), resulting in the reduced synthesis of leukotrienes. However, these three compounds were not inhibitory against inducible nitric oxide synthase-mediated nitric oxide production from RAW cells up to 50 micorM. These pharmacological properties may provide the additional scientific rationale for anti-inflammatory use of the fruits of E. rutaecarpa.

Up-Regulation of NOD1 and NOD2 through TLR4 and TNF-.ALPHA. in LPS-treated Murine Macrophages

NOD1 (Card4) and NOD2 (Card15) are thought to be responsible for cytoplasmic defense against bacterial entry. To gain further knowledge about how their expressions are regulated in murine macrophages, we investigated the expression of NOD1 and NOD2 mRNAs after stimulation with various endotoxins, lipopolysaccharide, lipoteichoic acid and peptidoglycan. In macrophage RAW264.7 cells, the first and second rises in NOD1 and NOD2 mRNAs were observed at 2 hr and at 8-12 hr after endotoxin treatment. Increases in NOD1 and NOD2 mRNAs at 2 hr in lipopolysaccharide-treated RAW264.7 cells were reduced with the use of NF-kappaB inhibitor, caffeic acid phenethyl ester. In RAW264.7 cells, lipopolysaccharide-induced increases in NOD1 and NOD2 mRNAs were inhibited with anti-TLR4 antibody, and partially reduced in peritoneal macrophages obtained from TLR4-deficient mice. Furthermore, NOD1 and NOD2 mRNA expressions in RAW264.7 cells were increased by the treatment with proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), or IL-6. In TNF-alpha deficient macrophages, the expression of NOD molecules was minimal at 12 hr, and the second rise in NOD mRNA seen in lipopolysaccharide-treated RAW264.7 cells was inhibited with anti-TNF-alpha, but not with anti-IL-1beta or anti-IL-6 antibody. These observations suggest that immediate response of NODs to endotoxins could result from NF-kappaB activation via TLR signaling, whereas the second rise in NOD mRNAs might have resulted from TNF-alpha production possibly through NF-kappaB, TLR, and/or NOD signalings.

Inhibition of inflammatory responses by FC-77, a perfluorochemical, in lipopolysaccharide-treated RAW 264.7 macrophages

This study tested whether FC-77, a perfluorochemical, inhibits inflammatory responses in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophages. The possible anti-inflammatory mechanisms involved were also investigated. RAW 264.7 macrophages were simultaneously incubated with pure FC-77 at final volume of 10% or 30% (v/v) and LPS (1 microg/ml) for 12 or 24 h on a mechanical shaker. In some tests FC-77 was added after cells stimulated by LPS for 12 h. Then the levels of prostaglandin E2(PGE2), tumor necrosis factor alpha (TNF-alpha), and interleukins (IL)-1beta, -6), and -10 were measured in medium. Alterations in cyclooxygenase (COX) 2 expression and nuclear transcription factor (NF) kappaB activation in cells were also evaluated. Pre- or posttreatment with FC-77 dose-dependently reduced the LPS-induced TNF-alpha, IL-1beta, and IL-6 formation and enhanced IL-10 production compared to LPS-stimulated alone cells. FC-77 also attenuated the LPS-induced PGE2 formation accompanied by suppressing COX-2 expression, the degradation of cytosolic inhibitor of kappaB-alpha and NF-kappaB activation. FC-77 inhibits inflammatory responses in LPS-stimulated macrophages by a mechanism that involves the attenuation of NF-kappaB dependent induction of COX-2/PGE2 pathway and the pro- /anti-inflammatory cytokine ratio.

Synthesis and Inhibitory Activity Against COX‐2 Catalyzed Prostaglandin Production of Chrysin Derivatives.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis and inhibitory activity against COX-2 catalyzed prostaglandin production of chrysin derivatives

A series of chrysin derivatives were prepared and evaluated for their inhibitory activities of cyclooxygenase-2 catalyzed prostaglandin production. Chrysin derivatives were prepared from 2-hydroxyacetophenone, 2,4-dihydroxyacetophenone and 2,6-dihydroxyacetophenone in 2 to 4 steps, respectively. Methxoylated chrysin derivatives were converted to the corresponding hydroxylated chrysin derivatives by the reaction with BBr3 in good yields. The inhibitory activity of the chrysin derivatives against prostaglandin production from lipopolysaccharide-treated RAW 264.7 cells was measured. We found that chrysin derivatives with 3′,4′-dichloro substituents (5e, 6e and 7e) exhibited good inhibitory activity of prostaglandin production.

황금약침액(黃芩藥針液)이 LPS로 유도(誘導)된 RAW 264.7 대식세포(大食細胞)에서의 항염증효과(抗炎症效果)

Objective : Recently, Herbal-acupuncture therapeutics has been used for the treatment of inflammatory diseases such as rheumatoid arthritis. Especially, we have been interested in chemical mediators concerned with inflammation such as prostaglandin, cytokine, nitric oxide. The purpose of this study is investigated that the effect of Scutellariae Radix-acupuncture solution in lipopolysaccharide-stimulated RAW 264.7 macrophages, performed several expeimental items : those are prostaglandin E. nitric oxide and cyclooxygenase-2. Method : The cytotoxicity of Scutellariae Radix-acupuncture solution in RAW 264.7 macrophages were measured by MTT-based cytotoxicity assay. In order to observe cyclooxygenase-2 mRNA expression in lipopolysaccharide-stimulated RAW 264.7 macrophages, RT-PCR was used. Prostaglandin formation and nitric oxide production was measured by competitive enzyme immunoassay and Griess assay. Results : 1. The MTT assay demonstrated that cytotoxic effect of Scutellariae Radix-acupuncture solution in RAW 264.7 macrophages were not appeared before concentration of 5mg/mL 2. Scutellariae Radix-acupuncture solution inhibited cyclooxygenase-2 mRNA expression in lipopolysaccharide-treated RAW 264.7 macrophages. 3. Scutellariae Radix-acupuncture solution inhibited nitric oxide production in lipopolysaccharide-treated RAW 264.7 macrophages. 4. Scutellariae Radix-acupuncture solution inhibited prostaglandin formation in lipopolysaccharide-treated RAW 264.7 macrophages. Conclusion : On the basis of these results, It was shown that Scutellariae Radix-acupuncture solution is significantly able to inhibit the production of and NO, as well as COX-2 mRNA expression. Our results may provide new mechanism by which Scutellariae Radix-acupuncture solution accounts for its beneficial effect on accelerating wound healing and anti-inflammation.

Anti-inflammatory activity of Sedum kamtschaticum

Sedum kamtschaticum Fischer (Crassulaceae) has been used as a folk medicine in North-East Asia for treating inflammatory disorders. The present investigation was carried out to establish in vivo anti-inflammatory activity and cyclooxygenase-2 modulating activity of this plant material. The methanol extract of Sedum kamtschaticum significantly inhibited mouse croton oil-induced ear edema (24–47% inhibition at 50–400 mg/kg) and rat paw edema (24–30% inhibition at 400–800 mg/kg) by oral administration. Prednisolone (10 mg/kg) showed 54 and 36% inhibition in the same animal models, respectively. Sedum kamtschaticum also showed significant inhibitory activity against mouse ear edema induced by multiple treatment of phorbol ester for 3 days. In addition, Sedum kamtschaticum exhibited potent analgesic activity against mouse acetic acid-induced writhing (IC 50=125 mg/kg), while aspirin (200 mg/kg) showed 57% inhibition. Using lipopolysaccharide-treated RAW 264.7 cells, down-regulation of cyclooxygense-2 expression was found to be one of the cellular action mechanisms of anti-inflammation by Sedum kamtschaticum.

Formation and stability of S-nitrosothiols in RAW 264.7 cells.

S-Nitrosothiols have been suggested to be mediators of many nitric oxide-dependent processes, including apoptosis and vascular relaxation. Thiol nitrosation is a poorly understood process in vivo, and the mechanisms by which nitric oxide can be converted into a nitrosating agent have not been established. There is a discrepancy between the suggested biological roles of nitric oxide and its known chemical and physical properties. In this study, we have examined the formation of S-nitrosothiols in lipopolysaccharide-treated RAW 264.7 cells. This treatment generated 17.4 +/- 1.0 pmol/mg of protein (means +/- SE, n =27) of intracellular S-nitrosothiol that slowly decayed over several hours. S-Nitrosothiol formation depended on the formation of nitric oxide and not on the presence of nitrite. Extracellular thiols were nitrosated by cell-generated nitric oxide. Oxygenated ferrous hemoglobin inhibited the formation of S-nitrosothiol, indicating the nitrosation occurred more slowly than diffusion. We discuss several mechanisms for S-nitrosothiol formation and conclude that the nitrosation propensity of nitric oxide is a freely diffusible element that is not constrained within an individual cell and that both nitric oxide per se and nitric oxide-derived nitrosating agents are able to diffuse across cell membranes. To achieve intracellular localization of the nitrosation reaction, mechanisms must be invoked that do not involve the formation of nitric oxide as an intermediate.

Chitosan inhibits prostaglandin E 2 formation and cyclooxygenase-2 induction in lipopolysaccharide-treated RAW 264.7 macrophages

Chitosan, a deacetylated chitin, has been reported to accelerate the wound healing and exert anti-inflammatory effect but the possible mechanisms involved are still unclear. Enhanced production of prostaglandin E 2 (PGE 2) and pro-inflammatory cytokines has been shown to contribute to immunosuppression and cytotoxicity during wound healing. In this study, we examined the effect of chitosan on cyclooxygenase pathway and cytokines production in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Our results first demonstrated that chitosans (MW=50,000, 150,000 or 300,000) significantly inhibit the overproduction of PGE 2 as well as cyclooxygenase-2 (COX-2) protein expression and activity accompanied by attenuation of pro-inflammatory cytokines production such as tumor necrosis factor-α and interleukin-1β formation but increase of the anti-inflammatory cytokine, IL-10, formation in LPS-treated RAW 264.7 macrophages. These results suggest that the beneficial effect of chitosan on wound healing may be associated, at least partly, with the inhibition of PGE 2 production by suppressing COX-2 induction and activity as well as attenuation of pro-inflammatory/anti-inflammatory cytokines ratio in activated macrophages.

Anti-inflammatory activity ofElsholtzia splendens

Elsholtzia splendens Nakai has been used in North-East Asia as an ingredient of folk medicines for treating cough, headache and inflammation. The present investigation was carried out to establish its in vivo anti-inflammatory activity using several animal models of inflammation and pain. The 75% ethanol extract of the aerial part of E. splendens significantly inhibited mouse croton oil-induced, as well as arachidonic acid-induced, ear edema by oral administration (44.6% inhibition of croton oil-induced edema at 400 mg/kg). This plant material also showed significant inhibitory activity against the mouse ear edema induced by multiple treatment of phorbol ester for 3 days, which is an animal model of subchronic inflammation. In addition, E. splendens exhibited significant analgesic activity against mouse acetic acid-induced writhing (50% inhibition at 400 mg/kg), while indomethacin (5 mg/kg) demonstrated 95% inhibition. E. splendens (5-100 microg/mL) significantly inhibited PGE2 production by pre-induced cyclooxygenase-2 of lipopolysaccharide-treated RAW 264.7 cells, suggesting that cyclooxygenase-2 inhibition might be one of the cellular mechanisms of anti-inflammation.