Xylene-induced Ear Edema In Mice Research Articles

Ilex asprella aqueous extracts exert in vivo anti-inflammatory effects by regulating the NF-κB, JAK2/STAT3, and MAPK signaling pathways

Ethnopharmacological relevanceIlex asprella (Hook. et Arn.) Champ. ex Benth. (IA) is a representative medicinal plant from the South of the Five Ridges of China. Its roots (RIA) and stems (SIA) have been traditionally used for the inflammation-related diseases, such as acute and chronic pharyngitis, cough, and sore throats. Aim of the studyTo evaluate the in vivo anti-inflammatory effects of IA extracts to provide evidence for its traditional use and to enhance the knowledge of the medicinal properties of IA. Materials and methodsModels of xylene-induced ear edema in mice and carrageenan-induced paw edema in rats were used for the pharmacological evaluations. The mice were randomly divided into eight groups (n = 10 per group): a model group, a positive control group [dexamethasone (Dex), 10 mg/kg, intragastrically (i.g.)], RIA aqueous extract groups with three dosages (30, 15, and 7.5 mg/kg, i.g.), and SIA aqueous extract groups with three dosages (60, 30, and 15 mg/kg, i.g.). The rats were randomly divided into eight groups (n = 6 per group): a model group, a positive control group [acetylsalicylic acid (ASA), 300 mg/kg, i.g.], RIA groups with three dosages (80, 40, and 20 mg/kg, i.g.) and SIA aqueous extract groups with three dosages (160, 80, and 40 mg/kg, i.g.). Histological examinations of the ear and paw tissues were observed by hematoxylin-eosin (HE) staining, and neutrophil elastase levels were assessed in ear tissues by immunohistochemical analysis. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were measured by ELISAs, and expression levels of TNF-α, IL-6, and IL-1β in rat paw tissues were measured by RT-PCR. The signal transduction proteins p65, IκBα, Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), p38 mitogen-activated protein kinases (p38), extracellular regulated protein kinases (ERK1/2), and c-Jun N-terminal kinase (JNK) in the rat paw tissues were investigated by western blot analyses. RIA and SIA were characterized by HPLC and LC-MS analyses, and the components were confirmed by comparison with isolated compounds. ResultsIntragastric administration with RIA (30 mg/kg) and SIA (60, 30 mg/kg) significantly mitigated ear edema in mice. RIA administration at 80 and 40 mg/kg reduced paw edema in rats 2‒3 h after injection. SIA administration with 160 mg/kg inhibited paw edema in rats after the injection of carrageenan for 1‒4 h, and SIA administration at 80 mg/kg inhibited paw edema after the injection of carrageenan for 2‒4 h. Meanwhile, RIA (80, 40 mg/kg) and SIA (160, 80 mg/kg) reduced inflammatory cell infiltration in the ear and paw tissues and infiltration of neutrophil leukocytes in rat paw tissues. RIA (80, 40, and 20 mg/kg) and SIA (160, 80, and 40 mg/kg) notably inhibited the increases of TNF-α, IL-6 and IL-1β in the serum and mRNA expression in the rat paw tissues. RIA (80, 40 mg/kg) and SIA (160, 80 mg/kg) reduced the p-p65/p-IκBα, p-JAK2/p-STAT3, and p-p38/p-ERK1/2/p-JNK levels in the pathological tissues of the animals. Phenolic acids and triterpenoids likely contributed to the anti-inflammatory activity. ConclusionsBoth RIA and SIA aqueous extracts showed anti-inflammatory effects in vivo in a dose-independent manner (20‒80 and 40‒160 mg/kg, respectively). The underlying mechanisms are mediated by inhibiting the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β via regulation of the NF-κB, JAK2/STAT3, and MAPK signaling pathways. The present results provided pharmacological evidence that stems are alternative medicinal parts of IA but function at different doses. Additionally, this study supports the use of IA as an anti-inflammatory herbal medicine.

Evaluation of the efficacy of Hylotelephium purpureum gel in the treatment of experimental periodontitis.

Local drug delivery systems have been proposed for the treatment of periodontitis, and Hylotelephium purpureum may be a suitable agent for use in such a system. The present study aimed to formulate a Hylotelephium purpureum gel (HPG) and evaluate the anti-inflammatory activity and antinociceptive effects of Hylotelephium purpureum and to assess the duration of action and efficacy of HPG in the treatment of experimental periodontitis in a KM mouse model. First, an acute toxicity study was performed, and secondly, xylene-induced mouse-ear edema, acetic acid-induced mouse peritoneal capillary permeability and carrageenan-induced hind-paw edema tests were used to investigate the anti-inflammatory activity of the gel. The acetic acid-induced writhing response and hot-plate tests were used to evaluate the antinociceptive activity. The therapeutic effects of HPG in experimental periodontitis were evaluated and minimum inhibitory concentration of the gel was determined. The results showed that intragastrically administration of 80 ml/kg of HPG produced no toxic effects. There were statistically significant changes in gingival indexes and sulcus bleeding indexes in the high-dose HPG-treated group. The serum levels of superoxide dismutase and glutathione peroxidase were significantly heightened, while the level of malondialdehyde was decreased. HPG exhibited 32.7% inhibition of edema, and altered the peritoneal capillary permeability in mice. The gel had relatively good bacteriostatic and bactericidal effects. It also exhibited antinociceptive activity, as demonstrated by the acetic acid-induced writhing response test and hot-plate test. In summary, the present study demonstrates that HPG is effective in the treatment of experimental periodontitis.

Antinociceptive and anti-inflammatory activities of a standardizedextract of bis-iridoids from Pterocephalus hookeri

Ethnopharmacological relevancePterocephalus hookeri (C.B. Clarke) Höeck, one of the most popular Tibetan herbs, has been widely applied in Tibetan medicine prescriptions. Chemical investigations have led to the isolation of many bis-iridoids. However, the pharmacological activities of bis-iridoid constituents of this plant have never been reported before. Aim of the studyThis study evaluated the anti-inflammatory and analgesic activities of afraction of bis-iridoid constituents of P. hookeri (BCPH) in order to provide experimental evidence for its traditional use, such as for cold, flu, and rheumatoid arthritis. Materials and methodsThe analgesic effects of BCPH were investigated using the hot-plate test and acetic acid-induced writhing test. The anti-inflammatory activities were observed using the following models: carrageenin-induced edema of the hind paw of rats and xylene-induced ear edema in mice. The effects of dexamethasone administration were also studied. ResultsBCPH significantly increased the hot-platepain threshold and reduced acetic acid-induced writhing response in mice. Moreover, BCPH remarkably inhibited xylene-induced ear edema and reduced the carrageenin-induced rat paw edema perimeter. ConclusionThe results reveal that BCPH has central, peripheral analgesic activities as well as anti-inflammatory effects, supporting the traditional application of this herb in treating various diseases associated with inflammation and pain.

Anti-inflammatory effect and mechanism of the spirocyclopiperazinium salt compound LXM-15 in rats and mice.

This study aimed to investigate the anti-inflammatory effects of a novel spirocyclopiperazinium salt compound LXM-15, and explore the underlying mechanisms. Xylene-induced mouse ear oedema and carrageenan-induced rat paw oedema tests were used to evaluate the anti-inflammatory effects of LXM-15. The protein levels of TNF-α, IL-6, phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) were detected by ELISA or Western blot analysis. Additionally, receptor blocking test was performed to explore the possible target. Intragastric administration with LXM-15 (2, 1, 0.5mg/kg in mice, and 6, 3, 1.5mg/kg in rats) produced distinct anti-inflammatory effects in vivo, the highest inhibition percentage was 60 and 52%, respectively (P < 0.01). Following treatment with LXM-15 (6mg/kg, i.g.), the levels of TNF-α and IL-6 in the rats paws were attenuated by 40 and 41%; and the phosphorylation of JAK2 and STAT3 was restrained by 35 and 45%, respectively (P < 0.01). All effects of LXM-15 were blocked by pretreatment with methyllycaconitine citrate or tropicamide. This study provides the first report that the spirocyclopiperazinium salt compound LXM-15 displays considerable anti-inflammatory effects. The underlying mechanism may be through activating the peripheral α7 nicotinic acetylcholine receptor and M4 muscarinic acetylcholine receptor, leading to the inhibition of the JAK2/STAT3 signalling pathway, eventually resulting in the reduction of TNF-α and IL-6.

Evaluation on Analgesic and Anti-Inflammatory Activities of Total Flavonoids from Juniperus sabina.

The leaves of Juniperus sabina (Cupressaceae) are used in traditional Uygur medicine for the treatment of rheumatism and arthritic pain. This study aimed to investigate the analgesic and anti-inflammatory effects of total flavonoids from leaves of Juniperus sabina (JSTF) on rodents. The anti-inflammatory activity was investigated using the carrageenan, egg albumin, or histamine-induced rat paw edema as well as xylene-induced ear edema, capillary permeability, and cotton pellet granuloma while the antinociceptive activity was evaluated using the mouse writhing, formalin, and hot-plate tests. JSTF (125, 250, 500 mg/kg) significantly inhibited xylene-induced ear edema in mice (inhibition ratio as 16.22%, 40.67%, and 51.78%, respectively) and also significantly ameliorated acetic acid increased vascular permeability in mice (inhibition ratio as 11.63%, 32.56%, and 53.49%, respectively). JSTF (250 and 500 mg/kg) gave significant reduction of carrageenin-induced paw oedema at the interval of 1 h and 5 h. Administration of JSTF (500 mg/kg) caused a significant anti-inflammatory effect against oedema induced by egg albumin or histamine at the interval of 0.5 h and 4 h, and both which induced the paw oedema were also inhibited by JSTF (250 mg/kg) at a point in 1, 2, or 3 h after the inflammation. Furthermore, JSTF (125, 250, and 500 mg/kg) produced time-course increase in pain threshold in hot-plate test also. JSTF produced concentration-dependent inhibition on cyclooxygenase-2 (COX-2) or 5-lipoxygenase (5-LO) activities in vitro, and their IC50 values were 31.92 and 129.26 μg/mL, respectively. Moreover, JSTF significantly caused a significant dose-dependent inhibition on acetic acid induced writhing response in mice (inhibition ratio as 23.27%, 36.91%, and 50.76%, respectively). JSTF also significantly ameliorated formalin-induced pain in mice in the late phase on dose-dependent way. These results confirms the clinical use of J. sabina for treatment of rheumatoid arthritis in ethnomedicine, and its effective mechanism will be further studied in the future.

Anti-Helicobacter pylori and Anti-Inflammatory Effects and Constituent Analysis of Modified Xiaochaihutang for the Treatment of Chronic Gastritis and Gastric Ulcer.

Chronic gastritis and gastric ulcers are prevalent throughout the world and are considered to be a global health problem. Modified Xiaochaihutang (MXCHT) prescription is broadly used in traditional medicine hospital for the treatment of gastritis. In order to assess the anti-Helicobacter pylori (H. pylori) effect of MXCHT, agar diffusion method in vitro and fluid dilution method for the minimal inhibitory concentration (MIC) were established. The anti-inflammatory effects were then evaluated using mouse ear edema model and rat paw edema model. The ethanol-induced gastric ulcer method was employed to verify the gastroprotective effect of active extracts in MXCHT. HPLC-TOF-MS/MS was used for analyzing the possible active constituents after oral administration of effective extracts in ethanol-induced gastric ulcer models. MXCHT and 4 different extracts of the bacterial inhibition diameter and MIC were dramatically decreased compared with control group, showing anti-Helicobacter pylori effects. High dose groups of MXCHT, water extract, EtOAc extract, and n-BuOH extract displayed significant anti-inflammatory effects in xylene-induced mouse ear edema model and carrageenan-induced rat paw edema model test. MXCHT and all active extracts exhibited gastroprotective activity and prevented gastric lesions induced by ethanol in rats. 4 prototype components and 4 metabolites were identified after oral administration of EtOAc extract. In addition, 6 prototype components and 6 metabolites were identified in n-BuOH extract. MXCHT, EtOAc extract, and n-BuOH extract demonstrate gastroprotective effects through anti-Helicobacter pylori and anti-inflammatory activities. Thus, this prescription may be a suitable natural source for the prevention and treatment of chronic gastritis and gastric ulcers.

Anti-inflammatory effects of 4-o-methyl-benzenesulfonyl benzoxazolone (MBB) in vivo and in vitro as a novel NSAIDs lead compound.

Great attention has been paid to the development of novel anti-inflammatory drugs to overcome the adverse reactions of traditional drugs. Recently, a new compound 4-o-methyl-benzenesulfonyl benzoxazolone (MBB) we have prepared attracted our attention for its promising anti-inflammatory activity and low toxicity. The present study aimed to further investigate the anti-inflammatory effects of MBB both in vivo and in vitro in order to determine its potential as a novel NSAIDs lead compound. The anti-inflammatory effects in vivo were evaluated using acetic acid-induced mice writhing, xylene-induced mice ear edema and collagen-induced rat arthritis. NO, TNF-α, IL-6, IL-1β and iNOS productions by LPS-stimulated RAW264.7 cells were determined to investigate the basis of anti-inflammatory effects. Finally, the COX inhibition effect was tested in vitro using COX inhibitor screening assay kit. MBB could significantly decrease the writhing and ear swelling in a dose-dependent manner, and it also had a moderate anti-arthritic potential associated with an attenuation of arthritis index score, arthritis swelling, and inhibition of TNF-α and IL-1β. MBB could inhibit the activity of NO, TNF-α, IL-6, IL-1β and iNOS to perform its activity in vitro, but it had no effect against COX-1 and COX-2. The anti-inflammation effect may be mediated via the inhibition of iNOS to reduce the production of inflammatory mediators which should be further confirmed. The compound MBB displayed anti-inflammatory and anti-arthritic effect, and it could be considered as a new NSAIDs lead compound for the further structure modification to develop novel anti-inflammatory drugs.

Physico-chemical characterization and pharmacological activities of polysaccharides from Opuntia microdasys var. rufida cladodes

The aim of this study is to isolate pectin from peel (WNPE) and pulp (WNPU) of Opuntia microdasys var. rufida’s (OMR) cladodes and to characterize these polysaccharides by size exclusion (SEC/MALS/VD/DRI), gas chromatography coupled to mass spectrometer (GC–MS), nuclear magnetic resonance (1H NMR), and Fourier transform infrared spectroscopy (FTIR) analysis. The polysaccharides were extracted in neutral aqueous media followed by ethanol precipitation and dialysis. Both WNPE and WNPU are mainly composed of uronic acids and some neutral sugars such as arabinose, galactose, rhamnose and mannose. Their molecular weight range from 2,180,000 and 4,920,000g/mol. The in-vivo pharmacological activities (anti-inflammatory, analgesic and gastroprotective activities) have been performed. The extracted pectin (50–100mg/kg, i.p. (intraperitoneal)) inhibited, in a dose-related manner, both carrageenan-induced paw edema in rats and Xylene-induced ear edema in mice. A dose-dependent action was obtained against chemical (writhing test) and thermic (hot plate test) stimuli, respectively, with doses of 50 and 100mg/kg. Moreover, a considerable gastroprotective effect was observed with these two biopolymers, the gastric ulcer was attenuated until 67.67% for WNPE and 81.93% for WNPU, at the dose of 100mg/kg.

Anti-Inflammatory Effects of Boldine and Reticuline Isolated from Litsea cubeba through JAK2/STAT3 and NF-κB Signaling Pathways.

The anti-inflammatory effects of boldine and reticuline isolated from Litsea cubeba were evaluated by using xylene-induced ear edema and carrageenan-induced paw edema in mice and rats. Our results demonstrated that intragastric administration with boldine and reticuline significantly mitigated ear weight in mice and decreased paw volume in rats. A combination administration of boldine (0.5 mg/kg) + reticuline (0.25 mg/kg) resulted in a potentiated inhibition in these two models. In parallel, boldine or reticuline reduce the infiltration of neutrophil leukocytes in rat paw tissue, respectively, and the combination of the two groups performed a better anti-inflammatory activity as shown in histopathologies. Boldine, reticuline, and their combination notably inhibited mRNA expressions of TNF-α, and IL-6 and reduced the phosphorylation levels of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). Beyond that, their combination also can reduce the phosphorylation levels of p65 and IκBα in the pathological tissues of animals, as observed by real-time PCR and western blot analyses, respectively. These findings indicate for the first time that boldine and reticuline have not only anti-inflammatory activity but also potential synergistic effects in vivo. The underlying mechanism may relate to the inhibition on the expression of pro-inflammatory cytokines, such as TNF-α and IL-6, which may be a consequence of JAK2/STAT3 and NF-κB pathway involvements. This study provides useful data for further exploration and application of boldine and reticuline as potential anti-inflammatory medicines.

In vivo and in vitro anti-inflammatory effects of ethanol fraction from Periploca forrestii Schltr.

To determine the anti-inflflammatory effects of an ethanol fraction of Periploca forrestii Schltr. (EFPF) and to investigate the potential mechanisms underlying in vivo and in vitro models. The antiinflflammatory effects of EFPF were evaluated using the xylene-induced mouse ear edema and carrageenan-induced rat paw edema models in vivo. In vitro, RAW264.7 cells were exposed to 0-800 μg/mL EFPF and the cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Then cells were treated with different concentrations of EFPF (100-400 μg/mL) and stimulated with lipopolysaccharide (LPS, 1 μg/mL) for 24 h. The supernatant was analyzed for nitric oxide (NO) using the Griess reagent, and the levels of inflflammatory mediators and cytokines were determined using enzyme-linked immunosorbent assays for prostaglandin E2 (PGE2), tumor necrosis factor α (TNF-α), interleukin (IL) 6, and IL-10. The protein expressions of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor κB (NF-κB), and mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK were examined by Western blot. Compared with the control group, EFPF signifificantly reduced mouse ear edema and rat paw edema rate (P<0.05 or P<0.01). Compared with the LPS group, EFPF signifificantly inhibited the LPS-stimulated production of NO, PGE2, TNF-α and IL-6 (P<0.05 or P<0.01), and increased the IL-10 production (P<0.05). EFPF also signifificantly inhibited LPS-induced protein expressions of iNOS and COX-2, suppressed the phosphorylation and degradation of inhibitor of NF-κB-α, decreased p65 level, and inhibited the phosphorylation of p38, ERK1/2 and JNK P<0.05 or P<0.01). EFPF exerted anti-inflflammatory effect by reducing protein expressions of iNOS and COX-2 and the production of the inflflammation factors, including TNF-α, IL-6, NO and PGE2, mainly through inhibition of LPS-mediated stimulation of NF-κB and MAPK signaling pathways.

Maydis Stigma Elicits Analgesia and Blocks Edema in Mice and Inhibits Inflammation in Macrophages.

Maydis Stigma (MS) is an herb traditionally used in many parts of the world. Previous studies have reported that MS plays a role in several biological activities, including antidiabetic and anticancer activities. However, the effects of a MS ethanolic extract (MSE) on the anti-inflammatory cellular mechanism remain unclear. Here, we investigated the anti-inflammatory properties of MSE and its molecular mechanism both in vitro and in vivo. The effects of MSE on the production of inflammatory mediators, cytokines, and related proteins and the identification of target genes were determined using LPS-stimulated macrophages. We also determined the analgesic and anti-inflammatory effects of MSE by examining acetic acid-induced writhing responses and xylene-induced ear edema in mice. Our results indicated that MSE markedly decreased iNOS and COX-2 levels without causing cytotoxicity and suppressed the secretion of NO in LPS-stimulated macrophages. MSE also inhibited the production of proinflammatory cytokines, such as TNF-[Formula: see text], IL-6, and IL-1[Formula: see text], and induced the expression of HO-1. Moreover, MSE treatment significantly reduced the LPS-stimulated activation of MAPK, NF-[Formula: see text]B, and AP-1. Furthermore, MSE exerted an analgesic effect on the acetic acid-induced abdominal writhing response test and an anti-inflammatory effect on xylene-induced ear edema in ICR mice. Finally, we investigated the components of MSE using UPLC-ESI-MS and found that it contains the maysin as a marker component. Overall, these observations demonstrate that MSE has anti-inflammatory and antinociceptive effects both in vitro and in vivo, which may provide new scientific evidence for its use as a potential therapeutic agent for the treatment of inflammation.

An Exploration of Traditional Chinese Medicinal Plants with Anti-Inflammatory Activities.

In a continuing effort to discover more anti-inflammatory medicinal plants in China, the anti-inflammatory activities of 101 extracts from different parts of 84 traditional medicinal plants were evaluated by a panel of in vitro and in vivo assays. Nuclear factor-kappa B (NF-κB) inhibitory effects were determined by luciferase assay in stably transfected Hela cells. Cytotoxic activities were assessed using the MTT assay. Inhibitory effects on LPS-induced nitric oxide production and proinflammatory mediators were assessed by Griess reaction and Real-Time PCR analysis, respectively. In vivo anti-inflammatory activities were examined by xylene-induced mice ear edema model. In total, 22 extracts showed promising NF-κB inhibitory effects whereas 9 of them did not affect the cell viability. The 9 hit extracts were active in at least one of the subsequently performed in vitro pharmacological test systems. The extract from Hemerocallis minor (root) was selected to perform the in vivo study because it demonstrated significant suppressive effects in all the in vitro assays. Results showed that the extract of Hemerocallis minor (Root) was able to alleviate ear edema effectively in xylene-induced mice ear edema mode. Collectively, our study provides evidence for the potential anti-inflammatory effects of the medicinal plants traditionally used in China. Further phytochemical and pharmacological studies remain to be clarified.

Analgesic and Anti-Inflammatory Activities of Resveratrol through Classic Models in Mice and Rats.

Background. Inflammation and pain are closely related to humans' and animals' health. Resveratrol (RSV) is a natural compound with various biological activities. The current study is aimed to evaluate the analgesic and anti-inflammatory activities of RSV in vivo. Materials and Methods. The analgesic effects were assessed by the acetic acid-induced writhing and hot plate tests. The anti-inflammatory effects were determined using the xylene-induced mouse ear oedema, the acetic acid-induced rat pleurisy, and carrageenan-induced rat synovitis tests, respectively. Results. The analgesic results showed that RSV could significantly inhibit the number of writhes and improve the time and pain threshold of mice standing on hot plate. The anti-inflammatory results showed that RSV could inhibit the ear oedema of mice. In acetic acid-induced pleurisy test, RSV could significantly inhibit the WBC and pleurisy exudates, could decrease the production of NO, and elevate the activity of SOD in serum. In carrageenan-induced synovitis test, RSV could reduce the content of MDA and elevate the T-SOD activity in serum; RSV could inhibit the expressions of TP, PGE2, NO, and MDA. Conclusion. Shortly, these results indicated that RSV had potent analgesic and anti-inflammatory activities and could be a potential new drug candidate for the treatment of inflammation and pain.

The anti-inflammatory effect of Sonchus oleraceus aqueous extract on lipopolysaccharide stimulated RAW 264.7 cells and mice

Context: Sonchus oleraceus L. (Asteraceae) (SO) is a dietary and traditional medicinal plant in China. However, its underlying mechanism of action as an anti-inflammatory agent is not known. Objective: This study evaluates the anti-inflammatory activity of aqueous extract of SO. Materials and methods: The extract of SO was used to treat RAW 264.7 cells (in the working concentrations of 500, 250, 125, 62.5, 31.3 and 15.6 μg/mL) for 24 h. Pro-inflammatory cytokines and mediators produced in LPS-stimulated RAW 264.7 cells were assessed. Meanwhile, the expression level of TLR-4, COX-2, pSTATs and NF-κB was tested. Moreover, the anti-inflammatory activity of the extract in vivo was assessed using xylene-induced mouse ear oedema model and the anti-inflammatory compounds in the extracts were analyzed by HPLC-MS. Results: SO extract significantly inhibited the production of pro-inflammatory cytokines and mediators at gene and protein levels with the concentration of 31.3 μg/mL, and suppressed the expression of TLR-4, COX-2, NF-κB and pSTAT in RAW 264.7 cells. The anti-inflammatory activity of SO in vivo has significant anti-inflammatory effects with the concentration of 250 and 125 mg/kg, and less side effect on the weights of the mice at the concentration of 250 mg/kg. Moreover, HPLC-MS analysis revealed that the anti-inflammatory compounds in the extract were identified as villosol, ferulaic acid, β-sitosterol, ursolic acid and rutin. Discussion and conclusion: This study indicated that SO extract has anti-inflammatory effects in vitro and in vivo, which will be further developed as novel pharmacological strategies in order to defeat inflammatory diseases.

Synthesis and anti-inflammatory activity evaluation of novel 3-alkyl-6-(4H-1,2,4-triazol-4-yl)-3,4-dihydro-2H-benzo[e][1,3]oxazine derivatives

To discover new compounds with anti-inflammatory activity, a series of novel 3-alkyl-6-(4H-1,2,4-triazol-4-yl)-3,4-dihydro-2H-benzo[e][1,3]oxazine derivatives were synthesized and their structures were confirmed by spectroscopic techniques. In vivo anti-inflammatory activity of the synthesized compounds was determined using the xylene-induced mouse ear edema model. 3-Heptyl-6-(4H-1,2,4-triazol-4-yl)-3,4-dihydro-2H-benzo[e] [1,3]oxazine and 3-p-tolyl-6-(4H-1,2,4-triazol-4-yl)-3,4-dihydro-2H-benzo[e][1,3]oxazine demonstrated higher anti-inflammatory activity (74.04 % and 64.99 %, respectively) at 0.5 h after intraperitoneal administration than the reference drug ibuprofen (62.65 %). Further, the time of peak effect after oral administration was 4 h for both compounds. Our results identify new compounds with anti-inflammatory activity in vivo that may have improved safety/side effect profiles relative to the currently approved nonsteroidal anti-inflammatory drugs.

Effect of Different Varieties of Jinfeicao Paste Topical Anti-inflammatory Analgesic

Objective: To investigate the different varieties of Jinfeicao paste topical anti-inflammatory and analgesic effects. Methods: The effects on formalin induced pain in mice, the mouse hot plate induced pain and other pharmacological experiments and making egg-induced rat paw edema model, xylene-induced mouse ear edema model was boiling grass paste topical anti-gold inflammatory and analgesic effects. Results: Jinfeicao paste can reduce the impact of formaldehyde in mice pain, increase the pain threshold in mice, significantly reduced ear swelling in mice, reducing the rat paw swelling degree. Conclusion: Different varieties of Jinfeicao Jinfeicao paste with a good anti-inflammatory topical analgesic effects.

Tiliroside, the major component of Agrimonia pilosa Ledeb ethanol extract, inhibits MAPK/JNK/p38-mediated inflammation in lipopolysaccharide-activated RAW 264.7 macrophages.

In the present study, the in vivo anti-inflammatory activity of Agrimonia pilosa Ledeb (AP) ethanol extract was confirmed in experimental animal models, including xylene-induced ear edema in mice and carrageenan-induced paw edema in rats. Tiliroside, the major component of AP extract, was isolated and purified by high-performance liquid chromatography. The anti-inflammatory mechanism of tiliroside was then examined using lipopolysaccharide (LPS)-activated RAW 264.7 macrophage cells. An MTT assay was used to determine cytotoxicity and a Griess assay was used to determine nitric oxide (NO) production. Concentration levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay. Protein expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), phosphorylated (p)-extracellular signal-regulated kinase (ERK) 1/2, p-c-Jun N-terminal kinases (JNK), p-p38 and inhibitor of κB-α were detected by western blot analysis. AP ethanol extract was revealed to inhibit xylene-induced ear edema in mice and carrageenan-induced paw edema in rats. Tiliroside significantly suppressed the overproduction of NO (P<0.01), but revealed no notable inhibition of the release of TNF-α and IL-6. In addition, tiliroside significantly downregulated the elevated expression levels of iNOS and COX-2 induced by LPS (P<0.01). The phosphorylation of JNK and p38 proteins were also significantly inhibited (P<0.01), however, tiliroside exhibited no obvious inhibition on the phosphorylation of ERK 1/2 and the degradation of IκB-α protein. In conclusion, the anti-inflammatory molecular mechanism of tiliroside may involve the downregulation of iNOS and COX-2 protein expression levels, and the inactivation of mitogen-activated protein kinase (MAPK)/JNK, in addition to the MAPK/p38 signaling pathway.

Anti-Inflammatory and Antinociceptive Properties of Flavonoids from the Fruits of Black Mulberry (Morus nigra L.).

We analyzed the anti-inflammatory and antinociceptive activities of total flavonoids (TF) found in black mulberry fruits. The TF content was 20.9 mg/g (dry weight). Two anthocyanins, cyanidin-3-O-glucoside (8.3 mg/g) and cyanidin-3-O-rutinoside (2.9 mg/g), were identified in the fruits by UPLC. The TF of black mulberry fruits had significant reducing power and radical (OH-,, DPPH and ABTS) scavenging activities that was demonstrated in a dose-response curve. The TF had inhibitory activities on xylene-induced ear edema and carrageenan-induced paw edema in mice. In addition, TF had antinociceptive activities in the two nociceptive phases of formalin test. We used ELISA to detect the pro-inflammatory cytokines IL-1β, TNF-α, IFN-γ, and NO in the serum of mice. These cytokines were significantly inhibited or scavenged by TF (50 and 100 mg/kg). The results demonstrated that TF of black mulberry possess anti-inflammatory and analgesic effects that might correlate to its antioxidant activities and inhibition of pro-inflammatory cytokines.

Anti-Inflammatory Constituents Of Randia Hispida K. Schum (Rubiaceae)

Randia hispida K. Schum (Rubiaceae) is a medicinal plant used by the Ijaws of the Niger Delta area in the southern part of Nigeria for the treatment of inflammation and pyrexia. The plant was extracted sequentially using n-hexane, dichloromethane and 70% methanol. Acute toxicity tests of the extracts were carried out using Lorkes method [1] and LD50 of the extracts were determined for n-hexane (866.02 mg/Kg), dichloromethane (1620.19 mg/kg) and methanolic extracts (2371.7 mg/kg). The anti-inflammatory studies were carried out using xylene-induced ear oedema in mice [2, 3] and egg albumin-induced paw oedema in rats [4]. The extracts were screened at various doses; n-hexane (86.60, 173.21, and 259.81 mg/kg), dichloromethane (162.02, 324.04 and 486.06 mg/kg), and methanolic extracts (237.17, 474.34 and 711.51 mg/kg). The dichloromethane and methanolic extracts displayed equal potency at all the doses used, inhibiting induced edema at 33%, 50% and 67%, the maximum dose showed equal potency with the standard drug dexamethasone (4 mg/kg) which inhibited 67% of xylene -induced inflammation, n-hexane extract gave the least inhibition. On egg albumin induced inflammation in rats, dichloromethane extract showed maximum inhibition of 80.3%, followed by n-hexane 44.9% and methanol extract 35.4%, while the standard drug acetylsalicylic acid 100 mg/kg gave 55.6% inhibition of inflammation.

Synthesis and biological evaluation of novel hydrogen sulfide releasing glycyrrhetic acid derivatives

A series of hybrids, which are composed of glycyrrhetic acid (GA) and slowly hydrogen sulfide-releasing donor ADT-OH, were designed and synthesized to develop anticancer and anti-inflammatory agents. Most of the compounds, whose inhibitory rates were comparable to or higher than those of GA and aspirin, respectively, significantly inhibited xylene-induced ear edema in mice. Especially, compound V4 exhibited the most potent inhibitory rate of 60.7%. Furthermore, preliminary structure–activity relationship studies demonstrated that 3-substituted GA derivatives had stronger anti-inflammatory activities than the corresponding 3-unsubstituted GA derivatives. In addition, anti-proliferative activities of compounds V1−9 were evaluated in three different human cancer cell lines. Compound V4 showed the most high potency against all three tumor cell lines with IC50 values ranging from 10.01 μM in Hep G2 cells to 17.8 μM in MDA-MB-231 cells, which were superior to positive GA.