Histamine-induced Inflammation Research Articles

Establishment of a human nasal epithelium model of histamine-induced inflammation to assess the activity of fexofenadine as an inverse agonist and its link to clinical benefit.

Fexofenadine (FEX) is an antihistamine that acts as an inverse agonist against histamine (HIS) receptor 1 (H1R), which mediates the allergic reaction. Inverse agonists may be more potent than neutral antagonists, as they bind the same receptor as the agonist (HIS) but stabilize the inactive form and induce an opposite pharmacological response, suppressing the basal activity of H1R and preventing HIS from binding. This study aims to establish and validate a model of HIS-induced inflammation based on fully reconstituted human nasal epithelial tissue to assess the activity of FEX as an inverse agonist in this model and explore its link to clinical benefit. The model was developed using nasal MucilAir™ (Epithelix) in vitro epithelium challenged by HIS. Two conditions were assessed in a side-by-side comparison: tissue was exposed to HIS + FEX with or without FEX pre-treatment (one-hour prior to HIS challenge). Tissue functionality, cytotoxicity, H1R gene expression, and inflammatory cytokines were assessed. HIS at 100µM induced significant 3.1-fold and 2.2-fold increases for inflammatory biomarkers interleukin (IL)-8 and IL-6, respectively (p < 0.0001), as well as rapid upregulation of H1R mRNA. Inflammatory biomarkers were inhibited by FEX and H1R expression was significantly reduced (p < 0.0001). FEX alone decreased H1R expression at all doses tested. With one-hour FEX pre-treatment, there was significantly higher downregulation of IL-8 (p < 0.05) and further downregulation of H1R expression and IL-6 versus without FEX pre-treatment; the effects of FEX were improved from 22% to 40%. A model of HIS-induced airway inflammation was established based on IL-8, IL-6 and H1R gene expression and was validated with FEX. FEX works as an inverse agonist, with a higher effect when used before+during versus only during the HIS challenge. Taking FEX before+during allergen exposure, or when symptoms first occur, may reduce basal activity and H1R gene expression, providing stronger protection against the worsening of symptoms upon allergen exposure.

Analgesic effect of a bradykinin antagonist – a 1,4-benzodiazepine-2-one derivative

Aim. To study the analgesic effect of a new 1,4-benzodiazepine-2-one derivative (codenamed PAV-0056) in pain models in mice, its anti-inflammatory effect in experimental exudative inflammation in rats, and its potential ulcerogenic effect.Materials and methods. A 1,4-benzodiazepine-2-one derivative (codenamed PAV-0056) was orally administered in polyvinylpyrrolidone (PVP) solution to 192 CD-1 mice weighing 20–25 g and 140 Sprague – Dawley rats weighing 250–300 g. The analgesic effect of the PAV-0056 compound at a dose of 0.01, 0.1, and 1 mg / kg was studied in murine acute thermal pain models (hot plate test, hot water immersion tail-flick test), acute chemogenic pain models (formalin test), and visceral spasticity-related pain models (acetic acid-induced writhing test). The anti-inflammatory effect of PAV-0056 at doses of 0.01, 0.1, and 1 mg / kg was studied in an experimental rat model of inflammation induced by subplantar administration of bradykinin and histamine. The potential ulcerogenic effect was studied in intact rats, who were injected with PAV-0056 at doses of 1 and 50 mg / kg four times. The analgesic effect of the PAV-0056 compound was compared to that of diclofenac sodium at a dose of 10 mg / kg and tramadol at a dose of 20 mg / kg. Its anti-inflammatory and potential ulcerogenic effects were compared to those of diclofenac sodium at a dose of 10 mg / kg.Results. In the hot plate test, the PAV-0056 compound at a dose of 0.1 mg / kg increased response latency in mice by 36%, and at a dose of 1 mg / kg, it increased response latency by 46% (p &lt; 0.05). In the tail-flick test, the PAV-0056 compound at a dose of 1 mg / kg increased response latency to heat stimulation in mice by 46% (p &lt; 0.05). After subplantar administration of formalin, PAV-0056 at doses of 0.01–1 mg / kg had a pronounced analgesic effect, as shown by a decrease in the number of pain responses by 39–55% (p &lt; 0.05). When mice were intraperitoneally injected with an acetic acid solution, the PAV-0056 compound at doses of 0.1 and 1 mg / kg reduced the frequency of writhings by 46 and 57%, respectively; at a dose of 0.1 mg / kg, it delayed the onset of the first writhing by 21% (p &lt; 0.05). In experiments on rats, the PAV-0056 compound prevented the development of exudative inflammation induced by subplantar administration of bradykinin and did not have an anti-inflammatory effect in histamine-induced inflammation. PAV-0056 did not cause formation of gastric ulcers and gastric mucosal bleeding.Conclusion. A 1,4-benzodiazepine-2-one derivative, PAV-0056, has a pronounced analgesic effect in models of thermal, chemogenic, somatic, and visceral pain in a wide range of doses (0.01–1 mg / kg). Its analgesic effects are the same as those of diclofenac sodium at a dose of 10 mg / kg and tramadol at a dose of 20 mg / kg. The analgesic effect of the PAV-0056 compound is selective, depends little on suppression of inflammatory exudation, and is caused by bradykinin antagonism. This substance has low toxicity and does not damage the gastric mucosa.

Anti-inflammatory activity of Indonesian polyherbal product containing Curcuma zanthorrhiza and Vitex trifolia as the main ingredients in carrageenan- and histamine-induced inflammation in Wistar rats

Anti-inflammatory activity of Indonesian polyherbal product containing Curcuma zanthorrhiza and Vitex trifolia as the main ingredients in carrageenan- and histamine-induced inflammation in Wistar rats

Synthesis, Spectroscopic and Biological Investigation of a New Ca(II) Complex of Meloxicam as Potential COX-2 Inhibitor.

Drug development on basis of coordination compounds provides versatile structural and functional properties as compared to other organic compounds. In the present study, a new Ca(II) complex of meloxicam was synthesized and characterized by elemental analysis, FT-IR, UV–Vis, 13C NMR, SEM–EDX, powder XRD and thermal analysis (TGA). The Ca(II) complex was investigated for its in vitro, in vivo biological activities and in silico docking analysis against COX-1 and COX-2. The spectral analysis indicates that the meloxicam acts as a deprotonated bidentate ligand (coordinated to the metal atom through the amide oxygen and the nitrogen atom of the thiazolyl ring) in the complex. SEM–EDX and powder XRD analysis depicted crystalline morphology of Ca(II) complex with a crystalline size of 32.86 nm. The in vitro biological activities were evaluated by five different antioxidant methods and COX inhibition assay, while in vivo activities were evaluated by carrageenan-, histamine- and PGE2-induced paw edema methods and acetic acid-induced writhing test. The Ca(II) complex showed prominent antioxidant activities and was found to be more selective toward COX-2 (43.77) than COX-1 as compared to meloxicam. It exhibited lower toxicity (LD50 1000 mg/Kg) and significantly inhibited carrageenan- and PGE2-induced inflammation at 10 mg/Kg (P < 0.05), but no significant effect was observed on histamine-induced inflammation. Moreover, Ca(II) complex significantly reduced the number of writhes induced by acetic acid (P < 0.05). The in silico molecular docking data revealed that Ca(II) complex obstructed COX-2 (dock score 6438) more effectively than COX-1 (dock score 5732) as compared to meloxicam alone.

Effects of Osthole on Inflammatory Gene Expression and Cytokine Secretion in Histamine-Induced Inflammation in the Caco-2 Cell Line.

Hyperactivity of the immune system in the gastrointestinal tract leads to the development of chronic, inflammation-associated disorders. Such diseases, including inflammatory bowel disease, are not completely curable, but the specific line of treatment may reduce its symptoms. However, the response to treatment varies among patients, creating a necessity to uncover the pathophysiological basis of immune-mediated diseases and apply novel therapeutic strategies. The present study describes the anti-inflammatory properties of osthole during histamine-induced inflammation in the intestinal Caco-2 cell line. Osthole reduced the secretion of cytokines (CKs) and the expression level of inflammation-associated genes, which were increased after a histamine treatment. We have shown that the secretion of pro-inflammatory CKs (IL-1β, IL-6, IL-8, and TNF-α) during inflammation may be mediated by NFκB, and, after osthole treatment, this signaling pathway was disrupted. Our results suggest a possible role for osthole in the protection against inflammation in the gastrointestinal tract; thus, osthole may be considered as an anti-inflammatory modulator.

Famotidine inhibits toll-like receptor 3-mediated inflammatory signaling in SARS-CoV-2 infection

Apart from prevention using vaccinations, the management options for COVID-19 remain limited. In retrospective cohort studies, use of famotidine, a specific oral H2 receptor antagonist (antihistamine), has been associated with reduced risk of intubation and death in patients hospitalized with COVID-19. In a case series, nonhospitalized patients with COVID-19 experienced rapid symptom resolution after taking famotidine, but the molecular basis of these observations remains elusive. Here we show using biochemical, cellular, and functional assays that famotidine has no effect on viral replication or viral protease activity. However, famotidine can affect histamine-induced signaling processes in infected Caco2 cells. Specifically, famotidine treatment inhibits histamine-induced expression of Toll-like receptor 3 (TLR3) in SARS-CoV-2 infected cells and can reduce TLR3-dependent signaling processes that culminate in activation of IRF3 and the NF-κB pathway, subsequently controlling antiviral and inflammatory responses. SARS-CoV-2-infected cells treated with famotidine demonstrate reduced expression levels of the inflammatory mediators CCL-2 and IL6, drivers of the cytokine release syndrome that precipitates poor outcome for patients with COVID-19. Given that pharmacokinetic studies indicate that famotidine can reach concentrations in blood that suffice to antagonize histamine H2 receptors expressed in mast cells, neutrophils, and eosinophils, these observations explain how famotidine may contribute to the reduced histamine-induced inflammation and cytokine release, thereby improving the outcome for patients with COVID-19.

Evaluation of anti-inflammatory and anti-arthritic property of ethanolic extract of Clitoria ternatea

ObjectiveClitoria ternatea is a well-known bioactive plant used to treat several inflammatory ailments in Ayurvedic system of medicine in India. The present investigation aimed to determine the anti-inflammatory and anti-arthritic activity of ethanolic extract of Clitoria ternatea roots (EECT) in animal models. MethodsThe anti-inflammatory activity of the EECT was evaluated by carrageenan and histamine-induced paw edema. ResultsEECT showed a significant reduction in mean paw edema volume in both carrageenan and histamine-induced inflammation. The efficacy of EECT in rheumatoid arthritis was tested against Freund’s complete adjuvant (CFA) induced arthritic model in Wistar rats. The anti-arthritic effect of EECT was determined by systematic scoring of arthritis symptoms and measuring paw edema. A considerable decrease in paw diameter was observed in the EECT (200 and 400 mg/kg) and diclofenac (10 mg/kg) treated groups after day 7. Diclofenac (10 mg/kg) and EECT (400 mg/kg) showed a significant reduction in paw diameter from day 14 compared with CFA control (P < 0.001). The anti-arthritic activity was also confirmed from the altered biochemical, haematological (Hb, RBC and WBC) and anti-oxidant parameters (SOD, MDA, CAT, and GSH). EECT (400 and 200 mg/kg) also showed a marked inhibition of joint destruction. ConclusionThis study provides a pharmacological rationale for the traditional use of C. ternatea against inflammation and rheumatoid arthritis in India.

Analysis of the variations in the marker compound of Glycyrrhiza glabra L. root with reference to age of the drug, storage conditions and pharmacological efficacy

Phyto-constituents and their efficacy vary with the age of the plant material and their affliction with environmental and storage conditions. Present study was conducted to evaluate the time dependent variation in physicochemical characters, glycyrrhizin content, microbial load and anti-inflammatory activity of Glycyrrhiza glabra L. root (GGR). Fresh GGR was dried and divided into three samples and stored as: sample A below 4 °C, sample B at room temperature and sample C at 40 ± 2 °C with relative humidity 75 ± 5% for six months. Afterwards, each sample was extracted in 50% alcohol and evaluated for physicochemical characters, glycyrrhizin content, microbial contamination and anti-inflammatory activity in histamine-induced inflammation in Wistar rats. Physicochemical characteristics exhibits less than 25% variation and qualitative analysis for plant metabolites exhibited similarity in all three samples. Glycyrrhizin was found more in sample C (5.07%) in comparison to sample B (4.52%) and A (4.72%) with variation less than 15%. As per the Ayurvedic Pharmacopeia of India these variations in physicochemical parameters and glycyrrhizin content are insignificant. Sample A revealed total microbial count more than B and C. Accelerated stability data extrapolation of sample C suggests that shelf life of GGR is 2 years. Inflammation was significantly reduced by sample C followed by A and B in comparison to the control with residual paw volume of 0.9%, 3.22%, 20.4% and 29.7% respectively at 163 mg/kg BW dose. From the present study it can be concluded that up to two years age dependent variations in GGR is insignificant but its anti-inflammatory effect are glycyrrhizin dependent.

Anti-inflammatory and In Silico Docking Studies of Heterophragma adenophyllum Seem Stem Constituents.

Heterophragma adenophyllum is a traditional medicinal plant that has been used as anti-inflammatory and to relief muscular tension. In the current research, four isolated constitutes namely lapacho (1), peshawaraquinone (2), indanone derivatives (3), α-lapachone (4) of H. adenophyllum were tested for anti-inflammatory effect using the carrageenan- and histamine-induced paw edema paradigm. The tested compounds (1-4) were evaluated for anti-inflammatory effect during the early and late phase of edema induction. In the early phase, all tested compounds (0.5 2.5mg/kg each i.p.) demonstrated less than 50% effect, while in the later phase, compounds (2 and 3) demonstrated 85.66 and 89.87% attenuation. In addition, compounds (1-4) were subjected to histamine-induced inflammation, where compounds 2 and 3 exhibited excellent effects 86.87 and 89.98%, respectively at 5mg/kg after the 2nd hour of administration, whereas compounds 1 and 4 did not exhibit any significant effect as compared with the negative control. Molecular docking results revealed a very high potency of compound based on the protein-ligand interaction (PLI) profile, which was further evaluated through a molecular dynamic simulation study. Therefore, the anti-inflammatory effect of H. adenophyllum attributed to the presence of these bioactive compounds (1-4) strongly supports the traditional uses of H. adenophyllum for treatment of inflammation. However, compounds 2 and 3 which exerted anti-inflammatory effect must be subjected for further mechanistic studies.

Anti-inflammatory, Antibacterial, Toxicological Profile, andIn SilicoStudies of Dimeric Naphthoquinones fromDiospyros lotus

Diospyros lotus, also known as date-plum, belongs to theEbenaceaefamily and is mostly recognized as a rootstock forD.kaki. Similar classes of naphthoquinones inD.lotusare investigated against cancer and inflammation and have antimicrobial, sedative, and analgesic properties. Six chemical constituents (1-6) were isolated fromDiospyros lotusand tested for anti-inflammatory effects at the dose of 2.5 and 5 mg/kg, i.p., using carrageenan (1%, 0.05 ml)-induced paw edema. The maximum protection against carrageenan-induced edema was observed for compounds 1 and 2. Both studied compounds demonstrated significant anti-inflammatory effect after the 3rdhour of posttreatment. The maximum anti-inflammatory effect of compound 1 was 85.96%, while that of compound 2 was 81.44%, followed by compounds 5 and 6, which exhibited 80.11% and 82.45% effect, respectively. Similarly, histamine-induced inflammation was significantly antagonized by 1, 2, 5, and 6 with 87.99%,82.18±1.8,80.40±1.59, and 77.44% effects, respectively, at 5 mg/kg after the 2ndhour of posttreatment. The rest of the tested compounds did not show any significant effect as compared to the negative control. Interestingly, no toxicity was observed at higher doses. Moreover, the extracted compounds showed remarkable antibacterial activity against the Gram-positive bacteria and no effect against the Gram-negative bacteria. Docking studies on target cyclooxygenases showed that all the compounds established interactions with the key amino acid residues present in the additional pocket of COX-2. Hence, these compounds may act as selective COX-2 inhibitors. In conclusion, the findings of the current study suggest that the roots ofDiospyros lotusmay contain some anti-inflammatory and antibacterial agents with minimal toxicological effects and accordingly this plant product is recommended for further investigations.

Methanol extract of Napoleona vogelii demonstrates anti-nociceptive and anti-inflammatory activities through dopaminergic mechanism and inhibition of inflammatory mediators in rodents

Napoleona vogelii (Lecythidaceae) is used in traditional medicine for the management of pain and inflammatory disorders. This study was conducted to investigate the anti-nociceptive and anti-inflammatory activity of the methanol stem bark extract of N. vogelii in rodents. The extract (100–400 mg/kg) was administered 1 h before intraperitoneal and intraplantar injection of 0.2 mL of 0.6% v/v acetic acid and 0.05 mL of 2% v/v formalin, respectively. Anti-inflammatory activity was investigated using the carrageenan-induced paw edema and formalin-induced arthritis models. Mechanistic studies were conducted by exploring opioidergic, dopaminergic pathways, and inflammatory mediators. There was 62.26% inhibition of inflammatory pain at 400 mg/kg in the formalin-induced paw licking test. In the acetic acid-induced mouse writhing assay, the extract produced a dose-dependent inhibition of writhes with peak effect at 400 mg/kg producing 54.87% inhibition compared with diclofenac at 71.09%. The extract produced 90.98% inhibition of the late phase of carrageenan-induced paw edema and 82.81% inhibition in the formalin-induced arthritis test. The anti-nociceptive activity of the extract was blocked by sulpiride (D2 receptor antagonist; 1 mg/kg) but not by naloxone (opioid receptor antagonist; 5 mg/kg). In addition, pre-treatment of mice with the extract produced 95.08% inhibition of histamine-induced inflammation similar to that of indomethacin at 97.54% and inhibition of serotonin-induced inflammation at 46.79% compared with indomethacin which produced 94.26%. This study demonstrates that the extract possesses anti-nociceptive and anti-inflammatory activity mediated through inhibition of dopaminergic pathways and inflammatory mediators.

Inonotus obliquus attenuates histamine-induced microvascular inflammation.

Cell-to-cell communication is a key element of microvascular blood flow control, including rapidly carrying signals through the vascular endothelium in response to local stimuli. This cell-to-cell communication is negatively impacted during inflammation through the disruption of junctional integrity. Such disruption is associated with promoting the onset of cardiovascular diseases as a result of altered microvascular blood flow regulation. Therefore, understanding the mechanisms how inflammation drives microvascular dysfunction and compounds that mitigate such inflammation and dysfunction are of great interest for development. As such we aimed to investigate extracts of mushrooms as potential novel compounds. Using intravital microscopy, the medicinal mushroom, Inonotus obliquus was observed, to attenuate histamine-induced inflammation conducted vasodilation in second-order arterioles in the gluteus maximus muscle of C57BL/6 mice. Mast cell activation by C48/80 similarly disrupted endothelial junctions and conducted vasodilation but only histamine was blocked by the histamine antagonist, pyrilamine not C48/80 suggesting the importance of mast cell activation. Data presented here supports that histamine induced inflammation is a major disruptor of junctional integrity, and highlights the important anti-inflammatory properties of Inonotus obliquus focusing future assessment of mast cells as putative target for Inonotus obliquus.

5,6-DiHETE attenuates vascular hyperpermeability by inhibiting Ca2+ elevation in endothelial cells

Although more than 100 lipid metabolites have been identified, their bioactivities remain unknown. In a previous study, we discovered that the production of several lipid metabolites in the intestines dramatically changed in colitis. Of these metabolites, 5,6-dihydroxyeicosatetraenoic acid (DiHETE) possesses novel anti-inflammatory activity in the vasculature. In this study, we used mouse and human umbilical vein endothelial cell (HUVEC) models to elucidate the mechanisms underlying the vascular activity of lipid metabolites, particularly those related to the release of histamine, a major proinflammatory mediator that stimulates endothelial cells to produce NO, a mediator of vascular relaxation and hyperpermeability, by activating intracellular Ca2+ concentration-dependent signaling. In a mouse ear, the administration of 5,6-DiHETE did not induce inflammatory reactions, and pretreatment with 5,6-DiHETE inhibited histamine-induced inflammation, specifically vascular dilation and hyperpermeability. In an isolated mouse aorta, 5,6-DiHETE treatment did not influence vascular contraction but attenuated acetylcholine-induced vascular relaxation. In HUVECs, treatment with 5,6-DiHETE inhibited histamine-induced endothelial barrier disruption and inhibited the production of NO. Most notably, 5,6-DiHETE inhibited histamine-induced increases in intracellular Ca2+ concentrations in HUVECs. Our findings suggest that 5,6-DiHETE attenuates vascular hyperpermeability during inflammation by inhibiting endothelial Ca2+ elevation, which might lead to a novel pharmacological strategy against inflammatory diseases.

Characterization of platelet-activating factor-induced cutaneous edema and erythema in dogs.

OBJECTIVE To characterize platelet-activating factor (PAF)-induced edema and erythema in the skin of dogs and compare those reactions with histamine-induced cutaneous reactions. ANIMALS 6 healthy Beagles. PROCEDURES Experiments were performed at ≥ 2-week intervals. Each dog received ID injections (5 μg/site) of PAF C16, PAF C18, lyso-PAF, and histamine. Edema (mean diameter) and erythema scores (none, mild, moderate, or severe) were assessed 30 minutes after the injections. Dogs received ID injections of PAF and histamine each with various concentrations of WEB 2086 (PAF receptor antagonist) or underwent ID testing with PAF and histamine before and 3 hours after oral administration of cetirizine hydrochloride or prednisolone (at 2 doses each). RESULTS ID injections of PAF C16 and PAF C18, but not lyso-PAF, induced comparable levels of edema and erythema. The PAF-induced edema and erythema peaked at 30 minutes and lasted for 6 hours after the injection; histamine-induced edema and erythema peaked at 30 minutes and lasted for 3 hours after the injection. Edema sizes and erythema scores were significantly smaller and lower, respectively, for PAF than for histamine. The WEB 2086 inhibited PAF-induced but not histamine-induced edema and erythema. Cetirizine slightly, but significantly, repressed PAF-induced edema and erythema as well as histamine-induced cutaneous reactions. Prednisolone suppressed both PAF-induced and histamine-induced edema and erythema. CONCLUSIONS AND CLINICAL RELEVANCE In canine skin, the duration of PAF-induced inflammation was longer than that of histamine-induced inflammation. The PAF- and histamine-induced cutaneous reactions were effectively suppressed by oral administration of prednisolone. The importance of PAF in dogs with anaphylaxis and allergic disorders warrants further investigation.

Topical Application of Fingolimod Perturbs Cutaneous Inflammation.

The prevalence of allergies, including rhinitis, eczema, and anaphylaxis, is rising dramatically worldwide. This increase is especially problematic in children who bear the greatest burden of this rising trend. Increasing evidence identifies neutrophils as primary perpetrators of the more severe and difficult to manage forms of inflammation. A newly recognized mechanism by which neutrophils are recruited during the early phase of histamine-induced inflammation involves the sphingosine kinase (SK)/sphingosine-1-phosphate axis. This study examines whether topical application of fingolimod, an established SK/sphingosine-1-phosphate antagonist already in clinical use to treat multiple sclerosis, may be repurposed to treat cutaneous inflammation. Using two mouse models of ear skin inflammation (histamine- and IgE-mediated passive cutaneous anaphylaxis) we topically applied fingolimod prophylactically, as well as after establishment of the inflammatory response, and examined ear swelling, SK activity, vascular permeability, leukocyte recruitment, and production of proinflammatory mediators. The present study reveals that when applied topically, fingolimod attenuates both immediate and late-phase responses to histamine with reduced extravasation of fluid, SK-1 activity, proinflammatory cytokine and chemokine production, and neutrophil influx and prevents ear swelling. Intravital microscopy demonstrates that histamine-induced neutrophil rolling and adhesion to the postcapillary venules in the mouse ears is significantly attenuated even after 24 h. More importantly, these effects are achievable even once inflammation is established. Translation into humans was also accomplished with epicutaneous application of fingolimod resolving histamine-induced and allergen-induced inflammatory reactions in forearm skin. Overall, this study demonstrates, to our knowledge for the first time, that fingolimod may be repurposed to treat cutaneous inflammation.

Conditioning pain stimulation does not affect itch induced by intra-epidermal histamine pricks but aggravates neurogenic inflammation in healthy volunteers

This study investigated whether itch induced by intra-epidermal histamine is subjected to modulation by a standardized conditioned pain modulation (CPM) paradigm in 24 healthy volunteers. CPM was induced by computer-controlled cuff pressure algometry and histamine was introduced to the volar forearm by skin prick test punctures. Moreover, neurogenic inflammation and wheal reactions induced by histamine and autonomic nervous system responses (heart rate variability and skin conductance) were monitored. CPM did not modulate the intensity of histamine-induced itch suggesting that pruriceptive signaling is not inhibited by pain-recruited endogenous modulation, however, CPM was found to aggravate histamine-induced neurogenic inflammation, likely facilitated by efferent sympathetic fibers.

Evaluation of Anti-inflammatory Activity of Seeds of Phalaris canariensis.

Chloroform extract (ALC) from the seeds of Phalaris canariensis were assayed for antiinflammatory activity by carrageenan-induced oedema, cotton pellets-induced granuloma, histamine-induced inflammation, croton oil-induced oedema, activity of myeloperoxidase (MPO), adjuvant-induced arthritis, quantification of TNFα, IL-1β, PGE2 and LTB4 and nitric oxide (NO) assay. ALC exhibited significant anti-inflammatory activity in different chemically-induced edemas in a dose dependent manner. In the chronic model cotton pellets-induced granuloma showed decreased formation of granuloma tissue. Also caused inhibition of ear inflammation edema and influx of polymorphonuclear cells, as evidence by a decrease in ear thickness and reduced myeloperoxidase activity and inhibit mediators of inflammation as TNFα, IL-1β, PGE2 and LTB4. When RAW 264.7 macrophages were treated with ALC together with LPS a significant inhibition of NO production was detected. These data provide evidence for antiinflammatory effect of P. canariensis by mechanisms that involve a reduced neutrophil influx and decreased production of inflammatory cytokines.

Saponins isolated from roots of Chlorophytum borivilianum reduce acute and chronic inflammation and histone deacetylase

ObjectiveThe roots of Chlorophytum borivilanum are used in traditional medicine for the treatment of arthritis and inflammation. The aim of the work was to evaluate the anti-inflammatory activity of isolated saponins from Chlorophytum borivilianum (ISCB). MethodsThe ISCB was screened using the carrageenan-induced paw edema, histamine-induced paw edema, cotton pellet-induced granuloma, and Freund's adjuvant-induced arthritis in rats at orally administered doses of 3, 10, and 30 mg/kg. Effect of ISCB on histone deacetylase (HDAC) level was measured by the HDAC assay at the highest dose (30 mg/kg). ResultsThe results showed that the ISCB significantly reduced carrageenan-induced inflammation, histamine-induced inflammation, cotton pellet-induced granuloma and Freund's adjuvant-induced arthritis in rats. The ISCB at a dose of 30 mg/kg significantly inhibited HDAC level in rat paw tissue. ConclusionIt is concluded that saponins isolated from roots of C. borivilianum possess anti-inflammatory and anti-arthritic properties. ISCB may act by inhibiting histamine, prostaglandin and HDAC. This suggests that ISCBs have potential for therapeutic use in the treatment of inflammation and arthritis.

Diallyl sulfide as a potential dietary agent to reduce TNF‐α‐ and histamine‐induced proinflammatory responses in A7r5 cells

Oxidative stress-aggravated chronic inflammatory diseases of the airway are well documented; hence, treatment with antioxidants to ameliorate oxidative stress might be an effective strategy to reduce airway complications. The aim of this study was to investigate the effect and molecular mechanism of diallyl sulfide (DAS), which is a natural organosulfuric compound found in garlic, on the inhibition of tumor necrosis factor-alpha (TNF-α)- or histamine-induced inflammation in rat aortic smooth muscle A7r5 cells. A7r5 cells were coincubated with DAS before exposure to TNF-α or histamine. DAS significantly blocked the accumulation of the nuclear p65 protein in TNF-α-induced A7r5 cells by attenuating the TNF-α receptor complex through the dissociation of the TNF receptor-associated death domain and TNF receptor-associated factor 2. Moreover, DAS inhibited histamine-induced inflammation by decreasing reactive oxygen species (ROS) levels by enhancing the nuclear factor-erythroid 2-related factor 2-related antioxidative enzyme. DAS also inhibited inflammation by suppressing interleukin-1β and TNF-α through the inhibition of ROS-induced PI3K/Akt and the downstream NF-κB and activator protein-1. Our results demonstrate that DAS is a potential phytochemical to inhibit TNF-α- and histamine-induced inflammation, suggesting that DAS might be an effective dietary agent for the prevention of oxidative stress-induced inflammation of the airway.

Analgesic and Anti-inflammatory Profile of n-Hexane Fraction of &lt;i&gt;Viola betonicifolia&lt;/i&gt;

Purpose: To evaluate the analgesic and anti-inflammatory activities of n-hexane extract of the whole plant of Viola betonicifolia Sm, family: Violaceace.Methods: The n-hexane fraction of Viola betonicifolia (VBHF) was tested for its analgesic and antiinflammatory activities (carrageenan-induced and histamine-induced edema models) in BALB/c mice.Results: VBHF exhibited significant (p &lt; 0.01) analgesic and anti-inflammatory activity at test doses of 100, 200 and 300 mg/kg. The analgesic effect of VBHF was dose-dependent in acetic acid pain modelwhile the extract was a weak analgesic at the dose of 300 mg/kg in hot plate and tail immersion test. Diclofenac sodium and tramadol showed better analgesic properties to the extract. Analgesia was not antagonized by naloxone in the hot plate model. Anti-inflammatory activity against carrageenan-induced edema was 60.8 %; however, histamine-induced inflammation was not antogonised by the extract.Conclusions: The extract has some analgesic and anti-inflammatory activities. This justifies its use in traditional medicine for pain of management.Keywords: Viola betonicifolia, Analgesic, Anti-inflammatory.