Acetic Acid-induced Vascular Permeability Research Articles

Analgesic and anti-inflammatory effects of galangin: a potential pathway to inhibit transient receptor potential vanilloid 1 receptor activation.

Galangin, commonly employed in traditional Chinese medicine for its diverse medicinal properties, exhibits potential in treating inflammatory pain. Nevertheless, its mechanism of action remains unclear. Mice were randomly divided into 4 groups for 7 days: a normal control group, a galangin-treated (25 and 50 mg/kg), and a positive control celecoxib (20 mg/kg). Analgesic and anti-inflammatory effects were evaluated using a hot plate test, acetic acid-induced writhing test, acetic acid-induced vascular permeability test, formalininduced paw licking test, and carrageenan-induced paw swelling test. The interplay between galangin, transient receptor potential vanilloid 1 (TRPV1), NF-κB, COX-2, and TNF-α proteins was evaluated via molecular docking. COX- 2, PGE2, IL-1β, IL-6, and TNF-α levels in serum were measured using ELISA after capsaicin administration (200 nmol/L). TRPV1 expression in the dorsal root ganglion was analyzed by Western blot. The quantities of substance P (SP) and calcitonin gene-related peptide (CGRP) were assessed using qPCR. Galangin reduced hot plate-induced licking latency, acetic acid-induced contortions, carrageenantriggered foot inflammation, and capillary permeability in mice. It exhibited favorable affinity towards TRPV1, NF- κB, COX-2, and TNF-α, resulting in decreased levels of COX-2, PGE2, IL-1β, IL-6, and TNF-α in serum following capsaicin stimulation. Galangin effectively suppressed the upregulation of TRPV1 protein and associated receptor neuropeptides CGRP and SP mRNA, while concurrently inhibiting the expression of NF-κB, TNF-α, COX-2, and PGE2 mRNA. Galangin exerts its anti-inflammatory pain effects by inhibiting TRPV1 activation and regulating COX-2, NF-κB/TNF-α expression, providing evidence for the use of galangin in the management of inflammatory pain.

Exploring the multifaceted effects of Ammi visnaga: subchronic toxicity, antioxidant capacity, immunomodulatory, and anti-inflammatory activities

ABSTRACT Ammi visnaga (A. visnaga) is an annual herb that has been used in traditional medicine to treat various ailments attributed to the presence of its bioactive compounds. The purpose of this study was to identify and examine the phytochemical properties of the hydroalcoholic extract of A. visnaga using in vitro and in vivo models. Our findings demonstrated that the extract contained a variety of beneficial components, including phenols, flavonoids, tannins, coumarins, saponins, khellin, and visnagin. The total polyphenolic content and total flavonoid content were 23.26 mg/GAE/g dry weight and 13.26 mg/GAE/g dry weight, respectively. In vitro tests demonstrated that the extract possessed antioxidant properties as evidenced by the ability to scavenge free radicals, including DPPH, ABTS, nitric oxide (NO), phosphomolybdate, and ferric-reducing antioxidant power (FRAP). Further, the extract was found to inhibit hydrogen peroxide (H2O2)-induced hemolysis. In a 90-d in vivo study, female Wistar rats were administered 1 g/kg of A. visnaga extract orally resulting in a significant increase in total white blood cell count. Although morphological changes were observed in the liver, no marked alterations were noted in kidneys and spleen. In a female Swiss albino mice model of acetic acid-induced vascular permeability, A. visnaga significantly inhibited extravasations of Evans blue at doses of 0.5 or 1 g/kg with inhibition percentages of 51 and 65%, respectively, blocking tissue necrosis. The extract also demonstrated potential immunomodulatory properties in mice by enhancing antibody production in response to antigens. In silico molecular docking studies demonstrated a strong affinity between khellin or visnagin and immunomodulatory proteins, NF-κB, p52, and TNF-α. These findings suggest that A. visnaga may be considered a beneficial antioxidant with immunomodulatory properties and might serve as a therapeutic agent to combat certain diseases.

Membrane Stabilization and Vascular Permeability as Mechanisms for the Evaluation of Anti-inflammatory Action of Omega-3-poly Unsaturated Fatty Acid Oil Extract

Introduction: The underlying molecular mechanisms responsible for omega-3 PUFAs’ biological effects are mediated by the production of pro-resolving mediators, which have been proposed to modulate and likely resolve inflammatory responses. The anti-inflammatory action of dietary omega-3-polyunsaturated fatty acid supplementation in animal models has been studied using membrane stabilization and vascular permeability methods. This study is, therefore, focused on the long-term therapeutic safety and efficacy of fish oil supplements as a safer alternative to traditional NSAIDs. Also, whether these methods serve as mechanisms of antiinflammation has been confirmed further. Method: Animals were distributed in six groups of five each (n = 5). Group 1 was administered 300mg/ml omega-3 fatty acids (n-3 FA) containing 180mg/ml EPA and 120mg/ml DHA; group 2 received 600mg/ml n-3 FA containing 360mg/ml EPA and 240mg/ml DHA; group 3 received 900mg/ml n-3 FA containing 540mg/ml EPA and 360mg/ml DHA; group 4 was administered 300mg/ml of the fish oil along with 20mg/ml celecoxib; group 5 was given 20mg/ml celecoxib that represented the positive control, and group 6 was administered 2 ml phosphate buffer saline alone, which served as the vehicle control group. Membrane stabilization of the rat’s red blood cells and aceticacid-induced vascular permeability were assayed. The percentage inhibition was determined. The analysis was performed using GraphPad InStat version 5 software and subjected to the Bonferroni test for the separation of means. Result: The results of membrane stabilization assays exhibited 30.59%, 27.70%, 49.63%, 55.41%, 57.28%, and 13.13% inhibitions, and vascular permeability inhibitions were found to be 80.05%, 53.27%, 74.31%, 86.33%, and 90.43%, respectively. The results provide scientific evidence for the use of dietary omega-3-polyunsaturated fatty acid as a food supplement capable of resolving inflammatory conditions without side effects produced by traditional NSAIDs. Conclusion: The restoration of altered membrane permeability and vasculature is a testament to the efficacy of omega-3 as an anti-inflammatory agent and indeed shows these methods as anti-inflammatory mechanisms. The bioactive components in omega-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in fish oil are capable of interrupting the prostaglandin metabolic pathway by competing with arachidonic acids for the COX active site, thereby inhibiting their synthesis.

Protective effects of Brenania brieyi (De Wild) E.M.A.Petit root bark fractions against inflammatory-mediated hemolysis and dyslipidemia in rats

Background and Aims: The inflammatory response, though protective, is the major cause of debilitating diseases when provoked excessively or if left unresolved. Brenania brieyi (De Wild) E.M.A.Petit is widely used in folk medicine for the treatment of inflammatory-related diseases. This study investigated the protective effects of methanol and chloroform root bark fractions of Brenania brieyi on inflammation-induced hemolysis and dyslipidemia. Methods: Anti-inflammatory activity was investigated by inserting 20 mg of autoclaved cotton pellets into forty-five rats randomly distributed into nine groups (n=5), this excluded group 1 (baseline). The extent of hemolysis and dyslipidemia in the inflamed rats was ascertained from hematological parameters, lipid profile, and lipidemic index, while the possible underlying mechanisms of inflammation were determined using standard procedures. Results: Treatment with varying doses of the root bark fractions of B. brieyi elicited a significant (p< 0.05) decrease in granuloma tissue and an increase (p<0.05) in hemoglobin, red and white blood cell count, packed cell volume, and platelets compared with the untreated group 2. A significant (p<0.05) decrease in cholesterol, triacylglycerols, and low-density lipoprotein, and a non-significant (p>0.05) increase in high-density lipoprotein were observed in almost all the test groups compared with group 2. There was a significant restoration of atherogenic and dyslipidemia indices and inhibition of acetic acid-induced vascular permeability, membrane hemolysis, and platelet aggregation in the fraction-treated groups compared with the control. Conclusion: The findings from this study suggest that B. brieyi inhibits exudation and proliferation of granuloma-forming cells and also has the potential to restore the hematological parameters and lipid anomalies to their physiologic state under chronic inflammation. The possible mechanisms of its action could be inhibition of vascular permeability, stabilization of the membrane, or inhibition of platelet aggregation. This justifies the use of the plant in traditional medicine and also demonstrates its potential as a target for the discovery of new anti-inflammatory agents.

Anti-Inflammatory Activation of Phellodendri Chinensis Cortex is Mediated by Berberine Erythrocytes Self-Assembly Targeted Delivery System.

Berberine (BBR) is the primary active component of Phellodendri Chinensis Cortex (PCC), which has been traditionally used to treat inflammatory diseases. However, the discrepancy between its low bioavailability and significant therapeutic effect remains obscure. The purpose of this study was to explore the previously unsolved enigma of the low bioavailability of BBR and its appreciable anti-inflammatory effect to reveal the action mechanism of BBR and PCC. The quantitative analysis of BBR and its metabolite oxyberberine (OBB) in blood and tissues was performed using high-performance liquid chromatography to investigate the conversion and distribution of BBR/OBB mediated by erythrocytes. Routine blood tests and immunohistochemical staining were used to explore the potential relationship between the amounts of monocyte/macrophage and the drug concentration in erythrocytes and tissues (liver, heart, spleen, lung, kidney, intestine, muscle, brain and pancreas). To comparatively explore the anti-inflammatory effects of BBR and OBB, the acetic acid-induced vascular permeability mice model and lipopolysaccharide-induced RAW 264.7 macrophages were employed. Nearly 92% of BBR existed in the erythrocytes in rats. The partition coefficient of BBR between plasma and erythrocytes (Kp/b) decreased with time. OBB was found to be the oxidative metabolite of BBR in erythrocytes. Proportion of BBR/OBB in erythrocytes changed from 9.38% to 16.30% and from 13.50% to 46.24%, respectively. There was a significant relationship between the BBR/OBB concentration in blood and monocyte depletion after a single administration of BBR. BBR/OBB was transported via erythrocytes to various tissues (liver, kidney, spleen, lung, and heart, etc), with the liver achieving the highest concentration. OBB exhibited similar anti-inflammatory effect in vitro and in vivo as BBR with much smaller dosage. BBR was prodominantly found in erythrocytes, which was critically participated in the biodistribution, pharmacokinetics, metabolism and target delivery of BBR and its metabolite. The anti-inflammatory activity of BBR and PCC was intimately associated with the metabolism into the active congener OBB and the targeted delivery to monocytes/macrophages mediated by the erythrocytes.

Anti-Inflammatory, Antipyretic, and Analgesic Properties of Potamogeton perfoliatus Extract: In Vitro and In Vivo Study.

Natural antioxidants, especially those of plant origins, have shown a plethora of biological activities with substantial economic value, as they can be extracted from agro-wastes and/or under exploited plant species. The perennial hydrophyte, Potamogeton perfoliatus, has been used traditionally to treat several health disorders; however, little is known about its biological and its medicinal effects. Here, we used an integrated in vitro and in vivo framework to examine the potential effect of P. perfoliatus on oxidative stress, nociception, inflammatory models, and brewer’s yeast-induced pyrexia in mice. Our results suggested a consistent in vitro inhibition of three enzymes, namely 5-lipoxygenase, cyclooxygenases 1 and 2 (COX-1 and COX-2), as well as a potent antioxidant effect. These results were confirmed in vivo where the studied extract attenuated carrageenan-induced paw edema, carrageenan-induced leukocyte migration into the peritoneal cavity by 25, 44 and 64% at 200, 400 and 600 mg/kg, p.o., respectively. Moreover, the extract decreased acetic acid-induced vascular permeability by 45% at 600 mg/kg, p.o., and chemical hyperalgesia in mice by 86% by 400 mg/kg, p.o., in acetic acid-induced writhing assay. The extract (400 mg/kg) showed a longer response latency at the 3 h time point (2.5 fold of the control) similar to the nalbuphine, the standard opioid analgesic. Additionally, pronounced antipyretic effects were observed at 600 mg/kg, comparable to paracetamol. Using LC-MS/MS, we identified 15 secondary metabolites that most likely contributed to the obtained biological activities. Altogether, our findings indicate that P. perfoliatus has anti-inflammatory, antioxidant, analgesic and antipyretic effects, thus supporting its traditional use and promoting its valorization as a potential candidate in treating oxidative stress-associated diseases.

Anti-inflammatory and analgesic activities of indigo through regulating the IKKβ/IκB/NF-κB pathway in mice.

This study investigated the anti-inflammatory and analgesic activities of indigo in mice and explored the possible related mechanisms. Xylene-induced ear edema, carrageenan-induced paw edema, and acetic acid-induced vascular permeability tests were used in investigating the anti-inflammatory activities. The anti-nociceptive effects of indigo were assessed through acetic acid-induced writhing, hot plate test, and formalin test, and spontaneous locomotor activity and motor performance were evaluated. The mechanisms of activities of indigo were explored by evaluating the expression levels of IκB kinase (IKK)β, p-IKKβ, inhibitor κB (IκB)α, p-IκBα, p65 nuclear factor (NF)-kB, p-p65 NF-κB, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) through western blotting and the expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) through enzyme-linked immunosorbent assay. The results showed that indigo significantly reduced xylene-induced ear edema, carrageenan-induced paw edema, and acetic acid-induced vascular permeation. In addition, indigo significantly inhibited nociception induced by acetic acid and formalin. However, the level of nociception was not decreased by indigo in the hot plate test, and indigo did not affect spontaneous locomotor activity and motor performance. The expression levels of p-IKKβ, p-IκBα, p65 NF-kB, p-p65 NF-κB, COX-2, iNOS, TNF-α, IL-1β, IL-6, and PGE2 decreased, whereas the expression level of IκBα increased obviously after indigo treatment. In conclusion, indigo exerts significant anti-inflammatory and analgesic activities in mice by inhibiting IKKβ phosphorylation and reducing the production of important pain mediators, such as PGE2 and COX-2, via the IKKβ/IκB/NF-κB pathway.

Mucoprotective effects of Saikosaponin-A in 5-fluorouracil-induced intestinal mucositis in mice model

5-Fluorouracil (5-FU)-induced intestinal mucositis (IM) is one of the most common oncological problem. It involves serious clinical consequences such as diarrhea, erythematous lesions of mucosa, and eventually development of ulcers accompanied by severe pain. The aim of the present study was to demonstrate the mucoprotective effects of Saikosaponin-A in 5-FU-induced intestinal mucositis in mice. Mucositis was induced in BALB/c mice by intraperitoneal injection of 5-FU (50 mg/kg/day) for three consecutive days and IM was assessed by both behavioral and histochemical analysis. While, Saikosaponin-A (1, 5, 10 mg/kg/day) was administered 1 h before 5-FU injection for consecutive seven days. Pre-treatment of Saikosaponin-A significantly ameliorated the severity of mucositis reflected as food intake, body weight loss, severity of diarrhea and mortality rate in a dose depended manner as compared to mice treated with 5-FU. Moreover, histopathological analysis furthered reinforced the mucoprotective potential of Saikosaponin-A against 5-FU-induced intestinal abnormalities referred as villus atrophy, mitotic crypt stem cells damage, inflammatory cells infiltration, vacuolization and edema. Furthermore, Saikosaponin-A administration strongly inhibited pro-inflammatory mediators (TNF-α, COX-2, IL-1β and IL-6) and apoptotic markers (p-JNK, Casp-3). Saikosaponin-A pre-treatment significantly reduced the production of nitric oxide (NO) in intestinal tissue, inhibited acetic acid-induced Evans blue vascular permeability. The Siaikosaponin-A treatment markedly enhanced the anti-oxidants enzymes (Nrf2, HO-1, SOD, GSH, GST and Catalase), while decreased the oxidative stress markers i.e. Malonaldehde (MDA). Hence, these data suggest that Saikosaponin-A maybe a potential candidate for the treatment of chemotherapy-induced intestinal mucositis.

Dihydroberberine, a hydrogenated derivative of berberine firstly identified in Phellodendri Chinese Cortex, exerts anti-inflammatory effect via dual modulation of NF-κB and MAPK signaling pathways

Dihydroberberine (DHB), a hydrogenated derivative of berberine (BBR), has been firstly identified in Phellodendri Chinese Cortex (PC) by HPLC-ESI-MS/MS. Nowadays most researches on PC focus on its main components like BBR, however, the role of its naturally-occurring derivatives remains poorly defined heretofore. The present work aimed to comparatively evaluate the in vivo anti-inflammatory properties and mechanisms of DHB and BBR in three typical inflammatory murine models. The results showed that DHB effectively mitigated acetic acid-induced vascular permeability, xylene-elicited ear edema and carrageenan-caused paw edema. Meanwhile, DHB markedly attenuated the inflammatory cell infiltration in pathological sections of ears and paws. DHB was also observed to significantly decrease the production and mRNA expression levels of IL-6, IL-1β, TNF-α, NO (iNOS) and PGE2 (COX-2), increase the release of IL-10, and inhibit the activation of NF-κB and MAPK signaling pathways. The anti-inflammatory effect of DHB was weaker than that of BBR. The results might further contribute to unraveling the pharmacodynamic basis of PC and support its ethnomedical use in the treatment of inflammatory diseases. DHB possesses good potential to be further developed into a promising anti-inflammatory alternative, and can serve as a lead template for novel anti-inflammatory candidate.

The anti-inflammatory and anti-oxidant properties of the aerial part of Atractylodes macrocephala and the active constituents' analysis by HPLC-ESI-MS/MS

The root of Atractylodes macrocephala Koidz (AMK) is an important crude drug widely used in Chinese folk medicines for treating various diseases. This study was aimed to investigate the anti-inflammatory and anti-oxidant activities of the aerial part of AMK (APA) and analyze its active constituents by LC-ESI-MS/MS. Total extracts of APA and different fractions of petroleum ether (PEE), ethyl acetate (ACE), n-butanol (BE) and the residues (WE) were prepared. The contents of total phenolics and flavonoids of APA extracts and the different fractions were determined. Then, anti-inflammatory effects of the extracts/fractions were evaluated in animal models by using dimethylbenzene-induced ear edema and acetic acid-induced vascular permeability in mice. The antioxidant activities were determined in vitro by DPPH radical scavenging and phosphor-molybdenum methods. The constituents in the most active fraction of ACE were analyzed by HPLC-ESI-MS/MS. The results demonstrated that APA extracts and all sub-fractions contain affluent phenolics and flavonoids. The APA extracts and different sub-fractions (especially ACE) showed notable anti-inflammatory effects and antioxidant activity. Furthermore, 10 constituents including protocatechuic acid, p-hydroxybenzoic acid, syringin, chlorogenic acid, caffeic acid, ferulic acid, ethyl caffeate, ethyl cinnamate, luteolin and apigenin were identified in ACE. In conclusion, APA (especially ACE) can be developed into effective and safe therapeutic agents for treating inflammation and oxidative stress in the future, and HPLC-ESI-MS/MS is an efficient method for analyzing active constituents in APA.

Anti-nociceptive and anti-inflammatory potentials of Akebia saponin D

Akebia saponin D, which is originates from Dipsacus asper Wall, has been used as a tonic, an analgesic and anti-inflammatory agent for the therapy of low back pain, rheumatic arthritis, traumatic hematoma, habitual abortion and bone fractures in traditional Chinese medicine. However, the anti-nociceptive and anti-inflammatory activity and mechanism of Akebia saponin D has been rarely reported. The aim of this study was to investigate the anti-nociceptive and anti-inflammatory activity of Akebia saponin D and to assess its possible mechanism. The anti-nociceptive effect was measured by formalin test, hot plate, and acetic acid-induced writhing in mice while the anti-inflammatory effect was measured by carrageenan induced paw edema test, xylene-induced ear swelling and acetic acid-induced vascular permeability in mice and rats. Furthermore, anti-inflammatory effect was also measured in vitro using LPS-induced RAW 264.7 cells. Our results demonstrated that Akebia saponin D dose-dependently decreased the licking time in the formalin test, delayed the reaction time of mice to the hot plate, and inhibited acetic acid-induced writhing. Treatment of Akebia saponin D attenuated the carrageenan induced paw edema in rats, inhibited the mouse ear swelling, and decreased Evans blue concentration in acetic acid induced vascular permeability test, revealing its strong anti-inflammatory effect. Akebia saponin D significantly decreased NO production and iNOS expression. Our results indicate that Akebia saponin D has anti-nociceptive and anti-inflammatory effects. It will provide experimental evidences for the use of Akebia saponin D and can be used to develop a therapeutic drug against pain and inflammation related diseases.

Curcumin's Metabolites, Tetrahydrocurcumin and Octahydrocurcumin, Possess Superior Anti-inflammatory Effects in vivo Through Suppression of TAK1-NF-κB Pathway.

Curcumin (CUR), a promising naturally occurring dietary compound, is commonly recognized as the potential anti-inflammatory agent. While the application of CUR was hampered by its low stability and poor systemic bioavailability, it has been suggested that the biological activities of CUR are intimately related to its metabolites. In the current investigation, we aimed to comparatively explore the anti-inflammatory effects of tetrahydrocurcumin (THC), octahydrocurcumin (OHC), and CUR, and to elucidate the underlying action mechanisms on experimental mice models of acute inflammation, i.e., xylene-induced ear edema, acetic acid-induced vascular permeability, and carrageenan-induced paw edema. The results showed that THC and OHC exerted significant and dose-dependent inhibitions on the formation of ear edema induced by xylene and paw edema provoked by carrageenan and inhibited the Evans blue dye leakage in peritoneal cavity elicited by acetic acid. Moreover, THC and OHC treatments were more effective than CUR in selectively inhibiting the expression of cyclooxygenase 2 (COX-2) and suppressing nuclear factor-κB (NF-κB) pathways via transforming growth factor β activated kinase-1 (TAK1) inactivation in the carrageenan-induced mouse paw edema model.

English

The anti-inflammatory effect of the extract of Parinari kerstingii leaves was investigated using egg albumin-induced rat paw oedema, leukocyte mobilization, and acetic acid-induced vascular permeability assay methods. Heat and hypotonicity-induced heamolysis of human red blood cell membrane were also used to assess its membrane stabilizing effect and to determine its inhibitory property on phospholipase A2 activity. Acute toxicity and phytochemical tests were also determined using standard methods. The methanol crude extract (MCE) of P. kerstingii reduced (p<0.05) the acetic acid-induced vascular permeability and increased agar-induced leukocyte mobilization in rats dose-dependently. Vascular permeability was inhibited by 24.85, 26.04 and 48.52% with 100, 200 and 400 mg/kg of the MCE, respectively. The total leukocyte count of the treated groups increased significantly (p<0.05) relative to the control group. The percentage membrane stability exhibited by the MCE was comparable with drug control, indomethacin. The MCE contains principles that protected the erythrocyte membranes effectively. More so, the extract inhibited (p<0.05) the activities of phospholipase A2 and showed no significant difference in the phospholipase A2 inhibitory effect as compared to the standard drug, prednisolone. The extract showed no toxicity at 5000 mg/kg. Phytochemical screenings revealed the presence of tannins, saponins, reducing sugars, phenols, soluble carbohydrates, alkaloids, terpenoids, steroids, hydrogen cyanide glycosides and flavonoids. This study indicated that the MCE of P. kerstingii leaf is relatively safe for consumption and has anti-inflammatory property. Also, it could prevent the haemolysis of human erythrocyte membrane. Key words: Anti-inflammatory, Parinari kerstingii, acute toxicity, phytochemicals, membrane stability.

Anti-inflammatory and antinociceptive activities of the leaf methanol extract of Miconia minutiflora (Bonpl.) DC. and characterization of compounds by UPLC-DAD-QTOF-MS/MS.

Some species of the genus Miconia are used in Brazilian folk medicine as analgesic and anti-inflammatory; however, several species of this genus are still poorly studied. Therefore, the aims of this study were to investigate the phytochemistry characterization by UPLC-DAD-QTOF-MS/MS, acute toxicity, anti-inflammatory and antinociceptive properties of Miconia minutiflora (Bonpl.) DC. The methanol extract of M. minutiflora (Mm-MeOH) was subjected to ultra-high-performance liquid chromatography (UPLC-DAD-QTOF-MS/MS) for the identification of the main phytocompounds. The anti-inflammatory properties of the extracts were studied using several inflammation models induced by carrageenan and acetic acid-induced vascular permeability. Antinociceptive effects of Mm-MeOH were assessed in nociception induced by intraperitoneal acetic acid or subplantar formalin injection. The role of α-adrenergic, cholinergic, and opioid receptors in modulating the extract's antinociceptive activity was determined. Analyses by UPLC-DAD-QTOF-MS/MS revealed the presence of ellagic acid, gallotannin, and terpenes in the methanol extract. Mm-MeOH (100mg/kg) reduced carrageenan-induced paw edema and vascular permeability and inhibited leukocyte migration toward the air pouch and pleural cavity. Furthermore, Mm-MeOH decreased tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels. Administration of Mm-MeOH reduced the number of writhes by 58.9% and increased the pain threshold in the formalin test. The anti-inflammatory action mechanism of Mm-MeOH is associated with inhibition of proinflammatory cytokines TNF-α and IL-1β, whereas the antinociceptive actions involve peripheral and central mechanisms with participation of α2-adrenergic receptors. These effects may be attributed to the presence of polyphenolics in the extract.

Attenuation of inflammatory pain by puerarin in animal model of inflammation through inhibition of pro-inflammatory mediators

In the current study, the puerarin was investigated for both acute Carrageenan and chronic CFA-induced inflammatory pain models. The Puerarin treatment significantly attenuated (P < 0.001) the mechanical hyperalgesia and mechanical allodynia in both Carrageenan and CFA-induced hyperalgesia. The Puerarin treatment also remarkably reduced (p < 0.001) the thermal hyperalgesic responses in both acute Carrageenan as well as chronic CFA-induced models. Furthermore, the Puerarin administration was also associated with significant inhibition of (p < 0.001) paw edema in both Carrageenan and CFA-induced models. The inflammatory mediators such as IL-1β, IL-6, TNF-α and vascular endothelial growth factor (VEGF) are significantly enhanced during inflammatory conditions, however, the Puerarin administration significantly altered (P < 0.001) the mRNA expression levels of these mediators. Additionally, the Puerarin treatment also significantly enhanced (P < 0.001) the mRNA expressions levels of the anti-oxidant enzymes such as Nrf2, HO-1 and SOD2. The Puerarin treatment is associated with significant (P < 0.001) inhibition of the acetic acid-induced Evans blue vascular permeability. Moreover, the concentration of Puerarin in various tissues was analyzed using High-performance liquid chromatography (HPLC) and the results showed that the Puerarin was significantly distributed towards the peripheral tissues such as liver and kidney and less distributed towards the brain.

Anti-Inflammatory Effect of &lt;i&gt;o&lt;/i&gt;-Vanillic Acid on Lipopolysaccharide-Stimulated Macrophages and Inflammation Models

Inflammation is an important biological reaction in the body in response to external stimuli. Excessive inflammation causes various inflammatory disorders such as allergic hypersensitivity, autoimmune disease, rheumatoid arthritis, and cancer. Macrophages play a major role in the inflammatory response by producing inflammatory mediators such as nitric oxide, prostaglandin E2, and pro-inflammatory cytokines. Natural products are often a source of bioactive compounds, which have great potential as novel therapeutic agents. Amomum xanthoides extract has been shown to possess various pharmacological activities including anti-inflammatory activity. This study evaluated the anti-inflammatory potential of o-vanillic acid (o-VA), a major compound in A. xanthoides, using lipopolysaccharide (LPS)-induced macrophages and in vivo animal models. o-VA decreased, in a concentration-dependent manner, the LPS-induced gene expression and production of inflammatory mediators, such as inducible nitric oxidase/cyclooxygenase-2 and pro-inflammatory cytokines, by reducing the nuclear factor-B activation. In addition, o-VA dose-dependently ameliorated acetic acid-induced vascular permeability and zymosan-induced leukocyte migration. Thus, we suggest that o-VA can be used as a pharmacological agent or food supplement in the treatment of inflammatory conditions.

Fatty Acid Profile and Anti-Inflammatory Activity of Fixed Plant Oils

Background: Many seed oils have been used as anti-inflammatory agents, administred by ingestion or topical application in traditional medicine. The objective of this research was to perform a chemical analysis of fatty profile and a pharmacological study through a topical experiment of TPA-induced ear edema test and an internal assay - acetic acid-induced vascular permeability in Swiss mice of some fixed oils popularly used for inflammatory problems, trying to confirm their action.Materials, Methods &amp; Results: Fixed lipids of Ouratea fieldingiana (batiputá), Caryocar coreaceum (pequi), Annacardium occidentale (cashew-nuts), Cocos nucifera (coco-da-bahia), Byrsonima crassifolia (murici) e Elaeis guineenses (palm) were selected for the identification of fatty acids profile by gas chromatography coupled to mass spectrometry (GC/MS) analysis and evaluation of anti-inflammatory activity by TPA-induced ear edema test and acetic acid-induced vascular permeability in Swiss male mice. The oils were purchased in local markets or extracted in Soxhlet apparatus with hexane. The oils of cashew nut, murici fruit, and pequi nut presented a high percentage of unsaturated fatty acids (81.80, 74.46 and 60.72 %, respectively). In the oils of batiputá and murici, linoleic acid was the main unsaturated fatty acid (45.06% and 74.66%, respectively) and oleic acid was main constituent in cashew nut, pequi and palm seed oils. Batiputá and palm oils exibit approximately equivalent content of saturated and unsaturated fatty acid and coconut oil more saturated fatty acids (80.72%) with predominance of lauric acid. The result of TPA-induced ear edema test revealed that all oils presented similar anti-inflammatory activity. In the acetic acid-induced vascular permeability model, the oil of O. fieldingiana was the only one who showed anti-inflammatory activity, while C. coreaceum and B. crassifolia oils showed pro-inflammatory activities. The presence of phenols and flavonoids was evaluated in the O. fieldingiana oil by spectrophometric methods.Discussion: All the oils showed anti-inflammatory action in the TPA-induced ear edema, probably the action of unsaturated fatty acids was more important in topical application, nevertheless in internal inflammation process the presence of antioxidant phenolic compounds could contribute to the higher activity of the oil from O. fieldingiana. The effect of linoleic and oleic acids was demonstrated on the inflammatory response of the skin during the healing process and on the release of pro-inflammatory cytokines by rat neutrophils in a prevoius study using sunflower oil. Both oleic and linoleic acids increased the wound healing tissue mass. The total protein and DNA contents of the wounds were increased by the treatment with linoleic acid. This pro-inflammatory effect of oleic and linoleic acids may contribute to the wound healing process. In this study with six plant oils, some of them have higher content in linoleic acid and others oleic acid is the major constituent so the antiinflamatory action on ear edema can be associated to these two unsaturaded fatty acids mechanism of action. In the internal model, probably other chemical constituents revealed in Ouratea fieldingiana as phenols, condensed tannins, flavones and flavanones, could contribute to the anti-inflammatory activity.

Anti-inflammatory and analgesic activity of ononitol monohydrate isolated from Cassia tora L. in animal models.

Ononitol monohydrate (OM) was isolated from Cassia tora L. leaves. The anti-inflammatory and analgesic activities of OM have been examined in male Wistar rats and mice. The efficacy of OM against inflammation was studied by using carrageenan-induced paw oedema, croton oil-induced ear oedema, acetic acid-induced vascular permeability, cotton pellet-induced granuloma and adjuvant-induced arthritis. The analgesic activity of OM was assessed using the acetic acid-induced abdominal constriction response, formalin-induced paw licking response and the hot-plate test. In acute type inflammation models, maximum inhibitions of 50.69 and 61.06% (P < .05) were noted with 20 mg/kg of OM in carrageenan-induced hind paw oedema and croton oil-induced ear oedema, respectively. Treatment of OM (20 mg/kg) meaningfully (P < .05) reduced the granuloma tissue formation by cotton pellet study at a rate of 36.25%. OM (20 mg/kg) inhibited 53.64% of paw thickness in adjuvant-induced arthritis model. OM has also been produced significant (P < .05) analgesic activity in acetic acid-induced abdominal constriction response, formalin-induced paw licking response and in hot-plate test suggesting its peripheral and central analgesic potential. The outcomes of the present study proposed that OM influenced on the anti-inflammatory and analgesic activities.

Imperatorin possesses notable anti‑inflammatory activity invitro and invivo through inhibition of the NF‑κB pathway.

Imperatorin (IMT) is a furanocoumarin from the root of Phlomis younghusbandii (Lamiaceae) with various activities. In the present study, the anti-inflammatory effects of IMT were evaluated by examining dimethylbenzene-induced ear edema, acetic acid-induced vascular permeability and by performing cotton pellet granuloma assessments in mice. In addition, the expression of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β, were detected using enzyme-linked immunosorbent assay kits in mice and using reverse transcription polymerase chain reaction analysis in RAW 264.7 cells. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear p65, cytosolic p65 and inhibitor of nuclear factor (NF)-κB (IκB) in RAW 264.7 cells were determined using western blot analysis. The results showed that the oral administration of IMT significantly inhibited the inflammatory reactions and reduced the release of TNF-α, IL-6 and IL-1β reactions and reduced and suppressed the mRNA expression of TNF-A expressionact1o, and the protein expression of iNOS and COX-2 in the RAW 264.7 cells. The results also indicated that IMT suppressed the activity of NF-κB via upregulating p65 and IκB in the cytoplasm and downregulating p65 in the nucleus. In conclusion, IMT possessed notable anti-inflammatory activities in vitro and in vivo through inhibiting the NF-κB pathway.

Anti-exudation effects of sodium ferulate and oxymatrine combination via modulation of aquaporin 1.

The present study aimed to investigate the anti-exudative effects of sodium ferulate combined with oxymatrine in a mouse model of acetic acid-induced peritonitis. Furthermore, the underlying mechanisms were explored by determining the effects of these drugs on the volume and aquaporin 1 (AQP1) expression in vascular endothelial cells on omentum majus and human umbilical vein endothelial cells (HUVEC). Treatment with sodium ferulate combined with oxymatrine was shown to significantly inhibit acetic acid-induced vascular permeability in the peritonitis model mice and furthermore to significantly decrease the optical density of Evans blue, the leukocyte number and the levels of interleukin-6, C-reactive protein and interferon-γ in peritoneal lavage fluid. Pathological analysis of the omentum majus revealed that sodium ferulate and oxymatrine combination treatment significantly alleviated vascular endothelial cell edema and capillary loss. In vitro, flow cytometry revealed that the volume of HUVECs was significantly reduced in the drug treatment groups, as reflected in the forward scatter value. The optical density of AQP1 on the membrane of the vascular endothelial cells on omentum majus and HUVECs were significantly increased in the drug treatment groups compared with the model group. These results indicated that sodium ferulate and oxymatrine combination treatment possessed prominent anti-exudative effects and that the underlying mechanisms are likely to include the improvement of vascular endothelial cellular edema, possibly by upregulation of AQP1 expression on their membrane, which requires further exploration.