Antioxidant and anti-inflammatory action (in vivo and in vitro) from the trunk barks of Cabreúva (Myrocarpus frondosus Allemao, Fabaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Myrocarpus frondosus, known as cabreúva, is a tree whose trunk barks are used in folk medicine as tea, syrup, ointments, and tinctures for the treatment of inflammation. However, there is no scientific evidence demonstrating this activity. AIM OF THE STUDY: The present investigation was focused on evaluating the antioxidant and anti-inflammatory activities of M. frondosus, using the in vitro model of RAW 264.7 macrophages induced by LPS and the in vivo model of mouse pleurisy induced by carrageenan. MATERIALS AND METHODS: M. frondosus trunk barks were dried at room temperature for seven days and subjected to exhaustive maceration with ethanol (70%) to obtain its crude extract (CE). CE was subjected to UPLC-HRMS analysis to establish its chemical profile. Its antioxidant activity was evaluated using the DPPH method, reducing power by the iron (III) to iron (II) reduction assay and the ß-carotene-linoleic acid bleaching assay. The RAW 264.7 macrophages were pretreated with the CE in a non-cytotoxic concentration and induced by LPS (1 µg/mL). After 24 h, using the supernatant, we evaluated the nitric oxide (NOx) and interleukin-6 (IL-6) levels. The anti-inflammatory effects of CE (at doses of 30, 100 and 300 mg/kg) were evaluated on leukocyte migration (total and differential), exudate concentrations, myeloperoxidase (MPO) and adenosine-deaminase (ADA) activities, NOx, tumor necrosis factor-α (TNF-α), and IL-6 levels, by using a murine model of neutrophilic inflammation. RESULTS: The UPLC-HRMS of CE revealed the presence of isoflavonones, including biochanin A and formononetin. CE exhibited good antioxidant activity by quenching and decreasing free radicals, as well as reducing pro-oxidant metals. CE did not show cytotoxicity at a concentration below 11 µg/mL and reduced the secretion of the pro-inflammatory NOx in the inflamed macrophages. In vivo assay revealed that CE caused a pronounced inhibition on leukocyte migration, and this inhibition was due to its ability to reduce neutrophil migration. Moreover, CE was also able to reduce the release of critical pro-inflammatory mediators such as MPO, NOx, TNF-α, and IL-6. CONCLUSIONS: All these findings indicate that M. frondosus exhibited antioxidant activity and anti-inflammatory effect.

Oridonin attenuates carrageenan-induced pleurisy via activation of the KEAP-1/Nrf2 pathway and inhibition of the TXNIP/NLRP3 and NF-κB pathway in mice.

The classic NLRP3 inflammasome and NF-κB molecular pathways are activated in many inflammatory-related diseases, such as pleurisy. Because oridonin (Ori) has been indicated as a covalent NLRP3 inhibitor with strong anti-inflammasome activity, we herein aimed to assess the effects of Ori in a mouse model of carrageenan (CAR)-induced pleurisy. The results showed that CAR caused hemorrhaging and exudation of lung tissues and the release of inflammatory factors (TNF-α, IL-6 and IL-1ß), effects that were significantly reduced by treatment with Ori. In addition, increased neutrophil infiltration, protein concentrations and volumes were found in the exudates of the CAR group, and these phenomena were suppressed by Ori treatment. Regarding cellular pathways, Ori could alleviate the CAR-activated NF-κB and TXNIP/NLRP3 pathways. Additionally, oxidative stress was shown to be involved in the pathogenesis of pleurisy, but possible mechanisms remain to be explored. Herein, Ori reversed the CAR-induced depletion of GSH and SOD and the CAR-induced increases in ROS, MPO and MDA levels. Furthermore, Ori inhibited NOX-4 levels, initiated the dissociation of KEAP-1 from Nrf2, activated the downstream genes HO-1 and exerted antioxidative effects on CAR-induced pleurisy. In conclusion, Ori conferred protection against CAR-induced pleurisy via Nrf2-dependent antioxidative and NLRP3-dependent anti-inflammatory properties.

Effects of Aliskiren, an RAAS inhibitor, on a carrageenan-induced pleurisy model of rats.

Our aim is to investigate the potentially preventive effects of Aliskiren in a carrageenan-induced lung pleurisy model and to compare the standard anti-inflammatory agents, indomethacin and dexamethasone. The pleurisy model was induced through the injection of carrageenan (0.2 ml-%2) into the pleural cavity. After the experiment, serum and lung tissues were collected and biochemical, molecular and pathological examinations were performed. In our study, pleural inflammation decreased superoxide dismutase activity and the glutathione level and increased the malondialdehyde level in the lung of rats, while Aliskiren increased the superoxide dismutase activity and glutathione level and decreased the malondialdehyde level. In addition, carrageenan-induced pleurisy caused a significant increase in pro-inflammatory cytokines mRNA expressions (TNF-α, IL-1ß, and NF-KB), while Aliskiren administration decreased their expressions as well as the standard treatments, indomethacin and dexamethasone, did. Aliskiren administration at the 200 mg/kg dose protected the lungs in the pathological evaluation, especially against inflammatory cell infiltration and edematous lesions. It appears that Aliskiren protects the lung from carrageenan-induced pleurisy damage by regulating inflammation and antioxidant-oxidant balance via Renin Angiotensin Aldosterone System inhibition.

Inhibition of inflammasome activation improves lung acute injury induced by carrageenan in a mouse model of pleurisy.

The inflammasome NLRP3 is a molecular pathway activated by a wide range of cellular insults to elicit innate immune defenses through the activation of caspase-1 and the maturation of proinflammatory cytokines, such as IL-1ß and IL-18. The expression of NRLP3 is abnormally elevated in numerous human inflammatory diseases, including pulmonary diseases. An injection of carrageenan (CAR) into the pleural cavity triggered an acute inflammatory response, leading to tissue damage, inflammatory exudates, leukocyte infiltration, and increased myeloperoxidase activity. The aim of this study was to assess the effect of the inflammasome blocking agents BAY 11-7082 (30 mg/kg, i.p.) and Brilliant Blue G (BBG) (45.5 mg/kg, i.p.) in a mouse model of CAR-induced pleurisy. Treatment with BAY 11-7082 or BBG 1 h after CAR injection attenuated pulmonary membrane thickening and polymorphonuclear leukocyte infiltration, reduced NF-κB translocation in the nucleus, and inhibited the assembly of the NRLP3/ASC/caspase-1 complex. Treatment with BAY 11-7082 or BBG also down-regulated iNOS, nitrotyrosine, and poly-ADP-ribosyl polymerase expression and inhibited CAR-induced apoptosis. Our results demonstrate that treatment with inflammasome-blocking agents can significantly reduce the development of acute CAR-induced lung injury.-Fusco, R. Gugliandolo, E., Biundo, F., Campolo, M., Di Paola, R., Cuzzocrea, S. Inhibition of inflammasome activation improves lung acute injury induced by carrageenan in a mouse model of pleurisy.

Toxicological analysis and antihyperalgesic, antidepressant, and anti-inflammatory effects of Campomanesia adamantium fruit barks.

OBJECTIVE: This study evaluates the anti-inflammatory, antihyperalgesic, and antidepressive potential of the hydroalcoholic extract of Campomanesia adamantium fruit barks (CAE) on rodents and determines the safety of this plant. METHODS: The acute toxicity of CAE was evaluated by oral administration to female rats as single doses of 0, 500, 1000, or 2000 mg/kg body weight. General behavior and toxic symptoms were observed for 14 days. In the subacute toxicity test, male and female rats received 125 or 250 mg/kg body weight of CAE for 28 days. The oral anti-inflammatory activity of CAE was evaluated in carrageenan-induced pleurisy in male mice. The effect of treatment with CAE (100 mg/kg) for 15 days was evaluated in mechanical hyperalgesia (electronic von Frey), depressive behavior (forced swimming test), and cold hypersensitivity in spared nerve injury (SNI) model in rats. RESULTS: No clinical signs of toxicity were observed in animals from the experimental groups during acute and subacute exposure to CAE. At pleurisy test, the oral administration of CAE significantly inhibited leukocyte migration and protein leakage at all doses tested when compared to control. Oral administration of CAE for 3-15 days significantly inhibited SNI-induced mechanical hyperalgesia and increased immobility in the forced swim test. Finally, on the 15th day, oral treatment with CAE prevented the increase in sensitivity to a cold stimulus induced by SNI. DISCUSSION: The present study shows that C. adamantium extract has anti-inflammatory, antihyperalgesic, and antidepressive properties in rodents without causing toxicity.

Anti-inflammatory, antioxidant and anti-Mycobacterium tuberculosis activity of viridiflorol: The major constituent of Allophylus edulis (A. St.-Hil., A. Juss. & Cambess.) Radlk.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Allophylus edulis (A. St.-Hil., A. Juss. & Cambess.) Radlk. (Sapindaceae) are traditionally used as a natural anti-inflammatory agent; however, there are no scientific studies demonstrating its activity essential oil. The content of essential oil in A. edulis may be the chemical basis to explain its ethnobotanical uses, since infusions of this plant are used to treat inflammation in the traditional medicine in Brazil. AIM OF THE STUDY: This study evaluated the anti-inflammatory, antioxidant and anti-mycobacterial activities of the essential oil (EOAE) and viridiflorol, its main compound. MATERIAL AND METHODS: Essential oil from fresh leaves of A. edulis (EOAE) was obtained by hydrodistillation in a Clevenger-type apparatus. Forty-one compounds, accounting for 99.10% of the oil, were identified by gas chromatography-mass spectrometry (GC-MS). The major constituent of the oil was viridiflorol (30.88%). Additionally, the essential oil and viridiflorol were evaluated using an in vitro test against Mycobacterium tuberculosis and in 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays. Both EOAE (30 and 100mg/kg) and viridiflorol (3 and 30mg/kg) by oral administration were assayed in carrageenan-induced mice paw oedema and pleurisy using subcutaneous injection of dexamethasone (0.5mg/kg) as the positive control. RESULTS: EOAE and viridiflorol displayed moderate in vitro activity in the M. tuberculosis assay. In all tests, EOAE and viridiflorol showed moderate antioxidant activity compared with reference standards. Both EOAE and viridiflorol showed significant inhibition in the carrageenan-induced mice paw oedema via oral administration of the oil (30 and 100mg/kg), compound (3 and 30mg/kg), and subcutaneous injection of dexamethasone (0.5mg/kg, reference drug). Also EOAE and viridiflorol significantly inhibited carrageenan (Cg) induced pleurisy, reducing the migration of total leucocytes in mice by 62±5% (30mg/kg of oil), 35±8% (100mg/kg of oil), 71±5% (3mg/kg of viridiflorol) and 57±3% (30mg/kg of viridiflorol). CONCLUSION: For the first time, the results from this work corroborate the literature, showing that A. edulis can be used as a natural anti-inflammatory agent. Moreover, both EOAE and viridiflorol exhibited biological activities, such as anti-mycobacterial, anti-inflammatory and antioxidant activity.

[Chronic cough, pleuritic chest pain, and night sweats in a 45­year-old female smoker]. / Chronischer Husten, atemabhängiger Thoraxschmerz und Nachtschweiß bei einer 45­jährigen Raucherin.

A 45-year-old woman presented with chronic cough, pleuritic chest pain, and night sweat. High-resolution computed tomography revealed multiple bilateral nodular lesions in a centrilobular distribution, primarily located in the upper and mid lung zones with relative sparing of the lung bases. No lymphadenopathy or pleural effusions were detected. Histological analysis confirmed the suspected diagnosis of pulmonary Langerhans cell histiocytosis. After smoking cessation the patient recovered completely.

Evidence for the involvement of TNF-α and IL-1ß in the antinociceptive and anti-inflammatory activity of Stachys lavandulifolia Vahl. (Lamiaceae) essential oil and (-)-α-bisabolol, its main compound, in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Stachys lavandulifolia Vahl (Lamiaceae) is a medicinal plant widely used in Turkey and Iranian folk medicine due to its analgesic and anti-inflammatory properties, but little is known about its essential oil. AIM OF THIS STUDY: We studied the antinociceptive and anti-inflammatory effects of S. lavandulifolia essential oil (EOSl) and (-)-α-bisabolol (BIS), its main compound, in algogen-induced orofacial nociceptive behavior in mice, and assessed the possible involvement of pro-inflammatory cytokines in these profiles. MATERIALS AND METHODS: The GC-FID and GC-MS analysis of EOSl demonstrated the presence of (-)-α-bisabolol (56.4%), bicyclogermacrene (5.3%), δ-cadinene (4.2%) and spathulenol (2.9%) as the main compounds. Male Swiss mice were pretreated with EOSl (25 or 50mg/kg, p.o.), BIS (25 or 50mg/kg, p.o.), morphine (3mg/kg, i.p.) or vehicle (saline 0.9% with two drops of tween 80, 0.2%), before formalin- (20µl, 2%), capsaicin- (20µl, 2.5µg) or glutamate- (20µl, 25Mm) injection into the right upper lip (perinasal area) in mice. The anti-inflammatory profile of EOSl or BIS (50mg/kg) was assessed by the inflammatory response induced by carrageenan (2% in 0.2mL) in mice (pleurisy model). RESULTS: Our results showed that p.o. treatment with EOSl and BIS displayed significant inhibitory (p<0.05 or p<0.01 or p<0.001) effects in different orofacial pain tests on mice, but BIS proved to be more effective, significantly reducing nociceptive behavior in all tests including both phases of the formalin test. The analgesic effect is not related to any abnormality since EOSl- or BIS-treated mice exhibited no performance alteration in grip strength. Moreover, EOS1 and BIS exhibited a significant anti-inflammatory effect (p<0.001) in the pleurisy model of inflammation, which seems to be related to a significant reduction (p<0.05) of the pro-inflammatory cytokine TNF-α in BIS treatment, and of the pro-inflammatory cytokine IL-1ß (p<0.01) in EOS1 treatment. CONCLUSION: Our results corroborate the use of S. lavandulifolia in traditional medicine as an analgesic and anti-inflammatory, which seems to be related to (-)-α-Bisabolol, the main compound of EOSl.

Toxicological analysis and anti-inflammatory effects of essential oil from Piper vicosanum leaves.

This study assessed the anti-inflammatory effects of the essential oil from Piper vicosanum leaves (OPV) and evaluated the toxicological potential of this oil through acute toxicity, genotoxicity and mutagenicity tests. The acute toxicity of OPV was evaluated following oral administration to female rats at a single dose of 2 g/kg b.w. To evaluate the genotoxic and mutagenic potential, male mice were divided into five groups: I: negative control; II: positive control; III: 500 mg/kg of OPV; IV: 1000 mg/kg of OPV; V: 2000 mg/kg of OPV. The anti-inflammatory activity of OPV was evaluated in carrageenan-induced pleurisy and paw edema models in rats. No signs of acute toxicity were observed, indicating that the LD50 of this oil is greater than 2000 mg/kg. In the comet assay, OPV did not increase the frequency or rate of DNA damage in groups treated with any of the doses assessed compared to that in the negative control group. In the micronucleus test, the animals treated did not exhibit any cytotoxic or genotoxic changes in peripheral blood erythrocytes. OPV (100 and 300 mg/kg) significantly reduced edema formation and inhibited leukocyte migration analyzed in the carrageenan-induced edema and pleurisy models. These results show that OPV has anti-inflammatory potential without causing acute toxicity or genotoxicity.

Esculin exhibited anti-inflammatory activities in vivo and regulated TNF-α and IL-6 production in LPS-stimulated mouse peritoneal macrophages in vitro through MAPK pathway.

Esculin, a coumarinic derivative found in Aesculus hippocastanum L. (Horse-chestnut), has been reported to have potent anti-inflammatory properties. The present study is designed to investigate the protective effects of esculin on various inflammation models in vivo and in vitro and to clarify the possible mechanism. Induced-animal models of inflammation and lipopolysaccharide (LPS)-challenged mouse peritoneal macrophages were used to examine the anti-inflammatory activity of esculin. In present study, xylene-induced mouse ear edema, carrageenan-induced rat paw edema, and carrageenan-induced mouse pleurisy were attenuated by esculin. In vitro, the pro-inflammatory cytokine levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in supernatant were reduced by esculin. Meanwhile, we found that esculin significantly inhibited LPS-induced activation of mitogen-activated protein kinase (MAPK) pathway in peritoneal macrophages. These results suggest that esculin has potent anti-inflammatory activities in vivo and in vitro, which may involve the inhibition of the MAPK pathway. Esculin may be a promising preventive agent for inflammatory diseases in human.

Anti-hyperalgesic and Anti-inflammatory Activity of Alternanthera Maritima Extract and 2″-O-α-L-rhamnopyranosylvitexin in Mice.

Alternanthera maritima are used in Brazilian popular medicine for the treatment of inflammatory and infectious diseases. Species of Alternanthera have demonstrated biological activities in previous scientific studies. The aim of this study was to determine whether the ethanol extract of the aerial parts of A. maritima (EEAM) and the isolated compound 2″-O-α-L-rhamnopyranosyl-vitexin inhibit mechanical hyperalgesia and parameters of inflammation in mice. The oral administration of EEAM significantly inhibited carrageenan (Cg)-induced paw edema and reduced leukocyte migration into the pleural cavity. 2″-O-α-L-rhamnopyranosylvitexin significantly inhibited paw edema and reduced both leukocyte migration and the leakage of protein into the pleural cavity. Both EEAM and 2″-O-α-L-rhamnopyranosylvitexin significantly prevented the Cg-induced hyperalgesia. Local administration of 2″-O-α-L-rhamnopyranosylvitexin significantly prevented the Cg- and tumor necrosis factor (TNF)-induced hyperalgesia. In conclusion, this study demonstrated that EEAM is an anti-inflammatory and anti-hyperalgesic agent, and the results suggested that 2″-O-α-L-rhamnopyranosylvitexin is responsible for the effects of EEAM and the mechanism involves the TNF pathway.

Naringin attenuates the development of carrageenan-induced acute lung inflammation through inhibition of NF-κb, STAT3 and pro-inflammatory mediators and enhancement of IκBα and anti-inflammatory cytokines.

Naringin has been reported to possess diverse pharmacological properties, including anti-arthritic and anti-inflammatory activities. The aim of the present study was to determine the potential anti-inflammatory effect of naringin in a mouse model of carrageenan-induced pleurisy. A single dose of naringin (40 and 80 mg/kg) was administered per oral (p.o.) 1 h before carrageenan (Cg) administration. Pro- and anti-inflammatory cytokines were analysed in pleural fluid. We also assessed the effects of naringin on the expression levels of iNOS, inducible cyclooxygenase isoform (COX-2), ICAM-1, MIP-2, PGE2, STAT3, TGF-ß1, nuclear factor kappa B (NF-κB) and inhibitor of kappa B (IκBα) in lung tissue. The histological examinations revealed anti-inflammatory effect of naringin while Cg group deteriorated. Naringin downregulated Th1 and upregulated Th2 cytokines. Western blot analyses revealed increased protein expression of NF-κB, STAT3 and COX-2 and decreased IκBα in response to Cg treatment, which were reversed by the treatment with naringin. In the Cg group, mRNA expression levels of pro-inflammatory mediators upregulated and anti-inflammatory mediators downregulated. Naringin reversed these actions.

The novel benzimidazole derivative BRP-7 inhibits leukotriene biosynthesis in vitro and in vivo by targeting 5-lipoxygenase-activating protein (FLAP).

BACKGROUND AND PURPOSE: Leukotrienes (LTs) are inflammatory mediators produced via the 5-lipoxygenase (5-LOX) pathway and are linked to diverse disorders, including asthma, allergic rhinitis and cardiovascular diseases. We recently identified the benzimidazole derivative BRP-7 as chemotype for anti-LT agents by virtual screening targeting 5-LOX-activating protein (FLAP). Here, we aimed to reveal the in vitro and in vivo pharmacology of BRP-7 as an inhibitor of LT biosynthesis. EXPERIMENTAL APPROACH: We analysed LT formation and performed mechanistic studies in human neutrophils and monocytes, in human whole blood (HWB) and in cell-free assays. The effectiveness of BRP-7 in vivo was evaluated in rat carrageenan-induced pleurisy and mouse zymosan-induced peritonitis. KEY RESULTS: BRP-7 potently suppressed LT formation in neutrophils and monocytes and this was accompanied by impaired 5-LOX co-localization with FLAP. Neither the cellular viability nor the activity of 5-LOX in cell-free assays was affected by BRP-7, indicating that a functional FLAP is needed for BRP-7 to inhibit LTs, and FLAP bound to BRP-7 linked to a solid matrix. Compared with the FLAP inhibitor MK-886, BRP-7 did not significantly inhibit COX-1 or microsomal prostaglandin E2 synthase-1, implying the selectivity of BRP-7 for FLAP. Finally, BRP-7 was effective in HWB and impaired inflammation in vivo, in rat pleurisy and mouse peritonitis, along with reducing LT levels. CONCLUSIONS AND IMPLICATIONS: BRP-7 potently suppresses LT biosynthesis by interacting with FLAP and exhibits anti-inflammatory effectiveness in vivo, with promising potential for further development.

Efficacy of vaccination against Actinobacillus pleuropneumoniae in two Belgian farrow-to-finish pig herds with a history of chronic pleurisy.

The efficacy of an Actinobacillus pleuropneumoniae subunit vaccine based on ApxIA, ApxIIA, ApxIIIA and OMP-2 (Porcilis App, MSD) was investigated in two farrow-to-finish pig herds (A and B) affected by chronic pleurisy. In total, 1161 pigs were included. At three weeks of age, the pigs were randomly allocated to non-vaccinated control (NV; n=580) and vaccinated (V; n=581) groups. At 6 and 10 weeks of age, pigs were injected with Porcilis-APP (V group) or adjuvant (NV group). At slaughter (26 weeks), pleurisy and pneumonia lesions were assessed. All pigs were weighed individually at 6 and 26 weeks of age, and average daily weight gain (ADG; g/pig/day) was calculated. Mortality and days of additional treatment (DAT) were registered during the whole experiment. Data were analysed using binary logistic regression or analysis of variance for proportions or continuous variables, respectively. The prevalence of pleurisy and pneumonia was (NV-A=19.3, V-A=7.9, (P=0.000); NV-B=17.9, V-B=0.7, (P=0.000)) and (NV-A=42.4, V-A=21.2, (P=0.000); NV-B=46.7, V-B=19.0, (P=0.000)), respectively. The ADG was NV-A=632±157, V-A=647±91, (P=0.162); NV-B=660±115, V-B=670±82, (P=0.232). The mortality during the experiment was NV-A=5.7, V-A=1.8, (P=0.015); NV-B=2.3, V-B=1.0, (P=0.170) per cent. The DAT was: NV-A=15.04±1.41, V-A=14.95±0.67, (P=0.010); NV-B=21.68±2.43, V-B=16.99±0.62, (P=0.000). The present study showed a significant reduction of the prevalence of pleurisy and pneumonia, and antimicrobial use in V pigs from both herds, and in mortality in V pigs from one herd.

Grape seed proanthocyanidin extract protects against carrageenan-induced lung inflammation in mice through reduction of pro-inflammatory markers and chemokine expressions.

Proanthocyanidins are the most abundant phenolic compounds and have been reported to exert anti-inflammatory actions. The aim of this study was to investigate the effects of grape seed proanthocyanidin extract (GSPE) in a mouse model of carrageenan-induced pleurisy. Following the induction of pleurisy using λ-carrageenan (Cg, 1 %), GSPE (25, 50 and 100 mg/kg) was administered per-oral (p.o.), and the glucocorticoid-induced tumour necrosis factor receptor (GITR), IL-17A expressing cells and other markers, such as cytokines (Th1/Th2 and Th17), were studied. We evaluate the effects of GSPE on the mRNA expression of pro-inflammatory and anti-inflammatory mediators. The results illustrated that the cell numbers of IL-17A and GITR expressing cells and the cytokine levels in Th1/Th17 cells were markedly increased in the Cg-group, whereas the cytokines produced by Th2 cells were significantly decreased in the same group. Treatment with GSPE reversed these effects. Histological examinations revealed anti-inflammatory effects of GSPE.

Acute effect of ß-sitosterol on calcium uptake mediates anti-inflammatory effect in murine activated neutrophils.

OBJECTIVES: To evaluate the effect of ß-sitosterol on 45Ca²âº uptake in activated murine neutrophils, and upon myeloperoxidase and adenosine deaminase activity, and interleukin-1ß (IL-1ß) and tumour necrosis factor-α (TNF-α) levels, in carrageenan-induced inflammation in the mouse air pouch model. METHODS: Dried Esenbeckia leiocarpa bark was macerated and extracted resulting in a crude hydroalcoholic extract (CHE) that was partitioned to obtain an alkaloid fraction. The alkaloid was then partitioned in polar and nonpolar subfractions. ß-Sitosterol was isolated from the nonpolar subfraction and identified by comparison with the literature. The effect of ß-sitosterol on 45Ca²âº uptake in activated murine neutrophils, and upon myeloperoxidase and adenosine deaminase activity, IL-1ß and TNF-α levels in carrageenan-induced inflammation in mice were evaluated. KEY FINDINGS: ß-Sitosterol promoted a time- and dose-dependent increase of the calcium uptake in activated neutrophils that was promptly reversed by nifedipine, BAPTA-AM, LY294002, and colchicine. ß-Sitosterol inhibited myeloperoxidase and adenosine deaminase activity, and IL-1ß and TNF-α levels. CONCLUSIONS: ß-Sitosterol inhibited either myeloperoxidase and adenosine deaminase activity or IL-1ß and TNF-α levels. This effect seemed to be mediated by the calcium uptake in activated neutrophils in a time- and concentration-dependent manner through L-type voltage dependent calcium channels, intracellular calcium, phosphoinositide kinase-3, and microtubule modulation.

Anti-inflammatory effect of (E)-4-(3,7-dimethylocta-2,6-dienylamino)phenol, a new derivative of 4-nerolidylcatechol.

OBJECTIVES: We have investigated the anti-inflammatory and antinociceptive effects of (E)-4-(3,7-dimethylocta-2,6-dienylamino)phenol (LQFM-015), which was designed through molecular simplification strategy from 4-nerolidylcatechol. METHODS: The possible anti-inflammatory and antinociceptive effects were assayed on carrageenan-induced paw oedema and pleurisy, acetic acid-induced abdominal writhing and formalin tests in mice. KEY FINDINGS: LQFM-015 reduced the activity of PLA2 enzyme in vitro by 18%. Docking studies into the catalytic site of PLA2 were used to identify the binding mode of the LQFM-015. LQFM-015 showed a moderate antinociceptive effect, since this compound reduced the number of writhings by approximately up to 40% in the acetic acid-induced pain model; this antinociceptive activity also emerged in the second phase of the formalin-induced pain model (58% of inhibition). The anti-inflammatory action of LQFM-015 was confirmed in acute inflammation models, in which it reduced the formation of oedema to 52.78 ± 8.6 and 46.64 ± 5.2 at the second and third hour of carrageenan-induced paw oedema, respectively. Also in the carrageenan-induced pleurisy model, LQFM-015 reduced the migration of leucocytes by 26.0% and decrease myeloperoxidase activity by 50%. LQFM-015 showed different concentrations to inhibit 50% of isoenzyme cyclooxygenase activity (IC50); COX-1 IC50 = 36 µM) and COX-2 IC50 = 28 µM. CONCLUSIONS: LQFM-015 demonstrated inhibition of both PLA2 and COX enzymes; thus, the moderate antinociceptive effect of this compound could be attributed to its anti-inflammatory activity.

Relationship of chemical structure and anti-inflammatory activity of dihydrocorynantheol and its analogues.

BACKGROUND: Dihydrocorynantheol (DHC) is an alkaloid compound isolated from Esenbeckia leiocarpa Engl. that has demonstrated anti-inflammatory properties in experimental models. The aim of this study was to investigate whether the modification of the chemical structure of DHC could alter its anti-inflammatory effect in a mouse model of pleurisy induced by carrageenan. METHODS: DHC was isolated from Esenbeckia leiocarpa Engl. Capillary electrophoresis, physical characteristics, spectral data produced by infrared analysis and nuclearmagnetic resonance ((1)H and (13)C), and mass spectrometry analysis were used to identify and elucidate DHC structure. The DHC compound was subjected to chemical structural modifications by nucleophilic substitution reactions, yielding five analogous compounds: acetyl (1), p-methylbenzoyl (2), benzoyl (3), p-methoxybenzoyl (4) and p-chlorobenzoyl (5). Swiss mice were used throughout the experiments. Pro-inflammatory parameters leukocyte migration, exudate concentrations and myeloperoxidase (MPO) activity were quantified in the fluid leakage from the mouse pleural cavities at 4 h after pleurisy induction. RESULTS: DHC and its analogues acetyl, p-methylbenzoyl, benzoyl, p-methoxybenzoyl and p-chlorobenzoyl inhibited total and differential leukocyte migration and MPO activity (p < 0.05). Only DHC significantly decreased the exudate concentrations (p < 0.01). CONCLUSIONS: DHC was more effective than its analogues as an anti-inflammatory agent in the mouse model of pleurisy induced by carrageenan. We did not determine what physicochemical modifications altered the anti-inflammatory effect of DHC, but this effect may be due to the modifications on the hydroxyl group at carbon 17 of the DHC.

Hypobaric hypoxia preconditioning attenuates acute lung injury during high-altitude exposure in rats via up-regulating heat-shock protein 70.

HHP (hypobaric hypoxia preconditioning) induces the overexpression of HSP70 (heat-shock protein 70), as well as tolerance to cerebral ischaemia. In the present study, we hypothesized that HHP would protect against HAE (high-altitude exposure)-induced acute lung injury and oedema via promoting the expression of HSP70 in lungs prior to the onset of HAE. At 2 weeks after the start of HHP, animals were exposed to a simulated HAE of 6000 m in a hypobaric chamber for 24 h. Immediately after being returned to ambient pressure, the non-HHP animals had higher scores of alveolar oedema, neutrophil infiltration and haemorrhage, acute pleurisy (e.g. increased exudate volume, increased numbers of polymorphonuclear cells and increased lung myeloperoxidase activity), increased pro-inflammatory cytokines [e.g. TNF-α (tumour necrosis factor-α), IL (interleukin)-1ß and IL-6], and increased cellular ischaemia (i.e. glutamate and lactate/pyruvate ratio) and oxidative damage [glycerol, NOx (combined nitrate+nitrite) and 2,3-dihydroxybenzoic acid] markers in the BALF (bronchoalveolar fluid). HHP, in addition to inducing overexpression of HSP70 in the lungs, significantly attenuated HAE-induced pulmonary oedema, inflammation, and ischaemic and oxidative damage in the lungs. The beneficial effects of HHP in preventing the occurrence of HAE-induced pulmonary oedema, inflammation, and ischaemic and oxidative damage was reduced significantly by pretreatment with a neutralizing anti-HSP70 antibody. In conclusion, HHP may attenuate the occurrence of pulmonary oedema, inflammation, and ischaemic and oxidative damage caused by HAE in part via up-regulating HSP70 in the lungs.

Avaliação da atividade antiinflamatória do coentro (Coriandrum sativum L. ) em roedores / Evaluation of the anti-inflammatory activity of coriander (Coriandrum sativum L. ) in rodents

Coriandrum sativum L. (Umbelliferae), conhecido popularmente por coentro, é uma planta doméstica cultivada nas diversas partes do mundo, inclusive no Brasil. As folhas e frutos do coentro são utilizados como condimento em culinária e na medicina popular como analgésica, antirreumática, carminativa e colagoga. O objetivo deste estudo foi avaliar o efeito do tratamento com o óleo essencial (OEC) e o extrato hidroalcóolico (EHC) do coentro em modelos experimentais de inflamação em roedores. A atividade antiinflamatória do coentro foi avaliada por meio dos testes de pleurisia em ratos e formação do edema de orelha em camundongos. A pleurisia foi induzida pela carragenina em animais tratados ou não com EHC. O edema de orelha induzido pela aplicação tópica de óleo de cróton e a atividade da mieloperoxidase foi avaliada em camundongos tratados ou não com OEC ou EHC. No teste da pleurisia o tratamento com EHC promoveu significativa diminuição no edema pleural, mas não sobre a migração leucocitária. Além disso, diferentemente ao observado com o tratamento com OEC, o uso tópico de EHC diminui significativamente o edema de orelha e a migração celular induzidos pela aplicação do óleo de cróton. Os dados indicam que EHC apresenta atividade antiinflamatória quando administrado pelas via oral e tópica, enquanto que OEC não apresenta atividade antiinflamatória tópica.

Commonly known as coriander, Coriandrum sativum L. (Umbelliferae) is a home plant grown in several parts of the world, including Brazil. Its leaves and fruits have been used as condiment in cooking and in folk medicine as analgesic, antirheumatic, carminative and cholagogue. The aim of this study was to evaluate the effect of essential oil (EO) and hydroalcoholic extract (HE) from coriander on experimental inflammation models in rodents. Coriander anti-inflammatory activity was evaluated by pleurisy tests in rats and ear edema formation in mice. Pleurisy was induced by carrageenan in HE-treated or non-treated animals. The ear edema was induced by topical application of croton oil and the myeloperoxidase activity was evaluated in EO-treated and HE-treated or non-treated mice. In the pleurisy test, HE treatment significantly decreased pleural edema but not the leukocyte migration. Furthermore, differently from EO, the topical use of HE significantly decreased ear edema and cell migration induced by croton oil application. The results indicate that HE had anti-inflammatory activity when orally and topically administered, whereas EO did not present topical anti-inflammatory activity.