Anti-inflammatory and analgesic activity of Indian Hypericum perforatum L

A standardised 50% aqueous ethanolic extract of the Indian variety of Hypericum perforatum (IHp) was examined for its putative anti-inflammatory and analgesic activity at the doses of 100 and 200 mg/kg, po. The experimental paradigms used were carrageenan induced pedal edema and cotton pellet induced granuloma for anti-inflammatory activity, whereas the tail flick, hot plate and acetic acid induced writhing methods were used to asses analgesic activity. Indomethacin (20 mg/kg, ip) was used as the standard anti-inflammatory drug. Pentazocine (10 mg/kg, ip) and aspirin (25 mg/kg, ip), both clinically used analgesics, were used as standard analgesics for comparison. IHp extract showed significant anti-inflammatory and analgesic activity at both dose levels, in all the paradigms used. Additionally, IHp potentiated the anti-inflammatory activity of indomethacin and analgesic activities of pentazocine and aspirin.     

两面针提取物(S-O)对小鼠镇痛、抗炎和止血作用的研究

本研究对两面针根的提取物S-O进行了镇痛、止血和抗炎药理实验,每种作用选用两种实验方法来评价。镇痛作用采用热板法和扭体法。热板法实验显示,S-O在150mg/kg剂量时,小鼠痛阈值明显提高（P〈0．01）;扭体法实验显示,S-O在150mg/kg剂量为时,对冰醋酸致痛的小鼠扭体反应次数减少了70．96％（P〈0．01）。抗炎实验采用二甲苯致小鼠耳廓肿胀法及腹腔染料渗出法。二甲苯致炎剂实验表明,S-O在150mg/kg剂量时,对二甲苯所致小鼠耳廓肿胀有明显抑制作用,抑制率为63．45％（P〈0．01）;冰醋酸所致的腹腔毛细血管通透性实验中,S-O在150mg/kg和75mg/kg两个剂量组时,对小鼠的抗炎效果分别为52．94％（P〈0．01）和52．00％（P〈0．01）。止血实验采用毛细玻璃管法和载玻片法。毛细玻璃管实验表明S-O在150mg/kg和75mg/kg两个剂量时,凝血时间明显缩短（P〈0．01）;载玻片实验表明S-O在150mg/kg剂量时,凝血时间明显缩短（P〈0．01）。总之,两面针中提取物S-O对小鼠具有显著的镇痛、止血和抗炎作用。     

两面针提取物(S0)对小鼠镇痛、抗炎和止血作用的研究(英文)

本研究对两面针根的提取物S0进行了镇痛、止血和抗炎药理实验,每种作用选用两种实验方法来评价。镇痛作用采用热板法和扭体法。热板法实验显示,S0在150mg/kg剂量时,小鼠痛阈值明显提高(P<0.01);扭体法实验显示,S0在150mg/kg剂量为时,对冰醋酸致痛的小鼠扭体反应次数减少了70.96%(P<0.01)。抗炎实验采用二甲苯致小鼠耳廓肿胀法及腹腔染料渗出法。二甲苯致炎剂实验表明,S0在150mg/kg剂量时,对二甲苯所致小鼠耳廓肿胀有明显抑制作用,抑制率为63.45%(P<0.01);冰醋酸所致的腹腔毛细血管通透性实验中,S0在150mg/kg和75mg/kg两个剂量组时,对小鼠的抗炎效果分别为52.94%(P<0.01)和52.00%(P<0.01)。止血实验采用毛细玻璃管法和载玻片法。毛细玻璃管实验表明S0在150mg/kg和75mg/kg两个剂量时,凝血时间明显缩短(P<0.01);载玻片实验表明S0在150mg/kg剂量时,凝血时间明显缩短(P<0.01)。总之,两面针中提取物S0对小鼠具有显著的镇痛、止血和抗炎作用。     

In-vivo antinociceptive,anti-inflammatory and antipyretic activity of pistagremic acid isolated from Pistacia integerrima

The current study was designed to explore the antinociceptive, antiinflammatory and antipyretic activity of pistagremic acid (PA), isolated from Pistacia integerima bark in various animal paradigms. The results illustrated significant inhibition of noxious stimulation in acetic acid induced writhing test with maximum effect of 68% at 10 mg/kg i.p. In tail immersion test, pretreatment with PA demonstrated marked activity during various assessment times in a dose dependent manner. The maximum pain inhibition was 59.46% at 10 mg/kg i.p. after 90 min of PA treatment. However, the injection of naloxone did not antagonize this induced effect. PA significantly ameliorated post carrageenan induced edema dose dependently during various stages of inflammation. The effect was most dominant (60.02%) after 3^rd h of drug administration when examined for 5 h. Similarly, it provoked dose dependent antipyretic effect in febrile mice with maximum of 60.04% activity at 10 mg/kg i.p. after 3rd hour of PA post treatment. Furthermore, molecular docking was carried out to understand the binding mode of PA. From the docking study it was observed that PA fits well in the active site of COX-2 enzyme due to hydrogen and hydrophobic moiety interactions to the important active site of molecule.In conclusion, PA possesses strong peripheral and central antinociceptive activity independent of opioidergic effect which was augmented by its anti-inflammatory and antipyretic activities.     

Molecular docking and analgesic studies of Erythrina variegata?s derived phytochemicals with COX enzymes

Secondary metabolites from plants are a good source for the NSAID drug development. We studied the analgesic activity of ethanolic extract of Erythrina variegata L. (Fabaceae) followed by molecular docking analysis. The analgesic activity of Erythrina variegata L. is evaluated by various methods viz., acetic acid-induced writhing test, hot plate and tail immersion test. Subsequently, molecular docking analysis has been performed to identify compounds having activity against COX-1 and COX-2 enzymes by using GOLD docking fitness. The result of preliminary phytochemical screening revealed that the extract contains alkaloids and flavonoids. In analgesic activity tests, the extract at the doses of 50, 100 and 200 mg/kg body weight (b.w.) produced a increase in pain threshold in a dose dependent manner. In acetic acid induced writhing test, the inhibitory effect was similar to the reference drug diclofenac sodium. The extract showed 18.89% writhing inhibitory effect at the dose 200 mg/kg b.w., whereas diclofenac sodium showed 79.42% inhibition of writhing at a dose of 10 mg/kg b.w. The results of tail immersion and hot plate test also showed potential analgesic activity of the extract which is also comparable to the standard drug morphine (5 mg/kg b.w.). Docking studies shows that phaseollin of Erythrina variegata L. has the best fitness score against the COX-1 which is 56.64 and 59.63 for COX- 2 enzyme. Phaseollin of Erythrina variegata L. detected with significant fitness score and hydrogen bonding against COX-1 and COX-2 is reported for further validation.     

Evaluation of the anti-inflammatory and antinociceptive properties of p-cymene in mice

We attempted to identify the antinociceptive and anti-inflammatory actions of the monoterpene p-cymene. Firstly, behavioural screening was carried out to verify the influence of p-cymene [25, 50, and 100 mg/kg intraperitoneal (i.p.)] on the central nervous system (CNS) activity. The antinociceptive activity of p-cymene was evaluated by the acetic acid-induced writhing response, formalin, and hot-plate test, respectively. The leukocyte migration induced by injection of carrageenan was used to assess the anti-inflammatory activity. p-Cymene showed depressant activity on CNS after 4 h of treatment and also a possible action on the autonomous nervous system (ANS), mainly at the dose of 100 mg/kg (i.p.). It was found that p-cymene (50 and 100 mg/kg, i.p.) significantly (p < 0.05) reduced the writhing responses induced by acetic acid. p-Cymene also decreased the licking time in the first and second phase, respectively, of the formalin test. The results of the hot-plate test showed that all doses of p-cymene increased significantly the latency time of the response to the thermal stimulus in both licking and jumping parameters. In addition, there was a significantly (p < 0.05) decreased leukocyte migration at all doses of p-cymene. The experimental data demonstrate that p-cymene possesses antinociceptive and anti-inflammatory activities.     

Evaluation of anti-nociceptive,anti-inflammatory and antipyretic potential of Mikania cordata (Burm. f.) Robinson in experimental animal model

Mikania cordata is widely used for the treatment of cuts, wounds, and dengue fever in Bangladesh. In the present study, essential oil (12.5, 25 and 50?mg/kg) and two extracts, viz., chloroform and ethyl acetate extracts (200, 400, 800?mg/kg b.w.) were tested for peripheral and central anti-nociceptive activity by acetic acid-induced writhing and hot plate method, respectively. Carrageenan-induced rat paw edema assay and yeast-induced hyperthermia assay were also carried out to evaluate anti-inflammatory and antipyretic properties of oil and extracts, respectively at aforesaid doses. The essential oil (50?mg/kg), chloroform extract (800?mg/kg) and ethyl acetate extract (800?mg/kg) showed potent peripheral anti-nociceptive activity having 47.33%, 29.33% and 16.65% of writhing inhibition, respectively, comparable with standard diclofenac (52.0%). Essential oil (50?mg/kg), chloroform extract (800?mg/kg) and ethyl acetate extract (800?mg/kg) presented promising central anti-nociceptive activity as well having 95.86%, 79.18% and 42.37% elongation of reaction time, respectively, at 90?min after administration of essential oil, ethyl acetate extract and 60?min after administration of chloroform extract. In anti-inflammatory activity screening, the essential oil (50?mg/kg) produced the highest 72.80% edema inhibition at 4?h after administration of carrageenan which was comparable with that of standard phenylbutazoe (87.87%). On the other hand, chloroform extract (800?mg/kg) and ethyl acetate extract (800?mg/kg) showed up to 34.31% and 15.27% of edema inhibition, respectively, at 4?h after administration of carrageenan. In antipyretic assay, the essential oil and chloroform extract displayed a strong antipyretic effect in yeast-induced rats, whereas the ethyl acetate extract had no antipyretic activity. The present study revealed anti-nociceptive, anti-inflammatory and antipyretic potential of M. cordata which could be the therapeutic option against fever, inflammations as well as painful conditions and confirmed the traditional use of M. cordata.     

A novel triterpenoid 16-hydroxy betulinic acid isolated from Mikania cordata attributes multi-faced pharmacological activities

The aerial parts of extensively used ethnomedicinal plant Mikania cordata (Burm. f.) Robinson growing wild in Bangladesh were investigated to isolate and characterize compounds responsible for the bioactivities of the plant. In the present study, a new derivatives of betulinic acid, 16-hydroxy betulinic acid [3β,16-dihydroxy-lup-20(29)-en-28-oic] was isolated and the structure of the compound was determined by NMR spectroscopic means and comparing with available literature data. The isolated compound was then investigated for different pharmacological activities including antibacterial, antifungal, analgesic, anti-inflammatory and antipyretic potential employing different methods. The compound showed potent antibacterial activity with inhibition zone of diameter ranging from 12.0 to 17.5?mm and antifungal activity with mycelial growth inhibition ranging from 37.6 to 54.5%. The MIC values for antibacterial and antifungal activities ranged from 31.5–125 and 250–1000?μg/mL respectively. The compound (50 and 100?mg/kg body weight) showed potent peripheral and central analgesic activity with 55.19% and 41% of writhing inhibition at 90?min after administration of the compound and the highest 55.98%, 79.18% elongation of reaction time, respectively. In anti-inflammatory activity screening, the compound (100?mg/kg b.w.) revealed the highest 77.08% edema inhibition at 4?h after administration of carrageenan. In antipyretic assay, 16-hydroxy betulinic acid displayed a strong antipyretic effect in yeast-induced rats. From the present study it is apparent that 16-hydroxy betulinic acid might play vital role to establish M. cordata as ethnomedicinal plant to treat wound, cuts and fever.     

Comparison with various parts of Broussonetia papyrifera as to the antinociceptive and anti-inflammatory activities in rodents

This study compared the antinociceptive and anti-inflammatory effects of various parts of Broussonetia papyrifera (L.) L'Herit. ex Vent. (BP, Moraceae) by chemical-induced pain and inflammation in rodents. All BP parts (1 and 2 g/kg, p.o.) effectively inhibited writhing responses induced by 1% acetic acid. The BP radix, leaf, and fruit effectively inhibited the late-phase licking responses caused by 1% formalin. But only the BP radix and fruit reduced the edema induced by 1% carrageenan at 1-2 h. Furthermore, the BP radix reduced the abdominal Evan's blue extravasations caused by inflammatory mediators, including serotonin and sodium nitroprusside. Finally, the radix had the highest contents of betulin and betulinic acid among all BP parts. In conclusion, the radix is the better medicinal BP part possessing antinociceptive and antiinflammatory effects, and its anti-inflammatory effects are partially related to the inhibition of vascular permeability via autocrines and nitric oxide.     

Synthesis, anti-inflammatory, analgesic and antioxidant activities of some tetrasubstituted thiophenes

Sets of tetrasubstituted thiophene esters 4a-4g, 5a-5f and 6a-6e were synthesized by reaction of 1-(alpha-Carbomethoxy-beta-aminothiocrotonoyl)-aryl/aroyl amines (3) with 3-(bromoacetyl)coumarin, 1,4-dibromodiacetyl and chloroacetone respectively. The compound 3 were synthesized by nucleophilic addition of aryl/aroylisothiocyanate and enamine (2). The synthesized targeted compounds (4a-4g, 5a-5f and 6a-6e) were evaluated for their in vivo anti-inflammatory activity in carrageenin-induced rat hind paw oedema model at three graded doses employed at 10, 20 and 40 mg/kg body weight using mefanamic acid, ibuprofen and in vivo analgesic activity in acetic acid induced writhing response model at 10 mg/kg dose using ibuprofen as standard drug. The compounds 4a-4f, 5c, 5f, 6c and 6e were evaluated for their in vitro antioxidant nitric oxide radical scavenging assay at the concentrations of 5, 10, 15, 20, 25, 30 and 35 microg/mL using ascorbic acid as standard drug. Among all the targeted compounds 4c showed maximum anti-inflammatory activity of 71% protection at 10 mg/kg and 77% protection at 20 mg/kg to inflamed paw and analgesic activity of 56% inhibition and also maximum in vitro nitric oxide radical scavenging activity having IC(50) value 31.59 microg/mL.     

Antiinflammatory and antiulcer activities of phytic acid in rats

Maximum antiinflammatory activity of phytic acid (PA) was seen at an oral dose of 150 mg/kg in the carrageenan induced rat paw edema model. Although PA showed ability to prevent denaturation of proteins, it showed less antiinflammatory activity than ibuprofen. Ability of PA to bring down thermal denaturation of proteins might be a contributing factor in the mechanism of action against inflammation. PA, at all the doses tested, showed significant protection from ulcers induced by ibuprofen, ethanol and cold stress, with a maximum activity at 150 mg/kg. There was a significant increase in gastric tissue malondialdehyde levels in ethanol treated rats but these levels decreased following PA pretreatment. Moreover, pretreatment with PA significantly inhibited various effects of ethanol on gastric mucosa, such as, reduction in the concentration of nonprotein sulfhydryl groups, necrosis, erosions, congestion and hemorrhage. These results suggested that gastro-protective effect of PA could be mediated by its antioxidant activity and cytoprotection of gastric mucosa.     

Protective effect of aqueous extract of Bombax malabaricum DC on experimental models of inflammatory bowel disease in rats and mice

There is little evidence regarding role of B. malabaricum in the treatment of inflammatory bowel disease (IBD); though it is clinically employed as a constituent of a polyherbal preparation for IBD. To establish its role as a monotherapy for IBD, preliminary phytochemical screening of aqueous extract of B. malabaricum (AEBM) was undertaken. Subsequently, its protective effect in indomethacin and iodoacetamide induced colitis in rats (45, 90, 180, 270 mg/kg) and acetic acid induced colitis in mice (65, 130, 250, 500 mg/kg) was assessed. AEBM (270 mg/kg) in indomethacin and iodoacetamide induced colitis significantly reduced the ulcer score and myeloperoxidase (MPO) activity. AEBM/500 mg/kg dose/significantly reduced the ulcer score and MPO activity in acetic acid induced colitis. The extract (270 mg/kg in rats and 500 mg/kg in mice) was found to be comparable with prednisolone (10 mg/kg) and 5-aminosalicylic acid (5-ASA) (100 mg/kg) used as standard treatments. AEBM provided reduction in edema of the intestinal tissues, ulcer protection and lowering of MPO activity in a dose dependent manner. AEBM (500 mg/kg) significantly reduced colonic and serum TNF-alpha level when compared with the positive control in acetic acid induced colitis model. The results suggest a protective role of AEBM in IBD.     

Immunomodulatory activity of boswellic acids of Boswellia serrata Roxb

Extract of gum resin of B. serrata containing 60% acetyl 11-keto beta boswellic acid (AKBA) along with other constituents such as 11-keto beta-boswellic acid (KBA), acetyl beta-boswellic acid and beta-boswellic acid has been evaluated for antianaphylactic and mast cell stabilizing activity using passive paw anaphylaxis and compound 48/80 induced degranulation of mast cell methods. The extract inhibited the passive paw anaphylaxis reaction in rats in dose-dependant manner (20, 40 and 80 mg/kg, po). However, the standard dexamethasone (0.27 mg/kg, po) revealed maximum inhibition of edema as compared to the extract. A significant inhibition in the compound 48/80 induced degranulation of mast cells in dose-dependant manner (20, 40 and 80 mg/kg, po) was observed thus showing mast cell stabilizing activity. The standard disodium cromoglycate (50 mg/kg, ip) was found to demonstrate maximum per cent protection against degranulation as compared to the extract containing 60% AKBA. The results suggest promising antianaphylactic and mast cell stabilizing activity of the extract.     

Pharmacological study of Stachytarpheta cayennensis Vahl in rodents

Freeze-dried aqueous extracts (AEs, 0.1–1 g/kg body wt., p.o.) obtained from entire or selected parts of Stachytarpheta cayennensis were tested for their effects on gastric secretion, gastric motility, inflammation and pain in rodents, with the purpose of validating the plant's ethnomedical uses. The AE-Total, AE-Flowers and AE-Leaves but not AE-Stems inhibited the gastric acid secretion in pylorus-ligated rats with varying potency. Purification of AEs yielded the semipurifed fractions EtFs rich in iridoids. All the EtFs with exception of EtF-Stems inhibited gastric acid secretion of pylorus ligated mice. While AE-Total stimulated the intestinal transit of mice by 43%, AE-Leaves delayed it by 38%. These effects on intestinal transit were not observed when the EtFs were tested. Only AE-Leaves and AE-Flowers altered the gastric emptying of semisolids, increasing it by 45% and 69%, respectively. These results indicate that the compounds related to inhibition of gastric acid secretion and gastrointestinal motility are different. The AE-Total reduced abdominal writhing induced by acetic acid potently (ED₅₀ VALUE=700 mg/kg, p.o.) without altering the writhes induced by acetylcholine. Attempts to identify the mechanism of analgesia were unsuccessful since the AE-Total did not show analgesic effects when tested in different models of pain such as formalin and capsaicin or the tail-flick test. Pretreatment of animals with AE-Total did not show antiinflammatory activity in any of the acute (paw edema induced by carrageenin, dextran or histamine, pleurisy induced by carrageenin and capsaicin-induced mouse ear edema) or chronic (air pouch) models used. No toxic signs were observed after administration of the different extracts up to 2 g/kg body wt., p.o.

Collectively, the results confirmed folk information indicating presence of analgesic, mild laxative and potent inhibition of gastric secretion activities in the aqueous extracts of S. cayennensis. The results do not, however confirm the folk use of the plant as an antiinflammatory medicine.     

Antinociceptive effect of leaf essential oil from Croton sonderianus in mice

The leaf essential oil from Croton sonderianus (EOCS) was evaluated for antinociceptive activity in mice using chemical and thermal models of nociception. Given orally, the essential oil at doses of 50, 100 and 200 mg/kg produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid and subplantar formalin or capsaicin injections. However, it evidenced no efficacy against thermal nociception in hot-plate test. More prominent inhibition of acetic acid-induced writhing and capsaicin-induced hind-paw licking responses was observed at 100 and 200 mg/kg of EOCS. At similar doses, the paw licking behavior in formalin test was more potently suppressed during the late phase (20-25 min, inflammatory) than in early phase (0-5 min, neurogenic). The EOCS-induced antinociception in both capsaicin and formalin tests was insensitive to naloxone (1 mg/kg, s.c.), but was significantly antagonized by glibenclamide (2 mg/kg, i.p.). In mice, the essential oil (100 and 200 mg/kg) neither significantly enhanced the pentobarbital-sleeping time nor impaired the motor performance in rota-rod test, indicating that the observed antinociception is unlikely due to sedation or motor abnormality. These results suggest that EOCS produces antinociception possibly involving glibenclamide-sensitive KATP+ channels, which merit further studies on its efficacy in more specific models of hyperalgesia and neuropathic pain.     

Analgesic,anti-inflammatory and anti-ulcer properties of Thai Perilla frutescence fruit oil in animals

Perilla frutescens fruit oil (PFO) is rich in α-linolenic acid (ALA) and exhibits biological activities. We aimed to investigate analgesic, anti-inflammatory and anti-ulcer activities of PFO and PFO-supplemented soybean milk (PFO-SM) in animal models. Analgesic activity was assessed in acetic acid-induced writhing in mice, while anti-inflammatory activity was performed in ethyl phenylpropiolate (EPP)-induced ear edema and carrageenan-induced hind paw edema in rats. Anti-ulcer effects were conducted in water immersion stress, HCl/ethanol and indomethacin-induced gastric ulcer in rats. Distinctly, PFO, containing 6.96 mg ALA and 2.61 mg LA equivalence/g, did not induce acute toxicity (LD₅₀ > 10 mL/kg) in mice. PFO (2.5 and 5 mL/kg) and PFO-SM (0.05 mL PFO equivalence/kg) inhibited incidences of writhing (16.8, 18.0 and 32.3%, respectively) in acetic acid-induced mice. In addition, topical applications of PFO (0.1 and 1 mL/ear) significantly inhibited EPP-induced ear edema (59.3 and 65.7%, respectively) in rats, while PFO-SM slightly inhibited ear edema (25.9%). However, PFO and PFO-SM did not inhibit carrageenan-induced hind paw edema in rats. Indeed, PFO (2.5 and 5 mL/kg) significantly inhibited gastric ulcers in rats that induced by water immersion stress (92.4 and 96.6%, respectively), HCl/ethanol (74.8 and 73.3%, respectively) and indomethacin (68.8 and 88.9%, respectively), while PFO-SM did not. PFO displayed potent analgesic, anti-inflammatory and anti-ulcer properties, while PFO-SM exerted only analgesic properties. Thus, Thai PFO and its functional drink offer potential benefits in treatment of analgesic, inflammatory diseases and gastric ulcer.     

Synthesis and biological activity evaluation of lignan lactones derived from (-)-cubebin

The anti-inflammatory and analgesic effects of three dibenzylbutyrolactone lignans, (-)-hinokinin (2), (-)-6,6'-dinitrohinokinin (3), and (-)-6,6'-diaminohinokinin (4), obtained by partial synthesis from (-)-cubebin (1), were investigated using different animal models. It was observed that compounds (1) and (2) inhibited the edema formation in the rat paw edema assay at the same level and that all responses were dose dependent. Also, at the dose of 30 mg/kg, compounds 1, 2, 3, and 4 inhibited the edema formation by 53%, 63%, 54%, and 82%, respectively, at the third hour of the experiment. In the acetic acid-induced writhing test in mice, compounds 2 and 4 produced inhibition levels of 97% and 92%, respectively, while 3 displayed lower effect (75%), which was still higher than 1. The assayed compounds neither displayed activity in the cell migration test nor in the hot plate test.     

Antiinflammatory effect of a protein kinase C inhibitor (K-252a) on the development of the dextran-induced paw edema in the rat (preliminary results).

The effect of a metabolite of Nocardiopsis sp. as a protein kinase C inhibitor from microbial origin was investigated on the onset and development of dextran-induced paw edema in the rat. It was published that this compound (K-252a) interferes with histamine release from mast cells, while dextran-induced paw and nose edema are induced by vasoactive agents, like histamine etc., released from the disrupted mast cells. The antiinflammatory effect of the K-252a is effectuated by the inhibition of protein kinase C. Groups of male Wistar rats with 180-200 g b.w. were used; each group consisted of 10-10 rats. The following groups were consisted: rats given orally DMSO (control), rats given 1 mg/kg, or 3 mg/kg b.w. of K-252a dissolved in DMSO and given p.o. one hour before dextran injection. Dextran (BDH Chem. LTD, molW: 200.000, England) was injected intraperitoneally in 10% solution, in a dose of one ml/100 g b.w. Volume of the hind leg was measured by a mercury plethysmometer. Time-sequence of the edema was followed. Increase in volume of hind leg paw was related to its 0-min volume in %. Results were analyzed by the Kruskal-Wallis-test. Edema of the legs and noses appeared in each of the control rats in one hour. The 1 mg/kg dose of K-252a retarded the appearance of the edema by 1 hour, the 3 mg/kg dose, however, prevented its onset for 4 hours.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antinociceptive effect of Nidularium procerum: a Bromeliaceae from the Brazilian coastal rain forest

Nidularium procerum, a common plant of the Brazilian flora, has not yet been studied for its pharmacological properties. We report here that extracts of N. procerum show both analgesic and anti-inflammatory properties. Oral (p.o.) or intraperitoneal (i.p.) administration of an aqueous crude extract from leaves of N. procerum (LAE) inhibited the writhing reaction induced by acetic acid (ED50 value = 0.2 mg/kg body weight, i.p.) in a dose-dependent manner. This analgesic property was confirmed in rats using two different models of bradykinin-induced hyperalgesia; there was 75% inhibition of pain in the modified Hargreaves assay, and 100% inhibition in the classical Hargreaves assay. This potent analgesic effect was not blocked by naloxone, nor was it observed in the hot plate model, indicating that the analgesic effect is not associated with the activation of opioid receptors in the central nervous system. By contrast, we found that LAE (0.02 microg/ml) selectively inhibited prostaglandin E2 production by cyclooxygenase (COX)-2, but not COX-1, which is a plausible mechanism for the analgesic effect. A crude methanol extract from the leaves also showed similar analgesic activity. An identical extract from the roots of N. procerum did not, however, block acetic acid-induced writhes, indicating that the analgesic compounds are concentrated in the leaves. Finally, we found that LAE inhibited an inflammatory reaction induced by lipopolysaccharide in the pleural cavity of mice.     

Preliminary studies on phospholipase A2-induced mouse paw edema as a model to evaluate antiinflammatory agents

Phospholipase A2 (PLA2) is a key component of the inflammatory process because of its role in the generation of eicosanoids and platelet-activating factor (PAF). Manipulation of PLA2 activity offers a novel therapeutic approach for the development of antiinflammatory agents; however, there is a need for a suitable in vivo model. Injection of 1 microgram of snake venom PLA2 (A. piscivorus piscivorus, D-49) into the mouse hind footpad produced a significant three- to four-fold rise in paw edema within 10 min, compared to the saline control. Edema formation depended on enzyme concentration and appeared specific for PLA2 since edema was negated by enzyme pretreatment with p-bromophenacyl bromide, a nonspecific PLA2 inhibitor. Moreover, injection of a protein such as bovine serum albumin did not result in significant edema. Coinjection of phenidone (lipoxygenase inhibitor, 50 micrograms), indomethacin (cyclooxygenase inhibitor, 50 micrograms), cyproheptadine (antihistamine/antiserotonin, 50 micrograms), aristolochic acid (putative PLA2 inhibitor, 100 micrograms), or kadsurenone (PAF antagonist, 50 micrograms) with PLA2 (1 microgram/paw) resulted in partial reduction (44.5, 34.2, 54.7, 64, and 50% inhibition, respectively) of edema formation. Oral administration of cyproheptadine (10 mg/kg), indomethacin (10 mg/kg), BW 755c (100 mg/kg), or dexamethasone (1 mg/kg) 1-3 h before challenge also decreased PLA2-induced edema (63.0, 30.1, 47.8, or 62.5% inhibition, respectively). The data suggest that mouse paw edema resulting from PLA2 injection is a multicomponent event, influenced by both autacoids and lipid mediators of inflammation.