白术醇提物的抗炎镇痛活性研究

目的 探讨白术醇提物的抗炎镇痛活性,为进一步研究白术抗炎镇痛的作用机制提供基础。方法 采用热板法测定白术不同剂量组小鼠的痛阈值,腹腔注射0.6%醋酸刺激致痛模型(扭体法)观察白术3个不同剂量的镇痛作用;采用二甲苯致小鼠耳廓肿胀实验和角叉菜胶致大鼠足肿胀实验观察白术3个不同剂量的抗炎作用。结果 高、中剂量的白术醇提物可显著增加小鼠的热板痛域值(P<0.01,P<0.01),减少腹腔注射醋酸引起的小鼠扭体反应次数(P<0.01,P<0.01),而白术低剂量组不能有效的提高小鼠的痛阈值(P>0.05)和减少扭体反应次数(P>0.05)。在抗炎试验中,高、中剂量的白术醇提取可显著抑制小鼠耳廓肿胀度(P＜0.01,P＜0.01),而低剂量组对小鼠耳廓肿胀抑制效果不明显(P＞0.05);高剂量组在2h后能显著抑制大鼠足跖肿胀,中剂量组(除6h时间点)与白术低剂量组(除3h时间点)在药后0.5-6h之间与模型组比较均无显著性差异(P＞0.05)。结论 白术醇提物具有较好的抗炎、镇痛作用,并且随着剂量的增大,抗炎镇痛活性增强。     

Anti-inflammatory and analgesic activities of the hydrolyzed sasanquasaponins from the defatted seeds of Camellia oleifera

The defatted seeds of Camellia oleifera (Abel.) are used for stopping itching and pain in old days, the effective compounds need to be investigated. Sasanquasaponin as a rich fraction was extracted with 70 % ethanol, purified by AB-8 macro-reticular resin, crystallized in 80 % ethanol, and further hydrolyzed by 4 % hydroxyl potassium or 2 M hydrochloride. Anti-inflammatory activities of the extracts were measured by carrageenan-induced paw edema in rats and croton oil induced ear inflammation in mice; the analgesic activities were analyzed by hot plate test, acetic acid induced writhing in mice; the levels of pain mediators of IL-1β, TNF-α and PGE₂ were determined; the antioxidative activities in vivo were evaluated by MDA, SOD and GSH-Px in serum of rats. The extracts showed significant (p < 0.01) anti-inflammatory and analgesic activities, remarkably (p < 0.01) inhibited production of pro-inflammatory cytokines and PGE₂, decreased MDA and increased SOD and GSH-Px in serum. Inhibition of IL-1β, TNF-α and PGE₂ may contribute to their anti-inflammatory and analgesic effects; elimination of free radicals is also involved. The sapogenin and acid hydrolyzed product have better anti-inflammatory, analgesic effects, and stronger antioxidative activity than sasanquasaponin and alkaline hydrolyzed product, and they are better candidate medicines for inflammation and pain.     

冷水七活性部位镇痛抗炎作用的研究

目的 研究冷水七活性部位I(IPB-I)的镇痛抗炎作用。方法 采用热板法、醋酸扭体法研究IPB I对小鼠的镇痛作用，并与0.9%氯化钠注射液、盐酸吗啡作对照；采用二甲苯致小鼠耳肿胀、醋酸致小鼠腹膜毛细血管通透性增加的实验研究IPB-I抗炎作用，并与0.9%氯化钠注射液、氢化可的松对照。结果IPB-I对两种痛刺激有非常显著的镇痛作用；对两种实验性炎症有非常显著的抑制作用。结论IPB-I具有显著的镇痛抗炎作用。     

Amide derivatives of [6-acyl-2-benzothiazolinon-3-yl] acetic acids as potential analgesic and anti-inflammatory compounds

In this study, we investigated the analgesic and anti-inflammatory activities of [6-acyl-2-benzothiazolinon-3-yl]acetic acids by the derivatization of the carboxylate moiety into amides. We have tested the analgesic and anti-inflammatory activities of the synthesized compounds in vivo by using p-benzoquinone-induced writhing test and carrageenan-induced hind paw edema model, respectively. Compounds 4h, 4i, 4n, and 4o showed comparable analgesic and anti-inflammatory activities to the references without gastric lesions in the tested animals. In addition, all compounds also tested for their inhibitory activity against cyclooxygenase (COX)-1, COX-2 and 5-lipoxygenase (LOX), but no significant inhibition was observed under assayed conditions.     

Synthesis and analgesic and antiinflammatory activity of methyl 6-substituted-3(2h)-pyridazinone-2-ylacetate derivatives

A series of methyl 6-substituted-3(2H)-pyridazinone-2-ylacetates 9 were synthesized and their analgesic and anti-inflammatory effects were evaluated in the phenylbenzoquinone-induced writhing test (PBQ test) and carrageenan-induced paw edema method, respectively. Side effects of the compounds were examined on gastric mucosa. None of the compounds showed gastric ulcerogenic effect compared with reference nonsteroidal anti-inflammatory drugs. Methyl 6-(4-(4-fluorophenyl)piperazine)-3(2H)-pyridazinone-2-ylacetate 9e was found to be more active than acetylsalicylic acid (ASA). Methyl 6-(4-(2-ethoxyphenyl)piperazine)-3(2H)-pyridazinone-2-ylacetate 9c has shown an anti-inflammatory activity as compared to the standard compound indometacin at the carrageenan-induced paw edema method.A significant dependence of the anti-inflammatory effect on the substituents has been observed. The pharmacological study of these compounds confirms that modification of the chemical group at the position 6 of the 3(2H)-pyridazinone system influences analgesic and anti-inflammatory activities. The structures of these new pyridazinone derivatives were confirmed by their IR and (1)H-NMR spectra and elemental analysis.     

Antiinflammatory and analgesic activities of Thesium chinense Turcz extracts and its major flavonoids, kaempferol and kaempferol-3-O-glucoside

The ethyl acetate, chloroform extracts, and the two flavonoids kaempferol 1 and kaempferol-3-O-glucoside 2 isolated from whole plants of Thesium chinense Turcz were investigated for their antiinflammatory and analgesic activities. For the antiinflammatory activity, carrageenan-induced hind paw edema and xylene-induced mouse ear edema models, and for the analgesic activity, the acetic acid-induced abdominal constriction test was used. The ethyl acetate extract and two flavonoids showed significant (p<0.05 and p<0.01) and dose-dependent antiinflammatory and analgesic activity. The chloroform extract was inactive in the assay.     

Synthesis and evaluation of the analgesic and anti-inflammatory activity of new 3(2H)-pyridazinone derivatives

A series of 6-substituted-3(2H)-pyridazinone derivatives were synthesized and evaluated for analgesic and anti-inflammatory activities. The structures of these new pyridazinone derivatives were confirmed by their IR, 1H-NMR spectra and elementary analysis. Analgesic and anti-inflammatory activities of the title compounds have been evaluated. Four of the ten tested compounds possessed significant analgesic effects in the phenylbenzoquinone-induced writhing test (PBQ test). The most active derivatives 8a, 8b, 8d, 8e were void of gastric ulcerogenic effect or acute toxicity at the maximal dose (200 mg/kg p.o.). In the carrageenan-induced paw edema model, compound 8d (6- [4- (2-fluorophenyl) piperazin-1-yl]-3(2H)-pyridazinone) showed anti-inflammatory activity similar to that of the standard drug indometacin (CAS 53-86-1). A significant dependence of the anti-inflammatory effect on the substituents was observed; The pharmacological study of these compounds confirms that modification of the chemical group at position 6 of the 3(2H)-pyridazinone ring influences analgesic and anti-inflammatory activities.     

Synthesis,analgesic and anti-inflammatory activities of new methyl-imidazolyl-1,3,4-oxadiazoles and 1,2,4-triazoles

Background

Long-term clinical employment of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with significant side effects including gastrointestinal (GI) lesions and kidney toxicity. In this paper we designed and synthesized new imidazolyl-1,3,4-oxadiazoles and 1,2,4-triazoles by molecular hybridization of previously described anti-inflammatory compounds in the hope of obtaining new safer analgesic and anti-inflammatory agents.

Methods

The target structures were synthesized by preparation of 5-methyl-1H-imidazole-4-carboxylic acid ethyl ester 5. The reaction of hydrazine hydrate with this ester afforded the 5-methyl-1H-imidazole-4-carboxylic acid hydrazide 6 which was converted to target compounds 7-15 according to the known procedures. In silico toxicity risk assessment and drug likeness predictions were done, in order to consider the privileges of the synthesized structures as drug candidates.

Results and discussion

The analgesic and anti-inflammatory profile of the synthesized compounds were evaluated by writhing and carrageenan induced rat paw edema tests respectively. Compounds 8, 9 and 11-13 and 15 were active analgesic agents and compounds 8, 9 and 11-13 showed significant anti-inflammatory response in comparison with control. Compounds 11 and 13 were screened for their ulcerogenic activities and none of them showed significant ulcerogenic activity. The active Compounds 11 and 12 showed the highest drug likeness and drug score.

Conclusions

The analgesic and anti-inflammatory activities of title compounds were comparable to that of standard drug indomethacin with a safer profile of activity. The results revealed that both of oxadiazole and triazole scaffolds can be determined as pharmacophores. The in silico predictions and pharmacological evaluations showed that compounds 11 and 12 can be chosen as lead for further investigations.     

Anti-inflammatory and analgesic activity of novel oral aspirin-loaded nanoemulsion and nano multiple emulsion formulations generated using ultrasound cavitation

The present study investigated the anti-inflammatory and analgesic activities of novel aspirin oil-in-water (O/W) nanoemulsion and water-in-oil-in-water (W/O/W) nano multiple emulsion formulations generated using ultrasound cavitation techniques. The anti-inflammatory activities of nanoemulsion and nano multiple emulsion were determined using the λ-carrageenan-induced paw edema model. The analgesic activities of both nanoformulations were determined using acetic acid-induced writhing response and hot plate assay. For comparison, the effect of pretreatment with blank nanoemulsion and reference aspirin suspension were also studied for their anti-inflammatory and antinociceptive activities. The results showed that oral administration of nanoemulsion and nano multiple emulsion containing aspirin (60 mg/kg) significantly reduced paw edema induced by λ-carrageenan injection. Both nanoformulations decreased the number of abdominal constriction in acetic acid-induced writhing model. Pretreatment with nanoformulations led to a significant increase in reaction time in hot plate assay. Nanoemulsion demonstrated an enhanced anti-inflammatory and analgesic effects compared to reference suspension while nano multiple emulsion exhibited a mild inhibitory effects in the three experimental animal model tests. The results obtained for nano multiple emulsion were relatively lower than reference. However, administration of blank nanoemulsion did not alter the nociceptive response significantly though it showed slight anti-inflammatory effect. These experimental studies suggest that nanoemulsion and nano multiple emulsion produced a pronounced anti-inflammatory and analgesic effects in rats and may be candidates as new nanocarriers for pharmacological NSAIDs in the treatment of inflammatory disorders and alleviating pains.     

Novel 2-(E)-substituted benzylidene-6-(N-substituted aminomethyl)cyclohexanones and cyclohexanols as analgesic and anti-inflammatory agents

Twenty-two new 2-(E)-substituted benzylidene-6-(N-substituted aminomethyl)cyclohexanones (6a–6j) and cyclohexanols (7a–7l) were designed and synthesized. Target compounds were obtained through Stork enamine, Mannich, and Grignard reactions taking cyclohexanone as starting material. The structures were confirmed by the application of IR, ¹H NMR, MS, and HR-MS data. The analgesic activities were evaluated by acetic acid-induced writhing test and hot plate method. The anti-inflammatory activities were assayed by xylene-induced ear swelling and carrageenan-induced paw edema in mice model. All tested compounds showed analgesic and anti-inflammatory capacities in oral administration. Some compounds (6a, 6c, 6h, 6i, 7c, 7h, and 7i) displayed the moderate analgesic activity compared with positive control ibuprofen, and some compounds (6a, 6b, 6d, 6h, 7a, and 7d) exhibited more anti-inflammatory activity than ibuprofen. Among them, compound 6a could be a potential nonsteroidal anti-inflammatory agent with significant analgesic activities and remarkable anti-inflammatory activities. Further research is being conducted.     

Design and synthesis of certain mesoionic sydnonyl styrylketones as potential nonsteroidal antiinflammatory agents

In an attempt to develop effective and safer analgesic anti-inflammatory agents, nine compounds belonging to 4-[1-oxo-3-(substituted aryl)-2-propenyl]-3-(4-methoxyphenyl) sydnones, containing the structural features of mesoionic sydnone and styrylketone, have been designed and synthesized by condensing 4-acetyl-3-(4-methoxyphenyl) sydnone with various substituted aryl aldehydes and characterized by spectral studies. They have been tested for analgesic activity by acetic acid induced writhing in mice and for anti-inflammatory activity by carrageenan induced rat paw edema at 100 mg/kg body weight p.o. The compounds containing furyl and chloro substituents showed highly significant analgesic effect, while those with dimethylamino, chloro and nitro substituents exhibited highly significant anti-inflammatory effect at the end of 3 h. The compounds that showed good analgesic and anti-inflammatory activities were evaluated for ulcerogenicity in rats to assess their gastric side effects at 100 mg/kg body weight p.o. They were found to be less ulcerogenic than the standard drug.     

Analgesic and anti-inflammatory activity of Argyreia speciosa root

Objective:

To study analgesic and anti-inflammatory activities of a methanolic extract (ME) of Argyreia speciosa (AS) root powder.

Materials and Methods:

The study was carried out using male albino mice (20-25 gm) and male wistar rats (100-150gm). The ME was prepared using soxhlet extraction process. The effect of ME of A. speciosa was investigated for analgesic activity using acetic acid-induced abdominal constriction, tail immersion method and hot plate method. The anti-inflammatory activity of ME of AS roots was studied using carrageenan-induced rat paw edema.

Result:

The ME of A. speciosa root was used in pain and inflammation models. The analgesic activity of AS at the dose of (30,100, and 300 mg/kg p.o) showed significant (P<0.01) decrease in acetic acid-induced writhing, whereas ME of A. speciosa at the dose of (100, 300 mg/kg p.o) showed significant (P<0.01) increase in latency to tail flick in tail immersion method and elevated mean basal reaction time in hot plate method. The ME of the A. speciosa at doses (30, 100, and 300mg/kg) showed significant (P < 0.01) inhibition of carrageenan induced hind paw edema in rats.

Conclusion:

The ME of A. speciosa showed significant analgesic and anti-inflammatory activity in mice and rat.     

Potential analgesic,anti-inflammatory and antioxidant activities of hydroalcoholic extract of Areca catechu L. nut

The hydroalcoholic extract of Areca catechu L. (ANE) nut was screened for its analgesic, anti-inflammatory and in vitro antioxidant potential. Three doses of ANE (250, 500 and 1000 mg/kg orally) were tested for analgesic and anti-inflammatory activities. Evaluation of analgesic activity of ANE was performed using hot plate and formalin test in mice. ANE showed maximum increase in hot plate reaction time (56.27%, p < 0.01), while reduced the duration of licking/biting behaviors in first (39.45%, p < 0.05) and second (92.71%, p < 0.01) phases of the formalin test indicating significant analgesic activity. ANE reduced the paw edema considerably (86.79% inhibition after 24 h, p < 0.01) in dose-dependent manner compared to carrageenan-induced rat. In addition, in vitro antioxidant activity of ANE was investigated by total phenolic content (TPC) and hydrogen peroxide assay. The IC₅₀ observed in hydrogen peroxide assay was 83.14 μg/ml and TPC 120.56 ± 21.09 mg QE/g. Altogether, these results suggest that the hydroalcoholic extract of Areca catechu could be considered as a potential analgesic, anti-inflammatory and antioxidant agent.     

Synthesis, analgesic and anti inflammatory activities of some new fenamate analogues

A series of fenamate quinazolinyl analogues, viz acids 6a-d, esters 6e-h, carbohydrazides 7a-d, arylidenes 8a-d, oxadiazol-2-ones 13a-d and oxadiazol-2-thiones 14a-d, have been prepared and screened for their analgesic (acetic acid-induced writhing), anti-inflammatory (carrageenan-induced rat paw edema) activities as well as their ulcerogenic effects. All the final compounds except 7a-d and 8a-d showed good dual activities. Compounds 6a, 6b, 6e, 6f, 13a and 14a showed activities comparable to that of mefenamic acid (CAS 61-68-7) in the acetic acid-induced writhing model as well as in the carrageenan-induced rat paw edema test at a dose level of 100 mg/ kg.Compounds 6a and 6b were highly ulcerogenic, while compounds 6e, 6f, 13a and 14a exhibited the lowest ulcerogenic effects.     

Synthesis of new Mannich bases of arylpyridazinones as analgesic and anti-inflammatory agents

A series of 2-[[4-(substituted-phenyl/ benzyl)-1-piperazinyllmethyl]-6-(4-methoxyphenyl)-3(2H)pyridazinone derivatives was prepared and examined for analgesic and anti-inflammatory activities. The structures of these new pyridazinone derivatives were confirmed by their IR and 1H-NMR spectra and elementary analysis. Among the compounds prepared, 2-[[4-(4-fluorophenyl)-1-piperazinyl]methyl]-6-(4-methoxyphenyl)-3(2H)pyridazinone IVe was found to be a most promising analgesic and anti-inflammatory agent. Compound IVe showed more potent analgesic activity than acetylsalicyclic acid in the phenylbenzoquinone-induced writhing test. Also IVe showed anti-inflammatory activity comparable to that of the standard compound indometacin against the carrageenan-induced paw edema. Side effects of the compounds were examined on gastric mucosa. None of the compounds showed a gastric ulcerogenic effect compared with reference nonsteroidal anti-inflammatory drugs. On the basis of the available data, the structure-activity relationship of the series of 2-[[4-(substituted-phenyl/benzyl)-1-piperazinyl]methyl]-6-(4-methoxyphenyl)-3(2H) pyridazinones is also discussed.     

Antinociceptive effect of Lafoensia pacari A. St.-Hil. independent of anti-inflammatory activity of ellagic acid

This study was performed to determine the antinociceptive and anti-inflammatory activities of ethanolic extract of Lafoensia pacari A. St.-Hil. (PEtExt) stem bark and its fractions using various animal models such as acetic acid-induced abdominal writhing, formalin-induced pain and croton oil-induced ear edema tests. The PEtExt inhibited the acetic acid-induced abdominal writhing, reduced the pain reaction time on both phases of the formalin test and decreased the edema in a dose-dependent manner. Pre-treatment with naloxone did not reverse the antinociceptive effect. Only the ethyl acetate fraction showed antinociceptive and anti-inflammatory effects. Our results also showed that this extract contains compounds with analgesic action independent of anti-inflammatory activity.     

番红花不同药用部位的镇痛和抗炎活性比较研究

目的:扩大名贵药用植物番红花的药用资源,寻找可以替代传统药用部位(柱头)的新药用部位.方法:分别采用醋酸致小鼠扭体和二甲苯致小鼠耳肿胀药理模型,分别以吲哚美辛和地塞米松为镇痛和抗炎药效学实验的阳性对照药,观察番红花球茎、顶芽、侧芽和柱头的乙醇和水提取物的镇痛和抗炎活性.结果:在镇痛实验中,与空白对照组相比,顶芽醇提取物和水提取物、柱头的醇提物和水提物以及侧芽的醇提物在高剂量时(相当于2.0 g生N/kg)都具有显著的镇痛活性(P＜0.05或P＜0.01);球茎的醇提物和水提物、侧芽醇提取物的低剂量和中剂量以及水提物均未见有镇痛活性;在抗炎试验中,与空白对照组相比,番红花柱头醇提物和侧芽醇提物均显示出显著的抗炎活性(P＜0.05或P＜0.01).项芽醇提物在低剂量(相当于0.75 g生药/kg)时也具有显著的抗炎活性(P＜0.05).球茎醇提取物和水提物及顶芽、侧芽和柱头的水提物对二甲苯致小鼠耳肿胀没有显著性影响.结论:以番红花的顶芽、侧芽替代传统药用部位柱头,分别用于镇痛和抗炎作用有潜在的应用价值,值得深入研究.     

Screening of Bauhinia purpurea Linn. for analgesic and anti-inflammatory activities

Objectives:

Ethanol extract of the stem of Bauhinia purpurea Linn. was subjected to analgesic and anti-inflammatory activities in animal models.

Materials and Methods:

Albino Wistar rats and mice were the experimental animals respectively. Different CNS depressant paradigms like analgesic activity (determined by Eddy''s hot plate method and acetic acid writhing method) and anti-inflammatory activity determined by carrageenan induced paw edema using plethysmometer in albino rats) were carried out, following the intra-peritoneal administration of ethanol extract of Bauhinia purpurea Linn. (BP) at the dose level of 50 mg/kg and 100 mg/kg.

Results:

The analgesic and anti-inflammatory activities of ethanol extracts of BP were significant (P < 0.001). The maximum analgesic effect was observed at 120 min at the dose of 100 mg/kg (i.p.) and was comparable to that of standard analgin (150 mg/kg) and the percentage of edema inhibition effect was 46.4% and 77% for 50 mg/kg and 100 mg/kg (i.p) respectively. Anti-inflammatory activity was compared with standard Diclofenac sodium (5 mg/kg).

Conclusion:

Ethanol extract of Bauhinia purpurea has shown significant analgesic and anti-inflammatory activities at the dose of 100 mg/kg and was comparable with corresponding standard drugs. The activity was attributed to the presence of phytoconstituents in the tested extract.     

Synthesis, anti-inflammatory and analgesic activity of some new 4(3H)-quinazolinone derivatives

4(3H)-quinazolinone and pyrazole derivatives have been shown to have analgesic and anti-inflammatory properties. In this study, 14 new 3-methyl-4(3H)quinazolinone derivatives bearing 2-[1'-phenyl-3'-(substituted-phenyl)-2'-propenylidene]hydrazino or 2[5'-(substituted phenyl)-3'-phenyl-2'-pyrazolin-1'-yl] groups have been synthesized with the aim of obtaining new analgesic and anti-inflammatory leads. The structures were elucidated by means of UV, IR, 1H-NMR, 13C-NMR, mass spectroscopy, and elemental analysis data. The anti-inflammatory activities of the synthesized compounds were determined by carrageenan-induced hind paw edema test in mice. All the compounds showed statistically significant effects. For analgesic activity assessment, p-benzoquinone-induced writhing test was applied in mice. The results obtained were in accordance with the anti-inflammatory activity tests.