Synthesis and anti-inflammatory and analgesic activities of phenoxyalkanoic acid derivatives

The synthesis of phenoxyalkanoic acid derivatives and their anti-inflammatory and analgesic activities are described. Analysis of structure-activity relationships shows that in trichlorophenoxy derivatives anti-edematous potency is associated with the presence of 1-thiopropyl moiety and 2 or 4-aminopyridyl moiety at R′ position contributes to the analgesic activity.     

The antinociceptive and anti-inflammatory effects of Salvia officinalis leaf aqueous and butanol extracts

Context: The leaf of sage Salvia officinalis L. (Lamiaceae) is reputed in the folk medicine of Arabia, and Jordan in particular, to relieve pain associated with gastrointestinal disturbance.

Objectives: Evaluation of the antinociceptive and anti-inflammatory activities of aqueous and butanol extracts of S. officinalis leaf.

Materials and methods: The analgesic effects of the aqueous extract (10, 31.6, 100, 316, 1000?mg/kg) and butanol extract (10, 31.6, 100, 316?mg/kg) were studied using the hot-plate test for mice and the formalin-induced paw licking in rats. The effects were compared to those of morphine and the influence of naloxone on these effects was also evaluated. The same concentrations of both extracts were used to evaluate their anti-inflammatory effects using the cotton pellet granuloma and carrageenan-induced paw edema in rats.

Results: The aqueous extract (10, 31.6, 100, 316, 1000?mg/kg) and butanol extract (10, 31.6, 100, 316?mg/kg) caused analgesic effect in the hot-plate latency assay as well as in early and late phases of formalin-induced paw licking in rats. These effects were reduced by the opioid receptor antagonist, naloxone (5?mg/kg). The same range of doses of both extracts caused dose-dependent inhibition of carrageenan-induced paw edema in rats as well as inhibition of cotton pellet granuloma.

Discussion and conclusion: These observations suggest that the sage leaf aqueous and butanol extracts have analgesic and anti-inflammatory effects, confirming the traditional use of this plant for pain alleviation.     

Synthesis and anti-inflammatory and analgesic activities of pyridyloxy- and phenoxyalkanoic acid derivatives

Synthesis of pyridyloxy-, pyridyloxyphenoxy- and phenoxylphenoxyalkanate derivatives and their anti-inflammatory and analgesic activities were investigated. Analysis of structure-activity relationships showed that in pyridyloxyalkanoic acid derivatives anti-edematous potency was associated with the presence of chlorophenoxypropionic acid moiety and 2-nitrated methyl propionates contributed to the analgesic activity.     

In vivo anti-inflammatory and analgesic activities of strictosamide from Nauclea officinalis

Context: Strictosamide is the main representative constituent of Nauclea officinalis Pierre ex Pitard (Rubiaceae), which has been used for a long time in China to treat diseases related to infection and inflammation, but its pharmacological activities are not well studied.

Objective: This work evaluates the anti-inflammatory and analgesic activities of strictosamide by in vivo experiments.

Materials and methods: The anti-inflammatory activity was assessed in mice by models of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema, acetic acid-elevated vascular permeability, and carboxymethylcellulose sodium (CMC–Na)-induced leukocyte migration. The analgesic activity was estimated in mice using acetic acid-induced writhing and hot-plate tests. Compound was injected to mice twice a day for 3?d at doses of 10, 20, and 40?mg/kg.

Results: At 20 and 40?mg/kg, strictosamide obviously decreased the TPA-induced mice ear edema (24.7 and 28.1% inhibition, respectively), and significantly inhibited acetic acid-stimulated peritoneal vascular permeability in mice (23.3 and 33.4% inhibition, respectively). It also significantly decreased the leukocytes in the mice peritoneal cavity induced by CMC–Na at all the tested doses (46.0, 49.1, and 58.7% inhibition, respectively). To acetic acid-induced writhing test in mice, strictosamide markedly prolonged the pain latency at 20 and 40?mg/kg and decreased the writhing counts at 40?mg/kg (49.7% inhibition). However, it did not obviously improve the pain threshold of mice in hot-plate test.

Discussion and conclusion: Strictosamide may have important effects on inflammation and inflammatory pain. The results provide scientific support for the role of strictosamide in the use of N. officinalis to treat inflammatory diseases.     

Xanthone-rich dichloromethane fraction of Securidaca inappendiculata,the possible antirheumatic material base with anti-inflammatory,analgesic, and immunodepressive effects

Context: Securidaca inappendiculata Hassk. is an traditional Chinese medicine curing rheumatoid arthritis, but there is a lack of reports on material base research.

Objective: To find the active fraction of S. inappendiculata contributing the most to antirheumatic activity.

Materials and methods: Prior to assays in vivo, mice were treated with different fractions from S. inappendiculata for 5?d at doses relative to 10, 5, and 2.5?g/kg of crude drug. Hot plate test and carrageenan-induced paw edema test were used to investigate analgesic and anti-inflammatory activities. PGE₂ levels in inflammatory paws were determined by a colorimetric method. Carbon clearance test in vivo and lymphocyte transformation test in vitro were employed to assess the immune regulation activity. HPLC was used to explore the main compounds in the active fraction.

Results: All the fractions, especially the dichloromethane fraction (SID), alleviated inflammation. High dose of SID (112?mg/kg) inhibited paw swelling by 63.1%, and decreased PGE₂ level to 38?ng/mL. The ethyl acetate fraction (SIE) and SID suppressed the carbon clearance rate (K?=?0.044, 0.038 for high dose) efficiently. All fractions hindered the transformation and proliferation of lymphocyte, and prolonged the reaction time of rats in the hot plate test. The concentrations of two typical xanthones: 2-hydroxyl-1,7-dimethoxyl-xanthone and 1,7-dihydroxyl-xanthone in SID were 0.93% and 1.19%, respectively, by HPLC analysis.

Conclusion: SID exhibited significant anti-inflammatory, analgesic, and immunodepressive effects in vivo and vitro, and deemed as the main material base for the antirheumatic activity.     

RP-HPLC法测定迷迭香中鼠尾草酸和迷迭香酸的含量

目的建立高效液相色谱法同时测定迷迭香药材中鼠尾草酸和迷迭香酸的含量。方法运用PhenomenexC18（250 mm×4.60 mm,5μm）为分析柱;柱温30℃;流动相为乙腈（A）-0.1%磷酸（B）梯度洗脱：0～10min,25%A,10～15 min：25%～75%A,15～25 min：75%A;流速1.0 mL min^-1;检测波长284 nm。结果迷迭香酸和鼠尾草酸与其他组分的分离效果好,两者分别在0.046 55～1.862 0μg和0.372 7～14.908μg呈良好的线性关系（r值为0.999 94和0.999 97）,平均回收率分别为99.0%（RSD=1.1%,n=9）和98.1%（RSD=1.5%,n=9）。结论该测定方法简便、准确、重现性好,方便了迷迭香药材中鼠尾草酸和迷迭香酸的含量测定。     

Isolation and anti-inflammatory activity of colchicinoids from Gloriosa superba seeds

Gloriosa superba L. (Liliaceae) seeds, known as “kalihari” (Hindi), were phytochemically investigated for colchicine (well known for gout treatment) and other related alkaloid content. Colchicine, 2- demethylcolchicine, 3-demethylcolchicine, and N-formyl-N-deacetylcolchicine were alkaloids isolated from the seeds. The isolated samples have been standardized for their purity with respect to the reference standard using HPLC. The structures were confirmed by NMR spectroscopy and were analyzed by spiking them along with colchicine reference by HPLC. The purity of colchicine, 2- demethylcolchicine, 3- demethylcolchicine and N-formyl-N-deacetylcolchicine were 99.82, 96.78, 98.71, and 98.13% respectively. The compounds were subjected to an anti-inflammatory study by using the formaldehyde inflammagen-induced inflammation model. Oral administration of colchicine at 2, 4, and 6?mg/kg body weight resulted in 48.9, 68.7, and 79.1% inhibition respectively, while 30.9% inhibition was seen in the phenylbutazone 100?mg/kg treated group once daily for a period of 4 days. The results clearly indicated that the colchicine is more effective as an anti-inflammatory agent compared with phenylbutazone, the standard drug used in the study, whereas the oral administration of 6?mg/kg body weight of 2- demethylcolchicine, 3-demethylcolchicine and N-formyl-N-deacetylcolchicine showed very poor activity (41.6, 40.4, and 41.1% activity respectively).     

Synthesis and evaluation of some gastrointestinal sparing anti-inflammatory aminoethyl ester derivatives of naphthalene-based NSAIDs

To overcome the local gastric toxicity associated with use of common non-steroidal anti-inflammatory drugs (NSAIDs), some aminoalcohol esters of NSAIDs bearing structural resemblance to the aminoalcohol ester class of anticholinergics were specially designed and synthesized. Besides blocking the acidic carboxyl group to overcome the local gastric irritation, the anticholinergic activity was incorporated with the expected advantage of reducing the gastric toxicity by decreasing gastric acid secretions and motility. Derivatives of naproxen and 6-methoxy-2-napthylacetic acid (6-MNA) were synthesized. The hydrolysis studies in buffers revealed the majority of the compounds to be sufficiently stable with a high enzymatic susceptibility in 80% human serum. Most of the derivatives exhibited a fairly good anticholinergic action against acetylcholine with a significant reduction in ulcerogenicity while retaining the anti-inflammatory potency of the parent drug. The combination of anti-inflammatory and anticholinergic activities, with a simultaneous reduction of the acidic character, may lead to development of therapeutically better compounds than the parent NSAIDs for long-term oral anti-inflammatory therapy.     

Synthesis of new imidazolyl acetic acid derivatives with anti-inflammatory and analgesic activities

We synthesized 2-(4-(4-fluorobenzylidene)-2-(4-fluorophenyl) 5-oxo-4,5-dihydroimidazol-1-yl) acetic acid 3. Chlorination afforded the chloro derivative 4, which reacted with different amines and hydrazine to afford compounds 5–8. Pyrazole, pyrazolone, and thiazolidinone derivatives were also synthesized from Imidazol-1-ylacetic acid hydrazide 8 to give compounds 9–12. Compounds were then evaluated for their anti-inflammatory activity against carrageenan-induced rat paw edema and their analgesic activity using the writhing test in albino mice. Compounds 5, 9, 10, 12 exhibited maximum anti-inflammatory activity, and all the compounds inhibited writhing, with 10 and 12 being two times more effective than the reference standard.     

病毒清的抗炎解热与免疫增强作用

灌胃给予病毒清 (BingDuQing ,BDQ) 0 5 5、1 1 0、2 2 0 g/kg显著抑制小鼠二甲苯性耳肿胀 ,此剂量连续给药 7d ,能提高小鼠体内碳粒廓清能力和绵羊红细胞诱导的血清溶血素抗体水平。大鼠灌胃给予BDQ 0 4 0、0 80、1 60 g/kg能显著抑制角叉菜胶性足肿胀和干酵母性发热时体温的升高。家兔灌胃给予BDQ 0 2 0、0 4 0、0 80g/kg可降低伤寒菌苗致热时的体温     

六应丸抗炎和镇痛活性的实验研究

目的：观察六应丸的抗炎和镇痛作用,为其在临床应用提供实验依据。方法：采用醋酸致小鼠扭体模型和热刺激致疼痛模型,考察其镇痛活性;采用二甲苯所致的小鼠耳肿胀和酵母所致大鼠足趾肿胀,考察其抗炎作用,并和六神丸的疗效进行比较。结果：六应丸能有效抑制醋酸引起的小鼠扭体反应、二甲苯所致的小鼠耳肿胀和酵母所致大鼠足趾肿胀,其抗炎镇痛作用与六神丸无显著差异。结论：六应丸具有显著的抗炎镇痛作用。     

In vivo evaluation of analgesic,anti-inflammatory,and neuropharmacological activities of the chemical constituent from Nepeta clarkei

Archives of Pharmacal Research - The plant species of genus Nepeta are used to treat various human diseases and for ornamental purposes as well. Nepethalate B (1) was isolated as a result of...     

山桔叶醇提物抗炎镇痛作用的研究

目的 观察山桔叶醇提物(GPE)对小鼠的抗炎镇痛作用.方法 通过二甲苯致小鼠耳廓肿胀、0.6％冰乙酸致小鼠腹腔毛细血管通透性、1％角叉菜胶致小鼠足肿胀及用小鼠棉球肉芽肿法观察GPE的抗炎作用;通过冰乙酸致小鼠扭体反应和热板致小鼠疼痛法观察GPE的镇痛作用.结果 GPE高、中、低剂量均可显著抑制二甲苯致小鼠耳廓肿胀的肿胀度、1％角叉菜胶致小鼠的足肿胀、0.7％冰乙酸致小鼠的扭体反应次数;GPE高、低剂量可显著抑制冰乙酸致小鼠腹腔毛细血管通透性的增高;GPE高、中剂量均可抑制角叉菜胶致小鼠足肿胀中PGE2的渗出及小鼠棉球肉芽肿的重量,可增高热板致小鼠疼痛的痛阈值.结论 GPE对小鼠有抗炎镇痛的作用.     

Mechanistic assessment of the analgesic,anti-inflammatory and antipyretic actions of Dalbergia saxatilis in animal models

Context: Aqueous root extract of Dalbergia saxatilis, Hook, f., (Leguminosae) (DS) is reported useful for toothache, pains, and fever, but not scientifically proven.

Objective: This study determined its effectiveness in pain, inflammation, and fever, applying scientific models.

Materials and methods: Swiss mice or Sprague–Dawley rats (n?=?5) were pretreated with distilled water, DS (100 or 200?mg/kg), or standard drug for 30?min. The analgesic activity was measured by acetic acid writhing, tail flick, tail immersion, tail clip, hot plate, and formalin pain tests; anti-inflammatory effects were determined via carrageenan and dextran rat paw oedema tests; antipyretic activity was measured by Escherichia coli lipopolysaccharide (ECL) and turpentine in rabbits, and d-amphetamine sulphate (d-AS) pyrexia test in rats.

Results: Writhing frequency inhibition was produced by 200?mg/kg DS (33.10%), aspirin (38.19%) and morphine (93.68%). Unlike morphine, DS did not produce significant prolongation of the reaction times in the hot-plate, tail immersion, tail flick, and tail clip tests. In the first and second phases of formalin test, respectively, % inhibition was: 200?mg/kg DS (25.70% and 0%), aspirin (4.76% and 67.33%), morphine (81.42% and 66.11%); for carrageenan and dextran tests, significant difference was recorded between 200?mg/kg DS and control up to 6?h. Significant reduction in ECL, turpentine and d-AS pyrexia was recorded at 100 and 200?mg/kg DS.

Conclusion: DS produces mild non-steroidal analgesic and anti-inflammatory, as well as significant antipyretic actions involving cyclooxygenase, α₂ adrenoceptor and interleukin-1 β1 due to any of glycosides, saponins or phenolic tannins.     

Combining anticholinergic and anti-inflammatory activities into a single moiety: a novel approach to reduce gastrointestinal toxicity of ibuprofen and ketoprofen

With the aim of reducing the local gastric irritation associated with non-steroidal anti-inflammatory drugs, a series of N,N-disubstituted aminoalcohol ester derivatives of ibuprofen and ketoprofen were synthesized and evaluated. The esters were specially designed to possess the anticholinergic activity in the intact form and exhibit the anti-inflammatory action after hydrolysis to the respective parent drug. The rationale being that besides blocking the acidic carboxylic group of the parent drug, the existence of the anticholinergic effect in the intact molecule would further aid in reducing the gastrointestinal mucosal damage by decreasing the gastric secretions and motility. All the ester derivatives were found to be stable in acidic and basic buffers. The synthesized derivatives, with experimentally proven good anti-inflammatory and anticholinergic activities, showed significant reduction of ulcerogenicity in the stomach. These results are attributed to the acquired anticholinergic activity with a simultaneous reduction of acidic character compared to the parent compounds. The study offers a new strategy for design and development of compounds with safer therapeutic profile for long-term treatment of inflammation-associated disorders.     

多根乌头不同部位提取物的急性毒性与抗炎镇痛活性的研究

目的 研究多根乌头不同部位提取物的急性毒性与抗炎镇痛活性.方法 ig给予小鼠不同浓度的多根乌头提取物,采用改进寇氏法计算小鼠的半数致死量(LD5o);采用二甲苯致小鼠耳廓肿胀与乙酸致小鼠扭体模型来考察其抗炎镇痛活性.结果 多根乌头的水、环己烷、乙酸乙酯与乙醇提取物对小鼠的LD50分别为1.04、0.65、0.38、1.48 g·kg-1;乙酸乙酯提取物对小鼠耳廓肿胀的抑制率为32.75％、扭体抑制率为66.67％,均为最大.结论 多根乌头的乙酸乙酯提取物有较大的毒性,但其抗炎镇痛活性最强.     

A pyrroloquinazoline derivative with anti-inflammatory and analgesic activity by dual inhibition of cyclo-oxygenase-2 and 5-lipoxygenase.

In a previous study, we reported a new pyrroloquinazoline derivative, 3-(4'-acetoxy-3',5'-dimethoxy)benzylidene-1,2-dihydropyrrolo[2,1-b]quinazoline-9-one (PQ), which inhibited human purified 5-lipoxygenase activity and prostaglandin E2 release in lipopolysaccharide-stimulated RAW 264.7 cells. In the present work, we show that PQ inhibits cyclo-oxygenase-2 activity in intact cell assays (human monocytes) and purified enzyme preparations (ovine isoenzymes) without affecting cyclo-oxygenase-1 activity. This behaviour was confirmed in vivo by using the zymosan-injected mouse air pouch model, where PQ caused a marked reduction in cell migration and leukotriene B4 levels at 4 h, as well as inhibition of prostaglandin E2 levels without affecting cyclo-oxygenase-2 expression at 24 h after zymosan stimulation. In addition, oral administration of this compound significantly reduced carrageenan-induced mouse paw oedema and phenyl-p-benzoquinone-induced writhings in mice. These results indicate that oral PQ exerts analgesic and anti-inflammatory effects, which are related to dual inhibition of cyclo-oxygenase-2 and 5-lipoxygenase activities.     

In vivo antiplasmodial activities of aqueous extract of Bridelia ferruginea stem bark against Plasmodium berghei berghei in mice

Context: Bridelia ferruginea Benth (Euphorbiaceae) is an indigenous medicinal plant in Nigeria. It is usually a gnarled shrub which sometimes reaches the size of a tree in suitable condition. Decoctions of parts of this plant have been employed in ethno medicine in many parts of Africa for treatment of many ailments including malaria fever.

Objective: In vivo antiplasmodial activity of aqueous stem bark extract of BF was investigated against Plasmodium berghei-infected mice.

Materials and methods: The aqueous stem bark extract of BF (100–400?mg/kg) was administered orally to P. berghei-infected mice in both early and established models of antiplasmodial studies.

Results: The extract exhibited significant (p?<?0.05) antiplasmodial activity in early and established infection tests with a considerable mean survival time comparable to that of chloroquine, 10?mg/kg. The oral LD₅₀ obtained was greater than 5000?mg/kg in mice.

Discussion and conclusions: The findings show that aqueous stem bark extract of Bridelia ferruginea possesses considerable antiplasmodial activity which can be developed in malaria therapy.     

Antimalarial,antiplasmodial and analgesic activities of root extract of Alchornea laxiflora

Context: Alchornea laxiflora (Benth.) Pax. &; Hoffman (Euphorbiaceae) root decoctions are traditionally used in the treatment of malaria and pain in Nigeria.

Objective: To assess the antimalarial, antiplasmodial and analgesic potentials of root extract and fractions against malarial infections and chemically-induced pains.

Material and methods: The root extract and fractions of Alchornea laxiflora were investigated for antimalarial activity against Plasmodium berghei infection in mice, antiplasmodial activity against chloroquine sensitive (Pf 3D7) and resistant (Pf INDO) strains of Plasmodium falciparum using SYBR green assay method and analgesic activity against experimentally-induced pain models. Acute toxicity study of the extract, cytotoxic activity against HeLa cells and GCMS analysis of the active fraction were carried out.

Results: The root extract (75–225?mg/kg, p.o.) with LD₅₀ of 748.33?mg/kg exerted significant (p?P. berghei infection in suppressive, prophylactive and curative tests. The root extract and fractions also exerted moderate activity against chloroquine sensitive (Pf 3D7) and resistant (Pf INDO) strains of P. falciparum with the ethyl acetate fraction exerting the highest activity with IC₅₀ value of 38.44?±?0.89?μg/mL (Pf 3D7) and 40.17?±?0.78?μg/mL (Pf INDO). The crude extract was not cytotoxic to HeLa cells with LC₅₀ value >100?μg/mL. The crude extract and ethyl acetate fraction exerted significant (p?Discussion and conclusions: These results suggest that the root extract/fractions of A. laxiflora possess antimalarial, antiplasmodial and analgesic potentials and these justify its use in ethnomedicine to treat malaria and pain.     

镰形棘豆总提取物的镇痛抗炎作用

目的研究藏药镰形棘豆总提取物的镇痛抗炎活性。方法使用小鼠扭体法和热板法观察镰形棘豆总提取物的镇痛效应,确定镇痛类型;采用小鼠耳廓肿胀法和大鼠棉球肉芽肿胀法观察镰形棘豆总提取物的抗炎效应。结果镰形棘豆总提取物经灌胃给药可明显减少由醋酸引起的小鼠扭体次数(P<0.05),但是不能明显提高小鼠热刺激的痛反应时间;可明显减轻二甲苯致小鼠耳廓肿胀程度和模型大鼠肉芽组织的增生。结论镰形棘豆具有良好的外周镇痛活性和抗炎活性。