In vivo analgesic and anti-inflammatory activities of Rosmarinus officinalis aqueous extracts,rosmarinic acid and its acetyl ester derivative

Abstract

Context: Despite several pharmacological applications of Rosmarinus officinalis L. (Lamiaceae), studies on its analgesic and anti-inflammatory properties have been scarce.

Objective: The aim of this work was to use in vivo models to evaluate the analgesic and anti-inflammatory activities of the aqueous extracts obtained from leaves (AEL) and stems (AES) of Rosmarinus officinalis, as well as its isolated compound – rosmarinic acid (RA). We also prepared and assessed the acetyl ester derivative of RA.

Materials and methods: The analgesic activity was evaluated using abdominal constriction and formalin tests. For the evaluation of the anti-inflammatory effects, carrageenin-induced paw edema in rats were used. The extracts were used at doses of 100, 200 and 400?mg?kg^?1 compounds were tested at 10, 20 and 40?mg?kg^?1.

Results: Orally administered AEL, AES and RA were not significantly active at any of the doses tested during the abdominal constriction test; the acetyl ester derivative of RA displayed significant analgesic activity. In the carrageenin-induced paw edema assay, the acetyl derivative of RA at all the tested doses produced significant anti-inflammatory effects and reduced the number of paw licks in the second phase of the formalin test.

Discussion and conclusion: The results suggest that the analgesic effects of the acetyl derivative of RA operate via a peripheral-mediated mechanism. The acetyl ester derivative of RA is potentially applicable as a new lead compound for the management of pain and inflammation.     

Two new indole alkaloids from Nauclea officinalis

Two new indole alkaloids, naucleactonin A and B, along with two known compounds, naucleficine and nauclefidine, were isolated from the bark and wood of Nauclea officinalis, which has been used as an anti-inflammatory and anti-bacterial agent in folk medicine. Their chemical structures were elucidated by the spectral data, especially 1D and 2D NMR experiments.     

In vitro immunomodulatory activity and in vivo anti-inflammatory and analgesic potential with gastroprotective effect of the Mediterranean red alga Laurencia obtusa

Context: Red algae have been recognized as a rich natural source of compounds possessing interesting biological and pharmacological activities.

Objective: This work investigates anti-inflammatory, analgesic and gastroprotective activities of MeOH/CH₂Cl₂ crude extract and its fractions F1 (50% MeOH) and F2 (80% MeOH) from the whole alga plant Laurencia obtusa Hudson (Rhodomelaceae).

Materials and methods: Anti-inflammatory activity was evaluated in vitro using cytometric bead array (CBA) technology to follow up the secretion of tumour necrosis factor alpha (TNF-α) in lipopolysaccharide activated THP-1 monocytic cells at doses of 10–250?μg/mL and in vivo using carrageenan-induced paw oedema in Wistar rats at doses of 25, 50, 100 and 200?mg/kg. Crude extract and fractions were tested at the doses of 25, 50, 100 and 200?mg/kg for peripheral and central analgesic activity by acetic acid-induced writhing test and hot-plate method, respectively, in Swiss albino mice. Gastroprotective activity was evaluated using HCl/ethanol-induced gastric ulcer test in rats at doses of 25, 50, 100 and 200?mg/kg.

Results: Crude extract, F1 and F2 showed an interesting inhibition of TNF-α secretion with IC₅₀ values of 25, 52 and 24?μg/mL, respectively, and a significant anti-inflammatory activity in vivo (p?< 0.01), 3?h after carrageenan injection, the oedema inhibition was 55.37%, 52.18% and 62.86%, respectively, at the dose of 100?mg/kg. Furthermore, they showed a significant peripheral analgesic activity with 53.79%, 55.92% and 57.37% (p?< 0.01) of writhing inhibition, respectively. However, no significant activity was found in the hot-plate test. An interesting gastroprotective effect was observed with crude extract and its fractions F1 and F2 with a gastric ulcer inhibition of 65.48%, 77.42% and 81.29%, respectively, at the dose of 50?mg/kg.

Discussion and conclusion: These results suggest that L. obtusa might be used as a potential source of natural anti-inflammatory and analgesic agents with gastroprotective effect.     

Antinociceptive and anti-inflammatory activities of Viburnum opulus

Water extract of Viburnum opulus L. (Caprifoliaceae) (VO) leaf was investigated for antinociceptive and anti-inflammatory activities in mice and rats. The tail flick test, acetic acid-induced writhing test, and the carrageenan-induced rat paw edema test were used to determine these effects. Our findings show that VO causes dose related inhibition in acetic acid-induced abdominal stretching in mice. VO inhibited abdominal stretching at 100 and 200?mg/kg. VO showed antinociceptive activity, which was quantified by the tail-flick test at doses of 100 and 200?mg/kg. However, VO did not have an anti-inflammatory effect at these doses. The LD₅₀ of VO was determined as 5.447?g/kg.     

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。     

鄂产竹节参多糖的抗炎、镇痛活性

目的:提取分离竹节参多糖,初步研究其化学组成及评价抗炎镇痛的活性。方法:采用化学法测定竹节参多糖的成分,红外光谱分析其结构;采用二甲苯致耳肿胀模型、腹腔毛细血管通透性试验和小鼠热板、扭体试验分别考察其抗炎、镇痛效果。结果:分析显示竹节参多糖中含有α-吡喃糖环结构;竹节参多糖能够有效延长小鼠痛阈值,减少扭体次数,抑制耳肿胀,降低毛细血管通透性。结论:竹节参多糖为竹节参中抗炎镇痛活性成分之一。     

In vivo anti-inflammatory and analgesic activities of a purified saponin fraction derived from the root of Ilex pubescens

The root of Ilex pubescens (Mao-Dong-Qing in Chinese, MDQ) has been commonly used for treatment of cardiovascular and inflammatory diseases in the Chinese medical system. The current studies aimed to investigate the anti-inflammatory and analgesic effects as well as the underlying mechanisms of a purified saponin fraction (PSF) derived from MDQ. PSF was found to significantly suppress the paw edema of rats induced by histamine given intraperitoneally at dosages ranging from 12.5-100 mg/kg. Meanwhile, PSF given orally at dosages of 200 and 100 mg/kg significantly inhibited acetic acid-induced abdominal writhing response of mice and prolonged the time required for mouse tail flick after exposure to a source of radiant heat. The mechanistic studies showed that cyclooxygenase-2 (COX-2) protein expression in carrageenan-injected paw tissues of rats was markedly attenuated by intraperitoneal injection of PSF at dosages of 12.5 to 100 mg/kg. PSF could also markedly inhibit production of proinflammatory cytokines, especially IL-1 beta, IL-6 and TNF-alpha, but enhance production of anti-inflammatory cytokines of IL-4 and IL-10 in the carrageenan-injected paw tissues in rats. These effects resulted in an overall attenuation of the ratio of proinflammatory/anti-inflammatory cytokines and, ultimately suppression of the paw edema. In conclusion, the current study has demonstrated the in vivo anti-inflammatory and analgesic effects of PSF, and suggested that the molecular mechanisms might be associated with inhibition of the elevated expression of COX-2 protein and the overproduction of the proinflammatory cytokines, as well as augmentation of the anti-inflammatory cytokines IL-4 and IL-10 in the carrageenan-injected paw tissues of rats.     

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...     

Antinociceptive and anti-inflammatory activities of Tabernaemontana catharinensis

In this work we describe the analgesic, anti-inflammatory and toxic activities as well as the phytochemical profile of the ethanol extract from Tabernaemontana catharinensis A. DC. (Apocynaceae) stem bark. Analgesic evaluation was carried out against chemical and thermal stimuli. Anti-inflammatory activity was investigated on carrageenan-induced edema in rats and toxicological studies (LD₅₀) were conducted in mice. Phytochemical analyses were performed by standardized methodology. In an analgesic assay, acetic acid-induced writhings were significantly inhibited by extract doses of 37.5?mg/kg (40.97%), 75?mg/kg (77.70%) and 150?mg/kg (88.98%). A central analgesia was also observed using T. catharinensis extract at all doses tested, particularly noticed at 60 and 90?min following administration. The extract significantly reduced edema development by 30.35% (37.5?mg/kg), 34.46% (75?mg/kg), and 56.42% (150?mg/kg) when assessed 180?min following carrageenan intraplantar injection, demonstrating an effective anti-inflammatory action. The LD₅₀ value was 2200?mg/kg. Phytochemical analyses of ethanol extract from Tabernaemontana catharinensis stem bark showed the presence of alkaloids and terpenoids, which may be responsible for the observed pharmacological activities described in this work.     

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.     

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.     

Antinociceptive and anti-inflammatory effects of isolated fractions from Apium graveolens seeds in mice

The antinociceptive and anti-inflammatory effects of the aqueous and hexane extracts obtained from Apium graveolens L. (Apiaceae) seeds were evaluated. Formalin and xylene-induced ear edema tests were used in mice. The fractions were administered intraperitoneally at doses of 100-500?mg/kg body weight (BW). Both extracts with the xylene-induced ear edema test showed significant anti-inflammatory activity at all doses as compared with control. Only the hexane fraction reduced the nociception produced by formalin solution in the first phase (0-5?min) at 300, 400, and 500?mg/kg BW, and in the second phase (20-30?min) at 500?mg/kg BW. It is concluded that the hexane fraction has major contribution to the overall antinociceptive activity. Both fractions showed remarkable anti-inflammatory effect which supported the traditional use of Apium graveolens in diseases associated with inflammation.     

Evaluation of anti-inflammatory and antinociceptive activities of Murraya exotica

Context:?Leaves of Murraya exotica L. (Rutaceae) are used for the treatment of various disorders such as cough, fever, and infectious wounds, as well as alleviating pains in folk medicine in southern China.

Objective:?The objectives of this study were to investigate the in vivo antinociceptive and anti-inflammatory activities of ethanol (70%) extracts and isolated compounds obtained from the dried leaves of M. exotica.

Materials and methods:?The antinociceptive activities were evaluated with the methods of acetic acid-induced writhing response and hot-plate latent pain response test. Carrageenan induced hind paw edema, xylene induced ear edema, and a rat knee osteoarthritis model were employed to measure the anti-inflammatory activities. The compounds were isolated using column chromatography and thin-layer chromatography, and the structures identified by ¹H NMR, ¹³C NMR, MS, and IR.

Results:?The ethanol (70%) extracts significantly decreased in the acetic acid-induced writhing response; increased in hot-plate latency; suppressed xylene induced ear swelling and the carrageenan-induced paw edema effectively. In the rat knee osteoarthritis model, the treatment of the ethanol (70%) extracts resulted in a significant increase in the activity of superoxide dismutase, an inhibition on inducible nitric oxide synthase activity, and a decrease in the contents of interleukin-1β and tumor necrosis factor-α of the rat serum. Following this, we explored the components of the ethanol (70%) extracts and isolated six known coumarins, including murracarpin, which exhibited the most potential in antinociceptive and anti-inflammatory activities.

Discussion and conclusion:?M. exotica displayed remarkable antinociceptive and anti-inflammatory activities.     

盐藻多糖体内抑菌及抗炎作用的研究

目的观察盐藻多糖体内抑菌和抗炎作用。方法通过小鼠腹腔注射感染金黄色葡萄球菌,考察盐藻多糖的体内抗菌作用;通过巴豆油致小鼠耳廓炎性肿胀和醋酸致小鼠腹腔通透性增加,考察盐藻多糖的体内抗炎作用。结果盐藻多糖100和200 mg/kg剂量组能显著增加感染金黄色葡萄球菌小鼠24 h内的存活数,显著抑制巴豆油所致的小鼠耳廓炎性肿胀;盐藻多糖50,100和200 mg/kg剂量组均能显著抑制醋酸引起的小鼠腹腔通透性的增加。结论盐藻多糖具有一定的体内抑菌和抗炎作用。     

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 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.     

Synthesis and anti-inflammatory and analgesic activities of 2,4-di-n-butyl-3,5-diarylimino-1,2,4-thiadiazolidines

Ten 1,2,4-thiadiazolidines were synthesized and screened for their anti-inflammatory and analgesic activities. Butyl isothiocyanate was used as a starting material. Several compounds showed significant anti-inflammatory and analgesic activities. The unsubstituted and o-methyl, p-acetoxy and o-chloro substituted compounds were found to be more potent anti-inflammatory and analgesic agents than the other compounds.     

Analgesic and anti-inflammatory activities of Nicotiana rustica total extract

The antinociceptive and anti-inflammatory activities of Nicotiana rustica Linn. (Solanaceae) total extract (NRTE) have been studied using chemical and thermal models in mice. NRTE was obtained by methanol extraction of dried leaves of N. rustica and was administered intraperitoneally at doses of 2.5, 5, 8.5, and 12?mg/kg body wt (bw). It showed significant protective effects against chemical stimuli in the acetic acid and formalin tests. The extract also showed an inhibitory effect in xylene-induced ear edema compared with the reference drug, diclofenac, and produced a significant increase of the latency time of the reaction in the hot-plate test. Furthermore, the antinociceptive effect of NRTE (at a dose of 12?mg/kg bw) was suppressed by naloxone (a non-specific antagonist of opioid receptors) in hot-plate and formalin tests. This is the first report on the analgesic properties of this plant. The extract might act through an opioid-mediated mechanism. These findings suggest that central and peripheral mechanisms are both involved in the analgesic and the anti-inflammatory effects of N. rustica.     

Antinociceptive,anti-inflammatory,and antioxidant properties of Phoradendron piperoides leaves

Phoradendron piperoides (Kunth) Trel. (Viscaceae) is a parasitic plant widely distributed in regions of the Brazilian northeast. Different species of Phoradendron are used in folk medicine for the treatment of cough, influenza, gastrointestinal and female disorders, and pain. In order to evaluate the actions of this plant, studies were performed on antinociceptive, anti-inflammatory, and antioxidant activities. The methanol extract (ME) and dichloromethane, ethyl acetate, and methanol partitions of P. piperoides leaves were used in the following experiments. Oral treatment with the ME elicited inhibitory activity (p?<?0.01) on the acetic acid effect at 100 (32.08%), 200 (34.46%), and 400?mg/kg (49.50%). P. piperoides ME reduced the formalin effect at the second phase (200 and 400?mg/kg, p?<?0.05); however, the ME did not elicit any inhibitory effect on the hot-plate test. Edema formation induced by carrageenan was reduced (p?<?0.05) with the ME by 28% (200?mg/kg) and 33% (400?mg/kg). ME, dichloromethane, ethyl acetate, and methanol partitions reacted with the DPPH radical and reduced the DPPH radical by 94.5, 37.2, 77.2, and 95.7%, respectively. ME, ethyl acetate, and methanol partitions exhibited low IC₅₀ values.