Anti-inflammatory, analgesic activity and acute toxicity of Sida cordifolia L. (Malva-branca)

Sida cordifolia L. (Malvaceae) is used in folk medicine for the treatment of inflammation of the oral mucosa, blenorrhea, asthmatic bronchitis and nasal congestion. The anti-inflammatory, analgesic effects and acute toxicity of an aqueous extract of S. cordifolia were evaluated in animal models. The extract was prepared using leaves collected before the flowering period. The aqueous extract (AE) showed a significant inhibition of carrageenin-induced rat paw edema at a dose of 400 mg/kg administered orally, but did not block the edema induced by arachidonic acid. The AE also increased the latency period for mice in the hot plate test, and inhibited the number of writhes produced by acetic acid at the oral dose of 400 mg/kg. The aqueous extract of S. cordifolia showed low acute toxicity in mice.     

Sida cordifolia leaf extract reduces the orofacial nociceptive response in mice

In this study, we describe the antinociceptive activity of the ethanol extract (EE), chloroform (CF) and methanol (MF) fractions obtained from Sida cordifolia, popularly known in Brazil as "malva branca" or "malva branca sedosa". Leaves of S. cordifolia were used to produce the crude ethanol extract and after CF and MF. Experiments were conducted on Swiss mice using the glutamate and formalin-induced orofacial nociception. In the formalin test, all doses of EE, CF and MF significantly reduced the orofacial nociception in the first (p < 0.001) and second phase (p < 0.001), which was also naloxone-sensitive. In the glutamate-induced nociception test, only CF and MF significantly reduced the orofacial nociceptive behavior with inhibition percentage values of 48.1% (100 mg/kg, CF), 56.1% (200 mg/kg, CF), 66.4% (400 mg/kg, CF), 48.2 (200 mg/kg, MF) and 60.1 (400 mg/kg, MF). Furthermore, treatment of the animals with EE, CF and MF was not able to promote motor activity changes. These data demonstrate that S. cordifolia has a pronounced antinociceptive activity on orofacial nociception. However, pharmacological and chemical studies are necessary in order to characterize the responsible mechanisms for this antinociceptive action and also to identify other bioactive compounds present in S. cordifolia.     

Analgesic, antiinflammatory and hypoglycaemic activities of Sida cordifolia

Sida cordifolia extracts of the aerial and root parts showed good analgesic, antiinflammatory and hypoglycaemic activities. The ethyl acetate (EA) extract of root (SCR-E) showed comparable antiinflammatory activity with indomethacin and possessed significantly higher activity when compared with that of the methanol extract of the root part (SCR-M). The ethyl acetate extract of both root and aerial parts of Sida cordifolia (SCR-E and SCA-E) showed very good central and peripheral analgesic activities at a dose of 600 mg/kg. The methanol extract of root (SCR-M) was found to possess significant hypoglycaemic activity.     

Pharmacological evaluation of the anxiolytic and sedative effects of Tilia americana L. var. mexicana in mice

The anxiolytic and sedative effects of Tilia americana L. var. mexicana (Schltdl.) Hardin inflorescence extracts and its acute toxicity were tested. Sodium pentobarbital (SP)-induced hypnosis potentiation (SPP), as well as ambulatory activity and anti-anxiety response in three different experimental models were evaluated with hexane and methanol extracts in mice. In order to determine the proper timing of assessments and to identify the most active extract, a 100mg/kg dosage of hexane, ethyl acetate and methanol crude extracts were tested on SPP after 15, 30 and 60min of the administration. Then a dose-response curve was made for the hexane (10-1000mg/kg) and methanol (10-300mg/kg) extracts in all experimental models. Both extracts produced a significant and dose-dependent lengthening in the time of SP, with the methanol extract being more potent than the hexane extract at 60min after administration. Moreover, a significant and dose-dependent attenuation in the anxiety-response in the plus-maze test and exploratory cylinder activity, but also a diminution in the ambulatory activity and in the head dipping response were observed resembling the response to diazepam. Acute toxicity was observed with less dose of methanol extract (LD(50)=375mg/kg) in comparison to the hexane extract (LD(50)>2900mg/kg). Results of the present study shows that Tilia americana var. mexicana possesses depressant activity on the CNS similar to the better-studied species of European Tilia and reinforces its use as anxiolytic and sedative in traditional medicine.     

Pharmacological evaluation of the folklore of Sphenostylis stenocarpa

The pharmacological effects of an aqueous extract of Sphenostylis stenocarpa seed were investigated in albino mice. Acute toxicity testing indicated the LD50 to be 570 mg/kg, i.p. The extract significantly potentiated pentobarbitone-induced sleeping time. Increasing the dose of the extract correspondingly increased the sleeping time up to a dose of 60 mg/kg i.p. The extract did not protect mice from convulsions and death resulting from the administration of strychnine (2 mg/kg, i.p.) or leptazol (100 mg/kg, s.c.).     

The antidiarrhoeal activity of Alchornea cordifolia leaf extract

Diarrhoea is a public health problem in developing countries. It is therefore important and useful to identify plants with antidiarrhoeal activity. Alchornea cordifolia is quoted by many traditional healers as a plant with this activity. The antidiarrhoeal activity of its leaf extract was investigated against castor oil induced diarrhoea in mice, using morphine as the standard reference drug. A significant (p < 0.01) dose related (100 mg/kg, 200 mg/kg, 400 mg/kg, 800 mg/kg) antidiarrhoeal activity of A. cordifolia leaf ethanol extract was observed with 800 mg/kg extract being the most effective. It delayed mouse intestinal transit accelerated by castor oil, inhibited the production of diarrhoeal faeces and modified the fluid and electrolyte transport across the colonic mucosa when administered intraluminally. Phytochemical screening revealed the presence of tannins and flavonoids which may account for the increased colonic water and electrolyte reabsorption, a mechanism suggested for the antidiarrhoeal activity of A. cordifolia.     

Skeletal muscle relaxant action of an aqueous extract of Portulaca oleracea in the rat

The aqueous extract of Portulaca oleracea produced skeletal muscle relaxation in rats following i.p. or oral administration, as assessed by the prolongation of pull-up time. The i.p. route of administration was more effective. When compared with chlordiazepoxide (20 mg/kg, i.p.), diazepam (40 mg/kg, i.p.) and dantrolene sodium (30 mg/kg, oral), the extract (200-1000 mg/kg, i.p.) proved a more effective skeletal muscle relaxant. With 1000 mg/kg i.p., 80% lethality was seen. The LD50 in an acute toxicity test in mice was 1040 mg/kg i.p.     

Effects of Papaver rhoeas extract on the acquisition and expression of morphine-induced behavioral sensitization in mice

In the present study, the effects of a water-alcohol extract of Papaver rhoeas on the acquisition and expression of morphine-induced behavioral sensitization in mice were investigated. The subcutaneous (s.c.) administration of morphine (50 mg/kg) induced locomotor activity in animals, whereas the drug did not show an effect at a dose of 5 mg/kg. On the other hand, intraperitoneal (i.p.) administration of the plant extract (25, 50 and 100 mg/kg) did not show any effect. The locomotor behavioral response was enhanced in mice pretreated with morphine (5 mg/kg, daily x 3 days) alone, indicating that sensitization had developed. Extract (25, 50 and 100 mg/kg, i.p.) administration, 30 min before each of the three daily doses of morphine decreased the development of sensitization. Moreover, intraperitoneal administration of the plant extract (25, 50 and 100 mg/kg) 30 min before the test reduced the expression of morphine-induced behavioral sensitization.The results indicate that administration of the extract of Papaver rhoeas reduced the acquisition and expression of morphine-induced behavioral sensitization in mice.     

Antinociceptive and antidepressant like effects of Securidaca longepedunculata root extract in mice

The aqueous root extract of Securidaca longepedunculata (polygalaceae) was investigated for possible antinociceptive and central nervous system (CNS) effects in mice. Three nociceptive models; acetic acid, formalin and tail-flick tests were used to study the antinociceptive activity. Rectal temperature test was employed as an adjunct to the nociceptive models. The extract at 200 and 400 mg/kg significantly and dose dependently reduced the nociception induced by the acetic acid and in the early phase of formalin test (P<0.05). The extract exerted significant (P<0.05) hypothermic effect in the 15 and 30 min of the rectal temperature test. The antinociceptive and hypothermic effects were partially reversed by naloxone (1mg/kg). The tail-flick test produced an insignificant increase in tail-flick latency at 400 mg/kg after 60 min of the test, but significantly (P<0.05) increase tail-flick latency in the 400mg/kg group of animals pre-treated with naloxone (1 mg/kg) after 120 min of the test. The extract also produced a significant (P<0.05) naloxone reversible antidepressant like effect in the forced swimming test (an animal model of depression). Collectively, these results suggest that the extract possess antinociceptive and antidepressant like effects with possible involvement of opioidergic pathways. The extract at limit dose of 2 g/kg body weight appeared to be safe in oral formulation.     

Analgesic and hepatotoxic effects of Ononis spinosa L

The present study investigated the analgesic and hepatoprotective activities of a water extract of Ononis spinosa L. (OS) in mice. Analgesic activity was based on the pain thresholds measured with the tail-flick test before administration at 30, 90 and 150 min. The results were analysed with one-way variance analysis. The extract of Ononis spinosa showed analgesic activity equivalent to aspirin at 30 and 90 min and even higher than aspirin with the 50 mg/kg dose. At a dose of 100 mg/kg OS showed an analgesic effect equivalent to aspirin at all time points.The hepatoprotective influence of OS on carbon tetrachloride (CCl(4))-induced acute liver toxicity was also studied. The extract had no significant effect on the increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin in CCl(4) treated animals (p > 0.05). Thus, the results reveal that the extract of OS had no hepatoprotective effect on CCl(4)-induced acute liver toxicity.     

The juice of fresh leaves of Boerhaavia diffusa L. (Nyctaginaceae) markedly reduces pain in mice

The decoction or juice of leaves of Boerhaavia diffusa L. (Nyctaginaceae) is used in Martinican folk medicine for its analgesic and anti-inflammatory properties. In the present investigation we studied the acute oral (p.o.) toxicity of a crude extract obtained from a lyophilized decoction (DE) and from the juice (JE) of fresh leaves. We observed no signs of toxicity up to the dose of 5000 mg/kg (p.o.) in mice. At the dose of 1000 mg/kg, neither extract altered sleeping time evoked by the administration of pentobarbital sodium (i.p.). The DE and JE of B. diffusa were assessed in standard rodent models of algesia and inflammation. We investigated the antinociceptive effect of DE and JE in chemical (acetic acid) and thermal (hot plate) models of hyperalgesia in mice. Dipyrone sodium (200 mg/kg), JE (1000 mg/kg) and DE at the same dose (p.o.), produced a significant inhibition of acetic acid-induced abdominal writhing in mice (100, 50 and 47% inhibition, respectively) when compared with the negative control (P<0.001). In the hot-plate test in mice, morphine and JE produced a significant increase in latency during the observation time. The DE, however, only raised the pain thresholds during the first period (30 min) of observation (P<0.05). The extracts of B. diffusa were also investigated for their anti-edematogenic effect on carrageenan-induced edema in mice. However, neither extract inhibited the paw edema induced in mice (P>0.05). In the acetic acid-induced abdominal writhing in mice, pre-treatment of the animals with naloxone (5 mg/kg, i.p.) significantly reversed the analgesic effect of morphine and JE but not that of DE. These data show that the active antinociceptive principle of B. diffusa is present mainly in the juice of fresh leaves and has a significant antinociceptive effect when assessed in these pain models. The mechanism underlying this analgesic effect of fresh leaves of B. diffusa remains unknown, but seems to be related to interaction with the opioid system.     

Anti-inflammatory,analgesic activity and acute toxicity of Glaucium grandiflorum extract

The species of Glaucium have been used in Iranian herbal medicine as laxative, hypnotic, antidiabetic agents and also in the treatment of dermatitis. The anti-inflammatory and analgesic effects of the aerial parts of Glaucium grandiflorum Boiss & Huet (Papaveraceae), a native plant of Iran, were studied using carrageenan induced edema, formalin and hot plate tests. The G. grandiflorum extract at the dose of 200 mg/kg had more edema inhibition than indomethacin at the doses of 10 (P<0.01) and 8 mg/kg (P<0.001) in the carrageenan test. The ED₅₀ (i.p.) in the edema induced by carrageenan was 13.59 mg/kg. In formalin test, the extract (60–90 mg/kg, i.p.) caused graded inhibition of both phases of formalin-induced pain. In hot plate test, the i.p. administration of the extract at the doses of 60, 70, 80 and 90 mg/kg significantly raised the pain threshold at a observation time of 45 min in comparison with control (P<0.001). The extract, at the antinociceptive doses, did not affect motor coordination of animals when assessed in the rotarod model. The 72 h acute LD₅₀ value of this extract after i.p. administration in mice was 797.94 mg/kg.     

Anticonvulsant effect of Uncaria rhynchophylla (Miq) Jack. in rats with kainic acid-induced epileptic seizure.

This study investigated the anticonvulsant effect of Uncaria rhynchophylla (UR) and the physiological mechanisms of its action in rats. A total of 70 male Sprague-Dawley (SD) rats were selected for study. Thirty four of these rats were divided into 5 groups as follows: 1) Control group (n = 6): received intraperitoneal injection (i.p.) of kainic acid (KA, 12 mg/kg); 2) UR1000 group (n = 10), 3) UR500 group (n = 6) 4) UR250 group, received UR 1000, 500, 250 mg/kg i.p. 30 min prior to KA administration, respectively; 5) Contrast group: received carbamazepine 20 mg/kg i.p. 30 min prior to KA administration. Behavior and EEG were monitored from 15 min prior to drug administration to 3 hours after KA administration. The number of wet dog shakes were counted at 10 min intervals throughout the experimental course. The remaining 36 rats were used to measure the lipid peroxide level in the cerebral cortex one hour after KA administration. These rats were divided into 6 groups of 6 rats as follows: 1) Normal group: no treatment was given; 2) Control group: received KA (12 mg/kg) i.p.; 3) UR1000 group, 4) UR500 group, 5) UR250 group, received UR 1000, 500, 250 mg/kg i.p. 30 min prior to KA administration, respectively; 6) Contrast group: received carbamazepine 20 mg/kg i.p. 30 min prior to KA administration. Our results indicated that both UR 1000 and 500 mg/kg decreased the incidence of KA-induced wet dog shakes, no similar effect was observed in the UR 250 mg/kg and carbamazepine 20 mg/kg group. Treatment with UR 1000 mg/kg, 500 mg/kg, or 250 mg/kg and carbamazepine 20 mg/kg decreased KA-induced lipid peroxide level in the cerebral cortex and was dose-dependent. These findings suggest that the anticonvulsant effect of UR possibly results from its suppressive effect on lipid peroxidation in the brain.     

Anticonvulsant properties of the methanolic extract of Cyperus articulatus (Cyperaceae)

The methanolic extract of rhizomes of Cyperus articulatus, a plant used in traditional medicine in Africa and Latin America for many diseases, possesses anticonvulsant activity in mice. This extract protected mice against maximal electroshock (MES)- and pentylenetetrazol (PTZ)-induced seizures. It also delayed the onset of seizures induced by isonicotinic acid hydrazide and strongly antagonized N-methyl-D-aspartate-induced turning behavior. The ED(50) for protection against seizures was 306 (154-541) mg/kg intraperitoneally (i.p.) for the PTZ test and 1005 (797-1200) mg/kg i.p. for the MES test. The ED(50) of methanolic extract against N-methyl-D-aspartate-induced turning behavior was 875 (623-1123) mg/kg i.p. C. articulatus L. methanolic extract protected 54% of mice from seizures induced by strychnine at the dose of 1000 mg/kg i.p. but had no or a moderate effect only against picrotoxin- or bicuculline-induced seizures. With these effects, the rhizome of C. articulatus L. possesses anticonvulsant properties in animals that might explain its use as a traditional medicine for epilepsy in Africa.     

Evaluation of xanthotoxol for central nervous system activity.

Xanthotoxol (XT), 8-hydroxypsoralen, exhibited dose-graded sedative activity in dogs, cats, rats, mice and hamsters. At doses of 5-20 mg/kg intraperitoneally (i.p.) in cats and 3-100 mg/kg orally (p.o.) in dogs, XT blocked predatory mouse/rat killing behavior. In mice, XT (10-300 mg/kg i.p.) exhibited a dose-dependent reduction in locomotor activity but was less potent in this regard than reference diazepam (10-100 mg/kg i.p.). XT in mice (0.1-10.0 mg/kg i.p.) and in hamsters (0.1-10.0 mg/kg p.o.) antagonized amphetamine-induced hypermobility but was less potent than diazepam. XT elevated the electrical threshold in foot-shock-induced fighting behavior in rats. XT (0.1-30.0 mg/kg p.o.) potentiated pentobarbital-induced narcosis in hamsters at otherwise subeffective doses of pentobarbital. Conditioned avoidance responses in rats were not significantly altered with 1-3 mg/kg i.p. and 30-100 mg/kg p.o. doses of XT but 300 mg/kg p.o. blocked both conditioned and unconditioned response. Doses of 100-1000 mg/kg i.p. of XT in mice were used to study 48-h acute toxicity of XT and its LD50 was estimated to be 468 mg/kg. Doses of 10, 40 and 80 mg/kg p.o. were used to study the chronic toxicity of XT in rats for 6 months and no side effects or abnormalities in reproductive activity or endocrine integrity were noted. The F1 generation of rats from 6-month XT-treated parents were free of teratogenic effects.     

Anticonvulsant, analgesic and antipyretic activities of Taxus wallichiana Zucc

Taxus wallichiana Zucc. (Himalayan Yew) is often used in northern areas of Pakistan for the treatment of pyrexia, acute pains and epilepsy. We have investigated certain pharmacological activities of the methanol leaf extract against convulsion, nociception and pyrexia induced in rodents. The aim was to justify and explore its folk uses in these pathological conditions, on scientific basis. The studies were carried out using acetic acid-induced nociception and pentylenetetrazole-induced convulsions in mice, while formalin test and yeast-induced pyrexia in rats. Significant analgesic (67.77 and 74.29%) effect was found in acetic acid-induced model at doses of 100 and 200mg/kg, i.p. respectively. Crude extract exhibited significant (P<0.05) inhibition of the formalin noxious stimulation on both early and late phases of pain by the extracts (100 and 200mg/kg doses). In case of yeast-induced pyrexia model, 200mg/kg dose showed very significant (P<0.01) inhibition while 50 and 100mg/kg dose caused a significant (P<0.05) inhibition. Plant extract has controlled the pentylenetetrazole-induced convulsions in mice. 100 and 200mg/kg i.p doses of the extract significantly (P<0.05) inhibited the mioclonus and clonus while inhibition of tonus and hind limb tonic extension (HLTE) was highly significant (P<0.01). The anticonvulsant activity of this plant has been reported for the first time throughout the whole genus. The observed pharmacological activities provide the scientific basis for the folkloric use of the plant in treating epilepsy, pyrexia and acute pain.     

Evaluation of antinociceptive,antinflammatory activities and phytochemical analysis of aerial parts of Urtica urens L.

The antinociceptive and antiinflammatory activities of the ethanol extract of the aerial part of Urtica urens were determined by experimental animal models. U. urens extract was found to possess significant antinociceptive activity in chemically induced mouse pain models (ED₅₀ 39.3 mg/kg: 17.2–74.5 mg/kg) in the writhing test and 62.8% inhibition of the licking time in the late phase of the formalin test at a dose of 500 mg/kg p.o. and antiinflammatory activity on carrageenan‐induced rat hind paw edema (41.5% inhibition at a dose of 300 mg/kg i.p.). The extract displayed activity neither in the thermal model of pain nor in the topical inflammation model. The major component of the extract was determined as chlorogenic acid (670 mg/1000 g dry weight) and could be partly responsible for this activity. Copyright © 2010 John Wiley & Sons, Ltd.     

Effects of Papaver rhoeas extract on the acquisition and expression of morphine-induced conditioned place preference in mice

In the present study, the effects of water-alcohol extract of Papaver rhoeas on the acquisition and expression of morphine-induced conditioned place preference (CPP) in mice were investigated. Subcutaneous (s.c.) administration of morphine (1, 10 and 20 mg/kg) produced place preference. On the other hand, intraperitoneal (i.p.) administration of the plant extract (25, 50 and 100 mg/kg) did not show any effect. Injection of extract (25, 50 and 100 mg/kg, i.p.) 30 min before the morphine administration decreased the acquisition of morphine CPP. Administration of the plant extract (25, 50 and 100 mg/kg, i.p.) 30 min before the test did not change the expression of morphine-induced CPP. It could be concluded that Papaver rhoeas reduced the acquisition but not the expression of morphine-induced conditioned place preference.     

Hypericum triquetrifolium Turra. extract exhibits antinociceptive activity in the mouse

The aim of the present study was to investigate the antinociceptive activity of Hypericum triquetrifolium Turra. extract. The lyophilized extract was administered to male Swiss mice. Formalin paw test and tail flick tests were used for the evaluation of the antinociceptive activity. Plant extract (10, 25, 50 and 60 mg kg(-1), i.p.) (n = 16-24 for each group) or vehicle (n = 27) was administered 30 min before the subplantar formalin injection. In the tail flick test, mice were examined for latency to withdraw their tails from a noxious thermal stimulus using a tail flick meter (n = 8 for each group). The effects of the extract on sensorimotor performance was also assessed (n = 16-24 for each group). The extract caused a significant dose-related inhibition of the first phase (50, 60 mg kg(-1), i.p.) and second phase (10, 25, 50 and 60 mg kg(-1), i.p.) of formalin induced hindpaw licking. Additionally, the extract administration (50, 60 mg kg(-1), i.p.) increased the tail flick latencies. No significant change was observed in any of the treatment groups in the sensorimotor performance test. The observed antinociceptive activity of the extract may be due to its noradrenaline and serotonin reuptake blocking activity. Moreover, the probable antiinflammatory activity of the extract may play a role in the dose-related inhibition of the second phase of formalin paw test.     

Alteration of lethal effects of gamma rays in Swiss albino mice by Tinospora cordifolia

Tinospora cordifolia is widely used in Ayurvedic medicines. It is known for its immunomodulatory, antihepatotoxic, antistress and antioxidant properties. It has been used in combination with other plant products to prepare a number of Ayurvedic preparations. The present study was undertaken to evaluate the radioprotective effect of an aqueous extract of Tinospora cordifolia (TC) against (60)Co gamma radiation. Oral administration of TC 5 mg/kg body wt to Swiss albino mice 1 h and 15 days prior to whole body radiation exposure (8 Gy) produced a significant protection in terms of survival percentage. After oral administration of TC 10 mg/kg body wt/day to mice 7 days prior to whole body irradiation (8 Gy) there was no mortality until day 13 and 50% of the animals survived until day 30. Mice exposed to radiation (8 Gy) without TC pretreatment exhibited signs of radiation sickness such as anorexia, lethargy, ruffled hair, diarrhoea and these animals died within 14 days of irradiation. The results from the present study suggest that Tinospora cordifolia has a radioprotective effect in Swiss albino mice, thereby enhancing the survival of mice against a sublethal dose of gamma radiation.