Antinociceptive and anti-inflammatory effects of the aerial parts of Artemisia dracunculus in mice

Context: Tarragon (Artemisia dracunculus L., Asteraceae) is an ancient herb, which is widely used as a medicine, flavoring, or fragrance.

Objective: To determine the antinociceptive and anti-inflammatory effects of aerial parts of tarragon, we investigated the effects of ethanolic extract of the plant in adult male Balb/c mice.

Materials and methods: Antinociceptive activity was determined using formalin, hot-plate, and writhing tests. The effect of the ethanolic extract on acute inflammation was evaluated by xylene-induced ear edema in mice. The ethanolic extract was administered at doses of 5, 10, 50, and 100?mg/kg, i.p. The control group received saline as vehicle of ethanolic extract.

Results: Our results showed that the ethanolic extract (50 and 100?mg/kg) decreased both phases of pain in the formalin test (ED₅₀?=?109.66 and 87.13?mg/kg, respectively). In the hot-plate test, the extract (50 and 100?mg/kg) increased pain threshold during 60?min (ED₅₀?=?81.03?mg/kg). The extract (50 and 100?mg/kg) exhibited antinociceptive activity against acetic acid-induced writhing (ED₅₀?=?66.99?mg/kg). The extract (50 and 100?mg/kg) showed significant activity in the xylene ear edema test (ED₅₀?=?78.20?mg/kg). Pretreatment of the animals with naloxone decreased the analgesia induced by the extract in hot-plate and formalin tests; therefore, opioid receptors may be involved, at least partly, in the analgesic effect of tarragon extract.

Discussion and conclusion: The results suggested that tarragon have significant analgesic and anti-inflammatory effects in mice, and, therefore, further studies are required to evaluate these effects and additional potential of the plant.     

Antinociceptive effect of methanol extract of Capparis ovata in mice

Context: Capparis ovata Desf. (Capparaceae) grows widely in Turkey. Flower buds and fruits of the plant are used in folk medicine for their analgesic, antirheumatismal, and diuretic effects.

Objective: This study evaluated the possible antinociceptive effect of the methanol extract of C. ovata (CME) in mice.

Materials: The antinociceptive effect of methanol extract, prepared with the C. ovata flower buds, was studied at the doses of 50, 100, and 200?mg/kg (i.p.) using tail-immersion, hot-plate, and writhing tests in mice. Morphine sulfate (5?mg/kg; i.p.) and dipyrone (100?mg/kg; i.p.) were used as reference analgesic agents. Naloxone (5?mg/kg; i.p.) was also tested.

Results: It was observed that the C. ovata extract had a significant antinociceptive effect in these tests. In the hot-plate and tail-immersion test results, the doses of 50, 100, and 200?mg/kg increased the percentage of the maximum possible effect (MPE%) value for nociception significantly according to the control value (P?<?0.001). All doses of the extract decreased the number of acetic acid-induced abdominal constrictions in mice when compared with control group (P?<?0.001). These effects were inhibited by pretreatment with naloxone.

Discussion and conclusion: Based on the results obtained, it can be concluded that CME is a potentially antinociceptive agent which acts as both at the peripheral and central levels.     

Antinociceptive activity of Ligusticum porteri preparations and compounds

Context: The roots and rhizomes of Ligusticum porteri Coulter &; Rose (Apiaceae) are widely used in Mexican folk medicine for several purposes, including painful complaints.

Objective: The main goal of this work was to demonstrate the analgesic action in mice of some preparations and major compounds from L. porteri.

Materials and methods: The extracts, aqueous (AE) and organic (OE), the essential oil (EO) and major compounds (10–316?mg/kg) from L. porteri were evaluated as potential antinociceptive agents using the acetic acid-induced writhing and hot plate tests in ICR mice.

Results: All preparations tested exhibited significant antinociceptive effect in the two animal pain models selected. AE and EO were more effective in the writhing test while OE had a better effect in the hot-plate model. On the other hand, Z-ligustilide (1) provoked an increment in the latency period to the thermal stimuli in the hot-plate test at a dose of 31.6?mg/kg, and a decrease in the number of abdominal writhes at 10?mg/kg. Z-3-butylidenephthalide (2) induced a dose-dependent antinociceptive action in the hot-plate assay; this compound was also effective for controlling the pain provoked by chemical irritation at the doses of 10 and 31.6?mg/kg. Finally, diligustilide (3) inhibited the number of writhing responses at all doses tested but was inactive in the hot-plate model.

Conclusion: The present investigation provides in vivo evidence supporting the use of L. porteri to treat painful conditions in folk medicine.     

Anti-inflammatory and antinociceptive activities of Homalium letestui

Abstract

Context. Homalium letestui Pellegr (Flacourtiaceae) is used in various decoctions traditionally by the Ibibios of the Niger Delta of Nigeria to treat stomach ulcer, malaria and other inflammatory diseases, as well as an aphrodisiac.

Objective: To investigate the anti-inflammatory and antinociceptive activities of the stem extract of the plant.

Materials and methods: The ethanol stem extract (500, 750, 1000?mg/kg, i.p.) of H. letestui was investigated for anti-inflammatory activity using carrageenan, egg albumin-induced and xylene-induced ear edema models and analgesic activity using acetic acid-induced writhing, formalin-induced paw licking and thermal-induced pain models. The ethanol extract was administered to the animals orally, 30?min to 1?h depending on the model, before induction of inflammation/pain. The LD₅₀ was also determined. GC–MS analysis of dichloromethane fraction was carried out.

Results: The extract caused a significant (p?<?0.05–0.001) reduction of inflammation induced by carrageenan (8.3–70.0%), egg albumin (10.0–71.42%) and xylene (39.39–84.84%). The extract also reduced significantly (p?<?0.05–0.001) pain induced by acetic acid (44.22–73.65%), formalin (55.89–79.21%) and hot plate (93.0–214.5%). The LD₅₀ was determined to be 4.38?±?35.72?g/kg.

Discussion and conclusion: The results of this study suggest that the ethanol stem extract of H. letestui possesses anti-inflammatory and analgesic properties which may in part be mediated through the chemical constituents of the plant as revealed by the GC–MS.     

Antinociceptive activity and chemical composition of Wei–Chang–An–Wan extracts

Abstract

Context: Currently, famous traditional Chinese medicine formulas have undergone re-evaluation and development in China. Wei–Chang–An–Wan (WCAW) as one of them has been used for treating various gastrointestinal diseases for several decades. The secondary development of WCAW is in progress so as to interpret the effective material basis or find new pharmacological activity.

Objective: To evaluate the antinociceptive effect of methanol extract of WCAW (ME) as well as four fractions (P.E., EtOAc, n-BuOH, H₂O) and obtain information on the correlation between the contents of the fractions and antinociceptive effect.

Materials and methods: ME was divided into four parts extracted by petroleum ether, ethyl acetate and n-butanol. Antinociceptive activity was evaluated by three models of acetic acid–induced writhing, formalin and hot-plate test in mice after repetitive administration of ME at 200, 400 or 800?mg/kg, P.E. 132?mg/kg, EtOAc 106?mg/kg, n-BuOH 176?mg/kg and H₂O 176?mg/kg for six days. The chemical compounds were analyzed by HPLC-ESI-MS.

Results: ME at 800?mg/kg inhibited acid-induced writhing by 84.69%, and reduced the licking time of second phase in formalin test by 53.23%. The inhibition rates in acid-induced writhing of P.E., EtOAc, n-BuOH and H₂O were 27.79, 33.85, 38.97 and 37.69%, respectively, and in formalin test about 50%. They had no effect on the hot-plate test. HPLC-ESI-MS analysis showed that 68 chemical compounds were detected and 41 compounds were identified from ME.

Discussion and conclusion: The results obtained herein indicate that WCAW possesses the antinociceptive activity that provides a new aspect in clinical application.     

An evaluation of the anti-inflammatory,antipyretic and analgesic effects of hydroethanol leaf extract of Albizia zygia in animal models

Context: The leaves of Albizia zygia (DC.) J.F. Macbr. (Leguminosae-Mimosoideae) are used in Ghanaian traditional medicine for the treatment of pain, inflammatory disorders and fever (including malaria).

Objectives: The present study evaluated the anti-inflammatory, antipyretic and analgesic effects of the hydroethanol leaf extract of Albizia zygia (AZE) in animal models.

Materials and methods: The anti-inflammatory and antipyretic effects of AZE were examined in the carrageenan-induced foot oedema model and the baker’s yeast-induced pyrexia test respectively. The analgesic effect and possible mechanisms of action were also assessed in the formalin test.

Results: AZE (30–300?mg/kg, p.o.), either preemptively or curatively, significantly inhibited carrageenan-induced foot edema in 7-day-old chicks (ED₅₀ values; preemptive: 232.9?±?53.33?mg/kg; curative: 539.2?±?138.28?mg/kg). Similarly, the NSAID diclofenac (10–100?mg/kg, i.p.) significantly reduced the oedema in both preemptive (ED₅₀: 21.16?±?4.07?mg/kg) and curative (ED₅₀: 44.28?±?5.75?mg/kg) treatments. The extract (30–300?mg/kg, p.o.) as well as paracetamol (150?mg/kg, p.o.) also showed significant antipyretic activity in the baker’s yeast-induced pyrexia test (ED₅₀ of AZE: 282.5?±?96.55?mg/kg). AZE and morphine (1–10?mg/kg, i.p.; positive control), exhibited significant analgesic activity in the formalin test. The analgesic effect was partly or wholly reversed by the systemic administration of naloxone, theophylline and atropine.

Conclusion: The results suggest that AZE possesses anti-inflammatory, antipyretic and analgesic properties, which justifies its traditional use. Also, the results show the involvement of the opioidergic, adenosinergic and the muscarinic cholinergic pathways in the analgesic effects of AZE.     

The validation of Calophyllum brasiliense (“guanandi”) uses in Brazilian traditional medicine as analgesic by in vivo antinociceptive evaluation and its chemical analysis

Calophyllum brasiliense is used as anti-inflammatory and analgesic in Brazilian traditional medicine. Thus, the main purpose of this study is to evaluate the antinociceptive effect of the chloroform fraction of C. brasiliense (CFCB) roots and to investigate its main mechanism of action. The antinociceptive effect of CFCB was evaluated in mice using acetic acid-induced writhing, formalin-induced paw licking, and hot-plate tests and capsaicin- and glutamate-induced nociception. Brasiliensic acid and 1,2-dimethoxyxanthone were isolated and evaluated in writhing test. The amount of 1,2-dimethoxyxanthone was determined in the fraction by UPLC-DAD. CFCB inhibited abdominal constrictions induced by acetic acid up to 97%, with an ID₅₀ of 9.4 mg/kg (i.p.) and 131.8 mg/kg (p.o.). In the formalin test, CFCB impaired paw licking with an ID₅₀ of 26.3 mg/kg for the first phase and 27.5 mg/kg for the second phase (i.p.). The painful response evoked by capsaicin and glutamate was significantly reduced (ID₅₀ 26.7 and 47.9 mg/kg, i.p.). The latency time was increased up to 76% at 60 mg/kg (i.p.) in the hot-plate test. 1,2-Dimethoxyxanthone was almost three times more potent (ID₅₀ 27.6 μmol/kg, i.p.) than brasiliensic acid (72.0 μmol/kg) in acetic acid-induced writhing test. The amount of the xanthone was estimated as 92.5 mg/g in the extract. CFCB inhibited the nociceptive response associated to several agents. TRPV1 channels play an important role in the mechanism of action of the fraction. In addition, 1,2-dimethoxyxanthone largely contributes to the antinociceptive effect of CFCB.

     

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.     

Study of anti-inflammatory and antinociceptive activity of hydroalcoholic extract of Schima wallichii bark

Hydroalcoholic extract of Schima wallichii Choisy. (Ternstroemiaceae) bark (HESW) was investigated for its anti-inflammatory, antinociceptive, and antipyretic activities. The anti-inflammatory effects of the HESW were assayed by using carrageenan and dextran (acute model) induced paw edema and cotton pellet granuloma assay (chronic model) in experimental rats. Oral administration of HESW at the doses of 150 and 300?mg/kg caused dose-dependent inhibition of carrageenan and dextran induced inflammation. HESW at the doses of 150 and 300?mg/kg caused significant dose-dependent reduction of the granuloma tissue formation in experimental rats. The extract at the oral doses of 50 and 100?mg/kg body weight exhibited significant central and peripheral analgesic activity in acetic acid induced writhing test and hot-plate test respectively in experimental mice. Treatment with HESW at the oral doses of 150 and 300?mg/kg body weight significantly reduced the yeast-provoked elevated body temperature in experimental rats in a dose-dependent manner.     

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.     

Evaluation of antinociceptive and antidiarrhoeal properties of Manilkara zapota leaves in Swiss albino mice

Context Manilkara zapota (L.). P. Royen. (Sapotaceae) has been used in folk medicine to treat pain, diarrhoea, inflammation, arthralgia, and other disorders.

Objective Screening of Manilkara zapota leaves ethanol extract and its different solvent soluble fractions for possible antinociceptive and antidiarrhoeal activities in Swiss albino mice.

Materials and methods The extract and various fractions (200 and 400?mg/kg body weight; p.o.) were tested for peripheral and central antinociceptive activity by acetic acid-induced writhing and radiant heat tail-flick method, respectively; castor oil-induced diarrhoeal model was used to evaluate antidiarrhoeal activity at both doses. All the samples were administered once in a day and the duration of study was approximately 5?h.

Results Ethanol extract (400?mg/kg), petroleum ether fraction (400?mg/kg), and ethyl acetate fraction (400?mg/kg) showed significant peripheral antinociceptive activity having 59.89, 58.24, and 46.7% (p?<?0.001) of writhing inhibition, respectively, which is comparable with that of standard diclofenac (59.34% inhibition). The ethanol extract (400?mg/kg) and petroleum ether fraction (400?mg/kg) also showed promising central analgesic activity having 74.15 and 82.15% (p?<?0.001) elongation of reaction time, respectively, at 90?min after administration of sample which is also similar to that obtained by morphine (85.84% elongation). In antidiarrhoeal activity screening, ethanol extract (200 and 400?mg/kg) showed significant inhibition of defecation by 53.57 and 60.71%, respectively (p?<?0.001) compared with that of loperamide (71.42%).

Discussion and conclusion The findings of the studies demonstrated antinociceptive and antidiarrhoeal activities of M. zapota leaves which could be the therapeutic option against pain and diarrhoeal disease.     

Pereskia aculeata: A plant food with antinociceptive activity

Abstract

Context: Pereskia aculeata Miller (Cactaceae) is a cactus distributed from south to northeast of Brazil, where its leaves are commonly used as a vegetable, in skin wound healing, and to treat inflammation.

Objectives: The objective of this study was to perform the chemical characterization and to evaluate the antinociceptive activity of the hydromethanolic fraction obtained from the methanol extract of P. aculeata leaves.

Materials and methods: Chemical characterization was performed by UPLC–MS analysis. The antinociceptive activity was evaluated by the acetic acid-induced writhing, formalin, and tail-flick tests in mice, administering the single oral doses of 100, 200, and 300?mg/kg 1?h before each test.

Results: Tryptamine, abrine, mescaline, hordenine, petunidin, di-tert-butylphenol isomers, and quercetin were identified. The antinociceptive activity was inversely proportional to the administered doses in the acetic acid test, as the dose of 100?mg/kg reduced by 78% the number of writhings, while the doses of 200 and 300?mg/kg reduced by 64% and 41%, respectively. In the formalin test, the dose of 300?mg/kg inhibited by 50% and 86% the licking paw time in the first and second phases, respectively, while the doses of 200?mg/kg (45% and 62%, respectively) and 100?mg/kg (15% and 48%, respectively) were less effective. The sample did not respond to the tail-flick test. Those results suggested a peripheral and central antinociception devoid of an opioid effect.

Conclusion: Pereskia aculeata not only is a plant food with high nutritional value but also presents analgesic potential. It is the first time that this bioactivity is reported for this species.     

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.     

Analgesic and anti-inflammatory effects of the methanol root extracts of some selected Nigerian medicinal plants

Context: The roots of Alafia barteri Oliver (Apocynaceae), Combretum mucronatum Schumach (Combretaceae) and Capparis thonningii Schum (Capparaceae) are used in Traditional African Medicine to alleviate painful and inflammatory conditions.

Objective: This study investigated the analgesic and anti-inflammatory effects of the methanol root extracts of Alafia barteri (MeAB), C. mucronatum (MeCM), and Capparis thonningii (MeCT).

Materials and methods: Analgesic activity of the extracts (50, 100, and 200?mg/kg, p.o. 1?h) was evaluated using acetic acid-, formalin- and hot plate-induced pain while anti-inflammatory actions (100 or 200?mg/kg) were investigated using the carrageenan- and xylene-induced edema tests.

Results: MeAB, MeCM, and MeCT (200?mg/kg) inhibited acetic acid-induced abdominal constriction by 55.07, 46.67, and 47.25%, respectively. In the formalin test, the index of pain inhibition of early and late phases was, respectively, 47.83 and 81.98% for MeAB, 56.10 and 63.81% for MeCM, and 42.84 and 63.29% for MeCT (200?mg/kg). MeAB and MeCT pretreatments significantly increased the reaction time by 46.67 and 25.53%, respectively, 120?min post-treatment in the hot-plate test. Naloxone (5?mg/kg, s.c.) pretreatment 15?min before extract administration, significantly (p?MeAB, MeCM, and MeCT showed significant anti-inflammatory activity with 60.44 and 30.39%, 63.74 and 58.08%, and 50.55 and 77.84% (200?mg/kg, 4?h), respectively, inhibition of paw and ear edema.

Discussion and conclusion: The analgesic and anti-inflammatory effects of MeAB and MeCT involve an interaction with opioid pathway and/or inhibition of chemical mediators of pain and inflammation.     

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.     

Antinociceptive and anticonvulsant effects of the monoterpene linalool oxide

Context: Linalool oxide (OXL) (a monoterpene) is found in the essential oils of certain aromatic plants, or it is derived from linalool. The motivation for this work is the lack of psychopharmacological studies on this substance.

Objective: To evaluate OXL’s acute toxicity, along with its anticonvulsant and antinociceptive activities in male Swiss mice.

Material and methods: OXL (50, 100 and 150?mg/kg, i.p.) was investigated for acute toxicity and in the Rota-rod test. Antinociceptive activity was evaluated by the acetic acid-induced writhing test, and by formalin testing. Anticonvulsant effects were demonstrated by testing for pentylenetetrazol (PTZ)-induced seizures and by Maximum Electroshock headset (MES) test. OXL was administered to the animals intraperitoneally 30?min before for pharmacological tests.

Results: OXL showed an LD₅₀ of ～721 (681–765) mg/kg. In the Rota-rod test, it was observed that OXL caused no damage to the animal’s motor coordination. OXL significantly reduced (p?p?p?p?p?p?p?Conclusion: The tested doses of OXL were safe, with no motor impairment, and show clear antinociceptive and anticonvulsant potential. Future investigations with this monoterpene may lead to the development of a new molecule with even higher potency and selectivity.     

A long-form α-neurotoxin from cobra venom produces potent opioidindependent analgesia

AIM: In light of the antinociceptive activity of the short-chain neurotoxin, cobrotoxin, and other acetylcholine antagonists, the antinociceptive activity and mechanisms of cobratoxin (CTX), a long-chain postsynaptic alpha-neurotoxin, was investigated in rodent pain models. METHODS: CTX was administered intraperitoneally (30, 45, 68 microg/kg), intra-cerebral ventricularly (4.5 microg/kg) or microinjected into periaqueductal gray (PAG; 4.5 microg/kg). The antinociceptive action was tested using the hot-plate and acetic acid writhing tests in mice and rats. The involvement of the cholinergic system and opioid system in CTX-induced analgesia was examined by pretreatment of animals with atropine (0.5 mg/kg, im; or 10 mg/kg, ip) or naloxone (1 and 5 mg/kg, ip). The effect of CTX on motor activity was tested using the Animex test. RESULTS: CTX exhibited a dose-dependent analgesic action in mice as determined by both the hot-plate and acetic acid writhing tests. The peak effect of analgesia was seen 3 h after administration. In the mouse acetic acid writhing test, the intra-cerebral ventricular administration of CTX at 4.5 microg/kg (1/12th of a systemic dose) produced marked analgesic effects. Microinjection of CTX (4.5 microg/kg) into the PAG region did not elicit an analgesic action in rats in the hot-plate test. Atropine at 0.5 mg/kg (im) and naloxone at 1 and 5 mg/kg (ip) both failed to block the analgesic effects of CTX, but atropine at 10 mg/kg (ip) did antagonize the analgesia mediated by CTX in the mouse acetic acid writhing test. Acetylsalicylic acid (300 mg/kg) did not enhance the analgesic effects of CTX. At the highest effective dose of 68 microg/kg the neurotoxin did not change the spontaneous mobility of mice. CONCLUSION: CTX has analgesic effects, which are mediated in the central nervous system though not through the PAG. The central cholinergic system but not opioid system appears to be involved in the antinociceptive action of CTX.     

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.     

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.     

A safety study on single intravenous dose of tetrachloro-diphenyl glycoluril [iodogen] dissolved in dimethyl sulphoxide (DMSO)

Abstract

1. Iodogen (tetrachloro-diphenyl glycoluril) dissolved in DMSO (dimethyl sulphoxide) appears indispensable in radioiodination of hypericin for a new anticancer strategy. We studied the safety of intravenously administered iodogen/DMSO in mice (n?=?132).

2. Median lethal dose (LD₅₀) of iodogen/DMSO was determined with doses of 40.0, 50.0, 55.0, 60.0, 65.0 and 70.0?mg/kg. Next, toxicity of iodogen/DMSO at 30.0?mg/kg was evaluated using saline and DMSO as controls. Changes in behaviour, body weight and serum biochemistry were evaluated. Histopathology of lungs, heart, liver and kidney was performed.

3. LD₅₀ values of iodogen/DMSO were 59.5?mg/kg (95% confidence limits (CI): 54.1–65.4?mg/kg) and 61.0?mg/kg (95%CI: 56.2–66.2?mg/kg) for female and male mice, respectively. Similar to that of control groups, no animal deaths were encountered after iodogen/DMSO administration at 30.0?mg/kg. Body weights over 24?h were not altered in all groups, but significantly higher in iodogen/DMSO and DMSO groups (p?<?0.05) 14?d post-injection. Blood urea nitrogen and alkaline phosphatase increased (p?<?0.05) in iodogen/DMSO group without clinical symptoms. No pathologies were found by gross and microscopic inspection.

4. A single dose of iodogen/DMSO up to 30.0?mg/kg, over 3000 times the dose in potential human applications, appears safe, with an LD₅₀ doubling that dose in mice.