The possible mechanisms of protocatechuic acid-induced central analgesia

It is aimed to investigate the central antinociceptive effect of protocatechuic acid and the involvement of stimulation of opioidergic, serotonin 5-HT_2A/2C, α2-adrenergic and muscarinic receptors in protocatechuic acid-induced central analgesia in mice. Time-dependent antinociceptive effects of protocatechuic acid at the oral doses of 75, 150 and 300?mg/kg were tested in hot-plate (integrated supraspinal response) and tail-immersion (spinal reflex) tests in mice. To investigate the mechanisms of action; the mice administered 300?mg/kg protocatechuic acid (p.o.) were pre-treated with non-specific opioid antagonist naloxone (5?mg/kg, i.p.), serotonin 5-HT_2A/2C receptor antagonist ketanserin (1?mg/kg, i.p.), α2-adrenoceptor antagonist yohimbine (1?mg/kg, i.p.) and non-specific muscarinic antagonist atropine (5?mg/kg, i.p.), respectively. The antinociceptive effect of protocatechuic acid was observed at the doses of 75, 150 and 300?mg/kg in tail-immersion test, at the doses of 150 and 300?mg/kg in hot-plate test at different time interval. The enhancement in the latency of protocatechuic acid-induced response to thermal stimuli was antagonized by yohimbine, naloxone and atropine in tail-immersion test, while it was antagonized only by yohimbine and naloxone pretreatments in hot-plate test. These results indicated that protocatechuic acid has the central antinociceptive action that is probably organized by spinal mediated cholinergic and opiodiergic, also spinal and supraspinal mediated noradrenergic modulation. However, further studies are required to understand how protocatechuic acid organizes the interactions of these modulatory systems. As a whole, these findings reinforce that protocatechuic acid is a potential agent that might be used for pain relief. Additionally, the clarification of the effect and mechanisms of action of protocatechuic acid will contribute to new therapeutic approaches and provide guidance for new drug development studies.     

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.     

Comparative study of the anti-inflammatory and antinociceptive effects of two varieties of Punica granatum

Context: Studies have shown that pomegranate, Punica granatum Linn. (Lythraceae), has remarkable biological and medicinal properties.

Objective: This work aimed to explore and compare the analgesic and anti-inflammatory activities of the methanol extract (MoE) obtained from fruit peels of two varieties of pomegranate: Amrouz (MoEA) and Sefri (MoES).

Materials and methods: Antinociceptive activity of MoEA and MoES was examined using four models of pain. The extracts were administered by the intraperitoneal route (i.p.) in writhing (50, 100 and 150?mg/kg) and formalin tests (25, 50 and 100?mg/kg) and by intra-cerebroventricular injection (i.c.v.) in hotplate and tail-immersion tests (10, 25 and 50 µg/3 µl/rat). anti-inflammatory activity was studied using the hind paw egg albumin test (50, 100 and 150?mg/kg, i.p.).

Results: In the writhing test, the index of pain inhibition (IPI) was 52% for MoEA (150?mg/kg, i.p.) and 29% for MoES (150?mg/kg, i.p.). In the formalin test, the IPI of early and late phase were, respectively, 75% and 82% for MoEA (100?mg/kg, i.p.) and 8% and 63% for MoES (100?mg/kg, i.p.). In the hotplate and tail-immersion test, MoEA and MoES increased in a dosedependent manner the reaction latency to the thermal stimuli. MoEA seems to be more potent than MoES. Only the analgesic effect of MoEA was partially inhibited by pretreatment with naloxone. Both extracts exerted a significant anti-inflammatory effect.

Discussion and conclusions: The results demonstrated that P. granatum contains active constituents, which possess antinociceptive and anti-inflammatory activity, justifying its popular uses.     

Anti-inflammatory and antinociceptive effect of Pachygone ovata leaves

Context: Pachygone ovata (Poir.) Miers ex Hook. F. et Thoms (Menispermaceae) is a rich source of bioactive bisbenzylisoquinoline and aporphine alkaloids.

Objective: This study investigates the in vitro and in vivo anti-inflammatory and antinociceptive potential of Pachygone ovata leaves.

Materials and methods: Lipoxygenase (LOX) assay for anti-inflammatory activity was conducted using MeOH, EA, H and Aq extracts; followed by alkaloid isolation. The anti-inflammatory potential was determined using carrageenan-induced paw oedema and formalin tests for evaluation of Pachygone ovata analgesic effect. Different doses (100, 300 and 400?μg/kg) were administered orally to Wistar rats for a period of one week, once daily.

Results: MeOH and EA extract efficiently inhibited LOX (IC₅₀ 1.43 and 2.15?μg/mL, respectively). MeOH extract had better inhibiting capacity (57%) than indomethacin (51%) in carrageenan induced rats. MeOH extract (300?μg/kg) significantly reduced the increased levels of nitric oxide (8?±?0.57 M), total leukocyte count (4.5?±?0.05 cells 10³/cells) and C-reactive protein (55?±?0.45?mg/mL). There was a decrease in various serum biochemical markers (ALT, AST). Histopathological studies revealed reduction in oedema and decreased cellular infiltration on supplementation with MeOH extract. Furthermore, MeOH extract (300?μg/kg) and alkaloid fraction (400?μg/kg) effected both phases (neurogenic and inflammatory) of formalin injected models.

Discussion and conclusion: Inflammatory mediators play a key role in inflammation; therefore, keeping it in control is of utmost importance. The usefulness of Pachygone ovata leaves on pain and inflammation has been described, probably due to its effect on inflammatory mediators and high alkaloid content.     

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.     

Effect of curcumin in mice model of vincristine-induced neuropathy

Abstract

Context: Curcumin exhibits a wide spectrum of biological activities which include neuroprotective, antinociceptive, anti-inflammatory, and antioxidant activity.

Objective: The present study evaluates the effect of curcumin in vincristine-induced neuropathy in a mice model.

Materials and methods: Vincristine sulfate (0.1?mg/kg, i.p. for 10 consecutive days) was administered to mice to induce neuropathy. Pain behavior was assessed at different days, i.e., 0, 7, 10, and 14?d. Sciatic nerve total calcium, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), nitric oxide (NO), and lipid peroxidation (LPO) were also estimated after the 14th day of study. Pregabalin (10?mg/kg, p.o.) and curcumin (15, 30, and 60?mg/kg, p.o.) were administered for 14 consecutive days.

Results: Curcumin at 60?mg/kg significantly attenuated the vincristine-induced neuropathic pain manifestations in terms of thermal hyperalgesia (p?<?0.001) and allodynia (p?<?0.001); mechanical hyperalgesia (p?<?0.001); functional loss (p?<?0.001); and in the delayed phase of formalin test (p?<?0.001). Curcumin at 30 and 60?mg/kg exhibited significant changes (p?<?0.001) in antioxidant levels and in total calcium levels in vincristine-injected mice.

Conclusion: Curcumin at 30 and 60?mg/kg dose levels significantly attenuated vincristine-induced neuropathy which may be due to its multiple actions including antinociceptive, calcium inhibitory, and antioxidant effect.     

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.

     

Antinociceptive effect of the essential oil of tarragon (Artemisia dracunculus)

Context: Tarragon [Artemisia dracunculus L. (Asteraceae)] is used as a commercial flavoring and in perfumery. In traditional folk medicine, tarragon has been used for treatment of pain and gastrointestinal disturbances.

Objective: This study investigated the antinociceptive effect of the essential oil of A. dracunculus (EOAD) in various experimental models.

Materials and methods: The median lethal dose (LD₅₀) of EOAD was estimated using the method of Lorke. The antinociceptive effect was assessed using chemical (formalin and acetic acid) and thermal (hot-plate) nociceptive tests in rats and mice. In all experiments, EOAD was administered intraperitoneally at the doses of 10, 30, 100 and 300?mg/kg.

Results: In the acute toxicity test, the value of estimated LD₅₀ for EOAD was 1250?mg/kg. EOAD (100 and 300?mg/kg) significantly reduced (p?p?Conclusions: This study reported the peripheral and central antinociceptive activity of the EOAD and rationalized the traditional use of the plant in the treatment of different painful conditions.     

Mechanisms Involved in the Antinociceptive Effect in Mice of the Hydroalcoholic Extract of Siphocampylus verticillatus

The antinociception caused by the hydroalcoholic extract of Siphocampylus verticillatus (Campanulaceae) has been investigated in chemical and thermal models of nociception in mice. We have also assessed some of the mechanisms underlying the antinociceptive effect of the extract. The hydroalcoholic extract of S. verticillatus (60–1000 mg kg^?1, i.p. or p.o.) produced dose-related, significant and long-lasting (6 to 8 h) inhibition of acetic acid-induced abdominal constriction in mice, with ID50 values of 204 and ～1000 mg kg^?1, respectively. In the formalin test, the extract (100–1000 mg kg^?1), given either intraperitoneally or orally, resulted in graded inhibition of both phases of formalin-induced pain, being about 2- to 4-fold more potent in attenuating the second phase of the pain. The calculated mean ID50 (mg kg^?1) values for the earlier and the later phases were: 491 and 186 and 640 and 441, respectively. In addition, the extract (60–1000 mg kg^?1, i.p. or p.o.) caused marked and dose-related inhibition of capsaicin-induced neurogenic pain with mean ID50 values of 420 and 485 mg kg^?1, respectively. The hydroalcoholic extract, at the same doses, did not significantly affect the performance of animals in the rota-rod test, nor did it have any analgesic effect in the tail-flick or hot-plate tests. The treatment of animals with naloxone (5 mg kg^?1, s.c.) significantly reversed the analgesic effect of both morphine (5 mg kg^?1, s.c.) and the extract (300 mg kg^?1, i.p.) when assessed against acetic acid-induced abdominal constrictions. The treatment of animals with l-arginine (600 mg kg^?1, i.p.) significantly attenuated the antinociceptive effects of N^G-nitro-l-arginine (l-NOARG) (75 mg kg^?1, i.p.), of the hydroalcoholic extract (600 mg kg^?1, i.p.) or of morphine (5 mgkg^?1, s.c.), when analysed against the formalin test. In addition, adrenalectomy of animals 7 days before the tests significantly reversed the antinociception caused by the hydroalcoholic extract (300 mg kg^?1, i.p.) in the formalin-induced pain. These data show that the hydroalcoholic extract of S. verticillatus has significant and long-lasting oral antinociception when assessed against both neurogenic and inflammatory models of nociception in mice. The precise mechanism responsible for the analgesic effect of the extract still remains unclear, but a great part of this effect seems to be partly related to an opioid-like action and involvement of the l-arginine-nitric oxide pathway. Finally, the antinociception caused by the hydroalcoholic extract of S. verticillatus is modulated by adrenal hormones.     

Central and Cardiovascular Effects of the Alcoholic Extract of the Leaves of Carica papaya

Abstract

The central effects of an alcoholic extract of Carica papaya leaf were investigated in male rats. The extract (≥ 10 mg kg^?1, i.p.) induced a dose-dependent sedative effect. The extract (≥ 5 mg kg, i.p.) also induced central muscle relaxation. The behavioral effects of the extract were associated with an initial desynchronization of the electroencephalogram (EEG) and an increased activity of the electromyogram (EMG). This was followed by a deactivating pattern in the optic chiasma while the EMG activity was diminished. The extract at doses ≥50 mg kg^?1 (i.p.) completely protected the rats against pentylenetetrazol-induced seizures, while doses of 5 mg kg^?1 (i.p.) gave 50% protection. The extract at doses of 100 and 200 mg kg^?1 (i.p.) also gave 100% protection against maximal electroshock-induced convulsions.     

Nephroprotective and curative effects of Ficus religiosa latex extract against cisplatin-induced acute renal failure

Abstract

Context. Ficus religiosa L. (Moraceae) is widely planted in the tropics. Its chemical constituents include tannin, saponin gluanol acetate, β-sitosterol, leucoanthocyanidin and leucoanthocyanin which are used for the treatment of pain, inflammation, impotence, menstrual disturbances, uterine tonic and urine related problems.

Objective: To determine the possible nephroprotective and curative effects of F. religiosa latex methanol extract against cisplatin induced acute renal failure.

Materials and methods: Methanol extract was obtained by maceration process. Rats were divided in five groups. Group 1 was administered acacia (2% w/v) of 5?ml/kg throughout the experiment; group 2 was treated with single dose of cisplatin (5?mg/kg i.p.) on the 1st day; group 3 (200?mg/kg p.o.) of extract control for the 1st to 10th day, group 4 (200?mg/kg p.o.) of extract from the 1st to 10th day and a single dose of cisplatin (5?mg/kg, i.p.) on 11th day while group 5 received the same dose of cisplatin on day 1 and extract (200?mg/kg p.o.) from the 7th to 16th day.

Results: Phytochemical screening of the extract revealed the presence of glycoside, alkaloids, tannins (phenolic compounds), flavonoids and amino acids. The half maximal inhibitory concentration (IC₅₀) values of the extract were 31.75?±?0.12 and 18.35?±?0.48?µg/ml, respectively. The cisplatin-treated group 2 showed significant changes; renal functions, biochemical parameters and histopathology were significantly (**p?<?0.01) recovered by 200?mg/kg curative and protective groups.

Discussion and conclusion: These findings demonstrated that F. religiosa latex and constituents have excellent nephroprotective and curative activities and thus have great potential as a source for natural health products.     

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.     

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.     

Methanol extract from mycelium of endophytic fungus Rhizoctonia sp. induces antinociceptive and anti-inflammatory activities in mice

The present study aimed to elucidate the antinociceptive and anti-inflammatory properties of the methanol extract from the mycelium of the endophytic fungus Rhizoctonia sp. (MEMRh) in mice. The antinociceptive activity was assessed using the abdominal constriction, hot plate, and formalin tests. The anti-inflammatory activity was assessed using a murine model of paw edema. Intraperitoneal administration of MEMRh (0.1, 1, 10 and 100?mg/kg, i.p.) produced an inhibition of acetic acid-induced writhing in mice for at least 8?h. In addition, all doses tested of the methanol extract were able to prevent thermal nociception in the hot-plate test. Furthermore, treatment with MEMRh (10?mg/kg, i.p.) inhibited both the early and late phases of formalin-induced nociception. This antinociceptive effect exhibited by MEMRh in the formalin test was reversed by the systemic administration of naloxone. MEMRh produced inhibition in a carrageenan-induced edema model at a dose of 10?mg/kg. The same extract also displayed significant activity against a histamine- or PGE(2)-induced edema model. The experimental data demonstrated that MEMRh showed remarkable anti-inflammatory and antinociceptive activities. Further studies are warranted to define and isolate the active anti-inflammatory and antinociceptive components from this endophytic fungus, which may yield effective agents for the treatment of inflammatory disorders.     

Analgesic Activity of Cistus laurifolius in Mice

The possible analgesic activity of Cistus laurifolius extracts has been evaluated by using tail flick and acetic acid-induced writhing tests in mice. The chloroform extract (500?mg/kg, i.p.) and the precipitated fraction (10, 30, 100?mg/kg, i.p.) obtained from C. laurifolius leaves showed significant analgesic activity on tail flick assay, while aqueous, ethanol and butanol extracts of the plant had no activity on the same test. Chloroform extract (500?mg/kg, i.p.) and precipitate fraction (30?mg/kg, i.p.) also inhibited number of writhings induced by acetic acid. These observations suggest that C. laurifolius leaves possess antinociceptive compound(s) which act through a central mechanism.     

Antinociceptive and anti-inflammatory effects of Costus spicatus in experimental animals

Context: Costus spicatus Swartz (Costaceae), commonly called “cana-do-brejo’” in Brazil’s northeast, is a medicinal plant found in wet coastal forests. In folk medicine an infusion of the aerial parts is taken to treat inflammation and pain.

Objective: The methanol extract obtained from the leaves of Costus spicatus (MECs) was evaluated for antinociceptive and anti-inflammatory activities.

Methods: Analgesic and anti-inflammatory activities were studied by measuring nociception through acetic acid, formalin, and hot-plate tests, while inflammation was induced by carrageenan. All experiments were conducted with experimental animals.

Results and discussion: Following oral administration, MECs (100, 200, and 400?mg/kg) significantly reduced the number of writhes (52.8, 43.1, and 55.3%, respectively) in the writhing test and the number of paw licks during phase 1 (61.9, 54.1, and 92.1%) and phase 2 (62.5, 82.9, and 98.1%, all doses) during the formalin test when compared to the control group animals. The reaction time during the hot-plate test was increased significantly and was dose-dependent, whereas pretreatment with naloxone rigorously reduced the analgesic potential of MECs, which suggested participation of the opioid system in the modulation of pain induced by MECs. Such results were unlikely to be provoked by motor abnormality, as MECs-treated mice did not exhibit any performance alteration during the Rota-rod test. The administration of 200 and 400?mg/ kg (i.p.) of MECs exhibited an anti-inflammatory effect during the carrageenan test, which was based on interference with inflammatory mediator synthesis.

Conclusion: We conclude that MECs has antinociceptive and anti-inflammatory activities in rodents.     

Hydroalcoholic extract of Urtica circularis: A neuropharmacological profile

Abstract

Context: The genus Urtica has been known since ancient times. It has known to be useful for the treatment of different human ailments.

Objective: The present work evaluated the neuropharmacological effects of a hydroalcoholic extract of Urtica circularis (Hicken) Sorarú (Urticaceae).

Materials and method: The effect on central nervous system of U. circularis hydroalcoholic extract (from leaves and stems) administered by the intraperitoneal route in mice was evaluated by several tests: Pentobarbital- and midazolam-induced hypnosis, open field, hole board, elevated plus-maze and forced swimming. Phytochemical analysis was performed by high-performance liquid chromatography.

Results: A total of 300?mg/kg i.p. of the extract produced a significant prolongation of pentobarbital- (40?mg/kg i.p.; 60.1?min versus 25.4?min) and midazolam- (50?mg/kg i.v.; 53.4?min versus 25.1?min) induced sleeping time. The extract’s administration caused a marked reduction of the head-dipping response (DE₅₀: 373?mg/kg i.p.) in the hole-board test. Urtica circularis extract (DE₅₀: 46?mg/kg i.p.) reduced the spontaneous locomotor activity in the open field test. Flumazenil and atropine significantly antagonized the extract’s effect on the locomotor activity. No motor coordination disturbance was observed in the rota rod test at any doses. In the forced swimming test, the extract did not produce any change in the immobility time and it had no significant effects in elevated plus maze test. The phytochemical analysis revealed the presence of chlorogenic acid, vanillic acid, caffeic acid, vicenin-2, p-cumaric acid, ferulic acid, vitexin and isovitexin.

Conclusion: This study revealed that U. circularis hydroalcoholic extract possesses sedative activity, facilitating GABAergic and cholinergic transmission.     

Peripheral and central antinociceptive effects of the butanolic fraction of <Emphasis Type="Italic">Byrsonima verbascifolia</Emphasis> leaves on nociception-induced models in mice

Byrsonima verbascifolia (Malpighiaceae), commonly known as ‘murici’, is used in folk medicine, for example, in the treatment of inflammation. The anti-inflammatory activity of the butanolic fraction of B. verbascifolia leaves (BvBF) was previously reported by our group, and the present study was designed to evaluate their antinociceptive effects. BvBF (25, 50, and 100 mg/kg) administered intraperitoneally (i.p.) inhibited acetic acid induced abdominal writhing. In the formalin test, BvBF (10, 30 and 100 mg/kg, i.p.) caused a reduction in licking time in both the neurogenic and inflammatory phases. Moreover, we demonstrated that BvBF (30 and 100 mg/kg, i.p.) caused an increase in the latency to response in the hot-plate test. These results demonstrate that BvBF possesses marked peripheral and central antinociceptive activities. Pre-treatment with the non-selective receptor antagonist naloxone (5 mg/kg, i.p.) abolished the antinociceptive effects of BvBF (100 mg/kg, i.p.) in the neurogenic phase of the formalin and hot-plate tests. The anti-inflammatory activity of BvBF (previously reported) as well as the participation of the opioidergic system seems to be responsible, at least in part, for these antinociceptive effects. Finally, BvBF at the doses investigated (25, 50 and 100 mg/Kg) did not cause any toxicity signals, showing that the antinociceptive activity is devoid of sedative and hypomotility effects.     

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.     

Neuropharmacological activity of hydroalcoholic extract of leaves of Colocasia esculenta

Context: Although Colocasia esculenta Linn. (Araceae), commonly known as elephant ear (English), possesses diverse pharmacological activities in animals, little is known about its neuropharmacological activity.

Objective: The present study evaluated the neuropharmacological activities of hydroalcoholic extract of leaves of Colocasia esculenta (HECE) using several experimental models.

Materials and methods: Adult Wistar albino rats were subjected to behavior despair and elevated plus maze (EPM) tests. Thiopental-induced sedation and rotarod tests were conducted on Swiss albino mice.

Results and discussion: The effects of HECE on anxiety, depression, thiopental-induced sleeping time, and rotarod performance were evaluated. The anxiolytic activity of HECE (100, 200, and 400?mg/kg) per os (p.o.) was characterized by increased time spent and number of entries in open arms in the EPM paradigm as compared to control group (p?<?0.001). The HECE (100, 200, and 400?mg/kg, p.o.) showed dose-dependent significant reduction in duration of immobility (p?<?0.01) in the behavior despair test. The HECE at the doses 50 and 100?mg/kg, i.p. was found to produce a significant reduction in motor coordination (p?<?0.001) and prolongation of thiopental-induced sleeping time (p?<?0.001). The phytochemical screening revealed the presence of flavonoids, β-sitosterol, and steroids.

Conclusions: The results of the study for the first time show that the plant possesses neuropharmacological activity, confirming the traditional claims. Future research should focus on the identification and the neurobehavioral activity of the constituents from this plant.