Antinociceptive activity of Rhoifoline A from the ethanol extract of Zanthoxylum nitidum in mice

Aim of the study

Antinociceptive activity of Rhoifoline A (RA), a benzophenanthridine alkaloid obtained from the ethanol extract of Zanthoxylum nitidum, was evaluated in mice using chemical and thermal models of nociception.

Materials and methods

RA was evaluated on anti-nociceptive activity in mice using chemical and thermal models of nociception.

Results

RA administered intraperitoneally at doses of 10, 20, 40 and 80 mg/kg exhibited significant inhibitions on chemical nociception induced by intraperitoneal acetic acid and subplantar formalin, and on thermal nociception in the tail-flick test and the hot plate test. RA neither significantly impaired motor coordination in the rotarod test nor did spontaneous locomotion in the open-field test. RA did not enhance the pentobarbital sodium induced sleep time. These results indicated that the observed antinociceptive activity of RA was unrelated to sedation or motor abnormality. Core body temperature measurement showed that RA did not affect temperature during a 2-hour period. Furthermore, RA-induced antinociception in the hot plate test was insensitive to naloxone or glibenclamide but significantly antagonized by L-NAME, methylene blue and nimodipine.

Conclusions

Therefore, it is reasonable that the analgesic mechanism of RA possibly involved the NO-cGMP signaling pathway and L-type Ca²⁺ channels.     

Anti-nociceptive activity of aqueous fraction from the MeOH extracts of Paederia scandens in mice

AIM OF THE STUDY: We examined the effects of the aqueous fraction (AF) on nociception models mice induced by the chemical and the thermal stimuli so as to elucidate the analgesic activity and provide scientific basis for the clinical use of Paederia scandens. MATERIALS AND METHODS: The AF of MeOH extract from P. scandens was evaluated on anti-nociceptive activity in mice using chemical and thermal models of nociception. RESULTS: Given orally, the aqueous fraction at doses of 200, 400 and 800 mg/kg produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid and subplantar formalin injections and on thermal nociception in the tail-flick test and in the hot plate test. More significant inhibition of nociception was observed at dose of 800 mg/kg of this fraction. In the pentobarbital sodium -induced sleeping time test and the open-field test, the aqueous fraction neither significantly enhanced the pentobarbital sodium -induced sleeping time nor impaired the motor performance, indicating that the observed anti-nociception was unlikely due to sedation or motor abnormality. CONCLUSIONS: These results suggested that the aqueous fraction produced anti-nociception possibly related to the iridoid glycosides and polysaccharides in this fraction.     

Pharmacological Effects of Aqueous Extract from Valeriana adscendens

A purified aqueous extract of Valeriana adscendens Trel. (Valerianaceae) was investigated for its pharmacological profile. The extract did not exert significant changes on the nociceptive threshold in the hot plate and tail flick test and no effect was registered on the guinea-pig ileum. On the other hand, the extract significantly reduced both the locomotor activity and motor coordination of mice; it also prolonged sleep induced by pentobarbital, whereas no significant cataleptic response was observed. These effects may suggest neuroleptic-like properties.     

Antinociceptive effects of the tubercles of Anredera leptostachys

The tubercles of Anredera leptostachys are used as an antinociceptive and anti-inflammatory in the popular medicine of the Caribbean basin. In the present work, the anti-nociceptive and central nervous system depressant (CNS) effects of the methanolic extract from the tubercles of A. leptostachys have been evaluated. The antinociceptive activity was assayed in several experimental models in mice: acetic acid, formalin and hot plate tests. The methanolic extract (250 and 500 mg/kg) significantly and in a dose-dependent manner reduced the nociception induced by the acetic acid (P < 0.001). In the hot plate test, the extract significantly increased the latency time of jump although it slightly increased the licking time. The naloxone partially reversed the antinociception of the extract in the hot plate test. In the formalin test, the methanolic extract also significantly reduced the painful stimulus but the effect was not dose-dependent. In the study of the CNS-depressant effects, the extract was found to produce a significant reduction of the exploratory capacity with both doses assayed (P < 0.001). The muscular relaxation only decreased with the higher doses assayed (P < 0.001). The escape instinct was also significantly reduced (P < 0.001) by the two doses of the extract and both were more effective than standard drugs morphine and diazepam.     

Evaluation of the antinociceptive activity of extracts of Sonchus oleraceus L. in mice

Ethnopharmacological relevance

Sonchus oleraceus L. has been used to relieve pain in Brazilian folk medicine.

Aim of the study

Sonchus oleraceus L. has been used to relieve pain in Brazilian folk medicine. This study was conducted to establish the antinociceptive properties of hydroethanolic and dichloromethane extracts from aerial parts of Sonchus oleraceus in mice using chemical and thermal models of nociception.

Materials and methods

The formalin, hot plate, and tail immersion tests as well as acetic acid-induced writhing were used to investigate the antinociceptive activity in mice.

Results

Given orally, the extracts at test doses of 30–300 mg/kg, produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid and subplantar formalin since decreased the number of writhing episodes and the time licking. Treatment with the extracts in the same doses produced a significant increase of the reaction time in tail immersion and in the hot plate test. The extracts administered at 300 mg/kg, p.o. had a stronger antinociceptive effect than indomethacin (5 mg/kg, p.o.) and morphine (10 mg/kg, p.o.).

Conclusion

The extracts of Sonchus oleraceus markedly demonstrated antinociceptive action in mice, which supports previous claims of its traditional use.     

Antinociceptive activity of alcoholic extract of Hemidesmus indicus R.Br. in mice

The ethanolic extract of roots of Hemidesmus indicus R.Br. (family: Asclepiadaceae) was investigated for possible antinociceptive effect in mice. Three models were used to study the effects of extracts on nociception, which was induced, by acetic acid (Writhing test), formalin (Paw licking test) and hot plate test in mice. Hemidesmus indicus R.Br. extract was administered in the dose range of 25, 50 and 100mg/kg orally 1h prior to pain induction. The preliminary phytochemical screening of the extract showed the presence of triterpenes, flavonoids, pregnane glycosides and steroids. Oral administration of Hemidesmus indicus extract revealed dose-dependent antinociceptive effect in all the models for antinociception and it blocked both the neurogenic and inflammatory pain and the nociceptive activity was comparable with the reference drug. The results indicate that alcoholic extract of Hemidesmus indicus R.Br. possesses a significant antinociceptive activity. The activity can be related with the significant phytochemicals such as triterpenes, flavonoids, and sterols reported in the root extract.     

Anti‐Inflammatory and Antinociceptive Activity of Urera aurantiaca

Urera aurantiaca Wedd. (Urticaceae) is a medicinal plant commonly used in traditional medicine to relieve pain in inflammatory processes. In the present study, the in vivo anti‐inflammatory and antinociceptive effects of U. aurantiaca methanolic extract and its possible mechanisms of action were investigated. The extract showed anti‐inflammatory activity in the ear edema in mice test (34.3% inhibition), myeloperoxidase (MPO) activity was markedly reduced in animals administered with the extract: within 49.6% and 68.5%. In the histological analysis, intense dermal edema and intense cellular infiltration of inflammatory cells were markedly reduced in the ear tissue of the animals treated with the extract. In the carrageenan‐induced hind paw edema in rats assay the extract provoked a significant inhibition of the inflammation (45.5%, 5 h after the treatment) and the MPO activity was markedly reduced (maximum inhibition 71.7%), The extract also exhibited significant and dose‐dependent inhibitory effect on the increased vascular permeability induced by acetic acid. The extract presented antioxidant activity in both 2,2‐diphenyl‐1‐picrylhydrazyl and 2,2′‐azinobis 3‐ethylbenzothiazoline 6‐sulfonic acid tests and its total phenol content was 35.4 ± 0.06 mg GAE/g of extract. Also, the extract produced significant inhibition on nociception induced by acetic acid (ED₅₀: 8.7 mg/kg, i.p.) administered intraperitoneally and orally. Naloxone significantly prevented this activity. Copyright © 2014 John Wiley & Sons, Ltd.     

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 antipyretic effects of Dodonaea angustifolia and Salvia africana-lutea

Water extracts of Dodonaea angustifolia L. and Salvia africana-lutea L., were investigated for analgesic and antipyretic activities using acetic acid writhing and hot plate tests, and lipopolysaccharide (LP)-induced pyrexia test in mice and rats, respectively. D. angustifolia and S. africana-lutea significantly inhibited acetic acid-induced writhing and also significantly delayed the time of reaction of mice to thermal stimulation produced by the hot plate. D. angustifolia and S. africana-lutea significantly reduced fever induced by LP. Paracetamol produced similar effects to D. angustifolia and S. africana-lutea on the acetic acid-induced writhing but has no effect on hot plate-induced nociception and on pyrexia produced by LP. These data indicate the analgesic and antipyretic potential of D. angustifolia and S. africana-lutea.     

Antinociceptive properties of 25‐methoxy hispidol A,a triterpinoid isolated from Poncirus trifoliata (Rutaceae) through inhibition of NF‐κB signalling in mice

The 25‐methoxy hispidol A (25‐MHA) is a triterpenoid, isolated from the immature fruit of Poncirus trifoliata (Rutaceae). The pretreatment with 25‐MHA markedly (p < 0.001) attenuated the formalin‐induced biphasic responses as well as acetic acid‐induced writhing responses. The intraperitoneal administration of 25‐MHA significantly attenuated the mechanical hyperalgesia (p < 0.001) and allodynia (p < 0.05). Similarly, 25‐MHA also significantly attenuated (p < 0.001) complete Freund's adjuvant (CFA)‐induced paw edema in mice. The 25‐MHA treatment significantly attenuated the production of nuclear kappa B (NF‐κB) (p65 nuclear subunit). The cytokines are the important mediators of inflammation and pain; however, treatment with 25‐MHA exhibited significant inhibition (p < 0.001) on the mRNA expression levels of various inflammatory mediators. The 25‐MHA administration also significantly enhanced antioxidant enzymes (p < 0.001) and inhibited the oxidative stress markers. The current study indicates that 25‐MHA significantly (p < 0.001) inhibited the nitric oxide (NO) in mice plasma. Similarly, the haematoxylin and eosin (H&E) staining shows that 25‐MHA administration significantly inhibited the inflammatory process in the mice paw tissue compared with the CFA‐treated group. The 25‐MHA treatment did not exhibited any toxicity on the liver, kidney, muscles strength, and motor co‐ordination in mice. The 25‐MHA was coadministered with the various drugs such as tramadol, piroxicam, and gabapentin to observe the synergistic effect.     

Antinociceptive activity of aerial parts of Polygonatum verticillatum: attenuation of both peripheral and central pain mediators

Polygonatum verticillatum All. is used traditionally as an analgesic and plant diuretic. The methanol extract of aerial parts of Polygonatum verticillatum (PA) was assessed in various experimental paradigms. The pain threshold in the form of abdominal constriction induced by acetic acid was significantly (p < 0.01) inhibited by PA at test doses (50, 100 and 200 mg/kg). In the formalin test, PA elicited a significant (p < 0.01) analgesic activity in both phases and strongly attenuated the formalin‐induced flinching behaviour. The hot plate test was used to evaluate central involvement in the analgesic profile of PA. The PA significantly relieved thermal‐induced pain. From a mechanistic point of view, the central antihyperalgesic activity was tested for antagonism with naloxone, but no antagonism was observed. The current investigations suggest that the active constituent(s) in PA has an analgesic profile with predominant peripheral activity which is augmented by an opioid independent central effect. In the diuretic assay, PA (300 and 600 mg/kg) showed mild insignificant diuretic activity. Our study rationalized the traditional use of Polygonatum verticillatum in the treatment of painful conditions. Copyright © 2011 John Wiley & Sons, Ltd.     

Investigations on the antinociceptive effect of Psidium guajava leaf essential oil and its major constituents

The antinociceptive effect of leaf essential oil from Psidium guajava and its major constituents, β-caryophyllene and α-pinene was assessed using chemical (formalin and acetic acid) and thermal (hot-plate) nociceptive tests in adult male albino mice. Oral administration of 100, 200 and 400 mg/kg of essential oil produced a significant antinociceptive effect in the formalin test and at 200 and 400 mg/kg in the acetic acid- induced writhing test. Of the major components only α-pinene, but not the β-caryophyllene, demonstrated significant antinociception in the formalin test. Neither the essential oil nor the major components could exert any significant effect in the hot-plate test. Pretreatment of mice with caffeine (20 mg/kg, i.p.), significantly inhibited the antinociceptive effect of essential oil in the formalin test. Naloxone (1 mg/kg, s.c.), the opioid antagonist, however, failed to antagonize it. These results suggest that the antinociceptive effect of P. guajava essential oil is probably mediated by endogenously released adenosine. © 1998 John Wiley & Sons, Ltd.     

Antinociceptive activity of aqueous extract and isolated compounds of Lithrea molleoides

Ethnopharmacological relevance

Lithrea molleoides (Vell.) Engl. (Anacardiaceae) is a medicinal plant commonly used in traditional medicine in South America.

Aim of the study

In the present study, the in vivo antinociceptive effect of L. molleoides' aqueous extract and its isolated compounds has been investigated.

Materials and Methods

Antinociceptive activity was evaluated through writhing, formalin and hot plate tests in mice. The phytochemical analysis was performed.

Results

The extract produced significant inhibition on nociception induced by acetic acid (ED50: 8.7 mg/kg, i.p.) and formalin (ED50: 7.7 mg/kg, i.p.) administered intraperitoneally and also orally. Yohimbine diminished the activity of the extract in the acetic acid test meanwhile haloperidol enhanced its effect. Two majority compounds, shikimic and vanillic acid were active in chemical nociceptive models used in this work, producing the highest inhibition of the writhing response at a dose of 30 mg/kg i.p. (55.4% and 57.1%, respectively) meanwhile at 100 mg/kg p.o. produced a slight response (23.3% and 23.9%, respectively).

Conclusions

These results suggest that L. molleoides' aqueous extract produced antinociception possibly related to the presence of shikimic and vanillic acid. The adrenergic and dopaminergic systems seem to be involved in the mechanism of antinociception of the extract.     

高良姜总黄酮对大鼠内脏高敏感性模型及镇痛作用研究

目的: 研究高良姜总黄酮(GLJ)对乙酸诱导内脏高敏性肠易激综合征(IBS)模型大鼠的治疗作用及其镇痛作用。 方法: 建立大鼠IBS模型,将实验动物随机分为模型组、匹维溴铵组(0.02 g·kg^-1)、GLJ高、中、低剂量组(1,0.5,0.25 g·kg^-1),连续给药2 周后评估乙酸诱导IBS模型大鼠的腹部回缩反射(AWR)状态,观察GLJ对乙酸诱导IBS模型大鼠的治疗作用;采用热板法、乙酸扭体法、压尾法、甲醛法研究GLJ的镇痛作用。 结果: GLJ能够有效降低乙酸诱导IBS模型大鼠内脏的敏感性(P<0.01或P<0.05);对热刺激、乙酸、甲醛所诱发的小鼠疼痛均有一定的抑制作用(P<0.01或P<0.05)。 结论: GLJ对IBS模型大鼠有较好的治疗作用及镇痛作用。     

Antinociceptive activity of Amaranthus spinosus in experimental animals

Aim of the study

50% ethanol extract (ASE) of Amaranthus spinosus (whole plant) has been evaluated for antinociceptive and antiinflammatory activities.

Materials and methods

Analgesic and antiinflammatory activities were studied by measuring nociception by formalin, acetic acid, hot plate, tail immersion method while inflammation was induced by carrageenan.

Results

ASE had significant dose dependent percentage protection against acetic acid (0.6% of 10 ml) induced pain and the effects were also compared to aspirin, morphine and naloxone while formalin induced pain (0.05 ml of 2.5%) was significantly blocked only at higher dose (400 mg/kg) in first phase. ASE significantly blocked pain emanating from inflammation at all the doses in second phase. The reaction time in hot plate was increased significantly and dose dependently where as pretreatment with naloxone rigorously reduced the analgesic potentials of ASE. Further in tail immersion test the same dose dependent and significant activity was observed. Aspirin had no effect on thermal induced pain i.e. hot plate and tail immersion tests but showed an effect on writhing test.

Conclusions

Our investigation show that Amaranthus spinosus possess significant and dose dependant antiinflammatory activity, it has also central and peripheral analgesic activity.     

Evaluation of the analgesic effect of alkaloid extract of Peganum harmala L.: possible mechanisms involved

The seeds of Peganum harmala L. (Pgh) (Zygophyllaceae) have been used in Moroccan traditional medicine for treatment of a various diseases and to relieve dolorous process. The major objective of this paper was to investigate the mechanism of the analgesia induced by alkaloid extract of Peganum harmala. In the present work, the antinociceptive action was assayed in several experimental models in mice: writhing, formalin, and hot plate tests. The alkaloid extract (12.5 and 25mg/kg) and in a dose-dependent manner significantly reduced the nociception by acetic acid intraperitoneal injection (p<0.001). In the formalin test, the extract also significantly reduced the painful stimulus in both phases of the test (p<0.001). Treatment with the extract when given by (i.p. or i.c.v.) or with morphine (10mg/kg, i.p.) produced a significant increase of the reaction time in hot plate test. These result showed that the alkaloid extract of Pgh contains active analgesic principles acting both centrally and peripherally. Furthermore, this antinociceptive effect has been avoided by naloxone at a dose of 1mg/kg in the first phase of formalin and hot plate tests indicating that this extract act partly through an opioid-mediated mechanism. In conclusion, the alkaloid extract of Peganum harmala seems to have both central and peripheral antinociceptive activities which may be mediated by opioid receptors.     

Anti-inflammatory and anti-nociceptive effects of Sphaeranthus senegalensis

Sphaeranthus senegalensis Vaill (Asteraceae) is used in traditional medicine as a remedy for rheumatic pains and other ailments. The anti-inflammatory and anti-nociceptive activity of the aqueous extract of the whole shoot of the plant was evaluated in mice and rats. Activity of the extract against egg-albumin induced hind paw oedema was measured to evaluate the anti-inflammatory activity while the anti-nociceptive potency was evaluated using three painful stimuli viz acetic acid induced abdominal constriction and hot plate test in mice, and the formalin test in rats. Results indicated that the extract possess remarkable dose dependent anti-inflammatory activities in rats. The extract also showed anti-nociceptive activities against acetic acid induced writhing, formalin and the hot plate pain models. The effects were significant (P < 0.05) when compared with the saline control group. The results suggest the presence of a potent anti-inflammatory and anti-nociceptive principle in the extract, which support the folkloric use of the plant in relieving rheumatic pains.     

Ursolic acid plays a role in Nepeta sibthorpii Bentham CNS depressing effects

The sedative, anticonvulsant and analgesic activity of ursolic acid, a terpenoid bioassay-isolated from Nepeta sibthorpii Bentham, was evaluated in mice. The oral administration of ursolic acid (2.3 mg/kg) produced a significant depressant effect on CNS by reducing spontaneous motor activity and the number and lethality of pentylenetetrazol (PTZ)-induced seizures. Two models of nociception, the writhing test and the hot plate test, were also used to examine the analgesic effect of ursolic acid. At a dose of 2.3 mg/kg, ursolic acid caused an inhibition of acetic acid-induced abdominal constriction, but was inactive in the hot plate test. Treatment at a higher dose (20 mg/kg) significantly increased the reaction time in the hot plate test. This effect, reversed by naloxone, evidently involves opioid receptors, but the analgesic activity of ursolic acid may be related also to the antiinflammatory and antioxidant properties of this compound.     

Antinociceptive effects of ethanolic extract from the flowers of Acmella oleracea (L.) R.K. Jansen in mice

Ethnopharmacological relevance

In Brazil, Acmella oleracea (L.) R.K. Jansen, popularly known as “jambu”, has been used by some communities from Amazon region to treat toothache. In this study we examined the antinociceptive effect of the ethanolic extract obtained from the flowers of Acmella oleracea (EEAO) in animal models of nociceptive (chemical and thermal) and neuropathic (partial sciatic nerve ligation) pain.

Materials and methods

Adult male mice were treated by intraperitoneal route (i.p.) with EEAO before the induction of nociceptive response by formalin, capsaicin and cinnamaldehyde, thermal heat hyperalgesia (hot plate test) and mechanical allodynia (traumatic sciatic nerve injury). Acute toxicity and non-specific sedative effects were evaluated.

Results

EEAO (10, 30 and 100 mg/kg) reduced both neurogenic and inflammatory phases of the formalin- and also capsaicin- and cinnamaldehyde-induced orofacial nociception. Interestingly, EEAO at 100 mg/kg (i.p.) also reversed capsaicin-induced heat hyperalgesia assessed as the latency to paw withdrawal in the hot plate test. Also in the hot plate test, paw withdrawal latency was increased by EEAO (100 mg/kg) and this response was only partially reversed by naloxone. Furthermore, EEAO (100 mg/kg) also reduced mechanical allodynia caused by partial sciatic nerve ligation for 3 h. The estimated LD50 value was 889.14 mg/kg and EEAO did not alter the locomotion of animals in the open-field test.

Conclusion

Taken together, our data show that EEAO produces prevalent antinociceptive effects and does not cause adverse effects. The presence of N-alkylamides, including spilanthol, suggests that the therapeutic effect of EEAO is related to its highest anesthetic activity.     

Antinociceptive and anti-inflammatory potential of extract and isolated compounds from the leaves of Salvia officinalis in mice

Ethnopharmacological relevance

Salvia officinalis L. has been used as a traditional herbal medicine for gastric disturbances and inflammatory processes. This study investigated the toxicological, antinociceptive and anti-inflammatory effects of the hydroalcoholic extract (HE) from leaves of Salvia officinalis and its isolated compounds in mice.

Materials and methods

Mice were treated with HE before the induction of nociceptive response by chemical agents (acetic-acid, formalin, glutamate, capsaicin and cinnamaldehyde). Total leukocytes and plasma extravasation induced by acetic acid and paw oedema induced by glutamate, capsaicin and cinnamaldehyde were also measured. The antinociceptive effect of carnosol and ursolic acid/oleanolic acid were evaluated on formalin and cinnamaldehyde models.

Results

In the acute toxicity test the value of estimated LD50 for HE was 44.7579 g/kg. Oral administration of HE (10, 30 and 100 mg/kg) inhibited the number of writhings, total leukocytes and plasma extravasation induced by acetic acid. In the formalin test, HE reduced both neurogenic and inflammatory phases, effect that was affected by naloxone. The glutamate-, capsaicin- and cinnamaldehyde-induced nociception and paw oedema were reduced by HE at doses that did not affect the locomotor activity of mice in the open field test. Carnosol (10 mg/kg) and ursolic acid/oleanolic acid (30 mg/kg) inhibited the inflammatory phase of formalin and the nociception and mechanical allodynia induced by cinnamaldehyde.

Conclusions

These results demonstrate that HE presents significant anti-inflammatory and also antinociceptive effects on chemical behavioral models of nociception that involves an opioid mechanism. In addition, carnosol and ursolic acid/oleanolic acid contained in this plant appears to contribute for the antinociceptive property of the extract, possibly through a modulatory influence on TRPA1-receptors. However, further studies regarding the precise site and the mechanism of action of HE and carnosol and ursolic acid/oleanolic acid merited exploring further.