Antinociceptive activity of methanol extract of flowers of Impatiens balsamina

Ethnopharmacological relevance

Impatiens balsamina Linn. (Balsaminaceae), an annual herb locally called “Dopati”, is cultivated as an ornamental garden plant in Bangladesh. Flowers of the plant are used in folk medicine to treat lumbago, neuralgia, burns and scalds.

Aim of the study

This study evaluated the antinociceptive effect of the methanol extract of I. balsamina flowers (MIB).

Materials and methods

The extract was evaluated for antinociceptive activity using chemical- and heat-induced pain models such as acetic acid-induced writhing, hot plate, tail immersion and formalin test. To verify the possible involvement of opioid receptor in the central antinociceptive effect of MIB, naloxone was used to antagonize the effect. The effect of MIB on central nervous system (CNS) was also studied using hole cross and open field tests.

Results

MIB demonstrated strong and dose-dependent antinociceptive activity in all the chemical- and heat-induced mice models (p<0.05). These findings imply the involvement of both peripheral and central antinociceptive mechanisms. The use of naloxone confirmed the association of opioid receptors in the central antinociceptive effect. MIB also showed significant central nervous system depressant effect (p<0.05).

Conclusion

This study reported the peripheral and central antinociceptive activity of the flowers of I. balsamina and rationalized the traditional use of the flower in the treatment of different painful conditions.     

Antinociceptive activity of fruits extracts and “arrope” of Geoffroea decorticans (chañar)

Ethnopharmacological relevance

Geoffroea decorticans (chañar) fruits and their derivate product (arrope) have been traditionally used as food and a folk medicine for the treatment of a wide variety of diseases including bronchopulmonary disorders and to relieve dolorous process.

Aim of the study

In order to evaluate the pharmacology action of this plant, studies were performed of antinociceptive and antioxidant activities.

Materials and methods

The aqueous and ethanolic extracts and arrope of chañar were evaluated in various established pain models, including chemical nociception induced by subplantar formalin and intraperitoneal acetic acid and thermal nociception method, such as tail immersion test in rats. To examine the possible connection of the opioid receptor to the antinociceptive activity of extracts and arrope it was performed a combination test with naloxone, a non-selective opioid receptor antagonist.

Results

The aqueous extract and arrope (1000 mg/kg) caused an inhibition of the pain in formalin test in the first phase, similar to morphine and decrease in the second phase. In a combination test using naloxone, diminished analgesic activity of aqueous extract and arrope were observed, indicating that antinociceptive activity is connected with the opioid receptor. The aqueous extract and arrope, caused an inhibition of the writhing response induced by acetic acid. Central involvement in analgesic profile was confirmed by the tail immersion test, in which the aqueous extract and arrope showed a significant analgesic activity by increasing latency time. The aqueous extract showed higher antioxidant activity than the arrope, it may be due to the cooking process.

Conclusions

This study has shown that the aqueous extract and arrope of Geoffroea decorticans (chañar) fruits, does possess significant antinociceptive effects. It is further concluded that aqueous extract with maximum inhibition of free radical is the most potent extract amount tested extracts. At the oral doses tested the aqueous extract and arrope were non-toxic. The present results justifies their popular use and constitutes the first validation study of the antinociceptive action.     

Antinociceptive activity of fractions from Couroupita guianensis Aubl. leaves

Ethnopharmacological relevance

Couroupitaguianensis Aubl. (Lecythidaceae) is popularly known in Brazil as “abricó-de-macaco”. Infusions or teas obtained from its leaves, flowers, and barks are used in South America for the treatment of several disorders such as pain and inflammatory processes.

Aim of the study

Evaluate antinociceptive effects of crude ethanol extract (CEE) and its fractions in three analgesic models (acetic acid-induced contortions, tail flick, and hot plate) and study the possible mechanism of their action.

Materials and methods

CEE, hexane, dichloromethane, ethyl acetate, and butanol fractions (10, 30, and 100 mg/kg, p.o.) and the reference drug morphine (5 mg/kg, s.c.) were evaluated. To elucidate the mechanism of action from the fractions, animals were pre-treated (30 min) with atropine (muscarinic receptor antagonist, 1 mg/kg, s.c.), mecamylamine (nicotinic receptor antagonist, 2 mg/kg, s.c.), naloxone (opioid receptor antagonist, 1 mg/kg, s.c.) or l-nitro arginine methyl ester (l-NAME, nitric oxide synthase inhibitor, 3 mg/kg, s.c.).

Results

CEE and fractions significantly inhibited the number of contortions induced by acetic acid. All fractions showed antinociceptive activity in the tail flick model, being the hexane and ethyl acetate the most potent and long acting fractions. In the hot plate method the highest effect observed was at the dose of 100 mg/kg from all fractions. Administration of naloxone inhibited the antinociceptive effect of fractions. Pre-treatment of mice with atropine reduced the antinociceptive activity of CEE and its fractions, the exception being the dichloromethane fraction. Mecamylamine did not inhibited the effect of dichloromethane fraction. l-NAME reduced the anti-hyperalgesic effect of all fractions, but the most prominent effect was observed in the antinociceptive activity caused by CEE and butanol fraction.

Conclusions

Results obtained demonstrated that Couroupita guianensis CEE and its fractions have antinociceptive activity that is mediated, at least in part, by opioid and cholinergic systems and nitric oxide pathway.     

Characterization of the antinociceptive and anti-inflammatory activities from Cocos nucifera L. (Palmae)

Aim of the study

Cocos nucifera cultivated in Brazil is known as “coco-da-Bahia” or “coqueiro-da-Índia”. The tea from the husk fiber is widely used to several inflammatory disorders. Crude extract and fractions obtained from Cocos nucifera “common variety” were evaluated to test the anti-inflammatory and antinociceptive activities.

Materials and methods

Crude extract (CE, 50, 100, and 150 mg/kg), fraction 1 (F1, molecular weight lesser than 1 kDa, 1, 10, and 50 mg/kg), fraction 2 (F2, molecular weight higher than 1 kDa, 1, 10, and 50 mg/kg), and the references drugs morphine (5 mg/kg), acetilsalicilic acid (200 mg/kg), prometazine (30 mg/kg), and metisergide (5 mg/kg) were evaluated on models of analgesia and inflammation.

Results

CE, F1, and F2 significantly develop peripheral and central antinociceptive activity but with less effect on supra-spinal regions of the brain. Administration of the opioid antagonist, naloxone (5 mg/kg) inhibited the antinociceptive effect indicating that Cocos nucifera crude extract and fractions may be acting in opioid receptors. CE and F1 also inhibited rat paw edema induced by histamine, and serotonin.

Conclusions

results demonstrated that Cocos nucifera and its fractions have antinociceptive and anti-inflammatory activities which confirm the popular use of this plant in several inflammatory disorders.     

Inhibitory effects of the root extract of Litsea cubeba (lour.) pers. on adjuvant arthritis in rats

Ethnopharmacological relevance

The dried root of Litsea cubeba (Lour.) Pers. (Family Lauraceae) has long been used as a folk remedy in Traditional Chinese Medicine (TCM) and Dai Ethnopharmacy for the treatment of rheumatic diseases in southwestern China.

Aim of the study

This study investigated the preventive efficacy of Litsea cubeba root in treating rheumatoid arthritis using Freund's complete adjuvant (CFA) induced arthritis (AA) in rat model.

Materials and methods

Arthritis was induced in male Wistar rats by immunization with CFA. Ethanol extract (EELC) and water extract (WELC) of Litsea cubeba root both at 50 mg/kg and 200 mg/kg were orally administered from a day after the induction of arthritis. Paw swelling, arthritic score, body weight growth rate, index of thymus and spleen were observed, and the production of TNF-α, IL-1β, IL-6 and IL-10 in serum were measured by enzyme-linked immunosorbent assay. The expression levels of inflammatory enzymes like cyclooxygenase and lipoxygenase were also measured by enzyme-linked immunosorbent assay. Moreover, histological changes in the ankle joint were analyzed in AA rats.

Results

Both EELC and WELC significantly suppressed paw swelling and arthritic score, increased the loss in body weight and decreased the index of thymus. Histopathological improvement in joint architecture was also observed in EELC, WELC-treated AA rats. The expression levels of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) were decreased on treatment with EELC and WELC. Furthermore, the overproduction of TNF-α, IL-1β and IL-6 were remarkably attenuated in serum of all Litsea cubeba-treated rats, however, IL-10 was markedly increased at doses of 50 mg/kg of EELC and WELC.

Conclusions

These results indicate that extract of Litsea cubeba root significantly attenuates adjuvant arthritis in rats by decreasing the levels of TNF-α, IL-1β and IL-6 and increasing of IL-10 in serum as well as down-regulate the levels of inflammatory enzymes such as COX-2 and 5-LOX. This suggests that Litsea cubeba root might be used as a therapeutic agent for the treatment of human arthritis.     

Bioguided isolation of myricetin-3-O-β-galactopyranoside with antinociceptive activity from the aerial part of Davilla elliptica St.-Hil

Ethnopharmacological relevance

Davilla elliptica St.-Hil. (Dilleniaceae) is a medicinal plant traditionally used in Brazil to treat inflammatory processes, to relieve pain, as diuretic, gastro- and hepatoprotective agents.

Aim of the study

To undertake the fractionation of the ethanolic extract from Davilla elliptica leaves guided by an antinociceptive assay.

Materials and methods

The antinociceptive activity was evaluated through the formalin test in mice. Extract fractionation was performed by percolation through silica gel and partition between immiscible solvents, followed by successive column chromatography over Sephadex LH-20 and preparative RP-HPLC. Structure elucidation of the isolated compound was accomplished by spectroscopic data.

Results

The EtOAc and MeOH fractions derived from the crude extract reduced significantly the licking time in the late phase of the formalin test. The bioguided fractionation of the MeOH fraction resulted in the isolation of myricetin-3-O-β-galactopyranoside, which produced significant inhibition on nociception induced by formalin (ID₅₀=0.26 mg/kg; p.o.).

Conclusions

These results point out that myricetin-3-O-β-galactopyranoside contributes for the antinociceptive effect of Davilla elliptica extract, a constituent considerably more potent than diclofenac, employed as reference drug.     

Antinociceptive activities of the methanol extract of the bulbs of Dioscorea bulbifera L. var sativa in mice is dependent of NO–cGMP–ATP-sensitive-K channel activation

Ethnopharmacological relevance

Dioscorea bulbifera var sativa is a medicinal plant commonly used in Cameroonian traditional medicine to treat pain and inflammation.

Aim

The present work evaluated the effects of the methanol extract of the bulbs of Dioscorea bulbifera in inflammatory and neuropathic models of pain and further investigated its possible mechanism of action.

Materials and methods

The effects of Dioscorea bulbifera administered orally at the doses of 250 and 500 mg/kg were tested in mechanical hypernociception induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA), lipopolysaccharides (LPS) or prostaglandin-E₂ (PGE₂), as well as in partial ligation sciatic nerve (PLSN), nociception induced by capsaicin and thermal hyperalgesia induced by i.pl. injection of CFA. The therapeutic effects of Dioscorea bulbifera on PGE₂-induced hyperalgesia were evaluated in the absence and in the presence of l-NAME, an inhibitor of nitric oxide synthase (NOS) and glibenclamide, an inhibitor of ATP-sensitive potassium channels.

Results

The extract showed significant antinociceptive effects in persistent pain induced by CFA and on neuropathic pain induced by PLSN. The effects of Dioscorea bulbifera persisted for 5 days after two administrations in CFA-induced hypernociception. Dioscorea bulbifera significantly inhibited acute LPS-induced pain but failed to reduce thermal hypernociception and capsaicin-induced spontaneous nociception. The antinociceptive effects of this plant extract in PGE₂ model was antagonized by either l-NAME or glibenclamide.

Conclusion

Present demonstrate the antinociceptive activities of Dioscorea bulbifera both in inflammatory and neuropathic models of pain and these effects may result, at least partially, from its ability to activate the NO–cGMP–ATP-sensitive potassium channels pathway.     

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.     

Antiinflammatory effects of Viola tricolor gel in a model of sunburn in rats and the gel stability study

Ethnopharmacological relevance

Viola tricolor, popularly known as heartsease has been empirically used in several skin disorders, including burns.

Aim of the study

The objective of this study was investigate the antinociceptive and antiinflammatory effect of a gel containing extract of Viola tricolor flowers on thermal burn induced by UVB irradiation and to perform gel stability study.

Methods

The antinociceptive and antiinflammatory effect were evaluated by static and dynamic mechanical allodynia model, paw edema, and neutrophilic cell infiltration. Metabolites compounds were quantified by HPLC. The gel stability study was performed analyzing organoleptical aspects, besides pH, viscosity, and quantification of rutin by HPLC.

Results

In the results were evidenced changes in threshold in statical and dynamic mechanical allodynia (I_max=100±10% and 49±10%, respectively), paw edema (I_max=61±6%), and myeloperoxidase activity (I_max=89±5%). Such effects may be attributed, in part, to rutin, salicylic and chlorogenic acids, and others compounds found in this species. No important changes were detected in the stability study, in all aspects analyzed in temperature below 25 °C.

Conclusion

These findings suggest that Viola tricolor gel has an antinociceptive and antiinflammatory effect in the ultraviolet-B-induced burn, since maintain the temperature below 25 °C.     

Analgesic and anti-inflammatory effects of Ligularia fischeri leaves in experimental animals

Aim of the study

The ethanol extract (LF) of Ligularia fischeri var. spiciformis (leaf) has been evaluated for antinociceptive and anti-inflammatory activities in mice.

Materials and Methods

Analgesic and anti-inflammatory activities were studied by measuring nociception induced by formalin, acetic acid and hot-plate, and inflammation induced by carrageenan, formalin, and arachidonic acid.

Results

The acute treatment of mice with LF at doses of 100 and 200 mg/kg, by oral administration, produced a significant antinociceptive effect in the acetic acid-induced writhing, formalin-induced pain licking and hot-plate-induced pain. Also, the LF significantly inhibited both carrageenan- and formalin-induced inflammation as well as arachidonic acid-induced ear edema in mice.

Conclusions

These inhibitions were statistically significant (P < 0.05). Thus, our investigation suggests a potential benefit of Ligularia fischeri in treating conditions associated with inflammatory pain.     

Characterization of the antinociceptive and anti-inflammatory activities of fractions obtained from Copaifera multijuga Hayne

Ethnopharmacological relevance

Copaifera multijuga Hayne (Leguminosae) is a tree that produces an oleoresin, which is extensively commercialized in Brazil as capsules or crude oil for the treatment of several disorders. Ethnopharmacological studies show a diversity of indications such as anti-inflammatory and epidermal wound cicatrization.

Aim of the study

In the present work three fractions obtained from Copaifera multijuga oleoresin (hexane (HF), chloroform (CF), and methanol (MF) from a KOH impregnated silica gel column chromatography, representing the three main classes of compounds in the Copaifera genus (hydrocarbon sesquiterpenes, oxygenated sesquiterpenes and acidic diterpenes), were evaluated using antinociceptive and anti-inflammatory models.

Materials and methods

HF, CF, and MF (doses ranging between 1 and 150 mg/kg, depending on the model used), Copaifera multijuga oleoresin (CMO, 100 mg/kg, p.o.) and the reference drug morphine (5 mg/kg, p.o.) were evaluated using models for analgesia (acetic acid-induced contortions and tail flick) or inflammation (rat paw oedema and increase in vascular permeability). To elucidate the mechanism of action from the fractions, animals were pre-treated with naloxone (opioid receptor antagonist, 5 mg/kg, i.p.).

Results

Fractions significantly inhibited (in a concentration-dependant way) the number of contortions induced by acetic acid and the second phase of formalin-induced licking response. Similar results were observed in the tail flick model. The central antinociceptive effect for HF and CF at the doses of 50 and 100 mg/kg was higher than the one observed for morphine (1 mg/kg). Administration of naloxone inhibited the antinociceptive effect of fractions indicating that HF, CF, and MF may be acting on opioid receptors. All three fractions also inhibited rat paw oedema and the increase in vascular permeability induced by several phlogistic agents (carrageenan, histamine, and serotonin).

Conclusions

Our results indicate that fractions obtained from Copaifera multijuga Hayne demonstrate an antinociceptive effect probably mediated by opioid receptors, and anti-inflammatory activity through inhibition of histaminergic and serotoninergic pathways.     

Antinociceptive effect of Lecythis pisonis Camb. (Lecythidaceae) in models of acute pain in mice

Ethnopharmacological relevance

Lecythis pisonis Camb., also known in Brazil as sapucaia, is used in folk medicine against pruritus, muscle pain and gastric ulcer.

Aim of the study

To investigate the antinociceptive effect of ethanol extract from Lecythis pisonis leaves (LPEE), fractions (hexane-LPHF, ether-LPEF and ethyl acetate-LPEAF) and mixture of triterpenes [ursolic and oleanolic acids (MT)] in mice.

Materials and methods

LPEE and LPEF were evaluated on the acetic acid induced writhings and formalin, capsaicin and glutamate tests. In addition, MT was investigated on the writhings induced by acetic acid, capsaicin and glutamate tests. In the study of some possible mechanisms involved on the antinociceptive effect of LPEF, it was investigated the participation of opioid system, K⁺_ATP channels and l-arginine-nitric oxide pathway.

Results

LPEE (12.5 and 25 mg/kg, p.o.), LPEF and MT (6.25, 12.5 and 25 mg/kg, p.o.) reduced the writhings in comparison to saline. LPEE (100 mg/kg, p.o.) and LPEF (50 mg/kg, p.o.) were effective in inhibiting both phases of formalin test. In capsaicin test, LPEE (100 and 200 mg/kg, p.o.), LPEF (12.5–50 mg/kg, p.o) and MT (6.25–25 mg/kg, p.o.) showed a significant antinociceptive effect compared to the control. LPEE (25 and 50 mg/kg, p.o.), LPEF (50 and 100 mg/kg, p.o.) and MT (12.5 and 25 mg/kg, p.o.) reduced the glutamate-evoked nociceptive response. Treatment with naloxone, l-arginine and glibenclamide reversed the effect of LPEF in glutamate test.

Conclusions

These results indicate the antinociceptive effect of Lecythis pisonis leaves and suggest that this effect may be related to opioid pathway, K⁺_ATP channels, and l-arginine-nitric oxide modulation. Furthermore, these data support the ethnomedical use of this plant.     

Korean red ginseng stimulates insulin release from isolated rat pancreatic islets

Ethnopharmacological relevance

Korean red ginseng (KRG), one of heat-processed Korean ginseng (Panax ginseng C.A. Meyer), has a long history as herbal remedy for antidiabetic effect.

Aim of the study

The effect and mechanism of KRG on stimulation of insulin release were investigated in isolated rat pancreatic islets.

Material and methods

Pancreatic islets isolated from rats were used to evaluate the insulinotropic action of KRG. The effect of Ca on the insulinotropic action of KRG was investigated.

Results

The aqueous ethanolic extract of KRG (AEE-KRG) (0.1–1.0 mg/ml) significantly evoked a stimulation of insulin release at 3.3 mM glucose compared to the control. Experiments at different glucose concentrations (8.4 and 16.7 mM) showed that AEE-KRG significantly stimulated on its own whereas it did not potentiate insulin secretion induced by glucose. The extracellular Ca²⁺-free condition, a L-type Ca²⁺ channel blocker and an ATP-sensitive K⁺ channel opener significantly inhibited insulin secretion evoked by AEE-KRG.

Conclusion

These findings suggest that KRG displays beneficial effects in the treatment of diabetes at least in part via the stimulation of insulin release in a glucose-independent manner.     

Antinociceptive activity of Mirabilis jalapa in mice

Ethnopharmacological relevance

The infusion or decoction of Mirabilis jalapa leaves is used in traditional medicine in Brazil to treat inflammatory and painful diseases.

Aim of the study

The present study examined the antinociceptive effect of Mirabilis jalapa extracts from leaves and stems in models of pain in mice.

Materials, methods and results

The crude hydroethanolic extract from leaves (CrdL) was more potent than the crude extract from stems (CrdS) to inhibit abdominal constrictions induced by acetic acid, with ID₅₀ values of 5.5 (2.3–13.1) and 18.0 (11.3–28.5) mg/kg, respectively. Among the fractions tested, the Eta fraction from leaves (Eta) was more effective (maximal inhibition of 83 ± 8%) and potent (ID₅₀ of 1.1 (0.6–2.1) mg/kg) to induce antinociception. Eta and CrdL also possessed an antinociceptive effect in the tail-flick test. Pre-treatment with naloxone did not modify the antinociceptive effect of Eta, but co-administration with atropine completely prevented it. This suggests that the antinociceptive effect might depend on the cholinergic system. Instead, Eta was not able to alter the acetylcholinesterase activity in blood or spinal cord. Concerning side effects, Eta did not alter locomotor activity, body temperature, gastrointestinal transit and did not produce gastric lesions.

Conclusion

Our results demonstrate that Mirabilis jalapa presents antinociceptive activity in mice, which supports its folkloric use as an analgesic.     

Anti-inflammatory and antinociceptive activities of the ethanolic extract of Bougainvillea xbuttiana

Ethnopharmacological relevance

Bougainvillea xbuttiana is widely distributed in Mexico and it is used as an analgesic in folk medicine.

Aim of the study

In the present study the in vivo antinociceptive and anti-inflammatory effects of the Bougainvillea xbuttiana ethanolic extract have been studied in mice.

Materials and methods

The phytochemical analysis was performed. Antinociceptive activity was evaluated through writhing and formalin test in mice. The anti-inflammatory activity was determined with the carrageenan-induced mice paw oedema model. IL-6, IL-10 and IFN-γ levels were determined by enzyme-like immunosorbent assay, whereas TNF and nitrite levels were detected by standard assay with L929 cells and colorimetric Griess reactive, respectively.

Results

The results showed that the ethanolic extract of the Bougainvillea xbuttiana has significant anti-inflammatory and antinociceptive activities, by inhibition of nociception induced by acetic acid and paw oedema. This extract also induced a decrease in TNF levels and an increase of IL-6, IFN-γ and NO levels that we observed up to 2 h. The highest levels of IL-10 were observed up to 4 h. The ratios of pro-/anti-inflammatory cytokines in sera from mice injected with the ethanolic extract, may be manifesting an anti-inflammatory status.

Conclusions

The present study provides convincing evidences that Bougainvillea xbuttiana extract possesses significant anti-nociceptive and anti-inflammatory effects.     

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.     

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.     

Acute toxicity, antinociceptive activity and indole alkaloids of aqueous extract from bark of Aspidosperma cuspa (Kunth) Blake

Etnopharmacological relevance

Aspidosperma cuspa (Kunth) Blake (Apocynaceae) is popularly known as “amargosa” or “cuspa”, and its bark is used in folk medicine primarily for pain.

Aim of the study

In the present study the acute toxicity, antinociceptive effect and alkaloids of the aqueous decoction extract of the Aspidosperma cuspa bark in mice was investigated.

Materials and methods

Acute toxicity was tested using a variation of the method described by Lichfield and Wilcoxon. The antinociceptive activity was evaluated using the acetic acid induced writhing and tail-flick tests. The phytochemical analysis was performed.

Results and conclusion

Oral administration of the extract did not cause animal death (LD₅₀>4 g/kg), and the histological analysis showed an absence of alterations in all organs examined. TD₅₀ of the extract was 0.5521 g/kg for male mice and 1.1565 g/kg for females. The aqueous extract at doses 276 mg/kg (p.o.) did not produce a significant inhibition of acetic acid-induced writhes, but showed a significant effect in tail-flick test. Naloxone, an opioid receptor antagonist, pretreatment inhibited significantly the antinociceptive activity of the extract. It is suggested that the aqueous decoction extract of the bark of Aspidosperma cuspa has an antinociceptive effect, and this may be mediated by opioid receptors. Three indole alkaloids (aspidocarpine, 11-methoxytubotaiwine and picraline) were isolated from the aqueous extract. The antinociceptive activity of the extract is presumed to be due to these compounds.     

Antinociceptive effectiveness of triterpenes from rosemary in visceral nociception

Ethnopharmacological relevance

Rosemary is a species used worldwide as a common spice, but also in folk medicine for their therapeutic properties against abdominal pain. The rationale of this study was to examine the involvement of triterpenes and to compare their effectiveness in the antinociceptive effect of an ethanol extract of Rosmarinus officinalis L. (Lamiaceae).

Material and methods

Fractionation and HPLC analyses allowed the identification of a mixture of micromeric (121 mg/g), oleanolic (64 mg/g) and ursolic (83 mg/g) acids as partial antinociceptive responsible in an ethyl acetate fraction of R. officinalis by using the acetic acid-induced abdominal constrictions model in mice.

Results

These triterpenes individually evaluated produced a significant and dose-dependent antinociceptive response with similar potency as follows: ED₅₀=1.1 mg/kg (0.9–1.3 mg/kg), 2.1 mg/kg (1.6–2.6 mg/kg) and 1.6 mg/kg (1.1–2.1 mg/kg), respectively, by using the intraperitoneal (i.p.) route of administration in mice. Their maximal antinociceptive efficacy resembled that produced by ketorolac (10 mg/kg, i.p.), a common clinic analgesic.

Conclusion

Our results provide evidence that these triterpenes participate in the antinociceptive activity of R. officinalis. In addition, each individual triterpene showed a similar potency to that observed with ketorolac, a non-steroidal anti-inflammatory drug, in this experimental model.     

Sesquiterpene lactones with antinociceptive and antipyretic activity from two Centaurea species

Ethnopharmacological relevance

Several Centaurea species are used to alleviate pain and inflammatory symptoms in rheumatoid arthritis, high fever, and head ache in Turkish folk medicine.

Aim of the study

The effectiveness of extracts, fractions and subfractions from dried Centaurea solstitialis L. subsp. solstitialis (CSS) (Asteraceae) roots and aerial parts were studied on mice.

Materials and methods

The antinociceptive and antipyretic effects of Centaurea solstitialis L. subsp. solstitialis have been investigated by using p-benzoquinone-induced writhing reflex for antinociceptive activity and Freund's Complete Adjuvant-induced pyrexia model for antipyretic activity assessment in mice.

Results

The ethanolic extract from the aerial parts of the plant was shown to possess significant antinociceptive (p < 0.01) and antipyretic activities (p < 0.01). The extract was then submitted to subsequent solvent extractions and chromatographic processes. Through bioassay-guided fractionation and isolation procedures two sesquiterpene lactones, solstitialin A and acetyl solstitialin, were isolated and defined as the active components of CSS. On the other hand, a comparative study was conducted on another species, Centaurea depressa Bieb., which has no similar folkloric utilization. Following the same fractionation chart same compounds were defined as the active ingredients.

Conclusion

Results of the present study proved that aerial part of CSS possesses antinociceptive and antipyretic activities supporting the folkloric assertion in Turkish folk medicine. However, these effects seem not limited to CSS, some other Centaurea species, in fact, having no folkloric use might be equally active.