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.     

Anti-inflammatory and antinociceptive properties of the leaves of Eriobotrya japonica

Aim of the study

The leaves of Eriobotrya japonica Lindl. have been widely used as a traditional medicine for the treatment of many diseases including coughs and asthma. The present study was designed to validate the anti-inflammatory and antinociceptive properties of the n-BuOH fraction of E. japonica (LEJ) leaves.

Materials and methods

The anti-inflammatory properties of LEJ were studied using IFN-γ/LPS activated murine peritoneal macrophage model. The antinociceptive effects of LEJ were assessed using experimental models of pain, including thermal nociception methods, such as the tail immersion test and the hotplate test, and chemical nociception induced by intraperitoneal acetic acid and subplantar formalin in mice. To examine the possible connection of the opioid receptor to the antinociceptive activity of LEJ, we performed a combination test with naloxone, a nonselective opioid receptor antagonist.

Results

In the IFN-γ and LPS-activated murine peritoneal macrophage model, LEJ suppressed NO production and iNOS expression via down-regulation of NF-κB activation. It also attenuated the expression of COX-2 and the secretion of pro-inflammatory cytokines like TNF-α and IL-6. Moreover, LEJ also demonstrated strong and dose-dependent antinociceptive activity compared to tramadol and indomethacin in various experimental pain models. In a combination test using naloxone, diminished analgesic activities of LEJ were observed, indicating that the antinociceptive activity of LEJ is connected with the opioid receptor.

Conclusions

The results indicate that LEJ had potent inhibitory effects on the inflammatory mediators including nitric oxide, iNOS, COX-2, TNF-α and IL-6 via the attenuation of NF-κB translocation to the nucleus. LEJ also showed excellent antinociceptive activity in both central and peripheral mechanism as a weak opioid agonist. Based on these results, LEJ may possibly be used as an anti-inflammatory and an analgesic agent for the treatment of pains and inflammatory diseases.     

Comparison of active constituents,acute toxicity,anti-nociceptive and anti-inflammatory activities of Porana sinensis Hemsl., Erycibe obtusifolia Benth. and Erycibe schmidtii Craib

Ethnopharmacological relevance

Erycibe obtusifolia and Erycibe schmidtii, which belong to the same genus as Erycibe, are widely used in traditional medicine for the treatment of joint pain and rheumatoid arthritis (RA). Porana sinensis has become a widely used substitute for Erycibe obtusifolia and Erycibe schmidtii as they have declined in the wild. In the present work, the content of the main active components, the acute toxicity, the anti-nociceptive and anti-inflammatory activities of Porana sinensis, Erycibe obtusifolia and Erycibe schmidtii were compared, and the mechanisms of anti-nociceptive and anti-inflammatory activities were discussed.

Materials and methods

A quantitative HPLC (high performance liquid chromatography) method was first developed to compare the content of the main active components (scopoletin, scopolin and chlorogenic acid). The anti-inflammatory and anti-nociceptive activities of 40% ethanolic extracts of the three plants were compared using the models of xylene-induced ear edema, formalin-induced inflammation, carrageenan-induced air pouch inflammation, acetic acid-induced writhing and formalin-induced nociception. The acute toxicity of the 40% ethanolic extracts of the three plants was studied.

Results

The assay suggested a large content of scopoletin, scopolin and chlorogenic acid in the three plants. The 40% ethanolic extracts of the three plants were almost non-toxic at the dose of 5 g/kg and all of them showed significant anti-inflammatory effects in the tests of xylene-induced ear edema and formalin-induced inflammation. In the carrageenan-induced air pouch inflammation test, the synthesis of PGE2 was significantly inhibited by all the extracts. They significantly inhibited the number of contortions induced by acetic acid and the second phase of the formalin-induced licking response. Naloxone was not able to reverse the analgesic effect of these extracts.

Conclusion

The study identifies the similarity of the three plants in their main active components as well as acute toxicity, anti-nociceptive and anti-inflammatory activities. It supports the use of Porana sinensis as a suitable substitute, but further studies are needed to confirm this.     

Pharmacological evidence favouring the use of Nauclea latifolia in malaria ethnopharmacy: Effects against nociception,inflammation, and pyrexia in rats and mice

Aim of the study

Nauclea latifolia Smith is used traditionally in the treatment of uncomplicated malaria and painful conditions among its several other applications. The objective of this study is to investigate the pharmacological activities of the plant relevant to the symptomatic treatment of malaria fever and other painful conditions as an initial step towards developing an effective therapy for the symptomatic management of malaria fever and relief of other painful conditions.

Materials and methods

Various concentrations of the aqueous extract of the root bark of this plant were evaluated for its anti-nociceptive, anti-inflammatory and anti-pyretic activities in mice and rats. Investigation of the anti-nociceptive activities was performed using the acetic acid-induced abdominal constriction and hot-plate tests in mice and formalin-induced pain test in rats, as models of nociception. The extract was also investigated for its effect against inflammation induced by egg-albumin and pyrexia induced by yeast in rats.

Results

Our data showed that the aqueous extract of Nauclea latifolia root bark (50–200 mg/kg p.o.) significantly (P < 0.05) attenuated writhing episodes induced by acetic acid and increased the threshold for pain perception in the hot-plate test in mice, dose-dependently. The product also remarkably decreased both the acute and delayed phases of formalin-induced pain in rats and also caused a significant reduction in both yeast-induced pyrexia and egg-albumin-induced oedema in rats. These effects were produced in a dose-dependent manner.

Conclusion

The results suggest the presence of biologically active principles in the extract with anti-nociceptive, anti-inflammatory and anti-pyretic activities that justifies its use in malaria ethnopharmacy and subsequent development for clinical application.     

In vivo anti-nociceptive and anti-inflammatory activities of the aqueous extract of the leaves of Piper sarmentosum

Ethnopharmacological relevance

Piper sarmentosum (Piperaceae) is a medicinal plant traditionally used by the Malays to treat headaches, toothaches, coughs, asthma and fever.

Aim of the study

In order to establish the pharmacological properties of the leaf of this plant, studies were performed on anti-nociceptive and anti-inflammatory activities.

Materials and methods

The aqueous extract of Piper sarmentosum (AEPS) was prepared in the doses of 30, 100 and 300 mg/kg. Anti-nociceptive activity of AEPS was evaluated by abdominal constriction and hot-plate tests. AEPS was also pre-challenged with 5 mg/kg naloxone to determine the involvement of opioid receptors. Anti-inflammatory activity was evaluated using carrageenan-induced paw edema assay.

Results

Subcutaneous administration of AEPS exhibited anti-nociceptive activity (P < 0.05) in a dose-dependent manner in the abdominal constriction and hot-plate tests. Pre-treatment with naloxone completely (P < 0.05) diminished the extract anti-nociceptive activity in both tests. The AEPS, at all doses used, exerted significant (P < 0.05) anti-inflammatory activity in a dose-dependent manner.

Conclusions

The AEPS exhibits opioid-mediated anti-nociceptive activity at the peripheral and central levels, as well as anti-inflammatory activity, which confirmed the traditional uses of the plant in the treatment of pain- and inflammatory-related ailments.     

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.     

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.     

Screening of analgesic and anti-inflammatory activities of Citrullus colocynthis from southern Tunisia

Ethnopharmacological relevance

Inflammations and immune-related diseases such as rheumatoid arthritis are growing global concerns. Most of the drugs from plants which have become important in modern medicine had a folklore origin and are traditional in systems of medicine. Citrullus colocynthis Schrad. (cucurbitaceae), endemic in Southern Tunisia, is used in folk medicine to treat many inflammation diseases.

Aim of study

To evaluate the acute toxicity of different parts of Citrullus colocynthis and then to screen the analgesic and anti-inflammatory activities of aqueous extracts from roots and stems of the plant and from fruits and seeds at different maturation stages.

Materials and methods

After identification and acute toxicity assay Citrullus colocynthis Schrad. aqueous extracts were screened for analgesic and anti-inflammatory activities using, respectively, the acetic acid writhing test in mice and the carrageenan-induced paw edema assay in rats.

Results

All extracts displayed analgesic and anti-inflammatory activities at different doses without inducing acute toxicity. Topic results were obtained with immature fruits followed by seeds. The stem and root extracts were shown to possess the less significant inhibitory activity against analgesic and anti-inflammatory models.

Conclusions

Based on this study, we confirmed that Citrullus colocynthis Schrad. is a potentially useful drug suitable for further evaluation for rheumatoid arthritis, and its folk medicinal use as an analgesic and anti-inflammatory agents is validated.     

Anti-nociceptive activity of Pereskia bleo Kunth. (Cactaceae) leaves extracts

Ethnopharmacological relevance

Local communities in Malaysia consume Pereskia bleo Kunth. (Cactaceae) leaves as raw vegetables or as a concoction and drink as a tea to treat diabetes, hypertension, rheumatism, cancer-related diseases, inflammation, gastric pain, ulcers, and for revitalizing the body.

Aim of the study

To evaluate anti-nociceptive activity of the extracts and vitexin, isolated for the first time in this species, in two analgesic models; formalin-induced licking and acetic acid-induced abdominal writhing.

Materials and methods

Three and a half kilos of P. bleo leaves were extracted using Soxhlet apparatus with ethanol for 72 h. The crude ethanol extract was treated with activated charcoal overnight and subjected to a liquid–liquid partition yielding hexane, dichloromethane, ethyl acetate and butanol extracts. All extracts, including the crude ethanol and vitexin isolated from the ethyl acetate partition were tested for peripheral anti-nociceptive activity using formalin test and acetic acid-induced abdominal writhing, besides having their acute toxicity assays performed.

Results

The phytochemical analyses resulted in the isolation of vitexin (1), β-sitosterol glucoside (2) and β-sitosterol (3) isolated from the ethyl acetate, dichloromethane and hexane extracts, respectively. This is the first time vitexin and β-sitosterol glucoside are isolated from this species. The anti-nociceptive activities for all extracts were only moderate. Vitexin, which was isolated from the ethyl acetate extract did not show any activity in all models tested when used alone at the same concentration as it appears in the extract.

Conclusion

This study showed that all the extracts possess moderate anti-nociceptive activity. Vitexin is not the compound responsible for the anti-nociceptive effect in the ethyl acetate extract. Further investigations are needed to identify the compound(s) that might be responsible for the anti-nociceptive activity in this plant.     

Anti-inflammatory and antinociceptive effects of Baccharis dracunculifolia DC (Asteraceae) in different experimental models

Aim of the study

The aerial parts of Baccharis dracunculifolia D.C., popularly known as “alecrim do campo”, are used in folk medicine as anti-inflammatory. The aim of the present study was to evaluate the anti-inflammatory and antinociceptive activities of the crude hydroalcoholic extract obtained from leaves of Baccharis dracunculifolia (BdE), which have not been reported.

Materials and methods

BdE was analyzed by HPLC and in vivo evaluated (doses ranging from 50 to 400 mg/kg, p.o.) by using the acetic acid-induced abdominal constrictions, paw oedema induced by carrageenan or histamine, overt nociception models using capsaicin, glutamate or phorbol myristate acetate (PMA), formalin-induced nociception and mechanical hypernociception induced by carrageenan or complete Freund adjuvant (CFA). As positive controls it was used paracetamol in both acetic acid and formalin tests; dipyrone in capsaicin, glutamate and PMA-induced nociception; indomethacin in CFA and carrageenan-induced hypernociception models. In addition, the in vitro effects of BdE on COX-2 activity and on the activation of NF-κB were also evaluated.

Results

BdE (50–400 mg/kg, p.o.) significantly diminished the abdominal constrictions induced by acetic acid, glutamate and CFA. Furthermore, BdE also inhibited the nociceptive responses in both phases of formalin-induced nociception. BdE, administered orally, also produced a long-lasting anti-hypernociceptive effect in the acute model of inflammatory pain induced by carrageenan. It was also observed the inhibition of COX-2 activity by BdE.

Conclusion

In summary, the data reported in this work confirmed the traditional anti-inflammatory indications of Baccharis dracunculifolia leaves and provided biological evidences that Baccharis dracunculifolia, like Brazilian green propolis, possess antinociceptive and anti-inflammatory activities.     

Analgesic and anti-inflammatory effects of Cassia siamea Lam. stem bark extracts

Aim of the study

The present study was carried out to investigate analgesic and anti-inflammatory activities of Cassia siamea Lam stem bark extracts. We have also determined the cytotoxicity of each extract.

Materials and methods

C. siamea, a widespread medicinal plant traditionally used in sub-Saharan Africa, was collected in Congo Brazzaville. Stem bark was extracted with petroleum ether (CSE1), chloroform (CSE2), ethanol (CSE3) and water (CSE4). Analgesic, anti-inflammatory and antipyretic activities of these extracts were assessed in rats with hot plate test, paw pressure and carrageenan induced paw oedema. Cytotoxicity was assessed against KB and Vero cells.

Results

At the doses used (100, 200, and 400 mg/kg) ethanol and water extracts showed significant and dose-dependent analgesic and anti-inflammatory effects. None of the extracts had cytotoxic activity on KB and Vero cell lines and the most active extracts (CSE3 and CSE4) had no acute toxicity.

Conclusions

The study highlighted the analgesic and anti-inflammatory of C. siamea stem bark. Four major families of compounds present in the plant may explain these activities: triterpenes (lupeol, oleanolic acid, ursolic acid, friedelin, betulin), flavonoids (apigenin, kaempferol, luteolin), anthraquinones (emodin), phytosterols (stigmasterol, beta-sitosterol).     

Anti-inflammatory,anti-angiogenic and anti-nociceptive activities of an ethanol extract of Salvia plebeia R. Brown

Ethnopharmacological relevance

Salvia plebeia R. Brown has been used for the treatment of a variety of inflammatory diseases, cold and tumors in many countries, including Korea and China.

Aim of the study

This study aimed to assess anti-inflammatory and related activities of an ethanol extract (SPEE) prepared from the dried whole parts of Salvia plebeia.

Materials and methods

Anti-angiogenic and anti-nociceptive activities of SPEE were analyzed using the chick chorioallantoic membrane (CAM) assay and acetic acid-induced writhing response, respectively. Anti-inflammatory activity of SPEE was evaluated using acetic acid-induced vascular permeability, carrageenan-induced inflammation in the air pouch and analyses of nitrite content and induced nitric oxide synthase (iNOS) level in the macrophage cells.

Results

SPEE gave rise to a significant inhibition in chick chorioallantoic membrane angiogenesis. SPEE exhibited anti-inflammatory activities in vascular permeability and air-pouch models. In the air-pouch model, SPEE was able to diminish exudate volume, number of polymorphonulcear leukocytes and nitrite content. SPEE also displayed anti-nociceptive activity in the writhing response model in mice. SPEE significantly decreased nitrite content and induced nitric oxide synthase (iNOS) in the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells, while it could not modulate cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 levels in the stimulated phages. SPEE decreased reactive oxygen species (ROS) level in the stimulated macrophages.

Conclusion

The ethanol extract (SPEE) of Salvia plebeia possesses anti-inflammatory and related anti-angiogenic, anti-nociceptive and antioxidant activities, which offers partial support to its folkloric use.     

Anti-inflammatory and analgesic activities of methanolic extract of Kigelia pinnata DC flower

Ethnopharmacological relevance

Kigelia pinnata DC is extensively used in Indian traditional medicine for several diseases including inflammatory and painful disorders.

Aim of the study

The aim of the present study is to investigate the possible anti-inflammatory and analgesic activities of methanolic extract of Kigelia pinnata flower (MKFL) to support the medicinal uses claimed by folklore practitioners.

Materials and methods

MKFL is evaluated for its anti-inflammatory activity in carrageenan-induced paw edema model in rats and analgesic activity in acetic acid-induced writhing, hot plate and formalin-induced paw licking models in mice.

Results

MKFL exhibited a significant (P < 0.01) anti-inflammatory and analgesic activities with the doses of 100, 200 and 400 mg/kg b.w. in rats and mice respectively.

Conclusions

The results of the experimental study thus strongly support the traditional use of this plant for inflammatory and pain disorders.     

Evaluation of anti-nociceptive,anti-inflammatory and antipyretic activities of Artemisia scoparia hydromethanolic extract

Ethnopharmacological relevance

Artemisia scoparia (redstem wormwood) locally known as jhahoo or jaukay, is traditionally used in pain, inflammation and febrile conditions. So far, little or no scientific work has been reported to validate its folk uses in the alleviation of pain, fever and inflammation. The present study was designed to explore the analgesic, anti-inflammatory and antipyretic effects of the Artemisia scoparia hydromethanolic extract (ASHME), and to validate its traditional use in Asia.

Materials and methods

This study made use of thermal (hot plate induced) and chemical (acetic acid induced) nociception models in mice. In addition, the mechanism of antinociception in hot plate test was further evaluated in the presence of caffeine (10 mg/kg), naloxone (2 mg/kg) and monosodium glutamate (1 g/kg). While carrageenan induced rat paw edema and yeast induced mouse pyrexia models were used to test the anti-inflammatory and antipyretic activities.

Results

Administration of single intraperitoneal doses (400 mg/kg and 800 mg/kg) of ASHME significantly reduced the carrageenan induced paw edema in rats (P<0.05, P<0.001) by 54% and 74%, increased the thermal nociception time in the hot plate test up to 2- and 2.5-fold (P<0.01, P<0.001), inhibited the acetic acid induced writhings in mice by 41.12% and 61.53% (P<0.001), and attenuated the yeast induced pyrexia in mice by nearly 74% and 90% respectively (P<0.01, P<0.001). Caffeine (10 mg/kg), naloxone (2 mg/kg) and monosodium glutamate (1 g/kg) significantly (P<0.001) abolished the anti-nociceptive response of ASHME (400 mg/kg).

Conclusion

These findings suggest that the Artemisia scoparia hydromethanolic extract of ASHME possesses anti-nociceptive, anti-inflammatory and antipyretic potentials, which support its use, for the said conditions, in traditional medicine and should be further exploited for its use in clinical medicine.     

Evaluation of the antinociceptive and anti-inflammatory effect of Caralluma dalzielii

Ethnopharmacological relevance

Caralluma dalzielii has been used for treating several ailments including convulsion, leprosy, snake bites, otitis (ear pain), fungal diseases and rheumatoid arthritis in Northern Nigeria. However there is no scientific evidence to support its use in literature. To evaluate the antinociceptive and anti-inflammatory properties of the aqueous extract of Caralluma dalzielii in animal models.

Materials and methods

The antinociceptive and anti-inflammatory properties were assessed using acetic acid induced writhing test in mice, sub plantar formalin induced nociception, the tail-flick test and formalin induced oedema in rats. Three doses of the extract (25, 50, 100 mg/kg) were used for the assessment.

Results

Caralluma dalzielii extract demonstrated strong dose-dependent antinociceptive and anti-inflammatory activities in all the models employed. All doses (25, 50, 100 mg/kg) produced a significant percentage inhibition (41.77, 77.11, and 90.76% in the early phase and 52.02, 85.35, 93.93% in the late phase) in the acetic acid writhing test and (42.85, 55.71, 86.43% in the early phase and 23.26, 37.98, 72.87 in the late phase) in the formalin induced nociception test, respectively. The tail-flick test showed a significant increase in the antinociceptive effect of the extract in both early and late phases when compared with the control. The inhibition of oedema in the formalin test was significant when compared to the control.

Conclusion

The results indicated that Caralluma dalzielii showed excellent antinociceptive and anti-inflammatory properties suggesting that its traditional use in the treatment of pains and inflammatory diseases may be valid.     

Antinociceptive and hypnotic properties of Celastrus orbiculatus

Ethnopharmacological relevance

Celastrus orbiculatus, a woody vine of the Celastraceae family, has been widely used as a traditional medicine for the treatment of many diseases, including rheumatoid arthritis and odontalgia. In this study, we assessed the sedative and antinociceptive activities of the methanolic extract of Celastrus orbiculatus (MCO).

Materials and methods

The antinociceptive effect of MCO was evaluated using several experimental pain models, including thermal nociception methods, such as the tail immersion and the hotplate tests, as well as chemical nociception induced by intraperitoneal acetic acid and subplantar formalin administration in mice. To verify the possible connection of the opioid receptor to the antinociceptive activity of MCO, we performed a combination test with naloxone, a nonselective opioid receptor antagonist. The sedative effect of MCO was studied using the pentobarbital-induced sleeping model.

Results

MCO demonstrated strong and dose-dependent antinociceptive activity compared to tramadol and indomethacin in various experimental pain models. The combination test using naloxone revealed that the antinociceptive activity of MCO is associated with activation of the opioid receptor. MCO also caused decreased sleep latency and increased sleeping time in the pentobarbital-induced sleeping model; however, MCO alone did not induce sleep.

Conclusions

In the present study, MCO showed potent antinociceptive and sedative activities. Based on these results, MCO may be considered a valuable anti-nociceptive and hypnotic agent for the treatment of various diseases.     

Pharmacological evaluation of Alstonia scholaris: Anti-inflammatory and analgesic effects

Ethnopharmacological relevance

Alstonia scholaris (Apocynaceae) has been historically used in “dai” ethnopharmacy to treat chronic respiratory diseases. The leaf extract, developed as a commercially available traditional Chinese medicine, used to release tracheitis and cold symptom, has also been prescribed in hospitals and sold over the counter in drug stores.

Aim of the study

The investigation evaluated the anti-inflammatory and analgesic activities of the ethanolic extract, fractions and main alkaloids of Alstonia scholaris leaf to provide experimental evidence for its traditional and modern clinical use. Besides, to discover the active fraction and components for further better use in Chinese medicine is hopeful.

Materials and methods

The leaf of Alstonia scholaris was extracted with ethanol and then separated into different fractions. Furthermore, alkaloids were isolated by phytochemical method. The analgesic activities were investigated using acetic acid-induced writhing, hot-plate and formalin tests in mice. The anti-inflammatory activities were carried out in vivo and in vitro, including xylene-induced ear edema and carrageenan-induced air pouch formation in mice, and COX-1, -2 and 5-LOX inhibition.

Results

It has been exhibited that the EtOAc and alkaloid fractions reduced acetic acid-induced writhing response in mice, significantly. The ethanolic extract, EtOAc and alkaloid fractions remarkably inhibited xylene-induced ear edema. Further investigation was focused on the alkaloids fraction and three main alkaloids isolated from the alkaloids fraction, in different animal models. Alkaloids reduced acetic acid-induced writhing response, and xylene-induced ear edema in mice. In the hot-plate test, alkaloids did not increase the latency period of mice obviously. In the formalin test, alkaloids did not inhibit the licking time in first phase, but significantly inhibited the licking time in second phase of mice. Alkaloids increased significantly SOD activity and decreased levels of NO, PGE2 and MDA significantly, in air pouch mice model. Moreover, some alkaloids isolated from the leaf of Alstonia scholaris exhibited inhibition of COX-1, COX-2 and 5-LOX in vitro anti-inflammatory assay, which supported alkaloids as the bioactive fraction.

Conclusions

The alkaloids fraction of Alstonia scholaris leaf, three main alkaloids, picrinine, vallesamine and scholaricine, may produce the anti-inflammatory and analgesic effect peripherally based on several in vivo assays. In in vitro tests, alkaloids exhibited inhibition of inflammatory mediators (COX-1, COX-2 and 5-LOX), which is accordant with results on animal models. Besides, COX-2/5-LOX dual inhibitors found in the experiment, such as 16-formyl-5α-methoxystrictamine, picralinal, and tubotaiwine might be valuable for further attention.