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.     

Antinociceptive activity of methanolic extract of Acmella uliginosa (Sw.) Cass

Ethnopharmacological relevance

Acmella uliginosa (Sw.) Cass. is a medicinal herbaceous plant that is commonly used by the Malay community in Malaysia to relieve pain often associated with mouth ulcers, toothache, sore throat, and stomach ache.

Aim

The study was carried out to investigate the antinociceptive effect of the methanolic extract of A. uliginosa (Sw.) Cass. flowers (MEAU) using murine models of chemicals and thermal nociception.

Materials and methods

Chemicals (acetic acid-induced abdominal constriction and formalin-, capsaicin-, glutamate-induced paw licking test) and thermal models (hot plate test) of nociception in mice were employed to evaluate the MEAU analgesic effect. The extract was given via oral administration at doses of 3, 10, 30 and 100 mg/kg.

Results

It was demonstrated that MEAU produced significant antinociceptive response in all the chemical- and thermal-induced nociception models, which indicates the presence of both centrally and peripherally mediated activities. Furthermore, the reversal of antinociception of MEAU by naloxone suggests the involvement of opioid system in its centrally mediated analgesic activity. Moreover, MEAU-treated mice did not show any significant motor performance alterations. No mortality and signs of toxicity were recorded following treatment of the MEAU.

Conclusion

The results from the present study appear to support the folkloric belief in the medicinal properties of A. uliginosa (Sw.) Cass. which against pain at both central and peripheral levels, in which the central antinociception is probably due to the participation of the opioid receptors.     

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.     

Anti-inflammatory and antinociceptive effects of the stem bark of Byrsonima intermedia A. Juss

Ethnopharmacological relevance

Byrsonima intermedia A. Juss. is popularly known as “murici pequeno” and is native to the Brazilian Cerrado. This species has been used as an antimicrobial, anti-hemorrhagic, anti-diarrheal and anti-inflammatory. Nevertheless, scientific information regarding Byrsonima intermedia is limited; there are no reports related to its possible anti inflammatory and antinociceptive effects. This study employed in vivo inflammatory and nociceptive models to evaluate the scientific basis for the traditional use of Byrsonima intermedia.

Materials and methods

Carrageenan-induced paw edema, peritonitis and fibrovascular tissue growth induced by s.c. cotton pellet implantation tests were used to investigate the anti-inflammatory activity of Byrsonima intermedia aqueous extract (BiAE) in rats. Mechanical nociceptive paw, formalin and hot plate tests were used to evaluate the antinociceptive activity in mice. High-performance liquid chromatography (HPLC), phytochemistry screening and determination of total phenolics and flavonoids were used to determine the chemical profile of the BiAE.

Results

BiAE at test doses of 30-300 mg/kg p.o. clearly demonstrated anti-inflammatory effects by reduced carrageenan-induced paw edema, by inhibited leukocyte recruitment into the peritoneal cavity and, in the model of chronic inflammation, by using the cotton pellet-induced fibrovascular tissue growth in rats. The extracts at test doses of 30-300 mg/kg p.o. clearly demonstrated antinociceptive activity in all tests. Administration of the opioid receptor antagonist naloxone completely inhibited the antinociceptive effect induced by BiAE (100 mg/kg).

Conclusion

BiAE markedly exhibits anti-inflammatory action in rats and antinociceptive activity in mice. Thus, it may be useful in the treatment of inflammatory hyperalgesic disorders, which supports previous claims of its traditional use.     

Analgesic effects and anti-inflammatory properties of the crude methanolic extract of Schwenckia americana Linn (Solanaceae)

Aim of the study

To evaluate analgesic effect and anti-inflammatory properties of Schwenckia americana (Solanaceae), a medicinal plant used for treating rheumatic pains and swelling in North-western Nigeria.

Materials and methods

Three doses (25 mg/kg, 50 mg/kg and 100 mg/kg) of the crude methanolic extract of Schwenkia americana were evaluated for analgesic and anti-inflammatory activities using acetic acid induced writhing test, formalin induced nociception, and formalin induced hind paw oedema in rats.

Results

All doses (25, 50, 100 mg/kg) of the extract tested were effective. The extract at the tested doses produced a percentage inhibition of the acetic acid induced abdominal constriction of (53.3, 58.0 and 86.7%), respectively. A percentage inhibition of the formalin induced nociception of 44.00, 56.04, and 56.04% (early phase) and 33.00, 36.63 and 59.71% (late phase) was also produced. The inhibition of oedema formation increased with increasing dosage from 25 to 100 mg/kg. The crude extract produced a statistically significant analgesic and anti-inflammatory activity comparable to the effect of standard drug (10 mg/kg Piroxicam).

Conclusion

This study demonstrated the potential analgesic and anti-inflammatory properties of crude methanolic extract of Schwenkia americana thus justifying its traditional usage.     

Anti-inflammatory and antinociceptive effects of Arrabidaea brachypoda (DC.) Bureau roots

Aim of the study

Arrabidaea brachypoda (DC.) Bureau has been used to relieve general pain, painful joints and kidney stones in Brazilian folk medicine. Nevertheless, scientific information regarding this species is scarce; there are no reports related to its possible analgesic and anti-inflammatory effects. This study was aimed at evaluating the traditional use of Arrabidaea brachypoda root using in vivo inflammatory and nociceptive models.

Materials and methods

Carrageenan-induced paw edema, peritonitis and fibrovascular tissue growth induced by s.c. cotton pellet implantation were used to investigate the anti-inflammatory activity of Arrabidaea brachypoda roots ethanolic extract (AbEE) in rats. Formalin and acetic acid-induced writhing tests were used to investigate the antinociceptive activity in mice. High-performance liquid chromatography (HPLC) was used to determine the fingerprint chromatogram of AbEE.

Results

The AbEE at test doses of 30-300 mg/kg p.o. demonstrated anti-inflammatory effects. AbEE reduced paw edema induced by carrageenan, inhibited leukocyte recruitment into the peritoneal cavity and, in the model of chronic inflammation using the cotton pellet-induced fibrovascular tissue growth in rats, significantly inhibited the formation of granulomatous tissue. The extracts at test doses of 30-300 mg/kg p.o. clearly demonstrated antinociceptive activity, except during the first phase of the formalin test. The presence of quercetin and phenolic compounds in the extract Arrabidaea brachypoda was confirmed using HPLC.

Conclusion

Arrabidaea brachypoda ethanol extract markedly demonstrated anti-inflammatory action in rats and antinociceptive activity in mice, which supports the previous claims of traditional use.     

Chemical composition, antinociceptive and anti-inflammatory effects in rodents of the essential oil of Peperomia serpens (Sw.) Loud

Ethnopharmacological relevance

Peperomia serpens (Piperaceae), popularly known as “carrapatinho”, is an epiphyte herbaceous liana grown wild on different host trees in the Amazon rainforest. Its leaves are largely used in Brazilian folk medicine to treat inflammation, pain and asthma.

Aim of the study

This study investigated the effects of essential oil of Peperomia serpens (EOPs) in standard rodent models of pain and inflammation.

Materials and methods

The antinociceptive activity was evaluated using chemical (acetic acid and formalin) and thermal (hot plate) models of nociception in mice whereas the anti-inflammatory activity was evaluated by carrageenan- and dextran-induced paw edema tests in rats croton oil-induced ear edema, as well as cell migration, rolling and adhesion induced by carrageenan in mice. Additionally, phytochemical analysis of the EOPs has been also performed.

Results

Chemical composition of the EOPs was analyzed by gas chromatography and mass spectrometry (GC/MS). Twenty-four compounds, representing 89.6% of total oil, were identified. (E)-Nerolidol (38.0%), ledol (27.1%), α-humulene (11.5%), (E)-caryophyllene (4.0%) and α-eudesmol (2.7%) were found to be the major constituents of the oil. Oral pretreatment with EOPs (62.5-500 mg/kg) significantly reduced the writhing number evoked by acetic acid injection, with an ED₅₀ value of 188.8 mg/kg that was used thereafter in all tests. EOPs had no significant effect on hot plate test but reduced the licking time in both phases of the formalin test, an effect that was not significantly altered by naloxone (0.4 mg/kg, s.c.). EOPs inhibited the edema formation induced by carrageenan and dextran in rats. In mice, EOPs inhibited the edema formation by croton oil as well as the leukocyte and neutrophil migration, the rolling and the adhesion of leukocytes.

Conclusions

These data show for the first time that EOPs has a significant and peripheral antinociceptive effect that seems unrelated to interaction with the opioid system. EOPs also displays a significant anti-inflammatory effect in acute inflammation models. This effect seems to be related to components which inhibit the production of several inflammatory mediators. These results support the widespread use of Peperomia serpens in popular medicine to treat inflammation and pain.     

Antinociceptive effect of extracts and compounds from Hofmeisteria schaffneri

Ethnopharmacological relevance

Hofmeisteria schaffneri (Asteraceae) is a medicinal plant widely commercialized in the most important Markets of Mexico City for the treatment of gastro-intestinal complaints and skin afflictions.

Aim of the study

The main goals of this study were to establish the potential acute toxicity and the antinociceptive activity in animal models of several preparations and compounds from Hofmeisteria schaffneri.

Materials and methods

The aqueous and organic extracts as well as the essential oil of Hofmeisteria schaffneri were prepared by infusion, maceration and hydrodistillation, respectively. Investigation of the acute toxicity was accomplished by the Lorke method. The antinociceptive effect was assessed using the writhing and the hot plate tests. Natural compounds were isolated by standard phytochemical procedures. In addition, a few thymol esters were prepared by chemical synthesis. The stability of natural and synthetic esters was qualitatively analyzed by measuring their susceptibility to hydrolysis by pig liver estearase and mouse plasma at 37 °C.

Results

The LD₅₀ for each preparation tested was higher than 5000 mg/kg revealing that they were not toxic to mice after exposure for short space of time. On the other hand, the extracts showed significant antinociceptive effect when tested in the hot plate model. The most active natural product as antinociceptive agent was hofmeisterin III (1) which also was the most stable in the stability study. Its pharmacological effect seems to be partially mediated by an opioid mechanism since naloxone inhibits its action. Using compound 1 as a lead molecule, several synthetic thymol esters were prepared and only compounds 13, 15 and 17 were antinoceptive at the dose of 1 mg/kg.

Conclusions

The present investigation provided evidence of the efficacy of several preparations of Hofmeisteria schaffneri as antinociceptive agents. The most active preparation was the essential oil which contained large amount of hofmeisterin III (1) and other thymol derivatives. Some novel synthetic analogs of hofmeisterin III with antinociceptive properties were discovered. The nature of the ester chain of these analogs did not have a clear impact on the antinociceptive activity. The phyto-preparations analyzed in this study were not toxic to mice according to the Lorke's test; therefore considering their long term use of the plant they might be secure for human consumption.     

Anti-inflammatory and antinociceptive effects of Garcinia brasiliensis

Aim of the study

In Brazilian folk medicine, the leaves of Garcinia brasiliensis are used to treat tumors, inflammation of the urinary tract and arthritis as well as to relieve pain. Nevertheless, scientific information regarding Garcinia brasiliensis is limited; there are no reports related to its possible anti-inflammatory and antinociceptive effects. This study employed in vivo inflammatory and nociceptive models to evaluate the scientific basis for the traditional use of Garcinia brasiliensis.

Materials and methods

Carrageenan-induced paw edema, peritonitis and fibrovascular tissue growth induced by s.c. cotton pellet implantation were used to investigate the anti-inflammatory activity of Garcinia brasiliensis ethanolic extract (GbEE) in rats. Formalin and acetic acid-induced writhing tests were used to investigate the antinociceptive activity in mice.

Results

GbEE at test doses of 30-300 mg/kg p.o. clearly demonstrated anti-inflammatory effects by reduced paw edema induced by carrageenan, inhibited leukocyte recruitment into the peritoneal cavity, and in the model of chronic inflammation using the cotton pellet-induced fibrovascular tissue growth in rats, the GbEE significantly inhibited the formation of granulomatous tissue.The extracts at test doses of 30-300 mg/kg, p.o., clearly demonstrated antinociceptive activity, except for the first phase of the formalin test.

Conclusion

GbEE markedly demonstrated anti-inflammatory action in rats and antinociceptive activity in mice, which supports previous claims of the traditional use of species of the Garcinia genus for inflammation and pain.     

Anti-inflammatory, analgesic and antipyretic properties of Thespesia populnea Soland ex. Correa seed extracts and its fractions in animal models

Ethnopharmacological relevance

Thespesia populnea Sol. ex Correa (Malvaceae) is commonly known as “Indian tulip tree”. The plant has been used as an astringent, antibacterial, anti-inflammatory, antinociceptive and hepatoprotective in Indian system of traditional medicine.

Materials and methods

Thespesia populnea seeds were successively extracted by soxhlet extraction using petroleum ether (40-60 °C) (TPO) and ethanol (TPE). Unsaponifiable matter (TPOUM) and fatty acids were separated from seed oil. A GC-MS analysis of fatty acid methyl esters was carried out. Ethanolic extract was fractionated using CHCl₃, EtOAc, n-BuOH and H₂O. Acute arthritis was induced by sub-plantar injection of carrageenan into the left hind paw of rats. The paw volume was measured using plethysmometer. Analgesic activity was assessed by heat induced pains (tail immersion model) and antipyretic activity assessed using brewers yeast-induced pyrexia model.

Results

Oral administration of TPO and TPE at 200 and 400 mg/kg b.w. and tested fractions at 200 mg/kg significantly reduced carrageenan induced paw edema and brewers yeast-induced pyrexia. In tail immersion method also extracts and fractions showed significant analgesic activity. Amongst all fractions EtOAc showed most significant results. TPOUM showed significant anti-inflammatory and analgesic activity. GC-MS analyses showed the presence of fourteen fatty acids, predominant fatty acids were palmitic and stearic acid.

Conclusion

These results highlighted anti-inflammatory, analgesic and antipyretic effects of Thespesia populnea seeds.     

Bioassay-guided isolation of anti-inflammatory, antinociceptive and wound healer glycosides from the flowers of Verbascum mucronatum Lam.

Ethnopharmacological relevance

The leaves, flowers and whole aerial parts of Verbascum L. species have been used to treat respiratory problems, haemorrhoids and other types of inflammatory conditions in traditional Turkish medicine.

Aim of the study

In order to evaluate this traditional information, the anti-inflammatory, antinociceptive and wound healing activities of Verbascum mucronatum Lam. which is used as haemostatic in Turkish folk medicine were investigated.

Materials and methods

In vivo inhibitory effect of the extracts on the carrageenan-induced hind paw edema model in mice was studied for the assessment of anti-inflammatory activity. Moreover, the wound healing potential of the plant were evaluated by using in vivo wound healing experimental models, i.e. incision and excision models on mice and rats, were comparatively assessed with a reference ointment Madecassol^®. Skin samples were also evaluated histopathologically.

Results

The results of these experimental studies exhibited that Verbascum mucronatum displays anti-inflammatory, antinociceptive and wound healing activities. Through bioassay-guided fractionation and isolation procedures four iridoid glucosides, ajugol (1), aucubin (2), lasianthoside I (3), catalpol (4), two saponins, ilwensisaponin A (5) and C (6) and a phenylethanoid glycoside, verbascoside (7) were isolated and their structures were elucidated by spectral techniques. Verbascoside (7) was found to possess significant wound healing activity as well as antinociceptive and anti-inflammatory potentials, per os without inducing any apparent acute toxicity or gastric damage.

Conclusion

The experimental study revealed that Verbascum mucronatum displays remarkable antinociceptive, anti-inflammatory and wound healing activities.     

Characterisation of the anti-inflammatory and antinociceptive activities of the Hyptis pectinata (L.) Poit essential oil

Aim of the study

Hyptis pectinata Poit (Lamiaceae) is grown in the northeastern regions of Brazil and is popularly known as “sambacaitá” or “canudinho”. It is extensively used in folk medicine to treat inflammatory conditions, bacterial infections, pain, and cancer.

Materials and methods

Hyptis pectinata essential oil (EO, 10, 30, and 100 mg/kg, p.o.) and the reference drugs morphine (5 mg/kg, p.o.) and acetylsalicylic acid (ASA, 200 mg/kg, p.o.) were evaluated using models for analgesia (acetic acid-induced contortions and hot plate) or inflammation (formalin-induced licking response and the subcutaneous air-pouch model). To elucidate the EO's mechanism of action, animals were pre-treated with the opioid receptor antagonist naloxone (1 mg/kg, i.p.), the cholinergic antagonist atropine (1 mg/kg, i.p.), or l-nitro arginine methyl ester (l-NAME, 3 mg/kg, i.p.) 30 min prior to the oral administration of the EO.

Results

The EO significantly inhibited the number of writhings and the time the animals spent licking their formalin-injected paws (second phase). The EO, at doses of 30 and 100 mg/kg, increased baseline measurements and area under the curve measurements in the hot plate model, respectively. The administration of naloxone reversed the antinociceptive effect of the EO in the hot plate model. l-NAME significantly reversed the effects of the EO in the contortions and hot plate models. Atropine completely reversed the antinociceptive activity of the EO in all models. Additionally, the EO inhibited the inflammatory process induced by subcutaneous carrageenan injection by reducing cell migration, exudate volume, protein concentration, and inflammatory mediators (nitric oxide, prostaglandin E2, IL-6, and TNF-α) produced in the pouch.

Conclusions

Our results indicate that the Hyptis pectinata essential oil exhibits antinociceptive effects, likely mediated by opioid and cholinergic receptors, and anti-inflammatory activity through the inhibition of nitric oxide and PGE2 production.     

Lonicera japonica Thunb.: ethnopharmacology, phytochemistry and pharmacology of an important traditional Chinese medicine

Ethnopharmacological relevance

Lonicera japonica Thunb. (Caprifoliaceae), a widely used traditional Chinese medicine, was known as Jin Yin Hua (Chinese: ), Ren Dong and Japanese honeysuckle. It was taken to treat the exopathogenic wind-heat, epidemic febrile diseases, sores, carbuncles and some infectious diseases. At the same time, Lonicera japonica could be used as healthy food, cosmetics, ornamental groundcover, and so on.

Aim of the review

The present paper reviewed the ethnopharmacology, the biological activities, toxicology and phytochemistry of Lonicera japonica.

Materials and methods

Information on Lonicera japonica was gathered via the Internet (using Google Scholar, Baidu Scholar, Elsevier, ACS, Medline Plus, CNKI and Web of Science) and libraries. Additionally, information also was obtained from some local books and brilliant scholars on ethnopharmacology.

Results

More than 140 chemical compounds have been isolated, and the main compositions are essential oils, organic acids and flavones, etc. Lonicera japonica and its active principles possess wide pharmacological actions, such as anti-inflammatory, antibacterial, antiviral, antioxidative and hepatoprotective activities.

Conclusions

As an important traditional Chinese medicine, further studies on Lonicera japonica can lead to the development of new drugs and therapeutics for various diseases, and how to utilize it better should be paid more attentions.     

Evaluation of the anti-inflammatory properties of Dodonaea polyandra, a Kaanju traditional medicine

Ethnopharmacological relevance

Extracts of the medicinal plant species Dodonaea polyandra were investigated as part of a collegial research partnership between Northern Kaanju traditional owners represented by Chuulangun Aboriginal Corporation (centred on the Wenlock and Pascoe Rivers, Cape York Peninsula, Queensland, Australia) and university-based researchers. D. polyandra, known as “Uncha” in Kaanju language, is used in Northern Kaanju Traditional Medicine for relief from pain associated with toothache and related ailments. The species has a restricted distribution in Cape York Peninsula and there has been no previous Western scientific investigation of its pharmacology or chemistry.

Aim of the study

The current study investigates the anti-inflammatory effects of several extracts from D. polyandra.

Materials and methods

Phytochemical screening was conducted using TLC. Anti-inflammatory effects of leaf extracts were determined using an acute mouse ear oedema model induced by croton oil and 12-o-tetradecanoylphorbol-13-acetate (TPA) chemical irritants.

Results

Flavonoid and terpenoid secondary compounds were detected in leaf extracts of D. polyandra. Non-polar hexane and methylene chloride/methanol extracts showed potent inhibition of inflammation in TPA-induced mouse ear oedema by 72.12 and 79.81%, respectively, after 24 h at 0.4 mg/ear.

Conclusion

In a mouse model of acute inflammation, this study revealed that leaf extracts of D. polyandra possess significant anti-inflammatory potential. These results contribute to a Western scientific understanding of the ethnopharmacological use of the plant in Northern Kaanju Medicine for reducing tooth-related pain.     

Identification of a new antinociceptive alkaloid isopropyl N-methylanthranilate from the essential oil of Choisya ternata Kunth

Ethnopharmacological relevance

Mexican people employed infusion of leaves of Choisya ternata Kunth for their antispasmodic and “simulative properties”.

Aim of the study

In the present study the detailed GC and GC-MS analyses of the essential oil of Choisya ternata Kunth (Rutaceae) were performed. The presence of a minor constituent isopropyl N-methylanthranilate (1) was revealed among other identified volatiles. A synthesis of 1 was undertaken in order to corroborate this find and obtain gram quantities that would allow the testing of its biological activity (peripheral and central antinociceptive activity).

Materials and methods

The oils were investigated by GC and GC-MS. Synthesized compounds were spectrally characterized (UV-Vis, IR, 1D and 2D NMR, MS). The obtained synthetic samples of compounds were assayed for peripheral and central antinociceptive activity in two models (effects on acetic acid induced writhing in mice and the hot plate test for nociception).

Results

Detailed GC and GC-MS analyses of the essential oil of Choisya ternata Kunth (Rutaceae) among 157 other identified volatiles revealed the presence of a minor constituent isopropyl N-methylanthranilate (1). Compound 1, named ternanthranin, is therefore detected as a natural product for the first time with a very restricted occurrence (samples of several citrus oils were screened for the presence of 1). The antinociceptive activities were assayed for ternanthranin, the two other synthetic analogs, methyl and propyl N-methylanthranilate, as well as the essential oil and the crude ethanol extract of the leaves. The results clearly demonstrate a very high (even significant at 0.3 mg/kg) dose dependent activity for the anthranilates (and the extracts). Isopropyl N-methylanthranilate showed the highest, while methyl N-methylanthranilate showed the lowest activity (with the methyl ester at 3 mg/kg still better than acetylsalicylic acid, at 200 mg/kg, in the first, or comparable with morphine, at 5 mg/kg, in the second test).

Conclusion

This study once again revealed that detailed investigations of plant species with ethnopharmacologically documented activity may yield new natural compounds—a new alkaloid (ternanthranin), a volatile simple anthranilate that can be considered responsible for the antinociceptive activity of the crude plant extracts.     

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 effect of extract of Emilia sonchifolia in mice

Aim of the study

Emilia sonchifolia (L.) DC. (Asteraceae) is a medicinal plant traditionally used in Brazilian folk medicine to treat asthma, fever, cuts, wounds and rheumatism. This study was conducted to establish the antinociceptive properties of hydroethanolic extract from aerial parts of Emilia sonchifolia in mice using chemical and thermal models of nociception.

Materials and methods

To evaluate the antinociceptive effect of Emilia sonchifolia hydroethanolic extract (EsHE) administered by oral route, peripheral (acetic acid-induced abdominal writhing and formalin), spinal (tail flick) and supra-spinal (hot plate) behavioral models of acute pain were used. High-performance liquid chromatography (HPLC) was used to determine the fingerprint chromatogram of the EsHE.

Results

The EsHE at test doses of 100 and 300 mg/kg, p.o. clearly demonstrated antinociceptive activity in all tests. The extract had a stronger antinociceptive effect than morphine. Administration of the opioid receptor antagonist, naloxone, completely inhibited the antinociceptive effect induced by EsHE (100 mg/kg). The presence of phenolic compounds in the extract of Emilia sonchifolia was confirmed using HPLC.

Conclusion

The extract of Emilia sonchifolia markedly exhibits opioid-mediated anti-nociceptive activity action in mice. Thus, may be useful in the treatment of inflammatory hyperalgesic disorders, which supports previous claims of its traditional use.     

Antinociceptive activity of ethanolic extract and isolated compounds of Urtica circularis

Ethnopharmacological relevance

Urtica circularis (Hicken) Sorarú is a medicinal plant commonly used in traditional medicine to relieve pain in inflammatory processes.

Aim of the study

In the present study, the in vivo antinociceptive effect of Urtica circularis ethanolic 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: 72.2 mg/kg, i.p.) and formalin (ED50: 15.8 mg/kg, i.p.) administered intraperitoneally and also orally. Atropine diminished the activity of the extract in the acetic acid test. In this model, at dose of 10 mg/kg i.p., vitexin was the most active of the isolated compounds (inhibition of 91%), and chlorogenic acid, caffeic acid and vicenin-2 (6,8-di-C-glucosyl apigenin) produced an inhibition of 72%, 41% and 41%, respectively, whereas apigenin did not show any activity.

Conclusions

These results suggest that Urtica circularis extract produced antinociception possibly related to the presence of vitexin, chlorogenic, caffeic acid and vicenin-2. The activation of cholinergic systems seems to be involved in the mechanism of antinociception of the extract.     

The analgesic and anti-inflammatory effect of WIN-34B, a new herbal formula for osteoarthritis composed of Lonicera japonica Thunb and Anemarrhena asphodeloides BUNGE in vivo

Ethnopharmacological relevance

: Lonicera japonica Thunb and Anemarrhena asphodeloides BUNGE have been used for the treatment of a variety of inflammatory diseases, cold and infective diseases in many countries, including Korea and China.

Aim of the study

: This study aimed to assess the anti-nociceptive and anti-inflammatory activities of n-butanol fraction (WIN-34B) prepared from dried flowers of Lonicera japonica and dried roots of Anemarrhena asphodeloides as potential novel treatment of osteoarthritis.

Materials and methods

: Anti-nociceptive activities of WIN-34B (100, 200 and 400 mg/kg, p.o.) were measured using acetic acid-induced writhing response, formalin-induced paw licking, hot plate, radiant heat tail-flick, carrageenan-induced paw pressure, and Hargreaves tests, respectively. Anti-inflammatory activities of WIN-34B (100, 200 and 400 mg/kg, p.o.) were assessed using acetic acid-induced vascular permeability, carrageenan-induced paw edema, and croton oil-induced ear edema. Anti-osteoarthritis effect of WIN-34B was analyzed using monosodium iodoacetate (MIA)-induced osteoarthritis animal model.

Results

: WIN-34B exhibited better anti-inflammatory activity than that of celecoxib in carrageenan at the dose of 200 mg/kg and croton oil-induced paw edema and ear edema at the doses of 200 and 400 mg/kg. WIN-34B exhibited significant anti-inflammatory effects on vascular permeability. WIN-34B also exhibited significant anti-nociceptive activities in the late phase of formalin-induced paw licking and writhing response model in mice. In radiant heat tail-flick and carrageenan-induced paw pressure tests, WIN-34B at the dose of 400 mg/kg and at the doses of 200 and 400 mg/kg presented similar activities to indomethacin and celecoxib. Compared to indomethacin WIN-34B at 400 mg/kg showed similar or better anti-nociceptive activities after 1 and 2 h of theraphy in the hot plate test and better anti-nociceptive activity than that of celecoxib in Hargreves test. In the MIA-induced osteoarthritis animal models, WIN-34B at 400 mg/kg exhibited similar or better anti-nociceptive property than that of celecoxib throughout the pain measurement periods.

Conclusion

: When compared to celecoxib, WIN-34B exhibited similar or better anti-nociceptive and anti-inflammatory activities in osteoarthritic animal models, which may become a potential novel treatment for osteoarthritis.     

Anti-inflammatory effect of a methanolic extract of leaves of Dregea volubilis

Aim of study

The aim of this study was to establish the anti-inflammatory activity of the methanolic extract of Dregea volubilis leaves (MEDV) with its fractions and to delineate the possible mechanism of action for MEDV.

Materials and methods

The anti-inflammatory activities of MEDV along with its petroleum ether and chloroform fractions were evaluated in a carrageenan induced model of acute inflammation. The effect of MEDV on lipopolysaccharide induced production of nitric oxide (NO) in macrophages was also studied.

Results

MEDV (100, 200 and 400 mg/kg body weight) significantly reduced carrageenan induced paw edema; chloroform fraction was most potent (66%, p < 0.001). MEDV was non-toxic up to 125 μg/ml in mouse peritoneal macrophages wherein it (0-100 μg/ml) reduced lipopolysaccharide induced NO production.

Conclusion

MEDV possesses significant anti-inflammatory activity. Chloroform fraction of MEDV showed best anti-inflammatory activity.