Antinociceptive Activity Of Ethanol Extract Research Articles

Gooderoside A from Anoectochilus elatus attenuates acute and chronic pains by inhibiting NO/cGMP and IRAK4/IRAK1/TAK1 signaling pathways

Ethnopharmacological relevanceAnoectochilus elatus Lindl. was traditionally used for pain treatment and Gooderoside A (GA) was regarded as its principal constituent. Aim of the studyTo investigate whether GA can be responsible for the antinociceptive activity of A. elatus and explore its underlying mechanism. Materials and methodsAcetic acid-induced abdominal writhing and tail flick tests were employed to evaluate the antinociceptive activity of ethanolic extract of A. elatus (EEA) and GA. Formalin test was used to ascertain the antinociceptive pattern of GA. Entobarbital sodium induced sleep test was adopted to exclude its hypnotic effect, while open-field test was performed to rule out its motor impairment effect. Chronic constriction injury (CCI)-induced neuropathic pain in rats was developed to evaluate its efficacy on neuropathic pain, and BV-2 cells were used to explore the underlying mechanism. ResultsEEA and GA, significantly inhibited chemical and thermal nociception. GA suppressed nociception in formalin test in both phase I and II, whereas methylene blue and L-NAME partially reversed its efficacy. GA located inner and slightly blocked sodium channel current, and did not show any hypnotic effect or motor impairment effect. Crucially, GA markedly attenuated chronic neuropathic pain in rats, inhibited the phosphorylation of IRAK4, IRAK1 and TAK1, and suppressed MAPKs pathway in BV-2 cells. ConclusionGA relieved acute and chronic pains in vivo. The mechanism of action involves the blocking of NO/cGMP and IRAK4/IRAK1/TAK1 pathways. These results suggested GA may be a promising candidate for antinociceptive drug development.

Antinociceptive activity of Pereskia sacharosa Griseb. (Cactaceae) and localization of bioactive compounds in mice brain

BackgroundPereskia sacharosa Griseb is mainly distributed in the Bolivian Amazon. It is widely used to treat infections and pain in traditional medicine, such as headache, muscle pain, stomachache, and inflammation. PurposeThis study aimed to evaluate the antinociceptive activity of the leaf ethanolic extract and fractions of P. sacharosa that was obtained through micropropagation, possible mechanisms of action, and to identify the main bioactive compound by high liquid chromatography-mass spectrometry, as well as its localization in the brain of mice by means of histological analysis and epifluorescence. MethodsThe fractions (C1F9 and C2F13) were isolated from the ethanolic extract of P. sacharosa leaves using open column chromatography. The antinociceptive activity of the ethanolic extract (10–100 mg kg−1, intra peritoneal, i.p.) and fractions C1F9 and C2F13 (30 mg kg−1, i.p.) were evaluated in a nociceptive pain model (formalin test) in mice. In addition, a possible mechanism of action was investigated by exploring some inhibitory receptors using naltrexone (NTX, a non-selective opioid receptor antagonist), flumazenil (FMZ, a benzodiazepine site antagonist in the Gamma-aminobutyric acid A [GABAA] receptor), or WAY100635 (a 5-hydroxytryptamine 1A [5-HT1A] serotonin 1A receptor antagonist). ResultsRegarding the mechanism of action, only antinociceptive activity of treatments in the neurogenic phase of the formalin test was inhibited in the presence of the three explored antagonists. Furthermore, the presence of phenolic compounds was confirmed at the central nervous system (CNS) using their epifluorescence in coronal brain sections and histological analysis. Finally, acid hydrolysis of the ethanolic extract was performed, and it was shown that kaempferol is a product of acid hydrolysis confirmed with a posterior high liquid chromatography-mass spectrometry analysis. ConclusionThe leaves of P. sacharosa contain bioactive metabolites with antinociceptive activity, whereby epifluorescence was an optimum property to detect them at CNS. To the best of our knowledge, this is the first report that provides preclinical evidence of the medicinal use of this species in folk medicine for pain relief.

Acute Toxicity Study and Anti-Nociceptive Activity of Ethanol Extract of Aesculus Indica Seeds on Experimental Animal Models

Aesculus indica, widely known as the horse chestnut tree, has long been used as antiangiogenic, antibacterial, antidiabetic, antiviral and antifungal. Ttraditionally it has been used as medicine for the treatment of skin diseases, rheumatism and different pain conditions. The current study was undertaken to investigate possible effects of ethanol extract of seeds of plant in experimentally produced pain in animals because there were no scientific publications on the use of Aesculus indica seeds for anti-nociceptive activity. Preliminary phytochemical screening revealed the presence of flavonoids, tannins, carbohydrates, Saponins, and phenolic substances in the extract. The OECD guideline 423 was followed for acute toxicity testing.At a dose of 2000 mg/kg, the extract was confirmed to be safe. The anti-nociceptive effect of three distinct dose levels of extract (100, 200, and 300 mg/kg) was tested in Swiss albino mice using a hot plate, tail immersion test, and acetic acid induced writhing. Extract had strong anti-nociceptive efficacy (P < 0.001) in a hot plate test. The extract significantly increased the tail withdrawal reaction in the tail immersion test (P < 0.001).The extract considerably reduced the number of writhes in the acetic acid writhing test (P < 0.001). The findings indicate that the extract has substantial anti-nociceptive effect.

In vivo Assessment of the Antinociceptive Activity of Ethanol Bark Extract of Thevetia peruviana (Family: Apocynaceae) in Swiss Albino Mice

Background: Thevetia peruviana, a common plant of Apocynaceae family has been used as Ayurvedic herbal medicine to treat hemorrhoids, hair loss, arthritis, and dysentery. The bark and leaf decoction has been used to loosen the bowels, as an emetic, and is said to be an effective curative agent for intermittent fevers. Aim of the study: The present study was an attempt to investigate the phytochemical constituents and to explore the antinociceptive activity of ethanol extract of the bark of Thevetia peruviana which is growing in Bangladesh. Methodology: The antinociceptive activity of ethanol extract of T. peruviana was evaluated by heat-induced (hot plate, tail immersion test) and chemical-induced (acetic acid induced writhing, formalin-induced nociception) pain models using Swiss albino mice as experimental animal. Results: The results of preliminary phytochemical screenings revealed that the extract contained alkaloids, tannins, terpenoids and flavonoids. For acetic acid-induced writhing test, the sample showed highest inhibition of writhing (40.04%) at the dose of 400 mg/kg body weight, whereas standard drug (Diclofenac sodium) showed 65.6% writhing inhibition. In formalin-induced nociception, extract of T. peruviana exhibited dose-dependent antinociceptive activity. On the other hand, ethanol extract of T. peruviana bark showed significant effect (p<0.05) in hot plate and tail immersion test in various phases. Conclusion: The ethanol extract of T. peruviana bark showed significant antinociceptive activity via multifactorial mechanism of action, indicating that the extract may be useful in the development of new analgesic drugs.

Efeitos anti-inflamatório tópico e antinociceptivo do extrato etanólico de Lychnophora pinaster (Arnica Brasileira)

Species of the genus Lychnophora, known in Brazil as arnica, are used in Brazilian popular medicine to treat inflammation, rheumatism, bruises and insect bites. Previous studies showed the anti-bacterial and antinociceptive effects of Lychnophora pinaster ethanolic extract. In the present work, the ethanolic extract of L. pinaster aereal parts was subjected to a chromatographic fractionation in a gel filtration column to obtain hexane, dichloromethane, ethyl acetate and methanolic fractions. The topical effect of the ethanolic extract and its fractions, into emulgel at 5%, was evaluated on Swiss mice paw oedema induced by carragenin. All treatments with ethanolic extract and its fractions were able to do reduce significantly the oedema, suggesting the presence of substances of low, medium and high polarity acting synergistically to the anti-inflammatory effect of the extract. Evaluation of the antinociceptive activity of ethanolic extract and its fractions were performed in mice, using hot plate and acetic acid induced contortion methods. The extract and its fractions were administered by oral route at 100 mg/kg. Indomethacin was used as reference drug for the contortions induced by acetic acid and morphine for the hot plate test. The ethanolic extract and its fractions presented antinociceptive activity observed by the contortion induced by acetic acid reduction, which suggests the peripheral effect, probably by the release modulation of the substances that induce nociception. The ethanolic extract and fractions of ethyl acetate and methanol showed effect at hot plate method, similarly to morphine. This result indicated the presence of substances of medium to high polarity, acting centrally. The results demonstrated the effects of arnica ethanolic extract to reduce inflammation and pain, as well as their potential to treat these conditions. The terpenes, flavonoids and phenolic acids of L. pinaster are maybe responsible for anti-inflammatory and antinociceptive effects of the ethanolic extract.

In vivo anti-arthritic and anti-nociceptive effects of ethanol extract of Moringa oleifera leaves on complete Freund's adjuvant (CFA)-induced arthritis in rats

BackgroundThe medicinal uses of plants are in many cases based exclusively on traditional knowledge without enough scientific evidences. Different parts of Moringa oleifera were traditionally used for the treatment of wide variety of ailments including arthritis and joints pain. The present study had been designed to evaluate the anti-arthritic and anti-nociceptive activities of ethanol extract of Moringa leaves, this being the most abundant plant part suitable for commercial mass production of botanical medicinal products. MethodsComplete Freund's adjuvant (CFA)-induced arthritis in rats was used as disease model. CFA-induced inflammatory paw edema, body weight, arthritic index, X-ray radiography, hematological parameters, and walk track and locomotion analysis were all evaluated for the assessment of disease progression. In addition to that, anti-nociceptive activity was examined at different dose levels in both normal and arthritic-induced rats using Eddy's hot plate and tail flick thermal analgesia. ResultsThe analysis of various arthritic assessment parameters used in this study revealed that Moringa extract has a considerable effect in preventing development or ameliorate arthritis disease severity. Moreover, the ethanol extract of Moringa leaves revealed significant anti-nociceptive activity at in both normal and CFA-induced arthritis rats in a dose-dependent manner. ConclusionEthanol extract of Moringa leaves appears to be a really promising as analgesic and arthritis medication, but a larger and more detailed preclinical and clinical studies especially in human is highly recommended.

Antidiarrheal and antinociceptive activities of ethanol extract and its chloroform and pet ether fraction of Phrynium imbricatum (Roxb.) leaves in mice.

The objective of the study was to evaluate the antidiarrheal and antinociceptive activities of ethanol extract and its chloroform and pet ether fraction of Phrynium imbricatum (Roxb.) leaves in mice. In the present study, the dried leaves of P. imbricatum were subjected to extraction with ethanol, and then it was fractioned by chloroform and pet ether solvent. Antidiarrheal effects were tested by using castor oil-induced diarrhea, castor oil-induced enteropooling, and gastrointestinal transit test. Antinociceptive activity was evaluated by using the acetic acid-induced writhing test and formalin-induced paw licking test. The standard drug loperamide (5 mg/kg) showed significant (p<0.001) inhibitory activity against castor oil-induced diarrhea, in which all the examined treatments decreased the frequency of defecation and were found to possess an anti-castor oil-induced enteropooling effect in mice by reducing both weight and volume of intestinal content significantly, and reducing the propulsive movement in castor oil-induced gastrointestinal transit using charcoal meal in mice. The results showed that the ethanol extract of P. imbricatum leaves has significant dose-dependent antinociceptive activity, and among its two different fractions, the pet ether fraction significantly inhibited the abdominal writhing induced by acetic acid and the licking times in formalin test at both phases. These findings suggest that the plant may be a potential source for the development of a new antinociceptive drug and slightly suitable for diarrhea, as it exhibited lower activity. Our observations resemble previously published data on P. imbricatum leaves.

Antidepressant, anxiolytic and anti-nociceptive activities of ethanol extract of Steudnera colocasiifolia K. Koch leaves in mice model

Antidepressant, anxiolytic and anti-nociceptive activities of ethanol extract of Steudnera colocasiifolia K. Koch leaves in mice model

Antinociceptive activity of Euadenia trifoliolata (Schum. & Thonn.) Oliv. leaves and roots in mice

The leaves and roots of Euadenia trifoliolata are used in Nigeria traditional medicine for the treatment of ear ache, head ache and inflammation. The aim of the study was to evaluate the antinociceptive activity of ethanolic extract of the leaves (EL) and roots (ER) of E. trifoliolata in mice. Oral toxicity testing was performed using OECD guidelines. Antinociceptive effect was studied in mice using acetic acid-induced writhing, formalin, tail immersion and hot plate tests. Total polyphenolic contents were determined using standard methods. No mortality was recorded 24 h after oral administration of both EL and ER up to 5000 mg/kg. At the dose of 50, 100 and 200 mg/kg, administration of EL and ER resulted in significant reduction in the number of writhes compared to control. The percentage inhibition of writhings was calculated as 35.67%, 46.71% and 67.94% (EL) and 55.41%, 57.32% and 72.61% (ER), respectively. In hot plate test, EL and ER showed statistically significant antinociceptive effect, although low percentage inhibition (<50%) was recorded for ER at all the doses tested. Only EL (100 and 200 mg/kg) significantly (p < 0.001) increased the reaction time in tail immersion test. Both extracts significantly (p < 0.001) reduced the licking time in both phases of formalin test compared to control. The content of total phenolic, flavonoid and proanthocyanidin varies between the two extracts and may be the basis of the observed antinociceptive effect. The results indicate antinociceptive activity for the leaves and roots of E. trifoliolata, with the extract of the leaves showing better activity.

Evaluation of antinociceptive activity of ethanol extract of bark of Polyalthia longifolia

Ethnopharmacological relevancePolyalthia longifolia var. pendula is a very popular herb in Bangladesh due to its traditional uses in treatment of rheumatism, bone fracture and gastric ulcer. The present study was conducted to investigate the antinociceptive activity of ethanol extract of P. longifolia (EEPL) bark. Materials and methodsHot plate and tail immersion tests, acetic acid-induced writhing test, glutamate and formalin-induced paw licking tests in mice were employed in this study. In all the experiments EEPL was administered orally at the doses of 50, 100 and 200mg/kg body weight. To investigate the possible participation of opioid system in EEPL-mediated effects, naloxone was used to antagonize the action. ResultsEEPL showed a significant antinociceptive activity against both heat and chemical-induced nociception. The effects were dose-dependent and significant at the doses of 100 and 200mg/kg of EEPL. Besides, pretreatment with naloxone caused significant inhibition of the antinociceptive activity induced by EEPL, revealing the possible involvement of the opioid receptors. ConclusionThese results indicate the antinociceptive activity of the bark of P. longifolia and support the ethnomedical use of this plant in treatment of different painful conditions.

Evaluation of Antinociceptive Activity of Ethanol Extract of Leaves of Adenanthera pavonina.

Adenanthera pavonina is a deciduous tree commonly used in the traditional medicine to treat inflammation and rheumatism. The aim of this study was to evaluate the antinociceptive activity of ethanol extract of leaves of A. pavonina (EEAP). EEAP was investigated using various nociceptive models induced thermally or chemically in mice including hot plate and tail immersion test, acetic acid-induced writhing, and glutamate- and formalin-induced licking tests at the doses of 50, 100, and 200 mg/kg body weight (p.o.). In addition, to assess the possible mechanisms, involvement of opioid system was verified using naloxone (2 mg/kg) and cyclic guanosine monophosphate (cGMP) signaling pathway by methylene blue (MB; 20 mg/kg). The results have demonstrated that EEAP produced a significant and dose-dependent increment in the hot plate latency and tail withdrawal time. It also reduced the number of abdominal constrictions and paw lickings induced by acetic acid and glutamate respectively. EEAP inhibited the nociceptive responses in both phases of formalin test. Besides, the reversal effects of naloxone indicated the association of opioid receptors on the exertion of EEAP action centrally. Moreover, the enhancement of writhing inhibitory activity by MB suggests the possible involvement of cGMP pathway in EEAP-mediated antinociception. These results prove the antinociceptive activity of the leaves of A. pavonina and support the traditional use of this plant.

Extracts from the leaves of Campomanesia velutina inhibits production of LPS/INF-γ induced inflammatory mediators in J774A.1 cells and exerts anti-inflammatory and antinociceptive effects in vivo

Campomanesia velutina (Cambess) O. Berg, Myrtaceae, popularly known as “gabiroba” or “guavira”, is used in traditional Brazilian medicine to treat several diseases, including inflammation and rheumatism. Extraction and isolation from leaves of the plant afforded the active compound myricetin 3-O-rhamnoside, also known as myricitrin. The ethanolic extract of leaves of C. velutina and its ethyl acetate and methanolic fractions were evaluated in inflammation (carrageenan-induced paw oedema) and analgesic models (acetic acid-induced abdominal writhing and hot plate test). Moreover, the ethanolic extract, its fractions and the isolated compound were also in vitro evaluated for their ability to modulate NO, TNF-α and IL-10 production from J774A.1 macrophages stimulated by LPS/IFN-γ. In vivo assays showed remarkable anti-inflammatory activity of ethanolic extract, ethyl acetate and methanolic fractions. The antinociceptive activity of ethanolic extract and A was demonstrated in acetic acid-induced abdominal writhing test. In vitro assays demonstrated that ethyl acetate and methanolic fractions fraction and myricitrin inhibited NO production from macrophages J774A.1. Also Myricitrin induced production of IL-10 anti-inflammatory cytokine. None of the samples was able to inhibited TNF-α production. The results demonstrated for the first time the anti-inflammatory and antinociceptive activity of C. velutina.

Antinociceptive activity of ethanolic extract and isolated compounds of Urtica circularis

Urtica circularis (Hicken) Sorarú is a medicinal plant commonly used in traditional medicine to relieve pain in inflammatory processes. In the present study, the in vivo antinociceptive effect of Urtica circularis ethanolic extract and its isolated compounds has been investigated. Antinociceptive activity was evaluated through writhing, formalin and hot plate tests in mice. The phytochemical analysis was performed. The extract produced significant inhibition on nociception induced by acetic acid (ED50: 72.2mg/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 10mg/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. 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.

Phytochemical investigation and evaluation of antinociceptive activity of ethanolic extract of Dalbergia sissoo (Roxb.) bark

The antinociceptive activity of ethanolic extract of the plant bark of Dalbergia sissoo (Roxb.) was investigated using tail flick method on Wistar rats. Three different dose levels (300, 500, and 1000 mg/kg) in 0.5% carboxyl methyl cellulose (CMC) were administered by p.o. route. The antinociceptive activities of the all doses were compared with that of the standard drug asprin (300 mg/kg) administered by p.o. route and the results were found to be significant (P < 0.01). At the above doses, the extract exhibited significant and dose-dependent antinociceptive activity. Phytochemical investigation of the ethanolic extract indicated the presence of carbohydrates, proteins, amino acids, phenolic compounds, and flavanoids. The antinociceptive activity of the bark extract of D. sissoo may be due to the presence of phytochemical constituents such as flavanoids. The acute toxicity study revealed that ethanolic extract was not toxic up to 3000 mg/kg body weight.