Wonder Kofi Mensah Abotsi

Analgesic effects of an ethanol extract of the fruits of Xylopia aethiopica (Dunal) A. Rich (Annonaceae) and the major constituent, xylopic acid in murine models

Background: Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders including rheumatism, headache, colic pain, and neuralgia. Little pharmacological data exists in scientific literature of the effect of the fruit extract and its major diterpene, xylopic acid, on pain. The present study evaluated the analgesic properties of the ethanol extract of X. aethiopica (XAE) and xylopic acid (XA), in murine models. Materials and Methods: XAE and XA were assessed in chemical (acetic acid-induced abdominal writhing and formalin tests), thermal (Tail-flick and Hargreaves thermal hyperalgesia tests), and mechanical (Randall-Selitto paw pressure test) pain models. Results: XAE and XA exhibited significant analgesic activity in all the pain models used. XAE (30-300 mg kg-1, p.o.) and XA (10-100 mg kg-1, p.o.) inhibited acetic acid-induced visceral nociception, formalin- induced paw pain (both neurogenic and inflammatory), thermal pain as well as carrageenan-induced mechanical and thermal hyperalgesia in animals. Morphine (1-10 mg kg-1, i.p.) and diclofenac (1-10 mg kg-1, i.p.), used as controls, exhibited similar anti-nociceptive activities. XAE and XA did not induce tolerance to their respective anti-nociceptive effects in the formalin test after chronic administration. Morphine tolerance did not also cross-generalize to the analgesic effects of XAE or XA. Conclusions: These findings establish the analgesic properties of the ethanol fruit extract of X. aethiopica and its major diterpene, xylopic acid.

Antinociceptive effect of an ethanolic extract of the aerial parts of Hilleria latifolia (Lam.) H. Walt. (Phytolaccaceae).

Background: Hilleria latifolia (Lam.) H. Walt. (Phytolaccaceae) is a perennial herb used in Ghanaian traditional medicine for the treatment of various painful conditions. Little scientific evidence exists in literature on the effect of this plant on pain. Materials and Methods: The present study examined the antinociceptive effect of the ethanolic extract of the aerial parts of H. latifolia in chemical (acetic acid-induced abdominal writhing, glutamate, formalin, and capsaicin tests) and thermal (tail immersion test) behavioral pain models in rodents. The possible mechanisms of the antinociceptive action were also assessed with various antagonists in the formalin test. Results: The H. latifolia extract (HLE) together with morphine and diclofenac (positive controls), showed significant antinociceptive activity in all the models used. The antinociceptive effect exhibited by HLE in the formalin test was partly or wholly reversed by the systemic administration of naloxone, theophylline, and atropine. Glibenclamide, ondansetron, yohimbine, nifedipine, and NG-L-nitro-arginine methyl ester (L-NAME), however, did not significantly block the antinociceptive effect of the extract. HLE, unlike morphine, did not induce tolerance to its antinociceptive effect in the formalin test after chronic administration; morphine tolerance did not also cross-generalize to HLE. Interestingly, also, the chronic concomitant administration of HLE and morphine significantly suppressed the development of morphine tolerance. Conclusion: Together, these results indicate that HLE produces dose-related antinociception in several models of chemical and thermal pain, without tolerance induction, through mechanisms that involve an interaction with adenosinergic, muscarinic cholinergic, and opioid pathways.

Anti-allodynic and Anti-hyperalgesic effects of an ethanolic extract and xylopic acid from the fruits of Xylopia aethiopica in murine models of neuropathic pain

Background: Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders including headache and neuralgia. An animal model of vincristine-induced sensory neuropathy was developed after repeated intraperitoneal injection in rats and used in the present work to study the effects of the ethanolic extract of X. aethiopica (XAE) and its diterpene xylopic acid (XA) in vincristine-induced neuropathic pain. Materials and Methods: Vincristine (0.1 mg kg-1 day-1) was administered during two cycles of five consecutive days to induce chemotherapy-induced neuropathic pain. Static tactile anti-allodynic, anti-hyperalgesic, and cold anti-allodynic effects of XAE (30-300 mg kg-1) and XA (10-100 mg kg-1) were assessed using Von Frey filaments of bending forces of 4, 8, and 15 g, the Randall-Selitto paw pressure test, and cold water (4.5°C), respectively. Results: Administration of vincristine caused the development of allodynia and hyperalgesia with no significant motor deficit, spontaneous pain, and foot deformity. XAE (30-300 mg kg-1) and XA (10-100 mg kg-1) exhibited anti-hyperalgesic, tactile, and cold anti-allodynic properties with XA exhibiting greater potency than XAE. Pregabalin (10-100 mg kg-1) used as control produced similar effect. Conclusion: These findings establish the anti-allodynic and anti-hyperalgesic effects of the ethanolic fruit XAE and its major diterpene XA in vincristine-induced neuropathtic pain.

Anti-inflammatory activity of aqueous leaf extract of Phyllanthus muellerianus (Kuntze) Exell. and its major constituent, geraniin

ETHNOPHARMACOLOGICAL RELEVANCE Phyllanthus muellerianus (Kuntze) Exell. which belongs to the Family Euphorbiaceae is a shrub widely distributed in West Africa. It is used traditionally to manage wounds and wound infections, menstrual disorders, fevers, pain and inflammation. Hence to confirm its ethnobotanical uses in managing inflammation, we investigated the anti-inflammatory properties of aqueous leaf extract of P. muellerianus (PLE) and its major isolate, geraniin in experimentally-induced inflammation in rats. MATERIALS AND METHODS Carrageenan induced oedema and adjuvant induced arthritis models in rats were used in this study. RESULTS In the carrageenan-induced acute inflammation, both 300mg/kg PLE-treated and 10mg/kg geraniin-treated groups significantly reduced the mean maximal swelling attained at 4h to 46.75±4.97% (p<0.01) and 61.65±6.70% (p<0.05), respectively, from the inflamed control response of 122.60±16.39%. In the adjuvant-induced chronic inflammation, both PLE-treated (100 and 300mg/kg) groups and geraniin-treated (10 and 30mg/kg) groups significantly (p<0.001) reduced the total limb swelling over 16 days in the polyarthritic phase compared to the arthritic control. These observations were supported by the radiograph records and the histological investigations of the hind limbs which showed reduced bone damage in both PLE and geraniin-treated rats. CONCLUSION The findings may confirm the ethnobotanical use of PLE in the management of inflammatory disorders or conditions and observed anti-inflammatory property of PLE may largely be due to its major constituent, geraniin.

Analgesic effects of stem bark extracts of Trichilia monadelpha (Thonn.) JJ De Wilde.

Objectives: Various parts of Trichilia monadelpha (Thonn) JJ De Wilde (Fam. Meliaceae) are used in Ghanaian traditional medicine for the treatment of painful and inflammatory conditions. The present study examined the analgesic properties of the petroleum ether (PEE), ethyl acetate (EAE), and the hydro-ethanolic (HAE) extract of the stem bark of the plant in murine models. Materials and Methods: PEE, EAE, and HAE were assessed in chemical (acetic acid-induced abdominal writhing and formalin tests), thermal (hot plate test), and mechanical (Randall-Selitto paw pressure test) pain models. The possible mechanisms of the antinociceptive action were also examined with various antagonists in the formalin test. Results: HAE, EAE, and PEE, each at doses of 10–100 mg/kg orally, and the positive controls (morphine and diclofenac) elicited significant dose-dependent antinociceptive activity in the chemical (acetic acid abdominal writhing and formalin tests), thermal (hot plate test), and mechanical (Randall-Selitto paw pressure test) pain models in rodents. The antinociceptive effect of HAE was partly or wholly reversed by systemic administration of atropine, naloxone, and glibenclamide. The antinociceptive effects of EAE and PEE were inhibited by atropine. Conclusion: The extracts HAE, EAE, and PEE caused dose-related antinociception in chemical, thermal, and mechanical models of pain in animals. The mechanism of action of HAE involves an interaction with muscarinic cholinergic, adenosinergic, opioidergic pathways, and ATP-sensitive K+ channels while that of EAE and PEE involve the muscarinic cholinergic system.

An isobolographic analysis of the antinociceptive effect of xylopic acid in combination with morphine or diclofenac.

Background: A common practice of managing pain globally is the combination of analgesics and this is aimed at facilitating patient compliance, simplifying prescription, and improving efficacy without increasing adverse effects. Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders and xylopic acid (XA) present in the fruit extract have been shown to possess analgesic properties in animals. There is the likelihood of concomitant use of XA and the commonly used analgesics in traditional settings. This study, therefore, evaluated the pharmacologic interaction between XA/morphine and xylopic/diclofenac combinations. Methods: The formalin test and acetic acid writhing test were used to study the antinociceptive activity of XA, morphine, and diclofenac. The isobolographic analysis was used to study the antinociceptive interactions between XA co-administered with morphine or diclofenac. Results: Results obtained revealed that XA (10–100 mg/kg), morphine (1–10 mg/kg), and diclofenac (1–10 mg/kg) produced dose-related antinociception with different potencies in the formalin and acetic acid writhing tests. Isobolographic analysis of XA/morphine and XA/diclofenac combinations revealed potentiation of their antinociceptive effects. The degree of potentiation calculated as interaction index showed synergism for both combinations in all the nociceptive tests. Conclusion: In conclusion, the present study demonstrated synergism for the co-administration of XA with morphine or diclofenac.

An evaluation of the anti-inflammatory, antipyretic and analgesic effects of hydroethanol leaf extract of Albizia zygia in animal models

Abstract Context: The leaves of Albizia zygia (DC.) J.F. Macbr. (Leguminosae-Mimosoideae) are used in Ghanaian traditional medicine for the treatment of pain, inflammatory disorders and fever (including malaria). Objectives: The present study evaluated the anti-inflammatory, antipyretic and analgesic effects of the hydroethanol leaf extract of Albizia zygia (AZE) in animal models. Materials and methods: The anti-inflammatory and antipyretic effects of AZE were examined in the carrageenan-induced foot oedema model and the baker’s yeast-induced pyrexia test respectively. The analgesic effect and possible mechanisms of action were also assessed in the formalin test. Results: AZE (30–300 mg/kg, p.o.), either preemptively or curatively, significantly inhibited carrageenan-induced foot edema in 7-day-old chicks (ED50 values; preemptive: 232.9 ± 53.33 mg/kg; curative: 539.2 ± 138.28 mg/kg). Similarly, the NSAID diclofenac (10–100 mg/kg, i.p.) significantly reduced the oedema in both preemptive (ED50: 21.16 ± 4.07 mg/kg) and curative (ED50: 44.28 ± 5.75 mg/kg) treatments. The extract (30–300 mg/kg, p.o.) as well as paracetamol (150 mg/kg, p.o.) also showed significant antipyretic activity in the baker’s yeast-induced pyrexia test (ED50 of AZE: 282.5 ± 96.55 mg/kg). AZE and morphine (1–10 mg/kg, i.p.; positive control), exhibited significant analgesic activity in the formalin test. The analgesic effect was partly or wholly reversed by the systemic administration of naloxone, theophylline and atropine. Conclusion: The results suggest that AZE possesses anti-inflammatory, antipyretic and analgesic properties, which justifies its traditional use. Also, the results show the involvement of the opioidergic, adenosinergic and the muscarinic cholinergic pathways in the analgesic effects of AZE.

Albizia zygia (DC.) J.F. Macbr. (Leguminosae-Mimosoideae) root extract exhibits anti-nociceptive and antipyretic activities in murine models

ETHNOPHARMACOLOGICAL RELEVANCE The root extract of Albizia zygia (DC.) J.F. Macbr. (Leguminosae-Mimosoideae) is traditionally used in the management of pain and fever. However, little scientific data exists in literature to support its use. AIM OF STUDY The present study evaluated the anti-nociceptive and antipyretic properties of the hydroethanolic extract of the roots of Albizia zygia in animal models. MATERIALS AND METHODS The analgesic effects were investigated in chemical (acetic acid-induced abdominal writhing and formalin tests), thermal (tail-immersion test) and mechanical (carrageenan-induced hyperalgesia) pain models. Possible mechanisms of anti-nociception were also assessed with antagonists in the formalin test. The anti-pyretic effect was evaluated using the baker yeast-induced pyrexia model in young rats. RESULTS The extract (30-300mg/kg, p.o.) and positive controls, diclofenac (3-30mg/kg, i.p.) and morphine (1-10mg/kg, i.p.), significantly (at least P<0.01) attenuated acetic acid-induced visceral pain, formalin- induced paw pain (both neurogenic and inflammatory), thermal pain as well as carrageenan-induced mechanical hyperalgesia in animals. The anti-nociceptive effect of the extract was reversed (at least P<0.05) by the pre-emptive administration of naloxone and atropine; the administration of theophylline, however, exhibited no significant (P>0.05) inhibition of anti-nociception. The extract (30-300mg/kg, p.o) and paracetamol (15-150mg/kg, p.o.) both reversed yeast-induced pyrexia in rats with ED50 values of 48.59±2.59 and 26.19±1.33mg/kg respectively. CONCLUSION The findings indicate that the extract possesses significant anti-nociceptive and antipyretic effects which justify its traditional use in the management of pain and fever. Also, anti-nociceptive effect of the extract involves opioidergic and muscarinic cholinergic mechanisms.

Effects of an ethanol extract and the diterpene, xylopic acid, of Xylopia aethiopica fruits in murine models of musculoskeletal pain.

Abstract Context: Fruits of Xylopia aethiopica (Dunal) A. Rich. (Annonaceae) are used traditionally to manage arthritis, headache and other pain disorders. Objective: The analgesic properties of the X. aethiopica ethanol fruit extract (XAE) and xylopic acid (XA) were evaluated in musculoskeletal pain models. Materials and methods: Acute muscle pain was induced in gastrocnemius muscle of Sprague–Dawley rats with 3% carrageenan (i.m.). Rats received XAE (30–300 mg/kg), XA (10–100 mg/kg) or morphine (1–10 mg/kg) after 12 h. Effects of XAE and XA on muscle pain were assessed by measuring post-treatment grip strength of the rats. Chronic muscle pain was similarly induced, but drug treatment was on the eighth day and effects of XAE and XA assessed with Randall–Selitto test for hyperlagesia. Acute-skeletal pain was induced in knee joints of rats with 3% carrageenan-kaolin mixture and effects determined 12-h later. Similar induction protocol was used for chronic knee pain with treatment and measurement as done for chronic muscle pain. Results: XAE and XA significantly and dose-dependently ameliorated both acute muscle (ED50 mg/kg: XAE = 22.9; XA = 6.2) and skeletal hyperalgesia (XAE = 39.9; XA = 17.7) induced by 3% carrageenan. Similarly, chronic skeletal hyperalgesia was reduced by XAE and XA treatment similar to morphine (ED50: XAE = 13.0; XA = 4.6). This reduction was also seen in chronic muscle hyperalgesia (ED50: XAE = 79.1; XA = 42.7). XAE and XA significantly reduced the spread of hyperalgesia to contralateral limbs in both models of chronic hyperalgesia. Conclusion: These findings establish analgesic properties of the ethanol fruit extract of X. aethiopica and xylopic acid in musculoskeletal pain.

Anticonvulsant effect of the hydroethanolic leaf extract of Psydrax subcordata (DC.) Bridson in murine models

ETHNOPHARMACOLOGICAL RELEVANCE Psydrax subcordata (DC.) Bridson is a tropical medicinal plant used traditionally for the management of epilepsy. However, there is little scientific evidence to support its use. AIM OF STUDY The current study investigated the anticonvulsant properties of the hydroethanolic leaf extract of Psydrax subcordata (PSE) in animal models. MATERIALS AND METHODS The anticonvulsant effects were evaluated in mouse models of acute seizures (pentylenetetrazole-, picrotoxin-, 4-aminopyridine-, strychnine- and maximal electroshock-induced seizure tests) and status epilepticus (Lithium/pilocarpine-induced SE). The role of GABAergic mechanisms in the actions of the extract was also examined by pre-treatment of animals with flumazenil in the pentylenetetrazole test. RESULTS The extract (30, 100 and 300mg/kg, p.o.) significantly delayed the onset and decreased the duration and frequency of pentylenetetrazole- and picrotoxin-convulsions. PSE also reduced the duration of tonic hind limb extensions in the maximal electroshock-induced seizure test. Furthermore, PSE pre-treatment significantly delayed the onset of seizures and improved survival in the 4-aminopyridine-induced seizure test. In the strychnine-induced seizure test, PSE treatment did not significantly affect the latency to convulsions and time until death when compared to controls. PSE exhibited anticonvulsant effects in the lithium/pilocarpine test by delaying the onset of seizures and status epilepticus as well as reducing the severity of seizures and mortality of mice. Again, the anticonvulsant effect of PSE (100mg/kg, p.o.) was blocked by pre-treatment with flumazenil in the PTZ test. CONCLUSION PSE has anticonvulsant activity in animal models, and this effect may be mediated, at least partly, through GABAergic mechanisms.