Maerua angolensis Extract Reduces Allodynia and Hyperalgesia in a Mouse Model of Vincristine-Induced Peripheral Neuropathy.

Allodynia and hyperalgesia comprise the main and frequent symptoms suffered by patients with neuropathic pain, which responds poorly to therapy. An earlier study reported that stem bark extracts of Maerua angolensis exhibited dose-dependent anti-nociceptive effect against the neurogenic and inflammatory phases of the formalin test. The current study evaluated the effect of petroleum ether/ethyl acetate stem bark extract of Maerua angolensis on vincristine-induced neuropathy. Neuropathic pain was induced by intraperitoneal injection of vincristine (0.1 mg/kg/day) using a 5-day-on, 2-day-off schedule over 12 days. On day 15, baseline responses were measured in the Randall-Selitto mechanical hyperalgesia test and paw withdrawal tests (using Von Frey filaments and cold water at 4.5 °C) and mice that developed allodynia/hyperalgesia were randomly assigned into 7 groups. Normal saline (i.p.), pregabalin (10, 30, and 100 mg/kg, p.o.) and extract (3, 10, and 20 mg/kg, p.o.) were administered to the individual groups. Allodynia/hyperalgesia was measured hourly for 5 hours post treatment. The extract produced significant (P<0.05) and dose-dependent inhibition of vincristine-induced mechanical hyperalgesia, tactile and cold allodynia responses. In all, the study shows that oral administration of Maerua angolensis stem bark extract inhibits vincristine-induced neuropathy in mice suggesting that it may exert analgesic effect in cancer patients with vincristine-induced neuropathic pain.

Evaluation of Analgesic Property of Petroleum Ether/Ethyl Acetate Stem Bark Extract and Fractions of Maerua angolensis in Murine Models of Pain.

This study investigated the possible antinociceptive action of the petroleum ether/ethyl acetate extract and fractions prepared from the stem barks of Maerua angolensis. The acetic acid-induced abdominal writhing, formalin–induced nociception, prostaglandin E2–induced mechanical hyperalgesia, bradykinin– and epinephrineinduced thermal hyperalgesia tests as well as Paw withdrawal test using Hargreaves thermal hyperalgesia model were used to assess the antinociceptive effects of the extract and the fractions after oral administration in rodents. Diclofenac and morphine were used as reference analgesic agents. Mice were submitted to the rotarod test in order to assess any non–specific muscle–relaxant effect of the extract and the fractions. The petroleum ether/ethyl acetate extract and the fractions of Maerua angolensis produced significant (P < 0.05) and dose-dependent antinociceptive effects in the acetic acid, formalin, prostaglandin E2, bradykinin, epinephrine and paw withdrawal tests. The extract and the fractions of Maerua angolensis (3 and 10 mg/kg) did not compromise the motor coordination of animals in the rotarod test, suggesting lack of central depressant effect. The petroleum ether/ethyl acetate extract and fractions of Maerua angolensis stem bark produced dose-dependent antinociception in murine models of chemical, mechanical and thermal nociception suggesting peripheral and central analgesic action.

Antidepressant-like properties of Antiaris toxicaria aqueous extract.

Background: Depression is a global burden whose therapy is plagued with inconsistent effi cacy. Hence, the need for the discovery of newer therapies. Methods: In this study, Antiaris toxicaria extract (200, 400 and 800 mg/kg, p.o.), was evaluated for antidepressant activity using behavioral tests battery particularly the forced swim test (FST) and tail suspension test (TST). In order to investigate its mechanism of action, animals groups were pretreated with α-methyldopa (α-MD), para-chlorophenylalanine (PCPA), reserpine, D-serine and 5-hydroxytryptophan. Results: It increased the mobility periods and decreased immobility periods signifi cantly in both the FST and the TST when compared to the control group. But the TST showed more promising effect than the FST. Pre-treatment with α-MD reversed the antidepressant property of A. toxicaria aqueous extract as did PCPA, reserpine and reserpine combined with α-MD. The extract increased the number of head twitches produced by 5-hydroxytryptophan confi rming the involvement of serotonin in the antidepressant property and inhibited carbachol-induced contractions on the isolated rat uterus, which was non-competitively antagonized by propranolol. Treatment with D-serine produced no signifi cant increase in the immobility time produced by the extract at the doses studied. This excludes the involvement of N-methyl-d-aspartate in the possible mechanisms of action. Conclusion: A. toxicaria possesses antidepressant-like action in rodents.

Ameliorative Effects of Ethanolic Leaf Extract of Palisota hirsuta K. Schum (Commelinaceae) on Vincristine-Induced Neuropathic Pain in rats.

Vincristine-induced neuropathy is a major dose-limiting side effect of cancer chemotherapy and thus effective therapeutic strategy is required. The present study utilized a rodent model of neuropathy to determine whether an ethanolic leaf extract of Palisota hirsuta (PHE), a plant widely used in West African traditional medicine for pain management and CNS disorders, could attenuate vincristine-induced neuropathic pain. Neuropathic pain was induced by injecting rats intraperitoneallywith vincristine (0.1 mg kg-1 day-1 in two 5-day cycles with a two-day break). Randall-Selitto Paw Pressure, Hargreaves, cold water (4-5˚C) and Von Frey Filaments tests were performed. These tests were used to assess the degree of mechanical hyperalgesia, thermal hyperalgesia and cold and tactile allodynia respectively as an index of peripheral and central pain sensation.Oral administrations of PHE (30-300 mg kg-1) significantly and dose-dependently ameliorated vincristine-induced pain-related behaviors. It significantly reduced both mechanical and thermal hyperalgesia and completely reversed vincristine-induced tactile allodynia at 100 and 300 mg kg-1 after 24 h. It however showed little effect on cold allodynia. These effects were similar to that of the gabapentin-treated group. In conclusion, oral administration of an ethanolic leaf extract of Palisota hirsuta attenuates pain-related behavior in vincristine-induced neuropathic pain model.

Acute and Sub-Chronic Toxicity Studies of Aqueous Extract of Root Bark of Cassia Sieberiana D.C. in Rodents.

Acute and sub-chronic toxicity studies of the aqueous extract of the root bark of C. sieberiana (Caesalpiniaceae), a plant used locally in Ghana for the treatment of pain, was carried out in rodents. In the acute study, a single oral dose (5000 mg/kg) of the aqueous extract of C. sieberiana (NPK) was administered to six rats and six mice, and observed for 14 days for signs of acute toxicity. In the sub-chronic study, rats were administered with NPK (15- 750 mg/kg) daily for three months. Urinalysis, haematological and biochemical analyses were carried out on urine, blood and serum samples collected at the end of the three-month treatment. Histological analyses of the liver, heart, kidney and lung tissues were also done. The results showed that administration of 5000 mg/kg of NPK to animals did not result in death. There were no significant differences (p>0.05) between control and test animals in the haematological assay. The albumin, alkaline phosphatase and total bilirubin were higher (p<0.05) in test animals compared to the controls. Liver micrographs showed centrilobular necrosis at the dose of 750 mg/kg. The findings, therefore, show that the oral toxicity of NPK in rodents is low (oral LD50 > 5000 mg/kg). However, the extract may have deleterious effects on the liver at high doses on prolonged administration.