Pharmacology and Toxicology

Studies on the Anti-Ulcer Activities of the Fruit Extract and Fractions of Cucumis Metuliferus (Cucurbitaceae)

Sat, 01 Oct 2016 00:00:00 GMT

Studies on the Anti-Ulcer Activities of the Fruit Extract and Fractions of Cucumis Metuliferus (Cucurbitaceae) Okpalaeke, Ebere Emilia The anti-ulcer and other gastrointestinal effects of the methanol extract and fractions of Cucumis metuliferus were investigated in rats and mice. Ethyl acetate (EAFCM), butanol (BFCM) and water (WFCM) fractions obtained from the methanol extract of Cucumis metuliferus (MECM) were screened for anti-ulcer activity. The anti-ulcer effect was investigated on gastric ulcers induced by absolute ethanol, hypothermic-restraint stress and indomethacin in rats. The median lethal dose (LD50) of the extract and its fractions were determined in mice by the oral route using technique of Locke. The effect of MECM and fractions on gastrointestinal propulsive movement in mice was investigated. Their effects on the rabbit jejunum and guinea pig ileum were also carried out. The results revealed that the extract and its fractions at doses up to 5000 mg/kg showed no signs of toxicity or death. The extract and fractions at doses of 100 - 400 mg/kg significantly (P< 0.05) reduced the ulcer indices in a dose-related manner. MECM and fractions produced a significant (P< -0.05) inhibition of gastrointestinal tract motility on the rabbit jejunum in a dose-dependent manner. MECM and fractions produced a concentration-dependent relaxation of rabbit jejunum. MECM and fractions did not show any effect on the guinea pig ileum. However the contractile effect produced by histamine was attenuated by the extract and fractions, contractile effect of acetylcholine on guinea pig ileum was not attenuated. Preliminary phytochemical analysis showed presence of flavonoids, alkaloids, saponins, carbohydrates, steroids, trepenoid, anthraquinones and cardiac glycosides. Put together, the results of the study showed that Cucumis metuliferus contain bioactive ingredients which have protective effects against gastroerosive ulcers induced by ethanol, stress and indomethacin.

Evaluation of the Antinociceptive and Anxiolytic-Like Activities of Leaf Extract and Fraction of Phyllanthus Muellerianus Kuntze

Fri, 02 Jun 2017 00:00:00 GMT

Evaluation of the Antinociceptive and Anxiolytic-Like Activities of Leaf Extract and Fraction of Phyllanthus Muellerianus Kuntze Umezinwa, Ogochukwu Jennifer The anxiolytic and antinociceptive properties of the leaf extract and fraction of Phyllanthus muellerianus Kuntze (Phyllanthaceae) were investigated.The extract (MME; 500.18 g; 10%w/w), obtained by cold maceration in 1:1 mixture of methylene chloride: methanol for 48 h, was fractionationed in a silica gel column which yielded the ethyl acetate fraction (EF; 199.2 g; 39.83% w/w). The extract and fraction were subjected to phytochemical analysis. Acute toxicity of MME was determined in mice using the oral route. Anxiolytic-like activity of MME and EF was investigated in mice using behavioural paradigms of anxiety on the Elevated Plus Maze (EPM) and the Light and Dark box tests. Antinociceptive activity was evaluated using abdominal writhing induced by acetic acid in rats and paw-licking induced by formalin in mice. The results showed that MME and EF gave positive reactions for alkaloids, carbohydrates, flavonoids, glycosides, reducing sugar, saponins, steroids, tannins, terpenoids and resins. Acute toxicity test on MME established an oral LD50>5000 mg/kg in mice. MME and EF caused a significant (P<0.05) increase in the duration of stay, time spent on the open arm and central platform of the EPM, the number of entries into the open arm and rearing behaviour. They also caused a significant (P<0.05) decrease in the duration of stay and number of entries in the closed arm, grooming activity, number of head dips, stretch attend posture and number of urine streaks and fecal boli. In the Dark and Light box, MME and EF significantly (P<0.05) increased the time spent in the light areaand decreased the time spent in the dark area, They also significantly (P<0.05) increased the number of line crossings and transition between the light and dark areas, the rate of peeking out of the dark box, and number of entries into the light chamber. They also caused significant (P<0.05) reduction in the number of fecal boli produced in the light and dark box. MME and EFsignificantly (P<0.05) reduced the number of abdominal writhes induced by acetic acid and the duration of paw-licking in the two phases of formalin-induced paw-licking test. A comparison of the magnitude of activity in all the tests showed the order of potency EF>MME.

Evaluation of the Subacute and Delayed Toxicity of Artemether-Lumefantrine Combination in Rats

Fri, 02 Jun 2017 00:00:00 GMT

Evaluation of the Subacute and Delayed Toxicity of Artemether-Lumefantrine Combination in Rats Ukekwe, Ikechukwu Francis Despite the reported rapid increase in demand for artemisinin and its derivatives, there is little independent collaboration of the toxicity patterns of artemether-lumefantrine combination besides those documented by the manufacturer in its application for approval. It is however, pertinent to conduct an independent evaluation of the subacute and delayed toxicity of artemether-lumefantrine combination (ALC). In this study, rats in groups I-VI were administered varying concentrations of oral artemether-lumefantrine combination as a single dose for 7 days. The animals in groups I-III were sacrificed while groups IV-VI were maintained on water and normal diet until the 15th day. On the 15th day, these animals were sacrificed to assess for delayed effects. The animals in group VII served as control and received only sterilized water and commercial feeds. Results indicated that ALC significantly (p<0.05) elevated the hemoglobin concentration (Hb), packed cell volume (PCV), reticulocyte count, total white cell count (WBC), and the percentage lymphocyte count (LC) , but decreased the percentage neutrophil count (NC) and hence caused a reversal of the neutrophil/ lymphocyte count ( N/L) ratio. ALC also caused a significant (P<0.05) increase in random blood sugar level in the subacute phase but not in the delayed phases. ALC did not have any significant (P>0.05) effects on serum electrolytes (Na+, K+, Cl- and HCO3-) level, blood urea, bilirubin, cholesterol, and liver enzymes (ALT, AST and ALP). Histopathological studies revealed no consistent evidence of significant toxicities on liver, kidney and the heart. Hepatic vascular congestion and lymphocytic infiltration as well as granular and eosinophilic hyaline casts in renal tubules were also observed, in addition to an isolated case of acute tubular necrosis with organizing fibrinous pericarditis were observed. The administration of increasing doses of oral artemether- lumefantrine combination given once daily to rats over an interval of one week, produced varying subacute and delayed hematological, biochemical and histopathological effects. ALC showed hyperglycemic effect as well as stimulatory effects on haemopoeisis and immunity but no significant subacute and delayed toxic effects on the liver, kidneys and heart. The isolated cases of acute tubular necrosis and organizing fibrinous pericarditis need further evaluation.

Wound Healing and Anti-Inflammatory Activities of Ceiba Pentendra (L.) Gaertn in Wistar Rats

Fri, 02 Jun 2017 00:00:00 GMT

Wound Healing and Anti-Inflammatory Activities of Ceiba Pentendra (L.) Gaertn in Wistar Rats Osifo, Itohan Mercy Wound healing is a natural process that enables tissue repair after an injury while inflammation is a pathophysiological response of living tissue to injuries. To shorten the duration and minimize associated complications of wounds, wounds are treated with medications. Currently there is a growing interest in the use of traditional wound dressing agents such as plant extracts. One plant used traditionally in wound treatment is Ceiba pentendra. In view of its use in wound care, we investigated the wound healing activities of whole extract and fractions of Ceiba pentendra extract using excision and incision wound models while the Anti-inflammatory activities of the whole extract and fractions was investigated using paw edema and cotton pellets model. Excision wounds were created, and treated with ointments prepared from Ceiba pentendra, incision wounds were also created in rats with both treated topically with preparations of extract and fractions with the wound healing activities of ointment assessed by rates of wound contraction and epithelialization. Anti-inflammatory activities were assessed by treating with extract and fractions orally. Ceiba pentendra ointments shows significantly (p < 0.05) accelerated wound healing with CPE-45% ointment having the highest percentage wound contraction and rate of epithelialization, with wound healing effects being seen from day 4 (20.30%) with total healing occurring at day 20 (100%). In excision wound healing activities involving the fractions. All fractions showed significantly (p<0.05) accelerated wound healing, with HXCP-30% being the most active with wound healing effects seen at day 4 (22.91%) and total healing occurring at the 16th day (100%).Wound breaking strengths in incision wound models involving the extract, significant (p<0.05) was seen at CPE-45% with other doses showing a non-significant effects. In incision wound model involving fractions the wound breaking strength showed significant with HXCP-30% and BNCP-30%. Anti-inflammatory effects using cotton-pellets showed that granuloma tissues formed in the extract treated groups were significantly (p < 0.05) higher than those of the control group, the significant was seen with CPE-200 mg/kg and 400 mg/kg. Anti-inflammatory effects using cotton-pellets showed that granuloma tissues formed in the fractions treated groups were significantly (p < 0.05) higher than those of the control group, the significant was seen with CPE-200 mg/kg and 400 mg/kg. The extracts showed significant anti-inflammatory activities after 2 h with maximum percentage inhibition of 60.00% seen at the sixth hour at 400 mg/kg dose level. Nevertheless inhibition was still observed at six hours after administration at all dose level. In paw oedema model involving various fractions, a significant inhibition (P<0.05) was seen with butanol fraction at all dose levels, with percentage inhibition of 13.68% occurring at 1 h for BNCP-200 mg/kg and percentage inhibition of 31.25%, at the fifth h for BNCP-100 mg/kg. There was a dose dependent inhibition for the hexane fractions; hence inhibition was seen at 200 mg/kg at the fourth hour with percentage inhibition of 31.25%, while no effect was seen with HXCP-100 mg/kg. The ethylacetate fraction also showed significant inhibition at all dose level starting at the third hour for EACP-100 mg/kg with percentage inhibition of 21.05% and the fourth hour for EACP-200 mg/kg with percentage of 22.22%. Maximum percentage inhibition was seen of 46.15% was seen at HXCP- 200 mg/kg, EACP-100 mg/kg and BNCP-200 mg/kg. The results obtained showed that Ceiba pentendra has good wound healing and antibacterial activities. These findings validate the use of this plant in traditional medicine for treatment of wounds.