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Pharmacokinetics study of ethyl acetate extract of cylicodiscus gabunensis (mimosaceae) after oral administration and its effect on the eradication of shigella dysenteriae infection on rats
Laure Brigitte Mabeku Kouitcheu , Joseph Lebel Tamesse and Oyono Essame Jean Louis
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Cylicodiscus gabunensis (CG) is a tropical plant traditionally known for its medicinal use. The plant has also been investigated for a number of pharmacological activities. However kinetic studies are lacking for this. Hence to better elucidate the effects of the body on this plant preparation, this study was planned. Sixty Wistar albino rats were giving orally a single dose of 500 mg/kg of plant extract. Blood samples were then collected in EDTA coated tubes prior to plant extract administration and at 10, 20, 40, 80, 160, 320, 640, 960 and 1280 minutes after. Plasma obtained was analyzed to measure concentration of plant extract using its anti-shigellosis properties. Various kinetic parameters were then calculated from the plasma concentrations. For the in vivo anti-shigellosis activity of the plant extract, a suspension of Shigella dysenteriae type I (sd1) was orally administered to thirty rats. The diarrheic rats were then divided into the control group and four others received 125, 250, 500 mg/kg of the plant extract and ciprofloxacin (20 mg/kg) respectively for 7 days. The frequency and weight of normal and diarrheic faeces emitted was recorded. The presence of stools containing mucus or blood and the number of sd1 in faeces were also recorded. The peak plasma levels (81.937 mg/ml) of CG were reached at 10.66 h. The concentration declined with a mean elimination half life of 6.61 ± 0.97 h. The AUC0-∞ was 1367.7 mg h/ml. CG reduces the frequency faeces released and sd1 density from 100% (diarrheic rats) to 50.79 and 45.33% (500 mg/kg) respectively. We concluded that CG extract is effectively absorbed though the intestinal wall. The elimination half life suggests that the drug needs to be given orally at the interval of seven hours. These parameters provide a baseline for the further exploration of what the body does to the drug and justify the pharmacodynamic correlation.
Guy Sedar Singor Njateng, Donatien Gatsing, Raymond Simplice Mouokeu, Jules-Roger Kuiate
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Polyscias fulva, a medium size tree which grows in the tropical forests of West and Central Africa, is a popular medicinal plant used to treat malaria, mental illness, venereal infections, pulmonary tuberculosis as well as dermatoses. To the best of our knowledge there is no documented evidence corroborating its safety. Thus this work aimed to determine dermal toxicity profile of the antidermatophytic oil-moistened dichloromethane-methanol (1:1 v/v) stem bark extract of Polyscias fulva. Guinea pig (male and female) animal model was used for both acute and sub-acute dermal toxicity studies. For acute toxicity, single doses (0.5, 4.25 and 8 g/kg body weight) of oilmoistened plant extract were administered to animals while in sub-acute dermal toxicity, doses (13, 256.5 and 500 mg/kg bw) of plant extract were administered daily during 28 days. The possible toxic effect of the plant extract was assessed based on the animal behaviors, the organ morphology and histology, the hematological and biochemical parameters. The single and repeated dermal toxicity tests on guinea pigs did not show any overt sign of toxicity on growth patterns. The lethal dose fifty (LD50) of the oil-moistened extract was higher than 8000 mg/kg. Moreover, the hematological and biochemical parameters, liver and kidney histopathology analysis collectively indicate that dermal application of the oil-moistened extract from the stem bark of Polyscias fulva is not associated with any toxicologically relevant effects in neither male nor female guinea pigs. The overall results of this study indicate that the oil-moistened dichloromethane-methanol (1:1 v/v) stem bark extract of Polyscias fulva could provide satisfactory preclinical evidence of safety to launch a clinical trial on a standardized formulation of the plant extracts.
Sylvie Lea Wansi, Idrice Kamtchouing, Jules Roger Kuiate, Telesphore Benoît Nguelefack, Hippolyte K. wabo, Albert Kamanyi
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Pentadesma butyracea Sabine (Clusiaceae) is a medicinal plant used in Cameroon to cure ailments such as gastrointestinal disorders. This study was aimed at investigating the antidiarrhoeal and antimicrobial activities of the methanolic extract from the stem bark of P. butyracea (MEPB). Plant extract was prepared by maceration in methanol. Its oral antidiarrhoeal effects were evaluated in vivo on castor oil (10ml/kg bw) and magnesium sulfate (3g/kg bw) induced diarrhea. Diarrheic rats were treated with 125, 250, and 500mg/kg extract or loperamide 2.5mg/kg. The frequency of defecation, the latency time and water content of stool were assessed. The broth microdilution method was used to evaluate the in vitro antibacterial activity against 10 bacterial strains: Enterococcus feacalis, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Klebsiella pneumonia, Shigella flexneri, Enterobacter cloacae, Staphylococcus epidermidis, Salmonella thiphymurium et Proteus mirabilis. In vivo antimicrobial activity of the extract was assessed using an S. flexneri-infected rat model. P. butyracea extract significantly and dose dependently increased the time of appearance of the first stools and decreased the frequency of defecation and the water content of stool. It also showed relatively good antimicrobial activity against all the tested microorganisms (MIC 64 – 256 µg/ml) and MBC (256 – 1024 µg/ml); with Enterococcus feacalis being the most sensitive. At dose 500 mg/ml, P. butyracea significantly reduced shigella flexneri density (80.37%). Results suggest that Pentadesma butyracea possesses antidiarrheic and antimicrobial properties and attest its usefulness in traditional treatment of gastrointestinal disorders such as diarrhea, and the treatment of some bacterial infections as shigellosis.
Donatien Gatsing and Godwin I. Adoga
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Typhoid fever continues to be a serious health problem in developing countries. In our search for therapeutic agents from natural sources with potential for the treatment of typhoid fevers, an anti-typhoid aqueous extract was obtained from the leaves of Cassia petersiana and tested for possible toxicity risks. Toxicological study was done in mice and rats using both acute and sub-chronic techniques. Results obtained showed that, at high doses, the extract may have a depressant effect on the central nervous system, and may induce hypersensitiveness. The LD50 (lethal dose 50) values of the extract were 20 g/kg and 22 g/kg, for male and female mice, respectively. Rats administered C. petersiana extract showed significantly increased kidneys and liver to body weight ratios, increased serum total protein, and a decrease in total protein titre of the liver at high doses. Also, significant increases in serum transaminase (ALT and AST) activities were observed at high doses. Significant decreases in serum total protein and urinary protein were seen in male and female rats administered the extract at 75 mg/kg. However, urinary protein showed a significant increase in male rats treated at 4800 mg/kg. Significant increases in haematocrit values were observed in male and female rats receiving the dose 300 mg/kg. These data suggest that this extract, at moderate doses, may be used without any toxicity risk, and besides may have strengthening effects on the liver and kidneys. However, at high doses, it may create injury to the liver and kidneys.
In vitro antioxidant and α-glucosidase inhibitory activities of aqueous extract and ethyl acetate fraction of hallea stipulosa (rubiaceae)
Poualeu Kamani Sylviane Laure, Wansi Sylvie Lea, Chouna Jean Rodolphe, Miaffo David, Nkeng-Efouet Pepin Alango, Kamanyi Albert
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Antioxidant potential of plants is useful in the management of diabetes mellitus. Aim of this study was to determine the in vitro antioxidant and a-glucosidase inhibitory activities of aqueous extract and ethyl acetate fraction of Hallea stipulosa. In vitro antioxidant assays were used DPPH (1,1-Diphenyl-2-Picrylhydrazyl) scavenging assay, nitric oxide (NO) inhibition assay, ferric reducing antioxidant power (FRAP), determination of total phenol and flavonoid contents. Aqueous extract and ethyl acetate fraction exhibited a scavenging activity by inhibiting DPPH and NO radicals and showed good reducing power capability. They contain a significant amount of phenols and flavonoids. Ethyl acetate fraction showed a considerable a-glucosidase inhibitory activity with an IC50 of 39.19 µg/ml. Results suggest that antioxidant potential and a-glucosidase inhibitory activity of H. stipulosa could be due to phenols and flavonoids and could be a part of the mechanism by which it manages diabetes.

Serge Secco ATSAFACK, Norbert KODJIO, Guy Sedar Singor NJATENG, Jean Baptiste SOKOUDJOU, Jules-Roger KUIATE and Donatien GATSING
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Typhoid fever is one such disease, still remains a serious problem and a major threat to the society in most of the developing countries. In our search for therapeutic agents from natural sources with potential for the treatment of typhoid fevers, this work aims to evaluate the in vivo antisalmonellal activity and the effect of bacterial infection on tissues oxidation of aqueous extract of Albizia gummifera. The Salmonella typhi-infected rats concurrently received different doses of plant extract (20, 40 and 80 mg/kg bw) or oxytetracyclin (5 mg/kg) daily for 9 days. The parameters such as, catalase peroxidase, nitric oxide, lipid peroxidation index, malondialdehyde, alkaline phosphatase and bilirubin were assessed. Results obtained showed that groups of treated animals at 20, 40 and 80 mg/kg bw of extract were healed respectively after 8, 7 and 6 days of treatment for females and after 9, 7 and 7 days of treatment for males. Antioxidant activity has shown that CAT (male) and peroxidase (both sex) activities for treated animals were increased significantly (p < 0.05) compared to the untreated control group animals while NO, MDA, ALP and bilirubin levels were significantly decreased (p > 0.05). Increase and reduction of theses antioxidants parameters to their normal value (that of the neutral control) was doses-dependent manner. The overall results of this study indicate that aqueous extract of Albizia gummifera exhibited in different in vivo systems, strong antisalmonellal activity and antioxidant activity on cell oxidation induced by infection with Salmonella typhi.
Laure Brigitte KOUITCHEU MABEKU, Thibau Flaurant TCHOUANGUEU, Emmanuel TALLA, Jacques KOUAM
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In this study, the cellular and non cellular antioxidant and free radical scavenging properties of the methanol and ethyl acetate extract of Cassia arereh leaves were evaluated. The antioxidant and free radical scavenging activity of the plant extracts and the standard (ascorbic acid and gallic acid) were assessed through DPPH radical, hydroxyl radical, nitric oxide scavenging activity and reducing power at various concentrations ranging from 1.62 to 200 mg/ml. For cellular antioxidant assay, we evaluated the haemolysis and the haematoprotective effect of Cassia arereh against hydrogen peroxide-mediated cytotoxicity of red blood cells (RBCs) induced with CuSO4/H2O2. Total polyphenol and flavonoid content of extracts were also determined using colorimetric methods. DPPH assay showed IC 50 values of 4.27 Plus or Minus 0.9 and 3.21 Plus or Minus 0.55 mg/ml respectively for methanol and ethyl acetate extract, instead of 12.5 Plus or Minus 2.99 ug/ml for standard. Methanol extract (IC50 = 41.597 Plus or Minus 7.46 mg/ml) had a significantly higher reducing power than the ethyl acetate one (IC50 = 238.89 Plus or Minus 26.56 mg/ml). The reducing power of the methanol extract was found to be not significantly different from standards. Our results showed a non significant decrease in the nitric oxide radical production due to the extracts compared to ascorbic acid or gallic acid. It was also found that, the methanol extract (IC50 = 17.06 Plus or Minus 0.82 mg/ml) was significantly more effective than that of ethyl acetate (IC50 = 76.34 Plus or Minus 3.4 mg/ml) as hydroxyl radical scavenging activity. Both extracts induced haemolysis of sheep RBCs in a dose dependant-manner. Incubation of RBCs with extracts before exposing them to CuSO4/H2O2 reduced the hydrogen peroxide-mediated cytotoxicity of RBCs respectively by 30.71 and 34.75 %, for methanol and ethyl acetate extracts after one hour. The antihaemolytic activity decreased with time for all the tested products. These results demonstrate the antioxidant properties of Cassia arereh and reveal that methanol is the best extractant for antioxidant agents of this plant.