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The study of analgesic effect of hydroalcoholic extract of Teucrium oliveranum in rat by formalin test
Abstracts / Toxicology Letters 196S (2010) S37–S351
In conclusion, pro-aspirin and related nitric oxide releasing compound hold significant therapeutic promise. The experiment which has given valuable results in an in vitro study will be continued in animal models. doi:10.1016/j.toxlet.2010.03.862
P302-033 The study of analgesic effect of hydroalcoholic extract of Teucrium oliveranum in rat by formalin test A. Arzi, F. Arzi, E.M. Arzi School of Pharmacy, Physiology Research Center, Ahwaz Jundishapur Univesity if Medical Sciences, Ahwaz, Iran The side effects of synthetic analgesic drugs in the clinical practice, have turned the attention of researchers to focus on development of herbal analgesic agents. The purpose of this study was the evaluation of analgesic effects of the hydroalcoholic extract of Teucrium oliveranum in comparison with morphine and aspirin. Maceration was performed with aqueous ethanol 70%.The prepared extract was concentrated by using rotary evaporator, and then it was dried in low temperature. Male Wister rat weighing 150–180 g were used during the study in cages and free accesses to food and water. The animals were divided into seven groups (n = 6 rats) .The test groups received 200, 400, 600 and 800 mg/kg of hydroalcoholic extract of T. oliveranum,“negative control” received normal saline (5 ml/kg) and the “positive control” groups received 2.5 mg/kg morphine and 300 mg/kg aspirin (ip), respectively. The analgesic effects of different doses of the extract and the positive and negative control groups were investigated via formalin test. In order to verify the role of opioid receptor on analgesic effect of T. oliveranum, one group of animals was treated with naloxone 1 mg/kg (ip) and extract 600 mg/kg (ip). The highest effect of analgesia was seen by dose of 600 mg/kg. Such effect was less than aspirin effect on the second phase of pain and morphine effect on both of the pain phases. The results revealed that the extract could have analgesic effect compared to the “negative control”. Naloxone could reduce the analgesic effect of extract on the second phase of pain. It may conclude that T. oliveranum extract induce its effect through opioid receptors activation or release of endogenous opioid peptides. doi:10.1016/j.toxlet.2010.03.863
P302-034 FK-3000 isolated from Stephania delavayi Diels. inhibits breast cancer cell proliferation by suppressing NF-fÛB and COX-2 M.J. Lee 1 , S.S. Han 2 1
Kangwon National University, South Korea, 2 Hoseo University, South Korea
Stephania delavayi Diels. was identified as the most promising candidate from a cell proliferation inhibitor screen of 509 plant extracts. Treatment of MDA-MB-231 breast cancer cells with S. delavayi Diels. extract effectively inhibited cell proliferation by inducing cell death. Treatment with S. delavayi Diels. downregulated NF-fÛB phosphorylation and COX-2 expression in a dose- and time-dependent manner. We identified 6,7-diO-acetylsinococuline (FK-3000) as the major active component in S. delavayi Diels. extract. The inhibitory effect of FK-3000 on
S259
cell proliferation was greater than that of the S. delavayi Diels. extract. Furthermore, treatment with FK-3000 downregulated NFfÛB phosphorylation and COX-2 expression. Finally, we tested FK-3000 in a mouse xenograft model using MDA-MB-231 cells. FK3000 inhibited tumor growth as effectively as Taxol without any visible signs of toxicity. In addition, FK-3000 exhibited a synergistic effect on in vivo tumor growth when combined with Taxol. In conclusion, FK-3000 isolated from S. delavayi Diels. is a potential anticancer agent that targets a specific pathway and exhibits low toxicity. Therefore, this compound should be further evaluated as an anticancer therapeutic. doi:10.1016/j.toxlet.2010.03.864
P302-035 Preclinical toxicity evaluation of Syngonanthus macrolepsis crude extract with antimicobacteria activity G. Honorato De Oliveira, V. Pereira Arantes School of Pharmaceutical Sciences Sao Paulo State University UNESP, Brazil Introduction: The Brazilian tropical forest functions as true laboratory of organic synthesis and many of these chemicals can be future drugs. However the tuberculosis continues being a serious problem of public health, causing death especially in underdeveloped countries. The resistance of the M. tuberculosis justified constant research for new drugs which can be obtained through the vegetal extracts which should have evaluated its toxicity. The objective of this work was evaluating the preclinical toxicity of the crude extract of Singonanthus macrolepsis, giving special attention to hepatic and renal systems. Method: The oral acute and subchronic toxicity were performed according to 423 and 408 OECD guideline using male and female Wistar rats. The acute toxicity was checked through “The limit test”; two experimental groups (2000 and 5000 mg/kg bw) and one control. The subchronic toxicity, during 90 days one control and three experimental groups received through drinking water (200, 400 and 800 g/ml) of extract. Results: To acute toxicity, light irritability in two females that received 5000 mg/kg. Heart, lung, spleen, lever and kidney were removed weighted, observed by gross necopsy they were unchangeable in relation to control. To subchronic toxicity, enzymatic analyses was carried out ALT, AST, y-GT, AP and biochemical metabolites billirubin, urea, creatinine, and protrombine time. Male rats have not presented any change while female rats have shown increased significant differences to protrombine time and y-GT, just to 800 g/ml in relation to control. Hematological analysis and histological light microscopy (H&E) of liver and kidneys was carried out and neither changes in hemogram nor injury in the tissue were observed. Conclusion: As this extract presented MIC = 62.5 g/ml in MABA, it is promissory to be used in human with little adverse effect. It encourages us to isolate the active principle and tests it in infected animals by M. tuberculoses. Supported by FUNDUNESP; PADC-FCF. doi:10.1016/j.toxlet.2010.03.865
In conclusion, pro-aspirin and related nitric oxide releasing compound hold significant therapeutic promise. The experiment which has given valuable results in an in vitro study will be continued in animal models. doi:10.1016/j.toxlet.2010.03.862
P302-033 The study of analgesic effect of hydroalcoholic extract of Teucrium oliveranum in rat by formalin test A. Arzi, F. Arzi, E.M. Arzi School of Pharmacy, Physiology Research Center, Ahwaz Jundishapur Univesity if Medical Sciences, Ahwaz, Iran The side effects of synthetic analgesic drugs in the clinical practice, have turned the attention of researchers to focus on development of herbal analgesic agents. The purpose of this study was the evaluation of analgesic effects of the hydroalcoholic extract of Teucrium oliveranum in comparison with morphine and aspirin. Maceration was performed with aqueous ethanol 70%.The prepared extract was concentrated by using rotary evaporator, and then it was dried in low temperature. Male Wister rat weighing 150–180 g were used during the study in cages and free accesses to food and water. The animals were divided into seven groups (n = 6 rats) .The test groups received 200, 400, 600 and 800 mg/kg of hydroalcoholic extract of T. oliveranum,“negative control” received normal saline (5 ml/kg) and the “positive control” groups received 2.5 mg/kg morphine and 300 mg/kg aspirin (ip), respectively. The analgesic effects of different doses of the extract and the positive and negative control groups were investigated via formalin test. In order to verify the role of opioid receptor on analgesic effect of T. oliveranum, one group of animals was treated with naloxone 1 mg/kg (ip) and extract 600 mg/kg (ip). The highest effect of analgesia was seen by dose of 600 mg/kg. Such effect was less than aspirin effect on the second phase of pain and morphine effect on both of the pain phases. The results revealed that the extract could have analgesic effect compared to the “negative control”. Naloxone could reduce the analgesic effect of extract on the second phase of pain. It may conclude that T. oliveranum extract induce its effect through opioid receptors activation or release of endogenous opioid peptides. doi:10.1016/j.toxlet.2010.03.863
P302-034 FK-3000 isolated from Stephania delavayi Diels. inhibits breast cancer cell proliferation by suppressing NF-fÛB and COX-2 M.J. Lee 1 , S.S. Han 2 1
Kangwon National University, South Korea, 2 Hoseo University, South Korea
Stephania delavayi Diels. was identified as the most promising candidate from a cell proliferation inhibitor screen of 509 plant extracts. Treatment of MDA-MB-231 breast cancer cells with S. delavayi Diels. extract effectively inhibited cell proliferation by inducing cell death. Treatment with S. delavayi Diels. downregulated NF-fÛB phosphorylation and COX-2 expression in a dose- and time-dependent manner. We identified 6,7-diO-acetylsinococuline (FK-3000) as the major active component in S. delavayi Diels. extract. The inhibitory effect of FK-3000 on
S259
cell proliferation was greater than that of the S. delavayi Diels. extract. Furthermore, treatment with FK-3000 downregulated NFfÛB phosphorylation and COX-2 expression. Finally, we tested FK-3000 in a mouse xenograft model using MDA-MB-231 cells. FK3000 inhibited tumor growth as effectively as Taxol without any visible signs of toxicity. In addition, FK-3000 exhibited a synergistic effect on in vivo tumor growth when combined with Taxol. In conclusion, FK-3000 isolated from S. delavayi Diels. is a potential anticancer agent that targets a specific pathway and exhibits low toxicity. Therefore, this compound should be further evaluated as an anticancer therapeutic. doi:10.1016/j.toxlet.2010.03.864
P302-035 Preclinical toxicity evaluation of Syngonanthus macrolepsis crude extract with antimicobacteria activity G. Honorato De Oliveira, V. Pereira Arantes School of Pharmaceutical Sciences Sao Paulo State University UNESP, Brazil Introduction: The Brazilian tropical forest functions as true laboratory of organic synthesis and many of these chemicals can be future drugs. However the tuberculosis continues being a serious problem of public health, causing death especially in underdeveloped countries. The resistance of the M. tuberculosis justified constant research for new drugs which can be obtained through the vegetal extracts which should have evaluated its toxicity. The objective of this work was evaluating the preclinical toxicity of the crude extract of Singonanthus macrolepsis, giving special attention to hepatic and renal systems. Method: The oral acute and subchronic toxicity were performed according to 423 and 408 OECD guideline using male and female Wistar rats. The acute toxicity was checked through “The limit test”; two experimental groups (2000 and 5000 mg/kg bw) and one control. The subchronic toxicity, during 90 days one control and three experimental groups received through drinking water (200, 400 and 800 g/ml) of extract. Results: To acute toxicity, light irritability in two females that received 5000 mg/kg. Heart, lung, spleen, lever and kidney were removed weighted, observed by gross necopsy they were unchangeable in relation to control. To subchronic toxicity, enzymatic analyses was carried out ALT, AST, y-GT, AP and biochemical metabolites billirubin, urea, creatinine, and protrombine time. Male rats have not presented any change while female rats have shown increased significant differences to protrombine time and y-GT, just to 800 g/ml in relation to control. Hematological analysis and histological light microscopy (H&E) of liver and kidneys was carried out and neither changes in hemogram nor injury in the tissue were observed. Conclusion: As this extract presented MIC = 62.5 g/ml in MABA, it is promissory to be used in human with little adverse effect. It encourages us to isolate the active principle and tests it in infected animals by M. tuberculoses. Supported by FUNDUNESP; PADC-FCF. doi:10.1016/j.toxlet.2010.03.865