Nociceptin (NC) and its 4 fragments have been synthesized by solid phase peptide synthesis. Their hypotensive activity and mechanism, MVD assay and structure-activity relationship have been investigated. Results show ...Nociceptin (NC) and its 4 fragments have been synthesized by solid phase peptide synthesis. Their hypotensive activity and mechanism, MVD assay and structure-activity relationship have been investigated. Results show that NC(1-13)NH2 is the smallest fragment that shares the same activity with NC. The truncation of C-terminal not only leads the decrease展开更多
Objective: To investigate the pharmacological basis of its uses of Phyla nodiflora(P. nodiflora) for the treatment of anomalies predominantly by smooth muscle containing tissues such as gastrointestinal/vascular/bronc...Objective: To investigate the pharmacological basis of its uses of Phyla nodiflora(P. nodiflora) for the treatment of anomalies predominantly by smooth muscle containing tissues such as gastrointestinal/vascular/broncho spasm and cardiovascular modulation.Methods: The crude hydroalcoholic extract of P. nodiflora(Pn.Cr) and its fractions were evaluated on isolated rabbit jejunum, rat trachea, aorta and atrium. To access the contractile or relaxant effects of testing materials, the tissues were mounted in isolated organ bath and responses were recorded with transducers coupled with data acquisition system.BALB/c mice were challenged with castor oil for the assessment of in-vivo antidiarrheal activity. Normotensive rats were used for in-vivo hypotensive study.Results: Hydroalcoholic extract of Pn.Cr at variable concentrations inhibited the natural spontaneous rhythm and 80 mmol/L K^+ mediated contractions in isolated segment of jejunum with EC_(50) values of 3.18 and 1.91 mg/mL respectively. Verapamil, a Ca^(2+) channel blocker, demonstrated akin pattern in jejunum and therefore possibly suggesting calcium blocking activity. On isolated rat tracheal tissue, Pn.Cr showed relaxation of high-K^+and carbachol mediated contractions(EC_(50) values: 1.24 and 2.42 mg/mL). Pn.Cr treatment relaxed the rat aortic ring in a cumulative doses with high-K^+ and phenylephrine-induced contractions(EC_(50) values 0.25 and 0.92 mg/mL). Activity based fractionation of Pn.Cr showed that dichloromethane fraction was more potent for relaxing the tissues spasm compared to aqueous fraction. In-vivo experiments, significant protection by Pn.Cr(P < 0.05) was observed in castor oil-induced diarrhea(50–500 mg/kg)whereas hypotensive effect in anesthetized rats was seen at the dose range of 1–10 mg/kg of Pn.Cr(P < 0.05).Conclusion: This study suggests the blockage of calcium channel in the smooth muscles as a pharmacological application to make usage of P. nodiflora in the management of diarrhea, asthma and hypotensive effect.展开更多
文摘Nociceptin (NC) and its 4 fragments have been synthesized by solid phase peptide synthesis. Their hypotensive activity and mechanism, MVD assay and structure-activity relationship have been investigated. Results show that NC(1-13)NH2 is the smallest fragment that shares the same activity with NC. The truncation of C-terminal not only leads the decrease
基金funded by Bahauddin Zakariya University,Multan,Pakistan(No.DR&EL/D-443)
文摘Objective: To investigate the pharmacological basis of its uses of Phyla nodiflora(P. nodiflora) for the treatment of anomalies predominantly by smooth muscle containing tissues such as gastrointestinal/vascular/broncho spasm and cardiovascular modulation.Methods: The crude hydroalcoholic extract of P. nodiflora(Pn.Cr) and its fractions were evaluated on isolated rabbit jejunum, rat trachea, aorta and atrium. To access the contractile or relaxant effects of testing materials, the tissues were mounted in isolated organ bath and responses were recorded with transducers coupled with data acquisition system.BALB/c mice were challenged with castor oil for the assessment of in-vivo antidiarrheal activity. Normotensive rats were used for in-vivo hypotensive study.Results: Hydroalcoholic extract of Pn.Cr at variable concentrations inhibited the natural spontaneous rhythm and 80 mmol/L K^+ mediated contractions in isolated segment of jejunum with EC_(50) values of 3.18 and 1.91 mg/mL respectively. Verapamil, a Ca^(2+) channel blocker, demonstrated akin pattern in jejunum and therefore possibly suggesting calcium blocking activity. On isolated rat tracheal tissue, Pn.Cr showed relaxation of high-K^+and carbachol mediated contractions(EC_(50) values: 1.24 and 2.42 mg/mL). Pn.Cr treatment relaxed the rat aortic ring in a cumulative doses with high-K^+ and phenylephrine-induced contractions(EC_(50) values 0.25 and 0.92 mg/mL). Activity based fractionation of Pn.Cr showed that dichloromethane fraction was more potent for relaxing the tissues spasm compared to aqueous fraction. In-vivo experiments, significant protection by Pn.Cr(P < 0.05) was observed in castor oil-induced diarrhea(50–500 mg/kg)whereas hypotensive effect in anesthetized rats was seen at the dose range of 1–10 mg/kg of Pn.Cr(P < 0.05).Conclusion: This study suggests the blockage of calcium channel in the smooth muscles as a pharmacological application to make usage of P. nodiflora in the management of diarrhea, asthma and hypotensive effect.
