Project 2 - Chinese Herbal Formula for the Treatment of Functional Bowel Disorder

项目2的目标是提供中国人的非临床安全性数据和药理学证据。 用于治疗肠易激综合征(IBS)的草药制剂。为了实现这一目标，这 该项目建议对该处方进行毒性测试和药理研究。为此， 将建立体外和体内模型，用于毒性和药理学评估。毒性试验 包括急性(单剂量)、亚急性(14天多剂量)和慢性毒性(3天多剂量 几个月)啮齿动物试验、使用细菌的致突变试验(Ames试验)、动物细胞(染色体畸变) 以及完整的动物(微核试验)。体外肠收缩的功能分析将是 设置用于测试抗胆碱能(抗乙酰胆碱)、抗5-羟色胺(抗组胺)、抗肌肉碱(M3 拮抗作用)，以及草药制剂和个别植物提取物的阿片类激动剂作用。 如有必要，将使用受体结合分析来确认效果。药物的治疗潜力 中药方剂将在新生儿内脏痛觉过敏动物模型中进行评估 母性分离。此外，我们将提供生物测定设施，以帮助分离有效成分。 草药。在本研究结束时，预计(1)将产生非临床安全性数据 补充人类在定义处方安全使用方面的传统经验，从而支持 临床应用；(2)将对该方剂的药理作用进行表征，以提供 为中药方剂的进一步开发提供了更好的见解。

The objective of Project 2 is to provide non-clinical safety data and pharmacological evidence of a Chinese herbal preparation used in the treatment of irritable bowel syndrome (IBS). To achieve this objective, this Project proposes to carry out toxicity tests and pharmacological studies of the prescription. Toward this end, in vitro and in vivo models will be established for toxicity and pharmacological evaluations. Toxicity tests include acute (single-dose), subacute (multiple-dose for 14 days), and chronic toxicity (multiple-dose for 3 months) tests in rodents, mutagenicity tests using bacteria (Ames test), animal cells (chromosome aberration test), as well as intact animals (micronucleus test). Functional assays for in vitro intestinal contractility will be set up to test for anticholinergic (against acetylcholine), antiserotonic (against histamine), antimuscarinic (M3 antagonism), and opioid agonistic effects of the herbal preparation as well as individual plant extracts. Receptor binding assays will be used to confirm the effects if necessary. The therapeutic potential of the Chinese medicinal recipe will be evaluated in an animal model of visceral hyperalgesia induced by neonatal maternal separation. In addition we will provide bioassay facilities to aid the isolation of active principles from the medicinal herbs. At the end of this study, it is anticipated that (1) Non-clinical safety data will be generated to supplement human traditional experience in defining safe use of the prescription, and thus supporting the clinical applications; (2) Pharmacological actions of the prescription will be characterized so as to provide a better insight for further development of the herbal prescription.