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

项目2——治疗功能性肠道疾病的中药配方

• 批准号: 7558692
• 负责人: BRIAN M BERMAN
• 金额: $ 12.74万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7558692
• 关键词: Abdomen; Acetylcholine; Acute; Address; Adverse effects; Animal Model; Animal Testing; Animals; Anti-Cholinergics; Antidiarrheals; Bacteria; Behavioral; Biological; Biological Assay; Botanicals; Cavia; Cells; Chinese Herbs; Chinese People; Cholinergic Agents; Chromosome abnormality; Chronic; Clinical; Clinical Trials; Collaborations; Colorectal; Data; Defecation; Development; Disease; Dose; Esthesia; Evaluation; Frequencies; Herb; Histamine; Hour; Human; Hyperalgesia; In Vitro; Individual; Ingredients and Chemicals; Intestines; Investigation; Irritable Bowel Syndrome; Medicinal Herbs; Micronucleus Tests; Modeling; Mutagenicity Tests; Neonatal; Neurotransmitters; Nociception; Opioid; Pain; Pain Threshold; Pathway interactions; Patients; Perception; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Plant Extracts; Plant Preparations; Preparation; Process; Rattus; Recipe; Rodent; Safety; Series; Serotonin; Serotonin Receptors 5-HT-3; Signal Transduction; Small Intestines; Spasmolytics; Stress; Testing; Therapeutic; Toxic effect; Toxicity Tests; Toxicology; Visceral; Visceral pain; Work; base; cholinergic; clinical application; day; experience; feeding; ileum; in vitro Assay; in vivo; in vivo Model; insight; maternal separation; prescription document; prescription procedure; programs; receptor; receptor binding; receptor expression; response

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.

项目2的目标是提供中国药物的非临床安全性数据和药理学证据 用于治疗肠易激综合症（IBS）的草药制剂。为了实现这一目标，本 项目拟对该方剂进行毒性试验和药理研究。为了这个目的， 将建立体外和体内模型进行毒性和药理评价。毒性测试 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） 月）啮齿动物试验、使用细菌的致突变性试验（艾姆斯试验）、动物细胞（染色体畸变试验） 测试），以及完整的动物（微核测试）。体外肠道收缩力的功能测定将是 用于测试抗胆碱能药（针对乙酰胆碱）、抗血清素（针对组胺）、抗毒蕈碱药（M3） 拮抗作用），以及草药制剂以及单个植物提取物的阿片类药物激动作用。 如有必要，将使用受体结合测定来确认效果。的治疗潜力 中药方将在新生儿内脏痛觉过敏动物模型中进行评价 母性分离。此外，我们将提供生物测定设施，以帮助从其中分离活性成分 草药。在本研究结束时，预计将产生（1）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) 表征处方的药理作用，以提供 更好地了解草药处方的进一步开发。