Mózsik Gyula, Past Tibor, Abdel Salam Omar M E, Kuzma Mónika, Perjési Pál
First Department of Medicine, Medical and Health Centre, University of Pécs, Hungary.
Inflammopharmacology. 2009 Jun;17(3):113-50. doi: 10.1007/s10787-009-0002-3. Epub 2009 Jun 26.
The plant origin capsaicinoids (capsaicin, dihydrocapsaicin, norcapsaicin, dihydrocapsaicin, homocapsaicin, homodihydrocapsaicin) are well known and used as nutritional additive agents in the every day nutritional practice from the last 9,500 years; however, we had have a very little scientifically based knowledge on their chemistry, physiology and pharmacology in animal observations, and in humans up to the mid-twentieth century. Our knowledge about their chemistry, physiology, pharmacology entered to be scientifically based evidence from the year 1980, dominantly in animal observations. The human observations with capsaicin (capsaicinoids), in terms of good clinical practice, have been started only in the last 10-year period (from 1997) in randomized, prospective, multiclinical studies. The name of "capsaicin" used only in the physiological and pharmacological research both in animal experiments and in human observation. The "capsaicin" (as a "chemically" used natural compound) modifies the so-called capsaicin-sensitive afferent nerves depending on their applied doses.
The specific action of capsaicin (capsaicinoids) on sensory afferent nerves modifying gastrointestinal (GI) function (under very specific conditions) offers a possibility for the production of an orally applicable drug or for other drug combinations, which can be used in the human medical therapy. The production of new drug is based on the critical interdisciplinary review of the results obtained with capsaicinoids.
This paper gives an interdisciplinary and critical overview on the chemical, physiological, pharmacological and toxicological actions of the natural origin capsaicinoids (from the point of drug production) under conditions of acute, subacute and chronic administration in animal experiments and human observations, toxicology, pharmacokinetics). This interdisciplinary review covers the following main chapters: (1) physiological and pharmacological research tool by capsaicin in the animals and human beings, (2) capsaicin research in animals (including the acute, subacute toxicology and chronic toxicology metabolism, genotoxicology), (3) capsaicin observation with capsaicin in human beings.
(1) The capsaicin used in the physiological and pharmacological observations (in animals and human beings) chemically represents different chemical compounds, which can be obtained from the plants (paprika, chilli, etc.), (2) capsaicinoids are able to modify the capsaicin-sensitive afferent nerves, which have principle roles in the defence of different organs (including the gastrointestinal tract [against the different chemicals, heat, strech, chemical millieu-induced damage], (3) the application of capsaicin (capsaicinoids) can be repeated for the beneficial effects on the gastrointestinal tract as those in animal experiments. After this interdisciplinary and critical review, this paper demonstrates the well-planned research pathways of the discoveries of capsaicinoids from plant chemistry, via physiology, pharmacology and toxicology in animal experiments and human observations.
植物源辣椒素类物质(辣椒素、二氢辣椒素、降辣椒素、高二氢辣椒素、高辣椒素、高二氢高辣椒素)广为人知,在过去9500年的日常营养实践中被用作营养添加剂;然而,直到20世纪中叶,我们在动物观察和人类研究中,对其化学、生理和药理学方面的科学认识还非常有限。从1980年起,我们关于它们化学、生理、药理学的知识开始有了科学依据,主要是在动物观察方面。关于辣椒素(辣椒素类物质)的人体观察,按照良好临床实践的标准,仅在过去10年期间(从1997年开始)才在随机、前瞻性、多中心研究中开展。“辣椒素”这个名称仅用于动物实验和人体观察中的生理和药理学研究。“辣椒素”(作为一种“化学上”使用的天然化合物)根据其应用剂量会改变所谓的辣椒素敏感传入神经。
辣椒素(辣椒素类物质)对感觉传入神经的特定作用,在非常特定的条件下可调节胃肠(GI)功能,这为生产口服适用药物或其他药物组合提供了可能性,可用于人类医学治疗。新药的研发基于对辣椒素类物质所获结果的关键跨学科综述。
本文从药物生产的角度,对天然来源辣椒素类物质在动物实验和人体观察中的化学、生理、药理和毒理学作用(急性、亚急性和慢性给药条件下)进行了跨学科的批判性综述(包括毒理学、药代动力学)。这一跨学科综述涵盖以下主要章节:(1)辣椒素在动物和人类中的生理和药理研究工具;(2)动物中的辣椒素研究(包括急性、亚急性毒理学以及慢性毒理学代谢、遗传毒理学);(3)人体中的辣椒素观察。
(1)在生理和药理观察中(在动物和人类中)使用的辣椒素在化学上代表不同的化合物,这些化合物可从植物(辣椒、红辣椒等)中获取;(2)辣椒素类物质能够改变辣椒素敏感传入神经,这些神经在不同器官的防御中起主要作用(包括胃肠道[抵御不同化学物质、热、拉伸、化学环境诱导的损伤]);(3)辣椒素(辣椒素类物质)的应用可以重复进行,以获得与动物实验中对胃肠道有益的相同效果。经过这一跨学科的批判性综述,本文展示了从植物化学开始,经动物实验和人体观察中的生理学、药理学和毒理学,对辣椒素类物质进行发现的精心规划的研究路径。