基于“组分-效用-靶点”研究厚朴“发汗”增味减燥作用机制

“Sweating”, one of the authentic Chinese medicine classic origin processing methods, is the essence of the enduring traditional Chinese medicine culture. Magnolia, a genuine crude drug in Sichuan, was defined to do “sweating” processing in each version of the Chinese Pharmacopoeia, in order to increase its drug properties and decreases its dry property, to ensure drug quality and the safety of its usage, however, the mechanism is not clear. In the early stage of our study, after sweating, chemical components absorption amount in vivo of magnolia changed, so was its efficacy and toxicity. Accordingly, a hypothesis, that the chemical components change of magnolia after sweating processing can regulateits drug properties and decreases its dry property, was put forward. First, do difference analysis on the chemical components and the serum pharmaceutical chemistry of magnolia before and after sweating to study the active components. Second, study the endogenous metabolites of magnolia before and after sweating based on metabonomics technology. Finally, build up differences in metabolic target network combine with network pharmacology, to explore its regulation on the body's metabolic pathways. So the drug properties change mechanism of sweating can be revealed by studying blood components differences and metabonomics network regulation of the magnolia before and after sweating through the thinking way of “components-efficacy –target”.

“发汗”是道地中药经典产地加工方法之一，是传统中医药文化历久弥新的精髓。川产道地药材厚朴在历版《中国药典》中，均明确规定需“发汗”加工。厚朴通过“发汗”以“增其味而减其燥”，提高药材品质，但其“增味减燥”的作用机制尚不明确，课题组在前期研究中药厚朴道地性中，发现厚朴“发汗”后化学组分的含量及体内吸收均有变化，其药材偏性也有改变。据此提出假说：厚朴经传统产地加工“发汗”后化学组分发生变化，进而增味减燥以调节偏性，提高药材品质。课题首先对“发汗”前后厚朴中化学组分进行差异性分析；结合血清药物化学技术对比研究其差异组分的入血行为；基于代谢组学技术，分析“发汗”前后厚朴的机体内源性代谢产物；结合网络药理学构建其差异性代谢靶标网络，以探寻其对机体代谢途径的调控。基于“组分-效用-靶点”研究思路，从入血组分差异和代谢网络调控研究厚朴“发汗”对药材效用的影响，揭示“发汗”的“增味减燥”机理。

“发汗”是中药经典产地加工方法之一，历版《中国药典》规定川产道地药材厚朴需“发汗”处理，课题针对厚朴发汗后“增其味而减其燥”的作用机制，从化学成分、药效变化、内源性代谢产物等角度，结合网络药理学构建差异代谢靶标网络，从“组分-效用-靶点”角度揭示厚朴“发汗”后增味减燥作用机理，结果发现：厚朴“发汗”后成分发生变化，厚朴酚、和厚朴酚及β-桉叶醇等化学成分含量变化是厚朴“发汗”前后疗效差异的主要原因；厚朴“发汗”后药效增强，增强抗氧化和抗炎作用改善乙醇诱发的大鼠急性胃溃疡，增强肠推进和胃排空作用改善大鼠胃肠动力障碍；厚朴“发汗”后作用机制改变，代谢组学和网络药理学研究表明，厚朴起效的机制可能是提高L-谷氨酸胺的含量，保护胃肠道屏障而改善胃肠动力障碍；厚朴“发汗”后，通过提高L-色氨酸和5-羟色胺含量来进一步增强胃肠动力，并避免有害代谢物生成而达增效减燥之功。并将厚朴醇提物制备为固体分散体，增加了厚朴主要成分的水溶性，提高其口服生物利用度，为临床应用提供依据。本课题的研究从厚朴对胃肠道疾病的作用，成功构建“组分-效用-靶点”模型阐释了厚朴“发汗”增效减燥作用机制，为传统炮制工艺提供新的研究模式。