苦寒类中药善于清热燥湿以改善机体内环境稳态，目前在临床上被广泛应用于糖尿病、肥胖、炎症、菌群失调等慢性或代谢性疾病，而这些疾病往往都伴随着机体生物钟系统的失衡。改善生物钟失衡可能是苦寒药治疗这些疾病的作用机制之一，同时，在生物钟的调控下，机体新陈代谢及内分泌等行为的节律性波动也可能影响苦寒药的药效。既往对苦寒药在临床应用上的研究大部分集中于胃肠动力及激素等基础研究上，从生物钟基因的角度鲜有见到深入的研究与阐述。因此，本文从临床常用苦寒药对生物钟基因的影响及生物钟基因对苦寒药作用的影响两个方面探讨苦寒药的应用，同时分析二者之间的关系和归纳苦寒药影响生物钟基因共同的物质基础，以期为苦寒药作用多靶点以及指导临床合理用药和中药药性物质基础研究提供参考。

Bitter and cold traditional Chinese medicines are good at clearing heat and dampness so as to improve the homeostasis of the body's internal environment. At present, they are widely used in clinical practice for chronic or metabolic diseases such as diabetes, obesity, inflammation and bacterial imbalance, which are often accompanied by the imbalance of the body clock system. Improving the imbalance of circadian clock may be one of the mechanisms of bitter-cold herbs in the treatment of these diseases. At the same time, under the regulation of circadian clock, the circadian fluctuations of metabolism and endocrine behaviors may also affect the efficacy of bitter-cold herbs. Most of the previous studies on the clinical application of bitter-cold herbs focused on the basic research of gastrointestinal dynamics and hormones, and there were few in-depth studies and explanations from the perspective of circadian clock genes. Therefore, this paper discussed the application of bitter-cold herbs from two aspects: the influence of common clinical bitter-cold herbs on circadian clock genes and the influence of circadian clock genes on the effect of bitter-cold herbs. At the same time, the relationship between the two was analyzed and the common material basis of bitter-cold herbs affecting clock genes was summarized in order to provide new ideas for the multi-target effect of bitter-cold herbs and the guidance of rational clinical drug use and basic research on medicinal properties of Traditional Chinese medicine.

国家自然科学基金委员会地区项目（81760787）：基于肠道菌群调节的湿热内蕴实质及葛根芩连汤苦寒燥湿机制研究，负责人：曾治君；江西省卫计委科技计划项目（2019B110）：黄柏与生物钟基因的关系研究，负责人：聂鹏；江西省卫计委科技计划项目（20203773）：黄连与生物钟基因的关系研究，负责人：吉燕华。