Li Huijun, Zhang Dandan, Wang Tianhe, Luo Xinyao, Xia Heyuan, Pan Xiang, Han Sijie, You Pengtao, Wei Qiong, Liu Dan, Zou Zhongmei, Ye Xiaochuan
Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.
Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China; Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Chin J Nat Med. 2023 Feb;21(2):83-98. doi: 10.1016/S1875-5364(23)60392-9.
Poria is an important medicine for inducing diuresis to drain dampness from the middle energizer. However, the specific effective components and the potential mechanism of Poria remain largely unknown. To identify the effective components and the mechanism of Poria water extract (PWE) to treat dampness stagnancy due to spleen deficiency syndrome (DSSD), a rat model of DSSD was established through weight-loaded forced swimming, intragastric ice-water stimulation, humid living environment, and alternate-day fasting for 21 days. After 14 days of treatment with PWE, the results indicated that PWE increased fecal moisture percentage, urine output, D-xylose level and weight; amylase, albumin, and total protein levels; and the swimming time of rats with DSSD to different extents. Eleven highly related components were screened out using the spectrum-effect relationship and LC-MS. Mechanistic studies revealed that PWE significantly increased the expression of serum motilin (MTL), gastrin (GAS), ADCY5/6, p-PKAα/β/γ cat, and phosphorylated cAMP-response element binding protein in the stomach, and AQP3 expression in the colon. Moreover, it decreased the levels of serum ADH, the expression of AQP3 and AQP4 in the stomach, AQP1 and AQP3 in the duodenum, and AQP4 in the colon. PWE induced diuresis to drain dampness in rats with DSSD. Eleven main effective components were identified in PWE. They exerted therapeutic effect by regulating the AC-cAMP-AQP signaling pathway in the stomach, MTL and GAS levels in the serum, AQP1 and AQP3 expression in the duodenum, and AQP3 and AQP4 expression in the colon.
茯苓是中医临床常用的利水渗湿药，具有健脾利水的功效。然而，茯苓发挥药效的具体成分及作用机制尚不清楚。为了探讨茯苓水提取物（PWE）治疗脾虚湿盛证（DSSD）的有效成分和作用机制，采用负重强迫游泳、灌胃冰水、潮湿环境、隔日禁食等方法建立DSSD大鼠模型，连续造模21天。造模14天后给予PWE灌胃，结果显示，PWE能不同程度地增加DSSD大鼠的粪便含水率、尿量、D-木糖水平和体重，提高淀粉酶、白蛋白和总蛋白水平，延长游泳时间。采用谱效关系结合LC-MS技术，筛选出11个与茯苓利水渗湿作用高度相关的成分。机制研究表明，PWE可显著上调血清胃动素（MTL）、胃泌素（GAS）水平，胃组织中腺苷酸环化酶5/6（ADCY5/6）、蛋白激酶Aα/β/γ催化亚基（p-PKAα/β/γ cat）及磷酸化环磷腺苷效应元件结合蛋白（p-CREB）的表达，结肠组织中水通道蛋白3（AQP3）的表达；下调血清抗利尿激素（ADH）水平，胃组织中AQP3和水通道蛋白4（AQP4）、十二指肠组织中AQP1和AQP3以及结肠组织中AQP4的表达。PWE对DSSD大鼠具有利水渗湿作用，筛选出11个主要有效成分，其作用机制可能与调节胃组织中AC-cAMP-AQP信号通路、血清MTL和GAS水平、十二指肠组织中AQP1和AQP3以及结肠组织中AQP3和AQP4的表达有关。
