Huang Tao, Ning Ziwan, Hu Dongdong, Zhang Man, Zhao Ling, Lin Chengyuan, Zhong Linda L D, Yang Zhijun, Xu Hongxi, Bian Zhaoxiang
Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Pharmacol. 2018 Mar 26;9:270. doi: 10.3389/fphar.2018.00270. eCollection 2018.
MaZiRenWan (MZRW, also known as Hemp Seed Pill) is a Chinese Herbal Medicine which has been demonstrated to safely and effectively alleviate functional constipation (FC) in a randomized, placebo-controlled clinical study with 120 subjects. However, the underlying pharmacological actions of MZRW for FC, are still largely unknown. We systematically analyzed the bioactive compounds of MZRW and mechanism-of-action biological targets through a novel approach called "focused network pharmacology." Among the 97 compounds identified by UPLC-QTOF-MS/MS in MZRW extract, 34 were found in rat plasma, while 10 were found in rat feces. Hierarchical clustering analysis suggest that these compounds can be classified into component groups, in which compounds are highly similar to each other and most of them are from the same herb. Emodin, amygdalin, albiflorin, honokiol, and naringin were selected as representative compounds of corresponding component groups. All of them were shown to induce spontaneous contractions of rat colonic smooth muscle . Network analysis revealed that biological targets in acetylcholine-, estrogen-, prostaglandin-, cannabinoid-, and purine signaling pathways are able to explain the prokinetic effects of representative compounds and corresponding component groups. In conclusion, MZRW active components enhance colonic motility, possibly by acting on multiple targets and pathways.
麻子仁丸(MZRW,也称为麻仁丸)是一种中药,在一项有120名受试者的随机、安慰剂对照临床研究中已被证明能安全有效地缓解功能性便秘(FC)。然而,麻子仁丸治疗FC的潜在药理作用仍 largely unknown。我们通过一种名为“聚焦网络药理学”的新方法,系统地分析了麻子仁丸的生物活性成分及其作用机制的生物学靶点。在麻子仁丸提取物中通过超高效液相色谱-四极杆飞行时间串联质谱(UPLC-QTOF-MS/MS)鉴定出的97种化合物中,34种在大鼠血浆中被发现,10种在大鼠粪便中被发现。层次聚类分析表明,这些化合物可分为成分组,组内化合物彼此高度相似,且大多数来自同一草药。大黄素、苦杏仁苷、芍药苷、厚朴酚和柚皮苷被选为相应成分组的代表性化合物。所有这些化合物均显示能诱导大鼠结肠平滑肌的自发收缩。网络分析表明,乙酰胆碱、雌激素、前列腺素、大麻素和嘌呤信号通路中的生物学靶点能够解释代表性化合物和相应成分组的促动力作用。总之,麻子仁丸的活性成分可能通过作用于多个靶点和途径来增强结肠动力。