基于HPLC-Q-TOF-MS/MS和网络药理学的补肺丸入血成分、肺病治疗潜能及新型冠状病毒感染恢复期的应用机制研究

HPLC-Q-TOF-MS/MS and network pharmacology reveal absorbed components of Bufei Pills,potential in treating respiratory disorders,and mechanism in recovery stage of COVID-19

该研究基于血清化学、药物体内分布、网络药理学等方法探讨补肺丸在肺系疾病的应用功能,并挖掘潜在的药理学功能。大鼠灌胃给药补肺丸后,通过HPLC-Q-TOF-MS/MS研究补肺丸体内成分,比较复方提取物、给药后含药血清、组织样本及空白样本,从大鼠血清中发现入血成分共56个,其中首次发现neocyclomorusin、asterinin A、neoisostegane、goimisin R、frehmaglutoside H等成分可以经口服吸收入血,相关成分还可分布于心、肝、脾、肺、肾、脑脊液、胰腺不同脏器。经网络药理学分析,发现ALB、IL6、AKT1、TNF、EGFR、ESR1、JUN、HSP90AA1等81个核心靶点,参与PI3K-AKT、MAPK、VEGFA、AGE-RAGE等信号通路。补肺丸可能通过介导靶点通路的参与抑制炎症反应、氧化应激、影响代谢、调节免疫功能等机制,干预DO富集的慢性阻塞性肺病、肺纤维化、肺炎等主要的肺部疾病,以及慢性阻塞性肺病并发症,如糖尿病、抑郁等,及新型冠状病毒感染恢复期气短乏力、身体疼痛等表型,相关活性具有开发价值,有待进一步研究。

This study employed the methods of serum chemistry,in vivo drug distribution analysis,and network pharmacology to investigate the potential therapeutic effects of Bufei Pills on respiratory disorders and decipher the underlying mechanisms.For the in vivo distribution study,rats were administrated with Bufei Pills,and the absorbed components were analyzed by HPLC-Q-TOF-MS/MS.The results showed that 56 components were present in the rat serum,including neocyclomorusin,asterinin A,neoisostegane,goimisin R,and frehmaglutoside H.These components were absorbed orally into the blood and distributed in various organs such as the heart,liver,spleen,lung,kidney,and pancreas as well as in the cerebrospinal fluid.The network pharmacological analysis identified 81 core targets such as ALB,IL6,AKT1,TNF,ECFR,ESR1,JUN,and HSP90AA1.These targets were involved in signaling pathways such as PI3K-AKT,MAPK,VECFA,and ACE-RACE.These findings suggested that Bufei Pills might be effective in treating respiratory disorders such as chronic obstructive pulmonary disease(COPD),pulmonary fibrosis,and pneumonia as well as COPD complications such as diabetes and depression by regulating inflammation,oxidative stress,metabolism,and immune function via the targets.In addition,Bufei Pills play a role in alleviating the shortness of breath,fatigue,and bodily pain during the recovery stage of COVID-19.Further research and development are needed to fully evaluate the potential of Bufei Pills.