CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China; Ganjiang Chinese Medicine Innovation Center, Nanchang, 330000, China.
CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.
J Ethnopharmacol. 2021 Nov 15;280:114488. doi: 10.1016/j.jep.2021.114488. Epub 2021 Aug 3.
Traditional Chinese medicine (TCM) has a long history in the prevention and treatment of pandemics. The TCM formula Lung Cleansing and Detoxifying Decoction (LCDD), also known as Qing Fei Pai Du Decoction, has been demonstrated effective against Coronavirus Disease 2019 (COVID-19).
This work aimed to elucidate the active ingredients, targets and pathway mechanism of LCDD related to suppression of inflammatory, immunity regulation and relaxation of airway smooth muscle for the treatment of COVID-19.
Mining chemical ingredients reported in LCDD, 144 compounds covering all herbs were selected and screened against inflammatory-, immunity- and respiratory-related GPCRs including GPR35, H1, CB2, B2, M3 and β2-adrenoceptor receptor using a label-free integrative pharmacology method. Further, all active compounds were detected using liquid chromatography-tandem mass spectrometry, and an herb-compound-target network based on potency and content of compounds was constructed to elucidate the multi-target and synergistic effect.
Thirteen compounds were identified as GPR35 agonists, including licochalcone B, isoliquiritigenin, etc. Licochalcone B, isoliquiritigenin and alisol A exhibited bradykinin receptor B2 antagonism activities. Atractyline and shogaol showed as a cannabinoid receptor CB2 agonist and a histamine receptor H1 antagonist, respectively. Tectorigenin and aristofone acted as muscarinic receptor M3 antagonists, while synephrine, ephedrine and pseudoephedrine were β2-adrenoceptor agonists. Pathway deconvolution assays suggested activation of GPR35 triggered PI3K, MEK, JNK pathways and EGFR transactivation, and the activation of β2-adrenoceptor mediated MEK and Ca. The herb-compound-target network analysis found that some compounds such as licochalcone B acted on multiple targets, and multiple components interacted with the same target such as GPR35, reflecting the synergistic mechanism of Chinese medicine. At the same time, some low-abundance compounds displayed high target activity, meaning its important role in LCDD for anti-COVID-19.
This study elucidates the active ingredients, targets and pathways of LCDD. This is useful for elucidating multitarget synergistic action for its clinical therapeutic efficacy.
传统中医（TCM）在预防和治疗大流行方面有着悠久的历史。TCM 配方清肺排毒汤（LCDD），也称为清肺排毒汤，已被证明对 2019 年冠状病毒病（COVID-19）有效。
本研究旨在阐明与抑制炎症、免疫调节和气道平滑肌松弛相关的 LCDD 的活性成分、靶点和途径机制，以治疗 COVID-19。
挖掘 LCDD 中报道的化学成分，选择涵盖所有草药的 144 种化合物，并使用无标记综合药理学方法筛选针对炎症、免疫和呼吸相关 GPCR 的化合物，包括 GPR35、H1、CB2、B2、M3 和β2-肾上腺素能受体。此外，使用液相色谱-串联质谱法检测所有活性化合物，并构建基于化合物效力和含量的草药-化合物-靶标网络，以阐明多靶标和协同作用。
鉴定出 13 种化合物为 GPR35 激动剂，包括甘草查尔酮 B、异甘草素等。甘草查尔酮 B、异甘草素和阿利松 A 表现出缓激肽受体 B2 拮抗剂活性。远志和姜酚分别作为大麻素受体 CB2 激动剂和组氨酸受体 H1 拮抗剂。水苏碱和白杨素作为毒蕈碱受体 M3 拮抗剂，而辛弗林、麻黄碱和伪麻黄碱是β2-肾上腺素能受体激动剂。途径分解测定表明，GPR35 的激活触发了 PI3K、MEK、JNK 途径和 EGFR 反式激活，β2-肾上腺素能受体的激活介导了 MEK 和 Ca。草药-化合物-靶标网络分析发现，一些化合物，如甘草查尔酮 B，作用于多个靶点，并且多个成分与同一靶点相互作用，如 GPR35，反映了中药的协同作用机制。同时，一些低丰度化合物显示出高靶标活性，这意味着其在 LCDD 抗 COVID-19 中的重要作用。
本研究阐明了 LCDD 的活性成分、靶点和途径。这对于阐明其多靶协同作用及其临床治疗效果很有帮助。
