Exploring the effective components and potential mechanisms of Zukamu granules against acute upper respiratory tract infections by UHPLC-Q-Exactive Orbitrap-MS and network pharmacology analysis

Acute upper respiratory tract infections (AURTIs) are common diseases of respiratory system, which are caused by adenoviruses and generate the mix of severe clinical presentation. Zukamu granules (ZKMG), a traditional Chinese medicine (TCM) prescription within Health Commission of Xinjiang Uygur Autonomous Region possesses anti-influenza virus, antibacterial and anti-inflammatory effects that exerts therapeutic effects in treatment of AURTIs. However, the main effective chemical components and their corresponding action mechanisms have not been clarified. Therefore, ultra-performance liquid chromatography coupled with quadrupole Exactive orbitrap tandem mass spectrometry (UHPLC-Q-Exactive Orbitrap MS) and network pharmacology were used to detect and identify potentially effective components in ZKMG as well as uncover their pharmacological mechanisms against AURTIs. As a result, a total of 265 components from all 12 composed herbal medicines were characterized based on self-built database and fragmentation patterns, of which 38 compounds were unambiguously confirmed using reference standards. Then, the compound-target-pathway network was constructed that implied potential therapeutic mechanisms of ZKMG on AURTIs. Compounds noscapine, cryptopine, steviol-19-O-glucoside, N-methylnarcotine, allocryptopine, naringenin, boldine, methyl rosmarinate with related targets EGFR, PTGS2, IL2, MMP9, TNF, AKT1, PIK3CA, F3 were considered as the key components and targets. Besides, the results also indicated that PI3K-Akt, AGE-RAGE, PD-L1, HIF-1 signaling pathways contributed significantly to the therapeutic effects of ZKMG on AURTIs. Overall, ZKMG could have an effect on AURTIs based on multicomponent, multitarget, and multichannel mechanisms of action as well as this method provides guiding significance for the further development of TCM treatment.