A Mechanism Exploration for the Yi-Fei-San-Jie Formula against Non-Small-Cell Lung Cancer Based on UPLC-MS/MS, Network Pharmacology, and In Silico Verification

Leihao Hu; Canfeng He; Aier Mo; Xingkai Zhan; Caizhi Yang; Wei Guo; Lingling Sun; Weiwei Su; Lizhu Lin

doi:10.1155/2023/3436814

A Mechanism Exploration for the Yi-Fei-San-Jie Formula against Non-Small-Cell Lung Cancer Based on UPLC-MS/MS, Network Pharmacology, and In Silico Verification

Evid Based Complement Alternat Med. 2023 Jan 9:2023:3436814. doi: 10.1155/2023/3436814. eCollection 2023.

Authors

Leihao Hu¹, Canfeng He¹, Aier Mo², Xingkai Zhan³, Caizhi Yang¹, Wei Guo⁴, Lingling Sun⁴, Weiwei Su⁵, Lizhu Lin⁴

Affiliations

¹ School of the First Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
² Dongguan Hospital of Integrated Chinese and Western Medicine, Dongguan, Guangdong, China.
³ School of Basic Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
⁴ Oncology Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 16 Airport Road, Guangzhou, Guangdong 510405, China.
⁵ Guangdong Engineering & Technology Research Center for Quality and Efficacy Reevaluation of Post Market Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, No. 135, Xingang Xi Road, Guangzhou, Guangdong 510275, China.

Abstract

Non-small-cell lung cancer (NSCLC) is one of the most prevalent cancers worldwide. A Yi-Fei-San-Jie formula (YFSJF), widely used in NSCLC treatment in south China, has been validated in clinical studies. However, the pharmacological mechanism behind it remains unclear. In this study, 73 compounds were identified using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), with 58 enrolled in network pharmacology. The protein-protein interaction network, functional enrichment analysis, and compound-target-pathway network were constructed using 74 overlapping targets from 58 drugs and NSCLC. YFSJF has many targets and pathways in the fight against NSCLC. PIK3R1, PIK3CA, and AKT1 were identified as key targets, and the PI3K/AKT pathway was identified as the key pathway. According to the Human Protein Atlas (THPA) database and the Kaplan-Meier Online website, the three key targets had varying expression levels in normal and abnormal tissues and were linked to prognosis. Molecular docking and dynamics simulations verified that hub compounds have a strong affinity with three critical targets. This study revealed multiple compounds, targets, and pathways for YFSJF against NSCLC and suggested that YFSJF might inhibit PIK3R1, PIK3CA, and AKT1 to suppress the PI3K/AKT pathway and play its pharmacological role.