Multitarget and Multipathway Regulation of Zhenqi Fuzheng Granule against Non-Small Cell Lung Cancer Based On Network Pharmacology and Molecular Docking

Abstract

Background and Objective. The morbidity and mortality rates of non-small cell lung cancer (NSCLC) remain high. Zhenqi Fuzheng (ZQFZ) granule, which consists of Astragali Radix and Ligustri Lucidi Fructus, is commonly used to improve the immunity of cancer patients. However, the mechanism of ZQFZ granule against NSCLC is still unclear. In this study, the network pharmacology and molecular docking approaches were used to investigate the potential mechanism of ZQFZ granule on NSCLC. Methods. The ingredients in the ZQFZ granule were considered in one study based on UPLC, and the potential targets were predicted in the SwissTargetPrediction database. NSCLC targets were gathered from GeneCards, OMIM, and TTD databases. The ingredient-target-NSCLC network was drawn by Cytoscape. The protein–protein interaction was obtained from the STRING database, and the gene function and biological pathways were analyzed by Metascape. AutoDock Vina was used to verify the molecular docking between the key compounds and core targets, and PyMol visualized the results. Results. 244 targets were related to 13 candidate compounds and 1904 targets were related to NSCLC, of which a total of 106 anti-NSCLC targets were predicted. The compound-target-NSCLC network indicated that sinapinic acid, ferulic acid, asiatic acid, pratensein, and glycitein might be the key components for treating NSCLC. The 41 vital targets (out of 106 targets) above the median calculated by PPI degree were selected for bioinformatics analysis. The top 10 targets out of 41 ranked by MCC were IL-6, SRC, CTNNB1, STAT3, CASP3, TNF, EGFR, MAPK8, HSP90AA1, and PTGS2. ZQFZ granule treatment for NSCLC involved many pathways through KEGG analyses, which included pathways in cancer (hsa05200), proteoglycans in cancer (hsa05205), endocrine resistance (hsa01522), microRNAs in cancer (hsa05206), PI3K-Akt signaling pathway (hsa04151), and IL-17 signaling pathway (hsa04657). Molecular docking studies revealed that sinapinic acid, ferulic acid, asiatic acid, pratensein, and glycitein had good infinity with most core targets. Conclusions. This study indicated that ZQFZ granule with multicompounds could treat NSCLC through multitargets and multipathways.

Phytochemicals in Cancer Treatment and Cancer Prevention—Review on Epidemiological Data and Clinical Trials

“…It is also possible for certain compounds to be more beneficial in their anticancer mode of action, although there is still a distinctive lack of research in this area to evaluate this statement. Such results strongly corelate with in vivo studies, where multiple plant-derived substances were found to have an anticancer and chemopreventive mode of action based on a variety of different mechanisms, including antioxidant, anti-inflammatory, induction of apoptosis, detoxification, cellular damage prevention, inhibition of cell proliferation, inhibition of cell cycle progression, inhibition of cell invasion, migration, and adhesion, and stimulation of the immune function [3][4][5][6][7][8][9][17][18][19][20][21][22][38][39][40][41][42][43][44][45][46][47][48][49]78,[106][107][108][109][110][111][112][113][114][115][116][117][118][119][120]124,[134][135]<...…”

“…The study conducted by Duke University Medical Center showed that the use of a stable topical formulation of 15% L-ascorbic acid, 1% alpha-tocopherol, and 0.5% ferulic acid was particularly effective for reducing the thymine dimer mutations known to be associated with a skin cancer. However, the relatively small number of patients evaluated limited this study [116].…”

The Molecular Basis of the Anti-Inflammatory Property of Astragaloside IV for the Treatment of Diabetes and Its Complications

“…As for safety, AS-IV is an active saponin isolated from Astragali Radix, which has been widely used in numerous TCM preparations, such as Qi-Shen-Yi-Qi pill, 103 Shen-Qi-Jiang-Tang granule 19 and Zhen-Qi-Fu-Zheng granule. 104 Thousands of years of clinical usage indicates a good safety. At present, although there is no systematic toxicology study, anecdotal studies show that AS-IV has no obvious toxicity or adverse reactions.…”

Virtual screening to investigate the potential targets and mechanisms of action of "Astragalus-Ligustrum" drug pair in the treatment of non-small cell lung cancer

“…Molecular docking was carried out using Auto Dock Vina software (https://vina.scripps.edu/) to investigate the binding interaction between the components and the target site. After docking, the binding energy was used as a reference for screening the active compounds and the a nity ≤ -5.0 kJ/mol was used as the basis for screening the active ingredient targets of the "Astragalus-Ligustrum" drug pair [20].…”

“…Chinese patent medicine preparations of Ligustrum lucidum and Astragalus membranaceus as the main components (such as Zhenqi Fuzheng capsule, Zhenqi Fuzheng granule and Zhenqi Fuzheng dispersible tablet) have been widely used in combination chemotherapy for tumor treatment. [9] However, the speci c mechanism of their anti-cancer mechanism has not been fully elucidated, and because of the multi-component and multi-target integrated regulation of traditional Chinese medicine in treating diseases, the traditional monomer research mode can hardly re ect this feature of Chinese medicine in treating diseases. The development of modern bioinformatics and systems pharmacology elaborated the special synergistic interactions among the herbs of Chinese medicine formulations through a multi-target and multi-pathway approach.…”