Abstract
Andrographolide (Andro) has known to treat various illnesses such as colds, diarrhea, fever and infectious diseases. However, the effect mechanism of Andro is still unclear. Therefore, we used high-throughput metabolomics analysis to discover biomarkers, metabolic profiles and pathways to reveal the pharmacological action and effective mechanism of Andro against lung cancer. The metabolic effects of Andro on lung cancer animal was explored by ultra-performance liquid chromatography-triple-time of flight/mass spectrometry (UPLC-TOF/MS) analysis. Our results showed that Andro exhibited significant protective effects against lung cancer. Compared with control group, a total of 25 metabolites biomarkers was identified in urine of model animals, which 18 of them were regulated toward the normal direction after Andro treatment, and network pharmacology analysis showed that they were related with 570 proteins. Biological pathways analysis showed that the 11 metabolism pathways were regulated by Andro treatment in lung cancer mouse, and amino acid metabolism and arachidonic acid metabolism have great potential as target pathways for Andro against lung cancer. It revealed that high-throughput metabolomics combined with network pharmacology analysis provides deeply insight into the therapeutic mechanisms of natural product for promoting medicine development and disease treatment.
Highlights
Lung cancer accounting for 20% of all cancer death has been the major murderer for many years, which mostly because it is asymptomatic in primary stage and typically perceived at advanced stages (de Groot et al, 2018; Barta et al, 2019; Kim et al, 2020)
The content of serum matrixmetallo proteinase-2 (MMP-2), tumor tissue toll like receptor 4 (TLR4), myeloid differentiation factor 88 (MYD88) were reduced by Andro treatment with statistical implications (p < 0.05)
According to urine metabolomics analysis, Andro can regulate 18 of 25 biomarkers associated with the pathogenesis of lung cancer, including alanine, L-glutamine, isoleucine, 3-hydroxybutyric acid, 12,13-EpOME, arginine, proline, valine, tyrosine, creatinine, inositol phosphate, lactic acid, thymine, xanthurenic acid, kynurenic acid, p-cresol sulfate, coproporphyrin III, arachidonic acid, which is mainly related to phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, arachidonic acid metabolism, arginine and proline metabolism, alanine, aspartate and glutamate metabolism, porphyrin and chlorophyll metabolism, pyruvate metabolism, arginine biosynthesis, pyrimidine metabolism, phosphatidylinositol signaling system and inositol phosphate metabolism
Summary
Lung cancer accounting for 20% of all cancer death has been the major murderer for many years, which mostly because it is asymptomatic in primary stage and typically perceived at advanced stages (de Groot et al, 2018; Barta et al, 2019; Kim et al, 2020). There are three main treatment methods for lung cancer, which are chemotherapy, radiation therapy and surgery (Wibowo et al, 2016; Azar et al, 2017; Saad and Mathew, 2020). Radiation therapy is only suitable for patients with small cell lung cancer, and it must be combined with some painkillers during the process of treatment (Forde et al, 2014; Postow et al, 2015; Verma and Simone, 2019). There is an imperative demand to find an emerging method with low side effects and intense activity for lung cancer treatment
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