The mechanism of Bai He Gu Jin Tang against non-small cell lung cancer revealed by network pharmacology and molecular docking

Abstract

Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related burden and deaths, thus effective treatment strategies with lower side effects for NSCLC are urgently needed. To systematically analyze the mechanism of Bai He Gu Jin Tang (BHGJT) against NSCLC by network pharmacology and molecular docking. Methods: The active compounds of BHGJT were obtained by searching the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine and Encyclopaedia of Traditional Chinese Medicine. Search tool for interactions of chemicals was used for acquiring the targets of BHGJT. The component-target network was mapped by Cytoscape. NSCLC-related genes were obtained by searching Genecards, DrugBank and Therapeutic Target Database. The protein-protein interaction network of intersection targets was established based on Search Tool for Recurring Instances of Neighboring Genes (STRING), and further, the therapeutic core targets were selected by topological parameters. The hub targets were transmitted to Database for Annotation, Visualization and Integrated Discovery for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, AutoDock Vina and MglTools were employed for molecular docking validation. Results: Two hundred fifty-six compounds and 237 putative targets of BHGJT-related active compounds as well as 1721potential targets of NSCLC were retrieved. Network analysis showed that 8 active compounds of BHGJT including kaempferol, quercetin, luteolin, isorhamnetin, beta-sitosterol, stigmasterol, mairin and liquiritigenin as well as 15 hub targets such as AKR1B10 and AKR1C2 contribute to the treatment of BHGJT against NSCLC. GO functional enrichment analysis shows that BHGJT could regulate many biological processes, such as apoptotic process. Three modules of the endocrine related pathways including the inflammation, hypoxia related pathways as well as the other cancer related pathways based on Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis might explain the biological mechanisms of BHGJT in treating BHGJT. The results of molecular docking verified that AKR1B10 and AKR1C2 had the strongest binding activity with the 8 key compounds of NSCLC. Conclusion: Our study reveals the mechanism of BHGJT in treating NSCLC involving multiple components, multiple targets and multiple pathways. The present study laid an initial foundation for the subsequent research and clinical application of BHGJT and its active compounds against NSCLC.

Research Progress of Baihe Gujin Decoction in the Treatment of Lung Cancer

“…Flavonoids are natural products that can reverse the immunosuppressive microenvironment of tumors. 43 As reported by a related study, kaempferol can induce apoptosis in NSCLC cells through down-regulating Nrf2 mRNA, thereby inhibiting cancer cell proliferation. 44 Also, kaempferol can slow down cancer progression via inhibiting TGF-β1-induced epithelial-mesenchymal transition, migration and invasion of NSCLC cells.…”

“…There are a large number of extracted constituents in this decoction, and the main anti-tumor constituents confirmed by modern pharmacological research include kaempferol, quercetin, isorhamnetin, glycyrrhizin, and β-sitosterol, etc. 43 Most of these components belong to flavonoids. Flavonoids are natural products that can reverse the immunosuppressive microenvironment of tumors.…”

“…Molecular docking validated a significant binding of AKR1B10 and AKR1C2 to the eight key compounds in NSCLC. 43 In addition to these aspects, the immunomodulatory and anti-inflammatory effects triggered by Baihe Gujin decoction are also crucial for demonstrating its potential in combating tumors.…”

The Genetic Basis of Future Pharmacological Strategies for the Management of Comorbid Obesity and Depression: A Scoping Review

“…Several plant compounds, including sulforaphane [107] and extracts of plants such as Prunus persica, Nelumbo nucifera, and Commiphora myrrha [108,109] have been shown to reduce elevated leptin levels in rodent models of obesity, and these effects correlate with their ability to prevent or attenuate obesity in these models. The carotenoid compound asthaxanthin [110] and the Chinese herbal preparation Bai He Gu Jin Tiang, which contains ten distinct herbs [111], have both been identified as acting on AKR1C2 in silico, which may be associated with anti-depressant and anti-obesity effects. Phytochemicals derived from Lysimachia vulgaris, Protium heptaphyllum and Salvia plebeia have been shown to reduce PCSK9 expression in vitro, though these have been investigated as lipid-lowering agents and not specifically for obesity or depression [112][113][114].…”

Elucidating the anti-cancer potential of Cinnamomum tamala essential oil against non-small cell lung cancer: A multifaceted approach involving GC-MS profiling, network pharmacology, and molecular dynamics simulations

“…Managing lung cancer involves various treatment modalities, including chemotherapy, systemic therapy, radiotherapy, and surgery [ 5 ]. However, the possibility of recurrence and side effects associated with chemotherapy and radiation and emerging drug resistance underline the need for alternative effective treatment approaches [ 6 , 7 ]. Consequently, acquiring the underlying mechanisms behind NSCLC occurrence and progression is essential for developing novel anti-cancer drugs.…”