Yiqi Huayu decoction alleviates bleomycin-induced pulmonary fibrosis in rats by inhibiting senescence

Abstract

Overview: In treating pulmonary fibrosis (PF), traditional Chinese medicine (TCM) has received much attention, but its mechanism is unclear. The pharmacological mechanisms of TCM can be explored through network pharmacology. However, due to its virtual screening properties, it still needs to be verified by in vitro or in vivo experiments. Therefore, we investigated the anti-PF mechanism of Yiqi Huayu Decoction (YHD) by combining network pharmacology with in vivo experiments.Methods: Firstly, we used classical bleomycin (BLM)-induced rat model of PF and administrated fibrotic rats with YHD (low-, medium-, and high-dose). We comprehensively assessed the treatment effect of YHD according to body weight, lung coefficient, lung function, and histopathologic examination. Second, we predict the potential targets by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) combined with network pharmacology. In brief, we obtained the chemical ingredients of YHD based on the UHPLC-MS/MS and TCMSP database. We collected drug targets from TCMSP, HERB, and Swiss target prediction databases based on active ingredients. Disease targets were acquired from drug libraries, Genecards, HERB, and TTD databases. The intersecting targets of drugs and disease were screened out. The STRING database can obtain protein-protein interaction (PPI) networks and hub target proteins. Molecular Complex Detection (MCODE) clustering analysis combined with enrichment analysis can explore the possible biological mechanisms of YHD. Enrichment analyses were conducted through the R package and the David database, including the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Reactome. Then, we further validated the target genes and target proteins predicted by network pharmacology. Protein and gene expression detection by immunohistochemistry, Western blot (WB), and real-time quantitative PCR (rt-qPCR).Results: The results showed that high-dose YHD effectively attenuated BLM-induced lung injury and fibrosis in rats, as evidenced by improved lung function, relief of inflammatory response, and reduced collagen deposition. We screened nine core targets and cellular senescence pathways by UHPLC-MS/MS analysis and network pharmacology. We subsequently validated key targets of cellular senescence signaling pathways. WB and rt-qPCR indicated that high-dose YHD decreased protein and gene expression of senescence-related markers, including p53 (TP53), p21 (CDKN1A), and p16 (CDKN2A). Increased reactive oxygen species (ROS) are upstream triggers of the senescence program. The senescence-associated secretory phenotypes (SASPs), containing interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-β1 (TGF-β1), can further exacerbate the progression of senescence. High-dose YHD inhibited ROS production in lung tissue and consistently reduced the SASPs expression in serum.Conclusion: Our study suggests that YHD improves lung pathological injury and lung function in PF rats. This protective effect may be related to the ability of YHD to inhibit cellular senescence.

Elucidation of the mechanism of Zhenbao pills for the treatment of spinal cord injury by network pharmacology and molecular docking: A review

“…Zhenbao pill was composed of 29 kinds of traditional Chinese medicines(TCMs), including Gan cao, Rou gui, Cao guo ren, Nigella Seeds, She xiang, and so on. Then we entered the names of these 29 TCMs, such as “Gan cao,” into the TCMSP database( https://tcmspw.com/tcmsp.php ), [ 9 ] and set oral bioavailability ≥ 30% and drug-likeness ≥ 0.18, [ 10 ] to retrieve the active ingredients and their targets contained in each traditional Chinese medicine. The HERB database ( http://herb.ac.cn ) [ 11 ] was used for the supplementation of active ingredients of Traditional Chinese medicine,which were not included in the TCMSP database.…”

Cepharanthine Ameliorates Pulmonary Fibrosis by Inhibiting the NF-κB/NLRP3 Pathway, Fibroblast-to-Myofibroblast Transition and Inflammation

“…RT-qPCR is commonly used to observe the changes of relevant indicators at the transcription level [ 57 ]. Total RNA was isolated from frozen lung specimens and cells using TRIZOL Reagent (Thermo, Waltham, MA, USA) in accordance with manufacturer’s protocols.…”

Investigation of the therapeutic role of Lichong Shengsui Drink for the treatment of ovarian cancer in sight of network pharmacology integrated molecular dynamics

“…2,3 Although surgery such as cytoreduction applied in the advanced stages remained the dominant therapeutic approach in ovarian cancer 4 , the Chinese herbal compound displayed an auxiliary effect in prognosis by inhibiting tumor cell proliferation, killing cancer cells, alleviating their adhesion and restraining angiogenesis 5 . With the global popularization of traditional Chinese herb medicine, they had been proven effective in a variety of cancer treatments, including liver cancer 6,7 , lung cancer 8 , breast cancer 9,10 , gastric cancer 11,12 , etc. In addition, the promotion of many Chinese herbal medicines had been proven to be effective against ovarian cancer, such as Spatholobi Caulis 13 , Brucea Javanica 14 , Polysaccharides 15 , Polyphyllin D 16 , and so on.…”