The Anti-Inflammatory Effect of a Combination of Five Compounds From Five Chinese Herbal Medicines Used in the Treatment of COPD

Abstract

Effective compound combination (ECC; i.e, 20-S-ginsenoside Rh1, astragaloside, icariin, nobiletin, and paeonol), derived from Chinese herbal medicine, significantly ameliorates chronic obstructive pulmonary disease (COPD) in rats; however, the underlying mechanisms of ECC remain largely unclear. In this study, network pharmacology analysis integrated with experimental validation was used to explore the therapeutic mechanisms of ECC against COPD. ECC targets and COPD genes and targets were identified from multiple databases, and then used for an analysis of protein–protein interaction (PPI) networks, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and biological functioning. BisoGenet was used to comprehensively analyze the hub-network. We validated the therapeutic effect and mechanisms of ECC both in vivo and in vitro. We identified 45 ECC targets, which were mainly related to inflammatory processes, such as the NOD-like and NF-kappa B signaling pathways, hematopoietic cell lineage, Th17 cell differentiation, cellular response to lipopolysaccharide, and interleukin-8 secretion. In addition, 1180 COPD genes and 70 COPD targets were identified as being involved in the biological functions associated with COPD development, such as cytokine–cytokine receptor interaction, the TNF signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, regulation of lymphocyte proliferation, and positive regulation of leukocyte migration. Integrative analysis of COPD genes and targets and ECC target networks revealed that 54 genes were mainly involved in the inflammatory process, such as IL-17 signaling, NF-kappa B signaling, innate immune response–activating signal transduction, and macrophage cell differentiation. Six targets (AR, ESR1, HNRNPA1, PAPR1, TP53, and VCAM1) contained in the hub-network and their four related compounds were obtained and recognized as the key molecules associated with the effects of ECC. Molecular docking validation demonstrated that four compounds could bind to six targets that interact with COPD genes. Finally, in vivo and in vitro experiments verified that ECC treatment ameliorated the symptoms of COPD in rats by improving their lung function, reducing pathological changes, and suppressing oxidative responses and pro-inflammatory cytokine secretion, while inhibiting inflammation in LPS-induced macrophages, which may be associated with NF-kappa B and MAPK signaling regulation. This study demonstrates the therapeutic mechanisms and effects of ECC on COPD via regulation of the underlying inflammatory process.

Pseudognaphalium affine Extract Alleviates COPD by Inhibiting the Inflammatory Response via Downregulation of NF-κB

“…Drug therapies targeting the NF-κB activation pathway have attracted attention as an interesting therapy to treat lung disease that occurs due to an inflammatory response [ 28 ]. Several studies have demonstrated that natural compounds, herbal extracts, and herbal formulas could exhibit protective effects against COPD by regulating inflammatory responses via NF-κB signaling [ 24 , 29 , 30 ]. Our results show that GAE could reverse the up-regulation of the expression level of p-IκBα, IκK, and NF-κB in COPD rats and BEAS-2B.…”

Effects of a physical exercise program on HIF-1α in people with Chronic Obstructive Pulmonary Disease living at high altitude: study protocol for a clinical trial

“…Currently, there is scientific evidence on how the pathophysiological mechanisms of COPD affect HIF-1 expression [ 12 – 14 ] and its relationship with the inflammatory response of the airway, chronic inflammation of the lung parenchyma [ 15 , 16 ], and vascular regeneration [ 17 ], especially in smokers. However, the expression of HIF-1α in patients with respiratory disease residing in hypobaric hypoxic environments which simultaneously have the hypoxemic stimulus associated with exercise (i.e., patients exercising at high altitude), is currently unknown [ 6 ].…”

Effective Component Compatibility of Bufei Yishen Formula III Which Regulates the Mucus Hypersecretion of COPD Rats via the miR-146a-5p/EGFR/MEK/ERK Pathway

“…Studies have shown that ECC-BYF II has beneficial effects equivalent to those of BYF and ECC-BYF I. ECC-BYF II significantly inhibits mucus hypersecretion, which may be related to the regulation of the EGFR/PI3K/mTOR pathway [ 27 , 28 ]. Since the composition of the total ginsenoside is still unclear, based on research screening, ECC-BYF II was further optimized to ECC-BYF III with 5 ingredients (ginsenoside Rh1, astragaloside, icariin, nobiletin, and paeonol; 5.5 mg/kg), and ECC-BYF III showed protective effects against COPD through anti-inflammatory and antioxidation effects [ 29 , 30 ].…”