Work

The mechanisms of Mahuang decoction in treating COPD: Insights from network pharmacology and in vivo studies

Year: 2025

Type: article

Abstract: Background Chronic obstructive pulmonary disease (COPD) is a major cause of significant mortality worldwide. Mahuang decoction (MHD), a classic traditional Chinese medicine, has demonstrated encouraging therapeutic potential for COPD due to its multiple pharmacological properties, including anti-inflammatory activity. However, its underlying mechanisms remain unclear. Objectives The purpose of this study was to investigate the mechanisms underlying MHD's efficacy against COPD. Methods The bioactive ingredients of MHD and the corresponding candidate targets, the potential factors related to COPD, and their shared candidate targets were identified. A protein-protein interaction (PPI) network of the shared targets and an MHD compound-target-COPD network were constructed. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were performed to observe biological functions. An in vivo rat model of COPD was established by cigarette smoke exposure and lipopolysaccharide (LPS) endotracheal instillation and subjected to MHD administration. Tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and IL-1β levels were detected by enzyme-linked immunosorbent assay. The number of apoptotic cells was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels were analyzed using the assay kits. The mRNA levels of akt serine/threonine kinase 1 (AKT1), TNF-α, IL-6, and IL-1β were detected by quantitative polymerase chain reaction (PCR). The protein levels of b-cell lymphoma 2 (BCL2), BCL2-associated x protein (BAX), cleaved-Caspase-3, TNF-α, TNF receptor 1 (TNFR1), phosphorylated nuclear factor kappa b (p-NF-κB) p65, and phosphorylated inhibitor of kappa b alpha (p-IκBα) were assessed by immunoblotting. Results This study identified 54 active components and 173 candidate targets of MHD, 1224 putative targets associated with COPD, and 110 shared targets. PPI analysis revealed the top 12 core candidate targets (e.g., AKT1, TNF, IL-6, and IL-1β) for MHD's efficacy in COPD treatment. Various components (e.g., quercetin, luteolin, and isorhamnetin) were identified as the main active ingredients in MHD for COPD treatment. GO enrichment analysis showed that these shared targets were closely correlated with response to xenobiotic stimuli and cellular response to LPS. KEGG enrichment analysis showed the potential implication of TNF-α pathway in MHD's efficacy against COPD. In COPD rats, MHD diminished lung pathological injury and reduced TNF-α, IL-6, and IL-1β levels in the BALF. Moreover, MHD reduced MDA amount, elevated SOD and CAT levels, decreased the mRNA expression of AKT1, TNF-α, IL-6, and IL-1β, diminished the percentage of TUNEL-positive cells, increased BCL2 expression, and reduced BAX and cleaved-Caspase-3 levels in lung tissues of COPD rats. Furthermore, MHD inactivated the TNF-α/NF-κB pathway in COPD rats. Conclusion Our study shows that MHD alleviates COPD by targeting TNF-α/NF-κB pathway, reducing inflammation, oxidative stress, and apoptosis via multiple bioactive components and targets, providing evidence for the potential of MHD to prevent or treat COPD.

Source: Letters in Drug Design & Discovery

DOI: 10.1016/j.lddd.2025.100048

Authors: Quan Qiu, Yaya Guo, Liangping Li, Feng Sang, Liran Xu

Institutions: Henan University of Traditional Chinese Medicine, First Affiliated Hospital of Henan University of Traditional Chinese Medicine

Language: English

Topic: Chronic Obstructive Pulmonary Disease (COPD) Research

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $2,300