Mechanisms of Xiangxue decoction in treating COVID-19 via HPLC‒Q-TOF‒MS/MS, network pharmacology, molecular docking and molecular dynamics simulation

Ma et al., Scientific Reports, doi:10.1038/s41598-026-45496-z, Jul 2026
In silico study using network pharmacology, molecular docking, and molecular dynamics simulation to investigate the mechanisms of Xiangxue Decoction (XXD) for COVID-19.
Ma et al., 1 Jul 2026, China, peer-reviewed, 6 authors. Contact: cj00123@zcmu.edu.cn.
In silico studies are an important part of preclinical research, however results may be very different in vivo.
Abstract: OPEN Mechanisms of Xiangxue decoction in treating COVID-19 via HPLC -Q-TOF -MS/MS, network pharmacology, molecular docking and molecular dynamics simulation Yuan Ma 1 , Donghui Lu 1 , Yuhong Ge 2 , Huimei Kong 2 , Jingbo Wang 3 & Jing Chen 1  To predict the active components of Xiangxue Decoction (XXD), and explore its mechanism in treatment of COVID-19. The chemical compositions of compounds were identified using HPLC -QTOF -MS/MS technology. Active components were screened using UNIFI, and potential targets were retrieved from TCMSP, GeneCards. The STRING database was used to construct PPI networks. Enrichment analysis was conducted using Metascape. Molecular docking and Molecular dynamics simulations were further used to evaluate the interactions between the active components and potential targets. 162 drug targets, 1458 disease targets and 64 intersection targets were identified. Quercetin, kaempferol, luteolin, nobiletin and β-carotene were identified as the key components. The core targets included TNF, AKT1, IL-6, IL1B, HIF1A, STAT3 and EGFR. GO and KEGG analyses revealed the primary signaling pathways, including the JAK-STAT, MAPK, PI3K / Akt, and NF-kappa B. Molecular dynamics simulations confirmed β-carotene-IL-6, β-carotene-EGFR and β-carotene-TNF revealed preferable stability. Finally, HPLC -Q-TOF -MS/MS analysis detected 158 low-abundance and 73 highabundance compounds in the XXD extract. The mechanism of XXD is complex and may be related to its signaling pathway. These results may support the use of XXD for the treatment of COVID-19. Keywords Xiangxue Decoction, COVID-19, Network pharmacology, Molecular docking, Molecular dynamics simulation, HPLC-Q-TOF-MS/MS COVID-19 is a respiratory tract infection caused by the SARS-CoV-2 virus, which has a considerable impact on human central nervous system, digestive system, respiratory system and other systems. Since its discovery in 2019, it has triggered a worldwide pandemic and brought great disaster to people around the world 1 . To date, more than 770 million people worldwide have suffered from COVID-19, and more than 7 million people have died according to World Trade Organization (WTO) data reports. During the pandemic years, although researchers have been working on COVID-19 treatments and have achieved significant progress, several challenges remain. At present, the main treatment methods for COVID-19 include monoclonal antibodies, neuropathy drugs, targeted drug therapy, immunomodulatory therapy, antifibrotic and anticoagulant therapy, metabolic modulators, recovery from cognitive impairment and other methods 2,3 . However, drug therapy has limited efficacy, drug resistance, side effects and other problems 4 . As a key strategy for containing the current pandemic, numerous relevant studies on COVID-19 are well underway and have yielded promising results. Current research falls into two categories: one focuses on specific viral components, while the other examines the whole virus. However, they also have problems such as antibody dependence and even some short-term or long-term harm to the human body 5,6 . Therefore, there is an urgent need for highly effective drugs with minimal side effects to treat COVID-19. Traditional Chinese medicine (TCM) has demonstrated significant advantages in preventing and controlling COVID-19. According to the guidance of TCM theory and the compatibility of various TCMs, it has a good effect on the..
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