Evidence of clinical efficacy and pharmacological mechanism of N-butylphthalide in the treatment of delayed encephalopathy after acute carbon monoxide poisoning

Huiping Song; Aochun Yue; Xudong Zhou; Wei Han; Qin Li

doi:10.3389/fneur.2023.1119871

Evidence of clinical efficacy and pharmacological mechanism of N-butylphthalide in the treatment of delayed encephalopathy after acute carbon monoxide poisoning

Front Neurol. 2023 Mar 16:14:1119871. doi: 10.3389/fneur.2023.1119871. eCollection 2023.

Authors

Huiping Song^{1

2}, Aochun Yue^{2

3}, Xudong Zhou¹, Wei Han², Qin Li^{2

4}

Affiliations

¹ First School of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
² Emergency Department, Shenzhen University General Hospital, Shenzhen, China.
³ Centre of Integrated Chinese and Western Medicine, School of Basic Medicine, Qingdao University, Qingdao, China.
⁴ Department of Integrated Chinese and Western Medicine, Yuhuangding Hospital Affiliated to Qingdao University, Yantai, China.

Abstract

Objective: Based on network meta-analysis (NMA) and network pharmacology approaches, we explored the clinical efficacy of different regimens, and clarified the pharmacological mechanisms of N-butylphthalide (NBP) in the treatment of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP).

Methods: Firstly, NMA was conducted to obtain the ranking of the efficacy of different regimens for the treatment of DEACMP. Secondly, the drug with a relatively high efficacy ranking was selected and its mechanism of treatment for DEACMP was identified through a network pharmacology analysis. By the use of protein interaction and enrichment analysis, the pharmacological mechanism was predicted, and molecular docking was subsequently carried out to verify the reliability of the results.

Results: A total of 17 eligible randomized controlled trials (RCTs) involving 1293 patients and 16 interventions were eventually included in our analysis from NMA. Mesenchymal stem cells (MSCs) + NBP significantly increased mini-mental state examination (MMSE) and Barthel index (BI) scores; NBP + dexamethasone (DXM) was the most effective treatment in improving the activity of daily living (ADL) scores; NBP significantly decreased national institutes of health stroke scale (NIHSS) scores; Xingzhi-Yinao granules (XZYN) had more advantages in improving Montreal cognitive assessment (MoCA) scores, translational direct current stimulation (tDCS) had a significant effect in improving P300 latency and P300 amplitude and Kinnado + Citicoline had the most obvious effect in improving malondialdehyde (MDA). Meanwhile, by network pharmacology analysis, 33 interaction genes between NBP and DEACMP were obtained, and 4 of them were identified as possible key targets in the process of MCODE analysis. 516 Gene ontology (GO) entries and 116 Kyoto Encyclopedia of Gene and Genome (KEGG) entries were achieved by enrichment analysis. Molecular docking showed that NBP had good docking activity with the key targets.

Conclusion: The NMA screened for regimens with better efficacy for each outcome indicator in order to provide a reference for clinical treatment. NBP can stably bind ALB, ESR1, EGFR, HSP90AA1, and other targets, and may play a role in neuroprotection for patients with DEACMP by modulating Lipid and atherosclerosis, IL-17 signaling pathway, MAPK signaling pathway, FoxO signaling pathway, PI3K/AKT signaling pathway.

Keywords: N-butylphthalide; clinical efficacy; delayed encephalopathy after acute carbon monoxide poisoning; network meta-analysis; network pharmacology; pharmacological mechanism.

Publication types

Systematic Review

Grants and funding

The authors are thankful for the support of the National Natural Science Foundation of China (Nos. 82071465 and 81571283), the Natural Science Foundation of Shandong (No. ZR2020MH154), the Sanming Project of Medicine and Health in Shenzhen (No. SZSM201911007), and the Key Project of Research and Development of Shandong Province (No. 2018GSF118215).