Multimodal investigation reveals the neuroprotective mechanism of Angong Niuhuang pill for intracerebral hemorrhage: Converging bioinformatics, network pharmacology, and experimental validation

Article

作者: Zhou, Jiawei ; Jiang, Huiyun ; Wang, Xiaohong ; Jiang, Tianlin ; Wang, Jiahua ; Wu, Weilan ; Jiao, Zhiyun ; Duan, Xiaochun

ETHNOPHARMACOLOGICAL RELEVANCEAngong Niuhuang Pill (ANP) is a traditional Chinese medicine formula that has been used clinically for many years in the treatment of cerebral hemorrhage. It is composed of ingredients such as calculus bovis, moschus, and others. Ancient texts have documented that ANP's multiple components possess properties such as heat-clearing, detoxification, and sedation, which can be effective in treating conditions such as coma and stroke. However, the underlying mechanisms of ANP's potential actions are still under investigation.AIM OF THE STUDYANP is a Chinese medicine widely utilized for the treatment of intracerebral hemorrhage (ICH). However, the precise mechanism underlying the therapeutic effects remains largely elusive. The present study aims to unravel the effects and pharmacological molecular mechanisms of ANP in combatting ICH, employing a comprehensive network pharmacology approach and experimental validation.MATERIALS AND METHODSThe molecular targets of ANP and ICH were obtained from various databases, followed by the construction of protein-protein interaction (PPI) networks using the STRING database. Further, gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) analyses were conducted using the Metascape database and Cytoscape, respectively. Finally, molecular docking was performed. We performed a series of behavioral tests, immunohistochemical staining, TUNEL staining, and Western Blot to verify the effects of ANP.RESULTSIL-6, JUN, MMP9, IL-1β, VEGFA were the main candidate targets and were associated with fluid shear stress and atherosclerosis, TNF signaling pathway, etc. It is suggested that the potential mechanism of ANP against ICH may be mainly related to pyroptosis, inflammation. In vivo validation showed that ANP treatment significantly reduced the number of TUNEL-positive cells and ANP inhibited the activation of Iba-1 positive neurons, and suppressed the expression of inflammatory factors and pyroptosis indicators. In addition, ANP improved the cognitive level and motor ability of ICH mice.CONCLUSIONThe results of the study combined with virtual screening and experimental validation showed that ANP has an important contribution in protecting the brain from neuronal damage by regulating the pathways of inflammation and pyroptosis, laying the foundation and innovative ideas for future studies.

2023-12-01·Journal of Chromatography A

Chemical composition and absorption characteristics of Angong Niuhuang Pill based on two-dimensional ultra-high-performance liquid chromatography-quadrupole Orbitrap high-resolution mass spectrometry

Article

作者: Chen, Yingying ; Wang, Lixia ; Tang, Liying ; Wu, Hongwei ; Wang, Zhuju ; Wu, Tong ; Yue, Chunyu ; Chen, Xiaoxu ; Ma, Qiang ; Yang, Hongjun

Angong Niuhuang Pill (ANP) is a traditional Chinese medicine (TCM) formula with significant clinical efficacy in the treatment of stroke. Due to its complex composition, little attention has been directed toward the analysis of chemical composition and absorption characteristics of ANP. In this study, a reliable two-dimensional ultra-high-performance liquid chromatography (2D-UHPLC) coupled with quadrupole-Orbitrap high-resolution mass spectrometry (Q-Orbitrap HRMS) method was established to characterize the chemical constituents in ANP as well as the prototype components and metabolites absorbed in plasma, urine, feces, and brain tissues after oral administration. The prototype components were identified by a high mass accuracy (within 5 ppm) and MS/MS data based on online, local, and ANP self-built databases. The metabolites were predicted and identified using Compound Discoverer metabolic platform. A total of 154 compounds mainly including 37 flavonoids, 35 alkaioids, 19 organic acid, 19 bile acid, 32 terpenoids and 12 others were identified in this way. In addition, 60 prototype components mainly including flavonoids, alkaioids, organic acid, terpenoids and 164 metabolites were confirmed or preliminarily identified in rats. The metabolic pathways phase I reaction (hydration, reduction, oxidation, demethylation, and hydroxylation) and phase II reaction (acetylation, stearyl conjugation, and methylation) for the absorbed constituents were explored and summarized. This is the first systematic and comprehensive chemical characterization in ANP and its metabolism in vivo by 2D-UHPLC-Q-Orbitrap HRMS. This approach provides an effective strategy for the characterization of compounds and metabolites in traditional Chinese medicine formulas.

2023-08-01·Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan

Effectiveness and safety of Angong Niuhuang pill in treatment of acute stroke: a systematic review and Meta-analysis.

Review

作者: Minglin, Sun ; Xue, Cao ; Liyun, H E ; Jia, Liu ; Yanke, A I ; Xiangran, Meng

OBJECTIVETo systematically evaluate the efficacy and safety of Angong Niuhuang pill (, ANP) in the treatment of acute stroke. This can provide ideas and basis for the treatment of this disease with integrated Traditional Chinese and Western Medicine.METHODSRandomized controlled trials (RCTs) of China National Knowledge Infrastructure Database, Wanfang Database, Chinese BioMedical Literature Database, PubMed, Embase, and the Cochrane Library were searched from the establishment to March 2022. Two researchers screened the literature and extracted the data according to inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.3 software.RESULTSA total of 28 RCTs were included, including 2745 patients in the acute stage of stroke (1375 in the experimental group and 1370 in the control group). Meta-analysis showed that compared with conventional treatment, combined treatment with ANP could improve the effective rate of acute stroke patients [relative risk () = 1.26, 95% confidence interval () (1.21, 1.31)], Glasgow Coma Scale scores [mean difference () = 2.01, 95% (1.04, 2.98)], Mini-mental State Examination scores [ = 4.79, 95% (2.22, 7.37)], Activities of Daily Living scores [ = 15.70, 95% (14.05, 17.36)] and the Barthel index scores [ = 13.89, 95% (12.12, 15.65)], reduce National Institute of Health stroke scale scores [ = -3.90, 95% (-4.96, -2.84)] and serum brain natriuretic peptide [ = -38.50, 95% (-46.85, -30.15)]. In terms of safety, the incidence of adverse reactions showed no statistical differences between the two groups [ = 0.71, 95% (0.43, 1.15), = 0.16], and no serious adverse reactions/events were observed, indicating a good safety.CONCLUSIONSExisting clinical research evidence shows that ANP has good efficacy and safety in the treatment of acute stroke, which can provide a basis for the treatment of integrated Traditional Chinese and Western Medicine. However, the quality of included research methodology needs to be improved, and the above conclusions need to be verified by more high-quality studies.

100 项与熊胆牛黄胶囊相关的药物交易

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