Li Min, Wei Zhuo-Chun, Zhang Feng-Xiang, Li Hai-Jun
Key Laboratory of Emergency and Trauma of Ministry of Education, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital, Hainan Medical University, Haikou, China.
Binhaiwan Central Hospital of Dongguan, Dongguan, China.
Rapid Commun Mass Spectrom. 2025 Oct 30;39(20):e10097. doi: 10.1002/rcm.10097.
Semen Hoveniae (SH), known as Zhijuzi in Chinese, is extensively utilized in China for the management of alcoholic liver disease (ALD) due to its recognized detoxification properties. Despite its extensive historical use, the detailed chemical profile and anti-ALD mechanisms of SH remain inadequately understood, significantly restricting its further therapeutic development.
The chemical constituents of SH were systematically profiled using ultra high-performance liquid chromatography coupled with time-of-flight mass spectrometry (UHPLC-Q-TOF MS). Potential molecular targets of identified compounds were predicted using the SwissTargetPrediction platform. Common targets were subsequently analyzed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using the DAVID database. Network pharmacology results were validated by molecular docking.
Seventy-six compounds were identified or tentatively characterized in SH, including 50 flavonoids, 15 saponins, 5 terpenes, 3 alkaloids, 2 phenylpropanoids, and 1 other type, among which seven were unambiguously identified using reference standards. Furthermore, seven potentially novel components were identified. Network pharmacology and molecular docking analyses elucidated the molecular mechanisms underlying SH's therapeutic effects on ALD. Three core molecular targets-AKT1, SRC, and EGFR-were identified. Key pathways closely related to ALD, such as glutathione metabolism and arachidonic acid metabolism, were notably enriched, suggesting their crucial roles in SH's hepatoprotective mechanisms. Molecular docking studies confirmed strong binding affinities (binding energies lower than -5.0 kcal/mol) between six active compounds (laricetrin, apigenin, quercetin, kaempferol, myricetin, and syringetin) and the three core targets (AKT1, SRC, and EGFR).
This study comprehensively characterizes the chemical compositions of SH and elucidates its potential mechanisms against ALD. These findings substantiate the hepatoprotective potential of SH, providing a solid scientific foundation for its traditional use and promoting the development of novel therapeutic approaches for ALD.
枳椇子在中国被广泛用于治疗酒精性肝病（ALD），因其具有公认的解毒特性。尽管枳椇子有着悠久的使用历史，但其详细的化学组成和抗ALD机制仍未得到充分了解，这严重限制了其进一步的治疗开发。
采用超高效液相色谱-飞行时间质谱联用（UHPLC-Q-TOF MS）系统分析枳椇子的化学成分。使用SwissTargetPrediction平台预测已鉴定化合物的潜在分子靶点。随后通过DAVID数据库，经基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析对共同靶点进行分析。通过分子对接验证网络药理学结果。
在枳椇子中鉴定或初步表征了76种化合物，包括50种黄酮类、15种皂苷类、5种萜类、3种生物碱类、2种苯丙素类和1种其他类型，其中7种通过参考标准明确鉴定。此外，还鉴定出7种潜在的新成分。网络药理学和分子对接分析阐明了枳椇子对ALD治疗作用的分子机制。确定了三个核心分子靶点——AKT1、SRC和EGFR。与ALD密切相关的关键通路，如谷胱甘肽代谢和花生四烯酸代谢，显著富集，表明它们在枳椇子的肝脏保护机制中起关键作用。分子对接研究证实了六种活性化合物（落叶松脂素、芹菜素、槲皮素、山柰酚、杨梅素和紫丁香苷）与三个核心靶点（AKT1、SRC和EGFR）之间具有很强的结合亲和力（结合能低于-5.0 kcal/mol）。
本研究全面表征了枳椇子的化学成分，并阐明了其抗ALD的潜在机制。这些发现证实了枳椇子的肝脏保护潜力，为其传统用途提供了坚实的科学基础，并促进了ALD新型治疗方法的开发。
