Network pharmacology of Epilobium angustifolium metabolites in relation to in vitro analyses of its extracts

IF 2.5 3区医学 Q3 CHEMISTRY, MEDICINAL

Fitoterapia Pub Date : 2025-04-19 DOI:10.1016/j.fitote.2025.106552

Benita Hryć , Aleksandra Cvetanović Kljakić , Mehmet Veysi Cetiz , Gunes Ak , Gokhan Zengin , Ismail Senkardes , Łukasz Świątek , Marcin Kunecki , Kinga Salwa , Elwira Sieniawska

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引用次数: 0

Abstract

Epilobium angustifolium L. is a perennial herbaceous plant known for various therapeutic properties, however its biological activity is not fully explored. In this study, we examined antioxidant activities of extracts of different polarity (n-hexane, ethyl acetate and 70 % ethanol in water) and their potential to inhibit amylase, glucosidase, tyrosinase, acetylcholinesterase and butyrylcholinesterase, as well as cytotoxic effects. Moreover, phytochemical analysis performed with liquid chromatography-mass spectrometry (LC-ESI-QTOF-MS) revealed the presence of hydrolysable tannins (gallotannins and ellagitannins), flavonoids, phenolic acids derivatives and esters of saccharides, triterpenoids and lipids. The aqueous-ethanolic extract exhibited the best radical scavenging and reducing abilities. The identified compounds in the extracts were subjected to Disease Ontology enrichment analysis and screening of potential targets, which identified significant associations with colon carcinoma and gastric adenocarcinoma. The predicted cytotoxicity was checked against cancerous and non-cancerous cell lines. The E. angustifolium aqueous-ethanolic extract showed weak cytotoxicity on non-cancerous monkey kidney fibroblasts (VERO cells) and moderate cytotoxicity against cancer-derived cells (malignant melanoma, human gastric adenocarcinoma, human hypopharyngeal squamous cell carcinoma, human colon cancer), with the highest toxicity and cytotoxic selectivity observed for hypopharyngeal (CC₅₀ = 37.52 μg/mL, SI = 6.39) and colon (CC₅₀ = 37.27 μg/mL, SI = 6.43) cancer-derived cells. Key drug targets were identified using CTD, STRING, GeneCards, and DisGeNET databases, followed by protein-protein interaction network analysis. Molecular docking using AutoDock Vina revealed that compounds gemin D and hamamelitannin demonstrated strong binding affinities with cancer-related proteins. These findings revealed the potential of indicated molecules as anti-proliferative agents and suggest the need for further research to optimize their efficacy.

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枇杷代谢物的网络药理学及其提取物的体外分析

毛叶是一种多年生草本植物，具有多种治疗作用，但其生物活性尚未得到充分的研究。在本研究中，我们研究了不同极性（正己烷、乙酸乙酯和70%乙醇）提取物的抗氧化活性，以及它们对淀粉酶、葡萄糖苷酶、酪氨酸酶、乙酰胆碱酯酶和丁基胆碱酯酶的抑制作用，以及细胞毒性作用。此外，通过液相色谱-质谱（LC-ESI-QTOF-MS）进行的植物化学分析显示，存在水解单宁（没食子单宁和鞣花单宁）、类黄酮、酚酸衍生物以及糖、三萜和脂类酯。水乙醇提取物具有较好的自由基清除和还原能力。对提取物中鉴定的化合物进行疾病本体富集分析和潜在靶点筛选，发现与结肠癌和胃腺癌有显著相关性。预测的细胞毒性对癌细胞和非癌细胞系进行了检查。水乙醇提取物对非癌变猴肾成纤维细胞（VERO细胞）的细胞毒性较弱，对恶性黑色素瘤、人胃腺癌、人下咽鳞状细胞癌、人结肠癌的细胞毒性中等，对下咽（CC50 = 37.52 μg/mL, SI = 6.39）和结肠癌（CC50 = 37.27 μg/mL, SI = 6.43）的细胞毒性和细胞毒性选择性最高。利用CTD、STRING、GeneCards和DisGeNET数据库确定关键药物靶点，然后进行蛋白-蛋白相互作用网络分析。利用AutoDock Vina进行分子对接发现，化合物gemin D和金缕梅单宁（hamamelitannin）与癌症相关蛋白具有很强的结合亲和力。这些发现揭示了所述分子作为抗增殖剂的潜力，并表明需要进一步研究以优化其功效。

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来源期刊

Fitoterapia 医学-药学

CiteScore

5.80

自引率

2.90%

发文量

198

审稿时长

1.5 months

期刊介绍： Fitoterapia is a Journal dedicated to medicinal plants and to bioactive natural products of plant origin. It publishes original contributions in seven major areas: 1. Characterization of active ingredients of medicinal plants 2. Development of standardization method for bioactive plant extracts and natural products 3. Identification of bioactivity in plant extracts 4. Identification of targets and mechanism of activity of plant extracts 5. Production and genomic characterization of medicinal plants biomass 6. Chemistry and biochemistry of bioactive natural products of plant origin 7. Critical reviews of the historical, clinical and legal status of medicinal plants, and accounts on topical issues.