Panchal Kavan, Nihalani Bhavya, Oza Utsavi, Panchal Aarti, Shah Bhumi
Pharmaceutical Chemistry, L. J. Institute of Pharmacy, L J University, Gujarat, Ahmedabad 382210, India.
World J Exp Med. 2023 Dec 20;13(5):142-155. doi: 10.5493/wjem.v13.i5.142.
Bitter melon has been used to stop the growth of breast cancer (BRCA) cells. However, the underlying mechanism is still unclear.
To predict the therapeutic effect of bitter melon against BRCA using network pharmacology and to explore the underlying pharmacological mechanisms.
The active ingredients of bitter melon and the related protein targets were taken from the Indian Medicinal Plants, Phytochemistry and Therapeutics and SuperPred databases, respectively. The GeneCards database has been searched for BRCA-related targets. Through an intersection of the drug's targets and the disease's objectives, prospective bitter melon anti-BRCA targets were discovered. Gene ontology and kyoto encyclopedia of genes and genomes enrichment analyses were carried out to comprehend the biological roles of the target proteins. The binding relationship between bitter melon's active ingredients and the suggested target proteins was verified using molecular docking techniques.
Three key substances, momordicoside K, kaempferol, and quercetin, were identified as being important in mediating the putative anti-BRCA effects of bitter melon through the active ingredient-anti-BRCA target network study. Heat shock protein 90 AA, proto-oncogene tyrosine-protein kinase, and signal transducer and activator of transcription 3 were found to be the top three proteins in the protein-protein interaction network study. The several pathways implicated in the anti-BRCA strategy for an active component include phosphatidylinositol 3-kinase/protein kinase B signaling, transcriptional dysregulation, axon guidance, calcium signaling, focal adhesion, janus kinase-signal transducer and activator of transcription signaling, cyclic adenosine monophosphate signaling, mammalian target of rapamycin signaling, and phospholipase D signaling.
Overall, the integration of network pharmacology, molecular docking, and functional enrichment analyses shed light on potential mechanisms underlying bitter melon's ability to fight BRCA, implicating active ingredients and protein targets, as well as highlighting the major signaling pathways that may be altered by this natural product for therapeutic benefit.
苦瓜已被用于阻止乳腺癌（BRCA）细胞的生长。然而，其潜在机制仍不清楚。
利用网络药理学预测苦瓜对BRCA的治疗效果，并探索其潜在的药理机制。
苦瓜的活性成分和相关蛋白质靶点分别取自《印度药用植物、植物化学与治疗学》和SuperPred数据库。在GeneCards数据库中搜索BRCA相关靶点。通过药物靶点与疾病靶点的交集，发现了潜在的苦瓜抗BRCA靶点。进行基因本体论和京都基因与基因组百科全书富集分析，以了解靶蛋白的生物学作用。使用分子对接技术验证苦瓜活性成分与建议的靶蛋白之间的结合关系。
通过活性成分-抗BRCA靶点网络研究，确定了三种关键物质，即苦瓜苷K、山奈酚和槲皮素，它们在介导苦瓜假定的抗BRCA作用中起重要作用。在蛋白质-蛋白质相互作用网络研究中，热休克蛋白90 AA、原癌基因酪氨酸蛋白激酶和信号转导子和转录激活子3被发现是前三种蛋白质。活性成分抗BRCA策略涉及的几种途径包括磷脂酰肌醇3激酶/蛋白激酶B信号传导、转录失调、轴突导向、钙信号传导、粘着斑、janus激酶-信号转导子和转录激活子信号传导、环磷酸腺苷信号传导、雷帕霉素哺乳动物靶点信号传导和磷脂酶D信号传导。
总体而言，网络药理学、分子对接和功能富集分析的整合揭示了苦瓜对抗BRCA能力的潜在机制，涉及活性成分和蛋白质靶点，并突出了这种天然产物可能改变以获得治疗益处的主要信号通路。
