利用计算机多维数据分析评估槲皮素、柚皮素和芦丁在基因、蛋白质和 miRNA 水平上的可能作用途径及保护作用。
Evaluation of the Possible Pathways Involved in the Protective Effects of Quercetin, Naringenin, and Rutin at the Gene, Protein and miRNA Levels Using In-Silico Multidimensional Data Analysis.
机构信息
Department of Biochemistry, College of Science, King Saud University, Riyadh 11495, Saudi Arabia.
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
出版信息
Molecules. 2023 Jun 21;28(13):4904. doi: 10.3390/molecules28134904.
Flavonoids are secondary metabolites that are non-essential for plant growth or survival, and they also provide numerous health benefits to humans. They are antioxidants that shield plants from the ill effects of ultraviolet light, pests, and diseases. They are beneficial to health for several reasons, including lowering inflammation, boosting cardiovascular health, and lowering cancer risk. This study looked into the physicochemical features of these substances to determine the potential pharmacological pathways involved in their protective actions. Potential targets responsible for the protective effects of quercetin, naringenin, and rutin were identified with SwissADME. The associated biological processes and protein-protein networks were analyzed by using the GeneMANIA, Metascape, and STRING servers. All the flavonoids were predicted to be orally bioavailable, with more than 90% targets as enzymes, including kinases and lyases, and with common targets such as NOS2, CASP3, CASP9, CAT, BCL2, TNF, and HMOX1. TNF was shown to be a major target in over 250 interactions. To extract the "biological meanings" from the MCODE networks' constituent parts, a GO enrichment analysis was performed on each one. The most important transcription factors in gene regulation were RELA, NFKB1, PPARG, and SP1. Treatment with quercetin, naringenin, or rutin increased the expression and interaction of the microRNAs' hsa-miR-34a-5p, hsa-miR-30b-5p, hsa-let-7a-5p, and hsa-miR-26a-1-3p. The anticancer effects of hsa-miR-34a-5p have been experimentally confirmed. It also plays a critical role in controlling other cancer-related processes such as cell proliferation, apoptosis, EMT, and metastasis. This study's findings might lead to a deeper comprehension of the mechanisms responsible for flavonoids' protective effects and could present new avenues for exploration.
类黄酮是植物生长或生存非必需的次生代谢物,它们也为人类提供了许多健康益处。它们是抗氧化剂,可以保护植物免受紫外线、害虫和疾病的不良影响。它们对健康有益有几个原因,包括降低炎症、促进心血管健康和降低癌症风险。本研究探讨了这些物质的物理化学特性,以确定其保护作用涉及的潜在药理途径。利用 SwissADME 鉴定了槲皮素、柚皮素和芦丁的潜在靶标。利用 GeneMANIA、Metascape 和 STRING 服务器分析了相关的生物过程和蛋白质-蛋白质网络。所有的类黄酮都被预测为口服生物可利用的,超过 90%的靶标是酶,包括激酶和裂解酶,并有共同的靶标,如 NOS2、CASP3、CASP9、CAT、BCL2、TNF 和 HMOX1。TNF 是 250 多个相互作用中的主要靶标。为了从 MCODE 网络的组成部分中提取“生物学意义”,对每个部分进行了 GO 富集分析。基因调控中最重要的转录因子是 RELA、NFKB1、PPARG 和 SP1。槲皮素、柚皮素或芦丁处理增加了 microRNAs 的 hsa-miR-34a-5p、hsa-miR-30b-5p、hsa-let-7a-5p 和 hsa-miR-26a-1-3p 的表达和相互作用。hsa-miR-34a-5p 的抗癌作用已得到实验证实。它还在控制其他与癌症相关的过程中起着关键作用,如细胞增殖、凋亡、EMT 和转移。本研究的发现可能会导致对类黄酮保护作用机制的更深入理解,并为探索提供新的途径。