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揭示绿豌豆废料在乳腺癌治疗中的潜力:一种利用 LC-MS/MS 代谢组学、分子网络和网络药理学的多靶点方法。

Uncovering the therapeutic potential of green pea waste in breast cancer: a multi-target approach utilizing LC-MS/MS metabolomics, molecular networking, and network pharmacology.

机构信息

Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.

Department of Pharmacognosy, Faculty of Pharmacy, Heliopolis University, Cairo, 4645241, Egypt.

出版信息

BMC Complement Med Ther. 2024 Oct 31;24(1):379. doi: 10.1186/s12906-024-04669-x.

DOI:10.1186/s12906-024-04669-x
PMID:39482666
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11526710/
Abstract

UNLABELLED

BACKGROUND PISUM SATIVUM: (PS) is a universal legume plant utilized for both human and animal consumption, particularly its seeds, known as green peas. The processing of PS in food industries and households produces a significant amount of waste that needs to be valorized.

METHODS

In this study, the metabolite profiles of the 70% ethanolic extracts of PS wastes, namely peels (PSP) and a combination of leaves and stems (PSLS), were investigated by liquid chromatography-electrospray ionization-quadrupole time-of-flight tandem mass spectrometry (LC-ESI-QTOF-MS/MS) followed by molecular networking.

RESULTS

Different classes of metabolites were identified, being flavonoids and their derivatives, along with phenolic acids, the most abundant categories. Additionally, a comprehensive network pharmacology strategy was applied to elucidate potentially active metabolites, key targets, and the pathways involved in cytotoxic activity against breast cancer. This cytotoxic activity was investigated in MCF-7 and MCF-10a cell lines. Results revealed that PSLS extract exhibited a potent cytotoxic activity with a good selectivity index (IC 17.67 and selectivity index of 3.51), compared to the reference drug doxorubicin (IC 2.69 µg/mL and selectivity index of 5.28). Whereas PSP extract appeared to be less potent and selective (IC 32.92 µg/mL and selectivity index of 1.62). A similar performance was also observed for several polyphenolics isolated from the PSLS extract, including methyl cis p-coumarate, trans p-coumaric acid, and liquiritigenin/ 7-methyl liquiritigenin mixture. Methyl cis p-coumarate showed the most potent cytotoxic activity against MCF-7 cell line and the highest selectivity (IC 1.18 µg/mL (6.91 µM) and selectivity index of 27.42). The network pharmacology study revealed that the isolated compounds could interact with several breast cancer-associated protein targets including carbonic anhydrases 1, 2, 4, 9, and 12, as well as aldo-keto reductase family 1 member B1, adenosine A3 receptor, protein tyrosine phosphatase non-receptor type 1, and estrogen receptor 2.

CONCLUSION

The uncovered therapeutic potential of PSLS and its metabolite constituents pave the way for an efficient and mindful PS waste valorization, calling for further in-vitro and in-vivo research.

摘要

未加标签

背景豌豆:(PS)是一种普遍的豆类植物,既用于人类食用,也用于动物食用,特别是其种子,称为青豆。PS 在食品工业和家庭中的加工会产生大量需要增值的废物。

方法

在这项研究中,通过液相色谱-电喷雾电离-四极杆飞行时间串联质谱(LC-ESI-QTOF-MS/MS)和分子网络分析研究了 PS 废物(PSP)皮和叶茎混合物(PSLS)的 70%乙醇提取物的代谢物图谱。

结果

鉴定出不同类别的代谢物,其中黄酮类化合物及其衍生物以及酚酸是最丰富的类别。此外,还应用了全面的网络药理学策略来阐明潜在的活性代谢物、关键靶标以及参与乳腺癌细胞毒性的途径。在 MCF-7 和 MCF-10a 细胞系中研究了这种细胞毒性。结果表明,与参考药物阿霉素(IC 2.69μg/mL 和选择性指数 5.28)相比,PSLS 提取物表现出更强的细胞毒性活性和更好的选择性指数(IC 17.67 和选择性指数 3.51)。而 PSP 提取物似乎效力较低且选择性较低(IC 32.92μg/mL 和选择性指数 1.62)。从 PSLS 提取物中分离出的几种多酚类化合物也表现出类似的性能,包括甲基顺式对香豆酸、反式对香豆酸和甘草素/7-甲基甘草素混合物。甲基顺式对香豆酸对 MCF-7 细胞系表现出最强的细胞毒性活性和最高的选择性(IC 1.18μg/mL(6.91μM)和选择性指数 27.42)。网络药理学研究表明,分离出的化合物可以与几种乳腺癌相关的蛋白靶标相互作用,包括碳酸酐酶 1、2、4、9 和 12,以及醛酮还原酶家族 1 成员 B1、腺苷 A3 受体、蛋白酪氨酸磷酸酶非受体 1 和雌激素受体 2。

结论

PSLS 及其代谢物成分的发现为 PS 废物的有效和明智增值开辟了道路,需要进一步的体外和体内研究。

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