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用两种具有抗 TGF-β促进前列腺基质细胞(WPMY-1)增殖活性的生物活性标志物对宽叶文殊兰叶的乙醇提取物进行标准化。

Standardization of the ethanolic extract of Crinum latifolium leaves by two bioactive markers with antiproliferative activity against TGF-β-promoted prostate stromal cells (WPMY-1).

机构信息

Center of Excellence in DNA Barcoding of Thai Medicinal Plants, Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.

Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.

出版信息

BMC Complement Med Ther. 2022 May 18;22(1):139. doi: 10.1186/s12906-022-03617-x.

DOI:10.1186/s12906-022-03617-x
PMID:35585532
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9118764/
Abstract

BACKGROUND

Crinum latifolium L. (Amaryllidaceae) has been used in Southeast Asian traditional medicine to alleviate the symptoms of benign prostatic hyperplasia (BPH). The pathological mechanism of BPH is associated with the induction of prostate stromal cell proliferation through transforming growth factor-beta (TGF-β). Standardization as well as investigation of the potential anti-BPH activity of C. latifolium extract could benefit the further development of BPH-related analyses and provide evidence to support the application of this extract for BPH treatment. This study aimed to standardize and investigate the antiproliferative activity of the ethanolic extract of C. latifolium leaves. The major alkaloids isolated from C. latifolium were also explored for their potential use as bioactive markers.

METHODS

Two major alkaloids were isolated from the ethanolic extract of C. latifolium leaves by chromatographic techniques, identified by NMR and MS, and quantified by a validated UHPLC method. Their antiproliferative activity was studied in human prostate stromal cells (WPMY-1) induced by TGF-β. The synergistic effect of combining the two major isolated alkaloids was analyzed by the zero interaction potency (ZIP) model.

RESULTS

Two alkaloids, lycorine (1) and 6α-hydroxybuphanidrine (2), were isolated from the ethanolic leaf extract of C. latifolium. A UHPLC method for the quantification of (1) and (2) was developed and validated in terms of linearity, precision, and accuracy. The C. latifolium leaf extract contained 0.279 ± 0.003% (1) and 0.232 ± 0.004% (2). The crude extract was more potent than either (1) and (2) alone against TGF-β-treated WPMY-1 cell proliferation. The drug combination study revealed that the greatest synergistic effect of (1) and (2) was achieved at a 1:1 ratio.

CONCLUSIONS

The results of this study support the anti-BPH activity of C. latifolium in traditional medicine and suggest that these the two isolated alkaloids may promote the efficacy of the C. latifolium extract. Additionally, major alkaloids (1) and (2) can be used as bioactive markers for the standardization of C. latifolium extracts.

摘要

背景

长梗水玉簪(Amaryllidaceae)在东南亚传统医学中被用于缓解良性前列腺增生(BPH)的症状。BPH 的病理机制与转化生长因子-β(TGF-β)诱导前列腺基质细胞增殖有关。C. latifolium 提取物的标准化以及对其潜在抗 BPH 活性的研究可以促进进一步的 BPH 相关分析,并为该提取物治疗 BPH 提供支持。本研究旨在标准化和研究长梗水玉簪叶乙醇提取物的抗增殖活性。还探索了从长梗水玉簪中分离出的主要生物碱,以探索其作为生物活性标志物的潜在用途。

方法

通过色谱技术从长梗水玉簪叶乙醇提取物中分离出两种主要生物碱,通过 NMR 和 MS 鉴定,并通过经过验证的 UHPLC 方法定量。在 TGF-β诱导的人前列腺基质细胞(WPMY-1)中研究了这两种主要分离生物碱的抗增殖活性。通过零相互作用潜力(ZIP)模型分析了两种主要分离生物碱的协同作用。

结果

从长梗水玉簪叶乙醇提取物中分离出两种生物碱,即石蒜碱(1)和 6α-羟基布非那嗪(2)。建立并验证了 UHPLC 方法,用于(1)和(2)的定量。长梗水玉簪叶提取物中含有 0.279±0.003%(1)和 0.232±0.004%(2)。与单独使用(1)和(2)相比,粗提物对 TGF-β处理的 WPMY-1 细胞增殖更有效。药物组合研究表明,(1)和(2)的最佳协同作用在 1:1 比例时达到。

结论

本研究结果支持长梗水玉簪在传统医学中的抗 BPH 活性,并表明这两种分离出的生物碱可能增强长梗水玉簪提取物的功效。此外,主要生物碱(1)和(2)可作为长梗水玉簪提取物标准化的生物活性标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0596/9118764/114dc3e14d8e/12906_2022_3617_Fig7_HTML.jpg
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