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圆叶玉兰叶活性部位化学成分分析及其对动物良性前列腺增生的作用评价

Chemical profiles of the active fraction from Prinsepia utilis Royle leaves and its anti-benign prostatic hyperplasia evaluation in animal models.

机构信息

School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai, 200240, People's Republic of China.

出版信息

BMC Complement Med Ther. 2021 Oct 29;21(1):272. doi: 10.1186/s12906-021-03446-4.

Abstract

BACKGROUND

The Prinsepia utilis Royle leaves (P. utilis) is a folk herb used for benign prostatic hyperplasia (BPH) control by ethnic minorities for centuries in China with rich in resources. Our previous studies have confirmed the anti-BPH effect of its water extract (QCJ) and the active fraction (Fr. B) separated from the QCJ by animal test. The Fr. B from P. utilis should be a potential candidate for BPH control.

METHODS

In this study, the chemical ingredients of Fr. B were identified by UPLC-QTOF-MS, and quantified by HPLC. Murine animal models were divided into 8 groups, Sham rats, BPH rats, BPH rats administered with finasteride (1 mg/kg), BPH rats administered with Pule'an (460 mg/kg), BPH rats administered with low, high dosage of QCJ (860 mg/kg, 2580 mg/kg respectively), BPH rats administered with low, high dosage of Fr. B (160 mg/kg, 480 mg/kg respectively). The expression of vascular endothelial growth factor (VEGF) in the prostate tissue of rats was tested, and serum levels of dihydrotestosterone (DHT), testosterone (T), estradiol (E2), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and total superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), malondialdehyde (MDA) in prostate homogenate were measured. One-way ANOVA followed by LSD was used for statistical analysis.

RESULTS

The BPH rats treated by Fr. B exhibited significant reductions of VEGF and MDA levels, as well as significant increases of SOD, GSH-Px and CAT in the prostate tissue after 28 day administration (P < 0.05). Moreover, Fr. B significantly reduced DHT, DHT/E2 ratio, TNF-α, while increased T levels in serum of BPH rats (P < 0.05). UPLC-QTOF-MS analysis revealed 10 flavonoids as the key constituents of this fraction, which accounted for 54.96% of all substance of Fr. B. The relative contents of compound 1, 2 are 11.1%, 13% in Fr. B respectively.

CONCLUSIONS

These results indicated that the Fr. B obtained from P. utilis alleviated the symptoms of BPH rats through multiple mechanisms including reduction of DHT/E2 ratio, inhibition of growth factor, anti-inflammation and anti-oxidation, in which flavonoids might be the key constituents. It supported the hypothesis that the Fr. B should be further explored as a candidate for BPH patients.

摘要

背景

瑞香科 Prinsepia utilis Royle 叶(P. utilis)是一种民间草药,几个世纪以来,中国少数民族一直将其用于治疗良性前列腺增生(BPH),资源丰富。我们之前的研究已经通过动物试验证实了其水提取物(QCJ)和从 QCJ 中分离出的活性部分(Fr. B)的抗 BPH 作用。瑞香科的 Fr. B 应该是控制 BPH 的潜在候选药物。

方法

在这项研究中,通过 UPLC-QTOF-MS 鉴定 Fr. B 的化学成分,并通过 HPLC 进行定量。将小鼠动物模型分为 8 组,假手术大鼠、BPH 大鼠、给予非那雄胺(1mg/kg)的 BPH 大鼠、给予普乐安(460mg/kg)的 BPH 大鼠、给予低、高剂量 QCJ(分别为 860mg/kg、2580mg/kg)的 BPH 大鼠、给予低、高剂量 Fr. B(分别为 160mg/kg、480mg/kg)的 BPH 大鼠。检测大鼠前列腺组织中血管内皮生长因子(VEGF)的表达,测量前列腺匀浆中血清中二氢睾酮(DHT)、睾酮(T)、雌二醇(E2)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和总超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)、丙二醛(MDA)的水平。采用单因素方差分析(One-way ANOVA),并进行 LSD 检验进行统计分析。

结果

Fr. B 处理 28 天后,BPH 大鼠前列腺组织中 VEGF 和 MDA 水平显著降低,SOD、GSH-Px 和 CAT 水平显著升高(P<0.05)。此外,Fr. B 还显著降低了 BPH 大鼠血清中的 DHT、DHT/E2 比值、TNF-α,同时增加了 T 水平(P<0.05)。UPLC-QTOF-MS 分析显示,10 种黄酮类化合物为该部分的关键成分,占 Fr. B 总物质的 54.96%。Fr. B 中化合物 1、2 的相对含量分别为 11.1%、13%。

结论

这些结果表明,瑞香科 Fr. B 通过降低 DHT/E2 比值、抑制生长因子、抗炎和抗氧化等多种机制缓解 BPH 大鼠的症状,其中黄酮类化合物可能是关键成分。这支持了 Fr. B 应该作为 BPH 患者的候选药物进一步探索的假设。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f719/8555178/c5ac04554e7e/12906_2021_3446_Fig1_HTML.jpg

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