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来源于知母的类黄酮通过调节 COX/LOX 通路改善良性前列腺增生的炎症。

Flavonoids derived from Anemarrhenae Rhizoma ameliorate inflammation of benign prostatic hyperplasia via modulating COX/LOX pathways.

机构信息

School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, China.

出版信息

J Ethnopharmacol. 2022 Feb 10;284:114740. doi: 10.1016/j.jep.2021.114740. Epub 2021 Nov 2.

DOI:10.1016/j.jep.2021.114740
PMID:34737006
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Flavonoids are the main components of the traditional Chinese medicine Anemarrhenae Rhizoma (dried rhizome of Anemarrhena asphodeloides Bge.), which has been reported to possess activity against inflammation and tumor.

AIM OF STUDY

Regulation of the arachidonic acid (AA) cascade through cyclooxygenase (COX) and lipoxygenase (LOX) represent the two major pathways to treat inflammatory of benign prostatic hyperplasia (BPH). In this study, Anemarrhenae Rhizoma flavonoids and its main compounds (mangiferin, neomangiferin and isomangiferin) were investigated for effects on AA metabolism.

METHODS

Ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was used to monitor AA metabolites in BPH rats and in PC-3 cells. COX-2 and 5-LOX protein and mRNA levels were measured by Western blot and qPCR, respectively, along with histopathological assessment of prostate tissues.

RESULTS

Treatment with flavonoids significantly ameliorated BPH-associated prostate inflammation and inhibited the expression of COX-2 and 5-LOX at the protein and mRNA levels. Quantitative metabolomic analysis of blood plasma showed flavonoids treatment decreased AA levels and its metabolites associated with the COX and LOX pathways. Further exploration of the flavonoid compounds mangiferin, neomangiferin and isomangiferin showed they inhibited AA metabolism to varying degrees in PC-3 cell cultures.

CONCLUSION

Anemarrhenae Rhizoma flavonoids act to inhibit BPH-related inflammation in vivo and in vitro by targeting AA metabolism and interfering with COX and LOX pathways. The identification of mangiferin, neomangiferin and isomangiferin as anti-inflammatory components suggests flavonoids interventions represent a promising therapeutic approach for BPH.

摘要

民族药理学相关性

类黄酮是中药知母(知母干燥根茎)的主要成分,据报道,知母具有抗炎和抗肿瘤作用。

研究目的

通过环氧化酶(COX)和脂氧合酶(LOX)调节花生四烯酸(AA)级联反应,代表了治疗良性前列腺增生(BPH)炎症的两种主要途径。在这项研究中,研究了知母黄酮及其主要化合物(芒果苷、新芒果苷和异芒果苷)对 AA 代谢的影响。

方法

采用超高效液相色谱-串联质谱法(UPLC-MS/MS)监测 BPH 大鼠和 PC-3 细胞中的 AA 代谢物。通过 Western blot 和 qPCR 分别测定 COX-2 和 5-LOX 蛋白和 mRNA 水平,并对前列腺组织进行组织病理学评估。

结果

黄酮类化合物治疗显著改善了 BPH 相关的前列腺炎症,并抑制了 COX-2 和 5-LOX 在蛋白和 mRNA 水平的表达。对血浆的定量代谢组学分析表明,黄酮类化合物治疗降低了 AA 水平及其与 COX 和 LOX 途径相关的代谢物。对知母黄酮类化合物芒果苷、新芒果苷和异芒果苷的进一步研究表明,它们在 PC-3 细胞培养中不同程度地抑制了 AA 代谢。

结论

知母黄酮类化合物通过靶向 AA 代谢并干扰 COX 和 LOX 途径,在体内和体外抑制 BPH 相关炎症。鉴定芒果苷、新芒果苷和异芒果苷为抗炎成分表明,黄酮类化合物干预代表了治疗 BPH 的一种有前途的治疗方法。

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