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家蚕标准化提取物对阿霉素诱导的小鼠模型心脏毒性的心脏保护作用的科学验证。

Scientific validation of cardioprotective attribute by standardized extract of Bombyx mori against doxorubicin-induced cardiotoxicity in murine model.

作者信息

Khan Masood S, Singh Mhaveer, Khan Mohammad A, Arya D S, Ahmad Sayeed

机构信息

Bioactive Natural Product Laboratory, Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, India-110062.

Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, India-110062.

出版信息

EXCLI J. 2014 Sep 5;13:1043-54. eCollection 2014.

Abstract

Doxorubicin (DOX) is an excellent antineoplastic agent used for the treatment of hematological and solid malignancies. The aqueous extract of Bombyx mori (BMAE) contains amino acids and some flavonoids with obvious cardioprotective effect. The aim of this study was to investigate the possible protective effect of BMAE against DOX-induced cardiotoxicity and its underlying mechanisms on murine model. The metabolic profiling of BMAE was carried out by Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) and the amino acid profiling by HPLC method using fluorescence detector (HPLC-FLD). The biochemical parameter like caspase-3, tumor necrosis factor-alpha (TNF-α), interleukin -6 (IL-6), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) and malondialdehyde (MDA) were studied. Tissue damage was further evaluated by histopathological studies. The metabolic profiling of BMAE exhibited presence of quercetin 7-O-ß-D-glucoside, kaempferol 7-O-ß-D-glucopyranoside, coumaric acid glucoside, 2-hydroxy-nonadecanoic acid and 9,12-dihydroxy stearic acid as important constituents. The amino acid profile by HPLC-FLD showed presence of 17 amino acids. The BMAE showed prominent free radical scavenging activity when assessed by the H2O2 and super-oxide method. The results of present investigation showed protection against DOX-induced oxidative stress (lipid peroxidation), by reverting activities of apoptotic markers (caspase-3 and TNF-α), cardiac markers (CK-MB and LDH activities) as well as pro-inflammatory marker IL-6 followed by oral administration of BMAE. In addition, results of histopathology also supported well the above results. It was observed that BMAE protects DOX-induced cardiotoxicity by virtue of its antioxidants possibly by flavonoids and amino acids.

摘要

多柔比星(DOX)是一种用于治疗血液系统恶性肿瘤和实体瘤的优秀抗肿瘤药物。家蚕水提取物(BMAE)含有氨基酸和一些具有明显心脏保护作用的黄酮类化合物。本研究的目的是探讨BMAE对DOX诱导的心脏毒性的可能保护作用及其在小鼠模型中的潜在机制。通过超高效液相色谱-质谱联用(UPLC-MS)对BMAE进行代谢谱分析,并采用带荧光检测器的高效液相色谱法(HPLC-FLD)进行氨基酸谱分析。研究了半胱天冬酶-3、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、肌酸激酶同工酶MB(CK-MB)、乳酸脱氢酶(LDH)和丙二醛(MDA)等生化参数。通过组织病理学研究进一步评估组织损伤情况。BMAE的代谢谱显示,槲皮素7-O-β-D-葡萄糖苷、山奈酚7-O-β-D-吡喃葡萄糖苷、香豆酸葡萄糖苷、2-羟基十九烷酸和9,12-二羟基硬脂酸是其重要成分。HPLC-FLD分析的氨基酸谱显示存在17种氨基酸。通过H2O2和超氧化物法评估时,BMAE表现出显著清除自由基的活性。本研究结果表明,口服BMAE可通过恢复凋亡标志物(半胱天冬酶-3和TNF-α)、心脏标志物(CK-MB和LDH活性)以及促炎标志物IL-6的活性,对DOX诱导的氧化应激(脂质过氧化)起到保护作用。此外组织病理学结果也很好地支持了上述结果。据观察,BMAE凭借其抗氧化剂(可能是黄酮类化合物和氨基酸)保护机体免受DOX诱导的心脏毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d0c/4464155/0380a116fa62/EXCLI-13-1043-t-001.jpg

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