研究动态
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生化、分子和计算研究证明,超高效液相色谱-四极杆飞行时间质谱表征的 Aerides odorata Lour 提取物可减轻动物模型中扑热息痛引起的肝毒性。

Ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry-characterized extract of Aerides odorata Lour alleviates paracetamol-induced hepatotoxicity in animal model evidenced by biochemical, molecular, and computational studies.

发表日期:2024 Jul 09
作者: A M Abu Ahmed, Md Atiar Rahman, Farjana Sharmen, A S M Ali Reza, Md Shahidul Islam, Md Mamunur Rashid, Md Khalid Juhani Rafi, Tanvir Ahmed Siddiqui, Md Muzahid Ahmed Ezaj, Srabonti Saha, Md Nazim Uddin, Walla Alelwani
来源: ANTIOXIDANTS & REDOX SIGNALING

摘要:

尽管尚未对其生物学功能进行充分的研究,但许多兰花都具有显着的健康益处。本研究探讨了附生仙鹤草甲醇提取物(AODE)对扑热息痛所致肝损伤的保护作用。通过分析其对肝功能参数、信使RNA(mRNA)表达和组织病理学结构的影响,研究AODE的保护作用。结果通过配体-受体相互作用的分子对接和多靶点相互作用的网络药理学分析得到证实。AODE显着(p< 0.05)最小化酸性磷酸酶、天冬氨酸转氨酶、丙氨酸转氨酶、碱性磷酸酶、γ-谷氨酰转移酶的剂量依赖性增加、乳酸脱氢酶和总胆红素与参考药物水飞蓟素相比。在 AODE 治疗的扑热息痛中毒大鼠中,丙二醛水平下降,抗氧化基因过氧化氢酶 (CAT)、超氧化物歧化酶 (SOD)、β-肌动蛋白、对氧磷酶-1 (PON1) 和磷酸果糖激酶-1 (PFK-1) 上调。采用超高效液相色谱-四极杆飞行时间质谱 (UPLC-qTOF-MS) 共鉴定出 376 种包含酚类和黄酮类化合物的化合物。使用 SwissADME 和 admetSAR 进行的在线毒性评估显示出类似药物、无毒和潜在的药理学特性。此外,计算机分析显示异类叶升麻苷(已鉴定的化合物之一)与肝脏蛋白人垂体腺苷酸环化酶-1(蛋白质数据库 ID:3N94)表现出最佳对接分数 (-11.42)。此外,网络药理学分析确定了前10个枢纽基因,即AKT1(蛋白激酶B)、CTNNB1(catenin beta-1)、SRC(原癌基因c-Src)、TNF(肿瘤坏死因子)、EGFR(表皮生长因子)受体)、HSP90AA1(热休克蛋白 90α)、MAPK3(丝裂原激活蛋白激酶 3)、STAT3(信号转导器和转录激活剂 3)、CASP3(半胱天冬酶蛋白)和 ESR1(雌激素受体 1),它们负责肝脏保护活性。通过进一步基于单一化合物的动物研究,研究结果表明,AODE 可能成为药物引起的肝损伤中的新型肝脏保护靶点。© 2024 作者。约翰·威利出版的动物模型和实验医学
Many kinds of orchids have significant health benefits although adequate research on their biological functions is yet to be carried out. This study investigated the paracetamol-induced liver damage-protecting effect of epiphytic Aerides odorata methanol extract (AODE).The protective effects of AODE were studied by analyzing its effect on liver function parameters, messenger RNA (mRNA) expression, and tissue histopathological architecture. The results were confirmed by ligand-receptor interaction of molecular docking and multitarget interaction of network pharmacological analyses.AODE significantly (p < 0.05) minimized the dose-dependent increase in acid phosphatase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamyl transferase, lactate dehydrogenase, and total bilirubin compared to the reference drug silymarin. Malondialdehyde level decreased, and the antioxidant genes catalase (CAT), superoxide dismutase (SOD), β-actin, paraoxonase-1 (PON1), and phosphofructokinase-1 (PFK-1) were upregulated in AODE-treated paracetamol-intoxicated rats. A total of 376 compounds comprising phenols and flavonoids were identified using ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-qTOF-MS). The online toxicity assessment using SwissADME and admetSAR exhibited drug-like, nontoxic, and potential pharmacological properties. Additionally, in silico analysis showed that isoacteoside, one of the identified compounds, exhibited the best docking score (-11.42) with the liver protein human pituitary adenylate cyclase-1 (Protein Data Bank ID: 3N94). Furthermore, network pharmacology analysis identified the top 10 hub genes, namely AKT1 (protein kinase B), CTNNB1 (catenin beta-1), SRC (proto-oncogene c-Src), TNF (tumor necrosis factor), EGFR (epidermal growth factor receptor), HSP90AA1 (heat shock protein 90α), MAPK3 (mitogen-activated protein kinase 3), STAT3 (signal transducer and activator of transcription 3), CASP3 (caspase protein), and ESR1 (estrogen receptor 1), which are responsible for hepatoprotective activity.The findings demonstrate that AODE could be a novel hepatoprotective target in drug-induced liver damage with a further single compound-based animal study.© 2024 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.