Apigenin and its derivative modulate nitric oxide production and interfere with TLR4-M2: In-vitro and in-silico insights

IF 4.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic Chemistry Pub Date : 2025-10-04 DOI:10.1016/j.bioorg.2025.109069

Samreen Soomro , M. Ahmed Mesaik , Farzana Shaheen , Sobia Ahsan Halim , Muhammad Waqas , Naira Nayeem , Mashael Alanazi , Ajmal Khan , Ahmed Al-Harrasi

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Abstract

The imbalance in reactive oxygen/nitrogen species causes oxidative stress which contributes to chronic inflammation and diseases. In this study, the immunomodulatory potential of the natural product ‘Apigenin (4,5,7-trihydroxyflavone)’ (APG) and its derivative ‘Apigenin-7-O-β-D-(6″-p-coumaroyl)-glucopyranoside’ (APG-7) was elucidated through cell-based spectrophotometry, chemiluminescence, and fluorescent microscopy. Their effects were assessed on the production of superoxide anion, myeloperoxidase-dependent hypochlorite anion, intracellular oxidative stress and nitric oxide (NO). Moreover, their cellular toxicity was investigated on 3 T3 fibroblast cell line. APG significantly reduced superoxide anion (48.2 %) and hypochlorite production (IC₅₀ = 27.2 μg/mL), while APG-7 showed minimal activity in these assays. Both compounds inhibited NO production, with APG showing stronger inhibition (98 %) than APG-7 (55 %). However, APG was more cytotoxic (IC₅₀ = 4.5 μg/mL) as compared to APG-7 (∼25 μg/mL), indicating a safer profile of APG-7. NO is produced by LPS triggered activation of Toll-like receptor 4 (TLR4), therefore in-silico molecular docking and dynamics simulation were performed to deduce the binding affinity of APG and APG-7 at TLR4/MD-2 interface. Our in-silico findings suggest that both the compounds may target TLR4/MD-2 interface to inhibit the production of NO. Overall, the results support the immunomodulatory potential of APG and APG-7, warranting further investigation.

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芹菜素及其衍生物调节一氧化氮的产生并干扰TLR4-M2：体外和计算机研究

活性氧/氮的不平衡导致氧化应激，从而导致慢性炎症和疾病。本研究通过细胞分光光度法、化学发光法和荧光显微镜等方法，对天然产物Apigenin（4,5,7-三羟基黄酮）（APG）及其衍生物APG-7 - o -β- d -（6″-对香豆醇基）-glucopyranoside （APG-7）的免疫调节电位进行了研究。评估了它们对超氧阴离子、脊髓过氧化物酶依赖性次氯酸阴离子、细胞内氧化应激和一氧化氮（NO）的产生的影响。并对3t3成纤维细胞株进行了细胞毒性研究。APG显著降低了超氧阴离子（48.2%）和次氯酸盐的产量（IC₅₀= 27.2 μg/mL），而APG-7在这些实验中显示出最小的活性。两种化合物均抑制NO的产生，其中APG的抑制作用（98%）强于APG-7（55%）。然而，与APG-7 （~ 25 μg/mL）相比，APG的细胞毒性更强（IC₅₀= 4.5 μg/mL），表明APG-7更安全。NO是由LPS触发toll样受体4 （TLR4）激活产生的，因此我们通过硅基分子对接和动力学模拟来推断APG和APG-7在TLR4/MD-2界面上的结合亲和力。我们的研究结果表明，这两种化合物都可能靶向TLR4/MD-2界面来抑制NO的产生。总的来说，这些结果支持APG和APG-7的免疫调节潜力，值得进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioorganic Chemistry 生物-生化与分子生物学

CiteScore

9.70

自引率

3.90%

发文量

679

审稿时长

31 days

期刊介绍： Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.