Laboratory for Molecular Design and Simulation (LMDS), Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, 50200, Thailand.
Computational Simulation and Modelling Laboratory (CSML), Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai, 50200, Thailand.
J Bioenerg Biomembr. 2018 Aug;50(4):315-327. doi: 10.1007/s10863-018-9756-x. Epub 2018 Apr 23.
Ligustrum lucidum secoiridoid glucosides have been demonstrated to treat various types of diseases such as inflammation, pain, hepatotoxicity and hyperlipidermic as well as tonic for liver and kidney. Matrix metalloproteinases (MMPs) play a key role upon the pathology of photoaging. The present computational study showed that among the six secoiridoid glucosides (ligustroside, lucidumoside A, lucidumoside C, neonuezhenide, oleoside dimethylester, and oleuropein), ligustroside and lucidumoside A competitively inhibit all MMP-1, MMP-3, and MMP-9 activities in the docking models. The molecular docking analysis revealed a network of interactions between MMP-1, MMP-3, and MMP-9 and the ligands; ligustroside and lucidumoside A, and oxygen-containing and hydrophobic functional groups appear to be responsible for these enhanced interactions. The effect of ligustroside and lucidumoside A on the transcription factor AP-1 action was also investigated using molecular docking and dynamics simulations. The experiments suggested that inhibition of an AP-1-DNA complex formation could be on account of the direct interference of AP-1 binding onto the DNA binding sequence by ligustroside and lucidumoside A. The results suggest that both compounds have the highest potential for application as an anti-aging agent with the MMP inhibitory and anti-transcriptional activities.
女贞子环烯醚萜葡萄糖苷已被证明可治疗各种类型的疾病，如炎症、疼痛、肝毒性和高脂血症，以及滋补肝肾。基质金属蛋白酶（MMPs）在光老化的病理学中起着关键作用。本计算研究表明，在 6 种环烯醚萜葡萄糖苷（梓醇、女贞苷 A、女贞苷 C、新女贞苷、橄榄苦苷二甲酯和橄榄苦苷）中，梓醇和女贞苷 A 竞争性抑制对接模型中所有 MMP-1、MMP-3 和 MMP-9 的活性。分子对接分析揭示了 MMP-1、MMP-3 和 MMP-9 与配体之间的相互作用网络；梓醇和女贞苷 A 以及含氧和疏水性官能团似乎负责这些增强的相互作用。还使用分子对接和动力学模拟研究了梓醇和女贞苷 A 对转录因子 AP-1 作用的影响。实验表明，AP-1-DNA 复合物形成的抑制可能是由于梓醇和女贞苷 A 直接干扰 AP-1 与 DNA 结合序列的结合。结果表明，这两种化合物都具有作为具有 MMP 抑制和反转录活性的抗衰老剂的最高应用潜力。
