Milošević Nataša, Milanović Maja, Medić Stojanoska Milica, Tipmanee Varomyalin, Smyrnioudis Ilias, Dedoussis George V, Milić Nataša
Department of Pharmacy, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia.
Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia.
Curr Issues Mol Biol. 2025 Jan 15;47(1):51. doi: 10.3390/cimb47010051.
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease without an approved pharmacological approach for its prevention/treatment. Based on the modified Delphi process, NAFLD was redefined as metabolic dysfunction-associated steatotic liver disease (MASLD) to highlight the metabolic aspect of liver pathogenesis. Chios mastiha ( var. , Anacardiaceae) resin demonstrated promising results in MASLD treatment. In this paper, molecular docking was applied to test 16 compounds from Chios mastiha as potential ligands for the receptors GR, LXRα, LXRβ, PPARα PPARγ, MC4R, AMPK, and VEGFR2, whose up- and down-regulation interfere with MASLD development and progression. The observed compounds had moderate and high affinity for LXR, GR, MC4R, and PPARγ in comparison to proven ligands, while their affinity for PPARα, AMPK, and VEGFR was less pronounced. The combination of active compounds from Chios mastiha rather than a single molecule may have a superior ability to control the intertwined MASLD metabolic pathways.
非酒精性脂肪性肝病(NAFLD)是最常见的慢性肝病,目前尚无经批准的预防/治疗药物方法。基于改良的德尔菲法,NAFLD被重新定义为代谢功能障碍相关脂肪性肝病(MASLD),以突出肝脏发病机制的代谢方面。希俄斯乳香(漆树科)树脂在MASLD治疗中显示出有前景的结果。本文应用分子对接技术,测试了希俄斯乳香中的16种化合物作为受体GR、LXRα、LXRβ、PPARα、PPARγ、MC4R、AMPK和VEGFR2的潜在配体,这些受体的上调和下调会干扰MASLD的发生和发展。与已证实的配体相比,观察到的化合物对LXR、GR、MC4R和PPARγ具有中等和高亲和力,而它们对PPARα、AMPK和VEGFR的亲和力则不太明显。希俄斯乳香中的活性化合物组合而非单一分子可能具有更好的能力来控制相互交织的MASLD代谢途径。