Permeability of Hypogymnia physodes Extract Component-Physodic Acid through the Blood-Brain Barrier as an Important Argument for Its Anticancer and Neuroprotective Activity within the Central Nervous System

大叶木犀提取物成分大叶木犀酸透过血脑屏障的能力是其在中枢神经系统内具有抗癌和神经保护作用的重要论据

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作者:Elżbieta Studzińska-Sroka, Aleksandra Majchrzak-Celińska, Przemysław Zalewski, Dominik Szwajgier, Ewa Baranowska-Wójcik, Marcin Żarowski, Tomasz Plech, Judyta Cielecka-Piontek

Abstract

Lichen secondary metabolites are characterized by huge pharmacological potential. Our research focused on assessing the anticancer and neuroprotective activity of Hypogymnia physodes acetone extract (HP extract) and physodic acid, its major component. The antitumor properties were evaluated by cytotoxicity analysis using A-172, T98G, and U-138 MG glioblastoma cell lines and by hyaluronidase and cyclooxygenase-2 (COX-2) inhibition. The neuroprotective potential was examined using COX-2, tyrosinase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) activity tests. Moreover, the antioxidant potential of the tested substances was examined, and the chemical composition of the extract was analyzed. For physodic acid, the permeability through the blood-brain barrier using Parallel Artificial Membrane Permeability Assay for the Blood-Brain Barrier assay (PAMPA-BBB) was assessed. Our study shows that the tested substances strongly inhibited glioblastoma cell proliferation and hyaluronidase activity. Besides, HP extract diminished COX-2 and tyrosinase activity. However, the AChE and BChE inhibitory activity of HP extract and physodic acid were mild. The examined substances exhibited strong antioxidant activity. Importantly, we proved that physodic acid crosses the blood-brain barrier. We conclude that physodic acid and H. physodes should be regarded as promising agents with anticancer, chemopreventive, and neuroprotective activities, especially regarding the central nervous system diseases.

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