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Molecular docking of 234 unique compounds identified in the softwood bark (W set) is presented with a focus on their inhibition potential to the main protease of the SARS-CoV-2 virus 3CL pro (6WQF). The docking results are compared with the docking results of 866 COVID19-related compounds (S set). Furthermore, machine learning (ML) prediction of docking scores of the W set is presented using the S set trained TensorFlow, XGBoost, and SchNetPack ML approaches. Docking scores are evaluated with the Autodock 4.2.6 software. Four compounds in the W set achieve a docking score below -13 kcal/mol, with (+)-lariciresinol 9'-p-coumarate (CID 11497085) achieving the best docking score (-15 kcal/mol) within the W and S sets. In addition, 50% of W set docking scores are found below -8 kcal/mol and 25% below -10 kcal/mol. Therefore, the compounds identified in the softwood bark, show potential for antiviral activity upon extraction or further derivatization. The W set molecular docking studies are validated by means of molecular dynamics (five best compounds). The solubility (Log S, ESOL) and druglikeness of the best docking compounds in S and W sets are compared to evaluate the pharmacological potential of compounds identified in softwood bark., (Copyright © 2022. Published by Elsevier B.V.)

Senkyunolide H (SNH) is a phthalide isolated from the rhizome of Ligusticum chuanxiong Hort. that has been reported to have several pharmacological activities, including anti-atherosclerotic, antiproliferative, and cytoprotective effects. In this study, we investigated the neuroprotective effects and potential mechanisms of SNH against 1-methyl-4-phenylpyridinium (MPP + )-induced oxidative stress. We demonstrated that SNH pretreatment significantly attenuated MPP + -induced neurotoxicity and apoptosis in PC12 cells. In addition, SNH attenuated the effect of MPP + on the expression of the pro-apoptotic factors Bax and caspase-3. Meanwhile, SNH prevented oxidative stress by reducing reactive oxygen species generation, mitochondrial membrane potential loss, cytochrome C release, and malondialdehyde levels while increasing antioxidant enzyme activity (e.g., superoxide dismutase, catalase, and glutathione peroxidase). In addition, SNH inhibited nuclear accumulation of nuclear factor-κB and c-Jun N-terminal kinase and phosphorylation p38 mitogen-activated protein kinases (MAPKs). Overall, this investigation provides novel evidence that SNH exerts neuroprotective effects via the ROS-mediated MAPK pathway and represents a potential preventive or therapeutic agent for neuronal disorders., (Copyright © 2018 Elsevier B.V. All rights reserved.)