Unveiling Lobophytum sp. the neuroprotective potential of Parkinson's disease through multifaceted mechanisms, supported by metabolomic analysis and network pharmacology.

Autor: Bakhsh HT; Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, 21589, Jeddah, Saudi Arabia., Abu-Baih DH; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Deraya University, New Minia City, Minia, 61111, Egypt.; Deraya Center for Scientific Research, Deraya University, New Minia City, Minia, 61111, Egypt., Abu-Baih RH; Drug Information Center, Faculty of Pharmacy, Minia University, Minia, Egypt., Saber EA; Department of Medical Science, Histology and Cell Biology, Faculty of Pharmacy, Deraya University, New Minia City, Minia, 61111, Egypt., Altemani FH; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, 71491, Tabuk, Saudi Arabia., Algehainy NA; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, 71491, Tabuk, Saudi Arabia., Alanazi MA; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, 71491, Tabuk, Saudi Arabia., Mokhtar FA; Fujairah Research Centre, Sakamkam Road, Fujairah, United Arab Emirates.; Department of Pharmacognosy, Faculty of Pharmacy, El Saleheya El Gadida University, El Saleheya El Gadida, Sharkia, 44813, Egypt., Bringmann G; Institute of Organic Chemistry, University of Würzburg, Am Hubland, 97074, Würzburg, Germany. gerhard.bringman@uni-wuerzburg.de., Abdelmohsen UR; Deraya Center for Scientific Research, Deraya University, New Minia City, Minia, 61111, Egypt. usama.ramadan@mu.edu.eg.; Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt. usama.ramadan@mu.edu.eg., El-Mordy FMA; Department of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, 11754, Egypt. fatmamohammed.pharmg@azhar.edu.eg.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Sep 18; Vol. 14 (1), pp. 21810. Date of Electronic Publication: 2024 Sep 18.
DOI: 10.1038/s41598-024-66781-9
Abstrakt: A main feature of neurodegenerative diseases is the loss of neurons. One of the most prevalent neurodegenerative illnesses is Parkinson disease (PD). Although several medications are already approved to treat neurodegenerative disorders, most of them only address associated symptoms. The main aim of the current study was to examine the neuroprotective efficacy and underlying mechanism of Lobophytum sp. crude extract in a rotenone-induced rat model of neurodegeneration mimicking PD in humans. The influence of the treatment on antioxidant, inflammatory, and apoptotic markers was assessed in addition to the investigation of TH (tyrosine hydroxylase) immunochemistry, histopathological changes, and α-synuclein. Metabolomic profiling of Lobophytum sp. crude extract was done by using High-Resolution Liquid Chromatography coupled with Mass Spectrometry (HR-LC-ESI-MS), which revealed the presence of 20 compounds (1-20) belonging to several classes of secondary metabolites including diterpenoids, sesquiterpenoids, steroids, and steroid glycosides. From our experimental results, we report that Lobophytum sp. extract conferred neuroprotection against rotenone-induced PD by inhibiting ROS formation, apoptosis, and inflammatory mediators including IL-6, IL-1β, and TNF-α, NF-кB, and subsequent neurodegeneration as evidenced by decreased α-synuclein deposition and enhanced tyrosine hydroxylase immunoreactivity. Moreover, a computational network pharmacology study was performed for the dereplicated compounds from Lobophytum sp. using PubChem, SwissTarget Prediction, STRING, DisGeNET, and ShinyGO databases. Among the studied genes, CYP19A1 was the top gene related to Parkinson's disease. Dendrinolide compounds annotated a high number of parkinsonism genes. The vascular endothelial growth factor (VEGF) pathway was the top signaling pathway related to the studied genes. Therefore, we speculate that Lobophytum sp. extract, owing to its pleiotropic mechanisms, could be further developed as a possible therapeutic drug for treating Parkinson's disease.
(© 2024. The Author(s).)
Databáze: MEDLINE
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