1. A comprehensive investigation of Clerodendrum Infortunatum Linn. using LC-QTOF-MS/MS metabolomics as a promising anti-alzheimer candidate.
- Author
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Atef F, Abdelkawy MA, Eltanany BM, Pont L, Fayez AM, Abdelhameed MF, Benavente F, Younis IY, and Otify AM
- Subjects
- Animals, Rats, Male, Chromatography, Liquid methods, Acetylcholinesterase metabolism, Scopolamine, Hippocampus drug effects, Hippocampus metabolism, Disease Models, Animal, Cholinesterase Inhibitors pharmacology, Cholinesterase Inhibitors therapeutic use, Alzheimer Disease drug therapy, Alzheimer Disease metabolism, Clerodendrum chemistry, Plant Extracts pharmacology, Plant Extracts therapeutic use, Plant Extracts chemistry, Metabolomics methods, Tandem Mass Spectrometry methods
- Abstract
Alzheimer's disease (AD) poses a global health challenge, demanding innovative approaches for effective treatments. Clerodendrum infortunatum Linn. (Lamiaceae) is a shrub traditionally used as a medicinal plant to treat inflammation, skin diseases, and bronchitis. This study aims to identify the main bioactive metabolites in C. infortunatum using LC-QTOF-MS/MS and investigate its potential in protecting against cognitive decline in rats with scopolamine-induced AD disease. Metabolite profiling was performed on the methanol extract of the plant's aerial parts using LC-QTOF-MS/MS. The inhibitory activity of the acetylcholinesterase enzyme was measured in vitro. To evaluate the cognitive effects, the methanol extract was orally administered at three doses (100, 200, and 400 mg/kg) to scopolamine-induced AD rats, and their cognitive functions were assessed using the novel object recognition test. Additionally, acetylcholinesterase enzyme activity, as well as the levels of acetylcholine, dopamine, noradrenaline, glutathione, malondialdehyde, tumor necrosis factor-α, interleukin-1β, and amyloid-β in the rat hippocampus, were measured using ELISA, followed by histopathological evaluation. A total of 79 metabolites, spanning various chemical classes, such as organic acids, phenolic acids, phenylpropanoids and phenylethanoids, flavonoids, coumarins, other phenolics, and fatty acids and their derivatives, were identified. The results showed that the extract promoted enhanced cognitive functions in the novel object recognition test. Scopolamine administration significantly altered the acetylcholinesterase enzyme activity and biomarker levels in the rat's hippocampus. However, treatment with C. infortunatum at 200 and 400 mg/kg almost restored these neurotransmitter levels to normal, which was further confirmed by histopathological analysis. This study demonstrates the therapeutic potential of C. infortunatum in mitigating cognitive decline in AD, with its first metabolite profiling revealing a range of bioactive compounds. The extract improved cognitive function in scopolamine-induced AD rats, restored acetylcholinesterase activity, normalized neurotransmitter levels, and reduced oxidative stress and inflammation. These findings suggest that C. infortunatum is a promising candidate for the development of natural therapies targeting AD., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The experiments adhered to the “Guide for the Care and Use of Laboratory Animals” published by the US National Institutes of Health (NIH Publication No 85–23, 2011). Approval was granted by the Research Ethics Committee of the Faculty of Pharmacy of Cairo University (approval code: MP (3118)). ARRIVE guidelines: The study is reported in accordance with ARRIVE guidelines. A statement naming the person who identified the plant: The aerial parts of C. infortunatum were authenticated by Agriculture Engineer Therese Labib, a plant taxonomy consultant of the Ministry of Agriculture (Giza, Egypt). Voucher specimen statement: The plant material was collected with permission in compliance with national guidelines from the Agriculture Research Center, Giza, Egypt at “9 Cairo University Road, Giza District, Giza Governorate”. Samples of the plant material were deposited at the herbarium of the Faculty of Pharmacy, Cairo University, Cairo, Egypt (sample No.10.3.2021)., (© 2024. The Author(s).)
- Published
- 2025
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