Presently, there is a lack of effective disease-modifying drugs for the treatment of Alzheimer’s disease (AD). Uncaria rhynchophylla (UR) and its predominant active phytochemicals alkaloids have been studied to treat AD. This study used a novel network pharmacology strategy to identify UR alkaloids against AD from the perspective of AD pathophysiological processes and identified the key alkaloids for specific pathological process. The analysis identified 10 alkaloids from UR based on high-performance liquid chromatography (HPLC) that corresponded to 127 targets correlated with amyloid-β (Aβ) pathology, tau pathology and Alzheimer disease pathway. Based on the number of targets correlated with AD pathophysiological processes, angustoline, angustidine, corynoxine and isocorynoxeine are highly likely to become key phytochemicals in AD treatment. Among the 127 targets, JUN, STAT3, MAPK3, CCND1, MMP2, MAPK8, GSK3B, JAK3, LCK, CCR5, CDK5 and GRIN2B were identified as core targets. Based on the pathological process of AD, angustoline, angustidine and isocorynoxeine were identified as the key UR alkaloids regulating Aβ production and corynoxine, isocorynoxeine, dihydrocorynatheine, isorhynchophylline and hirsutine were identified as key alkaloids that regulate tau phosphorylation. The findings of this study contribute to a more comprehensive understanding of the key alkaloids and mechanisms of UR in the treatment of AD, as well as provide candidate compounds for drug research and development for specific AD pathological processes.
Alzheimer’s disease (AD) is the most common cause of neurodegenerative dementia and one of the top medical concerns worldwide. Currently, the approved drugs to treat AD are effective only in treating the symptoms, but do not cure or prevent AD. Although the exact causes of AD are not understood, it is recognized that tau aggregation in neurons plays a key role. Chuanxiong Rhizoma (CR) has been widely reported as effective for brain diseases such as dementia. Thus, we explored the protections of CR in AD by a tau pathogenesis–based network pharmacology approach. According to ultra-HPLC with triple quadrupole mass spectrometry data and Lipinski’s rule of five, 18 bioactive phytochemicals of CR were screened out. They were shown corresponding to 127 tau pathogenesis–related targets, among which VEGFA, IL1B, CTNNB1, JUN, ESR1, STAT3, APP, BCL2L1, PTGS2, and PPARG were identified as the core ones. We further analyzed the specific actions of CR-active phytochemicals on tau pathogenesis from the aspects of tau aggregation and tau-mediated toxicities. It was shown that neocnidilide, ferulic acid, coniferyl ferulate, levistilide A, Z-ligustilide, butylidenephthalide, and caffeic acid can be effective in reversing tau hyperphosphorylation. Neocnidilide, senkyunolide A, butylphthalide, butylidenephthalide, Z-ligustilide, and L-tryptophan may be effective in promoting lysosome-associated degradation of tau, and levistilide A, neocnidilide, ferulic acid, L-tryptophan, senkyunolide A, Z-ligustilide, and butylidenephthalide may antagonize tau-mediated impairments of intracellular transport, axon and synaptic damages, and neuron death (especially apoptosis). The present study suggests that acting on tau aggregation and tau-mediated toxicities is part of the therapeutic mechanism of CR against AD.
The dried and ripe fruits of Alpinia oxyphylla and ripe fruits of Alpinia oxyphylla Miquel (AO) have the effects of tonifying kidney-essence and nourishing intelligence and thus have been widely used in treating dementia. Alzheimer’s disease (AD) is a typical form of neurodegenerative dementia with kidney-essence deficiency in Traditional Chinese Medicine (TCM). So far, there is a lack of systematic studies on the biological basis of tonifying kidney-essence and nourishing intelligence and the corresponding phytochemicals. In this study, we investigated the targets of AO in tonifying kidney-essence and nourishing intelligence based on the key pathophysiological processes of neurodegenerative dementia. According to ultra-high-performance liquid chromatography with triple quadrupole mass spectrometry data and Lipinski’s rule of five, 49 bioactive phytochemicals from AO were identified, and 26 of them were found to target 168 key molecules in the treatment of neurodegenerative dementia. Nine phytochemicals of AO were shown to target acetylcholinesterase (ACHE), and 19 phytochemicals were shown to target butyrylcholinesterase (BCHE). A database of neurodegenerative dementia with kidney-essence deficiency involving 731 genes was constructed. Furthermore, yakuchinone B, 5-hydroxy-1,7-bis (4-hydroxy-3-methoxyphenyl) heptan-3-one (5-HYD), oxyhylladiketone, oxyphyllacinol, butyl-β-D-fructopyranoside, dibutyl phthalate, chrysin, yakuchinone A, rhamnetin, and rhamnocitrin were identified as the key phytochemicals from AO that regulate the pathogenesis of neurodegenerative dementia in a multitargeted manner. The approach of studying the pharmacological mechanism underlying the effects of medicinal plants and the biological basis of TCM syndrome may be helpful in studying the translation of TCM.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.