A network pharmacology approach to identify the mechanisms and molecular targets of curcumin against Alzheimer disease

Abstract

Background: Alzheimer disease (AD) is a degenerative brain disease, which may lead to severe memory loss and other cognitive disorders. However, few effective drugs are available in the clinic at present. Curcumin, a major ingredient of traditional Chinese medicine, Curcuma Longa, has various pharmacological activities. Therefore, exploring clinical drugs based on the inhibition of AD pathological features is imperative. Methods: First, we utilized the HERB database and Swisstarget Prediction database to get the related targets of curcumin and intersected with the AD targets. The intersection targets were used to construct the protein-protein interaction network and performed gene ontology and kyoto encyclopedia of genes and genomes analyses. Further, we obtained targets of curcumin against AD-related tau and aβ pathology via the AlzData database. These targets were applied to perform GEO and receiver operating characteristic analyses. Finally, the reliability of the core targets was evaluated using molecular docking technology. Results: We identified 49 targets of curcumin against AD, and kyoto encyclopedia of genes and genomes pathway enrichment analysis demonstrated that the Alzheimer disease pathway (has05010) was significantly enriched. Even more, we obtained 16 targets of curcumin-related Aβ and tau pathology. Among these targets, 8 targets involved the Alzheimer disease pathway and the biological process analyses showed that positive regulation of cytokine production (GO:0001819) was significantly enriched. Bioinformatic analyses indicated that HMOX1, CSF1R, NFKB1, GSK3B, BACE1, AR, or PTGS1 expression was significantly different compared to the control group in the AD patients. Finally, molecular docking studies suggested these genes have a good binding force with curcumin. Conclusions: In this study, we identified curcumin exerted the effect of treating AD by regulating multitargets and multichannels through the method of network pharmacology.

Therapeutic considerations of bioactive compounds in Alzheimer's disease and Parkinson's disease: Dissecting the molecular pathways

“…and 150-300 mg/kg oral gavage per day treatment (Fikry et al, 2022;Rajeswari & Sabesan, 2008;Sharma & Nehru, 2018;Zheng et al, 2017). Also, in clinical trials of AD and PD patients, curcumin is reported to be used at doses from 0.08 to 4 g daily by oral administration (Ghodsi et (Maiti et al, 2021;Tello-Franco et al, 2013;Wu et al, 2022). Similar findings were also demonstrated by in vivo studies along with the improvement of memory functions in mice models of AD (Yang et al, 2005;Zheng et al, 2017).…”

“…Also, in clinical trials of AD and PD patients, curcumin is reported to be used at doses from 0.08 to 4 g daily by oral administration (Ghodsi et al, 2022; Parikh et al, 2008; Ringman et al, 2012). The inhibitory potential of curcumin upon AChE, Aβ fibril formation and BACE1 activity has been demonstrated by several in silico and in vitro studies (Maiti et al, 2021; Tello‐Franco et al, 2013; Wu et al, 2022). Similar findings were also demonstrated by in vivo studies along with the improvement of memory functions in mice models of AD (Yang et al, 2005; Zheng et al, 2017).…”

Selected Plant-Derived Polyphenols as Potential Therapeutic Agents for Peripheral Artery Disease: Molecular Mechanisms, Efficacy and Safety

“…Curcumin has been widely evaluated with respect to the modulation of endothelial function [ 102 ]. Curcumin also presents a neuroprotective potential in the pathogenesis of Alzheimer’s disease [ 103 , 104 , 105 ]. The many described biological activities of curcumin have been linked to its chemical instability that leads to the rapid autoxidation responsible for its antioxidant behavior.…”

Intranasally Co-administered Berberine and Curcumin Loaded in Transfersomal Vesicles Improved Inhibition of Amyloid Formation and BACE-1

“… 10 CUR can more precisely target AD cellular mechanisms and processes that control the production of cytokines. 11 CUR is extracted from the rhizomes of turmeric, which has long been used as a food spice in Southeast Asian countries. 12 The neuroprotection effect of BBR is associated with the inhibition of Akt/ERK1/2 survival/apoptotic signaling pathway/GSK3β/caspase-3 activity and the Jun aminoterminal kinase pathway.…”

“…When used separately or together, CUR and BBR significantly improve the management of AD . CUR can more precisely target AD cellular mechanisms and processes that control the production of cytokines . CUR is extracted from the rhizomes of turmeric, which has long been used as a food spice in Southeast Asian countries .…”