Therapeutic Potential of Vitamin D and Curcumin in an In Vitro Model of Alzheimer Disease

Abstract

Background: Alzheimer disease is a progressive neurodegenerative disease, affecting a very high proportion of the aging population. Several studies have demonstrated that one of the main contributors to this disease is oxidative stress (OS), which causes peroxidation of protein, lipids, and DNA resulting in the formation of advanced glycosylated end products (AGE) in the brain tissues. These AGE are usually associated with the amyloid β (Aβ), which could further aggravate its toxicity and its clearance. Antioxidants counteract the deterioration caused by OS. Objective: We aimed to evaluate the effect of vitamin D3 and curcumin on primary cortical neuronal cultures exposed to Aβ1-42 toxicity for different time periods. Methods: Primary cortical neuronal cultures were set up and exposed to Aβ1-42 for up to 72 hours. Cell viability was studied by 3[4,5-dimethylthiazole-2-yl]-2,5-dipheyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assay. Biochemical assays for OS such as lipid peroxidation, reduced Glutathione(GSH), Glutathione S-transferase (GST), catalase, and superoxide dismutase (SOD) were conducted. Sandwich enzyme-linked immunosorbent assay (ELISA) was used to study the neurotrophic growth factor (NGF) expression. Results: Treatments with Aβ1-42 caused an elevation in lipid peroxidation products, which were ameliorated in the presence of vitamin D3 and curcumin. Both enzymatic (GST, catalase, and SOD) and nonenzymatic antioxidants (reduced GSH) were raised significantly in the presence of vitamin D3 and curcumin, which resulted in the better recovery of neuronal cells from Aβ1-42 treatment. Treatment with vitamin D3 and curcumin also resulted in the upregulation of NGF levels. Conclusions: This study suggests that vitamin D3 and curcumin can be a promising natural therapy for the treatment of Alzheimer disease.

Can Brain Health Be Supported by Vitamin D-Based Supplements? A Critical Review

“…“Inflammaging” may be associated with an increase in incompetent memory T cells and inflammatory cytokines produced by macrophages, whereas the defective clearance of amyloid-beta Aβ1–42 may be related to the defective transcription of immune genes necessary for phagocytosis, β-1,4-mannosyl-glycoprotein, 4-β-N-acetylglucosaminyltransferase, and Toll-like receptors. The approaches used for re-balancing Aβ immunity and inflammation are being pursued in animal models and the peripheral blood mononuclear cells of patients [ 179 , 181 , 182 , 183 ]. Increased inflammation may represent the “first hit” and defective transcription of immune genes represent the “second hit” in the pathogenesis of AD.…”

“…Gagliardo et al conducted studies that showed that treatment with curcumin may decrease the predisposition of Aβ to accumulate in cells. Although the role of Aβ 1-42 as a potential causative agent in the pathophysiology of neurodegenerative disease has been documented extensively, the exact molecular mechanisms and their biochemical effect on brain tissues are not very clear [ 179 , 183 ]. An in vitro experiment by Alamro et al on primary neuronal cultures investigated the effect of Aβ 1-42 on the primary neuronal cells and the role of vitamin D3 or curcumin used as a natural therapy for AD treatment.…”

“…VDR stimulation induced by curcuminoids could shift this balance to and increase the inhibitory activity of VDRs on NF-κB [ 189 ]. Another study on primary cortical neuronal cells demonstrated that Aβ 1-42 caused a significant reduction in mitochondrial health or mitophagy, but treatment with vitamin D3 and curcuminoids could overturn this outcome [ 183 ]. The oxidative state of the primary cortical neuronal cells is one of the earliest hallmarks of neurodegenerative diseases [ 190 ].…”

“…These highly reactive electrophilic aldehydes are MDA and 4-hydroxy-2-nonenal (HNE) [ 193 ]. Alamro et al [ 183 ] showed that a significant amount of MDA in the Aβ 1–42 treated cultures produced high levels of these aldehydes, but the presence of vitamin D3 and curcumin in the culture categorically reduced its formation [ 190 ]. The synergistic effect of vitamin D3 and curcumin significantly increased the catalase enzyme expression.…”

“…These results further reiterated the beneficial therapeutic effect of both vitamin D3 and curcumin in the treatment of AD. The combined effect of vitamin D3 and curcumin has also been reported to accelerate the clearance of β-amyloid by activating the immune cells [ 183 ]. These results have been confirmed by SOD enzyme activity analysis, where the activity was significantly reduced with the treatment of Aβ 1–42 to the cells, but the synergistic effect of both vitamin D3 and curcumin has a positive effect on up-regulating SOD enzyme activity.…”