Genetic variants in FADS1 and ELOVL2 increase level of arachidonic acid and the risk of Alzheimer's disease in the Tunisian population

Hammouda, Souha; Ghzaiel, Imen; Khamlaoui, Wided; Hammami, S.; Mhenni, Samia Younes; Samet, S.; Hammami, Mohamed; Zarrouk, Amira

doi:10.1016/j.plefa.2020.102159

Cited by 28 publications

(22 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inflammatory mediators are chemical factors that participate in and mediate the inflammatory response in Alzheimer's disease. Studies have found that elevated serum arachidonic acid levels increase the risk of AD [ 11 , 12 ]. In this study, compared with the blank group, the content of PGH2 in the model group was lower than that in the blank group.…”

Section: Discussionmentioning

confidence: 99%

Explore the Therapeutic Composition and Mechanism of Schisandra chinensis-Acorus tatarinowii Schott on Alzheimer’s Disease by Using an Integrated Approach on Chemical Profile, Network Pharmacology, and UPLC-QTOF/MS-Based Metabolomics Analysis

Chen

Hao

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Background. Alzheimer’s disease places a heavy economic burden to healthcare systems around the world. However, the effective treatments are still lacking. Traditional Chinese medicines (TCM) of Schisandra chinensis and Acorus tatarinowii Schott have the pharmacological effects of sedation and neuroprotection and have been clinically proven to be effective in the treatment of AD. However, their main anti-Alzheimer’s compounds and functional mechanisms remain unclear. Purpose. To elucidate the main therapeutic components and possible mechanisms of Sc-At in AD using a comprehensive strategy combining metabolomics and network pharmacology. Methods. First, the UPLC-QTOF/MS method was used to identify the main chemical constituents of Schisandra chinensis and Acorus tatarinowii Schott alcohol extracts in vitro and in vivo. Secondly, the theoretical active ingredients, targets, and pathways of Sc-At for AD treatment were predicted by network pharmacology methods. Finally, plasma metabolomics were detected by UPLC-QTOF/MS to analyze the differential metabolites and metabolic pathways related to Sc-At. Based on the analyses above, the anti-AD mechanism of Sc-At was explored. Results. A total of 95 chemical components were identified in Sc-At extracts in vitro, and 34 prototype drug components were detected in rat plasma; network pharmacology screening identified 14 drug components in line with the principle of Lipinski, of which 10 were present for in vitro drug composition analysis. For these 10 components, 58 AD disease targets were predicted, and 85 AD-related KEGG signaling pathways were enriched. Six core biomarkers of Sc-At (cis-8,11,14,17-eicosatetraenoic acid, prostaglandin H2, sphingosine 1-phosphate, enol-phenylpyruvate, 3-methoxytyrosine, and pristanoyl-CoA) were regulated to a normal state during the treatment of AD. Conclusion. The mechanism of Sc-At for the treatment of AD can be achieved by the effect of the 10 compounds of Sc-At on TNF, MAPK8, MAPK14, PTGS1, and other targets, thereby affecting arachidonic acid metabolism, neurotransmitters, and sphingolipid metabolism.

show abstract

Section: Discussionmentioning

confidence: 99%

Explore the Therapeutic Composition and Mechanism of Schisandra chinensis-Acorus tatarinowii Schott on Alzheimer’s Disease by Using an Integrated Approach on Chemical Profile, Network Pharmacology, and UPLC-QTOF/MS-Based Metabolomics Analysis

Chen

Hao

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…To date, many previous findings had supported that more than 20% variability of both n-6 and n-3 PUFAs were associated with the genotypes of SNPs in the Fads1 , Fads2 , Fads3 , Elovl2 and Elovl5 [ 22 ]. However, the previous studies regarding the homozygous influences of various SNPs on the profiles of n-6 and n-3 PUFAs had produced the conflicting results, in which some had proved there were significant associations between the genotypes of SNPs and the profiles of PUFAs, especially EPA and DHA, in the colostrum, plasma and other tissues [ 23 – 28 ], the others did not find the above related correlations [ 29 , 30 ]. Exactly, Xie and Innis observed there were significantly lower proportion of ALA, but not DHA among the subjects with the minor allele homozygotes of Fads1/ rs174553 [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Maternal DHA-rich n-3 PUFAs supplementation interacts with FADS genotypes to influence the profiles of PUFAs in the colostrum among Chinese Han population: a birth cohort study

Chen

Song

et al. 2022

Nutr Metab (Lond)

View full text Add to dashboard Cite

Background The single nucleotide polymorphisms (SNPs) in the fatty acid desaturases and elongases might associate with the endogenous synthesis of polyunsaturated fatty acids (PUFAs). However, the related epidemiological evidence is still conflicting. So we aimed to clearly evaluate the interactions between maternal DHA-rich n-3 PUFAs supplementation and the known 26 SNPs on the profiles of PUFAs in the colostrum using a Chinese birth cohort. Methods Totally, 1050 healthy mother-infant pairs were enrolled in this study at gestational 6–8 weeks when they established their pregnancy files at Fuxing Hospital affiliated to Capital Medical University in Beijing from January to December 2018. Meanwhile, their venous blood samples were obtained for DNA extraction to detect the genotypes of SNPs in the Fads1, Fads2, Fads3, Elovl2 and Elovl5 using the Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry. Then the colostrum samples were collected to determine the profiles of PUFAs by gas chromatography. Results Maternal DHA-rich n-3 PUFAs supplementation from the early and middle pregnancy could reduce the infant BMI at birth, and impact the profiles of PUFAs in the colostrum, as higher n-3 PUFAs (EPA, DHA, DHA/ALA and DHA/EPA), lower n-6 PUFAs (AA and AA/LA) and ∑-6/n-3ΣPUFAs. Moreover, there were significant correlations between multiple SNPs and the profiles of n-6 PUFAs (rs76996928 for LA, rs174550, rs174553 and rs174609 for AA, rs174550 and rs76996928 for AA/LA) and n-3 PUFAs in the colostrum (rs174448, rs174537, rs174550, rs174553, rs174598, rs3168072, rs174455 and rs174464 for ALA, rs174550, rs174553 and rs174598 for EPA, rs174455 and rs174464 for DHA, rs174448 and rs3168072 for DHA/EPA) using the multiple linear regressions by adjusting the maternal age, gestational week, mode of delivery, infant sex and BMI at birth, and all these above significant SNPs had the cumulative effects on the profiles of PUFAs. Furthermore, the pairwise comparisons also showed the meaningful interactions between maternal DHA-rich n-3 PUFAs supplementation and related genotypes of SNPs (rs76996928 for LA, rs174598 for EPA, rs174448 for DHA and DHA/EPA) on the contents of PUFAs in the colostrum. Conclusions Results from this birth cohort study proved that the pregnant women with the following SNPs such as Fads3 rs174455 T, Fads3 rs174464 A and Fads1 rs174448 G alleles should pay more attention on their exogenous DHA supplementation from the early and middle pregnancy for the blocked endogenous synthesis. Trial registration: This study was approved by the Ethics Committee of Beijing Pediatric Research Institution, Beijing Children’s Hospital affiliated to Capital Medical University (2016–08), which was also registered at the website of http://www.chictr.org.cn/showproj.aspx?proj=4673 (No: ChiCTR-OCH-14004900).

show abstract

“…Several PUFAs such as DHA and AA are being studied for the development of new treatments against NDs and neurodegeneration [49,50]. Punicic acid (18:3, ∆9cis, 11trans, 13cis, n-5) is a promising candidate whose mechanism of action is yet to be completely understood.…”

Section: Aging Mechanismmentioning

confidence: 99%

Punicic Acid and Its Role in the Prevention of Neurological Disorders: A Review

Guerra-Vázquez

Martínez-Ávila

Guajardo‐Flores

et al. 2022

Foods

View full text Add to dashboard Cite

Millions of people worldwide are affected by neurodegenerative diseases (NDs). NDs are characterized by progressive damage and death of nerve cells accompanied by high levels of inflammatory biomarkers and oxidative stress conditions. Punicic acid, the main bioactive component of pomegranate (Punica granatum) seed oil, is an omega-5 isomer of conjugated α-linoleic acid that has shown strong anti-oxidative and anti-inflammatory effects that contributes towards its positive effect against a wide arrange of diseases. Punicic acid decreases oxidative damage and inflammation by increasing the expression of peroxisome proliferator-activated receptors. In addition, it can reduce beta-amyloid deposits formation and tau hyperphosphorylation by increasing the expression of GLUT4 protein and the inhibition of calpain hyperactivation. Microencapsulated pomegranate, with high levels of punicic acid, increases antioxidant PON1 activity in HDL. Likewise, encapsulated pomegranate formulations with high levels of punicic acid have shown an increase in the antioxidant PON1 activity in HDL. Because of the limited brain permeability of punicic acid, diverse delivery formulations have been developed to enhance the biological activity of punicic acid in the brain, diminishing neurological disorders symptoms. Punicic acid is an important nutraceutical compound in the prevention and treatment of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease.

show abstract

Genetic variants in FADS1 and ELOVL2 increase level of arachidonic acid and the risk of Alzheimer's disease in the Tunisian population

Cited by 28 publications

References 90 publications

Explore the Therapeutic Composition and Mechanism of Schisandra chinensis-Acorus tatarinowii Schott on Alzheimer’s Disease by Using an Integrated Approach on Chemical Profile, Network Pharmacology, and UPLC-QTOF/MS-Based Metabolomics Analysis

Explore the Therapeutic Composition and Mechanism of Schisandra chinensis-Acorus tatarinowii Schott on Alzheimer’s Disease by Using an Integrated Approach on Chemical Profile, Network Pharmacology, and UPLC-QTOF/MS-Based Metabolomics Analysis

Maternal DHA-rich n-3 PUFAs supplementation interacts with FADS genotypes to influence the profiles of PUFAs in the colostrum among Chinese Han population: a birth cohort study

Punicic Acid and Its Role in the Prevention of Neurological Disorders: A Review

Contact Info

Product

Resources

About