PMID- 28892789 OWN - NLM STAT- MEDLINE DCOM- 20180611 LR - 20191210 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 95 DP - 2017 Nov TI - Thymoquinone-rich fraction nanoemulsion (TQRFNE) decreases Abeta40 and Abeta42 levels by modulating APP processing, up-regulating IDE and LRP1, and down-regulating BACE1 and RAGE in response to high fat/cholesterol diet-induced rats. PG - 780-788 LID - S0753-3322(17)32299-0 [pii] LID - 10.1016/j.biopha.2017.08.074 [doi] AB - Though the causes of Alzheimer's disease (AD) are yet to be understood, much evidence has suggested that excessive amyloid-beta (Abeta) accumulation due to abnormal amyloid-beta precursor protein (APP) processing and Abeta metabolism are crucial processes towards AD pathogenesis. Hence, approaches aiming at APP processing and Abeta metabolism are currently being actively pursued for the management of AD. Studies suggest that high cholesterol and a high fat diet have harmful effects on cognitive function and may instigate the commencement of AD pathogenesis. Despite the neuropharmacological attributes of black cumin seed (Nigella sativa) extracts and its main active compound, thymoquinone (TQ), limited records are available in relation to AD research. Nanoemulsion (NE) is exploited as drug delivery systems due to their capacity of solubilising non-polar active compounds and is widely examined for brain targeting. Herewith, the effects of thymoquinone-rich fraction nanoemulsion (TQRFNE), thymoquinone nanoemulsion (TQNE) and their counterparts' conventional emulsion in response to high fat/cholesterol diet (HFCD)-induced rats were investigated. Particularly, the Abeta generation; APP processing, beta-secretase 1 (BACE1), gamma-secretases of presenilin 1 (PSEN1) and presenilin 2 (PSEN2), Abeta degradation; insulin degrading enzyme (IDE), Abeta transportation; low density lipoprotein receptor-related protein 1 (LRP1) and receptor for advanced glycation end products (RAGE) were measured in brain tissues. TQRFNE reduced the brain Abeta fragment length 1-40 and 1-42 (Abeta40 and Abeta42) levels, which would attenuate the AD pathogenesis. This reduction could be due to the modulation of beta- and gamma-secretase enzyme activity, and the Abeta degradation and transportation in/out of the brain. The findings show the mechanistic actions of TQRFNE in response to high fat and high cholesterol diet associated to Abeta generation, degradation and transportation in the rat's brain tissue. CI - Copyright (c) 2017 Elsevier Masson SAS. All rights reserved. FAU - Ismail, Norsharina AU - Ismail N AD - Nutricosmeceuticals and Nutrigenomics Programme, Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. Electronic address: norsharina@upm.edu.my. FAU - Ismail, Maznah AU - Ismail M AD - Nutricosmeceuticals and Nutrigenomics Programme, Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia; Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. Electronic address: maznahis@upm.edu.my. FAU - Azmi, Nur Hanisah AU - Azmi NH AD - Nutricosmeceuticals and Nutrigenomics Programme, Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. FAU - Bakar, Muhammad Firdaus Abu AU - Bakar MFA AD - Nutricosmeceuticals and Nutrigenomics Programme, Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. FAU - Yida, Zhang AU - Yida Z AD - Nutricosmeceuticals and Nutrigenomics Programme, Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia; Cardiology Department, Affiliated Hospital of Chengde Medical University, Chengde, Hebei 067000, China. FAU - Abdullah, Maizaton Atmadini AU - Abdullah MA AD - Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. FAU - Basri, Hamidon AU - Basri H AD - Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. LA - eng PT - Journal Article DEP - 20170908 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Benzoquinones) RN - 0 (Emulsions) RN - 0 (Low Density Lipoprotein Receptor-Related Protein-1) RN - 0 (Presenilin-2) RN - 0 (RNA, Messenger) RN - 0 (Receptor for Advanced Glycation End Products) RN - EC 3.4.- (Amyloid Precursor Protein Secretases) RN - EC 3.4.23.- (Aspartic Acid Endopeptidases) RN - EC 3.4.23.46 (Bace1 protein, rat) RN - EC 3.4.24.56 (Insulysin) RN - O60IE26NUF (thymoquinone) SB - IM MH - Amyloid Precursor Protein Secretases/*metabolism MH - Amyloid beta-Protein Precursor/*metabolism MH - Animals MH - Aspartic Acid Endopeptidases/*metabolism MH - Benzoquinones/*pharmacology MH - Diet, High-Fat MH - Down-Regulation/drug effects MH - Emulsions/chemistry MH - Gene Expression Regulation/drug effects MH - Hippocampus/drug effects/metabolism MH - Insulysin/*metabolism MH - Low Density Lipoprotein Receptor-Related Protein-1/*metabolism MH - Male MH - Nanoparticles/*chemistry MH - Presenilin-2/metabolism MH - Protein Processing, Post-Translational/drug effects MH - RNA, Messenger/genetics/metabolism MH - Rats, Sprague-Dawley MH - Receptor for Advanced Glycation End Products/*metabolism MH - *Up-Regulation/drug effects OTO - NOTNLM OT - Amyloid-beta OT - High fat/cholesterol diet OT - Nanoemulsion OT - Nigella sativa OT - Thymoquinone OT - Thymoquinone-rich fraction EDAT- 2017/09/12 06:00 MHDA- 2018/06/12 06:00 CRDT- 2017/09/12 06:00 PHST- 2017/05/10 00:00 [received] PHST- 2017/08/02 00:00 [revised] PHST- 2017/08/14 00:00 [accepted] PHST- 2017/09/12 06:00 [pubmed] PHST- 2018/06/12 06:00 [medline] PHST- 2017/09/12 06:00 [entrez] AID - S0753-3322(17)32299-0 [pii] AID - 10.1016/j.biopha.2017.08.074 [doi] PST - ppublish SO - Biomed Pharmacother. 2017 Nov;95:780-788. doi: 10.1016/j.biopha.2017.08.074. Epub 2017 Sep 8.