Alzheimer's disease (AD) is the most common dementia disorder of later life. Although there might be various different triggering events in the early stages of the disease, they appear to converge on a few characteristic final pathways in the late stages, characterized by inflammation and neurodegeneration. Here, we review the hypothesis that advanced glycation end products (AGEs), which reflect carbonyl stress, an imbalance between the production of reactive carbonyl compounds and their detoxification, can serve as biomarkers for the progression of disorder. AGE modification may explain many of the neuropathological and biochemical features of AD, such as extensive protein cross-linking shown as amyloid plaques and neurofibrillary tangles, inflammation, oxidative stress and neuronal cell death. Although accumulation of AGEs is a normal feature of aging, it appears to be significantly accelerated in AD. We suggest that higher AGE concentrations in brain tissue and in cerebrospinal fluid might be able to distinguish between normal aging and AD.

Advanced glycation endproducts (AGEs) accumulate on protein deposits including the beta-amyloid plaques in Alzheimer's disease. AGEs interact with the "receptor for advanced glycation endproducts", and transmit their signals using intracellular reactive oxygen species as second messengers. Ultimately, AGEs induce the expression of a variety of pro-inflammatory markers including the tumor necrosis factor (TNF-alpha) and inducible nitric oxide (NO) synthase. Antioxidants that act intracellularly, including polyphenols, have been shown to scavenge these "signaling" reactive oxygen species, and thus perform in an anti-inflammatory capacity. This study tested the pure compounds apigenin and diosmetin as well as extracts from silymarin, uva ursi (bearberry) and green olive leaf for their ability to attenuate AGE-induced NO and TNF-alpha production. All five tested samples inhibited BSA-AGE-induced NO production in a dose-dependent manner. Apigenin and diosmetin were most potent, and exhibited EC(50) values approximately 10 microM. In contrast, TNF-alpha expression was only reduced by apigenin, diosmetin and silymarin; not by the bearberry and green olive leaf extracts. In addition, the silymarin and bearberry extracts caused significant cell death at concentrations >or=10 microg/mL and >or=50 microg/mL, respectively. In conclusion, we suggest that plant-derived polyphenols might offer therapeutic opportunities to delay the progression of AGE-mediated and receptor for advanced glycation endproducts-mediated neuro-inflammatory diseases including Alzheimer's disease.

Destabilization of oil-water emulsion in coconut milk, in the production of virgin coconut oil (VCO), ABSTRAKDestabilisasi emulsi minyak-air pada santan kelapa yang menghasilkan virgin coconut oil (VCO) dapat dipercepat dengan bantuan fermentasi bakteri asam laktat. Penelitian ini bertujuan untuk mendapatkan karakteristik fisikokimia dan antibakteri yang dimiliki oleh VCO asal kelapa hibrida dengan metode fermentasi Lactobacillus casei galur komersial Yakult® dan Lactobacillus plantarum isolat mandai dan blondo kelapa terhadap Escherichia coli dan Staphylococcus aureus. Uji fisikokimia meliputi volume, berat jenis, kadar air, bilangan penyabunan, bilangan peroksida, dan uji asam lemak bebas. Uji aktivitas antibakteri dilakukan dengan metode sumur difusi dengan kloramfenikol sebagai kontrol positif. L. casei menghasilkan VCO-BAL dalam persentase volume secara signifikan (p<0.05) lebih besar (34.5% v/v) dibandingkan VCO-BAL asal L. plantarum asal isolat mandai (29.5% v/v) dan blondo kelapa (25.3% v/v). VCO-BAL asal L. casei memiliki berat jenis paling ringan (0.84±0.04 g.mL -1 ). Rerata kadar air (0.03-0.05%), bilangan penyabunan (161.3-163.6), bilangan peroksida (0.53-0.86), bilangan asam lemak bebas (0.11-0.12%) dari VCO-BAL tidak berbeda signifikan (p>0.05) dibandingkan VCO non BAL. VCO-BAL asal L. plantarum isolat blondo kelapa tidak menunjukkan aktivitas antibakteri yang signifikan (p>0.05) berbeda dibandingkan dengan VCO non BAL. VCO-BAL asal L. casei secara signifikan (p<0.05) memiliki zona penghambatan terbaik terhadap E. coli, yaitu 6.45±0.50 mm (58.3% dari kontrol positif) dan S. aureus, yaitu 5.23±0.40 (51.3% dari kontrol positif), dibandingkan kedua VCO-BAL asal L. plantarum. Aktivitas antibakteri VCO-BAL diduga kuat dipengaruhi oleh bakteriosin hidrofobik.

Around 7% of the study population aged 45-65 years reported the use of SSRIs or SNRIs, decreasing to 5% above 70 years of age. It is of concern that some individuals used an SSRI concurrently with St John's wort.

activity of β-carotene loaded nanostructured lipid carrier (NLC) from binary mixtures of palm stearin and palm olein, HELIYON, https://doi.org/10.1016/j.heliyon.2022.e08913. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Advanced glycation end products (AGEs) are involved in age-related diseases, including the complications of diabetes and chronic renal impairment with arterial stiffening. Alagebrium chloride (ALT-711) is an AGE-lowering agent with beneficial effects in renal structural and functional parameters in diabetes, decreased diabetes-accelerated atherosclerosis, and age-related myocardial stiffening. ALT-711 exhibits a structural homology to thiamine, and it was suggested to interfere with thiamine metabolism. Thiamine is converted to thiamine diphosphate (TDP) by thiamine diphosphokinase (TDPK). TDP is a cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase and transketolase. A decreased activity of these enzymes due to TDP deficiency results in disorders such as beriberi and Wernicke-Korsakoff syndrome. Therefore, we investigated whether ALT-711 is an inhibitor of TDPK. Molecular modeling studies showed that ALT-711 fits into the thiamine-binding pocket of TDPK, and there are three interactions between the thiazolium ring and the enzyme, as well as parallel stacking between the phenyl ring and the indole ring of Trp222B. Enzyme kinetic experiments also showed that ALT-711 dose-dependently decreased TDPK activity with K(i)s, calculated by different experiments and fitting models ranging from 0.88 to 1.09 mM. Fitting of the kinetic data favored mixed-mode inhibition with a major role for competitive inhibition. In summary, our results suggest that ALT-711 is a low-affinity inhibitor of TDPK, but is unlikely to interfere with thiamine metabolism at therapeutic concentrations. However, when new AGE-crosslink breakers based on thiamine are designed, care should be taken that they do not act as more potent competitive inhibitors than ALT-711.

Background: Mandai, the fermented inner skin of cempedak (Artocarpus integer), may have further use as an industrial ingredient while maintaining its antioxidative capacity. The starter culture of Lactobacillus casei may induce the Mandai fermentation. This research was carried out (i) to investigate the effect of temperature on yield, chemical properties, and antioxidant activity of starter induced fermented mandai powder, (ii) to find the best drying temperature for the powder, and (iii) to find correlations between phenolic contents and antioxidant activity of the powder. Methods: The drying temperature was used as the variable, and was set at 45, 50, and 55°C at a fixed duration of 18 hours. The control was spontaneously fermented mandai dried at 50°C for 18 hours. Total phenolic content (TPC), hydrolyzed tannic content (HTC), and total flavonoid content (TFC) were spectrophotometrically measured, expressed gallic acid (GAE), tannic acid (TAE), and catechin (CAE) equivalents. The DPPH assay measured antioxidant capacity.  Results: The best mandai powder had total phenolic content of 348.8±55.6 mg GAE kg -1, HTC of 143.8±9.3 mg TAE kg -1, TFC of 17.5±1.3 mg CAE kg -1, antioxidant activity (IC 50) of 56.96 ppm, ash content of 4.0±0.7%, pH value of 5.0±0.8, and yield of 9.3±0.8%. There was a strong correlation between TPC, HTC, TFC, and antioxidant activity. Conclusions: Drying temperature affected all observed parameters but not yield, ash and pH. The temperature of 45°C emerged as the best treatment to produce mandai powder from L. casei-inoculated mandai cempedak fermentation. The phenolic components contributed to the antioxidant activity of mandai cempedak.

Mitragyna is a genus belonging to the Rubiaceae family and is a plant endemic to Asia and Africa. Traditionally, the plants of this genus were used by local people to treat some diseases from generation to generation. Mitragyna speciosa (Korth.) Havil. is a controversial plant from this genus, known under the trading name “kratom”, and contains more than 40 different types of alkaloids. Mitragynine and 7-hydroxymitragynine have agonist morphine-like effects on opioid receptors. Globally, Mitragyna plants have high economic value. However, regulations regarding the circulation and use of these commodities vary in several countries around the world. This review article aims to comprehensively examine Mitragyna plants (mainly M. speciosa) as potential pharmacological agents by looking at various aspects of the plants. A literature search was performed and information collected using electronic databases including Scopus, ScienceDirect, PubMed, directory open access journal (DOAJ), and Google Scholar in early 2020 to mid-2021. This narrative review highlights some aspects of this genus, including historical background and botanical origins, habitat, cultivation, its use in traditional medicine, phytochemistry, pharmacology and toxicity, abuse and addiction, legal issues, and the potential of Mitragyna species as pharmaceutical products.