Use of serotonergic antidepressants and St John's wort in older Australians: a population-based cohort study.

OBJECTIVE: The study investigated the use of serotonergic antidepressants (SSRIs: selective serotonin reuptake inhibitors; SNRIs: serotonin-norepinephrine reuptake inhibitors) and St John's wort in a large NSW-based community sample, and sought to identify a potentially dangerous concomitant use of these medications. METHODS: Cross-sectional data from 266,848 participants from the '45 and Up' study were used. The questionnaire captures self-reported treatment for depression or anxiety and antidepressant medications in the last four weeks. RESULTS: 5.8% of participants received treatment for depression or anxiety, with 4.7% taking an SSRI and 1.3% an SNRI. St John's wort was taken by 0.3% of the participants. Use of SSRIs and SNRIs was reported more frequently by females than males (respectively, 64.1% vs 35.9%, 66.9% vs 33.1%). The gender difference was even more pronounced for St John's wort (75.6% vs. 24.4%). Use of antidepressants decreased after the age of 65 years. One hundred and forty people reported concurrent use of an SSRI and an SNRI, and 11 people of an SSRI with St John's wort. CONCLUSIONS: 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.

Bioaccessibility and antioxidant activity of ß-carotene loaded nanostructured lipid carrier (NLC) from binary mixtures of palm stearin and palm olein.

ß-carotene (ßC) is an essential nutrient for health. It is a potent antioxidant, anti-cancer, and anti-inflammatory substance. However, ßC has high hydrophobicity property, indicating a low absorption level in the digestive tract. The bioavailability of ßC is reasonably low. Lipid-based delivery systems such as nanostructured lipid carriers (NLC) potentially can help to overcome this problem. This research evaluated the bioaccessibility of the nanostructured mixture of palm stearin (PS) and palm olein (PO) and the antioxidant activity of ßC in the structure. ß-carotene bioaccessibility was studied by measuring the micellization during in vitro digestion. Antioxidants activity was measured by 2.2'-azino-bis (3-ethylbenzothiazoline- 6-sulphonic acid) (ABTS) and 2, 2 - diphenyl -1- picrylhydrazyl (DPPH) reduction methods. In vitro gastrointestinal digestion model indicated that nanostructured lipid carrier enhanced bioaccessibility and antioxidants activity of ßC. This suggests that the formulated NLC system can be used effectively to deliver lipophilic bioactive such as ßC in beverage products.

Mitragyna Species as Pharmacological Agents: From Abuse to Promising Pharmaceutical Products.

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.

Advanced glycation endproducts as gerontotoxins and biomarkers for carbonyl-based degenerative processes in Alzheimer's disease.

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.

Different drying temperatures modulate chemical and antioxidant properties of mandai cempedak ( Artocarpus integer).

Background: Mandai, the fermented inner skin of cempedak (Artocarpus integer), may have further use as industrial ingredient while maintaining its antioxidative capacity. To promote fermentation, Lactobacillus casei was induced as the starter culture. 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. Antioxidant capacity was measured by DPPH assay.  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 the antioxidant activity. Conclusions: Drying temperature affected all observed parameters but not ash and pH. Temperature of 45°C emerged as the best treatment to produce mandai powder from L. casei-inoculated mandai cempedak fermentation. The antioxidant activity of mandai cempedak was contributed by the phenolic components.

The advanced glycation end product-lowering agent ALT-711 is a low-affinity inhibitor of thiamine diphosphokinase.

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.

Effects of plant-derived polyphenols on TNF-alpha and nitric oxide production induced by advanced glycation endproducts.

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.