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[This corrects the article DOI: 10.1007/s40200-022-01074-4.].
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Objectives: Glucose intolerance and insulin resistance are hallmarks of metabolic syndrome and lead to Alzheimer's disease (AD). The purpose of this study is to elucidate the neuroprotective effect of metformin through insulin regulation with cardiometabolic and neurotransmitter metabolic enzyme regulation in high-fat, high-sucrose diet and streptozotocin (HFHS-STZ)-induced rats. Methods: Male Wistar rats were treated with metformin (180 mg/kg and 360 mg/kg). STZ (35 mg/kg i.p.) injection was performed on the 14th day of 42 days of HFHS diet treatment. Brain neurotransmitter metabolic enzymes (acetylcholinesterase and monoamine oxidase) were determined along with sodium-potassium ATPase (Na+K+-ATPase). Plasma lipids and homeostasis model assessment of insulin resistance (HOMA-IR) was performed. Mean arterial blood pressure, heart rate and electrocardiogram (QT, QTc and RR intervals) were analysed with PowerLab. Results: Metformin treatment significantly (p < 0.001) reduced the HOMA-IR index and decreased neurotransmitter metabolic enzymes such as AChE and MAO (p < 0.01 and p < 0.05). The lipid profile was significantly (p < 0.001) controlled with cardiometabolic functions. Conclusions: Our investigation revealed that metformin has a remarkable role in regulating brain insulin, vascular system with monoaminergic metabolic enzymes and enhancing synaptic plasticity. Metformin may be a selective early therapeutic agent in metabolic syndrome associated with cognitive decline.
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Background: A common contributory factor to falls is the use of medicines, especially those commonly known as "fall-risk increasing drugs" (FRIDs). The use of FRIDs is common among older people (OP). However, OP and their family caregivers (FCGs) are largely unaware of FRIDs and their risks in increasing the risk of falls (ROF). Methods: A booklet which aims to provide information on topics related to FRIDs was developed. The booklet was reviewed by a panel of 14 reviewers, and the content validity index (CVI) for each subsection of the booklet was computed. Pilot testing of the booklet utilized a pre-post intervention study design and included 50 OP and 50 FCGs as study participants. Perceived knowledge of the participants was assessed prior to and after completing the booklet. Participants' opinions on the usefulness and usability of the booklet were also obtained. Results: The booklet contained eight sections and each subsection of the booklet had a CVI ranging from 0.93 to 1.00. Completing the booklet resulted in improved perceived knowledge scores for each perceived knowledge item among both the OP and FCG groups (all items: p-value < 0.001). The participants perceived the booklet as useful and usable, as evidenced by almost all the perceived usefulness and usability items having a score of over 4.0. Conclusions: The FRIDs booklet developed in this study had good content validity and was widely accepted by the OP and FCGs. The positive effect on the participants' knowledge of topics related to FRIDs means that the booklet could be useful as a patient education tool to enhance FRIDs knowledge and awareness among OP and FCGs.
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Accidental Falls , Pamphlets , Humans , Aged , Accidental Falls/prevention & controlABSTRACT
OBJECTIVES: The aim of the present study was to isolate and evaluate cytotoxicity and anti-inflammatory activities of new novel compounds isolated from Prismatomeris glabra. MATERIALS AND METHODS: Dried root of P. glabra was extracted under reflux with methyl alcohol, fractionated through the vacuum liquid chromatography technique, and evaporated and then purified the compounds using column chromatography and preparative thin-layer chromatography. THP-1 cells were treated with amentoflavone, 5,7,4'-hydroxyflavonoid, and stigmasterol with various concentrations (0-30 µg/mL) and then incubated with MTS reagent for 2h. Treatment was done for 24, 48, and 72h. Then, effects of these compounds were also tested on PGE2, TNF-α, and IL-6 expression in human THP-1-derived macrophage cells for 24h. RESULTS: Three new compounds such as amentoflavone, 5,7,4'-hydroxyflavonoid, and stigmasterol were isolated. After 24h of incubation, a significant decrease in cell viability was reported with IC50 values of amentoflavone, 5,7,4'- hydroxyflavonoid, and stigmasterol (21 µg/mL ≡ 38 M), (18 µg/mL ≡ 66 M) and (20 µg/mL ≡ 48.5 M), respectively. Whereas for 48 and 72h treatment showed a less decreased cell viability compared with 24h treatment. These compounds also showed a significant reduction in the production of TNF-α, IL-6, and PGE2 in a dose-dependent manner. CONCLUSIONS: The isolated new compounds showed significant cytotoxicity and anti-inflammatory effects.
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Phenolic Schiff bases are known for their diverse biological activities and ability to scavenge free radicals. To elucidate (1) the structure-antioxidant activity relationship of a series of thirty synthetic derivatives of 2-methoxybezohydrazide phenolic Schiff bases and (2) to determine the major mechanism involved in free radical scavenging, we used density functional theory calculations (B3P86/6-31+(d,p)) within polarizable continuum model. The results showed the importance of the bond dissociation enthalpies (BDEs) related to the first and second (BDEd) hydrogen atom transfer (intrinsic parameters) for rationalizing the antioxidant activity. In addition to the number of OH groups, the presence of a bromine substituent plays an interesting role in modulating the antioxidant activity. Theoretical thermodynamic and kinetic studies demonstrated that the free radical scavenging by these Schiff bases mainly proceeds through proton-coupled electron transfer rather than sequential proton loss electron transfer, the latter mechanism being only feasible at relatively high pH.
