Interaction of 3-(1H-tetrazol-5-yl) Coumarin With Bovine Serum Albumin and Calf Thymus DNA: Deciphering the Mode of Binding by In Vitro Studies

Background: Coumarins comprise a large family of heterocyclic compounds with a benzo-a-pyrone moiety. Objectives: This study aimed to analyze the binding affinity of 3-(1H-tetrazol-5-yl) coumarin to bovine serum albumin (BSA) and calf thymus DNA (Ct-DNA) using fluorescence spectroscopy. The quenching of fluorescence was recognized during the interaction between 3-(1H-tetrazol-5-yl) coumarin and BSA, followed by a static mechanism. Methods: The hydrogen bonds, hydrophobic interactions, and Vander Waals forces were regarded as the principal part in the 3-(1H-tetrazol-5-yl) coumarin and BSA complexation process. The fluorescence spectral characteristics demonstrated an enhancement in fluorescence intensity of the 3-(1H-tetrazol-5-yl) coumarin in the presence of ct-DNA solution. Results: The experimental results indicated that the 3-(1H-tetrazol-5-yl) coumarin binds to DNA via interjection, hydrogen bonds, and Vander Waals forces. This work illustrated that BSA fluorescence was quenched by 3-(1H-tetrazol-5-yl) coumarin via a static mechanism and the ct-DNA fluorescence enhancement by 3-(1H-tetrazol-5-yl) coumarin was a static process. The secondary structure of proteins changed upon drug binding. Conclusion: It is deduced that 3-(1H-tetrazol-5-yl) coumarin represents a higher binding affinity to DNA compared to BSA. This finding can be useful in designing more effective new drugs with fewer side effects

Comparable assessment of adolescent repeated physical or psychological stress effects on adult cardiac performance in female rats

Abstract Extensive evidence highlights a robust connection between various forms of chronic stress and cardiovascular disease (CVD). In today's fast-paced world, with chronic stressors abound, CVD has emerged as a leading global cause of mortality. The intricate interplay of physical and psychological stressors triggers distinct neural networks within the brain, culminating in diverse health challenges. This study aims to discern the unique impacts of chronic physical and psychological stress on the cardiovascular system, unveiling their varying potencies in precipitating CVD. Twenty-one adolescent female rats were methodically assigned to three groups: (1) control (n = 7), (2) physical stress (n = 7), and (3) psychological stress (n = 7). Employing a two-compartment enclosure, stressors were administered to the experimental rats over five consecutive days, each session lasting 10 min. After a 1.5-month recovery period post-stress exposure, a trio of complementary techniques characterized by high specificity or high sensitivity were employed to meticulously evaluate CVD. Echocardiography and single-photon emission computed tomography (SPECT) were harnessed to scrutinize left ventricular architecture and myocardial viability, respectively. Subsequently, the rats were ethically sacrificed to facilitate heart removal, followed by immunohistochemistry staining targeting glial fibrillary acidic protein (GFAP). Rats subjected to psychological stress showed a wider range of significant cardiac issues compared to control rats. This included left ventricular hypertrophy [IVSd: 0.1968 ± 0.0163 vs. 0.1520 ± 0.0076, P < 0.05; LVPWd: 0.2877 ± 0.0333 vs. 0.1689 ± 0.0057, P < 0.01; LVPWs: 0.3180 ± 0.0382 vs. 0.2226 ± 0.0121, P < 0.05; LV-mass: 1.283 ± 0.0836 vs. 1.000 ± 0.0241, P < 0.01], myocardial ischemia [21.30% vs. 32.97%, P < 0.001], and neuroinflammation. This outcome underscores the imperative of prioritizing psychological well-being during adolescence, presenting a compelling avenue to curtail the prevalence of CVD in adulthood. Furthermore, extending such considerations to individuals grappling with CVD might prospectively enhance their overall quality of life

Cannabidiol Inhibits Tau Aggregation In Vitro

A hallmark of Alzheimer&rsquo;s disease (AD) is the accumulation of tau protein in the brain. Compelling evidence indicates that the presence of tau aggregates causes irreversible neuronal destruction, eventually leading to synaptic loss. So far, the inhibition of tau aggregation has been recognized as one of the most effective therapeutic strategies. Cannabidiol (CBD), a major component found in Cannabis sativa L., has antioxidant activities as well as numerous neuroprotective features. Therefore, we hypothesize that CBD may serve as a potent substance to hamper tau aggregation in AD. In this study, we aim to investigate the CBD effect on the aggregation of recombinant human tau protein 1N/4R isoform using biochemical methods in vitro and in silico. Using Thioflavin T (ThT) assay, circular dichroism (CD), and atomic force microscopy (AFM), we demonstrated that CBD can suppress tau fibrils formation. Moreover, by quenching assay, docking, and job&rsquo;s plot, we further demonstrated that one molecule of CBD interacts with one molecule of tau protein through a spontaneous binding. Experiments performed by quenching assay, docking, and Thioflavin T assay further established that the main forces are hydrogen Van der Waals and some non-negligible hydrophobic forces, affecting the lag phase of tau protein kinetics. Taken together, this study provides new insights about a natural substance, CBD, for tau therapy which may offer new hope for the treatment of AD