Cell survival and death are intricately governed by apoptosis, a meticulously controlled programmed cell death. Apoptosis is vital in facilitating embryonic development and maintaining tissue homeostasis and immunological functioning. It is a complex interplay of intrinsic and extrinsic signaling pathways that ultimately converges on executing the apoptotic program. The extrinsic pathway is initiated by the binding of death ligands such as TNF-α and Fas to their respective receptors on the cell surface. In contrast, the intrinsic pathway leads to increased permeability of the outer mitochondrial membrane and the release of apoptogenic factors like cytochrome c, which is regulated by the Bcl-2 family of proteins. Once activated, these pathways lead to a cascade of biochemical events, including caspase activation, DNA fragmentation, and the dismantling of cellular components. Dysregulation of apoptosis is implicated in various disorders, such as cancer, autoimmune diseases, neurodegenerative disorders, and cardiovascular diseases. This article focuses on elucidating the molecular mechanisms underlying apoptosis regulation, to develop targeted therapeutic strategies. Modulating apoptotic pathways holds immense potential in cancer treatment, where promoting apoptosis in malignant cells could lead to tumor regression. This article demonstrates the therapeutic potential of targeting apoptosis, providing options for treating cancer and neurological illnesses. The safety and effectiveness of apoptosis-targeting drugs are being assessed in ongoing preclinical and clinical trials (phase I–III), opening the door for more effective therapeutic approaches and better patient outcomes.

The excessive exposure of blue light, originated from electronic gadgets like smartphones, laptops, and tablets, may contribute to sleep problems. Long exposure to blue-wavelength light from these devices affects sleep by suppressing melatonin hormone and cause neurophysiologic consequences. This literature review highlights the most recent findings on the relationship between sleep disruption and blue light exposure among the high school and college student population. A variety of scientific studies have shown that blue light exposure, especially before bedtime, can create circadian disruptions and inhibit melatonin secretion in brain, which ultimately result in deteriorated sleep quality and duration. Sleep deprivation in duration and quality of sleep is reflected in negative effects on mood, learning memory, and academic performance of a student from middle school to college. In general, the accumulating evidence indicates that, to promote adolescent and young adult health, it is necessary to pay attention to the impacts of blue light exposure from modern technologies.

Objective: This study aimed to identify potential phytochemicals from Withania somnifera (ashwagandha) that can act as gamma-aminobutyric acid A (GABA-A) receptor agonists or stimulant, and evaluate their suitability as potential insomnia treatments. Methods: Various computational approaches were employed, including virtual screening, biological activity prediction, physicochemical and drug-likeness analysis, absorption, distribution, metabolism, excretion, and toxicity (ADME/T) analysis, and molecular dynamics simulations. The Diseases Plants Eliminate (DISPEL) server was used to identify suitable plant species in context to insomnia, and the Indian Medicinal Plants, Phytochemistry And Therapeutics 2.0 (IMPPAT 2.0) database was utilized to assess the phytochemicals from W. somnifera. Virtual screening was performed using AutoDock Vina, and biological activity prediction was carried out using the Prediction of Activity Spectra for Substances (PASS) web server. The SwissADME webserver was used for physicochemical and drug-likeness analysis, while the ADME/T analysis was conducted using the ADMETlab 2.0 and ProTox 3.0 servers. Molecular dynamics simulations were performed using the WEBGRO Macromolecular Simulations server. Results: The findings revealed that hygrine, tropine, and withasomnine exhibited promising GABA-A receptor agonist activity, favorable drug-likeness properties, low toxicity, and stable receptor-ligand interactions. These phytochemicals demonstrated desirable physiochemical properties, adhering to Lipinski’s rule of five, and exhibited favorable ADME profiles. Molecular dynamics simulations showed stable interactions between the compounds and the GABA-A receptor, with minimal conformational changes and high compactness observed for hygrine and tropine. Conclusion: The phytochemicals hygrine, tropine, and withasomnine from W. somnifera emerged as potential lead compounds for the development of novel insomnia treatments targeting the GABA-A receptor. These findings warrant further investigation through experimental validation and optimization to advance their development as potential therapeutic agents for insomnia.

The current study aimed to conduct a phytochemical screening of commonly known Withania somnifera leaf extract through gas chromatography and mass spectrometry (GC–MS) to identify the bioactive compounds responsible for its MAO-A inhibitory action and evaluate the pharmacological potentialities of the extract and its fractions against anxiety. In the in-silico analysis, various tools were employed, including molecular docking and molecular dynamics (MD) simulation. These methods assessed the binding affinity and stability of the phytochemicals (ligands) with MAO-A. The preclinical efficacy and safety of the phytochemicals were evaluated using ADMET/T analysis. Furthermore, the biological activity of the selected phytochemicals as potential “MAO-A” inhibitors was assessed using PASS analysis. Lipinski’s rule of five was applied to predict the drug-likeness properties of the compounds. The interacting residues and the types of interactions between the active site of MAO-A and the compounds were evaluated. The cumulative results of these analyses identified 2-Methoxy-4-vinylphenol, Hexadecanoic acid, N,N-Bis(2-hydroxyethyl) dodecanamide, 1,2 Benzene dicarboxylic acid diethyl ester, and Oxacycloheptadec-8-en-2-one as hit compounds from W. somnifera, suggesting their potential as MAO-A inhibitors. This research aims to provide an elaborative description of promising phytochemical entities with activities against MAO-A. However, the efficacy of these phytochemicals as potential anxiolytic compounds needs further validation via in vitro and in vivo studies.

Objective: This study aimed to identify and delineate the antagonistic effects of phytochemicals present in Rauwolfia serpentina (Indian snakehead) on the serotonin 2A receptor (5HT2AR) for insomnia treatment. Methods: Molecular docking and molecular dynamics simulations were performed to analyze the binding affinity and stability of protein–ligand complexes. The dynamic behavior of the complexes was studied via normal mode analysis performed via the iMODS server. The blood–brain barrier permeability of the phytochemicals was hence analyzed via the Brain or IntestinaL EstimateD permeation method (BOILED-Egg). The bioactivity of phytochemicals as “g-protein coupled receptor (GPCR) ligands” was analyzed via the MolInspiration server. Lipinski’s rule of five was used as a benchmark to assess the drug likeness of the phytochemicals. The SWISS ADME server was used to analyze the physiochemical properties of the selected phytocompounds. Furthermore, the preclinical efficacy and safety of the compounds were assessed via absorption, distribution, metabolism, excretion, and toxicity (ADME/T) analysis performed via the Deep-PK and ProTox 3.0 servers. Results: Cumulative results from various computational parameters yielded isorauhimbine and vinburnine as hit compounds because they are 5HT2AR antagonists. These phytochemicals exhibited promising docking scores, and their root mean square deviation, radius of gyration, and solvent accessible surface area confirmed their stability with the target protein. The ADME/T profile and drug-likeness values of these two compounds validated their safety, efficacy, and potential as drug candidates. Conclusion: We conclude that isorauhimbine and vinburnine stand out as potential phytochemicals from R. serpentina that could potentially serve as potential antagonistic drug candidates against 5HT2AR for insomnia treatment. However, these findings need to be validated through wet lab experiments to fully elucidate their therapeutic potential against insomnia.

Circadian rhythms are endogenous oscillations coordinating the physiological and behavioral activities with the daily light-dark cycle and are controlled by molecular mechanisms. Nicotinamide adenine dinucleotide (NAD+), a critical cofactor in redox processes and a substrate for many enzymes, is an important metabolite in circadian rhythms. NAD+ levels show strong circadian oscillations, which are caused by the rhythmic production of biosynthetic enzymes such as nicotinamide phosphoribosyl transferase. In contrast, the circadian clock system regulates the expression of NAD+ biosynthetic enzymes, resulting in a bidirectional regulatory loop. Sirtuins, a class of NAD+-dependent protein deacetylases, regulate the circadian clock by interacting with the core clock components and transcriptional regulators. Sirtuin (SIRT) 1 deacetylates and modulates the activity of key circadian transcription factors such as brain and muscle arnt-like 1 and period circadian regulator 2, while SIRT6 regulates the expression of circadian-controlled metabolic genes. This review explored the complex relationships among NAD+, sirtuins, and the circadian clock machinery, emphasizing their roles in sustaining metabolic homeostasis and coordinating cellular processes with daily environmental cycles. Moreover, circadian disruptions are strongly associated with aging, which results in the dysregulation of NAD+ homeostasis and sirtuin activity and contributes to the development of various age-related pathologies. Strategies to restore NAD+ levels or modify the sirtuin activity have emerged as promising treatment options for circadian rhythm disturbances and age-related disorders. This review also aimed to cover new horizons in this subject, such as the development of NAD+ boosters and sirtuin modulators, chrono-pharmacological methods, and the study of epigenetic mechanisms underlying sirtuin-mediated circadian regulation.