Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation to Elucidate the Molecular Targets and Potential Mechanism of Phoenix dactylifera (Ajwa Dates) against Candidiasis.

Candidiasis, caused by opportunistic fungal pathogens of the Candida genus, poses a significant threat to immunocompromised individuals. Natural compounds derived from medicinal plants have gained attention as potential sources of anti-fungal agents. Ajwa dates (Phoenix dactylifera L.) have been recognized for their diverse phytochemical composition and therapeutic potential. In this study, we employed a multi-faceted approach to explore the anti-candidiasis potential of Ajwa dates' phytochemicals. Utilizing network pharmacology, we constructed an interaction network to elucidate the intricate relationships between Ajwa dates phytoconstituents and the Candida-associated molecular targets of humans. Our analysis revealed key nodes in the network (STAT3, IL-2, PTPRC, STAT1, CASP1, ALB, TP53, TLR4, TNF and PPARG), suggesting the potential modulation of several crucial processes (the regulation of the response to a cytokine stimulus, regulation of the inflammatory response, positive regulation of cytokine production, cellular response to external stimulus, etc.) and fungal pathways (Th17 cell differentiation, the Toll-like receptor signaling pathway, the C-type lectin receptor signaling pathway and necroptosis). To validate these findings, molecular docking studies were conducted, revealing the binding affinities of the phytochemicals towards selected Candida protein targets of humans (ALB-rutin (-9.7 kJ/mol), STAT1-rutin (-9.2 kJ/mol), STAT3-isoquercetin (-8.7 kJ/mol), IL2-ß-carotene (-8.5 kJ/mol), CASP1-ß-carotene (-8.2 kJ/mol), TP53-isoquercetin (-8.8 kJ/mol), PPARG-luteolin (-8.3 kJ/mol), TNF-ßcarotene (-7.7 kJ/mol), TLR4-rutin (-7.4 kJ/mol) and PTPRC-rutin (-7.0 kJ/mol)). Furthermore, molecular dynamics simulations of rutin-ALB and rutin-STAT1 complex were performed to gain insights into the stability and dynamics of the identified ligand-target complexes over time. Overall, the results not only contribute to the understanding of the molecular interactions underlying the anti-fungal potential of specific phytochemicals of Ajwa dates in humans but also provide a rational basis for the development of novel therapeutic strategies against candidiasis in humans. This study underscores the significance of network pharmacology, molecular docking and dynamics simulations in accelerating the discovery of natural products as effective anti-fungal agents. However, further experimental validation of the identified compounds is warranted to translate these findings into practical therapeutic applications.

Green Carbon Dots: Synthesis, Characterization, Properties and Biomedical Applications.

Carbon dots (CDs) are a new category of crystalline, quasi-spherical fluorescence, "zero-dimensional" carbon nanomaterials with a spatial size between 1 nm to 10 nm and have gained widespread attention in recent years. Green CDs are carbon dots synthesised from renewable biomass such as agro-waste, plants or medicinal plants and other organic biomaterials. Plant-mediated synthesis of CDs is a green chemistry approach that connects nanotechnology with the green synthesis of CDs. Notably, CDs made with green technology are economical and far superior to those manufactured with physicochemical methods due to their exclusive benefits, such as being affordable, having high stability, having a simple protocol, and being safer and eco-benign. Green CDs can be synthesized by using ultrasonic strategy, chemical oxidation, carbonization, solvothermal and hydrothermal processes, and microwave irradiation using various plant-based organic resources. CDs made by green technology have diverse applications in biomedical fields such as bioimaging, biosensing and nanomedicine, which are ascribed to their unique properties, including excellent luminescence effect, strong stability and good biocompatibility. This review mainly focuses on green CDs synthesis, characterization techniques, beneficial properties of plant resource-based green CDs and their biomedical applications. This review article also looks at the research gaps and future research directions for the continuous deepening of the exploration of green CDs.

Structure-Guided Approach to Discover Tuberosin as a Potent Activator of Pyruvate Kinase M2, Targeting Cancer Therapy.

Metabolic reprogramming is a key attribute of cancer progression. An altered expression of pyruvate kinase M2 (PKM2), a phosphotyrosine-binding protein is observed in many human cancers. PKM2 plays a vital role in metabolic reprogramming, transcription and cell cycle progression and thus is deliberated as an attractive target in anticancer drug development. The expression of PKM2 is essential for aerobic glycolysis and cell proliferation, especially in cancer cells, facilitating selective targeting of PKM2 in cell metabolism for cancer therapeutics. We have screened a virtual library of phytochemicals from the IMPPAT (Indian Medicinal Plants, Phytochemistry and Therapeutics) database of Indian medicinal plants to identify potential activators of PKM2. The initial screening was carried out for the physicochemical properties of the compounds, and then structure-based molecular docking was performed to select compounds based on their binding affinity towards PKM2. Subsequently, the ADMET (absorption, distribution, metabolism, excretion and toxicity) properties, PAINS (Pan-assay interference compounds) patterns, and PASS evaluation were carried out to find more potent hits against PKM2. Here, Tuberosin was identified from the screening process bearing appreciable binding affinity toward the PKM2-binding pocket and showed a worthy set of drug-like properties. Finally, molecular dynamics simulation for 100 ns was performed, which showed decent stability of the protein-ligand complex and relatival conformational dynamics throughout the trajectory. The study suggests that modulating PKM2 with natural compounds is an attractive approach in treating human malignancy after required validation.

Plants in Anticancer Drug Discovery: From Molecular Mechanism to Chemoprevention.

Cancer is one of the primary causes of mortality globally, and the discovery of new anticancer drugs is the most important need in recent times. Natural products have been recognized as effective in fight against various diseases including cancer for over 50 years. Plants and microbes are the primary and potential sources of natural compounds to fight against cancer. Moreover, researches in the field of plant-based natural compounds have moved towards advanced and molecular level understandings from the last few decades, leading to the development of potent anticancer agents. Also, plants have been accepted as abundant and prosperous sources for the development of novel therapeutic agents for the management and prevention of different cancer types. The high toxicity of some cancer chemotherapy drugs, as well as their unfavorable side effects and drugs resistance, drives up the demand for natural compounds as new anticancer drugs. In this detailed evidence-based mechanistic review, facts and information about various medicinal plants, their bioactive compounds with their potent anticancer activities against different cancers have been gathered, with further approach to represent the molecular mechanism behind the anticancer activity of these plants. This review will be beneficial for investigators/scientists globally involved in the development of natural, safe, effective, and economical therapeutic agents/drugs against various cancers. This might be an important contribution in the field of drug discovery, where drugs can be used alone or in combination to increase the efficacy of newly synthesized drugs.