Phytochemical profiling, antioxidant, cytotoxic, and anti-inflammatory activities of Plectranthus rugosus extract and fractions: in vitro, in vivo, and in silico approaches.

BACKGROUND: Inflammation is a key biological reaction that comprises a complex network of signals that both initiate and stop the inflammation process. PURPOSE: This study targets to evaluate the anti-inflammatory potential of the leaves of the Plectranthus rugosus (P. rugosus) plant involving both in vitro and in vivo measures. The current available drugs exhibit serious side effects. Traditional medicines impart an essential role in drug development. P. rugosus is a plant used in traditional medicine of Tropical Africa, China, and Australia to treat various diseases. METHODS: Lipopolysaccharide (LPS), an endotoxin, kindles macrophages to discharge huge quantities of pro-inflammatory cytokines like TNF-α and IL-6. So, clampdown of macrophage stimulation may have a beneficial potential to treat various inflammatory disorders. The leaves of the P. rugosus are used for swelling purpose by local population; however, its use as an anti-inflammatory agent and associated disorders has no scientific evidence. RESULTS: The extracts of the plant Plectranthus rugosus ethanolic extract (PREE), Plectranthus rugosus ethyl acetate extract (PREAF), and the compound isolated (oleanolic acid) suppress the pro-inflammatory cytokines (IL-6 and TNF-α) and nitric oxide (NO), confirming its importance in traditional medicine. CONCLUSION: The pro-inflammatory cytokines are inhibited by P. rugosus extracts, as well as an isolated compound oleanolic acid without compromising cell viability.

Network Pharmacology Combined with Molecular Docking, Molecular Dynamics, and In Vitro Experimental Validation Reveals the Therapeutic Potential of Thymus vulgaris L. Essential Oil (Thyme Oil) against Human Breast Cancer.

Breast cancer is a major global health issue for women. Thyme oil, extracted from Thymus vulgaris L., has shown promising anticancer effects. In the present study, we investigated how Thyme oil can influence breast cancer treatment using a multimethod approach. We used network pharmacology to identify the active compounds of Thyme oil, their molecular targets, and the pathways involved in breast cancer. We found that Thyme oil can modulate several key proteins (EGFR, AKT1, ESR1, HSP90AA1, STAT-3, SRC, IL-6, HIF1A, JUN, and BCL2) and pathways (EGFR tyrosine kinase inhibitor resistance, prolactin signaling pathway, HIF-1 signaling pathway, estrogen signaling pathway, ERBB signaling pathway, AGE-RAGE signaling pathway, JAK-STAT signaling pathway, FoxO signaling pathway, and PI3K-AKT signaling pathway) related to breast cancer progression. We then used molecular docking and dynamics to study the interactions and stability of the Thyme oil-compound complexes. We discovered three potent compounds (aromadendrene, α-humulene, and viridiflorene) that can bind strongly to important breast cancer proteins. We also performed in vitro experiments on MCF-7 cells to confirm the cytotoxicity and antiproliferative effects of Thyme oil. We observed that Thyme oil can inhibit cancer cell growth and proliferation at a concentration of 365.37 µg/mL. Overall, our results provide a comprehensive understanding of the pharmacological mechanism of Thyme oil in breast cancer treatment and suggest its potential as a new or adjuvant therapy. Further studies are needed to validate and optimize the therapeutic efficacy of Thyme oil and its active compounds.

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.

Standardized Polyalthia longifolia leaf extract induces the apoptotic HeLa cells death via microRNA regulation: identification, validation, and therapeutic potential.

Polyalthia longifolia var. angustifolia Thw. (Annonaceae), is a famous traditional medicinal plant in Asia. Ample data specifies that the medicinal plant P. longifolia has anticancer activity; however, the detailed mechanisms of action still need to be well studied. Recent studies have revealed the cytotoxicity potential of P. longifolia leaf against HeLa cells. Therefore, the current study was conducted to examine the regulation of miRNAs in HeLa cancer cells treated with the standardized P. longifolia methanolic leaf extract (PLME). The regulation of miRNAs in HeLa cancer cells treated with the standardized PLME extract was studied through Illumina, Hi-Seq. 2000 platform of Next-Generation Sequencing (NGS) and various in silico bioinformatics tools. The PLME treatment regulated a subset of miRNAs in HeLa cells. Interestingly, the PLME treatment against HeLa cancer cells identified 10 upregulated and 43 downregulated (p < 0.05) miRNAs associated with apoptosis induction. Gene ontology (GO) term analysis indicated that PLME induces cell death in HeLa cells by inducing the pro-apoptotic genes. Moreover, the downregulated oncomiRs modulated by PLME treatment in HeLa cells were identified, targeting apoptosis-related genes through gene ontology and pathway analysis. The LC-ESI-MS/MS analysis identified the presence of Vidarabine and Anandamide compounds that were previously reported to exhibit anticancer activity. The findings of this study obviously linked the cell cytotoxicity effect of PLME treatment against the HeLa cells with regulating various miRNAs expression related to apoptosis induction in the HeLa cells. PLME treatment induced apoptotic HeLa cell death mechanism by regulating multiple miRNAs. The identified miRNAs regulated by PLME may provide further insight into the mechanisms that play a critical role in cervical cancer, as well as novel ideas regarding gene therapeutic strategies.

Identification of potential Escherichia coli DNA gyrase B inhibitors targeting antibacterial therapy: an integrated docking and molecular dynamics simulation study.

The alarming rise in the rate of antibiotic resistance is a matter of significant concern. DNA gyrase B (GyrB), a critical bacterial enzyme involved in DNA replication, transcription, and recombination, has emerged as a promising target for antibacterial agents. Inhibition of GyrB disrupts bacterial DNA replication, leading to cell death, making it an attractive candidate for antibiotic development. Although several classes of antibiotics targeting GyrB are currently in clinical use, the emergence of antibiotic resistance necessitates the exploration of novel inhibitors. In this study, we aimed to identify potential Escherichia coli GyrB inhibitors from a database of phytoconstituents sourced from Indian medicinal plants. Utilizing virtual screening, we performed a rigorous search to identify compounds with the most promising inhibitory properties against GyrB. Two compounds, namely Zizogenin and Cucurbitacin S, were identified based on their favorable drug likeliness and pharmacokinetic profiles. Employing advanced computational techniques, we analyzed the binding interactions of Zizogenin and Cucurbitacin S with the ATP-binding site of GyrB through molecular docking simulations. Both compounds exhibited robust binding interactions, evidenced by their high docking energy scores. To assess the stability of these interactions, we conducted extensive 100 ns molecular dynamics (MD) simulations, which confirmed the stability of Zizogenin and Cucurbitacin S when bound to GyrB. In conclusion, our study highlights Zizogenin and Cucurbitacin S as promising candidates for potential antibacterial agents targeting GyrB. Experimental validation of these compounds is warranted to further explore their efficacy and potential as novel antibiotics to combat antibiotic-resistant bacteria.Communicated by Ramaswamy H. Sarma.

Revisiting the Green Synthesis of Nanoparticles: Uncovering Influences of Plant Extracts as Reducing Agents for Enhanced Synthesis Efficiency and Its Biomedical Applications.

Background: Conventional nanoparticle synthesis methods involve harsh conditions, high costs, and environmental pollution. In this context, researchers are actively searching for sustainable, eco-friendly alternatives to conventional chemical synthesis methods. This has led to the development of green synthesis procedures among which the exploration of the plant-mediated synthesis of nanoparticles experienced a great development. Especially, because plant extracts can work as reducing and stabilizing agents. This opens up new possibilities for cost-effective, environmentally-friendly nanoparticle synthesis with enhanced size uniformity and stability. Moreover, bio-inspired nanoparticles derived from plants exhibit intriguing pharmacological properties, making them highly promising for use in medical applications due to their biocompatibility and nano-dimension. Objective: This study investigates the role of specific phytochemicals, such as phenolic compounds, terpenoids, and proteins, in plant-mediated nanoparticle synthesis together with their influence on particle size, stability, and properties. Additionally, we highlight the potential applications of these bio-derived nanoparticles, particularly with regard to drug delivery, disease management, agriculture, bioremediation, and application in other industries. Methodology: Extensive research on scientific databases identified green synthesis methods, specifically plant-mediated synthesis, with a focus on understanding the contributions of phytochemicals like phenolic compounds, terpenoids, and proteins. The database search covered the field's development over the past 15 years. Results: Insights gained from this exploration highlight plant-mediated green synthesis for cost-effective nanoparticle production with significant pharmacological properties. Utilizing renewable biological resources and controlling nanoparticle characteristics through biomolecule interactions offer promising avenues for future research and applications. Conclusion: This review delves into the scientific intricacies of plant-mediated synthesis of nanoparticles, highlighting the advantages of this approach over the traditional chemical synthesis methods. The study showcases the immense potential of green synthesis for medical and other applications, aiming to inspire further research in this exciting area and promote a more sustainable future.

Synergistic Antimicrobial Activity of Ceftriaxone and Polyalthia longifolia Methanol (MEPL) Leaf Extract against Methicillin-Resistant Staphylococcus aureus and Modulation of mecA Gene Presence.

Medicinal plants are an essential source of traditional curatives for numerous skin diseases. Polyalthia longifolia (Sonn.) Thwaites (Annonaceae family) is a medicinal plant used to cure skin illnesses. P. longifolia is usually applied in folkloric therapeutical systems to treat skin diseases. The methicillin-resistant Staphylococcus aureus (MRSA) bacteria is among the essential bacteria contributing to skin diseases. Hence, to verify the traditional medicinal claim of P. longifolia usage in skin disease treatment, the current research was performed to study the synergistic antibacterial activity of standardized Polyalthia longifolia methanol leaf extract (MEPL) against MRSA bacteria. The synergistic antimicrobial activity result of ceftriaxone, when mixed with MEPL, against MRSA was investigated by the disc diffusion method, broth microdilution method, checkerboard dilution test, and modulation of mecA gene expression by multiplex polymerase chain reaction (multiplex PCR). The MEPL extract exhibited good synergistic antimicrobial activity against MRSA. Using the checkerboard method, we confirmed the synergistic effect of MEPL from P. longifolia and ceftriaxone (2:1) for MRSA with a marked reduction of the MIC value of the ceftriaxone from 8000 µg/mL to 1000 µg/mL. Moreover, the combination of MEPL with ceftriaxone significantly (p < 0.05) inhibited the presence of the resistant mecA gene in the tested strain. The LC-ESI-MS/MS analysis identified compounds that were reported to exhibit antimicrobial activity. Conclusively, the MEPL extract, an important etiological agent for skin diseases, showed worthy synergistic antimicrobial action against MRSA bacteria, thus supporting the traditional use of P. longifolia.

Integrating network pharmacology approaches for the investigation of multi-target pharmacological mechanism of 6-shogaol against cervical cancer.

Traditional treatment of cancer has been plagued by a number of obstacles, such as multiple drug resistance, toxicity and financial constraints. In contrast, phytochemicals that modulate a variety of molecular mechanisms are garnering increasing interest in complementary and alternative medicine. Therefore, an approach based on network pharmacology was used in the present study to explore possible regulatory mechanisms of 6-shogaol as a potential treatment for cervical cancer (CC). A number of public databases were screened to collect information on the target genes of 6-shogaol (SuperPred, Targetnet, Swiss target prediction and PharmMapper), while targets pertaining to CC were taken from disease databases (DisGeNet and Genecards) and gene expression omnibus (GEO) provided expression datasets. With STRING and Cytoscape, protein-protein interactions (PPI) were generated and topology analysis along with CytoNCA were used to identify the Hub genes. The Gene Ontology (GO) database Enrichr was used to annotate the target proteins, while, using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, signaling pathway enrichment analysis was conducted. Molecular docking and survival analysis for the Hub genes revealed four genes (HSP90AA1, HRAS, ESR1 and EGFR) with lowest binding energy and majority of the Hub genes (EGFR, SRC, CASP-3, HSP90AA1, MTOR, MAPK-1, MDM2 and ESR1) were linked with the overall survival of CC patients. In conclusion, the present study provides the scientific evidence which strongly supports the use of 6-shogoal as an inhibitor of cellular proliferation, growth, migration as well as inducer of apoptosis via targeting the hub genes involved in the growth of CC.Communicated by Ramaswamy H. Sarma.

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.

Report on Vincristine-Producing Endophytic Fungus Nigrospora zimmermanii from Leaves of Catharanthus roseus.

Vincristine is an anti-cancer compound and one of the most crucial vinca alkaloids produced by the medicinal plant Catharanthus roseus (L.) G. Don. (Apocynaceae). This plant is home to hundreds of endophytic microbes, which produce a variety of bioactive secondary metabolites that are known for their medicinal properties. In this study, we focused on isolating an endophytic fungus that could increase the yield of vincristine under laboratory conditions as an alternative to plant-mediated extraction of vincristine. The endophytic fungus Nigrospora zimmermanii (Apiosporaceae) was isolated from Catharanthus roseus and it was found to be producing the anticancer compound vincristine. It was identified using high-performance thin-layer chromatography by matching the Rf value and spectral data with the vincristine standard and mass spectrometry data and the reference molecule from the PubChem database. The generation study of this microbe showed that the production of vincristine in the parent fungus was at its maximum, i.e., 5.344 µg/mL, while it was slightly reduced in subsequent generations. A colonization study was also performed and it showed that the fungus N. zimmermanii was able to re-infect the plant Catharanthus roseus after 20 days of inoculation. The colonization study showed that N. zimmernanii could infect the plant after isolation. This method is an efficient and easy way to obtain a high yield of vincristine, as compared to plant-mediated production.

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.

(-)-Epigallocatechin gallate (EGCG) pharmacokinetics and molecular interactions towards amelioration of hyperglycemia, hyperlipidemia associated hepatorenal oxidative injury in alloxan induced diabetic mice.

Diabetes mellitus has become a serious problem associated with health complications, such as metabolism disorders and liver-kidney dysfunction. The inadequacies associated with conventional medicines have led to a determined search for alternative natural therapeutic agents. The present study was conducted to evaluate the hypoglycemic, antilipidemic, and antioxidant effects of EGCG in surviving diabetic mice. Alloxan diabetic mice were treated with EGCG. Their bloods were collected and submitted to various biochemical measurements, including blood glucose, cholesterol, triglycerides, urea, creatinine, and transaminases. Their livers and kidneys were isolated to assess oxidative damage and to perform histological analysis. Both EGCG and insulin treatment of diabetic mice resulted in a significant reduction in fasting blood glucose levels. EGCG supplementation also ameliorated hepatic as well as renal toxicity indices. Moreover, diabetic mice injected with EGCG exhibited significant changes in antioxidant enzyme activities in the liver and kidney. Histological analyses also showed that it exerted an ameliorative action on these organs and efficiently protected the liver-kidney functions of diabetic mice. EGCG was found to bind α-amylase, PTP1B, and α-glucosidase with good affinities ranging from -6.1 to -8.4 kcal/mol. The findings revealed that EGCG administration induced attractive curative effects on diabetic mice, particularly in terms of liver-kidney function. EGCG can, therefore, be considered as a potential strong candidate for future applications to treat and alleviate diabetic burden. Its pharmacokinetics, high affinities, and molecular interactions with the targeted receptors satisfactory explain the in vivo findings.

Comparative Study of Antibacterial, Antibiofilm, Antiswarming and Antiquorum Sensing Activities of Origanum vulgare Essential Oil and Terpinene-4-ol against Pathogenic Bacteria.

Essential oils from aromatic and medicinal plants have many bioactive compounds known for their important biological activities mainly their antibacterial effects. Here we evaluated qualitatively and quantitatively the biofilm formation capability of pathogenic bacterial strains (n = 8). Then, we investigated the antibacterial, antibiofilm, antiquorum-sensing, and antiswarming efficacy of Origanum vulgare essential oil (EO) and terpinene-4-ol. Our results revealed that EO exhibited a more potent inhibitory effect against the tested strains. While the terpinene-4-ol was found to be more effective against developed Staphylococcus aureus biofilm. Regarding the anti quorum-sensing activity, we noticed that O. vulgare displayed better inhibition percentages in violacein production even at a low concentration (MIC/4). Additionally, this EO showed better inhibition of Pseudomonas aeruginosa PAO1 migration in comparison with the terpinene-4-ol. Our findings revealed that using pure O. vulgare EO demonstrated better competitive effects against pathogenic bacteria with a different mode of action when compared to the terpinene-4-ol. Hence, exploration and development of efficient anti-infection agents from natural resources such as full EOs represent promising tools in anti-infective therapy.

Withania somnifera (L.) Dunal (Ashwagandha) for the possible therapeutics and clinical management of SARS-CoV-2 infection: Plant-based drug discovery and targeted therapy.

Coronavirus disease 2019 (COVID-19) pandemic has killed huge populations throughout the world and acts as a high-risk factor for elderly and young immune-suppressed patients. There is a critical need to build up secure, reliable, and efficient drugs against to the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Bioactive compounds of Ashwagandha [Withania somnifera (L.) Dunal] may implicate as herbal medicine for the management and treatment of patients infected by SARS-CoV-2 infection. The aim of the current work is to update the knowledge of SARS-CoV-2 infection and information about the implication of various compounds of medicinal plant Withania somnifera with minimum side effects on the patients' organs. The herbal medicine Withania somnifera has an excellent antiviral activity that could be implicated in the management and treatment of flu and flu-like diseases connected with SARS-CoV-2. The analysis was performed by systematically re-evaluating the published articles related to the infection of SARS-CoV-2 and the herbal medicine Withania somnifera. In the current review, we have provided the important information and data of various bioactive compounds of Withania somnifera such as Withanoside V, Withanone, Somniferine, and some other compounds, which can possibly help in the management and treatment of SARS-CoV-2 infection. Withania somnifera has proved its potential for maintaining immune homeostasis of the body, inflammation regulation, pro-inflammatory cytokines suppression, protection of multiple organs, anti-viral, anti-stress, and anti-hypertensive properties. Withanoside V has the potential to inhibit the main proteases (Mpro) of SARS-CoV-2. At present, synthetic adjuvant vaccines are used against COVID-19. Available information showed the antiviral activity in Withanoside V of Withania somnifera, which may explore as herbal medicine against to SARS-CoV-2 infection after standardization of parameters of drug development and formulation in near future.

Pharmacological attributes of Bacopa monnieri extract: Current updates and clinical manifestation.

Bacopa monnieri has been used for centuries in Ayurvedic medicine, alone or in combination with other herbs, as a memory and learning enhancer, sedative, and anti-epileptic. This review aimed to highlight the health benefits of B. monnieri extracts (BME), focusing on anti-cancer and neurodegenerative diseases. We examined the clinical studies on phytochemistry and pharmacological application of BME. We further highlighted the mechanism of action of these extracts in varying types of cancer and their therapeutic implications. In addition, we investigated the underlying molecular mechanism in therapeutic interventions, toxicities, safety concerns and synergistic potential in cognition and neuroprotection. Overall, this review provides deeper insights into the therapeutic implications of Brahmi as a lead formulation for treating neurological disorders and exerting cognitive-enhancing effects.

Investigating neuroprotective roles of Bacopa monnieri extracts: Mechanistic insights and therapeutic implications.

Bacopa monnieri (Brahmi) is a well-known perennial, creeping herb of the Indian Ayurveda system; it contains numerous bioactive phytoconstituents implicated in the therapeutic management of several life-threatening diseases. This herb was used by Ancient Vedic scholars due to its pharmacological effect, especially as a nerve tonic and nootropic booster. However, to better understand the roles of Bacopa monnieri extract (BME) in neurological disorders and memory-related diseases, it is necessary to understand its active phytochemical constituents and their molecular mechanisms. Several clinical studies suggested that BME have neuroprotective effects, making it worth revising a notable herb. Here we investigated the contours of BME's phytochemistry and pharmacological features, focusing on neuronal disorders. We further analyzed the underlying molecular mechanisms in therapeutic intervention. Various clinical concerns and synergistic potential of BME were explored for their effective use in cognition and neuroprotection. The generation of reactive oxygen species increases neuroinflammation and neurotoxicity and is associated with Tau and amyloid-beta (Aß) aggregation, leading to a neurological disorder. Our findings provide deeper mechanistic insights into the neuroprotective roles of BME, which can be further implicated in the therapeutic management of neurological disorders and exerting cognitive-enhancing effects.

Chemical Composition and the Anticancer, Antimicrobial, and Antioxidant Properties of Acacia Honey from the Hail Region: The in vitro and in silico Investigation.

In consideration of the emergence of novel drug-resistant microbial strains and the increase in the incidences of various cancers throughout the world, honey could be utilized as a great alternative source of potent bioactive compounds. In this context, this study pioneers in reporting the phytochemical profiling and the antimicrobial, antioxidant, and anticancer properties of Acacia honey (AH) from the Hail region of Saudi Arabia, assessed using in vitro and molecular docking approaches. The phytochemical profiling based on high-resolution liquid chromatography-mass spectrometry (HR-LCMS) revealed eight compounds and three small peptide-like proteins as the constituents. The honey samples exhibited promising antioxidant activities (DPPH-IC50 = 0.670 mg/mL; ABTS-IC50 = 1.056 mg/mL; ß-carotene-IC50 > 5 mg/mL). In the well-diffusion assay, a high mean growth inhibition zone (mGIZ) was observed against Staphylococcus aureus (48.33 ± 1.53 mm), Escherichia coli ATCC 10536 (38.33 ± 1.53 mm), and Staphylococcus epidermidis ATCC 12228 (39.33 ± 1.15 mm). The microdilution assay revealed that low concentrations of AH could inhibit the growth of almost all the evaluated bacterial and fungal strains, with the minimal bactericidal concentration values (MBCs) ranging from 75 mg/mL to 300 mg/mL. On the contrary, high AH concentrations were required to kill the tested microorganisms, with the minimal bactericidal concentration values (MBCs) ranging from approximately 300 mg/mL to over 600 mg/mL and the minimal fungicidal concentration values (MFCs) of approximately 600 mg/mL. The AH exhibited effective anticancer activity in a dose-dependent manner against breast (MCF-7), colon (HCT-116), and lung (A549) cancer cell lines, with the corresponding IC50 values of 5.053 µg/mL, 5.382 µg/mL, and 6.728 µg/mL, respectively. The in silico investigation revealed that the observed antimicrobial, antioxidant, and anticancer activities of the constituent compounds of AH are thermodynamically feasible, particularly those of the tripeptides (Asp-Trp-His and Trp-Arg-Ala) and aminocyclitol glycoside. The overall results highlighted the potential of AH as a source of bioactive compounds with significant antimicrobial, antioxidant, and anticancer activities, which could imply further pharmacological applications of AH.

A Network-Guided Approach to Discover Phytochemical-Based Anticancer Therapy: Targeting MARK4 for Hepatocellular Carcinoma.

MAP/microtubule affinity-regulating kinase 4 (MARK4) is associated with various biological functions, including neuronal migration, cell polarity, microtubule dynamics, apoptosis, and cell cycle regulation, specifically in the G1/S checkpoint, cell signaling, and differentiation. It plays a critical role in different types of cancers. Hepatocellular carcinoma (HCC) is the one of the most common forms of liver cancer caused due to mutations, epigenetic aberrations, and altered gene expression patterns. Here, we have applied an integrated network biology approach to see the potential links of MARK4 in HCC, and subsequently identified potential herbal drugs. This work focuses on the naturally-derived compounds from medicinal plants and their properties, making them targets for potential anti-hepatocellular treatments. We further analyzed the HCC mutated genes from the TCGA database by using cBioPortal and mapped out the MARK4 targets among the mutated list. MARK4 and Mimosin, Quercetin, and Resveratrol could potentially interact with critical cancer-associated proteins. A set of the hepatocellular carcinoma altered genes is directly the part of infection, inflammation, immune systems, and cancer pathways. Finally, we conclude that among all these drugs, Gingerol and Fisetin appear to be the highly promising drugs against MARK4-based targets, followed by Quercetin, Resveratrol, and Apigenin.