Green Synthesis of Silver Nanoparticles and their Potential Applications in Mitigating Cancer.

In recent years, the field of nanotechnology has brought about significant advancements that have transformed the landscape of disease diagnosis, prevention, and treatment, particularly in the realm of medical science. Among the various approaches to nanoparticle synthesis, the green synthesis method has garnered increasing attention. Silver nanoparticles (AgNPs) have emerged as particularly noteworthy nanomaterials within the spectrum of metallic nanoparticles employed for biomedical applications. AgNPs possess several key attributes that make them highly valuable in the biomedical field. They are biocompatible, cost-effective, and environmentally friendly, rendering them suitable for various bioengineering and biomedical applications. Notably, AgNPs have found a prominent role in the domain of cancer diagnosis. Research investigations have provided evidence of AgNPs' anticancer activity, which involves mechanisms such as DNA damage, cell cycle arrest, induction of apoptosis, and the regulation of specific cytokine genes. The synthesis of AgNPs primarily involves the reduction of silver ions by reducing agents. Interestingly, natural products and living organisms have proven to be effective sources for the generation of precursor materials used in AgNP synthesis. This comprehensive review aims to summarize the key aspects of AgNPs, including their characterization, properties, and recent advancements in the field of biogenic AgNP synthesis. Furthermore, the review highlights the potential applications of these nanoparticles in combating cancer.

Nanogels as Drug Delivery Carrier: A Narrative Review on Formulation Techniques, Characterization, Applications, and Patents.

Under the umbrella of targeted drug delivery systems, several techniques are unleashed in the market that allow a drug or other pharmacologically active material to be delivered to the target cell to treat a condition or health problem. The improvement of the pharmaceutical delivery systems' effectiveness, safety, and stability is accomplished through the Formulation of the nano-gel-based delivery system. Nanogels are aqueous dispersions of submicronsized, three-dimensional, strongly cross-linked networks of hydrophilic polymers that are inflated by water. Through a variety of delivery routes, such as oral, pulmonary, nasal, parenteral, and intraocular, an active pharmaceutical agent or therapeutic agent with a high or low molecular weight can be easily encapsulated into nanogels. Nanogels have been researched as drug delivery systems due to their beneficial qualities, such as biocompatibility, high stability, flexible particle size, drug loading capacity, and potential surface modification for active targeting by attaching ligands that recognize cognate receptors on target cells or tissues. By responding to internal or external stimuli, including pH, temperature, light, and redox, nano gels can be made to be stimulus-responsive, allowing for regulated drug release. Thus, in the fact of said characteristics' of nano gels, this review manuscript aims to provide an overview of characterization, evaluation, formulation technique, recent applications, and patents of nano gels.

Sulfadiazine Exerts Potential Anticancer Effect in HepG2 and MCF7 Cells by Inhibiting TNFα, IL1b, COX-1, COX-2, 5-LOX Gene Expression: Evidence from In Vitro and Computational Studies.

Drug repurposing is a promising approach that has the potential to revolutionize the drug discovery and development process. By leveraging existing drugs, we can bring new treatments to patients more quickly and affordably. Anti-inflammatory drugs have been shown to target multiple pathways involved in cancer development and progression. This suggests that they may be more effective in treating cancer than drugs that target a single pathway. Cell viability was measured using the MTT assay. The expression of genes related to inflammation (TNFa, IL1b, COX-1, COX-2, and 5-LOX) was measured in HepG2, MCF7, and THLE-2 cells using qPCR. The levels of TNFα, IL1b, COX-1, COX-2, and 5-LOX were also measured in these cells using an ELISA kit. An enzyme binding assay revealed that sulfadiazine expressed weaker inhibitory activity against COX-2 (IC50 = 5.27 µM) in comparison with the COX-2 selective reference inhibitor celecoxib (COX-2 IC50 = 1.94 µM). However, a more balanced inhibitory effect was revealed for sulfadiazine against the COX/LOX pathway with greater affinity towards 5-LOX (IC50 = 19.1 µM) versus COX-1 (IC50 = 18.4 µM) as compared to celecoxib (5-LOX IC50 = 16.7 µM, and COX-1 IC50 = 5.9 µM). MTT assays revealed the IC50 values of 245.69 ± 4.1 µM and 215.68 ± 3.8 µM on HepG2 and MCF7 cell lines, respectively, compared to the standard drug cisplatin (66.92 ± 1.8 µM and 46.83 ± 1.3 µM, respectively). The anti-inflammatory effect of sulfadiazine was also depicted through its effect on the levels of inflammatory markers and inflammation-related genes (TNFα, IL1b, COX-1, COX-2, 5-LOX). Molecular simulation studies revealed key binding interactions that explain the difference in the activity profiles of sulfadiazine compared to celecoxib. The results suggest that sulfadiazine exhibited balanced inhibitory activity against the 5-LOX/COX-1 enzymes compared to the selective COX-2 inhibitor, celecoxib. These findings highlight the potential of sulfadiazine as a potential anticancer agent through balanced inhibitory activity against the COX/LOX pathway and reduction in the expression of inflammatory genes.

Cannabis Sativa in Phytotherapy: Reappraisal of Therapeutic Potential and Regulatory Aspects.

Cannabis sativa is widely used as a folk medicine in many parts of the globe and has been reported to be a treasure trove of phytoconstituents, including cannabinoids, terpenoids, and flavonoids. Accumulating evidence from various pre-clinical and clinical studies revealed the therapeutic potential of these constituents in various pathological conditions, including chronic pain, inflammation, neurological disorders, and cancer. However, the psychoactive effect and addiction potential associated with cannabis use limited its clinical application. In the past two decades, extensive research on cannabis has led to a resurgence of interest in the clinical application of its constituents, particularly cannabinoids. This review summarizes the therapeutic effect and molecular mechanism of various phytoconstituents of cannabis. Furthermore, recently developed nanoformulations of cannabis constituents have also been reviewed. Since cannabis is often associated with illicit use, regulatory aspects are of vital importance and this review therefore also documented the regulatory aspects of cannabis use along with clinical data and commercial products of cannabis.

Myrica esculenta Buch.-Ham. (ex D. Don): A Review on its Phytochemistry, Pharmacology and Nutritional Potential.

Myrica esculenta is an important ethnomedicinal plant used in the traditional system of medicine and as an important nutraceutical. Several studies on the plant justify its use in alternative systems of medicine and establish a scientific rationale for its possible therapeutic application. The plant contains a range of biologically active classes of compounds, particularly diarylheptanoids, flavonoids, terpenes, tannins, and glycosides. The nutraceutical potential of the plant can be particularly attributed to its fruit, and several studies have demonstrated the presence of carbohydrates, proteins, fats, fiber content, and minerals like sodium, potassium, calcium, manganese, iron, copper, and zinc, in it. The current review aims to provide complete insight into the phytochemistry, pharmacological potential, and nutritional potential of the plant, which would not only serve as a comprehensive source of information but also will highlight the scope of isolation and evaluation of these molecules for various disease conditions.

Convenient Synthesis of N-Alkyl-2-(3-phenyl-quinoxalin-2-ylsulfanyl)acetamides and Methyl-2-[2-(3-phenyl-quinoxalin-2-ylsulfanyl)acetylamino]alkanoates.

A series of 27 new quinoxaline derivatives (N-alkyl-[2-(3-phenyl-quinoxalin-2-ylsulfanyl)]acetamides, methyl-2-[2-(3-phenylquinoxalin-2-ylsulfanyl)-acetylamino]alkanoates, and their corresponding dipeptides) were prepared from 3-phenylquinoxaline-2(1H)-thione based on the chemoselective reaction with soft electrophiles. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to study the efficacy of 27 compounds on cancer cell viability and proliferation. A total of 13 compounds (4a-c, 5, 6, 8c, 9c, 9f, 10a, 10b, 11c, 12b, and 12c) showed inhibitory action on HCT-116 cancer cells and 15 compounds (4a-c, 5, 6, 8c, 9a, 9c, 9f, 9h, 10b, 11c, 12a, 12b, and 12c) showed activity on MCF-7 cancer cells, with compound 10b exhibiting the highest inhibitory action (IC50 1.52 and 2 µg/mL, respectively) on both cell lines. The molecular modeling studies on the human thymidylate synthase (hTS) homodimer interface showed that these compounds are good binders and could selectively inhibit the enzyme by stabilizing its inactive conformation. The study also identified key residues for homodimer binding, which could be used for further optimization and development.

WITHDRAWN: Cannabis Sativa In Phytotherapy : Reappraisal Of Therapeutic Potential And Regulatory Aspects

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Recent Advancements in CNS Acting Drugs: A Step Towards End of Illness.

Progressive degeneration in the morphology and functions of neuronal cells leads to multifactorial pathogenesis conditions of oxidative stress, mitochondrial dysfunction, excitotoxicity, nitric oxide toxicity, and neuro-inflammation to mediate heterogeneous types of neurodegenerative diseases, such as Epilepsy, Alzheimer's (AD) and Parkinson's (PD), more prominently among aging populations. In this editorial, complex mechanisms, challenges, and advancements made in the discovery of new neurotherapeutics, as well as designing approaches being adopted to fabricate brain-targeted delivery systems, are discussed.

Dysfunction of ABC Transporters at the Surface of BBB: Potential Implications in Intractable Epilepsy and Applications of Nanotechnology Enabled Drug Delivery.

Epilepsy is a chronic neurological disorder affecting 70 million people globally. One of the fascinating attributes of brain microvasculature is the (BBB), which controls a chain of distinct features that securely regulate the molecules, ions, and cells movement between the blood and the parenchyma. The barrier's integrity is of paramount importance and essential for maintaining brain homeostasis, as it offers both physical and chemical barriers to counter pathogens and xenobiotics. Dysfunction of various transporters in the (BBB), mainly ATP binding cassette (ABC), is considered to play a vital role in hampering the availability of antiepileptic drugs into the brain. ABC (ATP-binding cassette) transporters constitute a most diverse protein superfamily, which plays an essential part in various biological processes, including cell homeostasis, cell signaling, uptake of nutrients, and drug metabolism. Moreover, it plays a crucial role in neuroprotection by out-flowing various internal and external toxic substances from the interior of a cell, thus decreasing their buildup inside the cell. In humans, forty-eight ABC transporters have been acknowledged and categorized into subfamilies A to G based on their phylogenetic analysis. ABC subfamilies B, C, and G, impart a vital role at the BBB in guarding the brain against the entrance of various xenobiotic and their buildup. The illnesses of the central nervous system have received a lot of attention lately Owing to the existence of the BBB, the penetration effectiveness of most CNS medicines into the brain parenchyma is very limited (BBB). In the development of neurological therapies, BBB crossing for medication delivery to the CNS continues to be a major barrier. Nanomaterials with BBB cross ability have indeed been extensively developed for the treatment of CNS diseases due to their advantageous properties. This review will focus on multiple possible factors like inflammation, oxidative stress, uncontrolled recurrent seizures, and genetic polymorphisms that result in the deregulation of ABC transporters in epilepsy and nanotechnology-enabled delivery across BBB in epilepsy.

Nanotechnological Approaches for the Treatment of Triple-Negative Breast Cancer: A Comprehensive Review.

Breast cancer is the most prevalent cancer in women around the world, having a sudden spread nowadays because of the poor sedentary lifestyle of people. Comprising several subtypes, one of the most dangerous and aggressive ones is triple-negative breast cancer or TNBC. Even though conventional surgical approaches like single and double mastectomy and preventive chemotherapeutic approaches are available, they are not selective to cancer cells and are only for symptomatic treatment. A new branch called nanotechnology has emerged in the last few decades that offers various novel characteristics, such as size in nanometric scale, enhanced adherence to multiple targeting moieties, active and passive targeting, controlled release, and site-specific targeting. Among various nanotherapeutic approaches like dendrimers, lipid-structured nanocarriers, carbon nanotubes, etc., nanoparticle targeted therapeutics can be termed the best among all for their specific cytotoxicity to cancer cells and increased bioavailability to a target site. This review focuses on the types and molecular pathways involving TNBC, existing treatment strategies, various nanotechnological approaches like exosomes, carbon nanotubes, dendrimers, lipid, and carbon-based nanocarriers, and especially various nanoparticles (NPs) like polymeric, photodynamic, peptide conjugated, antibody-conjugated, metallic, inorganic, natural product capped, and CRISPR based nanoparticles already approved for treatment or are under clinical and pre-clinical trials for TNBC.

A Comprehensive Review on Journey of Pyrrole Scaffold Against Multiple Therapeutic Targets.

Heterocyclic compounds are that type of substances that are deeply intertwined with biological processes. Heterocycles are found in about 90% of commercially available medicines. In medicinal chemistry, finding new synthetic molecules with drug-like characteristics is a regular problem, which triggered the development of pharmacological molecules, the majority of which are based on N-heterocyclic motifs. Among the heterocycles, the pyrrole scaffold is the most commonly found heterocycle in both natural and synthetic bioactive compounds. Pyrrole has a fivemembered heterocyclic ring with a plethora of pharmacophores, resulting in a library of different lead compounds. Pyrrole derivatives are physiologically active heterocyclic compounds that can be used as scaffolds for antibacterial, antiviral, anticancer, antitubercular, anti-inflammatory, and as enzyme inhibitors. On account of their extensive pharmacological profile, pyrrole and its various synthetic derivatives have drawn much attention from researchers to explore it for the benefit of humankind. This review presents an overview of recent developments in the pyrrole derivatives against multiple therapeutic targets.

Brain-Derived Neurotropic Factor in Neurodegenerative Disorders.

Globally, neurodegenerative diseases cause a significant degree of disability and distress. Brain-derived neurotrophic factor (BDNF), primarily found in the brain, has a substantial role in the development and maintenance of various nerve roles and is associated with the family of neurotrophins, including neuronal growth factor (NGF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5). BDNF has affinity with tropomyosin receptor kinase B (TrKB), which is found in the brain in large amounts and is expressed in several cells. Several studies have shown that decrease in BDNF causes an imbalance in neuronal functioning and survival. Moreover, BDNF has several important roles, such as improving synaptic plasticity and contributing to long-lasting memory formation. BDNF has been linked to the pathology of the most common neurodegenerative disorders, such as Alzheimer's and Parkinson's disease. This review aims to describe recent efforts to understand the connection between the level of BDNF and neurodegenerative diseases. Several studies have shown that a high level of BDNF is associated with a lower risk for developing a neurodegenerative disease.

Recent Insights into Therapeutic Potential of Plant-Derived Flavonoids against Cancer.

Flavonoids, a class of polyphenolic secondary metabolites, are present in fruits, vegetables, beverages such as wine and tea abundantly. Flavonoids exhibit a diverse array of pharmacological activities, including anticancer activity, and are toxic to cancer cells but not harmful to healthy cells. Besides, humans and animals cannot synthesize flavonoids, which leads to a dramatic increase in the consumption of plant flavonoids. Flavonoids consist of a 15- carbon skeleton in C6-C3-C6 rings with divergent substitution patterns to form a series of compounds. Due to their multi-faceted mechanism of action by modulating various signaling pathways associated with apoptosis, cellular proliferation, inflammation, differentiation, metastasis, angiogenesis, they interrupt the initiation, promotion, and progression of cancer. The present review highlights the Structural Activity Relationship (SAR) of flavonoids and recent insights on the progress of natural flavonoids and their synthetic analogs as prospective drug candidates against cancer, along with molecular mechanisms of action.

Thymoquinone: Review of Its Potential in the Treatment of Neurological Diseases.

Thymoquinone (TQ) possesses anticonvulsant, antianxiety, antidepressant, and antipsychotic properties. It could be utilized to treat drug misuse or dependence, and those with memory and cognitive impairment. TQ protects brain cells from oxidative stress, which is especially pronounced in memory-related regions. TQ exhibits antineurotoxin characteristics, implying its role in preventing neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. TQ's antioxidant and anti-inflammatory properties protect brain cells from damage and inflammation. Glutamate can trigger cell death by causing mitochondrial malfunction and the formation of reactive oxygen species (ROS). Reduction in ROS production can explain TQ effects in neuroinflammation. TQ can help prevent glutamate-induced apoptosis by suppressing mitochondrial malfunction. Several studies have demonstrated TQ's role in inhibiting Toll-like receptors (TLRs) and some inflammatory mediators, leading to reduced inflammation and neurotoxicity. Several studies did not show any signs of dopaminergic neuron loss after TQ treatment in various animals. TQ has been shown in clinical studies to block acetylcholinesterase (AChE) activity, which increases acetylcholine (ACh). As a result, fresh memories are programmed to preserve the effects. Treatment with TQ has been linked to better outcomes and decreased side effects than other drugs.

Retraction Note to: A novel self-nanoemulsifying drug delivery system for curcumin used in the treatment of wound healing and inflammation.

[This retracts the article DOI: 10.1007/s13205-019-1885-3.].

Neuroinflammation: A Potential Risk for Dementia.

Dementia is a neurodegenerative condition that is considered a major factor contributing to cognitive decline that reduces independent function. Pathophysiological pathways are not well defined for neurodegenerative diseases such as dementia; however, published evidence has shown the role of numerous inflammatory processes in the brain contributing toward their pathology. Microglia of the central nervous system (CNS) are the principal components of the brain's immune defence system and can detect harmful or external pathogens. When stimulated, the cells trigger neuroinflammatory responses by releasing proinflammatory chemokines, cytokines, reactive oxygen species, and nitrogen species in order to preserve the cell's microenvironment. These proinflammatory markers include cytokines such as IL-1, IL-6, and TNFα chemokines such as CCR3 and CCL2 and CCR5. Microglial cells may produce a prolonged inflammatory response that, in some circumstances, is indicated in the promotion of neurodegenerative diseases. The present review is focused on the involvement of microglial cell activation throughout neurodegenerative conditions and the link between neuroinflammatory processes and dementia.

Berberine in the Treatment of Neurodegenerative Diseases and Nanotechnology Enabled Targeted Delivery.

BACKGROUND: Berberine (BBR), an alkaloidal compound found in many plants, is widely used for hundreds of years in the traditional system of Chinese medicine. OBJECTIVE/AIM: The present review is aimed to summarize the potential of Berberine in the amelioration of various neurological disorders. METHODS: The collection of data for the compilation of this review work was searched in PubMed Scopus, Google Scholar, and Science Direct. Of late, researchers are more focused on its beneficial role in neurodegenerative diseases. RESULTS: BBR has proven its protective role in numerous neurotoxicity models including, oxygen-glucose deprivation, mercury-induced, neurodegenerative model by ibotenic acid, and hypoxia caused by COCl2. BBR treatment averts the generation of reactive oxygen species in the oxygen-glucose deprivation model. Further, it subdues cytochrome c along with the divulge of apoptosis-inducing factors that indicate its beneficial action in the management of stroke. BBR diminished hydrogen peroxide-induced neuronal damage by enhancing the PI3k / Akt / Nrf-2 based pathway and showed a preventive impact on neurites of SH-SY5Y cells by averting the formation of ROS and inhibiting apoptosis. The impact of BBR on neurological disorder using a transgenic AD type mouse strain (TgCRND8) showed a reduction in the piling up of amyloid-ß plaque. In mice, administration of BBR in the dose range of 5-10m/kg has been reported to raise the levels of serotonin (47%), dopamine (31%), and norepinephrine (29%) in CNS to allay depression. CONCLUSION: The present review is aimed to summarize the potential of Berberine in the amelioration of various neurological disorders.

Structural Activity Relationship based Medicinal Perspectives of Pyrimidine Derivatives as Anti-Alzheimer's Agents: A Comprehensive Review.

Pyrimidine is an aromatic and heterocyclic organic compound containing a 6-membered ring consisting of four carbon and two nitrogen atoms on alternative positions. Pyrimidine scaffolds described their existence in the medicinal chemist's cause for their synthesizing practicability and nonpoisonous nature. However, the reason behind neurological disorders is still an open challenge for scientific research and development organizations. Efficacy voids are widespread before researchers, despite high throughput research in the field of anti-Alzheimer's drugs.Researchers have constantly investigated all the probabilities for restraining the unwanted adverse effects of the anti-Alzheimer's agents and are focusing more extensively to rehabilitate neurological disorders. The scientific literature on drug development has been an aspiration to medicinal chemists and other researchers to facilitate further research. Therefore, this review emphasizes the structure-activity relationship (SAR) based approach and the pharmacological advancements of pyrimidine moiety in the new era of therapeutics as anti-Alzheimer's agents.

Recent Advancement of Pyrazole Scaffold Based Neuroprotective Agents: A Review.

As a source of therapeutic agents, heterocyclic nitrogen-containing compounds and their derivatives are still interesting and essential. Pyrazole, a five-member heteroaromatic ring with two nitrogen atoms, has a major impact in chemical industries as well as pharmaceutical industries. Due to its wide range of biological activities against various diseases, it has been identified as a biologically important heterocyclic scaffold. The treatment of neurological disorders has always been a difficult task in both the past and present. Therefore, identifying therapeutically effective molecules for neurological conditions remains an open challenge in biomedical research and development. For developing novel entities as neuroprotective agents, recently, pyrazole scaffold has attracted medicinal chemists worldwide. The major focus of research in this area is discovering novel molecules as neuroprotective agents with minimal adverse effects and better effectiveness in improving the neurological condition. This review mainly covers recent developments in the neuropharmacological role of pyrazole incorporated compounds, including their structural-activity relationship (SAR), which also further includes IC50 values (in mM as well as in µM), recent patents, and a brief history as neuroprotective agents.