Nanomedicine: A New Frontier in Alzheimer's Disease Drug Targeting.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting elderly individuals, characterized by progressive cognitive decline leading to dementia. This review examines the challenges posed by anatomical and biochemical barriers such as the blood-brain barrier (BBB), blood-cerebrospinal fluid barrier (BCSFB), and p-glycoproteins in delivering effective therapeutic agents to the central nervous system (CNS) for AD treatment. This article outlines the fundamental role of acetylcholinesterase inhibitors (AChEIs) and NMDA(N-Methyl-D-Aspartate) receptor antagonists in conventional AD therapy and highlights their limitations in terms of brain-specific delivery. It delves into the intricacies of BBB and pglycoprotein-mediated efflux mechanisms that impede drug transport to the CNS. The review further discusses cutting-edge nanomedicine-based strategies, detailing their composition and mechanisms that enable effective bypassing of BBB and enhancing drug accumulation in brain tissues. Conventional therapies, namely AChEIs and NMDA receptor antagonists, have shown limited efficacy and are hindered by suboptimal brain penetration. The advent of nanotechnology-driven therapeutic delivery systems offers promising strategies to enhance CNS targeting and bioavailability, thereby addressing the shortcomings of conventional treatments. Various nanomedicines, encompassing polymeric and metallic nanoparticles (MNPs), solid lipid nanoparticles (SLNs), liposomes, micelles, dendrimers, nanoemulsions, and carbon nanotubes, have been investigated for their potential in delivering anti-AD agents like AChEIs, polyphenols, curcumin, and resveratrol. These nanocarriers exhibit the ability to traverse the BBB and deliver therapeutic payloads to the brain, thereby holding immense potential for effective AD treatment and early diagnostic approaches. Notably, nanocarriers loaded with AChEIs have shown promising results in preclinical studies, exhibiting improved therapeutic efficacy and sustained release profiles. This review underscores the urgency of innovative drug delivery approaches to overcome barriers in AD therapy. Nanomedicine-based solutions offer a promising avenue for achieving effective CNS targeting, enabling enhanced bioavailability and sustained therapeutic effects. As ongoing research continues to elucidate the complexities of CNS drug delivery, these advancements hold great potential for revolutionizing AD treatment and diagnosis.

Design, QSAR Methodology, Synthesis and Assessment of Some Structurally Different Xanthone Derivatives as Selective Cox-2 Inhibitors for their Anti-inflammatory Properties.

INTRODUCTION: Inflammation can be defined as a complex biological response that is produced by body tissues to harmful agents like pathogens, irritants, and damaged cells and thereby acts as a protective response incorporating immune cells, blood vessels, and molecular mediators. Histamine, serotonin, bradykinin, leukotrienes (LTB4), prostaglandins (PGE2), prostacyclins, reactive oxygen species, proinflammatory cytokines like IL-1, IL-11, TNF- anti-inflammatory cytokines like IL-4, IL-10, IL-11, IL-6 and IL-13, etc. all have different effects on both pro and anti-inflammatory mediators. Incorporation of combinatorial chemistry and computational studies have helped the researchers to design xanthones moieties with high selectivity that can serve as a lead compound and help develop potential compounds that can act as effective COX-2 inhibitors. The study aims to design and develop different series of substituted hydroxyxanthone derivatives with anti-inflammatory potential. METHODS: The partially purified synthetic xanthone derivatives were orally administered to the carrageenan induced paw oedemic rat models at the dose of 100 mg/kg, and their effect in controlling the degree of inflammation was measured at the time interval of 30 min, 1, 2, 3, 4 and 6 hrs. respectively. Further, these compounds were also subjected to modern analytical studies like UV, IR, NMR and mass spectrometry or their characterization. RESULTS: The results drawn out of the in silico, in vitro, in vivo and analytical studies concluded that the hydroxyxanthone derivatives can obstruct the enzyme COX-2 and produce anti-inflammatory action potentially. CONCLUSION: With the aim to evaluate the compounds for their anti-inflammatory activity, it was observed that the newly designed xanthonic compounds also possess a safe toxicity margin and hence can be utilized by the researchers to develop hybrid xanthonic moieties that can specifically target the enzyme COX-2.

Chitosan-based topical formulation integrated with green-synthesized silver nanoparticles utilizing Camellia sinensis leaf extracts: A promising approach for managing infected wounds.

This study explores the eco-friendly biosynthesis of silver nanoparticles (AgNPs) utilizing Camellia sinensis leaf extract. We assess their antioxidant and antibacterial properties. Furthermore, we impregnated AgNPs into 2 % chitosan (CHS) gel and assessed their wound-healing potential in Escherichia coli and Staphylococcus aureus infected wounds. Optimized AgNPs demonstrated a mean particle size of 36.90 ± 1.22 nm and a PDI of 0.049 ± 0.001. Green-synthesized AgNPs exhibited enhanced free radical inhibition (IC50: 31.45 µg/mL, 34.01 µg/mL, 27.40 µg/mL) compared to leaf extract (IC50: 52.67 µg/mL, 59.64 µg/mL, 97.50 µg/mL) in DPPH, hydrogen peroxide, and nitric oxide free radical scavenging assays, respectively. The MIC/MBC values of AgNPs against E. coli and S. aureus were 5 ppm/ 7.5 ppm and 10 ppm/ 15 ppm, respectively. Furthermore, our study showed that green-synthesized AgNPs at MIC significantly reduced the biofilm production of E. coli (70.37 %) and S. aureus (67.40 %). The CHS/AgNPs gel exhibited potent wound healing activities, comparable to a commercial cream with the re-epithelialization period of 8.16 ± 0.75. Histological analysis demonstrated enhanced skin regeneration with a thicker epidermal layer, well-defined papillary dermal structure, and organized collagen fibers. In summary, these findings hold promise for addressing bacterial infections, particularly those associated with biofilms-related wound infections.

Nanotheranostics: application of nanosensors in diabetes management.

Objectives: The objective of the present study is to discuss the use of nanomaterials like nanosensors for diagnosing Diabetes and highlight their applications in the treatment of Diabetes. Methods: Diabetes mellitus (D.M.) is a group of metabolic diseases characterized by hyperglycemia. Orally administered antidiabetic drugs like glibenclamide, glipalamide, and metformin can partially lower blood sugar levels, but long-term use causes kidney and liver damage. Recent breakthroughs in nanotheranostics have emerged as a powerful tool for diabetes treatment and diagnosis. Results: Nanotheranostics is a rapidly developing area that can revolutionize diabetes diagnosis and treatment by combining therapy and imaging in a single probe, allowing for pancreas-specific drug and insulin delivery. Nanotheranostic in Diabetes research has facilitated the development of improved glucose monitoring and insulin administration modalities, which promise to improve the quality of life for people with Diabetes drastically. Further, nanomaterials like nanocarriers and unique functional nanomaterials used as nano theranostics tools for treating Diabetes will also be highlighted. Conclusion: The nanosensors discussed in this review article will encourage researchers to develop innovative nanomaterials with novel functionalities and properties for diabetes detection and treatment.

Herbal medicine for the treatment of obesity-associated asthma: a comprehensive review.

Obesity is fast growing as a global pandemic and is associated with numerous comorbidities like cardiovascular disease, hypertension, diabetes, gastroesophageal reflux disease, sleep disorders, nephropathy, neuropathy, as well as asthma. Studies stated that obese asthmatic subjects suffer from an increased risk of asthma, and encounter severe symptoms due to a number of pathophysiology. It is very vital to understand the copious relationship between obesity and asthma, however, a clear and pinpoint pathogenesis underlying the association between obesity and asthma is scarce. There is a plethora of obesity-asthma etiologies reported viz., increased circulating pro-inflammatory adipokines like leptin, resistin, and decreased anti-inflammatory adipokines like adiponectin, depletion of ROS controller Nrf2/HO-1 axis, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) associated macrophage polarization, hypertrophy of WAT, activation of Notch signaling pathway, and dysregulated melanocortin pathway reported, however, there is a very limited number of reports that interrelates these pathophysiologies. Due to the underlying complex pathophysiologies exaggerated by obese conditions, obese asthmatics respond poorly to anti-asthmatic drugs. The poor response towards anti-asthmatic drugs may be due to the anti-asthmatics approach only that ignores the anti-obesity target. So, aiming only at the conventional anti-asthmatic targets in obese-asthmatics may prove to be futile until and unless treatment is directed towards ameliorating obesity pathogenesis for a holistic approach towards amelioration of obesity-associated asthma. Herbal medicines for obesity as well as obesity-associated comorbidities are fast becoming safer and more effective alternatives to conventional drugs due to their multitargeted approach with fewer adverse effects. Although, herbal medicines are widely used for obesity-associated comorbidities, however, a limited number of herbal medicines have been scientifically validated and reported against obesity-associated asthma. Notable among them are quercetin, curcumin, geraniol, resveratrol, ß-Caryophyllene, celastrol, tomatidine to name a few. In view of this, there is a dire need for a comprehensive review that may summarize the role of bioactive phytoconstituents from different sources like plants, marine as well as essential oils in terms of their therapeutic mechanisms. So, this review aims to critically discuss the therapeutic role of herbal medicine in the form of bioactive phytoconstituents against obesity-associated asthma available in the scientific literature to date.

Therapeutic potential of bioactive phytoconstituents found in fruits in the treatment of non-alcoholic fatty liver disease: A comprehensive review.

Nonalcoholic fatty liver disease (NAFLD), a chronic liver condition affects a large number of people around the world with a frequency of 25% of all the chronic liver disease worldwide. Several targets viz. anti-inflammatory, anti-apoptotic and, anti-fibrotic factors, anti-oxidant and insulin-sensitizing pathways, metabolic regulators as well as repurposing traditional medications have been studied for the pharmacologic therapy of NAFLD. Newer pharmacotherapies like caspases blockade, agonists of PPAR and farnesoid X receptor agonists are currently being investigated in treating human NAFLD. However, NAFLD has no FDA-approved pharmacological therapy, therefore there is a considerable unmet therapy need. Apart from the conventional treatment regime, the current approaches to treating NAFLD include lifestyle interventions including healthy diet with adequate nutrition and physical activity. Fruits are known to play a key role in the well-being of human health. Fruits are loaded with a repertoire of bioactive phytoconstituents like catechins, phytosterols, proanthocyanidin, genestin, daidzen, resveratrol, magiferin found in fruits like pear, apricot, strawberries, oranges, apples, bananas, grapes, kiwi, pineapple, watermelon, peach, grape seed and skin, mango, currants, raisins, dried dates, passion fruit and many more. These bioactive phytoconstituents are reported to demonstrate promising pharmacological efficacy like reduction in fatty acid deposition, increased lipid metabolism, modulation of insulin signaling pathway, gut microbiota and hepatic inflammation, inhibition of histone acetyltransferase enzymatic activity to name a few. Not only fruits, but their derivatives like oils, pulp, peel, or their preparations are also found to be equally beneficial in various liver diseases like NAFLD, NASH. Although most of the fruits contains potent bioactive phytoconstituents, however, the presence of sugar in fruits put a question mark on the ameliorative property of the fruits and there has been contrasting reports on the glycemic control post fruit consumption in type 2 diabetic patients. This review is an attempt to summarize the beneficial effects of fruit phytoconstituents on NAFLD based on epidemiological, clinical and experimental evidence, focusing especially on their mechanisms of action.

Recent Advances on Natural and Non-Natural Xanthones as Potential Anticancer Agents: A Review.

BACKGROUND: Xanthones, natural or synthetic, due to their wide range of biological activities, have become an interesting subject of investigation for many researchers. Xanthonic scaffold has proven to have a vital role in anticancer drug development since many of its derivatives have shown anticancer activities on various cell lines. In addition, targeting epigenetic markers in cancer has yielded promising results. There have also been reports on the impact of xanthone and related polyphenolic compounds on epigenetics markers in cancer prevention and therapy. OBJECTIVE: The objective of this review is to comprehensively highlight the main natural and nonnatural sources of xanthones having potential anti-cancer effects along with their key structural elements, structure-activity relationships (SARs), mechanisms of action, and epigenetic profile of xanthone- based anti-cancer compounds. The challenges and future directions of xanthone-based therapies are also discussed briefly. METHOD: The methods involved in the preparation of the present review included the collection of all recent information up to November 2021 from various scientific databases, indexed periodicals, and search engines such as Medline Scopus, Google Scholar, PubMed, PubMed Central, Web of Science, and Science Direct. RESULTS: Exploration of the diversity of the xanthone scaffold led to the identification of several derivatives having prominent anti-cancer activity. Their unique structural diversity and synthetic modifications showed the ongoing endeavour of enriching the chemical diversity of the xanthone molecular framework to discover pharmacologically interesting compounds. However, studies regarding their modes of action, pharmacokinetic properties, clinical data, epigenetics, and safety are limited. CONCLUSION: Elucidation of the exact biological mechanisms and the associated targets of xanthones will yield better opportunities for these compounds to be developed as potential anticancer drugs. Further clinical studies with conclusive results are required to implement xanthones as treatment modalities in cancer.

Green Synthesis of Titanium Dioxide Nanoparticles Using Ocimum sanctum Leaf Extract: In Vitro Characterization and Its Healing Efficacy in Diabetic Wounds.

Diabetes mellitus is one of the most prevalent metabolic disorders characterized by hyperglycemia due to impaired glucose metabolism. Overproduction of free radicals due to chronic hyperglycemia may cause oxidative stress, which delays wound healing in diabetic conditions. For people with diabetes, this impeded wound healing is one of the predominant reasons for mortality and morbidity. The study aimed to develop an Ocimum sanctum leaf extract-mediated green synthesis of titanium dioxide (TiO2) nanoparticles (NPs) and further incorporate them into 2% chitosan (CS) gel for diabetic wound healing. UV-visible spectrum analysis recorded the sharp peak at 235 and 320 nm, and this was the preliminary sign for the biosynthesis of TiO2 NPs. The FTIR analysis was used to perform a qualitative validation of the biosynthesized TiO2 nanoparticles. XRD analysis indicated the crystallinity of TiO2 NPs in anatase form. Microscopic investigation revealed that TiO2 NPs were spherical and polygonal in shape, with sizes ranging from 75 to 123 nm. The EDX analysis of green synthesized NPs showed the presence of TiO2 NPs, demonstrating the peak of titanium ion and oxygen. The hydrodynamic diameter and polydispersity index (PDI) of the TiO2 NPs were found to be 130.3 nm and 0.237, respectively. The developed TiO2 NPs containing CS gel exhibited the desired thixotropic properties with pseudoplastic behavior. In vivo wound healing studies and histopathological investigations of healed wounds demonstrated the excellent wound-healing efficacy of TiO2 NPs containing CS gel in diabetic rats.

Immunomodulatory effect of mushrooms and their bioactive compounds in cancer: A comprehensive review.

Despite enormous development in the field of drug development, cancer still remains elusive. Compromised immunity stands as a roadblock to the successful pharmacological execution of anti-cancer drugs used clinically currently. Recently some breakthrough cancer treatment strategy like nano-formulation, extracellular vesicles treatment, natural antioxidant therapy, targeted immunotherapy, gene therapy, thermal ablation and magnetic hyperthermia, and pathomics and radiomics has been developed and tested pre-clinically as well as clinically. However, clinical efficacy of such therapies is yet to establish and some are too costly to be utilized by patients from poor and developing countries. At this juncture, researchers are heading towards the search of medicines from natural sources that is higher safety margin and multitarget pharmacological efficacy compared to conventional treatments. Mushroom is used traditionally as food as well as drug since time immemorial due to its immunomodulatory effect which is loaded with proteins, low fat content and cholesterol. Mushrooms are recommended as one of the best vegetarian diets for immunosuppressed cancer and HIV/AIDS patients. Mushrooms are well-known for their anti-cancer activity that impacts hematopoietic stem cells, lymphocytes, macrophages, T cells, dendritic cells (DCs), and natural killer (NK) cells in the immune system. This comprehensive review article emphasizes on the molecular mechanisms of cancer genesis, conventional anti-cancer therapy as well as reported some significant breakthrough in anti-cancer drug development, anti-cancer activity of some selected species of mushrooms and their bioactive phytoconstituents followed by a brief discussion of recent anti-cancer efficacy of some metallic nanoparticles loaded with mushrooms.

Emerging advances in nanomedicine for breast cancer immunotherapy: opportunities and challenges.

Breast cancer is one of the most common causes of cancer-related morbidity and mortality in women worldwide. Early diagnosis and an appropriate therapeutic approach for all cancers are climacterics for a favorable prognosis. Targeting the immune system in breast cancer is already a clinical reality with notable successes, specifically with checkpoint blockade antibodies and chimeric antigen receptor T-cell therapy. However, there have been inevitable setbacks in the clinical application of cancer immunotherapy, including inadequate immune responses due to insufficient delivery of immunostimulants to immune cells and uncontrolled immune system modulation. Rapid advancements and new evidence have suggested that nanomedicine-based immunotherapy may be a viable option for treating breast cancer.

Cancer that begins in the breast is referred to as breast cancer. It may originate in either one or both breasts. It is one of the main causes of cancer-related death among women worldwide. Cancer immunotherapy is a game-changing treatment that improves the ability of the host defense system to spot and eliminate cancer cells with pinpoint accuracy. Cancer immunotherapy, also referred to as immuno-oncology, is a type of treatment option for breast cancer that uses the body's natural defense system to prevent, regulate and eliminate breast cancer. Immunotherapy is used to enhance or alter the functioning of the immune system so that it can locate and destroy cancer cells. Knowing how immunotherapy works and what to anticipate can often offer peace of mind to the patient who can then make informed decisions about care, especially if immunotherapy is part of the treatment plan for a particular patient.

Cancer Chemotherapy via Natural Bioactive Compounds.

BACKGROUND: Cancer-induced mortality is increasingly prevalent globally, which skyrocketed the necessity to discover new/novel, safe and effective anticancer drugs. Cancer is characterized by the continuous multiplication of cells in the human, which is unable to control. Scientific research is drawing its attention toward naturally-derived bioactive compounds as they have fewer side effects compared to the current synthetic drugs used for chemotherapy. OBJECTIVE: Drugs isolated from natural sources and their role in the manipulation of epigenetic markers in cancer are discussed briefly in this review article. METHODS: With advancing medicinal plant biotechnology and microbiology in the past century, several anticancer phytomedicines were developed. Modern pharmacopeia contains at least 25% herbal-based remedies, including clinically used anticancer drugs. These drugs mainly include the podophyllotoxin derivatives vinca alkaloids, curcumin, mistletoe plant extracts, taxanes, camptothecin, combretastatin, and colchicine artesunate, homoharringtonine, ellipticine, roscovitine, maytansine, tapsigargin,and bruceantin. RESULTS: Compounds (psammaplin, didemnin, dolastin, ecteinascidin, and halichondrin) isolated from marine sources and animals such as microalgae, cyanobacteria, heterotrophic bacteria, invertebrates. They have been evaluated for their anticancer activity on cells and experimental animal models and used chemotherapy.Drug-induced manipulation of epigenetic markers plays an important role in the treatment of cancer. CONCLUSION: The development of a new drug from isolated bioactive compounds of plant sources has been a feasible way to lower the toxicity and increase their effectiveness against cancer. Potential anticancer therapeutic leads obtained from various ethnomedicinal plants, foods, marine, and microorganisms are showing effective yet realistically safe pharmacological activity. This review will highlight important plant-based bioactive compounds like curcumin, stilbenes, terpenes, other polyphenolic phyto-compounds, and structurally related families that are used to prevent/ ameliorate cancer. However, a contribution from all possible fields of science is still a prerequisite for discovering safe and effective anticancer drugs.