SIRT1 (Sirtuin 1) is a NAD+-dependent deacetylase that functions through nucleoplasmic transfer and is present in nearly all mammalian tissues. SIRT1 is believed to deacetylate its protein substrates, resulting in neuroprotective actions, including reduced oxidative stress and inflammation, increased autophagy, increased nerve growth factors, and preserved neuronal integrity in aging or neurological disease. Nrf2 is a transcription factor that regulates the genes responsible for oxidative stress response and substance detoxification. The activation of Nrf2 guards cells against oxidative damage, inflammation, and carcinogenic stimuli. Several neurological abnormalities and inflammatory disorders have been associated with variations in Nrf2 activation caused by either pharmacological or genetic factors. Recent evidence indicates that Nrf2 is at the center of a complex cellular regulatory network, establishing it as a transcription factor with genuine pleiotropy. HO-1 is most likely a component of a defense mechanism in cells under stress, as it provides negative feedback for cell activation and mediator synthesis. This mediator is upregulated by Nrf2, nitric oxide (NO), and other factors in various inflammatory states. HO-1 or its metabolites, such as CO, may mitigate inflammation by modulating signal transduction pathways. Neurological diseases may be effectively treated by modulating the activity of HO-1. Multiple studies have demonstrated that SIRT1 and Nrf2 share an important connection. SIRT1 enhances Nrf2, activates HO-1, protects against oxidative injury, and decreases neuronal death. This has been associated with numerous neurodegenerative and neuropsychiatric disorders. Therefore, activating the SIRT1/Nrf2/HO-1 pathway may help treat various neurological disorders. This review focuses on the current understanding of the SIRT1 and Nrf2/HO-1 neuroprotective processes and the potential therapeutic applications of their target activators in neurodegenerative and neuropsychiatric disorders.

The human gut has 12 distinct phyla, among which Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes make up >90%. Depressed individuals are a significant phylum and are differentiated from healthy individuals by their firmicutes. The microbiome is a key component of the pathological basis of major depressive illness as a result of disruption of the microbiota-gut-brain (MGB) axis. The fact is that there is bidirectional communication inside the brain, stomach, and brain-gut, wherein the brain highlights a systemic disease characterized by both brain and peripheral dysfunction. According to the microbiota hypothesis, MGB axis dysfunction is a significant contributor to the pathogenic underpinnings of major depressive disorder (MDD). The etiology of MDD is complicated and includes an imbalance of neurotransmitters, an impaired hypothalamic-pituitary-adrenal (HPA) axis, inflammation, and the MGB axis. According to research, having an aberrant microbiome or a disjointed MGB axis may directly cause psychiatric diseases such as MDD. Hence, resolving these issues may help with depression symptoms. Probiotics may therefore have therapeutic benefits for psychiatric symptoms by fostering healthy and balanced gut flora. The probiotic Bifidobacterium longum NCC3001 has been shown to reduce depression scores. In this review, the unknown mysteries and myths of probiotics are unlocked with special attention given to MDD or depression.

The gastrointestinal (GI) microbiota benefits from the addition of probiotics, prebiotics, or synbiotics to the human diet. The human GI is colonized by a complicated environment of microorganisms. In addition to being commensal, intestinal bacteria coevolve with their host in a process known as synbiotic coevolution. Beneficial intestinal bacteria perform a wide range of crucial tasks for their host, including producing different nutrients, preventing infections brought on by intestinal pathogens, and regulating a healthy immune response. Therefore, changing the GI microbiota to accomplish, restore, and maintain a beneficial ecosystem balance as well as the activity of microorganisms found in the gastrointestinal tract are required for the host's enhanced health. In large part because of how probiotics and synbiotics affect the immune system's ability to regulate inflammation and the anti-inflammatory response, they are utilized to treat chronic disorders. Chronic immune system stimulation leads to discharge of pro-inflammatory mediators, such as C-reactive protein (CRP), TNF-β, and ILs (i.e., IL-6 and IL-1), which may lead to systemic inflammation. Numerous studies have shown a negative relationship between dietary fiber consumption and the biomarkers of systemic inflammation, even though dietary fibers like synbiotics have anti-inflammatory properties. Studies have also investigated how probiotics and synbiotics affect the biomarkers of oxidative stress and inflammation in different disease states. The resulting metabolite production from the helpful bacteria can control how immune markers change from having a pro-inflammatory phenotype to having an anti-inflammatory phenotype. The use of synbiotics to reduce oxidative stress and inflammatory biomarkers has drawn more attention recently.

Exosomes are a subgroup of extracellular vesicles that function as transmitters, allowing cells to communicate more effectively with each other. However, exosomes may have both beneficial and harmful impacts on central nervous system disorders. Hence, the fundamental molecular mechanisms of the origin of illness and its progression are currently being investigated. The involvement of exosomes in the origin and propagation of neurodegenerative illness has been demonstrated recently. Exosomes provide a representation of the intracellular environment since they include various essential bioactive chemicals. The latest studies have demonstrated that exosomes transport several proteins. Additionally, these physiological vesicles are important in the regeneration of nervous tissue and the healing of neuronal lesions. They also offer a microenvironment to stimulate the conformational variation of concerning proteins for aggregation, resulting in neurodegenerative diseases. The biosynthesis, composition, and significance of exosomes as extracellular biomarkers in neurodegenerative disorders are discussed in this article, with a particular emphasis on their neuroprotective effects.

INTRODUCTION:In the present study, solid lipid nanoparticles loaded with Rosiglitazone and probiotics were prepared via solvent emulsification diffusion method which is patented. As a lipid and surfactant, Gleceryl monostearate and Pluronic -68 were used in the formulation process. METHODS:During characterization, it was determined that ingredient quantity variations significantly impacted Rosiglitazone loading capacity, particle size, polydispersity index, etc. In an optimized formulation of RSG-PB loaded SLNs, spherical particles with a mean particle size of 147.66 ± 1.52 nm, PDI of 0.42 ± 0.02, and loading capacity of 45.36 ± 0.20 were identified. RESULTS:Moreover, the developed SLNs had the potential to discharge the drug for up to 24 hours, as predicted by Higuchi's pharmacokinetic model. The SLNs were stable at 25°C/60%RH for up to 60 days. There was little to no change in particle size, PDI, or loading capacity. In addition, the number of probiotic bacteria was determined using the standard plate count procedure. Further, the antioxidant effect of the prepared formulation is evaluated using the DPPH assay method. CONCLUSION:This study concludes that the method used to fabricate RSG-probiotic-loaded SLNs is straightforward and yields favorable results regarding various parameters, including sustained release property, particle size, PDI, and percent drug loading stability. Furthermore, DPPH radical scavenging activity shows the high antioxidant potential of RSG-PB SLNs when compared to RSG and probiotics alone.

In the present study, Probiotics (Lactobacillus plantarum) loaded-solid lipid nanoparticles were prepared and characterized. Probiotics have proven to possess significant potential in addressing a range of conditions, encompassing neurodegenerative disorders, cancers, cardiovascular diseases, and inflammatory conditions. Additionally, they show efficacy in sustaining a harmonious gut microbiota ecosystem. SLNs were prepared by using solvent emulsification-diffusion technique. The size and morphology of prepared probiotic-loaded SLNs were examined by transmission electron microscopy. The activity or viability of probiotics might be compromised in the challenging gastric conditions of the stomach or in the presence of bile salts. Furthermore, they may face vulnerability to thermal or oxidative stress during preparation and storage. Hence, there is a need for stable probiotic formulations to surmount diverse physicochemical, biopharmaceutical, and biological barriers, ensuring maximal therapeutic effectiveness and clinical applicability. In vitro experiments were carried out with the aim of examining the viability of bacterial cells under gastrointestinal conditions. Encapsulation of the cells protect the cell numbers (colony forming unit) when compared to free bacteria. Nevertheless, the number of probiotic cells decreased in gastrointestinal acidic condition in contrast to free cells. Overall encapsulation of Lactobacillus plantarum in SLN’s plays an important role in enhancing viability and stability which consequently enhance the survival of bacteria against gastrointestinal environmental conditions.

A significant number of deaths and disabilities worldwide are brought on by inflammatory lung diseases. Many inflammatory lung disorders, including chronic respiratory emphysema, resistant asthma, resistance to steroids, and coronavirus-infected lung infections, have severe variants for which there are no viable treatments; as a result, new treatment alternatives are needed. Here, we emphasize how oxidative imbalance contributes to the emergence of provocative lung problems that are challenging to treat. Endogenic antioxidant systems are not enough to avert free radical-mediated damage due to the induced overproduction of ROS. Pro-inflammatory mediators are then produced due to intracellular signaling events, which can harm the tissue and worsen the inflammatory response. Overproduction of ROS causes oxidative stress, which causes lung damage and various disease conditions. Invasive microorganisms or hazardous substances that are inhaled repeatedly can cause an excessive amount of ROS to be produced. By starting signal transduction pathways, increased ROS generation during inflammation may cause recurrent DNA damage and apoptosis and activate proto-oncogenes. This review provides information about new targets for conducting research in related domains or target factors to prevent, control, or treat such inflammatory oxidative stress-induced inflammatory lung disorders.

Silymarin, a bioflavonoid derived from the Silybum marianum plant, was discovered in 1960. It contains C25 and has been extensively used as a therapeutic agent against liver-related diseases caused by alcohol addiction, acute viral hepatitis, and toxins-inducing liver failure. Its efficacy stems from its role as a potent anti-oxidant and scavenger of free radicals, employed through various mechanisms. Additionally, silymarin or silybin possesses immunomodulatory characteristics, impacting immune-enhancing and immune-suppressive functions. Recently, silymarin has been recognized as a potential neuroprotective therapy for various neurological conditions, including Parkinson's and Alzheimer's diseases, along with conditions related to cerebral ischemia. Its hepatoprotective qualities, primarily due to its anti-oxidant and tissue-regenerating properties, are well-established. Silymarin also enhances health by modifying processes such as inflammation, β-amyloid accumulation, cellular estrogenic receptor mediation, and apoptotic machinery. While believed to reduce oxidative stress and support neuroprotective mechanisms, these effects represent just one aspect of the compound's multifaceted protective action. This review article further delves into the possibilities of potential therapeutic advancement of silymarin and silibinin for the management of neurodegenerative disorders via mechanics modules.

Lung cancer remains the leading cause of cancer-related deaths worldwide. According to the American Cancer Society (ACS), it ranks as the second most prevalent type of cancer globally. Recent findings have highlighted bidirectional gut-lung interactions, known as the gut-lung axis, in the pathophysiology of lung cancer. Probiotics are live microorganisms that boost host immunity when consumed adequately. The immunoregulatory mechanisms of probiotics are thought to operate through the generation of various metabolites that impact both the gut and distant organs (e.g., the lungs) through blood. Several randomized controlled trials have highlighted the pivotal role of probiotics in gut health especially for the prevention and treatment of malignancies, with a specific emphasis on lung cancer. Current research indicates that probiotic supplementation positively affects patients, leading to a suppression in cancer symptoms and a shortened disease course. While clinical trials validate the therapeutic benefits of probiotics, their precise mechanism of action remains unclear. This narrative review aims to provide a comprehensive overview of the present landscape of probiotics in the management of lung cancer.

Hypertension is a critical health problem. It is also the primary reason for coronary heart disease, stroke, and renal vascular disease. The use of herbal drugs in the management of any disease is increasing. They are considered the best immune booster to fight against several types of diseases. To date, the demand for herbal drugs has been increasing because of their excellent properties. This review highlights antihypertensive drugs, polyphenols, and synbiotics for managing hypertension. Evidence is mounting in favour of more aggressive blood pressure control with reduced adverse effects, especially for specific patient populations. This review aimed to present contemporary viewpoints and novel treatment options, including cutting-edge technological applications and emerging interventional and pharmaceutical therapies, as well as key concerns arising from several years of research and epidemiological observations related to the management of hypertension.

Introduction: The body of scientific evidence linking the microbiome to many diseases has grown dramatically over the past several years; neurological diseases have also shown a similar tendency. As a result, the gut-brain axis theory as well as the notion that there could be a connection between the gut microbiome and several CNS-related disorders whose pathophysiology is still not known have both emerged. Development: We look at the role played by gut microbiomes in the gut-brain axis as well as the neurological conditions neuromyelitis optica, Alzheimer's, amyotrophic lateral sclerosis, Parkinson's, and multiple sclerosis, where changes in the gut microbiota have been linked to human studies.Conclusions: The amount of data connecting gut microbiota to different neurological illnesses has significantly increased. Today, there is no longer any doubt that the gut microbiota of the host influences brain function. This review assembles a sizable body of credible research that is essential in emphasizing the crucial role of microbiota colonization in neurodevelopment and how changes in microbiota dynamics might have an age-dependent effect on brain function.

Abstract Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor with a short survival rate. Extensive research is underway for the last two decades to find an effective treatment for GBM but the tortuous pathophysiology, development of chemoresistance, and presence of BBB are the major challenges, prompting scientists to look for alternative targets and delivery strategies. Therefore, the nose to brain delivery emerged as an unorthodox and non-invasive route, which delivers the drug directly to the brain via the olfactory and trigeminal pathways and also bypasses the BBB and hepatic metabolism of the drug. However, mucociliary clearance, low administration volume, and less permeability of nasal mucosa are the obstacles retrenching the brain drug concentration. Thus, nanocarrier delivery through this route may conquer these limitations because of their unique surface characteristics and smaller size. In this review, we have emphasized the advantages and limitations of nanocarrier technologies such as polymeric, lipidic, inorganic, and miscellaneous nanoparticles used for nose-to-brain drug delivery against GBM in the past 10 years. Furthermore, recent advances, patents, and clinical trials are highlighted. However, most of these studies are in the early stages, so translating their outcomes into a marketed formulation would be a milestone in the better progression and survival of glioma patients.

It has been shown that the dysbiosis of the gut's microbes substantially impacts CNS illnesses, including Alzheimer's, Parkinson's, autism, and autoimmune diseases like multiple sclerosis (MS). MS is a CNS-affected autoimmune demyelination condition. Through a two-way communication pathway known as the gut-brain axis, gut microbes communicate with the CNS. When there is a disruption in the gut microbiome, cytokines and other immune cells are secreted, which affects the BBB and gastrointestinal permeability. Recent research using animal models has revealed that the gut microbiota may greatly influence the pathophysiology of EAE/MS. Any change in the gut might increase inflammatory cytokinesand affect the quantity of SCFAs, and other metabolites that cause neuroinflammation and demyelination. In- vivo and in-vitro studies have concluded that probiotics affect the immune system and can be utilized to treat gastrointestinal dysbiosis. Any alteration in the gut microbial composition caused by probiotic intake may serve as a preventive and treatment strategy for MS. The major goal of this review is to emphasize an overview of recent research on the function of gut microbiota in the onset of MS and how probiotics have a substantial impact on gastrointestinal disruption in MS and other neuro disorders. It will be easier to develop new therapeutic approaches, particularly probiotic-based supplements, for treating multiple sclerosis (MS) if we know the link between the gut and CNS.

Multiple sclerosis (MS) is a chronic neurodegenerative disease marked by oligodendrocyte loss, which results in central neuronal demyelination. AC/cAMP/CREB signaling dysregulation is involved in the progression of MS, including mitochondrial dysfunctions, reduction in nerve growth factors, neuronal inflammation, apoptosis, and white matter degeneration. Our previous research has shown that Forskolin (FSK), a naturally occurring direct adenylyl cyclase (AC)/cAMP/CREB activator, has neuroprotective potential to alleviate pathogenic factors linked with numerous neurological abnormalities. The current study intends to explore the neuroprotective potential of FSK at doses of 40 mg/kg and 60 mg/kg alone, as well as in combination with conventional medicines, such as Fingolimod (FNG), Donepezil (DON), Memantine (MEM), and Simvastatin (SIM) in EB-induced demyelinated experimental MS rats. Adult Wistar rats were divided into nine groups, and EB was infused stereotaxically in the rat brain's intracerebropeduncle (ICP) area. Chronic gliotoxin EB treatment results in demyelination as well as motor and cognitive dysfunctions. FSK, combined with standard medications, improves behavioral dysfunctions, such as neuromuscular and motor deficits and memory and cognitive abnormalities. Following pharmacological treatments improved remyelination by enhancing myelin basic protein and increasing AC, cAMP, and CREB levels in brain homogenates. Furthermore, FSK therapy restored brain mitochondrial-ETC complex enzymes and neurotransmitter levels while decreasing inflammatory cytokines and oxidative stress markers. The Luxol fast blue (LFB) stain results further indicate FSK's neuroprotective potential in preventing oligodendrocyte death. Therefore, the results of these studies contribute to a better understanding of the possible role that natural phytochemicals FSK could have in preventing motor neuron diseases, such as multiple sclerosis.

To date, no accepted therapy exists for treating the emerging infectious disease nCOVID-19 in a safe and effective way. Although various types of treatment options are under the developing phase around the world, among those, several studies concerning convalescent plasma (CP) from recovered patients reported promising effects against nCOVID-19 infected critically ill patients nowadays. The therapy showed very few adverse effects, and it helps to diminish the viral load when administered at an early stage of infection. Convalescent plasma appears to be safe for critically ill nCOVID-19 patients by decreasing serum viral loads, and most cases are virus negative after CP transfusion. The convalescent plasma can be good as it has already been utilized to treat previous pandemics like Ebola, influenza, and SARS-CoV infection. In this review article, we pointed out the background, rationality, mechanisms, and safety outcomes of CP to treat nCOVID-19 infected patients.

Cervical cancer (CC), the fourth worldwide incessant malignant neoplasia particularly in women, emerged as a serious public health problem. Metabolic syndrome (MetS) is an accumulation of different threats aspects, which could eventually cause diabetes and cardiovascular disease as co-morbidity, further contributing to mortality that is detected by central obesity, dyslipidemia, hyperglycemia, and hypertension. Accumulatively, endemic as well as research data supports the notion of MetS increasing general malignancies occurrences, further contributing to mortality rate. Nano-scale drug delivery system, provide targeted drug delivery, increases drug absorption rates, while drug decomposition and systemic adverse effects get decreased. This article has described the different metabolic syndromes playing role in cervical cancer, alongside cervical cancer nanocarriers modern therapy.

Parkinson's disease (PD) is characterised by dopaminergic neuronal loss in the brain area. PD is a complex disease that deteriorates patients' motor and non-motor functions. In experimental animals, the neurotoxin 6-OHDA induces neuropathological, behavioural, neurochemical and mitochondrial abnormalities and the formation of free radicals, which is related to Parkinson-like symptoms after inter-striatal 6-OHDA injection. Pathological manifestations of PD disrupt the cAMP/ATP-mediated activity of the transcription factor CREB, resulting in Parkinson's-like symptoms. Forskolin (FSK) is a direct AC/cAMP/CREB activator isolated from Coleus forskohlii with various neuroprotective properties. FSK has already been proven in our laboratory to directly activate the enzyme adenylcyclase (AC) and reverse the neurodegeneration associated with the progression of Autism, Multiple Sclerosis, ALS, and Huntington's disease. Several behavioural paradigms were used to confirm the post-lesion effects, including the rotarod, open field, grip strength, narrow beam walk (NBW) and Morris water maze (MWM) tasks. Our results were supported by examining brain cellular, molecular, mitochondrial and histopathological alterations. The FSK treatment (15, 30 and 45 mg/kg, orally) was found to be effective in restoring behavioural and neurochemical defects in a 6-OHDA-induced experimental rat model of PD. As a result, the current study successfully contributes to the investigation of FSK's neuroprotective role in PD prevention via the activation of the AC/cAMP/PKA-driven CREB pathway and the restoration of mitochondrial ETC-complex enzymes.

Immune dysregulation, neuronal inflammation, and oligodendrocyte degradation are key causes for autoimmune disorders like multiple sclerosis (MS) and various other immune dysregulated neurodegenerative complications responsible for CNS-mediated immune responses. Sirtuin (SIRT-1) is a nicotinamide adenosine dinucleotide (NAD)-dependent transcriptional protein that deacetylases and removes acetyl groups from its transcription factors like P53, FOXO, NF-Κb, PGC-1α. SIRT-1 mediates a wide range of physiological functions, including gene transcription, metabolism, neuronal apoptosis, and glucose production. SIRT-1 dysregulation targets transcription factors, and other molecular alterations such as gene expression modification influence neuronal plasticity, inhibit Th17 cells, and interleukin-1β can aggravate brain diseases. Preclinical and clinical findings show that the upregulation of SIRT-1 reduces autoimmunity, neurodegeneration, and neuroexcitation. Even though drugs are being developed for symptomatic therapies in clinical trials, there are particular pharmacological implications for improving post-operative conditions in neurodegenerative patients where intensive care is required. Understanding the SIRT-1 signaling and identifying immune-mediated neuron deterioration can detect major therapeutic interventions that could prevent neuro complications. Thus, in the current review, we have addressed the manifestations of disease by the downregulation of SIRT-1 that could potentially cause MS and other neurodegenerative disorders and provided data on existing available and effective drug therapies and disease management strategies.

Multiple Sclerosis (MS) is a progressive neurodegenerative disease with clinical signs of neuroinflammation and the central nervous system's demyelination. Numerous studies have identified the role of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) overexpression and the low level of peroxisome proliferator-activated receptor-gamma (PPAR-γ) in MS pathogenesis. Guggulsterone (GST), an active component derived from 'Commiphora Mukul,' has been used to treat various diseases. Traditional uses indicate that GST is a suitable agent for anti-inflammatory action. Therefore, we assessed the therapeutic potential of GST (30 and 60 mg/kg) in ethidium bromide (EB) induced demyelination in experimental rats and investigated the molecular mechanism by modulating the JAK/STAT and PPAR-γ receptor signaling. Wistar rats were randomly divided into six groups (n = 6). EB (0.1%/10 μl) was injected selectively in the intracerebropeduncle (ICP) region for seven days to cause MS-like manifestations. The present study reveals that long-term administration of GST for 28 days has a neuroprotective effect by improving behavioral deficits (spatial cognition memory, grip, and motor coordination) associated with lower STAT-3 levels. While elevating PPAR-γ and myelin basic protein levels in rat brains are consistent with the functioning of both signaling pathways. Also, GST modulates the neurotransmitter level by increasing Ach, dopamine, serotonin and by reducing glutamate. Moreover, GST ameliorates inflammatory cytokines (TNF, IL-1β), and oxidative stress markers (AchE, SOD, catalase, MDA, GSH, nitrite). In addition, GST prevented apoptosis, as demonstrated by the reduction of caspase-3 and Bax. Simultaneously, Bcl-2 elevation and the restoration of gross morphology alterations are also recovered by long-term GST treatment. Therefore, it can be concluded that GST may be a potential alternative drug candidate for MS-related motor neuron dysfunctions.

Nose to brain delivery of resveratrol can be a very useful method to overcome the limitations possessed by conventional delivery approaches namely, hepatic metabolism, low bioavailability and half-life of resveratrol, and presence of blood-brain barrier (BBB). The objective of this research work was to develop and optimize the resveratrol-loaded NLCs and coating these carriers with chitosan to increase the residence time of the formulation into the nasal cavity and enhanced permeation across the nasal mucosa. Three CQAs (Particle size, Entrapment efficiency, and PDI), and CMAs (Solid: total lipid concentration, surfactant concentration, and bioactive amount) were selected and the formulation was optimized using the Box-Behnken design (BBD) approach. The optimized batch was evaluated for physicochemical characteristics such as particle size (168.24 ± 8.24 nm), PDI (0.151 ± 0.003), and entrapment efficiency (77.42 ± 3.76 %). This optimized batch was coated with chitosan, which produced coated NLCs with a particle size of 317.7 ± 15.9 nm, and PDI was 0.089 ± 0.009. The morphological study using TEM confirmed the spherical shape, size, and surface coating of the NLCs. Furthermore, both the uncoated and coated particles were analyzed for in vitro resveratrol release, ex vivo diffusion study, and antioxidant assay. NLCs was founded to show sustained in vitro release characteristic, and enhanced bioactive diffusion across the nasal mucosa compared to the bioactive solution of resveratrol. The antioxidant assay revealed that the antioxidant property of resveratrol was intact in the formulation, and a slight increase in antioxidant activity of the formulation was also observed which may be due to the presence of sesame oil in the formulation. These results indicated that the chitosan-coated NLCs can be used to deliver therapeutic moieties more efficiently via the nose to brain drug delivery.