: Alzheimer’s disease (AD) is a commonly reported neurodegenerative disorder associated with dementia and cognitive impairment. The pathophysiology of AD comprises Aβ, hyperphosphorylated tau protein formation, abrupt cholinergic cascade,... more
: Alzheimer’s disease (AD) is a commonly reported neurodegenerative disorder associated with dementia and cognitive impairment. The pathophysiology of AD comprises Aβ, hyperphosphorylated tau protein formation, abrupt cholinergic cascade, oxidative stress, neuronal apoptosis, and neuroinflammation. Recent findings have established the profound role of immunological dysfunction and microglial activation in the pathogenesis of AD. Microglial activation is a multifactorial cascade encompassing various signalling molecules and pathways such as Nrf2/NLRP3/NF-kB/p38 MAPKs/ GSK-3β. Additionally, deposited Aβ or tau protein triggers microglial activation and accelerates its pathogenesis. Currently, the FDA-approved therapeutic regimens are based on the modulation of the cholinergic system, and recently, one more drug, aducanumab, has been approved by the FDA. On the one hand, these drugs only offer symptomatic relief and not a cure for AD. Additionally, no targeted-based microglial medicines are available for treating and managing AD. On the other hand, various natural products have been explored for the possible anti-Alzheimer effect via targeting microglial activation or different targets of microglial activation. Therefore, the present review focuses on exploring the mechanism and associated signalling related to microglial activation and a detailed description of various natural products that have previously been reported with anti-Alzheimer’s effect via mitigation of microglial activation. Additionally, we have discussed the various patents and clinical trials related to managing and treating AD.
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In the last few decades, carcinogenesis has been extensively explored and substantial research has identified immunogenic involvement in various types of cancers. As a result, immune checkpoint blockers and other immune-based therapies... more
In the last few decades, carcinogenesis has been extensively explored and substantial research has identified immunogenic involvement in various types of cancers. As a result, immune checkpoint blockers and other immune-based therapies were developed as novel immunotherapeutic strategies. However, despite being a promising therapeutic option, immunotherapy has significant constraints such as a high cost of treatment, unpredictable toxicity, and clinical outcomes. miRNAs are non-coding, small RNAs actively involved in modulating the immune system’s multiple signalling pathways by binding to the 3′-UTR of target genes. miRNAs possess a unique advantage in modulating multiple targets of either the same or different signalling pathways. Therefore, miRNA follows a ‘one drug multiple target’ hypothesis. Attempts are made to explore the therapeutic promise of miRNAs in cancer so that it can be transported from bench to bedside for successful immunotherapeutic results. Therefore, in the cur...
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: Lung cancer is the second most common cancer and the primary cause of cancer-related death in both men and women worldwide. Due to diagnosis at an advanced stage, it is associated with high mortality in the majority of patients. At... more
: Lung cancer is the second most common cancer and the primary cause of cancer-related death in both men and women worldwide. Due to diagnosis at an advanced stage, it is associated with high mortality in the majority of patients. At present, various treatment approaches are available, such as chemotherapy, surgery, and radiotherapy, but all these approaches usually cause serious side effects like degeneration of normal cells, bone marrow depression, alopecia, extensive vomiting, etc. To overcome the aforementioned problems, researchers have focused on the alternative therapeutic approach in which various natural compounds are reported, which possessed anti-lung cancer activity. Phytocompounds exhibit their anti lung cancer activity via targeting various cell-signaling pathways, apoptosis and cell cycle arrest, and by regulating antioxidant status and detoxification. Apart from the excellent anti-cancer activity, clinical administration of phytocompounds is confined because of their high lipophilicity and low bioavailability. Therefore, researchers show their concern in the development of a stable, safe and effective approach of treatment with minimal side effects by the development of nanoparticle-based delivery of these phytocompounds to the target site. Targeted delivery of phytocompound through nanoparticles overcomes the aforementioned problems. In this article, the molecular mechanism of phytocompounds, their emerging combination therapy, and their nanoparticles-based delivery systems in the treatment of lung cancer have been discussed.
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Alzheimer’s disease is a common and most chronic neurological disorder (NDs) associated with cognitive dysfunction. Pathologically, Alzheimer’s disease (AD) is characterized by the presence of β-amyloid (Aβ) plaques, hyper-phosphorylated... more
Alzheimer’s disease is a common and most chronic neurological disorder (NDs) associated with cognitive dysfunction. Pathologically, Alzheimer’s disease (AD) is characterized by the presence of β-amyloid (Aβ) plaques, hyper-phosphorylated tau proteins, and neurofibrillary tangles, however, persistence oxidative-nitrative stress, endoplasmic reticulum stress, mitochondrial dysfunction, inflammatory cytokines, pro-apoptotic proteins along with altered neurotransmitters level are common etiological attributes in its pathogenesis. Rivastigmine, memantine, galantamine, and donepezil are FDA approved drugs for symptomatic management of AD, whereas tacrine has been withdrawn because of hepatotoxic profile. These approved drugs only exert symptomatic relief and exhibit poor patient compliance. In the current scenario, the number of published evidence shows the neuroprotective potential of naturally occurring bioactive molecules via their antioxidant, anti-inflammatory, antiapoptotic and neur...
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Objective: The main objective of the current study was to observe the ameliorative effect of Withania somnifera on arsenic-induced testicular toxicity by exploring the crucial parameters such as sperm counts, sperm motility, hormonal... more
Objective: The main objective of the current study was to observe the ameliorative effect of Withania somnifera on arsenic-induced testicular toxicity by exploring the crucial parameters such as sperm counts, sperm motility, hormonal assay and lipid peroxidation including histopathology. Materials and Methods: In the present study, arsenic in the form of sodium arsenite was administered orally to male Charles Foster rats for 45 days. Thereafter, ethanolic root extract of Withania somnifera was administered for 30 days to observe its ameliorative effect on male reproductive system. Results: The study revealed that after administration of sodium arsenite, there was a decrease in the sperm counts and sperm motility accompanied by an increased incidence of sperm abnormalities and hormonal imbalance leading to infertility. However, after administration of Withania somnifera, there was significant reversal in the parameters denoting that it not only possesses antioxidant and rejuvenating ...
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A recent outbreak of novel coronavirus (nCoV-19) has put an enormous burden on global public health. Millions of people were affected by this pandemic, and as of now, no effective antiviral drug has been found for the management of this... more
A recent outbreak of novel coronavirus (nCoV-19) has put an enormous burden on global public health. Millions of people were affected by this pandemic, and as of now, no effective antiviral drug has been found for the management of this situation. Cytokine storm, acute respiratory distress, hypoxia and multi-organ failure are hallmark clinical conditions of this disease. Trials for several investigational and repurposed drugs are being conducted, but none of them were found to be safe and effective. However, for the critically ill patient, plasma therapy, dexamethasone, and remdesivir are included in the treatment protocol. For a long time, various natural drugs have been used as antiviral agents in Indian and Chinese traditional medicines, which can be explored as a potential therapeutic option in such situation. It is, therefore, speculated that the proper screening and standardization of these medicines can be a breakthrough in the management and treatment of nCoV-19 infection. A...
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The current study has been designed to appraise the efficacy of developed combinatorial lipid-nanosystem-based gel (linogel) of 5-fluorouracil and resveratrol for skin cancer treatment. Initially, linogel was prepared and characterized... more
The current study has been designed to appraise the efficacy of developed combinatorial lipid-nanosystem-based gel (linogel) of 5-fluorouracil and resveratrol for skin cancer treatment. Initially, linogel was prepared and characterized for different parameters, namely pH, texture, drug content uniformity, occlusiveness, etc. Then in vivo efficacy studies (tumor number, area, and volume, histopathology, ultrastructural and immunohistochemical analysis) of linogel were determined over-developed skin tumors. Developed linogel possessed significantly (p<0.05) better texture and occlusiveness than conventional gel formulation. Decreased tumor number, area, and volume showed significant results (p<0.05) in favor of linogel. Histopathological and ultrastructural analysis confirmed superior efficacy of linogel in terms of marked improvement in the nucleus and subcellular structures in photomicrographs. The antioxidants and anti-inflammatory analysis findings showed a significantly (p<0.05) potent effectiveness of linogel. The apoptotic and anti-proliferation activity of linogel was confirmed by analysis of caspase-3 and ki-67, which showed significant (p<0.05) elevation in the level of cleaved caspase-3 and reduction in the level of ki-67 than untreated and conventional gel formulation treated tumors, indicating antitumor effect due to cancerous cell death. Thus, developed linogel fulfilled all the criteria of dermal application and exhibited efficacious therapeutic results, which could be a beneficial therapeutic approach against skin cancer.
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At present, skin cancer is considered a widespread malignancy in human beings. Among diverse population types, Caucasian populations are much more prone to this malignancy in comparison to darker skin populations due to the lack of skin... more
At present, skin cancer is considered a widespread malignancy in human beings. Among diverse population types, Caucasian populations are much more prone to this malignancy in comparison to darker skin populations due to the lack of skin pigmentation. Skin cancer is divided into malignant and non-melanoma skin cancer, which is further categorized as basal and squamous cell carcinoma. Exposure to ultraviolet radiation, chemical carcinogen (polycyclic aromatic hydrocarbons, arsenic, tar, etc.), and viruses (herpes virus, human papillomavirus, and human T-cell leukemia virus type-1) are major contributing factors to skin cancer. There are distinct pathways available through which skin cancer develops, such as the JAK-STAT pathway, Akt pathway, MAPKs signaling pathway, Wnt signaling pathway, to name a few. Currently, several targeted treatments are available, such as monoclonal antibodies, which have dramatically changed the line of treatment of this disease but possess major therapeutic...
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In the present study, combinatorial nanostructured lipid carrier gel of 5-fluorouracil and resveratrol was formulated, optimized and characterized to enhance permeation in between epidermis and dermis layers of the skin to obtain a... more
In the present study, combinatorial nanostructured lipid carrier gel of 5-fluorouracil and resveratrol was formulated, optimized and characterized to enhance permeation in between epidermis and dermis layers of the skin to obtain a synergistic effect against skin cancer. After extensive trials, a newly modified emulsiosonication method was developed and additionally, for the first time, stability studies were done in the beginning to optimize formulation technique, which exhibited two major benefits simultaneously; first, it provided best-optimized technique for preparation of combinatorial lipid-nanosystem, and secondly, it also demonstrated a detailed report card of durability of formulations. In vitro release study showed a significantly improved, slow and prolonged release of drugs from the optimized lipid-nanosystem (***p<0.05), which followed non-Fickian Higuchi kinetics. Besides, mechanism of skin permeation enhancement study, dermatokinetic assessment, and depth analysis of optimized formulation on skin exhibited improved permeation and well distribution of drugs up to the dermis layer of skin. Moreover, combinatorial linogel possessed significantly greater efficacy (**p<0.01) on the A431 cell line, as compared to the conventional formulation. Thus, findings revealed that modified method of preparation for dual drug-loaded lipid-nanosystem lead to the production of a stable formulation that also improved the retention of both 5-fluorouracil and resveratrol in between the epidermis and dermis region of skin thereby helping in the management and treatment of skin cancer.
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: Neurological disorders are one of the major threat for health care system as they put enormous socioeconomic burden. All aged populations are susceptible to one or other neurological problems with symptoms of neuroinflammation,... more
: Neurological disorders are one of the major threat for health care system as they put enormous socioeconomic burden. All aged populations are susceptible to one or other neurological problems with symptoms of neuroinflammation, neurodegeneration and cognitive dysfunction. At present, available pharmacotherapeutics are insufficient to treat these diseased conditions and in most cases, they provide only palliative effect. It was also found that the molecular etiology of neurological disorders is directly linked with the alteration in genetic makeup, which can be inherited or triggered by the injury, environmental toxins and by some existing disease. Therefore, to take care of this situation, gene therapy has emerged as an advanced modality that claims to permanently cure the disease by deletion, silencing or edition of faulty genes and by insertion of healthier genes. In this modality, vectors (viral and non-viral) are used to deliver targeted gene into a specific region of the brain via various routes. At present, gene therapy has shown positive outcomes in complex neurological disorders, such as Parkinson's disease, Alzheimer's disease, Huntington disease, Multiple sclerosis, Amyotrophic lateral sclerosis and in lysosomal storage disease. However, there are some limitations such as immunogenic reactions non-specificity of viral vectors and a lack of effective biomarkers to understand the efficacy of therapy. Considerable progress has been made to improve vector design, gene selection and targeted delivery. This review article deals with the current status of gene therapy in neurological disorders along with its clinical relevance, challenges and future prospective.
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: Alzheimer’s disease (AD) is one of the common chronic neurological disorders and associated with cognitive dysfunction, depression and progressive dementia. The presence of β-amyloid or senile plaques, hyper-phosphorylated tau proteins,... more
: Alzheimer’s disease (AD) is one of the common chronic neurological disorders and associated with cognitive dysfunction, depression and progressive dementia. The presence of β-amyloid or senile plaques, hyper-phosphorylated tau proteins, neurofibrillary tangle, oxidative-nitrative stress, mitochondrial dysfunction, endoplasmic reticulum stress, neuroinflammation and derailed neurotransmitter status are the hallmarks of AD. Currently, donepezil, memantine, rivastigmine and galantamine are approved by the FDA for symptomatic management. It is well-known that these approved drugs only exert symptomatic relief and possess poor patient-compliance. Additionally, various published evidence showed the neuroprotective potential of various nutraceuticals via their antioxidant, anti-inflammatory and anti-apoptotic effects in the preclinical and clinical studies. These nutraceuticals possess a significant neuroprotective potential and hence, can be a future pharmacotherapeutic for the management and treatment of AD. However, nutraceuticals suffer from certain major limitations such as poor solubility, low bioavailability, low stability, fast hepatic- metabolism and larger particle size. These pharmacokinetic attributes restrict their entry into the brain via the blood-brain barrier. Therefore, to overcome such issues, various nanoformulations of nutraceuticals have been developed, that allow their effective delivery into the brain owing to reduced particle size, increased lipophilicity, increased bioavailability and avoidance of fast hepatic metabolism. Thus, in this review, we have discussed the etiology of AD, focusing on the pharmacotherapeutics of nutraceuticals with preclinical and clinical evidence, discussed pharmaceutical limitations and regulatory aspects of nutraceuticals to ensure safety and efficacy. We have further explored various nanoformulations of nutraceuticals as a novel approach to overcome the existing pharmaceutical limitations and for effective delivery into the brain.
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Natural products are increasing used in preventing and treating various diseases. Mangiferin belongs to the xanthone family, and has potential antiangiogenic, anticancer, immunomodulatory and anti-inflammatory activity along with the... more
Natural products are increasing used in preventing and treating various diseases. Mangiferin belongs to the xanthone family, and has potential antiangiogenic, anticancer, immunomodulatory and anti-inflammatory activity along with the antioxidant activity. It is also used in the treatment of cardiac problem, diabetes and neurodegenerative disease. Finding of various researchers proves that mangiferin has a broad spectrum therapeutic application. Motive of this review is to describe the various studies performed on mangiferin for its different pharmacological activities. It also discusses various challenges associated with mangiferin such as stability and bioavailability. Strategies and approaches to improve bioavailability of mangiferin have also been discussed. Both research and review articles were used to write the manuscript. They were collected from various search engines like Pub Med, Science Direct and Google Scholar, using keywords like mangiferin, polyphenol, bioavailability...
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A wound refers to the epithelial loss, accompanied by loss of muscle fibers collagen, nerves and bone instigated by surgery, trauma, frictions or by heat. Process of wound healing is a compounded activity of recovering the functional... more
A wound refers to the epithelial loss, accompanied by loss of muscle fibers collagen, nerves and bone instigated by surgery, trauma, frictions or by heat. Process of wound healing is a compounded activity of recovering the functional integrity of the damaged tissues. This process is mediated by various cytokines and growth factors usually liberated at the wound site. A plethora of herbal and synthetic drugs, as well as photodynamic therapy, is available to facilitate the process of wound healing. Generally, the systems used for the management of wounds tend to act through covering the ruptured site, reduce pain, inflammation, and prevent the invasion and growth of microorganisms. The available systems are, though, enough to meet these requirements, but the involvement of nanotechnology can ameliorate the performance of these protective coverings. In recent years, nano-based formulations have gained immense popularity among researchers for the wound healing process due to the enhance...
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The structure of the eye is very complex in nature which makes it a challenging task for pharmaceutical researchers to deliver the drug at the desired sites via different routes of administration. The development of the nano-based system... more
The structure of the eye is very complex in nature which makes it a challenging task for pharmaceutical researchers to deliver the drug at the desired sites via different routes of administration. The development of the nano-based system helped in delivering the drug in the desired concentration. Improvement in penetration property, bioavailability, and residence time has all been achieved by encapsulating drugs into liposomes, dendrimers, solid lipid nanoparticle, nanostructured lipid carrier, nanoemulsion, and nanosuspension. This review puts emphasis on the need for nanomedicine for ocular drug delivery and recent developments in the field of nanomedicine along with recent patents published in the past few years.
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The present study aimed to evaluate the neuroprotective potential of intranasally administered pitavastatin in the PTZ-induced kindling model. Subconvulsant dose of PTZ (35 mg/kg, i.p) was administered on an alternate day until the... more
The present study aimed to evaluate the neuroprotective potential of intranasally administered pitavastatin in the PTZ-induced kindling model. Subconvulsant dose of PTZ (35 mg/kg, i.p) was administered on an alternate day until the development of kindling. Behavioural test, biochemical tests and inflammatory cytokines were estimated. Comparative molecular docking study of sodium valproate (VPA) and pitavastatin was performed to predict the binding affinity with GABA and GABA transaminase. Intranasally administered pitavastatin (0.5 mg/kg and 1 mg/kg) and VPA (200 mg/kg) were used to investigate its protective effect. Comparative in-silico study showed docking score of -4.56 and -2.86 against GABA receptor whereas -5.56 and -1.86, against GABA transaminase. Root mean square deviation (RMSD) of 0.39A and 0.55A was found for pitavastatin and VPA, respectively. The present study showed the dose-dependent protective effect of intranasally administered pitavastatin and oral VPA against PT...
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Research Interests: Chemistry, Analytical Chemistry, Chromatography, Heat Treatment, Dosage Form, and 15 moreCalibration, Degradation, HPTLC, Accuracy, Formic Acid, Oxidation, Food Sciences, Correlation coefficient, Densitometry, Linear Regression, Capsules, Hydrolysis, Drug Stability, Molecular Structure, and Oral Contraceptive
Spinal cord injury (SCI) and associated pain and inflammation caused by trauma or infection are serious health care issues world-wide. The various inflammatory, redox-sensitive and apoptotic events are contributing factors, but altered... more
Spinal cord injury (SCI) and associated pain and inflammation caused by trauma or infection are serious health care issues world-wide. The various inflammatory, redox-sensitive and apoptotic events are contributing factors, but altered neuronal function, axonal degeneration, activated microglia, endothelial cells, astrocytes, fibroblasts, pericytes, Schwann cells, and meningeal cells are major players in its pathogenesis. Further, monocytes and neutrophil infiltration get recruited and facilitate the release of chemokines, cytokines, and other mediators of inflammation. This event leads to the production of different amino acids, neuropeptides kinin, prostaglandins, prostacyclin, thromboxane, leukotrienes, bradykinin, histamine, matrix metal proteinases, and serotonin that stimulate nerve endings and manifest the inflammation and pain processes, etc. Arachidonic acid (AA), NF-kB, NLRP3 inflammasome, and nitric oxide pathways along with P2X7 receptor and ion channel transient recepto...