The Influence of Phytoconstituents for the Management of Antipsoriatic Activity in Various Animal Models.

It is possible for psoriasis to manifest at any point in a person's life, regardless of their age, gender, or geographic location. It is a chronic immune-linked inflammatory skin ill-ness that affects individuals of various racial and ethnic origins. It is recognized to be a long-lasting condition. Because of the significant contribution that natural products have made, there has been a significant advancement in the treatment of skin illnesses such as psoriasis. The biggest number of phytochemicals derived from a wide range of plants and herbs are now being used in a variety of applications throughout the whole world. Additionally, a number of phyto-chemicals, including aloe-emodin, psoralen, curcumin, and others, have been effectively ex-tracted in pure or clear form, and they have shown a great deal of efficacy in the treatment of psoriasis illness. There is evidence that a few herbal remedies are effective, and the occurrence of these phytochemicals provides more proof. When synthetic medications are used for chronic therapy, they may cause a variety of adverse consequences; hence, the exploration of natural pharmaceuticals can give a successful natural treatment with a minimal amount of adverse ef-fects. Within the scope of this concise review, a number of plant sources that possess anti-pso-riatic activity are investigated, and the antipsoriatic effects of these plant sources are shown on a number of animal models using particular pathways.

Eco-friendly Synthesis of Azadirachta indica-based Metallic Nanoparticles for Biomedical Application & Future Prospective.

The process of producing the metallic nanoparticles (MNPs) in a sustainable and environment- friendly process is very desirable due to environmental hazards posed by climatic changes. Biomedical one of the fields classified under nanoscience, nanoparticles have a potential synthetic application, which makes it a vast area of research. These particles can be prepared using chemical, physical, and biological methods. One of the methods of synthesis of nanoparticles is by the use of plant extracts, known as green synthesis. Because of its low cost and nontoxicity, it has gained attention in recent times. This review was conducted to find the possible outcomes and uses of metallic nanoparticles synthesized using different parts like gum, root, stem, leaf, fruits, etc. of Azadirachta indica (AI). AI, a popular medicinal plant commonly known as neem, has been studied for the green synthesis of NPs by using the capping and reducing agents secreted by the plant. Various phytochemicals identified in neem are capable of metal ion reduction. Green synthesis of NPs from neem is an eco-friendly and low-cost method. These NPs are reported to exhibit good antimicrobial activity. The review covers the preparation, characterization, and mechanism associated with the antibacterial, anticancer, and neurological diseases of the MNPs. Furthermore, the limitations associated with the existing NPs and the prospects of these NPs are also examined.

New Emerging Aspect of Herbal Extracts for the Treatment of Osteoporosis: Overview.

As the global population ages, osteoporosis is becoming a more common silent disease. Osteoporosis is characterized by decreased bone quality and strength, which increases the risk of fragility fractures in the elderly. According to estimates, 50% of women eventually suffer from an osteoporotic fracture. Due to increasing disability, more frequent hospital hospitalizations, and most critically, fragility fractures have been linked to a reduced quality of life. Osteoporotic fractures have been linked to an increased mortality risk; and must be considered in awareness as a serious health concern. There are anti-osteoporotic medications available that improve bone quality. Considering the availability of various treatment options, still there are a lot of underserved needs in the treatment of fractures and osteoporosis. For example, the application of natural products and herbal resources for fracture healing, because of the androgen-like and antioxidant characteristics of the plants, they can play a crucial for accelerating the repair of bone fractures. In this article, we'll discuss the herbal remedies that are essential for treating osteoporosis (bone disease).

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.

Rationalizing the Use of Polyphenol Nano-formulations in the Therapy of Neurodegenerative Diseases.

Neurodegenerative diseases are a heterogeneous group of disorders among aging populations worldwide characterized by the progressive degeneration of the structure and function of brain cells and the nervous system. Alzheimer's disease and Parkinson's disease are common neurodegenerative diseases (NDs). Classic pathological features of AD are the accumulation of the amyloid betaprotein and aggregates of hyperphosphorylated tau protein around the brain cells. Dopaminergic neuronal death in the midbrain and accumulation of α- synuclein in the neurons are the hallmark of Parkinson's disease. The pathogenesis is multifactorial, and both neurodegenerative disorders have complex etiology. Oxidative stress closely linked with mitochondrial dysfunction, excitotoxicity, nitric oxide toxicity, and neuro-inflammation, is anticipated to trigger neuronal death. Ample evidence has implicated that oxidative stress and inflammation contribute to the pathology of neurodegeneration in AD and PD. Currently, acetylcholinesterase inhibitors are the main treatment option for AD, while L-DOPA is the gold standard therapy for PD. Along with the main therapy, many endogenous antioxidants, like vitamin E, selenium, etc., are also given to the patients to combat oxidative stress. Current treatment for these NDs is limited due to the blood-brain barrier (BBB) that hinders drug targeting towards neurons. In this review, we emphasize adjunct treatment with anti-inflammatory agents that act at the site of the disease and can halt the disease progression by attenuating the effect of ROS triggering neuro-inflammatory response. Polyphenols, either as purified compounds or extracts from various natural plant sources, have been well studied and documented for anti-inflammatory effects, but their use for ND is limited due to their physicochemical attributes. Nanoparticle-mediated drug delivery system exhibits immense potential to overcome these hurdles in drug delivery to the CNS, enabling nanoparticle-based therapies to directly target the inflammation and release bioactive compounds with anti-inflammatory properties to the site of action.

Review on Natural Bioactive Products as Radioprotective Therapeutics: Present and Past Perspective.

Among conventional treatment methodologies, surgery, hyperthermia, radiation, and chemotherapy have become integral components of treatment for most cancers. Radiation therapy in the treatment of many malignancies is always the better choice over surgery and chemotherapy. Ionizing radiation produced as a consequence of using these radiations has always been a concern in these treatment methods. Synthetic radio-protectors with their inherent limitations are being used to date to reduce the mortality of these radiations; still, it compromises the clinical efficacy of these administrations. Hence, investigations for alternative methods, including natural resources such as plant and fruit extracts, are being explored to treat radiation-mediated ailments. The present review article endeavors to provide a comprehensive, updated, and chronological account of these promising plants and fruit extracts and their bioactive principles as radio-protectors. We present the merits and demerits of radiation therapy and cell stress generation of reactive oxygen species (ROS) associated with radiation need and availability of radio-protectors. Finally, we discuss green-based bioactive compounds that have radioprotective properties.

Lipid Nanocarriers for Neurotherapeutics: Introduction, Challenges, Blood-brain Barrier, and Promises of Delivery Approaches.

Significant efforts have been made in research to discover newer neurotherapeutics, however, the rate of reported neurological disorders has been increasing at an alarming speed. Neurotherapeutics delivery in the brain is still posing a significant challenge, owing to the blood-brain barrier and blood-cerebrospinal fluid barrier. These physiological barriers restrict the passage of systemically available fractions of neurotherapeutics into the brain, owing to low permeability and drug localization factors. Neurotherapeutics encapsulating lipid carriers favor a significant increase in bioavailability of poorly water-soluble drugs by enhancing solubility in the gastrointestinal tract and favoring stability. Due to their small size and lipid-based composition, these carriers offer enhanced permeability across the semi-permeable blood-brain barrier to effectively transport encapsulated loads, such as synthetic drugs, nutraceuticals, phytoconstituents, herbal extracts, and peptides, thereby reducing incidences of off-target mediated adverse impacts and toxicity. The most significant advantage of such lipid-based delivery systems is non-invasive nature and targeting of neurotherapeutics to the central nervous system. Critical attributes of lipid-based carriers modulate release rates in rate-controlled manners, enable higher penetration through the blood-brain barrier, and bypass the hepatic first-pass metabolism leading to higher CNS bioavailability neurotherapeutics. The current review discusses a brief and introductory account of the limitations of neurotherapeutics, pharmacological barriers, challenges in brain-targeted delivery, and the potential of nanotechnology- processed lipid-based carriers in the clinical management of neuronal disorders.

Probiotics for the Chemoprotective Role against the Toxic Effect of Cancer Chemotherapy.

BACKGROUND: Chemo- and radiation therapy-based clinical management of different types of cancers is associated with toxicity and several side effects. Therefore, there is always an unmet need to explore agents that reduce such risk factors. Among these, natural products have attracted much attention because of their potent antioxidant and antitumor effects. In the past, some breakthrough outcomes established that various bacteria in the human intestinal gut are bearing growth-promoting attributes and suppressing the conversion of pro-carcinogens into carcinogens. Hence probiotics integrated approaches are nowadays being explored as rationalized therapeutics in the clinical management of cancer. METHODS: Here, published literature was explored to review chemoprotective roles of probiotics against toxic and side effects of chemotherapeutics. RESULTS: Apart from excellent anti-cancer abilities, probiotics alleviate toxicity & side effects of chemotherapeutics, with a high degree of safety and efficiency. CONCLUSION: Preclinical and clinical evidence suggests that due to the chemoprotective roles of probiotics against side effects and toxicity of chemotherapeutics, their integration in chemotherapy would be a judicious approach.

Withdrawal Notice: Lipid Carriers Mediated Targeted Delivery of Neurotherapeuticals: Challenges, Role of Blood Brain Barrier and Promises of Nanotechnology Based Approaches in Neuronal Disorders

The article has been withdrawn at the request of the editor of the journal Current Drug Metabolism due to incoherent content. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php. Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Lipid-based nanoformulations in the treatment of neurological disorders.

The neurological disorders affect millions of people worldwide, and are bracketed as the foremost basis of disability-adjusted life years (DALYs). The treatment options are symptomatic and often the movement of drugs is restricted by a specialized network of endothelial cell layers (adjoined by tight cell-to-cell junction proteins; occludin, claudins, and junctional adhesion molecules), pericytes and astroglial foot processes. In recent years, advances in nanomedicine have led to therapies that target central nervous system (CNS) pathobiology via altering signaling mechanisms such as activation of PI3K/Akt pathway in ischemic stroke arrests apoptosis, interruption of α-synuclein aggregation prevents neuronal degeneration in Parkinson's. Often such interactions are limited by insufficient concentrations of drugs reaching neuronal tissues and/or insufficient residence time of drug/s with the receptor. Hence, lipid nanoformulations, SLNs (solid lipid nanoparticles) and NLCs (nanostructured lipid carriers) emerged to overcome these challenges by utilizing physiological transport mechanisms across blood-brain barrier, such as drug-loaded SLN/NLCs adsorb apolipoproteins from the systemic circulation and are taken up by endothelial cells via low-density lipoprotein (LDL)-receptor mediated endocytosis and subsequently unload drugs at target site (neuronal tissue), which imparts selectivity, target ability, and reduction in toxicity. This paper reviews the utilization of SLN/NLCs as carriers for targeted delivery of novel CNS drugs to improve the clinical course of neurological disorders, placing some additional discussion on the metabolism of lipid-based formulations.

Raloxifene potentiates the effect of fluoxetine against maximal electroshock induced seizures in mice.

The evidence to guide clinicians regarding rationale polytherapy with current antiepileptic drugs (AEDs) is lacking, and current practice recommendations are largely empirical.  The excessive drug loading with combinatorial therapies of existing AEDs are associated with escalated neurotoxicity, and that emergence of pharmacoresistant seizures couldn't be averted. In pursuit of judicious selection of novel AEDs in combinatorial therapies with mechanism based evidences, standardized dose of raloxifene, fluoxetine, bromocriptine and their low dose combinations, were experimentally tested for their impact on maximal electroshock (MES) induced tonic hind limb extension (THLE) in mice. Hippocampal neuropeptide Y (NPY) levels, oxidative stress and histopathological studies were undertaken. The results suggest the potentiating effect of 4 mg/kg raloxifene on 14 mg/kg fluoxetine against MES induced THLE, as otherwise monotherapy with 4 mg/kg raloxifene was unable to produce an effect. The results also depicted better efficacy than carbamazepine (20 mg/kg), standard AED. Most profoundly, MES-induced significant (P < 0.001) reduction in hippocampal NPY levels, that were escalated insignificantly with the duo-drug combination, suggesting some other mechanism in mitigation of electroshock induced seizures. These results were later corroborated with assays to assess oxidative stress and neuronal damage. In conclusion, the results demonstrated the propitious therapeutic benefit of duo-drug low dose combination of drugs; raloxifene and fluoxetine, with diverse mode of actions fetching greater effectiveness in the management of generalized tonic clonic seizures (GTCS).

Bioinspired Nanocomposites: Applications in Disease Diagnosis and Treatment.

Recent advancement in the field of synthesis and application of nanomaterials provided holistic approach for both diagnosis as well as treatment of diseases. Briefly, three-dimensional scaffold and geometry of bioinspired nanocarriers modulate bulk properties of loaded drug at molecular/ atomic structures in a way to conjointly modulate pathological as well as altered metabolic states of diseases, in very predictable and desired manners at a specific site of the target. While, from the pharmacotechnical point of views, the bioinspired nanotechnology processes carriers either favor to enhance the solubility of poorly aqueous soluble drugs or enable well-controlled sustained release profiles, to reduce the frequency of drug regimen. Consequently, from biopharmaceutical point of view, these composite materials, not only minimize first pass metabolism but also significantly enhance in-vivo biodistribution, permeability, bio-adhesion and diffusivity. In lieu of the above arguments, the nano-processed materials exhibit an important role for diagnosis and treatments. In the diagnostic center, recent emergences and advancement in the tools and techniques to diagnose the unrevealed diseases with the help of instruments such as, computed tomography, magnetic resonance imaging etc; heavily depend upon nanotechnology-based materials. In this paper, a brief introduction and recent application of different types of nanomaterials in the field of tissue engineering, cancer treatment, ocular therapy, orthopedics, and wound healing as well as drug delivery system are thoroughly discussed.

Purple heart plant leaves extract-mediated silver nanoparticle synthesis: Optimization by Box-Behnken design.

The present research work describes a novel method for green synthesis of silver nanoparticles using purple heart plant leaves extract, which is recognized as frequently found in households as an ornamental plant. The aqueous methanolic extract of purple heart plant leaves was prepared and employed in the synthesis of stable silver nanoparticles via biological reduction method. The purple heart plant leaves extract-mediated synthesized silver nanoparticles were systematically optimized using Box-Behnken design considering the effect of various independent variables (factors) like concentration of AgNO3, temperature and volume of purple heart plant leaves extract solution on the responses like particle size and polydispersity index of synthesized silver nanoparticles were optimized. Mathematical modelling was performed using quadratic polynomial model and response surface analysis was done to understand the factor-response relationship. The synthesized silver nanoparticles at optimum condition were found to be of spherical in shape under TEM with particle size of 98 nm and polydispersity index of 0.15. Optimized silver nanoparticles were further characterized through UV-VIS spectrophotometry, FTIR spectroscopy and TEM imaging studies. Also, the silver nanoparticles were evaluated for antibacterial activity on E. coli and S. aureus. In a nutshell, the studies construed successful synthesis of silver nanoparticles along with thorough understanding of the associated factors influencing their quality characteristics and significantly improved antibacterial activity as beneficial effect.

The Synergistic Effect of Raloxifene, Fluoxetine, and Bromocriptine Protects Against Pilocarpine-Induced Status Epilepticus and Temporal Lobe Epilepsy.

The present antiepileptic drugs pose several problems in the management of seizures owing to their meager neuroprotective potential, adverse effects on bone, detrimental effects on cognitive function, chronic toxicity, drug interactions, side effects including aggression, agitation, and irritability and sometimes exacerbation of seizures. We followed up progressive preclinical investigation in mice against pilocarpine (PILO)-induced status epilepticus (SE) and temporal lobe epilepsy (TLE). To determine the response of raloxifene (RF) (4 and 8 mg/kg), fluoxetine (FT) (14 and 22 mg/kg), bromocriptine (BC) (6 and 10 mg/kg), and their low-dose combinations, oral treatment was scheduled for 28 days followed by PILO (300 mg/kg, i.p). The response was stalked for intensive behavioral monitoring of convulsions, hippocampal neuropeptide Y (NPY), and oxidative stress discernment along with histomorphological studies. The resultant data confirmed the therapeutic potential of triple drug combination of raloxifene (4 mg/kg) with fluoxetine (14 mg/kg) and bromocriptine (6 mg/kg) compared to monotherapy with raloxifene (4 mg/kg), and bromocriptine (6 mg/kg) as otherwise monotherapy with fluoxetine (14 mg/kg) was ineffective to suppress convulsions; an effect better than sodium valproate (300 mg/kg), a standard AED, was validated. Most profoundly, PILO-induced compensatory increases in hippocampal NPY levels (20.01%), which was escalated (100%) with the triple drug combination. The same pattern of results was superseded for oxidative stress indices and neuronal damage. The results for the first time demonstrate the propitious role of triple drug combination in the management of SE and TLE. Therapeutically, this enhancing profile of drugs fosters a safer and more effective drug-combination regimen. Graphical abstract.

Estrogen and Serotonin: Complexity of Interactions and Implications for Epileptic Seizures and Epileptogenesis.

A burgeoning literature documents the confluence of ovarian steroids and central serotonergic systems in the injunction of epileptic seizures and epileptogenesis. Estrogen administration in animals reduces neuronal death from seizures by up-regulation of the prosurvival molecule i.e. Bcl-2, anti-oxidant potential and protection of NPY interneurons. Serotonin modulates epileptiform activity in either direction i.e administration of 5-HT agonists or reuptake inhibitors leads to the activation of 5-HT3 and 5-HT1A receptors tending to impede focal and generalized seizures, while depletion of brain 5-HT along with the destruction of serotonergic terminals leads to expanded neuronal excitability hence abatement of seizure threshold in experimental animal models. Serotonergic neurotransmission is influenced by the organizational activity of steroid hormones in the growing brain and the actuation effects of steroids which come in adulthood. It is further established that ovarian steroids bring induction of dendritic spine proliferation on serotonin neurons thus thawing a profound effect on serotonergic transmission. This review features 5-HT1A and 5-HT3 receptors as potential targets for ameliorating seizure-induced neurodegeneration and recurrent hypersynchronous neuronal activity. Indeed 5-HT3 receptors mediate cross-talk between estrogenic and serotonergic pathways, and could be well exploited for combinatorial drug therapy against epileptogenesis.

Gum ghatti mediated, one pot green synthesis of optimized gold nanoparticles: Investigation of process-variables impact using Box-Behnken based statistical design.

Due to unique inherent catalytic characteristics of different size, shape and surface functionalized gold nanoparticles, their potential applications, are being explored in various fields such as drug delivery, biosensor, diagnosis and theranostics. However conventional process for synthesis of these metallic nanoparticles utilizes toxic reagents as reducing agents, additional capping agent for stability as well as surface functionalization for drug delivery purposes. Hence, in this work suitability of gum Ghatti for reducing, capping and surface functionalization during the synthesis of stable Gold nanoparticles were duly explored. Role and impact of key process variables i.e. volume of chloroauric acid solution, gum solution and temperature at their respective three different levels, as well as mechanism of formation of optimized gold nanoparticles were also investigated using Box- Behnken design. These novel synthesized optimized Gold nanoparticles were further characterized by UV spectrophotometer for its surface plasmon resonance (SPR) at around ∼530nm, dynamic light scattering (DLS) for its hydrodynamic size (112.5nm), PDI (0.222) and zeta potential (-21.3mV) while, transmission electron microscopy (TEM) further revealed surface geometry of these nanoparticles being spherical in shape.