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Central nervous system disorders are expected to profoundly impact the global healthcare needs of the human community in this era. Senile decay of neurons is (Alzheimers Disease) AD. The hallmark of the pathophysiology of AD disease has two pivotal features: extracellular beta-amyloid deposition and intracellular tau hyperphosphorylation. New medicine-based psychoactive treatments have met with modest effectiveness due to the multifactorial nature of these diseases. As a result there is an increasing need for new products that can address various receptors and enhance behavioral abilities independently or in tandem with traditional medications. Herbal products focused on conventional expertise have recently been widely popular in developed and developing countries. Ayurveda is a medical science that deals with the treatment of diseases using naturally occurring plant products. Ayurveda claims to have a large number of neuroprotective herbs. This review discusses the pharmacological effects and therapeutic properties of In vivo In vitro In silico and human clinical trials of (Bacopa monnieri) BM against AD.

The plant Alpinia officinarum of the ginger family originated in China and is used throughout South and South-East Asian countries to flavor food and as a traditional medicine to treat a variety of diseases. This review summarizes the biological pharmacological and phytochemical properties of extracts and subsequently isolated compounds from A. officinarum. In vitro and in vivo studies of both extracts and pure compounds indicate a wide variety of potent bioactivities including antiinflammatory antibacterial antioxidant antiobesity anticancer enzyme inhibitory and remarkable antiviral properties. The latter is particularly promising in the face of emerging virulent respiratory diseases in Asia and the Middle East.

Phenotyping by probe substrates of cytochrome P450 (CYP) and other metabolizing enzymes is widely used to assess the effects of genes environment and ethnicity on the in vivo metabolism of drugs and environmental chemicals. The caffeine metabolic ratio in urine plasma or saliva has been used extensively as an index of CYP1A2 N-acetyltransferase 2 (NAT2) xanthine oxidase (XO) and CYP2A6 enzymatic activities. Phenotyping using plasma or saliva samples to measure the paraxanthine to caffeine (17X/137X) ratio correlates well with many measures of CYP1A2 activity. Various urinary metabolic ratios for caffeine phenotyping have been proposed but shortcomings have been demonstrated for all the proposed urinary metabolic ratios. Several groups have proposed the urinary ratio of (1- methylxanthine (1X) + 1-methylurate (1U) + 5-acetylamino-6-formylamino-3-methyluracil (AFMU)) to 1 7-dimethylurate (17U) i.e. (1X + 1U + AFMU)/17U as the preferred metabolic ratio for CYP1A2 activity (independent of urine flow rate). There is no consensus on the best urinary metabolic ratio for NAT2 XO or CYP2A6 enzymatic activities. Caffeine has been used by different groups to evaluate the in vivo activity of CYP1A2 NAT2 XO and CYP2A6 in different populations and the effect of many factors on these activities. Caffeine has been also used as a constituent of a “cocktail” to phenotype several enzymes simultaneously. In conclusion phenotyping using caffeine as a probe substrate may still provide useful assessment of CYP1A2 NAT2 XO and CYP2A6 activities in epidemiologic and drug-drug interaction studies despite the limitations that are associated with its use.

Over the last decades gene therapy has emerged as a pioneering therapeutic approach to treat or prevent several diseases. Among the explored strategies the short-term silencing of protein coding genes mediated by siRNAs has a good therapeutic potential in a clinical setting. However the widespread use of siRNA will require the development of clinically suitable safe and effective vehicles with the ability to complex and deliver siRNA into target cells with minimal toxicity. Lately dendrimers have gained considerable attention as non-viral vectors in nucleic acid delivery due to their unique structural characteristics (globular well defined and highly branched structure multivalency low polydispersity and tunable nanosize) along with their relevant capacity to complex and protect nucleic acids in compact nanostructures which can be functionalized with targeting moieties in order to get cell specificity. Here we present an overview of the state-of-the-art of the most significant and recent advances on the use of dendrimers as siRNA delivery vectors with particular focus on the in vivo applications. We will cover the use of different dendrimers distinct administration routes toxicity issues as well as the target tissue or disease highlighting the potential of dendrimers as nanocarriers for therapeutic and biomedical applications.

Over the last decade much research has focused on the potential health benefits of antioxidants and indeed many synthetic and natural compounds have been evaluated for their antioxidant profile. However in several studies only a limited number of assays often poorly validated are used and the techniques available frequently lack specificity. These limitations may incorrectly influence the results. This review will therefore focus on several pitfalls that may emerge in vitro and in vivo antioxidant research. First different in vitro techniques to determine antioxidant potential are discussed including radical scavenging assays and fingerprinting methods. As a rule a panel of different assays is indispensable to characterize and establish in vitro antioxidant activity. Furthermore as problems of absorption distribution metabolism and excretion are only accounted for by in vivo studies the need for in vivo antioxidant research is pointed out. Several methods to characterize the in vivo activity of antioxidants including major drawbacks and pitfalls of some assays have been discussed. The availability of both a representative “oxidative stress” animal model and a battery of well-validated assays to assess the broad diversity of oxidative damage and antioxidative defence parameters are crucial for antioxidant research in vivo.

The blood-brain barrier (BBB) remains one of the greatest challenges for the discovery and development of treatments for CNS disorders which to this day remains one of the riskiest disease areas in terms of clinical success rates. Although the BBB is currently seen predominantly as a permeability obstacle for CNS drug delivery it is becoming increasingly clear that the BBB has many more implications for the pharmaceutical industry impacting on CNS pharmacology and pathology CNS pharmacokinetics and pharmacodynamics and adverse CNS effects to name but a few areas. The present review does not intend to summarize the activities in the field of BBB research per se which has been accomplished by a number of excellent recent reviews but instead to provide an overview of the role of BBB studies from a pharmaceutical industry perspective. This review will elaborate on the specific needs in terms of BBB-related issues across the different drug discovery and development phases i.e. target identification and validation lead generation and optimization candidate selection and profiling preclinical development and clinical studies. The specific approaches taken will be discussed in terms of specific requirements questions to be asked feasibility interpretability and impact. It becomes clear that few of the existing BBB models fully meet the requirements of the industrialized drug discovery process highlighting the need for an array of new or modified tools and approaches that are more effective in helping make decisions which are more specifically tailored to the various stages of the lengthy process from target to the clinic. In looking at the numerous ongoing activities in the area of BBB research from the drug discovery and development point of view an attempt has been made to place a stronger emphasis on the applicability of particular techniques and approaches to identify gaps and areas for future activities. In order to materialize the considerable knowledge gained in recent years the review is intended to foster an increased awareness of the need to better integrate basic academic research with the specific requirements of the pharmaceutical industry for the search of effective and safe new CNS medicines.

New infection treatments are urgently needed to combat the rising threat of multi-drug resistant bacteria. Despite early clinical set-backs attention has re-focused on host defense proteins (HDPs) as potential sources for new and effective antimicrobial treatments. HDPs appear to act at multiple targets and their repertoire includes disruptive membrane and intracellular activities against numerous types of pathogens as well as immune modulatory functions in the host. Importantly these novel activities are associated with a low potential for emergence of resistance and little crossresistance with other antimicrobial agents. Based on these properties HDPs appear to be ideal candidates for new antibiotics; however their development has been plagued by the many therapeutic limitations associated with natural peptidic agents. This review focuses on HDP mimetic approaches aimed to improve metabolic stability pharmacokinetics safety and manufacturing processes. Early efforts with β-peptide or peptoid analogs focused on recreating stable facially amphiphilic structures but demonstrated that antimicrobial activity was modulated by more complex structural properties. Several approaches have used lipidation to increase the hydrophobicity and membrane activity. One lead compound LTX-109 has entered clinical study as a topical agent to treat impetigo and nasal decolonization. In a more significant departure from the amino acid like peptidomimetics considerable effort has been directed at developing amphiphilic compounds that recapitulate the structural and biological properties of HDPs on small abiotic scaffolds. The lead compound from this approach brilacidin has completed two phase 2 studies as an intravenous agent for skin infections.

With the development of epidermal growth factor receptor (EGFR)-based tyrosine kinase inhibitors (TKIs) and their applications in the clinic non-small-cell lung cancer (NSCLC) treatment has entered a new era and a great number of patients have benefited. However there still exist other subgroups of patients who may not benefit from EGFR TKIs although EGFR mutation is the main driving mutation that leads to NSCLC. To identify potential NSCLC responders for TKI therapy and to detect EGFR status in vivo noninvasive technology such as TKI PET imaging has been developed in recent years and a great number of tyrosine kinase-targeted PET tracers have been reported. The visualization and quantification of EGFR expression in vivo by PET would provide the most important information for personalizing NSCLC therapy and prediction of response in clinical. This article reviews the progress of small molecular tyrosine kinase-targeted PET tracers and their applications in preclinical experiments and clinical studies. The current limitations and future development of these tracers are also briefly discussed.

Apicomplexian parasite of the genus Plasmodium is the causative agent of malaria one of the most devastating furious and common infectious disease throughout the world. According to the latest World malaria report there were 229 million cases of malaria in 2019 majorly consist of children under 5 years of age. Some of known analogues viz. quinine quinoline-containing compounds have been used for last century in the clinical treatment of malaria. Past few decades witnessed the emergence of multi-drug resistance (MDR) strains of Plasmodium species to existing antimalarials pressing the need for new drug candidates. Thus in those decades bioorganometallic approach to malaria therapy has been introduced which led to the discovery of noval metalcontaining aminoquinolines analogues viz. ferroquine (FQ or 1) Ruthenoquine (RQ or 2) and other related potent metalanalogues. It observed that some metal containing analogues (Fe- Rh- Ru- Re- Au- Zn- Cr- Pd- Sn- Cd- Ir- Co- Cu- and Mn-aminoquines) were more potent; however some were equally potent as Chloroquine (CQ) and 1. This is probably due to the intertion of metals in the CQ via various approaches which might be a very attractive strategy to develop a SAR of novel metal containing antimalarials. Thus this review aim to summarize the SAR of metal containing aminoquines towards the discovery of potent antimalarial hybrids to provide an insight for rational designs of more effective and less toxic metal containing amonoquines.

Safety and biocompatibility assessment of biomaterials are themes of constant concern as advanced materials enter the market as well as products manufactured by new techniques emerge. Within this context this review provides an up-to-date approach on current methods for the characterization and safety assessment of biomaterials and biomedical devices from a physical-chemical to a biological perspective including a description of the alternative methods in accordance with current and established international standards.