Essential oils extracted from Citrus macroptera and Homalomena aromatica (Spreng.) Schott. exhibit repellent activities against Aedes aegypti (Diptera: Culicidae).

BACKGROUND OBJECTIVES: Mosquitoes alone transmit diseases to around 700 million individuals annually, killing approximately 0.7 million people every year worldwide. Considering the potential health risks linked with synthetic repellents, it has become vital to identify eco-friendly, natural repellents for mosquito control as well as to understand the underlying mechanism for mosquito repellent activity. To address this, objectives were set to extract essential oils from Citrus macroptera peel and Homalomena aromatica (Spreng.) Schott. rhizomes, evaluate their mosquito repellent activity against Aedes aegypti, and further explore their mosquito odorant receptor inhibition potential. METHODS: The oils were extracted using Clevenger's apparatus, and properties like specific gravity, refractive index, and boiling point were evaluated and characterised using Fourier transform infrared spectroscopy (FTIR) and gas chromatography-mass spectroscopy (GC-MS). Aedes aegypti mosquito eggs collected from the Indian Council of Medical Research (ICMR), Dibrugarh, were reared in the Department of Pharmaceutical Sciences, Research Laboratory, to obtain adult Aedes aegypti mosquitoes for the mosquito repellent activity evaluation of the essential oils using the Human Bait technique'. Molecular docking studies were performed for the oil components against mosquito odorant binding proteins. Further, toxicity studies of these two oils were evaluated against human dermal fibroblast adult (HDFa) cells. RESULTS: The results revealed the presence of limonene (86.76%) and linalool (52.35%), respectively, in Citrus macroptera and Homalomena aromatica oils. It was found that the combination of the oils in a ratio of 1:1 showed mosquito repellent activity for up to 6.33 ± 0.23 h. Molecular docking studies showed the presence of major oil components having mosquito odorant receptor blocking potential comparable to N, N-diethyl-meta-toluamide (DEET), indicating a rationale for extended mosquito repellent action. Further, both of these oils were found to be non-cytotoxic against HDFa cells after 24 h. INTERPRETATION CONCLUSION: The encouraging mosquito repellent activity of these two oils as compared to synthetic mosquito repellent DEET might pave the way for the development of novel herbal mosquito repellent formulations containing these essential oils.

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

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

Adenoviral Vector-Based Vaccine Platform for COVID-19: Current Status.

The coronavirus disease (COVID-19) breakout had an unimaginable worldwide effect in the 21st century, claiming millions of lives and putting a huge burden on the global economy. The potential developments in vaccine technologies following the determination of the genetic sequence of SARS-CoV-2 and the increasing global efforts to bring potential vaccines and therapeutics into the market for emergency use have provided a small bright spot to this tragic event. Several intriguing vaccine candidates have been developed using recombinant technology, genetic engineering, and other vaccine development technologies. In the last decade, a vast amount of the vaccine development process has diversified towards the usage of viral vector-based vaccines. The immune response elicited by such vaccines is comparatively higher than other approved vaccine candidates that require a booster dose to provide sufficient immune protection. The non-replicating adenoviral vectors are promising vaccine carriers for infectious diseases due to better yield, cGMP-friendly manufacturing processes, safety, better efficacy, manageable shipping, and storage procedures. As of April 2022, the WHO has approved a total of 10 vaccines around the world for COVID-19 (33 vaccines approved by at least one country), among which three candidates are adenoviral vector-based vaccines. This review sheds light on the developmental summary of all the adenoviral vector-based vaccines that are under emergency use authorization (EUA) or in the different stages of development for COVID-19 management.

Therapeutic drug repositioning with special emphasis on neurodegenerative diseases: Threats and issues.

Drug repositioning or repurposing is the process of discovering leading-edge indications for authorized or declined/abandoned molecules for use in different diseases. This approach revitalizes the traditional drug discovery method by revealing new therapeutic applications for existing drugs. There are numerous studies available that highlight the triumph of several drugs as repurposed therapeutics. For example, sildenafil to aspirin, thalidomide to adalimumab, and so on. Millions of people worldwide are affected by neurodegenerative diseases. According to a 2021 report, the Alzheimer's disease Association estimates that 6.2 million Americans are detected with Alzheimer's disease. By 2030, approximately 1.2 million people in the United States possibly acquire Parkinson's disease. Drugs that act on a single molecular target benefit people suffering from neurodegenerative diseases. Current pharmacological approaches, on the other hand, are constrained in their capacity to unquestionably alter the course of the disease and provide patients with inadequate and momentary benefits. Drug repositioning-based approaches appear to be very pertinent, expense- and time-reducing strategies for the enhancement of medicinal opportunities for such diseases in the current era. Kinase inhibitors, for example, which were developed for various oncology indications, demonstrated significant neuroprotective effects in neurodegenerative diseases. This review expounds on the classical and recent examples of drug repositioning at various stages of drug development, with a special focus on neurodegenerative disorders and the aspects of threats and issues viz. the regulatory, scientific, and economic aspects.

A Comprehensive Review on Preclinical Diabetic Models.

BACKGROUND: Preclinical experimental models historically play a critical role in the exploration and characterization of disease pathophysiology. Further, these in-vivo and in-vitro preclinical experiments help in target identification, evaluation of novel therapeutic agents and validation of treatments. INTRODUCTION: Diabetes mellitus (DM) is a multifaceted metabolic disorder of multidimensional aetiologies with the cardinal feature of chronic hyperglycemia. To avoid or minimize late complications of diabetes and related costs, primary prevention and early treatment are therefore necessary. Due to its chronic manifestations, new treatment strategies need to be developed, because of the limited effectiveness of the current therapies. METHODS: The study included electronic databases such as Pubmed, Web of Science and Scopus. The datasets were searched for entries of studies up to June, 2018. RESULTS: A large number of in-vivo and in-vitro models have been presented for evaluating the mechanism of anti-hyperglycaemic effect of drugs in hormone-, chemically-, pathogen-induced animal models of diabetes mellitus. The advantages and limitations of each model have also been addressed in this review. CONCLUSION: This review encompasses the wide pathophysiological and molecular mechanisms associated with diabetes, particularly focusing on the challenges associated with the evaluation and predictive validation of these models as ideal animal models for preclinical assessments and discovering new drugs and therapeutic agents for translational application in humans. This review may further contribute to discover a novel drug to treat diabetes more efficaciously with minimum or no side effects. Furthermore, it also highlights ongoing research and considers the future perspectives in the field of diabetes.

Ziprasidone-loaded arabic gum modified montmorillonite-tailor-made pectin based gastroretentive composites.

Novel diethanolamine-grafted high-methoxyl pectin (DGP)-arabic gum (AG) modified montmorillonite (MMT) composites were developed for intragastric ziprasidone HCl (ZIP) delivery by combining floating and mucoadhesion mechanisms. The ZIP-loaded clay-biopolymer matrices were accomplished by ionotropic gelation protocol utilizing zinc acetate in the presence or absence of covalent crosslinker, glutaraldehyde (GA). Various formulations exhibited excellent drug entrapment efficiency (DEE, %) and sustained drug release profiles, which were influenced by the polymer-blend (DGP:AG) ratios, reinforcing filler (MMT) existence and crosslinking procedure. The optimal composites (F-3) demonstrated DEE of 61% and Q8h of 52% with outstanding buoyancy, mucin adsorption ability and biodegradability. The release profile of F-3 was best fitted in the Korsmeyer-Peppas model with Fickian diffusion driven mechanism. The mucin adsorption to composites F-3 followed Freundlich isotherms. The molar mass between crosslinks of composites (F-3) calculated employing Flory-Rehner equation was increased with temperature. Moreover, the thermal, X-ray and infrared analyses confirmed a compatible environment of drug in the composites, except certain extent of transformation of the crystalline drug to its amorphous form. The SEM studies revealed the spherical morphology of the composites. Thus, the newly developed DGP-AG-MMT composites are appropriate for gastroretentive ZIP delivery over an extended period of time.

Novel butyrylcholinesterase inhibitors through pharmacophore modeling, virtual screening and DFT-based approaches along-with design of bioisosterism-based analogues.

Ligand and structure-based pharmacophore models were used to identify the important chemical features of butyrylcholinesterase (BChE) inhibitors. A training set of 16 known structurally diverse compounds with a wide range of inhibitory activity against BChE was used to develop a quantitative ligand-based pharmacophore (Hypo1) model to identify novel BChE inhibitors in virtual screening databases. A structure-based pharmacophore hypothesis (Phar1) was also developed with the ligand-binding site of BChE in consideration. Further, the models were validated using test set, Fisher's Randomization and Leave-one-out validation methods. Well-validated pharmacophore hypotheses were further used as 3D queries in virtual screening and 430 compounds were finally selected for molecular docking analysis. Subsequently, ADMET, DFT and chemical similarity search were employed to narrow down on seven compounds as potential drug candidates. Analogues of the best hit were further developed through a bioisosterism-guided approach to further generate a library of potential BChE inhibitors.

Resveratrol and Omega-3 Fatty Acid: Its Implications in Cardiovascular Diseases.

The present review aims at summarizing the major therapeutic roles of resveratrol and omega-3 fatty acids (O3FAs) along with their related pathways. This article reviews some of the key studies involving the health benefits of resveratrol and O3FAs. Oxidative stress has been considered as one of the most important pathophysiological factors associated with various cardiovascular disease conditions. Resveratrol, with the potent antioxidant and free radical scavenging properties, has been proven to be a significantly protective compound in restoring the normal cardiac health. A plethora of research also demonstrated the reduction of the risk of coronary heart disease, hypertension, and stroke, and their complications by O3FAs derived from fish and fish oils. This review describes the potential cardioprotective role of resveratrol and O3FAs in ameliorating the endoplasmic reticulum stress.

Nanoplatforms for Delivery of siRNA to the Eye.

Drug delivery to the eye is challenging for formulation scientists due to physiological barriers that separate the eye from the rest of the body. A variety of ocular disorders demand the development of optimal drug delivery systems for the administration of drugs and therapeutic agents that can overcome barriers that restrict drug bioavailability. SiRNA inhibits the expression of target genes and has immense potential as a biological tool for the therapeutic inhibition of disease causing genes; however, delivery of siRNA to ocular tissue is a challenge. Recent literature suggests that nanoplatforms show great promise in enhancing ophthalmic drug delivery. A drug delivery system involving nanoparticles and siRNA could surpass problems faced in ocular delivery with improved biodistribution and lower toxicity. This review covers recent research in the area of nanocarrier siRNA drug delivery for various ocular disorders.

Antihyperglycemic and in vivo antioxidative activity evaluation of Cinnamomum bejolghota (Buch.-Ham.) in streptozotocin induced diabetic rats: an ethnomedicinal plant in Assam.

OBJECTIVE: To evaluate the antihyperglycemic property of Cinnamomum bejolghota (Buch.-Ham.) on streptozotocin induced type-2 diabetic rats. METHODS: Oral glucose tolerance test level was measured at 0, 30, 60, 90 and 120 min after the administration of extract. The extract was orally administered once daily at two dose levels of 250 and 500 mg/kg for 15 d. The effect of methanolic extract of Cinnamomum bejolghota (MECB) on the divergence of body weights, blood glucose levels and the biochemical parameters viz., total cholesterol, high density lipoprotein, low density lipoprotein, triglyceride, aspartate transaminase, alanine transaminase, alkaline phosphatase were measured in an autoanalyzer. Histopathology of pancreas and in vivo antioxidative status was studied. RESULTS: A significant increase in bodyweights and rapid decrease in hyperglycemic peak was experiential in animals treated with MECB. After 15 d treatment the total cholesterol, TG, low density lipoprotein level decreased and high density cholesterol level increased significantly. MECB reduced the levels of the elevated marker enzymes aspartate transaminase, alanine transaminase and alkaline phosphatase. MECB reduced the lipid peroxidation and improved the level of catalase and glutathione in liver. Histopathological studies of pancreas in diabetic and treated groups substantiate the cytoprotective action of extract. CONCLUSIONS: It can be evident from the research work that Cinnamomum bejolghota (Buch.-Ham.) has potent antihyperglycemic activity and supports the in vivo antioxidative status.

Study on Antibacterial Activity of the Bark of Garcinia lanceifolia Roxb.

Garcinia lanceifolia Roxb. is an important and endemic medicinal plant of Assam which has been used by various ethnic communities of Northeast India to treat various disorders like dysentery, dyspepsia, and biliousness. The plant is considered to be containing much medicinal value and is also eaten raw or made into pickles by the local people. Our present study has been focused on the evaluation of the antibacterial activity of the methanolic extract of the bark of Garcinia lanceifolia which may lead us to a scientific evidence of the use of this plant in cases of dysentery and diarrhoea.

Analgesic and anti-inflammatory activities of the methanolic stem bark extract of Nyctanthes arbor-tristis linn.

Stem bark of Nyctanthes arbor-tristis Linn. was extracted in methanol to evaluate their analgesic and anti-inflammatory activities. The analgesic activity was determined on Wistar albino rats by hot plate method, tail flick assay, and tail immersion method using Morphine sulphate as standard drug at a dose of 5 mg/kg of body weight and the results were expressed as mean increase in latency after drug administration ± SEM. The anti-inflammatory activity was assessed by Carrageenan-induced rat paw oedema using diclofenac sodium as standard drug at a dose of 100 mg/kg of body weight and expressed in terms of mean increase in paw volume ± SEM. Stem bark extract was given at a dose of 250 mg/kg and 500 mg/kg of body weight. Both standard drugs and extract were administered orally to the animals. Control received distilled water orally. Results showed that Nyctanthes arbor-tristis Linn. had potent analgesic and anti-inflammatory activities.