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Lead (Pb) is known to cause neurological changes, but antioxidants, chelators, and anti-inflammatory agents mitigates Pb toxicity. Previously, we reported antioxidant and anti-inflammatory effects of 3-hydroxy-3′,4′,5′-trimethoxyflavone (HTMF) derived from Ocimum basilicum L. leaves. This research investigates the neuroprotective properties of HTMF against Pb induced neurotoxicity in rats. Rats were orally administered lead acetate (100 mg/kg) daily for 30 days to induce neurotoxicity, then treated with HTMF (5 and 10 mg/kg) 30 min after Pb exposure. Cognitive and motor functions and brain biochemical parameters were determined to understand HTMF’s mechanism of action. Pb exposure impaired cognition and motor skills, elevated Pb levels, TBARS, TNF-α, IL-6 and MAO A & B, and reduced GSH levels in the brain. HTMF treatment significantly improved memory, motor deficits, and metabolic abnormalities induced by Pb, attributed to its chelating, antioxidative, anti-inflammatory, and monoaminergic modulating properties, suggesting its potential as a therapeutic agent for metal-induced brain injuries.

SARS-CoV, an RNA virus, is contagious and displays a remarkable degree of adaptability, resulting in intricate disease presentations marked by frequent genetic mutations that can ultimately give rise to drug resistance. Targeting its viral replication cycle could be a potential therapeutic option to counter its viral growth in the human body leading to the severe infectious stage. The Mpro of SARS-CoV-2 is a promising target for therapeutic development as it is crucial for viral transcription and replication. The derivatives of β-diketone and coumarin have already been reported for their antiviral potential and, thus, are considered as a potential scaffold in the current study for the computational design of potential analogs for targeting the viral replication of SARS-CoV-2. In our study, we used novel diketone-hinged coumarin derivatives against the SARS-CoV-2 MPro to develop a broad-spectrum antiviral agent targeting SARS-CoV-2. Through an analysis of pharmacokinetics and docking studies, we identified a list of the top 10 compounds that demonstrated effectiveness in inhibiting the SARS-CoV-2 MPro virus. On the basis of the pharmacokinetics and docking analyses, the top 5 novel coumarin analogs were synthesized and characterized. The thermodynamic stability of compounds KS82 and KS94 was confirmed by their molecular dynamics, and the stability of the simulated system indicated their inhibitory nature. Molecules KS82 and KS94 were further evaluated for their anti-viral potential using Vero E6 cells followed by RT-PCR assay against SARS-CoV-2. The test compound KS82 was the most active with the potential to inhibit SARS-CoV-2 replication in Vero E6 cells. These data indicate that KS82 prevents the attack of the virus and emerges as the primary candidate with promising antiviral properties.

Neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, pose a significant global health challenge, emphasizing the need for novel neuroprotective agents. Basil (Ocimum spp.) has been recognized for its therapeutic potential, and numerous studies have reported neuroprotective effects. In this manuscript, we present a computational protocol to extricate the underlying mechanism of action of basil compounds in neuroprotective effects. Molecular docking-based investigation of the chemical interactions between selected bioactive compounds from basil and key neuroprotective targets, including AChE, GSK3β, γ-secretase, and sirtuin2. Our results demonstrate that basil compound myricerone caffeoyl ester possesses a high affinity of −10.01 and −8.85 kcal/mol against GSK3β and γ-secretase, respectively, indicating their potential in modulating various neurobiological processes. Additionally, molecular dynamics simulations were performed to explore the protein–ligand complexes’ stability and to analyze the bound basil compounds’ dynamic behavior. This comprehensive computational investigation enlightens the putative mechanistic basis for the neuroprotective effects of basil compounds, providing a rationale for their therapeutic use in neurodegenerative disorders after further experimental validation.

Alzheimer’s disease (AD) is caused by plaque agglomeration and entanglement in several areas of the neural cells, which leads to apoptosis. The main etiology of AD is senile dementia, which is linked to amyloid-beta (Aβ) deregulation and tau perivascular pathogeny. Hyperphosphorylated tau has a propensity for microtubules, which elevate the instability and tau-protein congregates, leading to accumulation of neurofibrillary tangles (NFTs). Tau hyperphosphorylation is susceptible to GSK-3, which has led to an emerging hypothesis regarding the pathogenesis of AD. Accordingly, attempts have been made to conduct investigations and achieve further advancements on new analogues capable of inhibiting the GSK-3 protein, which are currently in the clinical trials. In this analysis, we have evaluated certain GSK-3 inhibitor variants utilising scaffolding and framework devised techniques with pharmacological characteristics, accompanied by computational screenings (pharmacokinetics and docking). The structure-based designed analogues interacted effectively with the active amino acids of GSK-3β target protein. The in silico pharmacokinetic studies revealed their drug-like properties. The analogues with best interactions and binding scores will be considered in the future to completely demonstrate their potential relevance as viable GSK-3 inhibitors.

No drug on the market, as a single entity, participates in different pathways involved in the pathology of Alzheimer’s disease. The current study is aimed at the exploration of multifunctional chalcone derivatives which can act on multiple targets involved in Alzheimer’s disease. A series of novel aminoethyl-substituted chalcones have been developed using in silico approaches (scaffold morphing, molecular docking, and ADME) and reported synthetic methods. The synthesized analogs were characterized and evaluated biologically using different in vitro assays against AChE, AGEs, and radical formation. Among all compounds, compound PS-10 was found to have potent AChE inhibitory activity (IC50 = 15.3 nM), even more than the standard drug (IC50 = 15.68 nM). Further, the in vivo evaluation of PS-10 against STZ-induced dementia in rats showed memory improvement (Morris Water Maze test) in rats. Also, PS-10 inhibited STZ-induced brain AChE activity and oxidative stress, further strengthening the observed in vitro effects. Further, the molecular dynamic simulation studies displayed the stability of the PS-10 and AChE complex. The novel aminoethyl-substituted chalcones might be considered potential multifunctional anti-Alzheimer’s molecules.

Alzheimer’s disease (AD) is the prime cause of 65–80% of dementia cases and is caused by plaque and tangle deposition in the brain neurons leading to brain cell degeneration. β-secretase (BACE-1) is a key enzyme responsible for depositing extracellular plaques made of β-amyloid protein. Therefore, efforts are being applied to develop novel BACE-1 enzyme inhibitors to halt plaque build-up. In our study, we analyzed some Elenbecestat analogues (a BACE-1 inhibitor currently in clinical trials) using a structure-based drug design and scaffold morphing approach to achieve a superior therapeutic profile, followed by in silico studies, including molecular docking and pharmacokinetics methodologies. Among all the designed compounds, SB306 and SB12 showed good interactions with the catalytic dyad motifs (Asp228 and Asp32) of the BACE-1 enzyme with drug-likeliness properties and a high degree of thermodynamic stability confirmed by the molecular dynamic and stability of the simulated system indicating the inhibitory nature of the SB306 and SB12 on BACE 1.

Introduction: Cinnamon essential oil (CEO) is a volatile oil, obtained from Cinnamomum zeylanicum has become one of the most important natural oil due to its antimicrobial activity. CEO suffers from various limitations such as instability and skin irritation. This problem has been overcome by formulating CEO-loaded nanosponges incorporated in carbopol gel with increased antimicrobial property and reduced skin irritation. Methods: The nanosponges were fabricated by solvent emulsion diffusion method and evaluated for Fourier transform infrared spectroscopy (FTIR) studies, particle size, field emission scanning electron microscopy studies (FE-SEM), in vitro dissolution studies, in vitro antibacterial studies, using agar diffusion method, in vivo antibacterial activity and skin irritation studies and stability studies. Results: Nanosponge NS1 batch was found to be in the nanosize range. FTIR studies confirmed the absence of drug-polymer interaction. NS1 confirmed a porous structure with a uniform spherical shape using FE-SEM studies. In vitro dissolution studies of optimized NS1 revealed 80% drug release in 5 h whereas, incorporating the formulation into carbopol gel showed 100% release in 5h from G1 formulation. In vitro antibacterial study of the nanosponge (NS1 and NS3) showed remarkable antibacterial activity as seen from the zone of inhibition and gel formulation G1 also showed the highest zone of inhibition with 50±1.2 mm. NS1 and G1 were stable for 2 months under accelerated conditions and 3 months under room temperature conditions. Furthermore, the in vivo and skin irritation studies were performed with selected formulation against Staphylococcus aureus, where the results confirmed the significant antimicrobial activity with no skin irritation. Conclusion: Nanosponge carriers can be more therapeutically effective for essential oils which can further be incorporated into topical gels for convenient application.

Introduction: Irbesartan (IBS), an angiotensin II receptor (AT1 subtype) antagonist which blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selective binding to AT1 angiotensin II receptor. It belongs to BCS class II drug (low aqueous solubility and high permeability). Improvement of dissolution characteristics of the drug by formulating is being investigated in the current study. Methods: Solid dispersions (SD) formulations were prepared by the melting fusion technique and nanocomposites (NC) were prepared by a single emulsion technique. Eight batches of SD and three batches of NC were formulated in three ratios of drug to polymer (1:1, 1:2, and 1:3). The batches were evaluated for equilibrium solubility studies, Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), field emission SEM (FESEM), transmission electron microscopy (TEM), and in vitro dissolution studies. Results: Solubility studies revealed maximum solubility at a 1:2 ratio of solid dispersions and a 1:1 ratio of nanocomposites. No drug-polymer interaction was observed in FTIR results. DSC, SEM, and XRD analysis revealed changes in drug crystallinity i.e. conversion to the amorphous state of drugs. Nanosize of particles in the NC1 batch was confirmed in TEM studies. Solid dispersions and nanocomposites showed significant enhancement of dissolution in comparison to that of the pure drug (100% drug release in approximately 1 hour). Conclusion: Nanocomposites proved superior carriers to solid dispersions in terms of the dissolution enhancement. Further, in vivo studies indicated that the induction of systolic and diastolic blood pressure in the optimized formulation (NC1) was significantly decreased in comparison to the disease control group (P

Nutraceuticals are the nourishing components (hybrid of nutrition and pharmaceuticals) that are biologically active and possess capability for maintaining optimal health and benefits. These products play a significant role in human health care and its endurance, most importantly for the future therapeutic development. Nutraceuticals have received recognition due to their nutritional benefits along with therapeutic effects and safety profile. Nutraceuticals are globally growing in the field of services such as health care promotion, disease reduction, etc. Various drug nutraceutical interactions have also been elaborated with various examples in this review. Several patents on nutraceuticals in agricultural applications and in various diseases have been stated in the last section of review, which confirms the exponential growth of nutraceuticals’ market value. Nutraceuticals have been used not only for nutrition but also as a support therapy for the prevention and treatment of various diseases, such as to reduce side effects of cancer chemotherapy and radiotherapy. Diverse novel nanoformulation approaches tend to overcome challenges involved in formulation development of nutraceuticals. Prior information on various interactions with drugs may help in preventing any deleterious effects of nutraceuticals products. Nanotechnology also leads to the generation of micronized dietary products and other nutraceutical supplements with improved health benefits. In this review article, the latest key findings (clinical studies) on nutraceuticals that show the therapeutic action of nutraceutical’s bioactive molecules on various diseases have also been discussed.

Neurodegenerative diseases (NDDs) are the primary cause of disabilities in the elderly people. Growing evidence indicates that oxidative stress, mitochondrial dysfunction, neuroinflammation and apoptosis are associated with aging and the basis of most neurodegenerative disorders. Quercetin is a flavonoid with significant pharmacological effects and promising therapeutic potential. It is widely distributed among plants and typically found in daily diets mainly in fruits and vegetables. It shows a number of biological properties connected to its antioxidant activity. Neuroprotection by quercetin has been reported in many in vitro as well as in in vivo studies. However, the exact mechanism of action is still mystery and similarly there are a number of hypothesis exploring the mechanism of neuroprotection. Quercetin enhances neuronal longevity and neurogenesis by modulating and inhibiting wide number of pathways. This review assesses the food sources of quercetin, its pharmacokinetic profile, structure activity relationship and its pathophysiological role in various NDDs and it also provides a synopsis of the literature exploring the relationship between quercetin and various downstream signalling pathways modulated by quercetin for neuroprotection for eg. nuclear factor erythroid 2-related factor 2 (Nrf2), Paraoxonase-2 (PON2), c-Jun N-terminal kinase (JNK), Tumour Necrosis Factor alpha (TNF-α), Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (PGC-1α), Sirtuins, Mitogen-activated protein kinases (MAPKs) signalling cascades, CREB (Cyclic AMP response element binding protein) and Phosphoinositide 3- kinase(PI3K/Akt). Therefore, the aim of the present review was to elaborate on the cellular and molecular mechanisms of the quercetin involved in the protection against NDDs.

Carbamazepine is a commonly prescribed antiepileptic drug with a potential to cause fatal toxicity in acute overdose in children. Symptoms of acute toxicity include central nervous system depression, seizures, anticholinergic toxidrome, and arrhythmias. We report a 5 year old male child with accidental carbamazepine toxicity treated sussessfully with good suppotrive management. Intestinal decontamination therapies may be beneficial if used at the appropriate time. Multidose activated charcoal may be used if multiple controlled release tablets are ingested. Extracorporeal therapies for drug removal may be required in life-threatening toxicity to reduce plasma drug levels and hasten recovery. Appropriate and timely management leads to excellent neurological outcome.

Aim: The purpose of the present study was to examine whether clinical differences exist between the biodegradable polymer (BDP)–coated Tetrilimus everolimus-eluting stent (EES) and the durable polymer (DP)–coated Xience EES by comparing the major adverse cardiac event (MACE) rate at 12 months in all-comer patients. Methods: This study was designed as a multicentre, observational, retrospective, investigator-initiated study between January 2016 and October 2016. Two hundred thirteen patients who underwent percutaneous coronary intervention (PCI) with the BDP-EES were compared with 204 patients who underwent PCI with the DP-EES, irrespective of lesion complexity, comorbidities and acute presentation. The primary end point was MACE defined as a composite of cardiac death, myocardial infarction and target lesion revascularization. Results: Baseline clinical and lesion characteristics of both the groups were similar, although the BDP-EES group had a significantly higher number of patients with diabetes mellitus (39.9% vs. 30.4%; p = 0.042) and type C lesion (67.4% vs. 48.1%; p

Chondroitin sulfate is a proteoglycan component of the extracellular matrix (ECM) that supports neuronal and non-neuronal cell activity, provides a negative domain to the extracellular matrix, regulates the intracellular positive ion concentration, and maintains the hypersynchronous epileptiform activity. Therefore, the present study hypothesized an antiepileptic potential of chondroitin sulfate (CS) in pentylenetetrazole-induced kindled epilepsy and pilocarpine-induced status epilepticus in mice. Levels of various oxidative stress markers and inflammatory mediators were estimated in the brain tissue homogenate of mice, and histopathological changes were evaluated. Treatment with valproate (110 mg/kg; i.p.) as a standard drug and chondroitin sulfate (100 & 200 mg/kg, p.o.) significantly (p < 0.01) and dose-dependently prevented the severity of kindled and spontaneous recurrent seizures in mice. Additionally, chondroitin sulfate showed its antioxidant potential by restoring the various biochemical levels and anti-inflammatory properties by reducing NF-kB levels and pro-inflammatory mediators like TNF-alpha, IL-1β, and IL-6, indicating the neuroprotective effect as well as the suppressed levels of caspase-3, which indicated a neuroprotective treatment strategy in epilepsy. The proteoglycan chondroitin sulfate restores the normal physiology and configuration of the neuronal tissue. Further, the molecular docking of chondroitin sulfate at the active pockets of TNF-alpha, IL-1β, and IL-6 showed excellent interactions with critical amino acid residues. In conclusion, the present work provides preclinical evidence of chondroitin sulfate as a new therapeutic approach in attenuating and preventing seizures with a better understanding of the mechanism of alteration in ECM changes influencing abnormal neuronal activities.

Introduction Pharmacologic treatment options for allergic rhinitis include intranasal corticosteroids, oral and topical antihistamines, decongestants, intranasal cromolyn, intranasal anticholinergics and leukotriene receptor antagonists. The present study was undertaken to compare the efficacy of leukotriene receptor antagonist and antihistamines in relieving nasal congestion/ obstruction symptom and itching /irritation in eyes. Material and Methods The study was conducted among 125 patients clinically diagnosed suffering from allergic rhinitis Patients were divided into 5 groups and were given oral treatment with oral antihistamines (chlorpheniramine maleate, levocetrizine, fexofenadine, desloratadine) and leukotriene receptor antagonist (montelukast) for a period of 6 weeks. The results were tabulated and analyzed by Chi-square and Kruskal-Wallis test with p value

Background: Cultivation of algae for conversion to biofuels has gained global interest. Outdoor raceway cultivation is preferred because of its lower capital and operating costs. A major disadvantage of outdoor cultivation is susceptibility of algal crops to attack by predatory rotifers. In order to quantify the impact of rotifer attack on different species of algae, we evaluated the growth of eleven microalgal species over a 21-d period after being infected by the predatory rotifer Brachionus rubens. Results: Of the eleven species, Chlorella sorokiniana was the most susceptible with rapid decline in algal growth concomitant with increase in rotifer population growth (3.82/d). In contrast, Synechococcus elongatus and Scenedesmus dimorphus were both resistant to the rotifer and suppressed rotifer growth (-0.06/d). An index of algal species susceptibility to be consumed by the rotifer was generated with C. sorokiniana as the baseline (index = 1.000) indicating most susceptible among species tested. Other species' susceptibilities are indicated in parenthesis as follows: Monoraphidium spp. (0.997), Chlamydomonas globosa (0.827), Botryococcus braunii (0.740), Chlorella minutissima (0.570), Chlamydomonas augustae (0.530), Chlamydomonas yellowstonensis (0.500), Scenedesmus bijuga (0.420), and Haematococcus pluvialis (0.360). Two species, namely, S. dimorphus and S. elongatus were unique in that they exhibited an ability to suppress the growth of the rotifer as indicated by the decline in rotifer populations in their presence. Conclusions: Variations in susceptibility of algal species to rotifer predation could be a result of their individual morphology, cell walls structure, or the biochemical composition of individual species.

The aim of the study was to investigate the protective effect of isoniazid–curcumin conjugate (INH–CRM) in INH-induced hepatic injury by biochemical analysis and histology examination of liver in Wistar rats. The biochemical analysis included determination of the levels of plasma cholesterol, triglycerides (TG), albumin content, and lipid peroxidation (MDA). INH–CRM administration resulted in a significant decrease in plasma cholesterol, TG, and MDA levels in the liver tissue homogenate with an elevation in albumin level indicating its hepatoprotective activity. Histology of the liver further confirmed the reduction in hepatic injury. The hepatoprotective with INH–CRM can be attributed to the antioxidant activity of curcumin. The conjugate probably stabilizes the curcumin molecule, preventing its presystemic metabolism thereby enhancing its bioavailability and therefore, its hepatoprotective activity. Thus, the novel INH–CRM has the potential to alleviate INH-induced liver toxicity in antitubercular treatment.

Objective: The present study was undertaken to establish the effect of pollutants in the form of auto-exhaust, gases, etc. on the respiratory airways of healthy, non-smoking bus drivers in the age group of 20-55 years, by measuring the peak expiratory flow rate (PEFR) values. Materials and Methods: One hundred healthy, non-smoking bus drivers in the age group of 20 years to 55 years. were selected randomly from a bus stand of the PRTC (Punjab Roadways Transport Corporation) in the Patiala district and their PEFR values were compared with those of one hundred healthy, non-smoking persons in the age group of 20 years to 55 years, who were engaged in professions other than bus driving. Subjects with a prior history of reactive airways or bronchodilator intake were excluded. The influence of age, height, weight, body surface area and the duration of exposure on PEFR were studied. The PEFR test was performed by using Mini Wright’s Peak Flow Meter. Results: The mean PEFR of the bus drivers was found to be less than that of the control subjects in each group and the results were found to be statistically highly significant (p

This document provides information on various compounds, specifically N-formyl derivatives, and their spectroscopic data. The compounds mentioned include a wide range of derivatives with different functional groups. The compounds were purified and their spectroscopic data were compared to existing literature, confirming their identities. The document also acknowledges the scholarship awarded to one of the researchers. [Extracted from the article]