Anticonvulsant potential of Grewia tiliaefolia in pentylenetetrazole induced epilepsy: insights from in vivo and in silico studies.

Epilepsy, a chronic neurological condition, impacts millions of individuals globally and remains a significant contributor to both illness and mortality. Available antiepileptic drugs have serious side effects which warrants to explore different medicinal plants used for the management of epilepsy reported in Traditional Indian Medicinal System (TIMS). Therefore, we explored the antiepileptic potential of the Grewia tiliaefolia (Tiliaeceae) which is known for its neuroprotective properties. Aerial parts of G. tiliaefolia were subjected to extraction with increasing order of polarity viz. hexane, chloroform and methanol. Antioxidant potential of hexane, chloroform and methanol extracts of G. tiliaefolia was evaluated by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay, total antioxidant capacity (TAC) assay, reducing power assay (RPA) and DNA nicking assay. Additionally, quantitative antioxidant assays were also conducted to quantify total phenolic (TPC) and total flavonoid content (TFC). As revealed by in vitro assays, methanol extract was found to contain more phenolic content. Hence, the methanol extract was further explored for its anticonvulsant potential in pentylenetetrazole (PTZ) induced acute seizures in mice. The methanol extract (400 mg/kg) significantly increased the latency to occurrence of myoclonic jerks and generalized tonic clonic seizures (GTCS). Additionally, it also reduced duration and seizure severity score associated with GTCS. The Grewia tiliaefolia methanol extract was further screened by Ultra High-Performance Liquid Chromatography (UHPLC) for presence of polyphenolic compounds, among which gallic acid and kaempferol were present in higher amount and were further analysed by in silico study to predict their possible binding sites and type of interactions these compounds show with gamma amino butyric acid (GABA) receptor and glutamate α amino-3- hydroxyl-5-methyl-4-isoxazolepropionic acid (Glu-AMPA) receptor. It was revealed that gallic acid and kaempferol had shown agonistic interaction for GABA receptor and antagonistic interaction for Glu-AMPA receptor. We concluded that G. tiliaefolia showed anticonvulsant potential possibly because of gallic acid and kaempferol possibly mediated through GABA and Glu-AMPA receptor.

Role of polyphenolic compounds and their nanoformulations: a comprehensive review on cross-talk between chronic kidney and cardiovascular diseases.

Chronic kidney disease (CKD) affects a huge portion of the world's population and frequently leads to cardiovascular diseases (CVDs). It might be because of common risk factors between chronic kidney disease and cardiovascular diseases. Renal dysfunction caused by chronic kidney disease creates oxidative stress which in turn leads to cardiovascular diseases. Oxidative stress causes endothelial dysfunction and inflammation in heart which results in atherosclerosis. It ends in clogging of veins and arteries that causes cardiac stroke and myocardial infarction. To develop an innovative therapeutic approach and new drugs to treat these diseases, it is important to understand the pathophysiological mechanism behind the CKD and CVDs and their interrelationship. Natural phytoconstituents of plants such as polyphenolic compounds are well known for their medicinal value. Polyphenols are plant secondary metabolites with immense antioxidant properties, which can protect from free radical damage. Nowadays, polyphenols are generating a lot of buzz in the scientific community because of their potential health benefits especially in the case of heart and kidney diseases. This review provides a detailed account of the pathophysiological link between CKD and CVDs and the pharmacological potential of polyphenols and their nanoformulations in promoting cardiovascular and renal health.

Neuroprotective activity of novel phenanthrene derivative from Grewia tiliaefolia by in vitro and in silico studies.

Medicinal plants possess range of phytochemicals accountable for their diverse biological activities. Presently, such compounds have been isolated from medicinal plants, characterized and evaluated for their pharmacological potential. In the present study, the efforts have been made to isolate the compound(s) from Grewia tiliaefolia Vahl., plant known for its ameliorative effect on brain related diseases such as anxiety, depression, cognitive disorders and Parkinson's disease. Plant extract was subjected to isolation of compound(s) using column chromatography and isolated compound was characterized by NMR FTIR and LCMS. The isolated compound was novel with the IUPAC name of the compound is propyl 3-hydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylate, designated as A-1 and has not been reported before. A-1 was further evaluated for its antioxidant potential using in vitro antioxidant assays (2,2-diphenyl-1-picryl-hydrazyl-hydrate, DPPH assay and reducing power assay, RPA). Also, Acetylcholinesterase (AChE) inhibitory potential of A-1 and extract was analysed. Results showed that A-1 exhibited significantly higher antioxidant activity in both DPPH and RPA assay as compared to plant extract. In case of AChE inhibitory activity again, A-1 has shown significantly higher activity as compared to plant extract. In silico study was conducted to predict its action on proteins playing crucial role in neurological and neurodegenerative disorders such as gamma amino butyric acid (GABA) receptor and glutamate α amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (Glu AMPA) receptor in epilepsy and AChE enzyme in Alzheimer's diseases. The compound has shown interaction in following order: AChE > GABA receptor > Glu AMPA receptor. Further, molecular dynamic simulations and ADME studies of A-1 and AChE enzyme revealed that A-1 yielded good results in all parameters and hence can relieve Alzheimer's like symptoms.

Shikonin derivatives as potent xanthine oxidase inhibitors: in-vitro study.

Induction of hypersensitivity reactions (may be fatal too) by specific XO inhibitors has led to development of new molecules that are efficacious and have safer ADME profile. Among natural compounds, biologically active Alkannin/Shikonin (A/S) derivatives have unexplored XO inhibition potential. Therefore, their iso-hexenylnaphthazarin nucleus was studied and found that the nucleus is similar to that of allopurinol, signifying the XO inhibitory potential of these derivatives. For confirmation of their potential, ß,ß-dimethylacrylshikonin and deoxyshikonin were successfully isolated and characterised from Arnebia euchroma (Royle.) Johnst. (Boraginaceae) and were evaluated for in vitro XO inhibitory potential. ß,ß-dimethylacrylshikonin and deoxyshikonin showed a good XO inhibition potential with IC50 values of 7.475 ± 1.46 µg/mL and 4.487 ± 0.88 µg/mL, respectively. Results also validated the pharmacophore hypothesis, and it was concluded that nucleus iso-hexenylnaphthazarin can be remodelled for optimising the efficacy.

A Comprehensive Review on Medicinal Herbs and Novel Formulations for the Prevention of Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases reported in the aging population across the globe. About 46.8 million people are reported to have dementia, and AD is mainly responsible for dementia in aged people. Alzheimer's disease (AD) is thought to occur due to the accumulation of ß-amyloid (Aß) in the neocortex portion of the brain, nitric oxide mediated dysfunctioning of blood-brain barrier, reduced activity of serine racemase enzyme, cell cycle disturbances, damage of N-methyl-D-aspartate (NMDA) receptors and glutamatergic neurotransmission. Modern treatment methods target the pathways responsible for the disease. To date, solely symptomatic treatments exist for this disease, all making an attempt to counterbalance the neurotransmitter disturbance. Treatments able to prevent or at least effectively modifying the course of AD, referred to as 'disease-modifying' drugs, are still under extensive research. Effective treatments entail a better indulgence of the herbal bioactives by novel drug delivery systems. The herbal bioactive administered by novel drug delivery systems have proved beneficial in treating this disease. This review provides detailed information about the role of medicinal plants and their formulations in treating Alzheimer's disease which will be highly beneficial for the researchers working in this area.

Recent Advances in the Local Drug Delivery Systems for Improvement of Anticancer Therapy

The conventional anticancer chemotherapies not only cause serious toxic effects but also produce resistance in tumor cells exposed to long-term therapy. Usually, the selective killing of metastasized cancer cells requires long-term therapy with higher drug doses because the cancer cells develop resistance due to the induction of poly-glycoproteins (P-gps) that act as a transmembrane efflux pump to transport drugs out of the cells. During the last few decades, scientists have been exploring new anticancer drug delivery systems such as microencapsulation, hydrogels, and nanotubes to improve bioavailability, reduce drug-dose requirement, decrease multiple drug resistance, and save normal cells as non-specific targets. Hopefully, the development of novel drug delivery vehicles (nanotubes, liposomes, supramolecules, hydrogels, and micelles) will assist in delivering drug molecules at the specific target site and reduce undesirable side effects of anticancer therapies in humans. Nanoparticles and lipid formulations are also designed to deliver a small drug payload at the desired tumor cell sites for their anticancer actions. This review will focus on the recent advances in drug delivery systems and their application in treating different cancer types in humans.

Vertically standing nanoporous Al-Ag zig-zag silver nanorod arrays for highly active SERS substrates.

Surface enhanced Raman scattering (SERS) has emerged as a promising technique for chemical and biological sensing. "Hot spots" are the areas on noble metal nanostructures where light is highly concentrated into small volumes and enhances the local electromagnetic field near the metal nanostructures. These hot spots have been claimed to provide extraordinary enhancements to the SERS signal. Here, we report the fabrication of nanoporous zig-zag Ag nanostructures with built-in high density hot spots. The zig-zag Ag nanostructures were fabricated by glancing angle deposition of Ag and Al, with Al deposited on the edges of the zig-zag structure during growth. A 2.5 wt% HCl solution was used for etching Al from the Ag-Al zig-zag structure. The etching process produced intra-particle gaps by leaching less stable Al from fully alloyed Al-Ag nanostructures. This step of mild acid etching (2.5% v/v HCl for 45 min) allowed the formation of Raman hot spots on the elbows of zig-zag nanorods while maintaining the zig-zag morphology of highly active Ag nanostructures. A high enhancement factor of ∼106 was observed on nanoporous zig-zag Ag nanostructures obtained by de-alloying, making them very appealing as Raman sensors. The role played by nanogap hot spots in Ag zig-zag nanostructures towards SERS enhancement is modelled by using finite difference time domain (FDTD) simulations.

An improved method of bisulfite treatment and purification to study precise DNA methylation from as little as 10 pg DNA.

Methylation of vertebrate DNA is one of the most important epigenetic alterations which have become a center of scientific attraction, especially because of its important role in the regulation of transcription, genomic imprinting, developmental process, and pathogenesis of various diseases. Currently, there are wide ranges of methods available to produce quantitative and qualitative information on genomic DNA methylation. The vast majority of these methods rely on the optimization of the efficient bisulfite treatment. However, all the available methods for bisulfite treatment suffer from major disadvantages, such as large amount of starting material, poor conversion efficiency as well as low recovery and integrity of DNA after bisulfite treatment. Here, we developed a simple, rapid, and convenient column-based bisulfite treatment method by improving the several critical steps, which leads to consistent C-to-U conversion rate 99-100 %, >75 % recovery of DNA after bisulfite treatment. In addition, it is commercially viable and requires very less amount (~10 pg) of DNA.

A column-based rapid method for the simultaneous isolation of DNA, RNA, miRNA and proteins.

In the 21st century, systems biology is a holistic approach to understand life by the cross-talk study between the genome, Rnome and proteome of a cell. We describe a column-based rapid method for the simultaneous extraction of DNA, RNA, miRNA (microRNA) and proteins from the same experimental sample without prior fractionation, which allows a direct correlation between genomic, epigenomic, transcriptomic and proteomic data. This method provides a simple and effective way to analyse each of these biomolecules without affecting yield and quality. We also show that isolated biomolecules are of the highest purity and compatible for all the respective downstream applications, such as PCR amplification, RT-PCR (reverse transcription-PCR), real-time PCR, reverse Northern blotting, SDS/PAGE and Western blot analysis. The buffers and reagents used in this method are optimized extensively to achieve the cost effective and reliable procedure to separate the functional biomolecules of the cell.