Green synthesis of Piper nigrum copper-based nanoparticles: in silico study and ADMET analysis to assess their antioxidant, antibacterial, and cytotoxic effects

Nanobiotechnology is a popular branch of science that is gaining interest among scientists and researchers as it allows for the green manufacturing of nanoparticles by employing plants as reducing agents. This method is safe, cheap, reproducible, and eco-friendly. In this study, the therapeutic property of Piper nigrum fruit was mixed with the antibacterial activity of metallic copper to produce copper nanoparticles. The synthesis of copper nanoparticles was indicated by a color change from brown to blue. Physical characterization of Piper nigrum copper nanoparticles (PN-CuNPs) was performed using UV-vis spectroscopy, FT-IR, SEM, EDX, XRD, and Zeta analyzer. PN-CuNPs exhibited potential antioxidant, antibacterial, and cytotoxic activities. PN-CuNPs have shown concentration-dependent, enhanced free radical scavenging activity, reaching maximum values of 92%, 90%, and 86% with DPPH, H2O2, and PMA tests, respectively. The antibacterial zone of inhibition of PN-CuNPs was the highest against Staphylococcus aureus (23 mm) and the lowest against Escherichia coli (10 mm). PN-CuNPs showed 80% in vitro cytotoxicity against MCF-7 breast cancer cell lines. Furthermore, more than 50 components of Piper nigrum extract were selected and subjected to in silico molecular docking using the C-Docker protocol in the binding pockets of glutathione reductase, E. coli DNA gyrase topoisomerase II, and epidermal growth factor receptor (EGFR) tyrosine to discover their druggability. Pipercyclobutanamide A (26), pipernigramide F (32), and pipernigramide G (33) scored the highest Gibbs free energy at 50.489, 51.9306, and 58.615 kcal/mol, respectively. The ADMET/TOPKAT analysis confirmed the favorable pharmacokinetics, pharmacodynamics, and toxicity profiles of the three promising compounds. The present in silico analysis helps us to understand the possible mechanisms behind the antioxidant, antibacterial, and cytotoxic activities of CuNPs and recommends them as implicit inhibitors of selected proteins

Antihyperlipidemic Activity of Terminalia Chebula Retz Extract-Loaded Phytosomes: Development and Characterization

Ethnopharmacological evidence has demonstrated that Terminalia chebula Retz is traditionally employed for the management of hepatic ailments. Presently, a significant number of prevalent diseases and nutritional disorders are managed through the utilization of natural remedies. The efficacy of herbal medications relies on the administration of a sufficient dosage of the therapeutically active component. However, there is a significant constraint in terms of their bioavailability when taken via oral or topical routes. Phytosomes are a novel class of herbal formulations that have been recently introduced. These formulations exhibit enhanced absorption properties, leading to improved bioavailability and efficacy compared to traditional phyto compounds or botanical extracts. The objective of the current investigation was to assess the qualitative and quantitative phytochemical analysis, high-performance liquid chromatography, optical microscopic research, and in vitro antioxidant properties of Terminalia chebula Retz leaves obtained from the Bhopal region of Madhya Pradesh. The hydroalcoholic extract of phytosome was prepared using a mixture of phospholipids and cholesterol. The characterization of phytosome was conducted using various analytical techniques, including Fourier-transform infrared spectroscopy, determination of entrapment efficiency, measurement of particle size and size distribution, examination under an optical microscope, high-performance liquid chromatography analysis. The concurrent utilization of phospholipids and Terminalia chebula Retz has the potential to produce a synergistic outcome. This synergistic effect can be assessed by evaluating the free radical scavenging activity using the DPPH model

Evaluation of Herbal Extracts of Momordica Charantia and Fenugreek Seeds for Management of Diabetes

The present study discloses a composition for regulating blood sugar levels, comprising a synergistic blend of Momordica Charantia extract, Fenugreek seed extract, and additional natural extracts. The composition offers a natural and holistic approach to blood sugar regulation, harnessing the potential benefits of these extracts to support glycemic control. Momordica Charantia extract, derived from the fruits of the Momordica Charantia plant, contains bioactive compounds such as charantin, polypeptide-p, and vicine. Fenugreek seed extract, obtained from Trigonella foenum graecum seeds, comprises soluble dietary fibers, saponins, and alkaloids, known for their potential in blood sugar regulation

Nanogels as novel drug nanocarriers for CNS drug delivery

Nanogels are highly recognized as adaptable drug delivery systems that significantly contribute to improving various therapies and diagnostic examinations for different human diseases. These three-dimensional, hydrophilic cross-linked polymers have the ability to absorb large amounts of water or biological fluids. Due to the growing demand for enhancing current therapies, nanogels have emerged as the next-generation drug delivery system. They effectively address the limitations of conventional drug therapy, such as poor stability, large particle size, and low drug loading efficiency. Nanogels find extensive use in the controlled delivery of therapeutic agents, reducing adverse drug effects and enabling lower therapeutic doses while maintaining enhanced efficacy and patient compliance. They are considered an innovative drug delivery system that highlights the shortcomings of traditional methods. This article covers several topics, including the involvement of nanogels in the nanomedicine sector, their advantages and limitations, ideal properties like biocompatibility, biodegradability, drug loading capacity, particle size, permeability, non-immunological response, and colloidal stability. Additionally, it provides information on nanogel classification, synthesis, drug release mechanisms, and various biological applications. The article also discusses barriers associated with brain targeting and the progress of nanogels as nanocarriers for delivering therapeutic agents to the central nervous system

Development and Evaluation of Curcumin Loaded Nanoparticles for Treatment of Diabetes

A nanometer is one billionth of a metre, hence nanotechnology is an intersection of science, engineering, and technology that works with structures and materials at the nanoscale scale, often in the range of 1 to 100 nanometers. Materials frequently display distinctive and innovative features at this scale that are distinct from those at the macroscopic or even microscopic levels. Nanotechnology is the manipulation, design, and control of materials and devices at the nanoscale to produce new products, technologies, and applications. Nanotechnology is essential to the development of tailored medication delivery systems, imaging agents, and diagnostic instruments in medicine. It offers the promise for more targeted treatments that are also less likely to cause negative effects. Since ancient times, turmeric (Curcuma longa L.) has been widely used as a spice and a remedy. Curcumin, a polyphenol that aids in the prevention and management of neurological, pulmonary, cardiovascular, metabolic, inflammatory, and autoimmune illnesses as well as some malignancies, is the primary active component of turmeric. Curcumin does have certain disadvantages, though, including limited water solubility, poor absorption, rapid metabolism, rapid systemic elimination, inadequate bioavailability subpar pharmacokinetics, low stability, and subpar penetration targeting effectiveness. A typical approach is to encapsulate curcumin in nanocarriers for targeted distribution to get over these disadvantages. Concerns have been raised about the degradation of nanocarrier products. In this study, curcumin nanoparticles and nanocurcumin were created without the aid of nanocarriers. To do this, raw turmeric rhizome was soxhlet extracted to obtain curcumin. The stock solutions of various curcumin concentrations made in dichloromethane were sonicated for varying lengths of time and included in boiling water at various flow rates. With 5.00 mg/mL of stock solution concentration, 0.10 mL/min flow rate, and 30 minutes of sonication, an average particle size of 82 04 nm was produced. Particle size seems to decline with sonication time but tends to increase with flow rate and curcumin content in the stock solution. Although nanocurcumins are amorphous, X-ray diffraction reveals crisp and powerful diffraction peaks for curcumin, suggesting its integrity and high crystallinity. The presence of all the functional groups of curcumin in nanocurcumin is confirmed by Fourier-transform infrared spectroscopy spectra. Images obtained using transmission and scanning electron microscopy display the morphology of completely spherical objects

Efficient extraction of small and large RNAs in bacteria for excellent total RNA sequencing and comprehensive transcriptome analysis.

BACKGROUND: Next-generation transcriptome sequencing (RNA-Seq) has become the standard practice for studying gene splicing, mutations and changes in gene expression to obtain valuable, accurate biological conclusions. However, obtaining good sequencing coverage and depth to study these is impeded by the difficulties of obtaining high quality total RNA with minimal genomic DNA contamination. With this in mind, we evaluated the performance of Phenol-free total RNA purification kit (Amresco) in comparison with TRI Reagent (MRC) and RNeasy Mini (Qiagen) for the extraction of total RNA of Pseudomonas aeruginosa which was grown in glucose-supplemented (control) and polyethylene-supplemented (growth-limiting condition) minimal medium. All three extraction methods were coupled with an in-house DNase I treatment before the yield, integrity and size distribution of the purified RNA were assessed. RNA samples extracted with the best extraction kit were then sequenced using the Illumina HiSeq 2000 platform. RESULTS: TRI Reagent gave the lowest yield enriched with small RNAs (sRNAs), while RNeasy gave moderate yield of good quality RNA with trace amounts of sRNAs. The Phenol-free kit, on the other hand, gave the highest yield and the best quality RNA (RIN value of 9.85 ± 0.3) with good amounts of sRNAs. Subsequent bioinformatic analysis of the sequencing data revealed that 5435 coding genes, 452 sRNAs and 7 potential novel intergenic sRNAs were detected, indicating excellent sequencing coverage across RNA size ranges. In addition, detection of low abundance transcripts and consistency of their expression profiles across replicates from the same conditions demonstrated the reproducibility of the RNA extraction technique. CONCLUSIONS: Amresco\u27s Phenol-free Total RNA purification kit coupled with DNase I treatment yielded the highest quality RNAs containing good ratios of high and low molecular weight transcripts with minimal genomic DNA. These RNA extracts gave excellent non-biased sequencing coverage useful for comprehensive total transcriptome sequencing and analysis. Furthermore, our findings would be useful for those interested in studying both coding and non-coding RNAs from precious bacterial samples cultivated in growth-limiting condition, in a single sequencing run

Neuroprotective potential of Marsilea quadrifolia Linn against monosodium glutamate-induced excitotoxicity in rats

Background: Excitotoxicity is a condition in which neurons are damaged/injured by the over-activation of glutamate receptors. Excitotoxins play a crucial part in the progression of several neurological diseases. Marsilea quadrifolia Linn (M. quadrifolia) is a very popular aquatic medicinal plant that has been utilised for a variety of therapeutic benefits since ancient times. Its chemical composition is diverse and includes phenolic compounds, tannins, saponins, flavonoids, steroids, terpenoids, alkaloids, carbohydrates and several others that possess antioxidant properties.Objective: The objective of the present study was to investigate the neuroprotective potential of M. quadrifolia against monosodium glutamate (MSG)-induced excitotoxicity in rats.Methods: A high-performance thin-layer chromatography (HPTLC) analysis of chloroform extract of M. quadrifolia (CEMQ) was conducted to identify the major constituents. Further, the in silico docking analysis was carried out on selected ligands. To confirm CEMQ’s neuroprotective effects, the locomotor activity, non-spatial memory, and learning were assessed.Results and discussion: The present study confirmed that CMEQ contains quercetin and its derivatives in large. The in-silico findings indicated that quercetin has a better binding affinity (−7.9 kcal/mol) towards the protein target 5EWJ. Animals treated with MSG had 1) a greater reduction in the locomotor score and impairment in memory and learning 2) a greater increase in the blood levels of calcium and sodium and 3) neuronal disorganization, along with cerebral edema and neuronal degeneration in the brain tissues as compared to normal control animals. The changes were however, significantly improved in animals which received standard drug memantine (20 mg/kg) and CEMQ (200 and 400 mg/kg) as compared to the negative control. It is plausible that the changes seen with CEMQ may be attributed to the N-methyl-D-aspartate (NMDA) antagonistic properties.Conclusion: Overall, this study indicated that M. quadrifolia ameliorated MSG-induced neurotoxicity. Future investigations are required to explore the neuroprotective mechanism of M. quadrifolia and its active constituents, which will provide exciting insights in the therapeutic management of neurological disorders

Development of a new drug candidate for the inhibition of Lassa virus glycoprotein and nucleoprotein by modification of evodiamine as promising therapeutic agents

The Lassa virus (LASV), an RNA virus prevalent in West and Central Africa, causes severe hemorrhagic fever with a high fatality rate. However, no FDA-approved treatments or vaccines exist. Two crucial proteins, LASV glycoprotein and nucleoprotein, play vital roles in pathogenesis and are potential therapeutic targets. As effective treatments for many emerging infections remain elusive, cutting-edge drug development approaches are essential, such as identifying molecular targets, screening lead molecules, and repurposing existing drugs. Bioinformatics and computational biology expedite drug discovery pipelines, using data science to identify targets, predict structures, and model interactions. These techniques also facilitate screening leads with optimal drug-like properties, reducing time, cost, and complexities associated with traditional drug development. Researchers have employed advanced computational drug design methods such as molecular docking, pharmacokinetics, drug-likeness, and molecular dynamics simulation to investigate evodiamine derivatives as potential LASV inhibitors. The results revealed remarkable binding affinities, with many outperforming standard compounds. Additionally, molecular active simulation data suggest stability when bound to target receptors. These promising findings indicate that evodiamine derivatives may offer superior pharmacokinetics and drug-likeness properties, serving as a valuable resource for professionals developing synthetic drugs to combat the Lassa virus

A global view of the nonprotein-coding transcriptome in Plasmodium falciparum

Nonprotein-coding RNAs (npcRNAs) represent an important class of regulatory molecules that act in many cellular pathways. Here, we describe the experimental identification and validation of the small npcRNA transcriptome of the human malaria parasite Plasmodium falciparum. We identified 630 novel npcRNA candidates. Based on sequence and structural motifs, 43 of them belong to the C/D and H/ACA-box subclasses of small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs). We further observed the exonization of a functional H/ACA snoRNA gene, which might contribute to the regulation of ribosomal protein L7a gene expression. Some of the small npcRNA candidates are from telomeric and subtelomeric repetitive regions, suggesting their potential involvement in maintaining telomeric integrity and subtelomeric gene silencing. We also detected 328 cis-encoded antisense npcRNAs (asRNAs) complementary to P. falciparum protein-coding genes of a wide range of biochemical pathways, including determinants of virulence and pathology. All cis-encoded asRNA genes tested exhibit lifecycle-specific expression profiles. For all but one of the respective sense–antisense pairs, we deduced concordant patterns of expression. Our findings have important implications for a better understanding of gene regulatory mechanisms in P. falciparum, revealing an extended and sophisticated npcRNA network that may control the expression of housekeeping genes and virulence factors

Experimental identification and characterization of 97 novel npcRNA candidates in Salmonella enterica serovar Typhi

We experimentally identified and characterized 97 novel, non-protein-coding RNA candidates (npcRNAs) from the human pathogen Salmonella enterica serovar Typhi (hereafter referred to as S. typhi). Three were specific to S. typhi, 22 were restricted to Salmonella species and 33 were differentially expressed during S. typhi growth. We also identified Salmonella Pathogenicity Island-derived npcRNAs that might be involved in regulatory mechanisms of virulence, antibiotic resistance and pathogenic specificity of S. typhi. An in-depth characterization of S. typhi StyR-3 npcRNA showed that it specifically interacts with RamR, the transcriptional repressor of the ramA gene, which is involved in the multidrug resistance (MDR) of Salmonella. StyR-3 interfered with RamR–DNA binding activity and thus potentially plays a role in regulating ramA gene expression, resulting in the MDR phenotype. Our study also revealed a large number of cis-encoded antisense npcRNA candidates, supporting previous observations of global sense–antisense regulatory networks in bacteria. Finally, at least six of the npcRNA candidates interacted with the S. typhi Hfq protein, supporting an important role of Hfq in npcRNA networks. This study points to novel functional npcRNA candidates potentially involved in various regulatory roles including the pathogenicity of S. typhi