Deciphering Multi-target Pharmacological Mechanism of Cucurbita pepo Seeds against Kidney Stones: Network Pharmacology and Molecular Docking Approach.

BACKGROUND: Urolithiasis is a prevalent condition with significant morbidity and economic implications. The economic burden associated with urolithiasis primarily stems from medical expenses. Previous literature suggests that herbal plants, including Cucurbita pepo, have lithotriptic capabilities. C. pepo is an annual, herbaceous, widely grown, and monoecious vegetative plant known for its antioxidants, fibers, and fatty acids. Recent studies on C. pepo seeds have shown therapeutic potential in reducing bladder stones and urodynamic illnesses, like kidney stones. However, the precise molecular and pharmacological mechanisms are unclear. OBJECTIVE: In this research, we employed network pharmacology and molecular docking to examine the active compounds and biological mechanisms of Cucurbita pepo against kidney stones. METHODS: Active constituents were obtained from previous studies and the IMPPAT database, with their targets predicted using Swiss target prediction. Kidney stone-associated genes were collected from DisGeNET and GeneCards. The active constituent-target-pathway network was constructed using Cytoscape, and the target protein-protein interaction network was generated using the STRING database. Gene enrichment analysis of C. pepo core targets was conducted using DAVID. Molecular docking was performed to identify potential kidney stone-fighting agents. RESULTS: The findings revealed that Cucurbita pepo contains 18 active components and has 192 potential gene targets, including AR, EGFR, ESR1, AKT1, MAPK3, SRC, and MTOR. Network analysis demonstrated that C. pepo seeds may prevent kidney stones by influencing disease-related signaling pathways. Molecular docking indicated that key kidney stone targets (mTOR, EGFR, AR, and ESR1) effectively bind with active constituents of C. pepo. CONCLUSION: These findings provide insight into the anti-kidney stone effects of Cucurbita pepo at a molecular level. In conclusion, this study contributes to understanding the potential of Cucurbita pepo in combating kidney stones and lays the foundation for further research.

Extracellular synthesis of silver nanoparticle using yeast extracts: antibacterial and seed priming applicationss.

The evolution and rapid spread of multidrug-resistant (MDR) bacterial pathogens have become a major concern for human health and demand the development of alternative antimicrobial agents to combat this emergent threat. Conventional intracellular methods for producing metal nanoparticles (NPs) using whole-cell microorganisms have limitations, including binding of NPs to cellular components, potential product loss, and environmental contamination. In contrast, this study introduces a green, extracellular, and sustainable methodology for the bio-materialization of silver NPs (AgNPs) using renewable resource cell-free yeast extract. These extracts serve as a sustainable, biogenic route for both reducing the metal precursor and stabilizing the surface of AgNPs. This method offers several advantages such as cost-effectiveness, environment-friendliness, ease of synthesis, and scalability. HR-TEM imaging of the biosynthesized AgNPs revealed an isotropic growth route, resulting in an average size of about ~ 18 nm and shapes ranging from spherical to oval. Further characterization by FTIR and XPS results revealed various functional groups, including carboxyl, hydroxyl, and amide contribute to enhanced colloidal stability. AgNPs exhibited potent antibacterial activity against tested MDR strains, showing particularly high efficacy against Gram-negative bacteria. These findings suggest their potential role in developing alternative treatments to address the growing threat of antimicrobial resistance. Additionally, seed priming experiments demonstrated that pre-sowing treatment with AgNPs improves both the germination rate and survival of Sorghum jowar and Zea mays seedlings. KEY POINTS: •Yeast extract enables efficient, cost-effective, and eco-friendly AgNP synthesis. •Biosynthesized AgNPs showed strong antibacterial activity against MDR bacteria. •AgNPs boost seed germination and protect against seed-borne diseases.

Assessing phytotoxicity and cyto-genotoxicity of two insecticides using a battery of in-vitro biological assays.

Intensive use of chemical pesticides in agriculture poses environmental risks and may have negative impacts on agricultural productivity. The potential phytotoxicity of two chemical pesticides, chlorpyrifos (CPS) and fensulfothion (FSN), were evaluated using Cicer arietinum and Allium cepa as model crops. Different concentrations (0-100 µgmL-1) of both CPS and FSN decreased germination and biological attributes of C. arietinum. High pesticide doses significantly (p ≤ 0.05) caused membrane damage by producing thiobarbituric acid reactive substances (TBARS) and increasing proline (Pro) content. Pesticides elevated ROS levels and substantially increased the superoxide anions and H2O2 concentrations, thus aggravating cell injury. Plants exposed to high pesticide dosages displayed significantly higher antioxidant levels to combat pesticide-induced oxidative stress. Ascorbate peroxidase (APX), guaiacol peroxidase (GPX), catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) increased by 48%, 93%, 71%, 52% and 94%, respectively, in C. arietinum roots exposed to 100 µgFSNmL-1. Under CLSM, pesticide-exposed C. arietinum and 2',7'-dichlorodihydrofluorescein diacetate (2'7'-DCF) and 3,3'-diaminobenzidine stained roots exhibited increased ROS production in a concentration-dependent manner. Additionally, enhanced Rhodamine 123 (Rhd 123) and Evan's blue fluorescence in roots, as well as changes in mitochondrial membrane potential (ΔΨm) and cellular apoptosis, were both associated with high pesticide dose. Allium cepa chromosomal aberration (CAs) assay showed a clear reduction in mitotic index (MI) and numerous chromosomal anomalies in root meristematic cells. Additionally, a-dose-dependent increase in DNA damage in root meristematic cells of A. cepa and conversion of the super-coiled form of DNA to open circular in pBR322 plasmid revealed the genotoxic potential of pesticides. The application of CPS and FSN suggests phytotoxic and cyto-genotoxic effects that emphasize the importance of careful monitoring of current pesticide level in soil before application and addition at optimal levels to soil-plant system. It is appropriate to prepare both target-specific and slow-release agrochemical formulations for crop protection with concurrent safeguarding of agroecosystems.

A rapid, high-yield and bioinspired synthesis of colloidal silver nanoparticles using Glycyrrhiza glabra root extract and assessment of antibacterial and phytostimulatory activity.

Silver nanoparticles (AgNPs) have emerged as highly effective antimicrobial agents against multidrug-resistant (MDR) pathogens. This study aims to employ green chemistry principles for AgNP synthesis involving phytochemical-rich extract from Glycyrrhiza glabra roots. The approach highlights using renewable feedstocks, safer chemicals, minimum byproducts, and process scale-up. The synthesis of AgNPs was assessed using a surface plasmon resonance band at 420 nm, and structural properties were characterized using TEM, x-ray diffraction, Fourier-transform infrared spectroscopy, and X-ray photoelectron spectroscopy. This method enables the production of high-yield dispersions of AgNPs with desired physicochemical characteristics, including dark yellow solution, size (~20 nm), spherical to an oval shape, crystal structure, and stable colloidal properties. The antimicrobial activity of AgNPs was investigated against the MDR bacteria strains of gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli). This work reveals that the antimicrobial activity of AgNPs can be influenced by bacterial cell wall components. The results demonstrate the strong interaction between AgNPs and E. coli, exhibiting a dose-dependent antibacterial response. The green approach facilitated the safer, facile, and rapid synthesis of colloidal dispersions of AgNPs, providing a sustainable and promising alternative to conventional chemical and physical methods. Furthermore, the effect of AgNPs on various growth parameters, including seed germination, root and shoot elongation, and dry weight biomass, was assessed for mung bean seedlings. The results revealed phytostimulatory effects, suggesting the promising prospects of AgNPs in the nano-priming of agronomic seeds. RESEARCH HIGHLIGHTS: Glycyrrhiza glabra root extract enabled rapid, high-yield, and eco-friendly synthesis of silver nanoparticles (AgNPs). Spectrophotometric analysis examined the optical properties, scalability, and stability of AgNPs. Transmission electron microscopy provided insights into the size, shape, and dispersity of AgNPs. Scanning electron microscopy revealed significant damage to gram-negative bacterial cell morphology and membrane integrity. AgNPs were found to enhance seed germination, seedling growth, and biomass yield of Vigna radiata.

Effects of magnesite on nitrogen conversion and bacterial community during pig manure composting.

The objective of this research was to elucidate the effect of varying proportions of magnesite (MS) addition - 0% (T1), 2.5% (T2), 5% (T3), 7.5% (T4), and 10% (T5) - on nitrogen transformation and bacterial community dynamics during pig manure composting. In comparison to T1 (control), MS treatments amplified the abundance of Firmicutes, Actinobacteriota, and Halanaerobiaeota, bolstered the metabolic functionality of associated microorganisms, and enhanced the nitrogenous substance metabolic pathway. A complementary effect in core bacillus species played a key role in nitrogen preservation. Compared to T1, 10% MS demonstrated the most substantial influence on composting because Total Kjeldahl Nitrogen increased by 58.31% and NH3 emission decreased by 41.52%. In conclusion, 10% MS appears to be optimal for pig manure composting, as it can augment microbial abundance and mitigate nitrogen loss. This study offers a more ecologically sound and economically viable method for curtailing nitrogen loss during composting.

Antibacterial, antioxidant, and haemolytic potential of silver nanoparticles biosynthesized using roots extract of Cannabis sativa plant.

In this study, Cannabis sativa roots extract has been employed for the biosynthesis of silver nanoparticles (AgNPs). The appearance of reddish-brown colour followed by absorption peak of AgNPs at 408 nm through UV-vis spectrophotometry suggested biosynthesis of AgNPs. The size of the particles ranged from 90-113 nm, confirmed using DLS and TEM along with zeta potential of -25.3 mV. The FTIR provided information regarding the phytochemical capping. The study was further elaborated for determining AgNPs antibacterial, antioxidant, and cellular toxicity using MIC, DPPH, MTT, and haemolytic assays, respectively. The AgNPs were significantly effective against Staphylococcus aureus (Gram-positive), as compared to that of Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli (Gram-negative). AgNPs also exhibited remarkable antioxidant potential wherein 58.01 ± 0.09% free radical scavenging was observed at a concentration of 100 µg/ml. AgNPs revealed lower cytotoxicity where cell viability was observed to be 52.38 ± 0.6% at a very high concentration of 500 µg/ml in HEK 293 cells. Further, very low toxicity was seen in RBCs i.e. 6.47 ± 0.04% at a high concentration of 200 µg/ml. Thus, the current study beholds anticipation that Cannabis sativa ethanolic root extract-mediated AgNPs may play a vital role in therapeutic.

Biorational Control of Callosobruchus maculatus (Coleoptera: Buchidae) in Stored Grains with Botanical Extracts.

Globally, around 2000 plant species are used against pest control. The utilization of botanicals is considered the most economic and biodegradable methods for the control of stored grains pests. Therefore, the current study was carried out to investigate the repellency potential of five botanicals against Callosbruchus maculatus F. in Haripur, Pakistan. The concentrations of Azadirachta indica L., Nicotiana tabacum L., Melia azedarach L., Nicotiana rustica L., and Thuja orientalis L. were, i.e., 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0% in four replicates to establish contact effects. The data were recorded after 1, 2, 3, 6, 24, 48, 72, and 96 hours. The repellency effect of these plant species against C. maculatus were increased in both the time- and dose-dependent manner, and highest effect was observed at 72 h. In addition, the repellency effect was 91% for A. indica (class: V), 86% M. azedarach, 82%, N. tabacum (class: V), 79% N. rustica (class: IV), and 75% T. orientalis (class: IV) at 3% concentration against C. maculatus. Furthermore, following 96 hours' exposure to treatment the sensitivity response of insects decreases as the time interval increases, i.e., 86% A. indica (class: V) was followed by 71% M. azedarach (class: IV), 65% N. tabacum (class: IV), 61% N. rustica (class: IV), and T. orientalis 57% (class: III) repellency at highest concentration of 3%. The current study concluded that A. indica and M. azedarach can be incorporated for the management of C. maculatus and these plant species might be helpful in the productions of new biopesticides.

Enhanced photodegradation of rifampicin and co-trimoxazole by ZnO/ZnMn2O4/ZnS-PVA and its genotoxicity studies on Allium cepa.

Oxygen vacancies and its associated defect states have a great influence on the electronic and structural aspects of semiconductor photocatalysts, yet there is paucity of investigations about the influence of the defect states on their photocatalytic properties. Herein, this study reports the hierarchical fabrication of oxygen vacancy enriched ZnO/ZnMn2O4/ZnS-PVA nanocomposite (NCs) for the enhanced photodegradation of rifampicin and co-trimoxazole. The formation of lattice expansion induced oxygen vacancies and its associated Urbach tail energy, and n-p-n heterojunction-based S-scheme charge transfer path synergistically contributed to the boosted photocatalytic performance of the as prepared NCs. The photocatalytic performance of the nanomaterial towards rifampicin and co-trimoxazole has been determined to be 80% and 90% under visible light irradiation, respectively. Furthermore, various operating parameters including the concentration of NCs and drug, pH and interference of various ions have been evaluated. The degraded product intermediates have been elucidated by GC-MS analysis. The toxicity of the as-prepared nanomaterials has been evaluated by treating the samples with root tips of Allium cepa, where the NCs was found to be non-toxic. The study provides a new-fangled insight on the preparation and fabrication of non-toxic and defect rich nanomaterials which may help stimulate this area of research.

Efficient One-Pot Synthesis of TiO2/ZrO2/SiO2 Ternary Nanocomposites Using Prunus × Yedoensis Leaf Extract for Enhanced Photocatalytic Dye Degradation.

A simple, efficient, and ecofriendly method was employed to synthesize TiO2/ZrO2/SiO2 ternary nanocomposites using Prunus × yedoensis leaf extract (PYLE) that shows improved photocatalytic and antibacterial properties. The characterization of the obtained nanocomposites was done by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, field-emission scanning electron microscopy (FE-SEM), and energy-dispersive X-ray spectroscopic (EDS) analysis. The synthesized ternary nanocomposites with nanoscale pore diameters were investigated for the elimination of Reactive Red 120 (RR120) dye. The obtained results showed about 96.2% removal of RR120 dye from aqueous solution under sunlight irradiation. Furthermore, it shows promising antibacterial activity against Staphylococcus aureus and Escherichia coli. The improved photocatalytic and antibacterial activity of TiO2/ZrO2/SiO2 may bring unique insights into the production of ternary nanocomposites and their applications in the environment and biomedical field.

Novel Bioengineered Antibacterial and Anticancer ZnO Nanoparticles.

Transition metal oxide NPs have delivered wide applications in various fields. Therefore, in this study, a novel fungus, Alternaria sp. (NCBI Accession No: MT982648) was isolated and characterized from the vicinity of medicinal plants. Eventually, in this method extracted proteins from isolated fungus were utilized to synthesize highly biocompatible zinc nanoparticles (ZnO NPs). The various physical techniques including UV-visible spectroscopy, TEM, HR-TEM, XRD, DLS, zeta potential, and FTIR were used to characterize particles. The UV-visible absorption (λMax) and binding energy for the as-synthesized particles were found to be 329 nm and 3.91 eV, respectively. Further, the polydispersed particles were revealed to have regular crystallinity with hexagonal wurtzite phase of ZnO with the spacing of ~2.46 Å under XRD and HR-TEM. The average size of a particle under TEM was found to be ~18 nm. The evaluation of various surface functional groups of particles was done by FTIR. The average hydrodynamic diameter of particles was found to be ~57 d. nm with 0.44 particle distribution index whereas the nanoemulsion stability was explained by Zeta potential (-9.47 mV). These particles were found to exhibit potential antibacterial and anticancer activities. They were found to be bactericidal against S. abony (MIC 5.73 µg/mL); B. pumilis (MIC 6.64 µg/mL); K. pneumonia (MIC 14.4 µg/mL); E. coli (MIC 8.7 µg/mL); B. subtilis (MIC 5.63 µg/mL) and S. aureus (MIC 12.04 µg/mL). Further, they are also found to be concentration-dependent anticancer and inhibited the growth of A549 cells (IC50-65.3 µg/mL) whereas they were found to demonstrate no any cytotoxicity against NRK normal kidney cell line. The internalization of particles into the nucleus (i.e., nuclear fragmentation and DNA damage) was confirmed by DAPI staining. The intracellular particles were found to generate excessive ROS. Further, the anticancer potential was also estimated by noticing a hike in oxidative stress parameters, cell viability, cell morphology, and change in mitochondrial membrane potential. We effectively synthesized potentially potent antibacterial and anticancer novel bioengineered ZnO NPs.

Plant growth promoting strain Bacillus cereus (RCS-4 MZ520573.1) enhances phytoremediation potential of Cynodon dactylon L. in distillery sludge.

Elevated levels of physico-chemical pollution including organic pollutants, metals and metalloids were detected in distillery sludges despite of the anaerobic digestion treatment prior to disposal. The concentrations of the metals were (in mg kg-1): Fe (400.98 ± 3.11), Zn (17.21 ± 0.54), Mn (8.32 ± 0.42), Ni (8.00 ± 0.98), Pb (5.09 ± 0.43), Cr (4.00 ± 0.98), and Cu (3.00 ± 0.10). An invasive grass species, Cynodon dactylon L., demonstrated its ability to remediate the distillery waste sludge (DWS) in the field study. All the physico-chemical parameters of the sludge significantly improved (up to 70-75%) in the presence of Cynodon dactylon L. (p < 0.001) than the control with no plant growth. The highest phytoremediation capacity was associated with the uptake of Fe in the root and shoot. Sludge samples collected near the rhizosphere also showed lower amount of organic compounds compared to control sludge samples. Metal resistant Bacillus cereus (RCS-4 MZ520573.1) was isolated from the rhizosphere of Cynodon dactylon L. and showed potential to enhance the process of phytoremediation via plant growth promoting activities such as production of high level of ligninolytic enzymes: manganese peroxidase (35.98 U), lignin peroxidase (23.98 U) and laccase (12.78 U), indole acetic acid (45.87(mgL-1), phosphatase activity (25.76 mg L-1) and siderophore production (23.09 mg L-1). This study presents information on the performance of Cynodon dactylon L., an abundant invasive perennial grass species and its associated plant growth promoting rhizobacteria demonstrated good capacity to remediate and restore contaminated soil contained complex organic and inorganic pollutants, they could be integrated into the disposal system of distillery sludge to improve the treatment efficiency.

Fruit Derived Potentially Bioactive Bioengineered Silver Nanoparticles.

INTRODUCTION: Protein-derived biogenic syntheses of inorganic nanoparticles have gained immense attention because of their broad spectrum of applications. Proteins offer a reducing environment to enable the synthesis of nanoparticles and encapsulate synthesized nanoparticles and provide them temporal stability in addition to biocompatibility. METHODS: In the present study, Benincasa hispida fruit proteins were used to synthesize silver nanoparticles (AgNPs) at 37 °C over five days of incubation. The synthesis of AgNPs was confirmed by UV-Vis spectroscopy, TEM, zeta potential, and DLS analyses. Further, these NPs depicted antibacterial and antibiofilm effects. Additionally, the anticancer activities of nanoparticles were also tested against the lung cancer cell line (A549) with respect to the normal cell line (NRK) using MTT assay. Further, the estimation of ROS generation through DCFH-DA staining along with a reduction in mitochondrial membrane potential by Mito Tracker Red CMX staining was carried out. Moreover, nuclear degradation in the AgNPs treated cells was cross-checked by DAPI staining. RESULTS: The average size of AgNPs was detected to be 27 ±1 nm by TEM analysis, whereas surface encapsulation by protein was determined by FTIR spectroscopy. These NPs were effective against bacterial pathogens such as Escherichia coli, Staphylococcus aureus, Salmonella enteric, and Staphylococcus epidermis with MICs of 148.12 µg/mL, 165.63 µg/mL, 162.77 µg/mL, and 124.88 µg/mL, respectively. Furthermore, these nanoparticles inhibit the formation of biofilms of E. coli, S. aureus, S. enteric, and S. epidermis by 71.14%, 73.89%, 66.66%, and 64.81%, respectively. Similarly, these nanoparticles were also found to inhibit (IC50 = 57.11 µM) the lung cancer cell line (A549). At the same time, they were non-toxic against NRK cells up to a concentration of 200 µM. DISCUSSION: We successfully synthesized potentially potent antibacterial, antibiofilm and anticancer biogenic AgNPs.

Exploring the Antibacterial and Antibiofilm Efficacy of Silver Nanoparticles Biosynthesized Using Punica granatum Leaves.

The current research work illustrates an economical and rapid approach towards the biogenic synthesis of silver nanoparticles using aqueous Punica granatum leaves extract (PGL-AgNPs). The optimization of major parameters involved in the biosynthesis process was done using Box-Behnken Design (BBD). The effects of different independent variables (parameters), namely concentration of AgNO3, temperature and ratio of extract to AgNO3, on response viz. particle size and polydispersity index were analyzed. As a result of experiment designing, 17 reactions were generated, which were further validated experimentally. The statistical and mathematical approaches were employed on these reactions in order to interpret the relationship between the factors and responses. The biosynthesized nanoparticles were initially characterized by UV-vis spectrophotometry followed by physicochemical analysis for determination of particle size, polydispersity index and zeta potential via dynamic light scattering (DLS), SEM and EDX studies. Moreover, the determination of the functional group present in the leaves extract and PGL-AgNPs was done by FTIR. Antibacterial and antibiofilm efficacies of PGL-AgNPs against Gram-positive and Gram-negative bacteria were further determined. The physicochemical studies suggested that PGL-AgNPs were round in shape and of ~37.5 nm in size with uniform distribution. Our studies suggested that PGL-AgNPs exhibit potent antibacterial and antibiofilm properties.

Assessment of Chemopreventive Potential of the Plant Extracts against Liver Cancer Using HepG2 Cell Line.

The edible parts of the plants Camellia sinensis, Vitis vinifera and Withania somnifera were extensively used in ancient practices such as Ayurveda, owing to their potent biomedical significance. They are very rich in secondary metabolites such as polyphenols, which are very good antioxidants and exhibit anti-carcinogenic properties. This study aims to evaluate the anti-cancerous properties of these plant crude extracts on human liver cancer HepG2 cells. The leaves of Camellia sinensis, Withania somnifera and the seeds of Vitis vinifera were collected and methanolic extracts were prepared. Then, these extracts were subjected to DPPH, α- amylase assays to determine the antioxidant properties. A MTT assay was performed to investigate the viability of the extracts of HepG2 cells, and the mode of cell death was detected by Ao/EtBr staining and flow cytometry with PI Annexin- V FITC dual staining. Then, the protein expression of BAX and BCl2 was studied using fluorescent dye to determine the regulation of the BAX and BCl2 genes. We observed that all the three extracts showed the presence of bioactive compounds such as polyphenols or phytochemicals. The W. somnifera bioactive compounds were found to have the highest anti-proliferative activity on human liver cancer cells.

Biogenic Synthesis of NiO Nanoparticles Using Areca catechu Leaf Extract and Their Antidiabetic and Cytotoxic Effects.

Nanoworld is an attractive sphere with the potential to explore novel nanomaterials with valuable applications in medicinal science. Herein, we report an efficient and ecofriendly approach for the synthesis of Nickel oxide nanoparticles (NiO NPs) via a solution combustion method using Areca catechu leaf extract. As-prepared NiO NPs were characterized using various analytical tools such as powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and UV-Visible spectroscopy (UV-Vis). XRD analysis illustrates that synthesized NiO NPs are hexagonal structured crystallites with an average size of 5.46 nm and a hexagonal-shaped morphology with slight agglomeration. The morphology, size, and shape of the obtained material was further confirmed using SEM and TEM analysis. In addition, as-prepared NiO NPs have shown potential antidiabetic and anticancer properties. Our results suggest that the inhibition of α-amylase enzyme with IC 50 value 268.13 µg/mL may be one of the feasible ways through which the NiO NPs exert their hypoglycemic effect. Furthermore, cytotoxic activity performed using NiO NPs exhibited against human lung cancer cell line (A549) proved that the prepared NiO NPs have significant anticancer activity with 93.349 µg/mL at 50% inhibition concentration. The biological assay results revealed that NiO NPs exhibited significant cytotoxicity against human lung cancer cell line (A549) in a dose-dependent manner from 0-100 µg/mL, showing considerable cell viability. Further, the systematic approach deliberates the NiO NPs as a function of phenolic extracts of A. catechu with vast potential for many biological and biomedical applications.

PGMD/curcumin nanoparticles for the treatment of breast cancer.

The present study aims at developing PGMD (poly-glycerol-malic acid-dodecanedioic acid)/curcumin nanoparticles based formulation for anticancer activity against breast cancer cells. The nanoparticles were prepared using both the variants of PGMD polymer (PGMD 7:3 and PGMD 6:4) with curcumin (i.e. CUR NP 7:3 and CUR NP 6:4). The size of CUR NP 7:3 and CUR NP 6:4 were found to be ~ 110 and 218 nm with a polydispersity index of 0.174 and 0.36, respectively. Further, the zeta potential of the particles was - 18.9 and - 17.5 mV for CUR NP 7:3 and CUR NP 6:4, respectively. The entrapment efficiency of both the nanoparticles was in the range of 75-81%. In vitro anticancer activity and the scratch assay were conducted on breast cancer cell lines, MCF-7 and MDA-MB-231. The IC50 of the nanoformulations was observed to be 40.2 and 33.6 µM at 48 h for CUR NP 7:3 and CUR NP 6:4, respectively, in MCF-7 cell line; for MDA-MB-231 it was 43.4 and 30.5 µM. Acridine orange/EtBr and DAPI staining assays showed apoptotic features and nuclear anomalies in the treated cells. This was further confirmed by western blot analysis that showed overexpression of caspase 9 indicating curcumin role in apoptosis.

Vincamine, a safe natural alkaloid, represents a novel anticancer agent.

Vincamine, a well-known plant alkaloid, has been used as a dietary supplement and as a peripheral vasodilator to combat aging in humans. In this study, for the very first time, we demonstrated that vincamine can function as an anticancer agent in a human alveolar basal epithelial cell line A549 (IC50 = 309.7 µM). The anticancer potential of vincamine in A549 cells was assessed by molecular assays to determine cell viability, generation of intracellular ROS, nuclear condensation, caspase-3 activity and inhibition, and change in mitochondrial membrane potential (ΔΨm). In silico studies predicted that the anti-proliferative potential of vincamine is enhanced by its interaction with the apoptotic protein caspase-3, and that this interaction is driven by two hydrogen bonds and has a high free energy of binding (-5.64 kcal/mol) with an estimated association constant (Ka) of 73.67 µM. We found that vincamine stimulated caspase-3-dependent apoptosis and lowered mitochondrial membrane potential, which ultimately led to cytochrome C release. Vincamine was also found to quench hydroxyl free radicals and deplete iron ions in cancer cells. As a dietary supplement, vincamine is almost non-toxic in BEAS-2B and 3T3-L1 cells. Therefore, we propose that vincamine represents a safe anticancer agent in lung cancer cells. Its role in other cancers has yet to be explored.

Preparation, Spectroscopic Characterization, Theoretical Investigations, and In Vitro Anticancer Activity of Cd(II), Ni(II), Zn(II), and Cu(II) Complexes of 4(3H)-Quinazolinone-Derived Schiff Base.

Herein, we report the synthesis and characterization of a new Schiff base ligand 3-[[(E)-(3-hydroxyphenyl)-methylidene]amino]-2-methyl-quinazolin-4(3H)-one (HAMQ) and its Cd(II), Ni(II), Zn(II), and Cu(II) complexes (C1-C4). The ligand HAMQ was synthesized by reacting 3-hydroxybenzaldehyde and 3-amino-2-methyl-4(3H)-quinazolinone in a 1:1 molar ratio. The structure of the ligand and its complexes (C1-C4) were evaluated using ultraviolet (UV)-visible (Vis) light spectroscopy, 1H-NMR, Fourier-transform infrared (FT-IR) spectroscopy, MS, elemental analysis, conductance data, and thermogravimetric analysis (TGA). The characterization results suggested that the bidentate ligand, HAMQ, coordinated to the metal center through the lactum oxygen and the azomethine nitrogen. Moreover, all the metal complexes were analyzed using powder X-ray diffraction studies, which revealed that all of them belong to a triclinic crystal system. The research was supplemented by density functional theory (DFT) studies on the IR and UV-Vis spectra, as well as the chemical reactivity of the HAMQ and its four metallic derivatives making use of conceptual density functional theory (CDFT) by means of KID (Koopmans in DFT) methodology. The synthesized complexes displayed significant in vitro anticancer activity against human cancer cell lines (HeLa and HCT-115).

Alzheimer's Disease and Herbal Combination Therapy: A Comprehensive Review.

Alzheimer's disease (AD) was first described in 1907 and got its name after Alois Alzheimer, a German psychiatrist and neuropathologist. This disease starts slow, increasing gradually to worsen in the due course of time. AD is mainly characterized by the associated dementia, which is a decline of cognitive effects such as memory, praxis, and orientation. The dementia is further highlighted by the presence of psychological and behavioral symptoms. Additionally, AD is also associated with the multiple interconnected pathways linked neuropathological changes such as the formation of neurofibrillary tangles and amyloid-ß plaques inside the brain. AD therapeutics have been of prime concern over the decades, resulting in the elucidation of promising therapeutic targets. The requirement of AD stage dependent optimized conditions has necessitated a combinatorial approach toward treatment. The priority in AD research has remained to develop disease-modifying and development-reducing drugs for treatment regimens followed during the early and later stages, respectively.

Phyto-Mediated Synthesis of Silver Nanoparticles Using Terminalia chebula Fruit Extract and Evaluation of Its Cytotoxic and Antimicrobial Potential.

The increasing interest in developing potent non-toxic drugs in medicine is widening the opportunities for studying the usage of nanostructures in the treatment of various diseases. The present work reports a method for a facile and an eco-friendly synthesis of silver nanoparticles (AgNPs) using Terminalia chebula fruit extract (TCE). The obtained AgNPs was characterized by using different spectroscopic and microscopic techniques. The analysis of the results revealed that the as-obtained AgNPs have spherical morphology with an average diameter of 22 nm. Furthermore, the preliminary bioactivity evaluations revealed that the bio-conjugation of AgNPs, using TCE, significantly enhanced the antibacterial and anti-breast cancer potentials of the latter. The antibacterial activity of the as-prepared AgNPs showed that B. subtilis was more sensitive towards the AgNPs, followed by P. aeruginosa; while, E. coli and S. mutans showed comparatively minimal sensitivity toward the AgNPs. The IC50 values of TCE, AgNPs and TCE + AgNPs treatment of MCF-7 were found to be 17.53, 14.25 and 6.484 µg/mL, respectively. Therefore, it can be ascertained that the bio-conjugation may provide a headway with regard to the therapeutic employment of T. chebula, upon mechanistically understanding the basis of observed antibacterial and anticancer activities.