Biosynthesis of zinc oxide nanoparticles via neem extract and their anticancer and antibacterial activities.

In the present study, zinc oxide nanoparticles (ZnO-NPs) were synthesized using neem leaf aqueous extracts and characterized using transmission electron microscopy (TEM), ultraviolet visible spectroscopy (UV-Vis), and dynamic light scattering (DLS). Then compare its efficacy as anticancer and antibacterial agents with chemically synthesized ZnO-NPs and the neem leaf extract used for the green synthesis of ZnO-NPs. The TEM, UV-vis, and particle size confirmed that the developed ZnO-NPs are nanoscale. The chemically and greenly synthesized ZnO-NPs showed their optical absorbance at 328 nm and 380 nm, respectively, and were observed as spherical particles with a size of about 85 nm and 62.5 nm, respectively. HPLC and GC-MS were utilized to identify the bioactive components in the neem leaf aqueous extract employed for the eco-friendly production of ZnO-NPs. The HPLC analysis revealed that the aqueous extract of neem leaf contains 19 phenolic component fractions. The GC-MS analysis revealed the existence of 21 bioactive compounds. The antiproliferative effect of green ZnO-NPs was observed at different concentrations (31.25 µg/mL-1000 µg/mL) on Hct 116 and A 549 cancer cells, with an IC50 value of 111 µg/mL for A 549 and 118 µg/mL for Hct 116. On the other hand, the antibacterial activity against gram-positive and gram-negative bacteria was estimated. The antibacterial result showed that the MIC of green synthesized ZnO-NPs against gram-positive and gram-negative bacteria were 5, and 1 µg/mL. Hence, they could be utilized as effective antibacterial and antiproliferative agents.

Assessment of microbial flora and pesticidal effect of vermicast generated from Azadirachta indica (neem) for developing a biofertilizer-cum-pesticide as a single package.

The soil comprising organic matter, nutrients, serve as substrate for plant growth and various organisms. In areas where there are large plantations, there is a huge leaf litter fall. The leaf litter upon decomposition releases nutrients and helps in nutrient recycling, for which the soil engineers such as earthworms, ants and termites are important key players. In this context, the present study was conducted to assess the characteristics of the vermicast obtained by vermicomposting neem leaf litter in terms of microbial flora, plant growth promoting properties and antagonistic activities of the vermicast against phytopathogens. Vermicomposting of neem leaf litter was done using two epigeic earthworm species Eisenia fetida and Eudrilus eugeniae. The vermicast exhibited antagonistic potential against plant pathogens. Out of the four vermiwash infusions studied, the 75 % formulation reduced the disease incidence against mealybug by 82 % in the tree Neolamarkia cadamba. The result of the study suggests that vermicast made from neem leaf litter may be a potent combination of a biofertilizer and a pesticide.

Green and efficient extraction of phenolic compounds from Neem leaves using deep eutectic solvents based ultrasonic-assisted extraction.

Deep eutectic solvent (DES) combined with ultrasonic-assisted extraction was employed as an environmentally friendly technique for extracting antioxidant phenolic compounds from Neem leaves in place of organic solvents. Choline chloride-Ethylene glycol (1:2) with 40% V/V water content (DES-1) was investigated as a potential total phenolic content extractant (38.2 ± 1.2 mg GAE/g DW, where GAE: gallic acid equivalent, DW: dry weight). The optimal operational parameters assessed using single-factor experiments to maximize the total phenolic compounds content were as follows: extraction time of 30 min, 40% V/V water content, liquid-solid ratio of 15:1, and room temperature. Additionally, the in-vitro antioxidant experiments (2,2-diphenyl-1- picrylhydrazyl radical scavenging assay and ferric reducing antioxidant power assay) demonstrated the DES-1-based extract of Neem leaves as a potent antioxidant agent, compared to traditional solvents. Moreover, microscopic morphological analysis supported the effectiveness of DES-1 for the noticeable alteration in the fiber surface structure of Neem leaves after extraction which benefited in the release of polyphenols from these leaves. Eventually, the mass analysis of the extract disclosed the presence of eleven polyphenols in the extract. The Green Analytical Procedure Index revealed the greenness of the extraction method.

In Silico Comparison of Bioactive Compounds Characterized from Azadirachta indica with an FDA-Approved Drug against Schistosomal Agents: New Insight into Schistosomiasis Treatment.

The burden of human schistosomiasis, a known but neglected tropical disease in Sub-Saharan Africa, has been worrisome in recent years. It is becoming increasingly difficult to tackle schistosomiasis with praziquantel, a drug known to be effective against all Schistosoma species, due to reports of reduced efficacy and resistance. Therefore, this study seeks to investigate the antischistosomal potential of phytochemicals from Azadirachta indica against proteins that have been implicated as druggable targets for the treatment of schistosomiasis using computational techniques. In this study, sixty-three (63) previously isolated and characterized phytochemicals from A. indica were identified from the literature and retrieved from the PubChem database. In silico screening was conducted to assess the inhibitory potential of these phytochemicals against three receptors (Schistosoma mansoni Thioredoxin glutathione reductase, dihydroorotate dehydrogenase, and Arginase) that may serve as therapeutic targets for schistosomiasis treatment. Molecular docking, ADMET prediction, ligand interaction, MMGBSA, and molecular dynamics simulation of the hit compounds were conducted using the Schrodinger molecular drug discovery suite. The results show that Andrographolide possesses a satisfactory pharmacokinetic profile, does not violate the Lipinski rule of five, binds with favourable affinity with the receptors, and interacts with key amino acids at the active site. Importantly, its interaction with dihydroorotate dehydrogenase, an enzyme responsible for the catalysis of the de novo pyrimidine nucleotide biosynthetic pathway rate-limiting step, shows a glide score and MMGBSA of -10.19 and -45.75 Kcal/mol, respectively. In addition, the MD simulation shows its stability at the active site of the receptor. Overall, this study revealed that Andrographolide from Azadirachta indica could serve as a potential lead compound for the development of an anti-schistosomal drug.

Azadirachta indica leaf extract based green-synthesized ZnO nanoparticles coated on spent tea waste activated carbon for pharmaceuticals and personal care products removal.

Pharmaceuticals and personal care products (PPCPs) are emerging contaminants in aqueous systems, posing threat to both human health and environment. In prior research, predominant focus has been on examining various adsorbents for removing PPCPs from single-pollutant systems. However, no study has delved into simultaneous adsorption of PPCPs multi-pollutant mixture. This study evaluates performance of Azadirachta indica leaf extract-based green-synthesized ZnO nanoparticles coated on spent tea waste activated carbon (ZTAC) for removing sulfadiazine (SZN) and acetaminophen (ACN). Adsorption investigations were conducted in single-component (ACN/SZN) and binary-component (ACN + SZN) systems. The synthesized ZTAC was characterized using SEM, XRD, FTIR, EDX, porosimetry and pHpzc analysis. The study examines impact of time (1-60 min), dose (0.2-4 g/L), pH (2-12) and PPCPs concentration (1-100 mg/L) on ACN and SZN removal. Various kinetic and isotherm models were employed to elucidate mechanisms involved in sorption of PPCPs. Furthermore, synergistic and antagonistic aspects of sorption process in multi-component system were investigated. ZTAC, characterized by its crystalline nature and surface area of 980.85 m2/g, exhibited maximum adsorption capacity of 47.39 mg/g for ACN and 34.01 mg/g for SZN under optimal conditions of 15 min, 3 g/L and pH 7. Langmuir isotherm and pseudo-second-order kinetic model best-fitted the experimental data indicating chemisorption mechanism. Removal of ACN and SZN on ZTAC demonstrated synergistic nature, signifying cooperative adsorption. Overall, valorization of ZTAC offers effective and efficient adsorbent for elimination of PPCPs from wastewater.

Insights into Nimbolide molecular crosstalk and its anticancer properties.

Nimbolide, one of the main ingredients constituent of Azadirachta indica (neem) leaf extract, has garnered attention for its potential as an anticancer agent. Its efficacy against various cancers and chemopreventive action has been demonstrated through numerous in vivo and in vitro studies. This updated review aims to comprehensively explore the chemopreventive and anticancer properties of nimbolide, emphasizing its molecular mechanisms of action and potential therapeutic applications in oncology. The review synthesizes evidence from various studies that examine nimbolide's roles in apoptosis induction, anti-proliferation, cell death, metastasis inhibition, angiogenesis suppression, and modulation of carcinogen-metabolizing enzymes. Nimbolide exhibits multifaceted anticancer activities, including the modulation of multiple cell signaling pathways related to inflammation, invasion, survival, growth, metastasis, and angiogenesis. However, its pharmacological development is still in the early stages, mainly due to limited pharmacokinetic and comprehensive long-term toxicological studies. Nimbolide shows promising anticancer and chemopreventive properties, but there is need for systematic preclinical pharmacokinetic and toxicological research. Such studies are essential for establishing safe dosage ranges for first-in-human clinical trials and further advancing nimbolide's development as a therapeutic agent against various cancers. The review highlights the potential of nimbolide in cancer treatment and underscores the importance of rigorous preclinical evaluation to realize its full therapeutic potential.

Neem leaf glycoprotein binding to Dectin-1 receptors on dendritic cell induces type-1 immunity through CARD9 mediated intracellular signal to NFκB.

BACKGROUND: A water-soluble ingredient of mature leaves of the tropical mahogany 'Neem' (Azadirachta indica), was identified as glycoprotein, thus being named as 'Neem Leaf Glycoprotein' (NLGP). This non-toxic leaf-component regressed cancerous murine tumors (melanoma, carcinoma, sarcoma) recurrently in different experimental circumstances by boosting prime antitumor immune attributes. Such antitumor immunomodulation, aid cytotoxic T cell (Tc)-based annihilation of tumor cells. This study focused on identifying and characterizing the signaling gateway that initiate this systemic immunomodulation. In search of this gateway, antigen-presenting cells (APCs) were explored, which activate and induce the cytotoxic thrust in Tc cells. METHODS: Six glycoprotein-binding C-type lectins found on APCs, namely, MBR, Dectin-1, Dectin-2, DC-SIGN, DEC205 and DNGR-1 were screened on bone marrow-derived dendritic cells from C57BL/6 J mice. Fluorescence microscopy, RT-PCR, flow cytometry and ELISA revealed Dectin-1 as the NLGP-binding receptor, followed by verifications through RNAi. Following detection of ß-Glucans in NLGP, their interactions with Dectin-1 were explored in silico. Roles of second messengers and transcription factors in the downstream signal were studied by co-immunoprecipitation, western blotting, and chromatin-immunoprecipitation. Intracellularization of FITC-coupled NLGP was observed by processing confocal micrographs of DCs. RESULTS: Considering extents of hindrance in NLGP-driven transcription rates of the cytokines IL-10 and IL-12p35 by receptor-neutralization, Dectin-1 receptors on dendritic cells were found to bind NLGP through the ligand's peripheral ß-Glucan chains. The resulting signal phosphorylates PKCδ, forming a trimolecular complex of CARD9, Bcl10 and MALT1, which in turn activates the canonical NFκB-pathway of transcription-regulation. Consequently, the NFκB-heterodimer p65:p50 enhances Il12a transcription and the p50:p50 homodimer represses Il10 transcription, bringing about a cytokine-based systemic-bias towards type-1 immune environment. Further, NLGP gets engulfed within dendritic cells, possibly through endocytic activities of Dectin-1. CONCLUSION: NLGP's binding to Dectin-1 receptors on murine dendritic cells, followed by the intracellular signal, lead to NFκB-mediated contrasting regulation of cytokine-transcriptions, initiating a pro-inflammatory immunopolarization, which amplifies further by the responding immune cells including Tc cells, alongside their enhanced cytotoxicity. These insights into the initiation of mammalian systemic immunomodulation by NLGP at cellular and molecular levels, may help uncovering its mode of action as a novel immunomodulator against human cancers, following clinical trials.

Effect of nanoformulation Azadirachta indica on some factors associated with the vectorial capacity and competence of Anopheles aquasalis experimentally infected with Plasmodium vivax.

Malaria remains a highly prevalent infectious disease worldwide, particularly in tropical and subtropical regions. Effectively controlling of mosquitoes transmitting of Plasmodium spp. is crucial in to control this disease. A promising strategy involves utilizing plant-derived products, such as the Neem tree (Azadirachta indica), known for its secondary metabolites with biological activity against various insect groups of agricultural and public health importance. This study investigated the effects of a nanoformulation prototype Neem on factors linked to the vector competence of Anopheles aquasalis, a malaria vector in Latin America. Different concentrations of the nanoformulation were supplied through sugar solution and blood feeding, assessing impacts on longevity, fecundity, fertility, and transgenerational survival from larvae to adults. Additionally, the effects of the Neem nanoformulation and NeemAZAL® formulation on the sporogonic cycle of P. vivax were evaluated. Overall, significant impacts were observed at 100 ppm and 1,000 ppm concentrations on adult survival patterns and on survival of the F1 generation. A trend of reduced oviposition and hatching rates was also noted in nanoformulation-consuming groups, with fertility and fecundity declining proportionally to the concentration. Additionally, a significant decrease in the infection rate and intensity of P. vivax was observed in the 1,000 ppm group, with a mean of 3 oocysts per female compared to the control's 27 oocysts per female. In the commercial formulation, the highest tested concentration of 3 ppm yielded 5.36 oocysts per female. Concerning sporozoite numbers, there was a reduction of 52 % and 87 % at the highest concentrations compared to the control group. In conclusion, these findings suggest that the A. indica nanoformulation is a potential as a tool for malaria control through reduction in the vector longevity and reproductive capacity, possibly leading to decreased vector population densities. Moreover, the nanoformulation interfered with the sporogonic development of P. vivax. However, further basic research on Neem formulations, their effects, and mechanisms of action is imperative to gain a more specific perspective for safe field implementation.

Enhanced azadirachtin production in neem (Azadirachta indica) callus through NaCl elicitation: Insights into differential protein regulation via shotgun proteomics.

With their remarkable bioactivity and evolving commercial importance, plant secondary metabolites (PSMs) have gained significant research interest in recent years. Plant tissue culture serves as a credible tool to examine how abiotic stresses modulate the production of PSMs, enabling clear insights into plant stress responses and the prospects for controlled synthesis of bioactive compounds. Azadirachta indica, or neem has been recognized as a repository of secondary metabolites for centuries, particularly for the compound named azadirachtin, due to its bio-pesticidal and high antioxidant properties. Introducing salt stress as an elicitor makes it possible to enhance the synthesis of secondary metabolites, specifically azadirachtin. Thus, in this research, in vitro callus cultures of neem were micro-propagated and induced with salinity stress to explore their effects on the production of azadirachtin and identify potential proteins associated with salinity stress through comparative shotgun proteomics (LCMS/MS). To induce salinity stress, 2-month-old calli were subjected to various concentrations of NaCl (0.05-1.5%) for 4 weeks. The results showed that the callus cultures were able to adapt and survive in the salinity treatments, but displayed a reduction in fresh weight as the NaCl concentration increased. Notably, azadirachtin production was significantly enhanced in the salinity treatment compared to control, where 1.5% NaCl-treated calli produced the highest azadirachtin amount (10.847 ± 0.037 mg/g DW). The proteomics analysis showed that key proteins related to primary metabolism, such as defence, energy, cell structure, redox, transcriptional and photosynthesis, were predominantly differentially regulated (36 upregulated and 93 downregulated). While a few proteins were identified as being regulated in secondary metabolism, they were not directly involved in the synthesis of azadirachtin. In conjunction with azadirachtin elicitation, salinity stress treatment could therefore be successfully applied in commercial settings for the controlled synthesis of azadirachtin and other plant-based compounds. Further complementary omics approaches can be employed to enhance molecular-level modifications, to facilitate large-scale production of bioactive compounds in the future.

Revolutionizing the effect of Azadirachta indica extracts on edema induced changes in C-reactive protein and interleukin-6 in albino rats: in silico and in vivo approach.

OBJECTIVE: The aim of the present study is to determine the in vivo and in silico anti-inflammatory effect of Azadirachta indica (A. indica) in carrageenan-induced rats and its blood biomarkers. A. indica (Neem) is a widely used medicinal plant across the world, especially in Pakistan. Neem leaves have been traditionally used for the synthesis of drugs and treatment of a wide variety of diseases. MATERIALS AND METHODS: In this study, sixty albino rats (160-200 g) were divided into 4 groups: control (group I), standard (group II), ethanolic and aqueous (group III and IV) at doses of 50, 100, 200 and 400 mg/kg. RESULTS: Ethanolic and aqueous extracts showed maximum inhibition in paw size at the 5th hour (400 mg/kg). Similarly, biomarkers measured, including Interleukin-6 and C-reactive protein, exhibited significant anti-inflammatory activity at the highest dose of 400 mg/kg in both experimental groups but were more distinct in the group treated with ethanolic extracts. Correlation between C-reactive protein (CRP) and inter-leukin-6 (IL-6) showed positive correlation in group III, while negative in group IV. Similarly, positive and negative correlations were observed between CRP biomarkers and paw size in group III and IV, and the same results were also shown in the case of IL-6 and paw size. In molecular docking, the binding energy value of protein CRP and IL-1ß with the identified ligands quercetin and nimbosterol showed (-8.2 kcal/mol and -7.7 kcal/mol) the best binding affinity as compared to standard drug diclofenac with -7.0 kcal/mol binding energy respectively. CONCLUSIONS: In conclusion, in silico and in vivo analysis revealed that the extracts of A. indica leaves can be used as an effective drug to manage inflammation.

Identifying druggable targets from active constituents of Azadirachta indica A. Juss. for non-small cell lung cancer using network pharmacology and validation through molecular docking.

INTRODUCTION: Azadirachta indica A. Juss. is a well-known medicinal plant that has been used traditionally to cure various ailments in every corner of the globe. There are many in vitro and in vivo experimental evidences in connection with the bioactivity of the extracts of this plant. Lung cancer is the deadliest form of cancer and contributes to the most cancer related deaths. The mode of action of anticancer components of this plant is still to be established explicitly. OBJECTIVE: The objective of this study is to identify druggable targets of active constituents of A. indica A. Juss. for non-small cell lung cancer (NSCLC) using network pharmacology and validation of activity through molecular docking analysis. METHODOLOGY: Targets of all the active phytochemicals from A. indica were predicted and genes related to NSCLC were retrieved. A protein-protein interaction (PPI) network of the overlapping genes were prepared. Various databases and servers were employed to analyse the disease pathway enrichment analysis of the clustered genes. Validation of the gene/protein activity was achieved by performing molecular docking, and ADMET profiling of selected phytocompounds was performed. RESULT: Gene networking revealed three key target genes as EGFR, BRAF and PIK3CA against NSCLC by the active components of A. indica. Molecular docking and ADMET analysis further validated that desacetylnimbin, nimbandiol, nimbin, nimbinene, nimbolide, salannin and vepinin are the best suited anti- NSCLC among all the phytocompounds present in this plant. CONCLUSION: The present study has provided a better understanding of the pharmacological effects of active components from A. indica and its potential therapeutic effect on NSCLC.

Network Pharmacology and Molecular Modeling to Elucidate the Potential Mechanism of Neem Oil against Acne vulgaris.

Acne vulgaris is a common skin disorder with a complicated etiology. Papules, lesions, comedones, blackheads, and other skin lesions are common physical manifestations of Acne vulgaris, but the individual who has it also regularly has psychological repercussions. Natural oils are being utilized more and more to treat skin conditions since they have fewer negative effects and are expected to provide benefits. Using network pharmacology, this study aims to ascertain if neem oil has any anti-acne benefits and, if so, to speculate on probable mechanisms of action for such effects. The neem leaves (Azadirachta indica) were collected, verified, authenticated, and assigned a voucher number. After steam distillation was used to extract the neem oil, the phytochemical components of the oil were examined using gas chromatography-mass spectrometry (GC-MS). The components of the oil were computationally examined for drug-likeness using Lipinski's criteria. The Pharm Mapper service was used to anticipate the targets. Prior to pathway and protein-protein interaction investigations, molecular docking was performed to predict binding affinity. Neem oil was discovered to be a potential target for STAT1, CSK, CRABP2, and SYK genes in the treatment of Acne vulgaris. In conclusion, it was discovered that the neem oil components with PubChem IDs: ID_610088 (2-(1-adamantyl)-N-methylacetamide), ID_600826 (N-benzyl-2-(2-methyl-5-phenyl-3H-1,3,4-thiadiazol-2-yl)acetamide), and ID_16451547 (N-(3-methoxyphenyl)-2-(1-phenyltetrazol-5-yl)sulfanylpropanamide) have strong affinities for these drug targets and may thus be used as therapeutic agents in the treatment of acne.

Genotoxicity and maternal-fetal safety of the dried extract of leaves of Azadirachta indica A. Juss (Meliaceae) in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Azadirachta indica A. Juss (Meliaceae), popularly known as "neem", is used for the treatment of rheumatism, cancer, ulcers, diabetes, respiratory problems, among others. This species is present on six continents and contains more than 400 bioactive compounds. Practically all parts of the plant are used in the treatment of diseases. Although it is widely used, no study has evaluated the safety of this species throughout the gestational period in Wistar rats. AIM OF THE STUDY: To evaluate the genotoxicity and the effect of treatment with dried extract of leaves of Azadirachta indica on maternal toxicity and fetal development. MATERIALS AND METHODS: The dried extract of leaves of A. indica was obtained by spray drying after percolation of the plant material in 30% ethanol (w/w). The total flavonoids and rutin contents of the extract were determined by spectrophotometric method and HPLC-DAD, respectively. Pregnant Wistar rats (n = 40) were divided into four groups (n = 10/group): one control and three groups treated with dried extract of leaves of A. indica at doses of 300, 600 or 1200 mg/kg. Treatments were carried out from gestational day (GD) 0-20. During gestation, clinical signs of toxicity, weight gain, feed and water consumption of the dams were evaluated. On GD 21, rats were euthanized and cardiac blood was collected. Liver, kidneys, lung, heart, uterus, ovaries and bone marrow were collected. Reproductive performance parameters, histopathological analysis, biochemistry and genotoxicity were evaluated. Fetuses were evaluated for external morphology, skeletal and visceral changes. RESULTS: The total flavonoid content of the extract ranged from 2.64 to 3.01%, and the rutin content was 1.07%. There was no change in body mass gain, food and water consumption between the evaluated groups. There was also no difference between the groups in terms of biochemical parameters, reproductive performance, histopathological analysis of the mother's organs and genotoxicity. Supernumerary ossification sites of the sternum were observed, and other skeletal and visceral alterations were not significant. CONCLUSIONS: The treatment did not induce maternal toxicity, it was neither embryotoxic nor fetotoxic. The extract was not potentially genotoxic, and at a dose of 1200 mg/kg, it caused changes in the ossification of the sternum.

Neem-based products as potential eco-friendly mosquito control agents over conventional eco-toxic chemical pesticides-A review.

Mosquitoes cause serious health hazards for millions of people across the globe by acting as vectors of deadly communicable diseases like malaria, filariasis, dengue and yellow fever. Use of conventional chemical insecticides to control mosquito vectors has led to the development of biological resistance in them along with adverse environmental consequences. In this light, the recent years have witnessed enormous efforts of researchers to develop eco-friendly and cost-effective alternatives with special emphasis on plant-derived mosquitocidal compounds. Neem oil, derived from neem seeds (Azadirachta indica A. Juss, Meliaceae), has been proved to be an excellent candidate against a wide range of vectors of medical and veterinary importance including mosquitoes. It is environment-friendly, and target-specific at the same time. The active ingredients of neem oil include limonoids like azadirachtin A, nimbin, salannin and numerous other substances that are still waiting to be discovered. Of these, azadirachtin has been shown to be very effective and is mainly responsible for its toxic effects. The quality of the neem oil depends on its azadirachtin content which, in turn, depends on its manufacturing process. Neem oil can be used directly or as nanoemulsions or nanoparticles or even in the form of effervescent tablets. When added to natural breeding habitat waters they exert their mosquitocidal effects by acting as ovicides, larvicides, pupicides and/or oviposition repellents. The effects are generated by impairing the physiological pathways of the immature stages of mosquitoes or directly by causing physical deformities that impede their development. Neem oil when used directly has certain disadvantages mainly related to its disintegration under atmospheric conditions rendering it ineffective. However, many of its formulations have been reported to remain stable under environmental conditions retaining its efficiency for a long time. Similarly, neem seed cake has also been found to be effective against the mosquito vectors. The greatest advantage is that the target species do not develop resistance against neem-based products mainly because of the innumerable number of chemicals present in neem and their combinations. This makes neem-based products highly potential yet unexplored candidates of mosquito control agents. The current review helps to elucidate the roles of neem oil and its various derivatives on mosquito vectors of public health concern.

Neem extract-blended nanocellulose derived from jackfruit peel for antibacterial packagings.

The use of jackfruit peel as a source for natural and fully biodegradable "nanocellulose" (NC) for the production of bioplastics with Azadirachta indica (A. indica) extracts and polyethylene glycol (PEG) for the antibacterial properties is investigated. The characterization of the biocomposite using FT-IR and WXRD was reported. The physicochemical properties including thickness, moisture content, water holding capacity, swelling, porosity, and biodegradability in soil were investigated. The incorporation of A. indica extract revealed an increased shelf life due to the strong antibacterial activity, and these biocomposites were degraded in soil within 60 days after the end use without any harm to the environment. Jackfruit-derived nanocellulose film blended with A. indica extract exhibited strong antibacterial activity against gram-positive and gram-negative food spoilage bacteria. Disc diffusion assay, live/dead assay, and CFU analysis confirmed the antibacterial property of the synthesized film. Moreover, the films clearly prevented the biofilm formation in bacteria. Thus, the developed bioplastics can be utilized as appropriate substitutes to food packaging materials and also for biomedical applications such as wound dressings.

Azadirachta indica leaf extract mediated silver nanoparticles impregnated nano composite film (AgNP/MCC/starch/whey protein) for food packaging applications.

In order to be used in food packaging, the study aims to develop a composite film based on microcrystalline cellulose (MCC) and coated with silver nanoparticles (AgNPs). The MCC was derived from sugar cane bagasse. Protein, starch, and poly-ethylene glycol 1500 (PEG-1500) are employed to improve the tensile strength, flexibility, and durability of the packaging film. The AgNPs was synthesized by a green route employing Azadirachtaindica leaf extract as reducing agent. The determined average crystallite size of AgNPs was seen at 20 nm. The X-ray diffraction (XRD) studies of the final film prepared have an elevated peak with a crystallinity of 37.5%. The scanning electron microscopic images (SEM) of the AgNPs and the prepared samples, reveal their surface morphology. The Fourier transform infrared spectroscopic studies (FT-IR) disclose the functional group changes during the film preparation. The antibacterial activity of the amalgamated AgNPs against five bacterial pathogens studied was found to be highly active against tested food pathogens, except for Proteus vulgari. When coated over a vegetable, the produced nanocomposite film displayed an increased shelf life for the vegetable by limiting the decay impact caused by food pathogens. According to the findings, the AgNPs-impregnated MCC/Starch/Whey protein has the potential to be employed as an antimicrobial packaging material.

Potential of Azadirachta indica as a Capping Agent for Antiviral Nanoparticles against SARS-CoV-2.

A rare type of pneumonia later on referred to as COVID-19 was reported in China in December 2019. Investigations revealed that this disease is caused by a coronavirus previously identified as SARS-CoV-2, and since then, it has become a global pandemic with new strains emerging rapidly as a result of genetic mutations. Various therapeutic options are being explored in order to eradicate this pandemic even though approved vaccine candidates are being currently rolled out globally. Most medicinal plant extracts have astonishing properties, and they can therefore be used in the biosynthesis of effective antiviral nanoparticles. In this systematic review, we aimed to highlight the specific attributes that make Azadirachta indica (neem plant) a suitable candidate for the biosynthesis of anti-SARS-CoV-2 nanoparticles. A systematic investigation was therefore carried out in PubMed, Scopus, Web of Science, and AJOL databases with the keywords "Nanoparticles," "Biosynthesis," "Antivirals," "SARS-CoV-2," and "Azadirachta indica." 1216 articles were retrieved by the 21st of February 2022, but we screened studies that reported data on biomedical and antimicrobial assessment of Azadirachta indica extracts. We also screened studies that were reporting nanoparticles possessing antiviral properties against SARS-C0V-2, narrowing our results to 98 reports. Herein, the SARS-CoV-2 viral structure is briefly discussed with nanoparticles of biomedical importance in the design of SARS-CoV-2 antivirals. Most importantly, we focused on the biomedical and antiviral properties of Azadirachta indica extracts that could be of importance in the design of potential anti-SARS-CoV-2 nanoformulations.

Biochemometry-Based Discovery of Phenylpropanoids from Azadirachta indica Fruits as Inhibitors of In Vitro Osteoclast Formation.

(1) Background: Inhibition of osteoclast differentiation is the key approach in treating osteoporosis. However, using state-of-the-art treatments such as bisphosphonates and estrogen-based therapy is usually accompanied by many side effects. As opposed to this, the use of natural products as an osteoporotic remedy delivers promising outcomes with minimal side effects. (2) Methods: In the present study, we implemented a biochemometric workflow comprising (i) chemometric approaches using NMR and mass spectrometry and (ii) cell biological approaches using an osteoclast cytochemical marker (TRAP). The workflow serves as a screening tool to pursue potential in vitro osteoclast inhibitors. (3) Results: The workflow allowed for the selective isolation of two phenylpropanoids (coniferyl alcohol and sinapyl alcohol) from the fruits of neem tree (Azadirachta indica). These two isolated phenylpropanoids showed a very promising dose-dependent inhibition of osteoclast differentiation with negligible effects in terms of cell viability. (4) Conclusion: The presented workflow is an effective tool in the discovery of potential candidates for osteoclast inhibition from complex extracts. The used biochemometric approach saves time, effort and costs while delivering precise hints to selectively isolate bioactive constituents.

Anti-Cancer Activity of Gedunin by Induction of Apoptosis in Human Gastric Cancer AGS Cells.

Currently, gastric cancer is considered one of the major causes of high mortality and morbidity worldwide. Recent advances in therapeutics, clinical treatment, staging procedures, and imaging techniques are high, yet the prevalence of gastric cancer has not been reduced. Usage of the synthetic drug has many side effects that can lead to other ailments. Gedunin, a phytochemical derived from Azadirachta indica (neem tree), exhibits several pharmacological activities including antitumor, anti-inflammatory, antiulcer, antipyretics, antibacterial, antifungal, anti-diabetic, and antimalarial properties. In the current investigation, the effect of gedunin on the cell viability; reactive oxygen species (ROS) generation by DCFH-DA staining; mitochondrial membrane potential (MMP) by Rh-123 staining; apoptosis by AO/EtBr staining; cell migration and wound healing ability by wound scratch assay; and Bcl-2, Bax, caspase-3, and caspase-9 by ELISA techniques were analyzed in the AGS cells. The treatment with gedunin effectively inhibited the cell viability with IC50 = 20µM, increased the ROS generation, and triggered the apoptosis in AGS cells. The gedunin-treated AGS cells also demonstrated a decreased MMP status. The increment in the ROS generation leads to oxidative stress which in turn induce the apoptosis. The activity of Bax gene was upregulated and the activity of Bcl-2 gene was down-regulated in the AGS cells after the treatment with gedunin. In the AGS cells treated with gedunin, the caspase-3 and caspase-9 activities were increased. In overall, these findings suggested that gedunin can be used as a potent chemotherapeutic agent in the future to treat gastric cancer.

In-vitro and in-silico antibacterial activity of Azadirachta indica (Neem), methanolic extract, and identification of Beta.d-Mannofuranoside as a promising antibacterial agent.

BACKGROUND: Antimicrobial resistance became the leading cause of death globally, resulting in an urgent need for the discovery of new, safe, and efficient antibacterial agents. Compounds derived from plants can provide an essential source of new types of antibiotics. A. indica (neem) plant is rich in antimicrobial phytoconstituents. Here, we used the sensitive and reliable gas chromatography-mass spectrometry (GC-MS) approach, for the quantitative and quantitative determination of bioactive constituents in methanolic extract of neem leaves grown in Sudan. Subsequently, antibacterial activity, pharmacokinetic and toxicological properties were utilized using in silico tools. RESULTS: The methanolic extract of neem leaves was found to have antibacterial activity against all pathogenic and reference strains. The lowest concentration reported with bacterial activity was 3.125%, which showed zones of inhibition of more than 10 mm on P. aeruginosa, K. pneumoniae, Citrobacter spp., and E. coli, and 8 mm on Proteus spp., E. faecalis, S. epidermidis, and the pathogenic S. aureus. GC-MS analysis revealed the presence of 30 chemical compounds, including fatty acids (11), hydrocarbons (9), pyridine derivatives (2), aldehydes (2), phenol group (1), aromatic substances (1), coumarins (1), and monoterpenes (1). In silico and in vitro tools revealed that.beta.d-Mannofuranoside, O-geranyl was the most active compound on different bacterial proteins. It showed the best docking energy (-8 kcal/mol) and best stability with different bacterial essential proteins during molecular dynamic (MD) simulation. It also had a good minimum inhibitory concentration (MIC) (32 µg/ml and 64 µg/ml) against S. aureus (ATCC 25,923) and E. coli (ATCC 25,922) respectively. CONCLUSION: The methanolic extract of A. indica leaves possessed strong antibacterial activity against different types of bacteria. Beta.d-Mannofuranoside, O-geranyl was the most active compound and it passed 5 rules of drug-likeness properties. It could therefore be further processed for animal testing and clinical trials for its possible use as an antibacterial agent with commercial values.