Synthesis, Characterization, Phytochemistry, and Therapeutic Potential of Azadirachta indica Conjugated Silver Nanoparticles: A Comprehensive Study on Antidiabetic and Antioxidant Properties.

Nanotechnology has become a major topic of study, particularly in the medical and health domains. Because nanomedicine has a higher recovery rate than other conventional drugs, it has attracted more attention. Green synthesis is the most efficient and sustainable method of creating nanoparticles. The current work used ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, scanning electron microscopy, energy dispersive X-ray, and X-ray diffraction to thoroughly characterize the synthesized silver nanoparticles (AgNPs) from Azadirachta indica leaf extract. Characterization confirmed the synthesis of the AgNPs along with the possible linkage of the phytochemicals with the silver as well as the quantitative analysis and nature of NPs. The antioxidant activity of AgNPs and neem extract was measured by the 2,2-diphenyl-1-picrylhydrazyl assay using various concentrations (20, 40, 60, 80, and 100 µg/ml). Additionally, using diabetic mice that had been given alloxan, the in vivo antidiabetic potential of biosynthesized AgNPs was assessed. Eight groups of mice were used to assess the antidiabetic activity: one control group and seven experimental groups (untreated, extract-treated, AgNPs at low and high doses, standard drug, low dose of AgNPs + drug, and high dose of AgNPs + drug). At days 0, 7, 14, 21, and 28, blood glucose levels and body weight were measured. After 28 days, the mice were dissected, and the liver, kidney, and pancreas were examined histologically. The results depicted that the AgNPs showed higher (significant) radical scavenging activity (IC50 = 35.2 µg/ml) than extract (IC50 = 93.0 µg/ml) and ascorbic acid (IC50 = 64.6 µg/ml). The outcomes demonstrated that biosynthesized AgNPs had a great deal of promise as an antidiabetic agent and exhibited remarkable effects in diabetic mice given AgNPs, extract, and drug. Remarkable improvement in the body weight and blood glucose level of mice treated with high doses of AgNPs and drug was observed. The body weight and blood glucose level of diabetic mice treated with a high dose of AgNPs + standard drug showed significant improvement, going from 28.7 ± 0.2 to 35.6 ± 0.3 g and 248 ± 0.3 to 109 ± 0.1 mg/dl, respectively. Significant regeneration was also observed in the histomorphology of the kidney, liver's central vein, and islets of Langerhans after treatment with biosynthesized AgNPs. Diabetic mice given a high dose of AgNPs and drug displayed architecture of the kidney, liver, and pancreas that was nearly identical to that of the control group. According to the current research, biosynthesized AgNPs have strong antioxidant and antidiabetic potential and may eventually provide a less expensive option for the treatment of diabetes.

Natural Enemies of the fall armyworm (Spodoptera frugiperda Smith) and comparing Neem aqueous extracts with its larvae, Gurage zone, central Ethiopia.

The fall armyworm (Spodoptera frugiperda Smith) is an invasive and polyphagous insect pest. It poses a significant threat to maize crops, uncontrolled infestation can result 100 % loss. However, natural enemies play a vital role in regulating the population of this pest. Additionally, botanical sources extracts have the potential to be effective insecticides. The objectives of the study were to investigate the natural enemies of S. frugiperda in the Gurage zone and to compare efficacy of Neem seed and leaf aqueous extracts with S. frugiperda larvae, central Ethiopia. S. frugiperda larvae and egg masses, cocoons and larvae cadavers collected from infested maze farms. From each round collection 25 healthy and inactive larvae were sampled to rear until emerging adults. Observed predator species recorded. Neem seed and leaf aqueous extracts was tested against S. frugiperda in laboratory condition. The study found a diverse range of natural enemies associated with S. frugiperda, including parasitoids, predators, and entomopathogenic fungi. Three species of parasitoids (Exorista xanthaspis, Tachina spp., and Charops annulipes) were documented in Ethiopia for the first time. Predatory insects belonging to four distinct orders: Hemiptera, Dermaptera, Coleoptera, and Mantodea also identified. In particular, various Hemipterans were observed in the maize farms infested with S. frugiperda. In terms of Neem seed and leaf aqueous extracts, they demonstrated similar mortality rates for S. frugiperda larvae after 72 h, although differences were observed at 24 and 48 h. For effective management of S. frugiperda, more research is needed to fully exploit the potential of natural enemies and botanical source insecticides.

Pharmacological Effect of Copper Oxide Nanoparticles of Azadirachta indica Leaf Extract and Application for its Antibacterial Properties.

Nanoparticles prepared from bio-reduction agents are of keen interest to researchers around the globe due to their ability to mitigate the harmful effects of chemicals. In this regard, the present study aims to synthesize copper oxide nanoparticles (CuO NPs). CuNPs show a characteristic absorption peak at 347 nm, while SEM reveals the spherical but agglomerated shape of CuNPs of the size within the range of 51.26-56.66 nm. The crystallite size measured by using XRD was found to be within a range of 23.38-46.64 nm for ginger-doped CuO and 26-56 nm for garlic-doped CuO. The X-ray diffraction analysis shows the crystalline structure of copper nanoparticles with prominent peaks. Bragg's reflection of copper nanoparticles shows diffraction peaks around 2θ =43.4°, 50.3°, and 74.39°, representing [111], [200], and [220] crystallographic planes of face-centered cubic (fcc). The synthesized CuO NPs tested antibacterial properties against various strains of microorganisms, including Escherichia coli, 25 µg/mL 2.3 ± 0.21 and 100 µg/mL 6.5 ± 0.17, Staphylococcus aureus, 25 µg/mL 2.3 ± 0.29 and 100 µg/mL 11.5 ± 1.17, Streptococcus mutans, 25 µg/mL 01.05 ± 0.21 and 100 µg/mL 15.8 ± 0.17, Enterococcus faecalis). The short novelty of Azadirachta indica lies in its potential relevance to human health, as it has been found to possess bioactive compounds with various medicinal properties, such as antimicrobial, antioxidant, and anti-inflammatory activities, making it a promising natural resource for therapeutic applications.

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 Extract Exhibits Anti-Aging and Antioxidant Effects from Yeast to Human Cells.

Neem leaves have long been used in traditional medicine for promoting longevity. However, the precise mechanisms underlying their anti-aging effects remain elusive. In this study, we investigated the impact of neem leaf extract (NLE) extracted from a 50% ethanol solution on the chronological lifespan of Saccharomyces cerevisiae, revealing an extension in lifespan, heightened oxidative stress resistance, and a reduction in reactive oxygen species. To discern the active compounds in NLE, LC/MS and the GNPS platform were employed. The majority of identified active compounds were found to be flavonoids. Subsequently, compound-target pharmacological networks were constructed using the STP and STITCH platforms for both S. cerevisiae and Homo sapiens. GOMF and KEGG enrichment analyses of the predicted targets revealed that "oxidoreductase activity" was among the top enriched terms in both yeast and human cells. These suggested a potential regulation of oxidative stress response (OSR) by NLE. RNA-seq analysis of NLE-treated yeast corroborated the anti-oxidative effect, with "oxidoreductase activity" and "oxidation-reduction process" ranking high in enriched GO terms. Notably, CTT1, encoding catalase, emerged as the most significantly up-regulated gene within the "oxidoreductase activity" cluster. In a ctt1 null mutant, the enhanced oxidative stress resistance and extended lifespan induced by NLE were nullified. For human cells, NLE pretreatment demonstrated a decrease in reactive oxygen species levels and senescence-associated ß-galactosidase activity in HeLa cells, indicative of anti-aging and anti-oxidative effects. This study unveils the anti-aging and anti-oxidative properties of NLE while delving into their mechanisms, providing novel insights for pharmacological interventions in aging using phytochemicals.

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.

The therapeutic role of Azadirachta indica leaves ethanolic extract against detrimental effects of Aeromonas veronii infection in Nile tilapia, Oreochromis niloticus.

Bacterial pathogens cause high fish mortalities and in turn economic losses in fish farms. Innovative strategies should be applied to control bacterial infections instead of antibiotics to avoid the resistance problem. Consequently, the present investigation studied the curative potential of Azadirachta indica leave ethanolic extract (AILEE) on Aeromonas veronii infection in Oreochromis niloticus. A preliminary trial was assessed to evaluate the curative dose of AILEE which was found to be 2.5 mg/L. One hundred and sixty fish were divided into equal four groups in four replications, where group 1 and group 2 were non-challenged and treated with 0- and 2.5-mg/L AILEE, respectively. Group 3 and group 4 were challenged with A. veronii and treated with 0- and 2.5-mg/L AILEE, respectively for 10 days. A. veronii infection produced severe clinical manifestations and a high mortality rate in the infected fish. Furthermore, the infected fish exhibited a significant rise in the hepatorenal indices (aspartate aminotransferase, alanine aminotransferase, and creatinine), the oxidant biomarker (malondialdehyde), and the stress indicators (glucose and cortisol). A significant reduction in the protein profile and antioxidant/immune parameters (catalase, immunoglobulin M, lysozyme, nitric oxide, and phagocytic activity) was observed in the infected fish. Water application of the infected group to 2.5-mg/L AILEE notably ameliorated the hepatorenal indices, the oxidant biomarker, and the stress indicators. Furthermore, AILEE improved the antioxidant/immune indices. Water application of 2.5-mg/L AILEE could be useful against A. veronii infection in O. niloticus culture.

A Comparative Evaluation of Antimicrobial and Cytotoxic Efficacy of Biosynthesized Silver Nanoparticles and Chemically Synthesized Silver Nanoparticles Against Enterococcus faecalis: An In Vitro Study.

Introduction Effective root canal cleaning and sealing are essential for a successful endodontic procedure. For the purpose of disinfecting root canals, both herbal and non-herbal medications are recommended. This study aimed to analyze the antimicrobial and cytotoxic properties of biosynthesized silver nanoparticles (AgNPs) synthesized from Azadirachta indica/neem and chemically synthesized AgNPs from trisodium citrate (TSC) against oral pathogens to be further used as an irrigant in endodontic treatment. Materials and methods To synthesize A. indica AgNPs, powdered fresh A. indica leaves were weighed, added to double distilled water, heated for 30 minutes, and then combined with silver nitrate solution. TSC was also used to create TSC AgNPs. X-ray diffraction (XRD), scanning electron microscopy (SEM), ocular observation, and the ultraviolet-visible light (UV-vis) spectrum were used to characterize the AgNPs. Studies were conducted on the extract's characteristics, including its cytotoxicity and antibacterial activity. Results The hue shift and peak on the UV-vis spectrophotometer were signs that AgNPs were forming. The XRD pattern showed that the sample included crystalline AgNPs, mostly spherical ones. By using SEM, the presence of AgNPs was also verified. AgNPs that were synthesized showed antimicrobial efficacy against Enterococcus faecalis. Compared to chemically synthesized AgNPs, A. indica AgNPs showed lower minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values, a bigger zone of inhibition (ZOI), and less cytotoxic action. Conclusion This study demonstrates the minimal cytotoxicity and antibacterial activity of A. indica AgNPs against E. faecalis. This suggests that they might also be employed as root canal cleaners. Before experimenting with animals or cell lines in clinical trials for endodontic treatment, further research should be done.

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.

Nimbolide: promising agent for prevention and treatment of chronic diseases (recent update).

Background: Nimbolide, a bioactive compound derived from the neem tree, has garnered attention as a potential breakthrough in the prevention and treatment of chronic diseases. Recent updates in research highlight its multifaceted pharmacological properties, demonstrating anti-inflammatory, antioxidant, and anticancer effects. With a rich history in traditional medicine, nimbolide efficacy in addressing the molecular complexities of conditions such as cardiovascular diseases, diabetes, and cancer positions it as a promising candidate for further exploration. As studies progress, the recent update underscores the growing optimism surrounding nimbolide as a valuable tool in the ongoing pursuit of innovative therapeutic strategies for chronic diseases. Methods: The comprehensive search of the literature was done until September 2020 on the MEDLINE, Embase, Scopus and Web of Knowledge databases. Results: Most studies have shown the Nimbolide is one of the most potent limonoids derived from the flowers and leaves of neem (Azadirachta indica), which is widely used to treat a variety of human diseases. In chronic diseases, nimbolide reported to modulate the key signaling pathways, such as Mitogen-activated protein kinases (MAPKs), Wingless-related integration site-ß (Wnt-ß)/catenin, NF-κB, PI3K/AKT, and signaling molecules, such as transforming growth factor (TGF-ß), Matrix metalloproteinases (MMPs), Vascular Endothelial Growth Factor (VEGF), inflammatory cytokines, and epithelial-mesenchymal transition (EMT) proteins. Nimbolide has anti-inflammatory, anti-microbial, and anti-cancer properties, which make it an intriguing compound for research. Nimbolide demonstrated therapeutic potential for osteoarthritis, rheumatoid arthritis, cardiovascular, inflammation and cancer. Conclusion: The current review mainly focused on understanding the molecular mechanisms underlying the therapecutic effects of nimbolide in chronic diseases.

Anthelmintic screening of Bangladeshi medicinal plants and related phytochemicals using in vitro and in silico methods: An ethnobotanical perspective.

ETHNOPHARMACOLOGICAL RELEVANCE: Infections caused by parasitic worms or helminth continue to pose a great burden on human and animal health, particularly in underdeveloped tropical and subtropical countries where they are endemic. Current anthelmintic drugs present serious limitations and the emergence of drug resistance has made it increasingly challenging to combat such infections (helminthiases). In Bangladesh, medicinal plants are often used by indigenous communities for the treatment of helminthiases. Knowledge on such plants along with screening for their anthelmintic activity has the potential to lead to the discovery of phytochemicals that could serve as novel molecular scaffolds for the development of new anthelminthic drugs. AIM OF THE STUDY: The purpose of this study was i) to conduct an ethnobotanical survey to gather data on Bangladeshi medicinal plants used in the treatment of helminthiases, ii) to test plants with the highest use values for their in vitro anthelmintic activity, and iii) to carry out in silico screening on phytochemicals present in the most active plant extract to investigate their ability to disrupt ß-tubulin function in helminths. METHODS: The ethnobotanical survey was conducted across three sub-districts of Bangladesh, namely Mathbaria, Phultala and Khan Jahan Ali. The in vitro screening for anthelmintic activity was performed in a motility test using adult Haemonchus contortus worms. Virtual screening using PyRx was performed on the phytochemicals reported from the most active plant, exploring their interactions with the colchicine binding site of the ß-tubulin protein target (PDB ID: 1SA0). RESULTS: The survey respondents reported a total of 32 plants for treating helminthiases. Based on their use values, the most popular choices were Ananas comosus (L.) Merr., Azadirachta indica A.Juss., Carica papaya L., Citrus maxima (Burm.) Merr., Curcuma longa L., Momordica charantia L., Nigella sativa L. and Syzygium cumini (L.) Skeels. In vitro anthelmintic testing revealed that A. indica leaves and bark had the highest activity with LC50 values of 16 mg/mL in both cases. Other plant extracts also exhibited good anthelmintic activity with LC50 values ranging from 16 to 52 mg/mL, while the value for albendazole (positive control) was 8.39 mg/mL. The limonoids nimbolide and 28-deoxonimbolide showed a binding affinity of -8.9 kcal/mol, and satisfied all drug-likeness parameters. The control ligand N-deacetyl-N-(2-mercaptoacetyl)colchicine had a binding affinity of -6.9 kcal/mol. CONCLUSION: Further in silico and in vitro studies are warranted on the identified limonoids to confirm the potential of these derivatives as novel drug templates for helminthiases. The current study supports the need for an ethnobotanical survey-based approach to discover novel drug templates for helminthiases.

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.

Antimicrobial phytoconstituents from Azadirachta indica (neem) with potential inhibitor against FtsZ protein of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a well-known pathogen for its rapid development of multi-drug antibiotic resistance. This pathogen is responsible for numerous human diseases, particularly affecting immunocompromised and elderly patients. Hence, discovering novel therapeutics has become necessary in the fight against antimicrobial resistance. This study is focused on evaluating the potential inhibitory activity of eleven phytocompounds from Azadirachta indica against the nucleotide-binding site of the FtsZ protein of P. aeruginosa through a cheminformatics approach. FtsZ is an indispensable and highly conserved protein in prokaryotic cell division. Docking studies revealed favourable binding energies (ΔG= - 8.3 to - 5.4 kcal/mol) for all selected phytoconstituents. Finally, we selected Nimbiol (CID 11119228), as a lead compound, exhibiting a binding energy (ΔG= -7.8 kcal/mol) for the target. Based on our findings, Nimbiol shows potential as an anti-FtsZ compound, making it a promising candidate for further in vitro and in vivo investigations to assess its antimicrobial activity.

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.

Alternative first-line malaria treatment.

Malaria is a disease affecting millions of people, especially in Africa, Asia, and South America, and has become a substantial economic burden. Because malaria is contracted through the bite of a mosquito vector, it is very challenging to prevent. Bed nets and insect repellents are used in some homes; others do not have or use them even when available. Thus, treatment measures are crucial to controlling this disease. Artemisinin-based combination therapy (ACT) is currently the first-line treatment for malaria. ACT has been used for decades, but recently, there has been evidence of potential resistance. This threat of resistance has led to the search for possible alternatives to ACT. In sub-Saharan Africa, Azadirachta indica, or simply neem, is a plant used to treat a variety of ailments, including malaria. Neem is effective against one of the more deadly malaria parasites Plasmodium falciparum. Reports show that neem inhibits microgametogenesis of P. falciparum and interferes with the parasite's ookinete development. Although there is substantial in vitro research on the biological activity of A. indica (neem), there is limited in vivo research. Herein, we discuss the in vivo effects of neem on malaria parasites. With A. indica, the future of malaria treatment is promising, especially for high-risk patients, but further research and clinical trials are required to confirm its biological activity.

Résumé Le paludisme est une maladie qui touche des millions de personnes, notamment en Afrique, en Asie et en Amérique du Sud, et est devenu un problème économique majeur fardeau. Le paludisme étant contracté par la piqûre d'un moustique vecteur, il est très difficile à prévenir. Moustiquaires et insectifuges sont utilisés dans certaines maisons ; d'autres ne les possèdent pas ou ne les utilisent pas même lorsqu'ils sont disponibles. Les mesures thérapeutiques sont donc cruciales pour contrôler cette maladie. La thérapie combinée à base d'artémisinine (ACT) constitue actuellement le traitement de première intention contre le paludisme. L'ACT est utilisé depuis des décennies, mais récemment, il y a eu des preuves d'une résistance potentielle. Cette menace de résistance a conduit à la recherche d'alternatives possibles à l'ACT. En Afrique subsaharienne, Azadirachta indica, ou simplement neem, est une plante utilisée pour traiter diverses maladies, dont le paludisme. Le Neem est efficace contre l'un des des parasites du paludisme plus mortels, Plasmodium falciparum. Des rapports montrent que le neem inhibe la microgamétogenèse de P. falciparum et interfere avec le développement de l'ookinète du parasite. Bien qu'il existe d'importantes recherches in vitro sur l'activité biologique d'A. indica (neem), il existe la recherche in vivo est limitée. Nous discutons ici des effets in vivo du neem sur les parasites du paludisme. Avec A. indica, l'avenir du traitement du paludisme est prometteur, en particulier pour les patients à haut risque, mais des recherches et des essais cliniques supplémentaires sont nécessaires pour confirmer son activité biologique. Mots-clés: Azadirachta indica, paludisme, neem, Plasmodium falciparum.

Eco-friendly Synthesis of Azadirachta indica-based Metallic Nanoparticles for Biomedical Application & Future Prospective.

The process of producing the metallic nanoparticles (MNPs) in a sustainable and environment- friendly process is very desirable due to environmental hazards posed by climatic changes. Biomedical one of the fields classified under nanoscience, nanoparticles have a potential synthetic application, which makes it a vast area of research. These particles can be prepared using chemical, physical, and biological methods. One of the methods of synthesis of nanoparticles is by the use of plant extracts, known as green synthesis. Because of its low cost and nontoxicity, it has gained attention in recent times. This review was conducted to find the possible outcomes and uses of metallic nanoparticles synthesized using different parts like gum, root, stem, leaf, fruits, etc. of Azadirachta indica (AI). AI, a popular medicinal plant commonly known as neem, has been studied for the green synthesis of NPs by using the capping and reducing agents secreted by the plant. Various phytochemicals identified in neem are capable of metal ion reduction. Green synthesis of NPs from neem is an eco-friendly and low-cost method. These NPs are reported to exhibit good antimicrobial activity. The review covers the preparation, characterization, and mechanism associated with the antibacterial, anticancer, and neurological diseases of the MNPs. Furthermore, the limitations associated with the existing NPs and the prospects of these NPs are also examined.

Elucidating the structural, catalytic, and antibacterial traits of Ficus carica and Azadirachta indica leaf extract-mediated synthesis of the Ag/CuO/rGO nanocomposite.

The present exploration demonstrates the efficient, sustainable, cost-effective, and environment-friendly green approach for the synthesis of silver (Ag)-doped copper oxide (CuO) embedded with reduced graphene oxide (rGO) nanocomposite using the green one-pot method and the green deposition method. Leaf extracts of Ficus carica and Azadirachta indica were used for both methods as reducing and capping agents. The effect of methodology and plant extract was analyzed through different characterization techniques such as UV-visible spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), x-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM). The lowest band gap of 3.0 eV was observed for the Ag/CuO/rGO prepared by the green one-pot method using F. carica. The reduction of graphene oxide (GO) and the formation of metal oxide was confirmed through functional group detection using FT-IR. Calculation of thermodynamic parameters showed that all reactions involved were nonspontaneous and endothermic which shows the stability of nanocomposites. XRD studies revealed the crystallinity, phase purity and small average crystallite size of 32.67 nm. SEM images disclosed that the morphology of the nanocomposites was spherical with agglomeration and rough texture. The particle size of the nanocomposites calculated through HRTEM was found in agreement with the XRD results. The numerous properties of the synthesized nanocomposites enhanced their potential against the degradation of methylene blue, rhodamine B, and ciprofloxacin. The highest percentage degradation of Ag/CuO/rGO was found to be 97%, synthesized using the green one-pot method with F. carica against ciprofloxacin, which might be due to the lowest band gap, delayed electron-hole pair recombination, and large surface area available. The nanocomposites were also tested against the Gram-positive and Gram-negative bacteria. RESEARCH HIGHLIGHTS: Facile synthesis of Ag/CuO/rGO nanocomposite using a green one-pot method and the green deposition method. The lowest band gap of 3.0 eV was observed for nanocomposite prepared by a green one-pot method using Ficus carica. Least average crystallite size of 32.67 nm was found for nanocomposite prepared by a green one-pot method using F. carica. Highest antibacterial and catalytic activity (97%) was obtained against ciprofloxacin with nanocomposite prepared through green one-pot method using F. carica. A mechanism of green synthesis is proposed.

A new method in the production of protective sheets against X-ray radiation.

Today, the use of X-rays in diagnosing and sometimes treating patients is inevitable. Despite the many benefits of using X-rays in medical and other sciences, the harmful effects of this radiation on human tissue should not be neglected. One of the best ways to prevent the harmful effects of X-rays on the human body is to use appropriate covers against these rays. It seems that it is necessary to find effective particles to weaken X-rays and choose a suitable substrate with high mechanical resistance to scatter particles in it. In this study, the synthesis of SnO2 nanoparticles from SnCl2.2H2O precursor and BaSO4 nanoparticles from BaCl2.2H2O precursor using neem tree extract (Azadirachta indica) as a reducing and stabilizing agent is reported. After the synthesis of nanoparticles, their structure was investigated by X-ray diffraction, scanning electron microscopy and energy dispersive X-ray analysis. Then the desired composite and nanocomposite were prepared in the polymer substrate. The sheets were prepared using an extruder and then a hot hydraulic press. The output sheets had a thickness of 1 mm. The structural characteristics of the produced sheets such as surface morphology, density of prepared composites, mechanical properties, thermal gravimetric analysis and retention of loaded particles after three times washes were investigated. The X-ray attenuation capability of each sample was evaluated by calculating the linear attenuation coefficient for each prepared sample. The results show that all sheets filled with tin and barium micro and nano particles have more X-ray attenuation capabilities than pure polymer. Among the prepared sheets, the nanocomposite prepared from low-density polyethylene (77 %) + SnO2 (10 %) + BaSO4 (10 %) + multi-walled carbon nanotubes (3 %) showed the highest X-ray attenuation.

Azadirachta indica (AI)leaf extract coated ZnO-AInanocore-shell particles for enhanced antibacterial activity against methicillin-resistantStaphylococcus aureus(MRSA).

With the rise in microbial resistance to traditional antibiotics and disinfectants, there is a pressing need for the development of novel and effective antibacterial agents. Two major approaches being adopted worldwide to overcome antimicrobial resistance are the use of plant leaf extracts and metallic nanoparticles (NPs). However, there are no reports on the antibacterial potential of NPs coated with plant extracts, which may lead to novel ways of treating infections. This study presents an innovative approach to engineer antibacterial NPs by leveraging the inherent antibacterial properties of zinc oxide NPs (ZnO NPs) in combination withAzadirachta indica(AI) leaf extract, resulting in enhanced antibacterial efficacy. ZnO NPs were synthesised by the precipitation method and subsequently coated withAIleaf extract to produce ZnO-AInanocore-shell structures. The structural and morphological characteristics of the bare and leaf extract coated ZnO NPs were analysed by x-ray diffraction and field emission scanning electron microscopy, respectively. The presence of anAIleaf extract coating on ZnO NPs and subsequent formation of ZnO-AInanocore-shell structures was verified through Fourier transform infrared spectroscopy and photoluminescence techniques. The antibacterial efficacy of both ZnO NPs and ZnO-AInanocore-shell particles was evaluated against methicillin-resistantStaphylococcus aureususing a zone of inhibition assay. The results showed an NP concentration-dependent increase in the diameter of the inhibition zone, with ZnO-AInanocore-shell particles exhibiting superior antibacterial properties, owing to the combined effect of ZnO NPs and the poly phenols present inAIleaf extract. These findings suggest that ZnO-AInanocore-shell structures hold promise for the development of novel antibacterial creams and hydrogels for various biomedical applications.

Starch-based antibacterial food packaging with ZnO nanoparticle.

Starch-based biofilms with embedded nanoparticles (NPs) are used to wrap food in biodegradable packaging system that has high antibacterial action against a variety of microorganisms. In this study, ZnO NPs were synthesised using both a green synthesis approach utilising Azadirachta indica (Neem) and a chemical synthesis approach using the sol-gel technique. The structural and morphological properties of all synthesized NPs were characterized through XRD, UV-VIS, UV-DRS, FTIR, and FESEM analysis. Further, these NPs were employed in the development of starch-based biodegradable films. A meticulous comparative analysis was performed to evaluate the functional properties of the nanocomposites, encompassing crucial parameters such as film thickness, moisture content, swelling index, opacity, solubility, water vapor permeability, and tensile strength. In comparison to films embedded with chemically synthesised NPs (F1), nanocomposite with green synthesised NPs (F2) showed 15.27% greater inhibition against Escherichia coli growth and 22.05% stronger inhibition against Staphylococcus aureus bacterial strains. Based on the biodegradability analysis, the nanocomposite film-F2 showed a 53.33% faster degradation rate compared to the film-F1. The developed films were utilized to assess the quality of both wrapped and unwrapped grapes, leading to the generalization of the research for the development of starch-based antibacterial and environmentally friendly food packaging material. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05834-9.