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.

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.

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 β-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.

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.

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.

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.

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.

UNASSIGNED: 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.
UNASSIGNED: The comprehensive search of the literature was done until September 2020 on the MEDLINE, Embase, Scopus and Web of Knowledge databases.
UNASSIGNED: 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-β (Wnt-β)/catenin, NF-κB, PI3K/AKT, and signaling molecules, such as transforming growth factor (TGF-β), 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.
UNASSIGNED: The current review mainly focused on understanding the molecular mechanisms underlying the therapecutic effects of nimbolide in chronic diseases.

BACKGROUND: 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.
OBJECTIVE: 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 β-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 β-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.
CONCLUSIONS: 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.

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.