In Vivo, In Vitro and In Silico Anticancer Activity of Ilama Leaves: An Edible and Medicinal Plant in Mexico.

Ilama leaves are an important source of secondary metabolites with promising anticancer properties. Cancer is a disease that affects a great number of people worldwide. This work aimed to investigate the in vivo, in vitro and in silico anticancer properties of three acyclic terpenoids (geranylgeraniol, phytol and farnesyl acetate) isolated from petroleum ether extract of ilama leaves. Their cytotoxic activity against U-937 cells was assessed using flow cytometry to determine the type of cell death and production of reactive oxygen species (ROS). Also, a morphological analysis of the lymph nodes and a molecular docking study using three proteins related with cancer as targets, namely, Bcl-2, Mcl-1 and VEGFR-2, were performed. The flow cytometry and histomorphological analysis revealed that geranylgeraniol, phytol and farnesyl acetate induced the death of U-937 cells by late apoptosis and necrosis. Geranylgeraniol and phytol induced a significant increase in ROS production. The molecular docking studies showed that geranylgeraniol had more affinity for Bcl-2 and VEGFR-2. In the case of farnesyl acetate, it showed the best affinity for Mcl-1. This study provides information that supports the anticancer potential of geranylgeraniol, phytol and farnesyl acetate as compounds for the treatment of cancer, particularly with the potential to treat non-Hodgkin's lymphoma.

Annona squamosa Fruit Extract Ameliorates Lead Acetate-Induced Testicular Injury by Modulating JAK-1/STAT-3/SOCS-1 Signaling in Male Rats.

Lead (Pb) is a common pollutant that is not biodegradable and gravely endangers the environment and human health. Annona squamosa fruit has a wide range of medicinal uses owing to its phytochemical constituents. This study evaluated the effect of treatment with A. squamosa fruit extract (ASFE) on testicular toxicity induced in male rats by lead acetate. The metal-chelating capacity and phytochemical composition of ASFE were determined. The LD50 of ASFE was evaluated by probit analysis. Molecular docking simulations were performed using Auto Dock Vina. Forty male Sprague Dawley rats were equally divided into the following groups: Gp1, a negative control group; Gp2, given ASFE (350 mg/kg body weight (b. wt.)) (1/10 of LD50); Gp3, given lead acetate (PbAc) solution (100 mg/kg b. wt.); and Gp4, given PbAc as in Gp3 and ASFE as in Gp2. All treatments were given by oro-gastric intubation daily for 30 days. Body weight changes, spermatological parameters, reproductive hormone levels, oxidative stress parameters, and inflammatory biomarkers were evaluated, and molecular and histopathological investigations were performed. The results showed that ASFE had promising metal-chelating activity and phytochemical composition. The LD50 of ASFE was 3500 mg/kg b. wt. The docking analysis showed that quercetin demonstrated a high binding affinity for JAK-1 and STAT-3 proteins, and this could make it a more promising candidate for targeting the JAK-1/STAT-3 pathway than others. The rats given lead acetate had defective testicular tissues, with altered molecular, biochemical, and histological features, as well as impaired spermatological characteristics. Treatment with ASFE led to a significant mitigation of these dysfunctions and modulated the JAK-1/STAT-3/SOCS-1 axis in the rats.

Comprehensive Chemical Profiling and Mechanistic Insight into Anticancer Activity of Annona muricata Leaves Extract.

The aqueous extract of Annona muricata L. leaves was thoroughly analyzed using the UPLC-MS/MS, in addition to a new approach of examination of the extract's impact on cancer of EAC(Ehrlich ascites carcinoma) in albino male mice. The aim was to investigate the diversity of the phytochemical constituents of the aqueous leaf capsule extract and their impacts on EAC as anticancer agents. The UPLC-ESI-MS/MS screening resulted in 410 tentatively identified metabolites. Among them, 384 compounds were tentatively identified in a previous study, besides a number of 26 compounds belonging to acetogenins, phenolics, flavonoids, alkaloids, and other miscellaneous compounds, which were exclusively identified in the aqueous extract of the leaf capsule. Interestingly, a new compound was tentatively characterized as galloyl-quinic acid-rutinoside. This study also demonstrated that treating EAC mice with an extract from A. muricata leaves significantly improved the abnormalities in the expression of pro-apoptotic (Bax and caspase-3) and anti-apoptotic (Bcl-2) genes. Furthermore, the extract showed good protection against induced Ehrlich hepatocarcinoma, according to the microscopical, histological, and immune-histochemical analyses of the liver tissues and tumor mass.

Unveiling the Multifaceted Capabilities of Endophytic Aspergillus flavus Isolated from Annona squamosa Fruit Peels against Staphylococcus Isolates and HCoV 229E-In Vitro and In Silico Investigations.

Recently, there has been a surge towards searching for primitive treatment strategies to discover novel therapeutic approaches against multi-drug-resistant pathogens. Endophytes are considered unexplored yet perpetual sources of several secondary metabolites with therapeutic significance. This study aims to isolate and identify the endophytic fungi from Annona squamosa L. fruit peels using morphological, microscopical, and transcribed spacer (ITS-rDNA) sequence analysis; extract the fungus's secondary metabolites by ethyl acetate; investigate the chemical profile using UPLC/MS; and evaluate the potential antibacterial, antibiofilm, and antiviral activities. An endophytic fungus was isolated and identified as Aspergillus flavus L. from the fruit peels. The UPLC/MS revealed seven compounds with various chemical classes. The antimicrobial activity of the fungal ethyl acetate extract (FEA) was investigated against different Gram-positive and Gram-negative standard strains, in addition to resistant clinical isolates using the agar diffusion method. The CPE-inhibition assay was used to identify the potential antiviral activity of the crude fungal extract against low pathogenic human coronavirus (HCoV 229E). Selective Gram-positive antibacterial and antibiofilm activities were evident, demonstrating pronounced efficacy against both methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA). However, the extract exhibited very weak activity against Gram-negative bacterial strains. The ethyl acetate extract of Aspergillus flavus L exhibited an interesting antiviral activity with a half maximal inhibitory concentration (IC50) value of 27.2 µg/mL against HCoV 229E. Furthermore, in silico virtual molecular docking-coupled dynamics simulation highlighted the promising affinity of the identified metabolite, orienting towards three MRSA biotargets and HCoV 229E main protease as compared to reported reference inhibitors/substrates. Finally, ADME analysis was conducted to evaluate the potential oral bioavailability of the identified metabolites.

Untargeted metabolomics using UHPLC-Q-Orbitrap HRMS for identifying cytotoxic compounds on MCF-7 breast cancer cells from Annona muricata Linn leaf extracts as potential anticancer agents.

INTRODUCTION: The leaves of Annona muricata L., known as "soursop" or "sirsak" in Indonesia, are used traditionally for cancer treatment. However, the bioactive components remain largely unidentified. OBJECTIVE: This study used untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomics to identify potential cytotoxic compounds in A. muricata leaf extracts on MCF-7 breast cancer cells in vitro. METHODS: A. muricata leaves were macerated with water, 99% ethanol, and aqueous mixtures containing 30%, 50%, and 80% ethanol. Cytotoxic activity of the extracts against MCF-7 breast cancer cells was determined using the MTT assay. Ultra-high-performance liquid chromatography-Q-Orbitrap high-resolution mass spectroscopy (UHPLC-Q-Orbitrap-HRMS) was used to characterize the metabolite composition of each extract. The correlations between metabolite profile and cytotoxic activities were evaluated using orthogonal partial least square discriminant analysis (OPLS-DA). The binding of these bioactive compounds to the tumorigenic alpha-estrogen receptor (3ERT) was then evaluated by in silico docking simulations. RESULTS: Ninety-nine percent ethanol extracts demonstrated the greatest potency for reducing MCF-7 cell viability (IC50 = 22 µg/ml). We detected 35 metabolites in ethanol extracts, including alkaloids, flavonoids, and acetogenins. OPLS-DA predicted that annoreticuin, squadiolin C, and xylopine, and six unknown acetogenin metabolites, might reduce MCF-7 cell viability. In silico analysis predicted that annoreticuin, squadiolin C, and xylopine bind to 3ERT with an affinity comparable to doxorubicin. CONCLUSION: Untargeted metabolomics and in silico modeling identified cytotoxic compounds on MCF-7 cells and binding affinity to 3ERT in A. muricata leaf extracts. The findings need to be further verified to prove the screening results.

Storage and time course effects on the quality of oil extracted from Phyllanthus amarus Schumach and Annona muricata Linn and their antidiabetic potentials.

With the advent of modern technology, advancements in processing and storage techniques, and increasing medical knowledge, people are becoming aware of deterioration in the quality of medicinal products due to storage methods and time. In most cases, herbal products are not consumed immediately after production; as such, improper storage can result in physical, chemical, and microbiological changes. The study evaluated the effect of storage methods and time on the quality of oil extracted from Phyllanthus amarus Schumach and Annona muricata Linn and assessed their antidiabetic and antioxidative effects. Plants were air-dried, pulverized, and then subjected to Soxhlet extraction in petroleum ether. The oil was evaluated for phytochemical constituents and the effects of time and storage methods on its physicochemical properties. Characterization of the oil was done by spectroscopic techniques. Oils from both plants contained tannins, flavonoids, alkaloids, steroids, glycosides, terpenoids, phlobotannins, resins, reducing sugar, phenols, and saponins in different proportions. The oil from A. muricata had higher phenolic (3.11 ± 0.31 mg GAE/g), flavonoid (11.82 ± 0.08 mg QUE/g), alkaloid (16.37 ± 0.56 mg APE/g), and tannin (7.13 ± 0.47 mg CE/g) contents than the oil from P. amarus, which had 0.54 ± 0.08 mg GAE/g, 7.83 ± 0.13 mg QUE/g, 9.87 ± 0.15 mg APE, and 3.16 ± 0.12 mg CE/g for total phenolic, flavonoids, alkaloids, and tannins, respectively. Initial acid, iodine, peroxide, and saponification values recorded for P. amarus were 5.63 ± 0.82 mg KOH/g, 97.17 ±0.53 Wijis, 9.31 ± 0.15 mEq/kg, and 116.11 ± 0.74 mg KOH/g, respectively, significantly different from those of A. muricata , which had values of 1.17 ± 0.08 mg KOH, 76.23 ± 0.03 Wijis, 6.75 ± 0.47 mEq/kg, and 193.31 ± 0.52 mg KOH/g, respectively. FT-IR characterization of the oils revealed the presence of carboxylic acid, alkyl, alkene, alkane, haloalkane, aldehyde, aromatic amine, α-unsaturated and ß-unsaturated esters, and phenol functional groups. P. amarus oil inhibited α-amylase (IC50 0.17 ± 0.03 mg/ml), α-glucosidase (IC50 0.64 ± 0.03 mg/ml), and xanthine oxidase (0.70 ± 0.01 mg/ml) to a greater extent than A. muricata oil, with IC50 values of 0.43 ± 0.05 mg/ml (α-amylase), 2.25 ± 0.31 mg/ml (α-glucosidase), and 0.78 ± 0.07 mg/ml (xanthine oxidase). This study showed that oils from the tested plants have low rancidity with a moderate shelf life. The extracts contained essential phytoconstituents that significantly inhibited α-glucosidase and xanthine oxidase. These effects of the oil indicate their potential to prevent diabetes, gout, and oxidative stress. Consequently, the supply of P. amarus and A. muricata in homemade diets is strongly encouraged for healthy living.

Integrative phytochemical, ligand structure based drug design nephroprotective potential of Annona muricata flower-petals.

This study was aimed at investigating the ability of extract of Annona muricata (AM) flower-petals in ameliorating the toxic effects of acetaminophen on the kidneys of albino rats. The biochemical results showed a marked increase in AM 200 mg (32.84 ± 0.14) and AM 400 mg (32.64 ± 0.78). Increase levels of total protein in AM 200 mg (77.00 ± 5.65) displays nephroprotective potential of the flower extract. Reduction of renal activities of serum urea in AM 400 mg group (6.41 ± 0.22) indicates its protective potency against acetaminophen induced kidney damage. Increased activities of SOD levels at 200 mg (4.97 ± 0.05) and CAT levels at 200 mg (23.39 ± 1.13). This study showed that A. muricata has good prospects of being a nephroprotective drug candidate.

Hepatoprotective effects of leaf extract of Annona senegalensis against aflatoxin B1 toxicity in rats.

Global aflatoxin contamination of agricultural commodities is of the most concern in food safety and quality. This study investigated the hepatoprotective effect of 80% methanolic leaf extract of Annona senegalensis against aflatoxin B1 (AFB1)-induced toxicity in rats. A. senegalensis has shown to inhibit genotoxicity of aflatoxin B1 in vitro. The rats were divided into six groups including untreated control, aflatoxin B1 only (negative control); curcumin (positive control; 10 mg/kg); and three groups receiving different doses (100 mg/kg, 200 mg/kg, and 300 mg/kg) of A. senegalensis extract. The rats received treatment (with the exception of untreated group) for 7 days prior to intoxication with aflatoxin B1. Serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, and creatinine were measured. Hepatic tissues were analysed for histological alterations. Administration of A. senegalensis extract demonstrated hepatoprotective effects against aflatoxin B1-induced toxicity in vivo by significantly reducing the level of serum aspartate aminotransferase and alanine aminotransferase and regenerating the hepatocytes. No significant changes were observed in the levels of alkaline phosphatase, lactate dehydrogenase, and creatinine for the AFB1 intoxicated group, curcumin+AFB1 and Annona senegalensis leaf extract (ASLE)+AFB1 (100 mg/kg, 200 mg/kg, and 300 mg/kg body weight [b.w.]) treated groups. Annona senegalensis is a good candidate for hepatoprotective agents and thus its use in traditional medicine may at least in part be justified.Contribution: The plant extract investigated in this study can be used in animal health to protect the organism from toxicity caused by mycotoxins.

Safety assessment of crude aqueous methanol extract of Annona senegalensis stem bark: acute and sub-chronic toxicity studies.

Annona senegalensis Pers., (wild custard apple), is a shrub used traditionally to treat respiratory and skin diseases. Previous studies have demonstrated its anti-malaria, anti-snake envenomation and anti-cancer activities. However, its toxicological profile remains limited, particularly in male and female animals. This study aims to evaluate the safety of crude aqueous methanol extract of Annona senegalensis stem bark (AMEAS) through acute and sub-chronic toxicity studies. The stem bark of A. senegalensis was collected, air-dried, pulverized, and extracted using 70% methanol. Phytochemical screening, elemental analysis, and acute toxicity evaluation were carried out on AMEAS. Sub-chronic toxicity study was conducted on Wistar rats of both sexes at different doses administered orally for 28 days. Elemental analysis revealed the presence of heavy metals and essential mineral elements with the highest contents being calcium (59.88%) and potassium (25.39%). Acute toxicity testing showed no mortality up to 5000 mg/kg, suggesting an LD50 greater than 5000 mg/kg. In the sub-chronic toxicity study, no mortality or significant harmful effects were observed. The blood glucose decreased from 13.68 mMol/L at 250 mg/kg to 10.71 mMol/L at 1000 mg/kg, much lower than the distilled water group (17.06 mMol/L). In conclusion, the extract appeared to be well-tolerated, with no obvious adverse effects. AMEAS is rich in Calcium (Ca) and potassium (K). It has been shown to have LD50 greater than 5000 mg/kg and is assumed to be safe. On repeated use, AMEAS may cause hypoglycemia and weight loss which may be useful in managing diabetes and obesity respectively.

Exploring the antifungal potential of Annona muricata leaf extract-loaded hydrogel in treating vulvovaginal candidiasis.

Vulvovaginal candidiasis, mostly caused by Candida albicans, remains a prevalent concern in women's health. Annona muricata L. (Annonaceae), a plant native from Brazil, is well-known for its therapeutic potential, including antitumor, anti-inflammatory, and antimicrobial properties. This study presents an innovative hydrogel formulation containing the ethanolic extract from A. muricata leaves designed to control C. albicans in an in vivo model of vulvovaginal candidiasis. Here, we report the development, thermal, physicochemical and rheological characterization of a Carbopol®-based hydrogel containing A. muricata extract. Furthermore, we evaluated its activity in a vulvovaginal candidiasis in vivo model. Thermal analyses indicated that the addition of the extract increased the polymer-polymer and polymer-solvent interactions.Rheological analysis showed a decrease in the viscosity and elasticity of the formulation as the A. muricata extract concentration increased, suggesting a liquid-like behavior. After treatment with the Carbopol®-based hydrogel with A. muricata, our in vivo results showed a significant reduction in vulvovaginal fungal burden and infection, as well as a reduction in mucosal inflammation. The current research opens up possibilities for the application of the Carbopol®-based hydrogel with A. muricata as a natural therapeutic option for the treatment of vulvovaginal candidiasis.

Assessment of the changes in product characteristics, total ascorbic acid, total flavonoid content, total polyphenol content and antioxidant activity of dried soursop fruit tea (Annona muricata L.) during product storage.

Soursop (Annona muricata L.) fruit tea is a health-beneficial product that promotes economic development and addresses the issue of excessive agricultural waste. Prolonging the shelf-life of soursop fruit tea has been of scientific interest currently. This study evaluated the effects of three types of packaging materials of soursop fruit tea (e.g., paper, paper-combined Polyetylen (PE), and aluminum-combined PE) and different storage temperatures (5, 15, 30, and 45°C) on various product characteristics, total polyphenol content (TPC), total flavonoid content (TFC), total ascorbic acid (TAA), and 2,2-diphenyl-1-picryl hydrazyl (DPPH)/2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging capacity during 4 weeks of storage. The results revealed that the sample stored in aluminum-combined PE packaging at 30°C retained most of the product's characteristics and nutritional values. This was evidenced by the moisture content of 2.49%, TAA of 3.9 ± 1.4 mg/100 g dry weight, TPC of 12.89 ± 0.47 mgGAE/g, TFC of 0.54 ± 0.004 mgQE/g, DPPH scavenging activity of 4.06 ± 0.02 mgAA/g, and ABTS scavenging activity of 13.34 ± 0.32 mgAA/g. Additionally, the microbiological quality of the sample met the standard of TCVN 9740:2013. Overall, the study highlights the importance of packaging materials and storage temperatures to maintain the nutritional quality of soursop fruit tea. It provides valuable insights into the suitable storage conditions for preserving the quality and health-promoting effects of this product.

Araticum (Annona crassiflora Mart.): A critical review for the food industry.

This review aimed to critically and comparatively analyze the physicochemical, proximate, nutritional, phytochemical composition, and bioactivities of araticum (Annona crassiflora Mart.) (AAc), a fruit from the Brazilian Cerrado. Additionally, the potential applications of this fruit in the food industry were reviewed. Data and information were collected from the Scopus, Web of Science, and Google Scholar databases. AAc, a fruit mainly studied in the Brazilian regions of Minas Gerais and Goiás, has well-documented physicochemical, proximate, and nutritional characteristics. It is rich in fiber, sugars, vitamins A and C, minerals, and oil, making it attractive to the food industry. However, there are research gaps, such as the impact of climatic conditions on the AAc chemical composition. Additional studies are needed, especially for the peel and seeds, and investigations of pre-treatments effect on the chemical composition are recommended. The application of AAc in food products is mainly limited to pulp, but there is potential for using peels and seeds. AAc is a rich source of phytochemical compounds with various biological properties, such as antioxidants, hepatoprotective, and antimicrobial activities. Future studies should explore other phytochemicals present in the fruit beyond phenolic compounds. The consumption of AAc can contribute to combating food insecurity malnutrition, and promoting the conservation of the Brazilian Cerrado.

Pulp or Peel? Comparative Analysis of the Phytochemical Content and Selected Cosmetic-Related Properties of Annona cherimola L., Diospyros kaki Thumb., Cydonia oblonga Mill. and Fortunella margarita Swingle Pulp and Peel Extracts.

Fruit peels might be a valuable source of active ingredients for cosmetics, leading to more sustainable usage of plant by-products. The aim of the study was to evaluate the phytochemical content and selected biological properties of hydroglycolic extracts from peels and pulps of Annona cherimola, Diospyros kaki, Cydonia oblonga, and Fortunella margarita as potential cosmetic ingredients. Peel and pulp extracts were compared for their antiradical activity (using DPPH and ABTS radical scavenging assays), skin-lightening potential (tyrosinase inhibitory assay), sun protection factor (SPF), and cytotoxicity toward human fibroblast, keratinocyte, and melanoma cell lines. The total content of polyphenols and/or flavonoids was significantly higher in peel than in pulp extracts, and the composition of particular active compounds was also markedly different. The HPLC-MS fingerprinting revealed the presence of catechin, epicatechin and rutoside in the peel of D. kaki, whereas kaempferol glucoside and procyanidin A were present only in the pulp. In A. cherimola, catechin, epicatechin and rutoside were identified only in the peel of the fruit, whereas procyanidins were traced only in the pulp extracts. Quercetin and luteolinidin were found to be characteristic compounds of F. margarita peel extract. Naringenin and hesperidin were found only in the pulp of F. margarita. The most significant compositional variety between the peel and pulp extracts was observed for C. oblonga: Peel extracts contained a higher number of active components (e.g., vicenin-2, kaempferol rutinoside, or kaempferol galactoside) than pulp extract. The radical scavenging potential of peel extracts was higher than of the pulp extracts. D. kaki and F. margarita peel and pulp extracts inhibited mushroom and murine tyrosinases at comparable levels. The C. oblonga pulp extract was a more potent mushroom tyrosinase inhibitor than the peel extract. Peel extract of A. cherimola inhibited mushroom tyrosinase but activated the murine enzyme. F. margarita pulp and peel extracts showed the highest in vitro SPF. A. cherimola, D. kaki, and F. margarita extracts were not cytotoxic for fibroblasts and keratinocytes up to a concentration of 2% (v/v) and the peel extracts were cytotoxic for A375 melanoma cells. To summarize, peel extracts from all analyzed fruit showed comparable or better cosmetic-related properties than pulp extracts and might be considered multifunctional active ingredients of skin lightening, anti-aging, and protective cosmetics.

The American Cherimoya Genome Reveals Insights into the Intra-Specific Divergence, the Evolution of Magnoliales, and a Putative Gene Cluster for Acetogenin Biosynthesis.

Annona cherimola (cherimoya) is a species renowned for its delectable fruit and medicinal properties. In this study, we developed a chromosome-level genome assembly for the cherimoya 'Booth' cultivar from the United States. The genome assembly has a size of 794 Mb with a N50 = 97.59 Mb. The seven longest scaffolds account for 87.6% of the total genome length, which corresponds to the seven pseudo-chromosomes. A total of 45,272 protein-coding genes (≥30 aa) were predicted with 92.9% gene content completeness. No recent whole genome duplications were identified by an intra-genome collinearity analysis. Phylogenetic analysis supports that eudicots and magnoliids are more closely related to each other than to monocots. Moreover, the Magnoliales was found to be more closely related to the Laurales than the Piperales. Genome comparison revealed that the 'Booth' cultivar has 200 Mb less repeats than the Spanish cultivar 'Fino de Jete', despite their highly similar (>99%) genome sequence identity and collinearity. These two cultivars were diverged during the early Pleistocene (1.93 Mya), which suggests a different origin and domestication of the cherimoya. Terpene/terpenoid metabolism functions were found to be enriched in Magnoliales, while TNL (Toll/Interleukin-1-NBS-LRR) disease resistance gene has been lost in Magnoliales during evolution. We have also identified a gene cluster that is potentially responsible for the biosynthesis of acetogenins, a class of natural products found exclusively in Annonaceae. The cherimoya genome provides an invaluable resource for supporting characterization, conservation, and utilization of Annona genetic resources.

Targeting human inosine 5' monophosphate dehydrogenase type 2 for anti-dengue lead identification - a computational approach.

Dengue is a rapidly evolving arboviral disease that mainly affects tropical and subtropical regions of the world. The lack of therapeutic drugs and effective vaccines suggests that further resources need to be investigated. The effectiveness of the existing dengue vaccine is improbable as its efficacy depends on prior exposure to the dengue virus(DENV). Although the mechanism underlying the action of bioactive compounds to limit viral replication is less studied and still needs to be further explored, medicinal plants are excellent alternatives to combat DENV infection. In the current study, an in silico screening of phytochemicals from Annona reticulata Linn. against human Impdh2 was performed using Autodock Vina. Daucosterol (-9.0 kcal/mol) and Kaurenoic acid (-8.5 kcal/mol) were chosen as the top hits based on molecular interaction analysis. The hits were further exposed to pharmacokinetics and toxicity properties to determine their drug-like parameters. Molecular dynamics simulation studies of the Impdh2-top hits were carried out to investigate their kinetic behaviour and structural stabilities. The binding free energies of the Impdh2-hit complexes were determined using MM-PBSA analysis. According to the overall conclusions of the study, Daucosterol showed good binding affinity and high structural stability to the binding site residues of the target, therefore it is recommended as a lead compound against dengue.Communicated by Ramaswamy H. Sarma.

Silica/Annona muricata nano-hybrid: Synthesis and anticancer activity against breast cancer.

Biogenically derived silica nanoparticles may serve as a well-defined target vehicle for drug delivery and have a wide range of applications in biomedicine. Silica nanoparticles are an excellent candidate as drug carriers due to their mesoporous structure, high drug loading capacity, low toxicity, environmental friendliness and low economic synthesis procedures. In this study, nano structured silica was extracted from sugarcane bagasse through an alkali leaching extraction and conjugated with A. muricata extract overcoming its poor solubility and improving its bioavailability within the host system. The Silica Nanoparticles (SNP) and Annona muricata conjugated Silica Nanoparticles (AM/SNP) were characterized using SEM, FTIR, TGA, EDAX, XRD and zeta potential. The AM/SNP was subjected to kinetic release studies and exhibited a sustained release of 64 % over the course of 12 h in contrast to extract, indicating the slow release of the drug under synthetic conditions. A. muricata pose a high affinity against tumor cells as an anti-cancer agent, and the potential of binding was testified using in-silico virtual screening against breast cancer receptors with lead acetogenins with Annomuricin (-7.4 kcal/mol) and Gigantecin (-7.4 kcal/mol) exhibiting a high binding affinity against ER and HER2+ receptors respectively. The AM/SNP conjugate exhibited high cytotoxicity against the MCF-7 breast cancer cell line with an IC50 value of 33.43 µg, indicating high potency of the conjugate at low concentrations, facilitating low systemic toxicity on administration.

The effect of Annona muricata (Graviola) on the prevention of brain damage due to ionizing radiation in rats.

In this study, it was aimed to evaluate the effect of ethanol extract of Annona Muricata (AM) leaves in the prevention of brain damage caused by ionizing radiation (IR). This study was conducted in the Experimental Animal Research Unit of a university with 28 adults female Wistar Albino rats. The experimental groups were as follows: Control group (n = 8), AM group (n = 6), IR group (n = 8), AM + IR group (n = 6). In the IR group, astrocyte hypertrophy, microglial reaction and inflammatory reaction levels were significantly higher than the control and AM groups (P < 0.001). Edema was significantly higher in the IR group compared to the control group (P=0.001). The MDA of the IR group was significantly higher compared to the control group and AM group (P=0.031, P=0.006, respectively). The MDA of the AM + IR group was significantly higher than the AM group (P=0.039). Our findings show that histomorphology and oxidant damage caused by IR can be ameliorated using AM, as demonstrated by the comparison of the controls to AM + IR recipients, which showed similar histomorphology and oxidant damage levels.

Assessment of changes in product quality and antioxidant activity of dried soursop (Annona muricata L.) during product storage.

Innovations for product preservation have attracted interest as they may increase the shelf-life of items when stored properly. In this study, the effects of various storage conditions, including four types of packaging (paper packaging, paper combined PE packaging, aluminum combined PE packaging, and plastic jar packaging) and temperatures (5, 15, 30, and 45 °C) on the quality of dried soursop were evaluated. The results demonstrated that the combination of plastic jar packaging and a storage temperature of 15 °C retained a significant portion of the initial total ascorbic acid content, total polyphenol content, and total flavonoid content. After four weeks of storage, the dried soursop preserve packaged in a plastic jar and stored at 15 °C exhibited a moisture content of 22.977 ± 0.093 %, total ascorbic acid content of 9.7 ± 0.46 mg/100gDW, total polyphenol content of 8.12 ± 0.06 mgGAE/gDW, total flavonoid content of 0.18 ± 0.02 mgQE/gDW, DPPH and ABTS scavenging activity of 0.69 ± 0.01 mgAA/gDW and 0.82 ± 0.01 mgAA/gDW, respectively. Moreover, the product meets the requirements of decision 46/2007/QD-BYT regulating the limits on biological and chemical contamination in food. The study offers valuable insights for the food industry in optimizing packaging and storage conditions to ensure the storage of quality and health-beneficial properties of this product.

Comprehensive Tools of Alkaloid/Volatile Compounds-Metabolomics and DNA Profiles: Bioassay-Role-Guided Differentiation Process of Six Annona sp. Grown in Egypt as Anticancer Therapy.

Trees of the Annona species that grow in the tropics and subtropics contain compounds that are highly valuable for pharmacological research and medication development and have anticancer, antioxidant, and migratory properties. Metabolomics was used to functionally characterize natural products and to distinguish differences between varieties. Natural products are therefore bioactive-marked and highly respected in the field of drug innovation. Our study aimed to evaluate the interrelationships among six Annona species. By utilizing six Start Codon Targeted (SCoT) and six Inter Simple Sequence Repeat (ISSR) primers for DNA fingerprinting, we discovered polymorphism percentages of 45.16 and 35.29%, respectively. The comparison of the profiles of 78 distinct volatile oil compounds in six Annona species was accomplished through the utilization of GC-MS-based plant metabolomics. Additionally, the differentiation process of 74 characterized alkaloid compound metabolomics was conducted through a structural analysis using HPLC-ESI-MSn and UPLC-HESI-MS/MS, and antiproliferative activities were assessed on five in vitro cell lines. High-throughput, low-sensitivity LC/MS-based metabolomics has facilitated comprehensive examinations of alterations in secondary metabolites through the utilization of bioassay-guided differentiation processes. This has been accomplished by employing twenty-four extracts derived from six distinct Annona species, which were subjected to in vitro evaluation. The primary objective of this evaluation was to investigate the IC50 profile as well as the antioxidant and migration activities. It should be noted, however, that these investigations were exclusively conducted utilizing the most potent extracts. These extracts were thoroughly examined on both the HepG2 and Caco cell lines to elucidate their potential anticancer effects. In vitro tests on cell cultures showed a significant concentration cytotoxic effect on all cell lines (HepG2, HCT, Caco, Mcf-7, and T47D) treated with six essential oil samples at the exposure time (48 h). Therefore, they showed remarkable antioxidant activity with simultaneous cytotoxic effects. In total, 50% and 80% of the A. muricata extract, the extract with the highest migratory activity, demonstrated a dose-dependent inhibition of migration. It was strong on highly metastatic Caco cells 48 h after treatment and scraping the Caco cell sheet, with the best reduction in the migration of HepG2 cells caused by the 50% A. reticulata extract. Also, the samples showing a significant IC50 value showed a significant effect in stopping metastasis and invasion of various cancer cell lines, making them an interesting topic for further research.

Unveiling Annona Reticulata's Bioactive Arsenal for Enhanced Antibiotic Effects.

OBJECTIVE: To study the antibacterial and phytochemical activities of bioactive elements in the leaves of Annona reticulata Linn, a historically used Bangladeshi medicinal plant. METHODS: Shade-dried and crushed plant leaves were soaked with various solvents to obtain samples for different chemical analyses. All extracts were selected for antimicrobial, physicochemical, and Pharmacological investigations. The antimicrobial activity was evaluated using disc diffusion assay, and broth microdilution methods determined potentiation of the activities of the antibiotic antibacterial activity of the plant extracts was investigated using either gram-positive or gram-negative pathogenic wild-type bacteria. RESULTS: From the initial phytochemical and pharmacological studies, it was clear that all extracts, methanol, chloroform, and ethyl acetate, of the leaves of A. reticulata, were proven to process potent bioactive constituents. While differential antimicrobial properties were found to be possessed by all extracts, methanolic extract was the most potent one against all tested microorganisms. It also has potentiated the activities of antibiotics in E. coli. CONCLUSION: Bioactive constituents in the plant extracts were shown to possess phytochemical and antimicrobial activities. More investigation is needed to segregate the chemical components responsible for the respective phytochemical and antimicrobial activities.