Modification of the physicochemical, functional, biochemical and structural properties of a soursop seed (Annona muricata L.) protein isolate treated with high-intensity ultrasound.

The obtained seeds from fruit processing are considered by-products containing proteins that could be utilized as ingredients in food manufacturing. However, in the specific case of soursop seeds, their usage for the preparation of protein isolates is limited. In this investigation a protein isolate from soursop seeds (SSPI) was obtained by alkaline extraction and isoelectric precipitation methods. The SSPI was sonicated at 200, 400 and 600 W during 15 and 30 min and its effect on the physicochemical, functional, biochemical, and structural properties was evaluated. Ultrasound increased (p < 0.05) up to 5 % protein content, 261 % protein solubility, 60.7 % foaming capacity, 30.2 % foaming stability, 86 % emulsifying activity index, 4.1 % emulsifying stability index, 85.4 % in vitro protein digestibility, 423.4 % albumin content, 83 % total sulfhydryl content, 316 % free sulfhydryl content, 236 % α-helix, 46 % ß-sheet, and 43 % ß-turn of SSPI, in comparison with the control treatment without ultrasound. Furthermore, ultrasound decreased (p < 0.05) up to 50 % particle size, 37 % molecular flexibility, 68 % surface hydrophobicity, 41 % intrinsic florescence spectrum, and 60 % random coil content. Scanning electron microscopy analysis revealed smooth structures of the SSPI with molecular weights ranging from 12 kDa to 65 kDa. The increase of albumins content in the SSPI by ultrasound was highly correlated (r = 0.962; p < 0.01) with the protein solubility. Improving the physicochemical, functional, biochemical and structural properties of SSPI by ultrasound could contribute to its utilization as ingredient in food industry.

Influence of intensity ultrasound on rheological properties and bioactive compounds of araticum (Annona crassiflora) juice.

The use of extracts rich in bioactive compounds is becoming increasingly common in the food, cosmetics, and pharmaceutical industries for the production of functional products. Araticum is a potential fruit to be analyzed due to its content of phenolic compounds, carotenoids and vitamins, with antioxidant properties. Therefore, this study aimed to investigate the effect of ultrasound on total phenolic compounds, total carotenoids, ascorbic acid, color, turbidity and rheology in araticum juice. Response surface methodology based on a central composite design was applied. Araticum juice was subjected to sonication at amplitude levels ranging from 20 to 100 % of the total power (400 W) at a constant frequency of 20 kHz for different durations (2 to 10 min). Morphological analysis was conducted to observe microscopic particles, and viscosity and suitability to rheological models (Newtonian, Power Law, and Herschel-Bulkley) were assessed. The ultrasonic probe extraction method was compared to the control juice. According to the responses, using the desirability function, the optimal conditions for extraction were determined to be low power (low amplitude) applied in a short period of time or low power applied in a prolonged time. These conditions allowed an ultrasonic probe to act on releasing bioactive compounds without degrading them. All three rheological models were suitable, with the Power Law model being the most appropriate, exhibiting non-Newtonian pseudoplastic behavior.

Cytotoxic naphtho- and benzofurans from an endophytic fungus Epicoccum nigrum Ann-B-2 associated with Annona squamosa fruits.

Chemical exploration of the total extract derived from Epicoccum nigrum Ann-B-2, an endophyte associated with Annona squamosa fruits, afforded two new metabolites, epicoccofuran A (1) and flavimycin C (2), along with four known compounds namely, epicocconigrone A (3), epicoccolide B (4), epicoccone (5) and 4,5,6-trihydroxy-7-methyl-1,3-dihydroisobenzofuran (6). Structures of the isolated compounds were elucidated using extensive 1D and 2D NMR along with HR-ESI-MS. Flavimycin C (2) was isolated as an epimeric mixture of its two diastereomers 2a and 2b. The new compounds 1 and 2 displayed moderate activity against B. subtilis, whereas compounds (2, 3, 5, and 6) showed significant antiproliferative effects against a panel of seven different cancer cell lines with IC50 values ranging from 1.3 to 12 µM.

Antimutagenic and antitumor activities of a water-soluble fraction of soursop (syn Graviola, Annona muricata L.) fruit pulp.

Soursop (Annona muricata) is a tropical tree whose decoction derived from bark, root, seed, or leaf has been used for medicinal uses. In addition, the fruit itself is considered a food, and the juice is utilized to treat heart and liver diseases. The aim of this study was to determine the phenolic content. In addition, a water-soluble fraction of the soursop fruit pulp (WSSP) was examined for the following properties: antioxidant, mutagenic, and antimutagenicity. UV-visible spectrophotometry determined total phenolic content by the Folin-Ciocalteu method to be 11.22 ± 0.6 mg of gallic acid equivalent per gram dried extract, and free-radical scavenging activity by the 2,2'-diphenyl-1-picryl-hydrazyl (DPPH•) showed an EC50 of 1032 µg/ml. In the Salmonella/microsome assay, no marked mutagenicity was induced following WSSP treatment, and a chemopreventive capacity was observed in the antimutagenic assay. The cytotoxicity assays were carried out using the water-soluble tetrazolium salt and lactate dehydrogenase (LDH) assays demonstrated that WSSP induced significant cytotoxicity in MCF-7 and Caco-2 cells, indicating greater effectiveness of cytotoxic action by destroying cell membrane integrity. Data suggest that WSSP may exert beneficial effects as a DNA chemopreventive and antitumor agent.

Overcoming multi drug resistance mediated by ABC transporters by a novel acetogenin- annonacin from Annona muricata L.

ETHNOPHARMACOLOGICAL RELEVANCE: Multi-Drug Resistance (MDR), mediated by P-glycoprotein (P-gp) is one of the barriers to successful chemotherapy in colon cancer patients. Annona muricata L. (A.muricata), commonly known as soursop/Graviola, is a medicinal plant that has been traditionally used in treating diverse diseases including cancer. Phytochemicals of A.muricata (Annonaceous Acetogenins-AGEs) have been well-reported for their anti-cancer effects on various cancers. AIM OF THE STUDY: The study aimed to examine the effect of AGEs in reversing MDR in colorectal cancer cells. METHODS: Based on molecular docking and molecular dynamic simulation, the stability of annonacin upon P-gp was investigated. Further in vitro studies were carried in oxaliplatin-resistant human colon cancer cells (SW480R) to study the biological effect of annonacin, in reversing drug resistance in these cells. RESULTS: Molecular docking and simulation studies have indicated that annonacin stably interacted at the drug binding site of P-gp. In vitro analysis showed that annonacin was able to significantly reduce the expression of P-gp by 2.56 folds. It also induced apoptosis in the drug-resistant colon cancer cells. Moreover, the intracellular accumulation of P-gp substrate (calcein-AM) was observed to increase in resistant cells upon treatment with annonacin. CONCLUSION: Our findings suggest that annonacin could inhibit the efflux of chemotherapeutic drugs mediated by P-gp and thereby help in reversing MDR in colon cancer cells. Further in vivo studies are required to decipher the underlying mechanism of annonacin in treating MDR cancers.

LCMS/MS Phytochemical Profiling, Molecular, Pathological, and Immune-Histochemical Studies on the Anticancer Properties of Annona muricata.

Annona muricate is a tropical plant that is well-known for its edible fruit of therapeutic interest. LCMS/MS analyses were applied to identify phytoconstituents of the ethanolic extract of the whole fruits and the aqueous extract of the edible fruit part, in addition to the investigation of their anticancer properties against Ehrlich ascites carcinoma (EAC) in male albino mice. LCMS/MS analyses resulted in the identification of 388 components, representing a wide array of classes of compounds, including acetogenins as the major constituents, alkaloids, flavonoids, and phenolics. Among them, four compounds were tentatively characterized as new compounds (1-4), including an acid derivative, protocatechuic-coumaroyl-quinic acid (1), and three flavonoid derivatives, dihydromyricetin galloyl hexoside (2), apigenin gallate (3), and dihydromyricetin hexouronic acid hexoside (4). Induction with EAC cells resulted in abnormalities in the gene expression of pro-apoptotic genes (Bax and caspase-3) and anti-apoptotic gene (Bcl-2) in the tumor mass. Moreover, microscopic, histopathological, and immune-histochemical examinations of the tumor mass and liver tissues exhibited extensive growth of malignant Ehrlich carcinoma cells and marked hydropic degeneration of hepatocytes and infiltration by tumor cells to liver tissue with marked inflammatory reaction. These abnormalities were markedly ameliorated aftertreatment of EAC mice with A. muricata extracts.

Application of effect-directed analysis using TLC-bioautography for rapid isolation and identification of antidiabetic compounds from the leaves of Annona cherimola Mill.

INTRODUCTION: Type 2 diabetes mellitus is a globally prevalent chronic disease characterised by hyperglycaemia and oxidative stress. The search for new natural bioactive compounds that contribute to controlling this condition and the application of analytical methodologies that facilitate rapid detection and identification are important challenges for science. Annona cherimola Mill. is an important source of aporphine alkaloids with many bioactivities. OBJECTIVE: The aim of this study is to isolate and identify antidiabetic compounds from alkaloid extracts with α-glucosidase and α-amylase inhibitory activity from A. cherimola Mill. leaves using an effect-directed analysis by thin-layer chromatography (TLC)-bioautography. METHODOLOGY: Guided fractionation for α-glucosidase and α-amylase inhibitors in leaf extracts was done using TLC-bioassays. The micro-preparative TLC was used to isolate the active compounds, and the identification was performed by mass spectrometry associated with web-based molecular networks. Additionally, in vitro estimation of the inhibitory activity and antioxidant capacity was performed in the isolated compounds. RESULTS: Five alkaloids (liriodenine, dicentrinone, N-methylnuciferine, anonaine, and moupinamide) and two non-alkaloid compounds (3-methoxybenzenepropanoic acid and methylferulate) with inhibitory activity were isolated and identified using a combination of simple methodologies. Anonaine, moupinamide, and methylferulate showed promising results with an outstanding inhibitory activity against both enzymes and antioxidant capacity that could contribute to controlling redox imbalance. CONCLUSIONS: These high-throughput methodologies enabled a rapid isolation and identification of seven compounds with potential antidiabetic activity. To our knowledge, the estimated inhibitory activity of dicentrinone, N-methylnuciferine, and anonaine against α-glucosidase and α-amylase is reported here for the first time.

An evaluation of the quality of Annona muricata leaf products.

OBJECTIVES: Annona muricata, also known as graviola, is traditionally used for the treatment of a range of disorders including cancer. Interest in A. muricata use has increased in recent years. This study investigated the quality and safety of a selection of commercially available A. muricata leaf products. METHODS: Seven commercially available products were purchased via online shopping sites. Each product was assessed for quality indicators including weight variation, quantification of the bioactive constituent annonacin, presence of annonaceous acetogenins and contaminants. The samples were evaluated by thin-layer chromatography, high-performance liquid chromatography, liquid chromatography-mass spectroscopy, low-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Microbial analysis was carried out in accordance with the British Pharmacopoeia. Heavy metals were analysed by inductive coupled plasma mass spectrometry. KEY FINDINGS: Of the seven products analysed, one product contained less than half of the content stated on the label. The labelled dosage recommendation varied between products. There was a high variation in annonacin concentration (1.05-3.09 mg/g) and the presence of annonaceous acetogenins. One of the products was found to have a total aerobic microbial count above the United States Pharmacopoeia limit. CONCLUSIONS: The variation in the indicators of quality and safety of commercially available A. muricata leaf products tested have implications for clinicians and people living with cancer who use these herbal products.

Evaluation of Antimalarial Activity of Ethanolic Extract of Annona muricata L.: An in vivo and an in silico Approach.

In Nigeria, Annona muricata L. has been used to treat a variety of ailments. The mechanism of the antimalarial activity of ethanolic leaf extract of Annona muricata (EEAML) was investigated using both an in vivo and an in silico approach. The experimental mice were divided into five groups: A-F. The mice in groups B-F were inoculated with Plasmodium berghei NK-65 and treated accordingly. Groups A and B are the negative and positive controls (infected and untreated), respectively. Group C received 10 mg/kg chloroquine (standard drug), whereas groups D-F received 100, 200, and 300 mg/kg body weight of the extract orally respectively. The mice were euthanized eight days after infection, and their liver and blood were collected and used in biochemical tests. Molecular docking was performed using the extract's HPLC compounds and Plasmodium falciparum proteins. In the suppressive, prophylactic, and curative tests, there was a significant decrease (p < 0.05) in parasitemia levels in groups treated with the extract compared to the positive control and standard drug. When compared to the positive control, there was a significant (p < 0.05) reduction in liver MDA, total cholesterol, and total triglyceride levels. The binding energies of luteolin and apigenin-pfprotein complexes were significantly (p < 0.05) higher compared to their respective references. The anti-plasmodial activity of the extract may result from its hypolipidemic effect, which deprives the parasite of essential lipid molecules needed for parasite growth, as well as from the inhibitory effects of apigenin and luteolin on specific proteins required for the Plasmodium metabolic pathway.

Investigation of the chemical structure and analgesic and anti-inflammatory properties of polysaccharides that constitute the dietary fibers of soursop (Annona muricata) fruit.

Soursop fruits are widely used in the folk medicine to treat a variety of health conditions. Once the chemical structure of dietary fibers from fruits is closely related to its biological functions in the human body, we aimed to explore structural features and biological activity of dietary fibers from soursop. Polysaccharides that constitute the soluble and insoluble fibers were extracted and further analyzed using monosaccharide composition, methylation, molecular weight determination and 13C NMR data. Soursop soluble fibers (SWa fraction) were characterized as having type II arabinogalactan and a highly methyl esterified homogalacturonan, while non-cellulosic insoluble fibers (SSKa fraction) were mainly composed by a pectic arabinan, a xylan-xyloglucan complex and a glucuronoxylan. The oral pre-treatment with SWa and SSKa promoted antinociception in mice writhing test, reducing the number of pain-like behaviors (in 84.2 % and 46.9 %, respectively, at 10 mg/kg) and peritoneal leucocyte migration (55.4 % and 59.1 %, at 10 mg/kg), effects possibly associated with the pectins present in fruit pulp extractions. SWa also significantly inhibited the plasmatic extravasation of Evans blue dye in 39.6 % at 10 mg/kg. This paper describes for the first time the structural features of soursop dietary fibers that may be of biological significance in future.

Green Synthesis of Fluorescent Carbon Dots from Annona squamosa Leaves: Optical and Structural Properties with Bactericidal, Anti-inflammatory, Anti-angiogenesis Applications.

A hydrothermal method was employed for green synthesis of fluorescent carbon dots (GCDs) from Annona squamosa leaves. The synthesized GCDs were confirmed by microscopic and spectroscopic techniques such as: High Resolution Transmission Electron Microscopy (HR-TEM), Atomic Force Microscopy (AFM), UV-Vis spectrometry, Fluorescence spectrometry, X-Photoelectron Spectroscopy (XPS), X-ray Diffraction spectroscopy (XRD), and Fourier Transform Infrared Spectroscopy (FTIR). The produced GCDs had shown multiple properties, including massive antibacterial activity at concentration 200 µg/ml. The stabilization of human red blood cells served as a method to assess the anti-inflammatory activity. We also looked at how GCDs affected the angiogenesis process. The density of blood vessels was significantly decreased after treatment with GCDs, according to the results of the Chorio-Allantoic Membrane assay (p < 0.05). As per the study prepared GCDs from fallen leaves of Annona squamosa have multifunctional applications.

GC/MS Analysis, Cytotoxicity, and Antiviral Activities of Annona glabra Hexane Extract Supported by In Silico Study.

Annona glabra Linn is employed in conventional medicine to treat a number of human disorders, including cancer and viruses. In the present investigation, the significant phytochemical components of Annona glabra hexane extract were identified using gas chromatography-mass spectrometry (GC-MS) analysis. Three major compounds were identified in the hexane extract: tritriacontane (30.23%), 13, 17-dimethyl-tritriacontane (22.44%), and limonene (18.97%). MTT assay was used to assess the cytotoxicity of the extract on six human cancer cell lines including liver (HepG-2), pancreas (PANC-1), lung (A-549), breast (MCF-7, HTB-22), prostate (PC-3), and colon (CACO-2, ATB-37). The extract exhibited significant cytotoxic activity against both CACO-2 and A-549 cancer cell lines (IC50 = 47 ± 0.74 µg/mL and 56.82 ± 0.92 µg/mL) in comparison with doxorubicin (IC50 = 31.91 ± 0.81 µg/mL and 23.39 ± 0.43 µg/mL) and of SI of 3.8 and 3.1, respectively. It also induced moderate-to-weak activities against the other cancerous cell lines: PC-3, PANC-1, MCF-7, and HepG-2 (IC50 = 81.86 ± 3.26, 57.34 ± 0.77, 80.31 ± 4.13, and 57.01 ± 0.85 µg/mL) in comparison to doxorubicin (IC50 = 32.9 ± 1.74, 19.07 ± 0.2, 15.48 ± 0.84 and 5.4 ± 0.22 µg/mL, respectively) and SI of 2.2, 3.1, 2.2, and 3.1, respectively. In vitro anti-HSV1 (Herpes simplex 1 virus) and HAV (Hepatitis A virus) activity was evaluated using MTT colorimetric assay with three different protocols to test protective, anti-replicative, and anti-infective antiviral activities, and three separate replications of each experiment were conducted. The plant extract showed promising protective and virucidal activity against HSV1 with no significant difference with acyclovir (79.55 ± 1.67 vs. 68.44 ± 7.62 and 70.91 ± 7.02 vs. 83.76 ± 5.67), while it showed mild protective antiviral activity against HAV (48.08 ±3.46) with no significant difference vs. acyclovir (36.89 ± 6.61). The selected main compounds were examined for their bioactivity through in silico molecular docking, which exhibited that limonene could possess the strongest antiviral properties. These findings support Annona glabra's conventional use, which is an effective source of antiviral and anticancer substances that could be used in pharmaceuticals.

Identification of Annonaceous Acetogenins and Alkaloids from the Leaves, Pulp, and Seeds of Annona atemoya.

Annonaceae is a large family composed of more than 119 genera and more than 2500 species that are distributed in both tropical and subtropical areas. The Annona genus is a member of Annonaceae family, which encompasses about 175 species, most of which are native to Brazil and tropical America. This plant is commonly found on tropical and subtropical continents. Annona atemoya is a commercially important hybrid of A. squamosa and A. cherimola. Phytochemical investigations of A. atemoya leaves, fruit, and seeds have been conducted in limited studies. The purpose of this study was to investigate the constituents of the leaves, fruit pulp, and seeds of A. atemoya because few studies have reported their constituents. Annonaceous acetogenins were identified in the leaves and pulp of A. atemoya for the first time. Twenty compounds were identified: sixteen were acetogenins and four were alkaloids. Additionally, two compounds were isolated, and their structures were confirmed by spectroscopic analysis and compared with the results of previous studies. The concentration of acetogenins in the pulp was very low compared with that in the leaves, whereas the seeds were found to contain the highest concentrations and greatest diversity of compounds.

The inhibitory and anticancer properties of Annona squamosa L. seed extracts.

Although Annona squamosa Linn. (Annonaceae) has been used in traditional medicine and is known to have several pharmacological properties, its impact on EGFR kinase has not been fully investigated. An assay (biochemical) was used to govern the potential of different A. squamosa seed extracts to scavenge free radicals in petroleum ether, acetone, ethanol, and methanol. We also tested A. squamosa leaf extracts for their ability to inhibit the growth of HEK 293, MCF7, and HepG2 cell lines. The PSE, ASE, ESE, and MSE all contained anti-cancer substances like anethole, cyclopentane, 1,1,3-trimethyl, and phosphonate oxide tributyl, according to phytochemical analysis. ESE extracts from A. squamosa seeds have been selected based on free radical generation probabilities, cytotoxicity studies, and phytochemical analysis. Subsequent insilico studies have been conducted, and the results have shown that interactions between compounds present in ESE extracts and the EGFR kinase are what give these compounds their inhibitory effects. Preliminary phytochemical and pharmacological activities were studied and reported. A. squamosa ESE extracts inhibited the growth of MCF7 cells, and a pharmacokinetic study showed that the compounds anethole, cyclopentane, 1,1,3-trimethyl, and phosphonium oxide tributyl had few undesirable side effects. These substances can be used to both prevent and treat cancer diseases.

New ent-kaurene-type nor-diterpene and other compounds isolated from Annona vepretorum Mart. (Annonaceae).

A new nor-ent-kaurene diterpene and ten other compounds were isolated from Annona vepretorum stems, including four kaurene diterpenes, three alkamides, one sesquiterpene and two steroids. Their chemical structures were elucidated using spectroscopic methods, including 1D-, 2D-NMR, and HRESIMS. The absolute configuration of compounds 1, 5, 8, 9 and 10 was confirmed by CD experiments. Compounds 1-5 and 8-10 were evaluated for cytotoxic activity using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT method, against three human carcinoma cell lines: human colon (HCT-116), glioblastoma (SF295) and prostate (PC3). However, all isolated compounds exhibited low cytotoxic activity.

Antifungal Annona muricata L. (soursop) extract targets the cell envelope of multi-drug resistant Candida albicans.

ETNOPHARMACOLOGICAL RELEVANCE: Annona muricata L. (soursop) is traditionally used in the treatment of inflammatory diseases, cancer, and infections caused by fungi. The therapeutic activity explored by its medicinal use is generally associated with its phytoconstituents, such as acetogenins and alkaloids. However, its potential antifungal bioactivity as well as its mechanism of action remains to be established. AIM OF THE STUDY: To evaluate the antifungal activity of the ethanolic extract of A. muricata leaves against multidrug-resistant Candida albicans (ATCC® 10231). MATERIAL AND METHODS: Phytoconstituents were detected by UFLC-QTOF-MS. The minimum inhibitory concentration was determined, followed by the determination of the minimum fungicidal concentration. For planktonic cells, the growth curve and cell density were evaluated. Studies to understand the mechanism of action on the cell envelope involved crystal violet permeability, membrane extravasation, sorbitol protection, exogenous ergosterol binding assay, metabolic activity, and cell viability. Furthermore, mitochondrial membrane potential was assessed. RESULTS: Our analyses demonstrated a significant inhibitory effect of A. muricata, with the ability to reduce fungal growth by 58% and cell density by 65%. The extract affected both the fungal plasma membrane and cell wall integrity, with significant reduction of the cell viability. Depolarization of the fungal mitochondrial membrane was observed after treatment with A. muricata. Rutin, xi-anomuricine, kaempferol-3O-rutinoside, nornuciferine, xylopine, atherosperminine, caffeic acid, asimilobine, s-norcorydine, loliolide, annohexocin, annomuricin, annopentocin, and sucrose were identified as extract bioactive components. CONCLUSIONS: Our findings show that the A. muricata extract is a source of chemical diversity, which acts as a potential antifungal agent with promising application to the therapy of infections caused by C. albicans.

Anonazepine, a new alkaloid from the leaves of Annona muricata (Annonaceae).

From the CHCl3-soluble extract of Annona muricata L. (Annonaceae) leaves, one new 3-benzazepine-type alkaloid, anonazepine (1), and four known aporphine-type alkaloids, (+)-laurotetanine (2), (+)-norglaucine (3), (-)-xylopine (4), and lanuginosine (5), were isolated. Except for (-)-xylopine (4), these remaining known alkaloids were first reported in A. muricata. The structures of the isolated alkaloids were established by 1D and 2D NMR spectroscopy and MS, as well as comparison with literature data. The new 3-benzazepine-type alkaloid existed in an inseparable mixture of two equilibrium conformers. Its absolute configuration was determined based on comparing their experimental and calculated ECD data. The anti-inflammatory activity of the isolated alkaloids was investigated, but none of the alkaloids showed a significant result.

Ecological linkages between biotechnologically relevant autochthonous microorganisms and phenolic compounds in sugar apple fruit (Annona squamosa L.).

Our study investigated the potential of Annona squamosa (L.) fruit as a reservoir of yeasts and lactic acid bacteria having biotechnological implications, and phenolics capable of modifying the ecology of microbial consortia. Only a single species of lactic acid bacteria (Enterococcus faecalis) was identified, while Annona fruit seemed to be a preferred niche for yeasts (Saccharomyces cerevisiae, Hanseniaspora uvarum), which were differentially distributed in the fruit. In order to identify ecological implications for inherent phenolics, the antimicrobial potential of water- and methanol/water-soluble extracts from peel and pulp was studied. Pulp extracts did not show any antimicrobial activity against the microbial indicators, while some Gram-positive bacteria (Staphylococcus aureus, Staphylococcus saprophyticus, Listeria monocytogenes, Bacillus megaterium) were susceptible to peel extracts. Among lactic acid bacteria used as indicators, only Lactococcus lactis and Weissella cibaria were inhibited. The chemical profiling of methanol/water-soluble phenolics from Annona peel reported a full panel of 41 phenolics, mainly procyanidins and catechin derivatives. The antimicrobial activity was associated to specific compounds (procyanidin dimer type B [isomer 1], rutin [isomer 2], catechin diglucopyranoside), in addition to unidentified catechin derivatives. E. faecalis, which was detected in the epiphytic microbiota, was well adapted to the phenolics from the peel. Peel phenolics had a growth-promoting effect toward the autochthonous yeasts S. cerevisiae and H. uvarum.

Estudo comparativo dos perfis fitoquímicos e citotóxicos do extrato alcoólico de folhas de graviola (annona muricata) e fruta do conde (annona squamosa) / Comparative study of the phytochemical and cytotoxic profiles of the alcoholic extract of soursop (annona muricata) and custard apple (annona squamosa) leaves / Estudio comparativo de los perfiles fitoquímicos y citotóxicos del extracto alcohólico de hojas de guanábana (annona muricata) y del conde (annona squamosa)

Introdução: As plantas apresentam potencial medicinal devido aos metabólitos secundários e possuem compostos com alto potencial anti-inflamatório, com possibilidades terapêuticas. Das espécies vegetais de interesse destacamos e comparamos a graviola (Annona muricata) e a fruta do conde (Annona squamosa). Objetivo: Comparar o potencial do extrato alcoólico bruto de folhas da graviola e fruta do conde em ensaios fitoquímicos e citotóxicos. Método: Os extratos de folhas de graviola e fruta do conde foram obtidos por percolação, com o uso de 20g de folhas secas e trituradas com 100 ml de álcool de cereais. Na padronização dos extratos foram utilizadas análises de idenficação de componentes químicos, os taninos, flavonoides, saponinas e alcaloides, por meio de difrentes reações químicas e os antioxidantes foram analisados pela atividade do DPPH. A citotoxicidade das diferentes concentrações dos extratos também foram analisadas por hemólise e pelo teste da membrana corioalantide (CAM). Resultados: As análises fitoquímicas indicaram a presença de alcaloides, taninos, flavonoides e saponinas para ambos os extratos com alta capacidade antioxidante. Os testes de hemólise e CAM mostraram ausência de citotoxicidade na concentração de 2% e 4% para ambos os extratos e elevada citotoxicidade em 10% para o extrato de graviola. Conclusão: O extrato alcoólico das folhas da graviola e fruta do conde mostraram importante perfil antioxidante e com compostos anti-inflamatórios com pouca diferença entre os extratos o que estimula estudos futuros e continuidade para exploração anti-inflamatória.

Introduction: Plants have medicinal potential due to secondary metabolites and have compounds with high antiinflammatory potential, with therapeutic possibilities. Of the plant species of interest we highlight and compare the graviola (Annona Muricata) and the fruit of the count (Annona squamosa). Objective: To compare the potential of crude alcoholic extract of soursop and conde fruit leaves in phytochemical and cytotoxic assays. Method: The leaves extracts of soursop and fruit of the count were obtained by percolation, with the use of 20g of dry leaves and crushed with 100 ml of grain alcohol. In the standardization of the extracts were used idenfication analyzes of chemical components, tannins, flavonoids, saponins and alkaloids, through different chemical reactions and antioxidants were analyzed by the activity of DPPH. The cytotoxicity of the different concentrations of the extracts were also analyzed by hemolysis and by the corioalantide membrane test (CAM). Results: Phytochemical analysis indicated the presence of alkaloids, tannins, flavonoids and saponins for both extracts with high antioxidant capacity. The hemolysis and CAM tests showed absence of cytotoxicity at the concentration of 2% and 4% for both extracts and high cytotoxicity in 10% for graviola extract. Conclusion: The alcoholic extract of the leaves of soursop and fruit of the count showed important antioxidant profile and with anti-inflammatory compounds with little difference between the extracts which stimulates future studies and continuity for anti-inflammatory exploration.

Introducción: Las plantas tienen potencial medicinal debido a los metabolitos secundarios y poseen compuestos con alto potencial antiinflamatorio, además de ser utilizadas en tratamientos terapéuticos. De las especies vegetales de interés, destacamos y comparamos la guanábana (Annona muricata) y la fruta del conde (Annona squamosa). Objetivo: Comparar el potencial del extracto alcohólico crudo de hojas de guanábana y chirimoya en ensayos fitoquímicos y citotóxicos. Método: El extracto de hojas de guanábana y fruta del conde se obtuvo por percolación, utilizando 20g de hojas secas y trituradas con 100 ml de alcohol de grano. En la estandarización de los extractos se utilizaron análisis para identificar componentes químicos, taninos, flavonoides, saponinas y alcaloides, a través de diferentes reacciones químicas y los antioxidantes fueron analizados por la actividad de DPPH. También se analizó la citotoxicidad de diferentes concentraciones de extractos por hemólisis y por la prueba de membrana de corioalantida (CAM). Resultados: Los análisis fitoquímicos indicaron la presencia de alcaloides, taninos y flavonoides y saponinas para ambos extractos con alta capacidad antioxidante. Las pruebas de hemólisis y CAM mostraron ausencia de citotoxicidad a una concentración del 4% y alta citotoxicidad a partir del 10% también para ambos extractos. Conclusión: El extracto alcohólico de hojas de guanábana y chirimoya mostró importantes perfiles antioxidantes y con compuestos antiinflamatorios, lo que estimula futuros estudios y continuidad para la exploración antiinflamatoria.

Understanding the Antilymphoma Activity of Annona macroprophyllata Donn and Its Acyclic Terpenoids: In Vivo, In Vitro, and In Silico Studies.

Annona macroprophyllata Donn (A. macroprophyllata) is used in traditional Mexican medicine for the treatment of cancer, diabetes, inflammation, and pain. In this work, we evaluated the antitumor activity of three acyclic terpenoids obtained from A. macroprophyllata to assess their potential as antilymphoma agents. We identified the terpenoids farnesyl acetate (FA), phytol (PT) and geranylgeraniol (Gg) using gas chromatography-mass spectroscopy (GC-MS) and spectroscopic (1H, and 13C NMR) methods applied to petroleum ether extract of leaves from A. macroprophyllata (PEAm). We investigated antitumor potential in Balb/c mice inoculated with U-937 cells by assessing brine shrimp lethality (BSL), and cytotoxic activity in these cells. In addition, to assess the potential toxicity of PEAm, FA, PT and Gg in humans, we tested their acute oral toxicity in mice. Our results showed that the three terpenoids exhibited considerable antilymphoma and cytotoxic activity. In terms of lethality, we determined a median lethal dose (LD50) for thirteen isolated products of PEAm. Gg, PT and AF all exhibited a higher lethality with values of 1.41 ± 0.42, 3.03 ± 0.33 and 5.82 ± 0.58 µg mL-1, respectively. To assess cytotoxic activity against U-937 cells, we calculated the mean cytotoxic concentration (CC50) and found that FA and PT were closer in respect to the control drug methotrexate (MTX, 0.243 ± 0.007 µM). In terms of antilymphoma activity, we found that FA, PT and Gg considerably inhibited lymph node growth, with median effective doses (ED50) of 5.89 ± 0.39, 6.71 ± 0.31 and 7.22 ± 0.51 mg kg-1 in females and 5.09 ± 0.66, 5.83 ± 0.50 and 6.98 ± 0.57mg kg -1 in males, respectively. Regarding acute oral toxicity, we classified all three terpenoids as category IV, indicating a high safety margin for human administration. Finally, in a molecular docking study of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, we found binding of terpenoids to some amino acids of the catalytic site, suggesting an effect upon activity with a resulting decrease in the synthesis of intermediates involved in the prenylation of proteins involved in cancer progression. Our findings suggest that the acyclic terpenoids FA, PT, and Gg may serve as scaffolds for the development of new treatments for non-Hodgkin's lymphoma.