Low-dose of phenolic rich extract from Annona squamosa Linn leaves ameliorates insulin sensitivity and reduces body weight gain in HF diet-induced obesity.

Obesity is associated with metabolic abnormalities that increase the risk and severity of several diseases. This study aimed to explore whether the aqueous extract of Annona squamosa Linn leaves (ASE) can ameliorate metabolic abnormalities associated with high fat (HF) diet-induced obesity. Forty-eight male Wistar rats were distributed among four treatment groups: a standard low-fat diet group, a HF diet group, and two HF diet groups with a daily oral dose of ASE (100 or 200 mg/kg body weights) administered for 9 weeks. Daily energy intake, body weight, blood glucose levels and glucose tolerance, and insulin tolerance were evaluated. At the end of the study, organs, and tissues were collected and weighed for analysis, and blood samples were collected to determine the serum insulin levels and serum liver enzymes. Total phenolic and flavonoid contents and 2,2-Diphenyl-1-picrylhydrazyl free radical antioxidant activity of the ASE were evaluated. Oral administration of the low dose of ASE to HF diet-fed rats significantly reduced the long-term food intake and body weight gain without altering adiposity compared with untreated HF diet-fed rats. This outcome was accompanied by a significant improvement in insulin sensitivity and a reduction in fasting blood glucose (FBG) levels measured at weeks 6 and 9 of the study. The high dose of ASE had a short-term effect on body weight gain and food and caloric intake, and in the long-term, it improved FBG levels measured at weeks 6 and 9 of the study. The high dose of ASE resulted in hyperinsulinemia and high homeostatic model assessment for insulin resistance (HOMA-IR) value compared to healthy rats. Total phenolic and flavonoid contents were 74.9 ± 0.491 mg of gallic acid equivalent and 20.0 ± 0.091 mg quercetin equivalent per g of ASE, respectively. The antioxidant activity of ASE expressed as half-maximal inhibitory concentration (IC50) value was 8.43 ± 0.825 mg/mL. These data suggest that ASE can safely and potently reduce the development of insulin resistance induced by HF diet feeding and lowering body weight gain in a dose-dependent manner.

The Molluscicidal Activity of Green Synthesized Copper Oxide-Based Annona squamosa Seed Extract Nanoparticles on the Feeding Behavior, Biochemical, Molecular, and Immunohistochemical Alterations of Biomphalaria alexandrina Snails.

Because of their low ecological impact, plant molluscicides have garnered much attention. The work aimed to find out if Annona squamosa (AS) seed extract has a molluscicidal impact on Biomphalaria alexandrina snails and enhances this extract by adding CuO nanoparticles (NPs). Using a scanning electron microscope (SEM), transmission electron microscope (TEM), and PANalytical X'Pert PRO X-ray diffractometer (XRD), the presence of the green A. squamosa-based CuO NPs (AS-CuO NPs) was confirmed. After 24 h of exposure, the half-lethal concentration (LC50) of AS-CuO NPs was more toxic to mature B. alexandrina than the aqueous extract of AS seeds (LC50: 119.25 mg/L vs. 169.03 mg/L). The results show that snails exposed to sublethal doses of AS-CuO NPs at LC10 or LC25 (95.4 or 106.7 mg/L, respectively) had much higher glucose levels and alkaline phosphatase activity than those not exposed. Nevertheless, there was no discernible change in the protein content in general or glycogen phosphorylase production. Histological and immunohistochemical analysis showed that snails exposed to A. squamosa-derived CuO NPs LC10 had shrinking digestive tubules and degeneration as well as vacuolation of many digestive, secretory, ova, and sperm cells, with PCNA expressing positively in the hermaphrodite gland and digestive tubule cells. The toxic profile of green CuO NPs produced by A. squamosa may damage the biological activity of B. alexandrina snails; thus, this compound could be used as a molluscicidal base. Furthermore, B. alexandrina proved to be a useful biomarker of nanomaterial contamination.

In Vitro Effect on Plasmodium falciparum and In Vivo Effect on Plasmodium berghei of Annomaal, an Oily Fraction Obtained from the Seeds of Annona squamosa.

Malaria remains a life-threatening health problem and is responsible for the high rates of mortality and morbidity in the tropical and subtropical regions of the world. The increasing threat of drug resistance to available artemisinin-based therapy warrants an urgent need to develop new antimalarial drugs that are safer, more effective, and have a novel mode of action. Natural plants are an excellent source of inspiration in searching for a new antimalarial agent. This research reports a systematic investigation for determining the antimalarial potential of the seeds of A. squamosa. The study shows that the crude seed extract (CSE), protein, saponin, and the oily fractions of the seeds were nontoxic at a 2000 mg/kg body weight dose when tested in Wistar rats, thus revealing high safety is classified as class 5. The oily fraction, Annomaal, demonstrated pronounced antimalarial activity with low IC50 (1.25 ± 0.183 µg/mL) against P. falciparum in vitro. The CSE and Annomaal significantly inhibited the growth of P. berghei parasites in vivo with 58.47% and 61.11% chemo suppression, respectively, while the standard drug artemether showed chemo suppression of 66.75%. Furthermore, the study demonstrated that oral administration of Annomaal at a daily dose of 250 mg/kg/day for 3 days was adequate to provide a complete cure to the P. berghei-infected mice. Annomaal thus holds promise as being patient-compliant due to the shorter treatment schedule, eliminating the need for frequent dosing for extended time periods as required by several synthetic antimalarial drugs. Further studies are needed to determine the active compounds in the oily fraction responsible for antimalarial activity.

A New Lignan from Annona squamosa L. (Annonaceae) Demonstrates Vasorelaxant Effects In Vitro.

Esquamosan, a new furofuran lignan, has been isolated by bio-guided assays from the methanolic extract of the leaves of Annona squamosa L., and its structure was elucidated by spectroscopic methods. Esquamosan inhibited the rat aortic ring contraction evoked by phenylephrine in a concentration-dependent manner and showed an inhibitory effect on vasocontraction of the depolarized aorta with high-concentration potassium. The vasorelaxant effect by esquamosan could be attributed mainly to the inhibition of calcium influx from extracellular space through voltage-dependent calcium channels or receptor-operated Ca2+ channels and also partly mediated through the increased release of NO from endothelial cells. The ability of esquamosan to modify the vascular reactivity of rat aortic rings incubated with high glucose (D-glucose 55 mM) was then evaluated, and this furofuran lignan reverted the endothelium-dependent impairment effect of high glucose in rat aortic rings. The antioxidant capacity of esquamosan was assessed using DPPH and FRAP assays. Esquamosan exhibited a similar antioxidant capacity compared to ascorbic acid, which was used as a positive control. In conclusion, this lignan showed a vasorelaxant effect, free radical scavenging capacity, and potential reductive power, suggesting its potential beneficial use to treat complex cardiometabolic diseases due to free radical-mediated diseases and its calcium antagonist effect.

Effect of Annona squamosa leaf extract on human promyelocytic leukemia cells subjected to oxidative stress.

OBJECTIVES: Annona squamosa has beneficial properties. However, its cytotoxicity and antioxidative effects on human promyelocytic leukemia cells (HL60) deserve investigation. Therefore, the efficacy of its crude extracts in offsetting damage in HL60 cells subjected to oxidative stress was studied. METHODS: Crude extracts at different concentrations were incubated with HL60 cells. The beneficial properties of the plant extract against oxidative damage were evaluated post-induction of oxidative stress utilizing hydrogen peroxide. RESULTS: Extracts at concentrations 600 and 800 µg/mL were most effective at increasing the viability of damaged cells compared to the control group after 48 h of incubation. Significant increases in lipid peroxidation were observed in exposed cells treated with 600 µg/mL extract after 72 h of incubation. Superoxide dismutase (SOD) and catalase activities significantly increased in exposed cells after 24 h of incubation at all extract concentrations. Exposed cells treated with 600 and 1,000 µg/dL of the extract showed significantly increased catalase activity after 48 h, and a similar profile was maintained after 72 h of exposure. SOD activity in exposed cells remained significantly increased at all treatment concentrations after 48 and 72 h of incubation. Treatment with 400, 600, and 800 µg/mL of the extract resulted in significantly increased reduced glutathione levels compared to the other groups after 24 and 72 h of incubation. However, after 48 h of incubation, significant increases were noted in glutathione levels in exposed cells incubated with either 400, 800, or 1,000 µg/mL extract. CONCLUSIONS: The findings suggest that A. squamosa might effectively protect against oxidative damage in a time and extract concentration-dependent manner.

Influence of methanolic extracts from seeds and pulp of Annona squamosa L. on osmotic and morphological fragility in human erythrocytes.

Medicinal plants have been used for many years by communities to treat illnesses. The need for scientific proof of these vegetable's curative effects is as necessary as the proof of the inexistence of toxicity related to the use of extracts with therapeutic potential. Annona squamosa L. (Annonaceae), popularly known as "pinha", "ata" or "fruta do conde", has been used in traditional medicine for its analgesic and antitumor activities. The toxic effects attributed to this plant have also been explored as a pesticide and an insecticide. The aim of the present study was to investigate the toxicity of the methanolic extract of A. squamosa seeds and pulp against human erythrocytes. Blood samples were treated with methanolic extract at different concentrations, osmotic fragility was determined using saline tension assays and morphological analyzes were performed using optical microscopy. The extracts were analyzed using high performance liquid chromatography with diode array detection (HPLC-DAD) for phenolic quantification. The seed's methanolic extract showed toxicity above 50% from a concentration of 100 µg/mL, while also presenting echinocytes in the morphological analysis. The pulp's methanolic extract did not show toxicity to red blood cells or morphological changes at the concentrations tested. HPLC-DAD analysis revealed the presence of caffeic acid in the seed extract and gallic acid in the pulp extract. The seed's methanolic extract is toxic and the pulp's methanolic extract showed no toxicity against human erythrocytes.

Management of Oral Squamous Papilloma Using Annona squamosa (Custard Apple) Leaves: A Novel Case.

This report presents the case of a 36-year-old male who was diagnosed with oral squamous papilloma in the palatal region. Excision was planned. The patient in the meantime chewed upon custard apple leaves and reported that the lesion prolapsed over the next few days. On examination, the site showed no signs of scarring or contracture and presented with healthy palatal tissue. The patient was prevented from requiring surgery, which would have shown a longer healing period with heavy reliance on an expensive resource base. This novel observation highlights the benefits of custard apple (Annona squamosa) leaves and warrants that its hepatoprotective, anticancer, antidiabetic, antioxidant, antibacterial, anti-obesity, and lipid-lowering properties are studied in an astute scientific setup with a well-drawn-out research plan.

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.

Antioxidant, Immunostimulant, and Growth-Promoting Effects of Dietary Annona squamosa Leaf Extract on Nile Tilapia, Oreochromis niloticus, and Its Tolerance to Thermal Stress and Aeromonas sobria Infection.

Plant extracts are a phytochemically-rich alternative to antibiotic and synthetic feed additives, with high systemic bioactivity in animals. The present study aimed to evaluate the effect of a hydroalcoholic extract of custard apple (Annona squamosa) leaf (ASLE) on the growth, hematobiochemical parameters, digestive enzyme activities, redox status, nonspecific immune response, and cold and bacterial infection tolerance in Nile tilapia (Oreochromis niloticus). A total of 300 Nile tilapia fingerlings (11.87 ± 0.48 g) were fed ASLE-supplemented diets at increasing levels of 0, 5, 10, 15, and 20 g/kg for 60 days. At the end of the feeding period, the fish were experimentally challenged with cold water stress or Aeromonas sobria, and mortalities were recorded for 10 days. The results revealed that the growth performance and feed conversion ratio were significantly improved with an increasing level of ASLE supplementation. The hematologic profile and hepato-renal functions were retained within a healthy range in the various groups supplemented with an ASLE diet. Antioxidant status was significantly improved in the serum of fish fed ASLE-supplemented diets, in terms of superoxide dismutase (SOD), catalase (CAT) activities, reduced glutathione, and total antioxidant capacity. Meanwhile, the myeloperoxidase (MPO) and malondialdehyde (MDA) levels decreased significantly. Similarly, there was a noticeable improvement in the hepatic CAT and SOD activities and a reduction of hepatic MDA. Marked improvements in lysozyme activity, nitric oxide production, complement3 level, and phagocytic activity were recorded in groups fed ASLE-supplemented diets, which peaked with the 20 g ASLE/kg diet. Moreover, the serum glucose and cortisol levels significantly declined in groups fed ASLE at levels of 15-20 g/kg compared to the other groups. Supplementation with ASLE increased the activities of protease, lipase, and α-amylase. ASLE supplementation at a concentration of 10-20 g/kg diet enhanced the resistance of Nile tilapia to A. sobria infection. According to this study, ASLE supplementation enhanced the antioxidant balance, non-specific immune response, physiological status, resistance against infection, and growth performance of Nile tilapia at supplementation levels of 10-20 g/kg diet.

Biogenic Synthesis of Fluorescent Carbon Dots (CDs) and Their Application in Bioimaging of Agricultural Crops.

Fluorescent nanoparticles have a transformative potential for advanced sensors and devices for point-of-need diagnostics and bioimaging, bypassing the technical burden of meeting the assay performance requirements. Carbon dots (CDs) are rapidly emerging carbon-based nanomaterials. Regardless of their fate, they will find increasing applications. In this study, a simple approach for synthesizing CDs from fruit peels was developed. The CDs were fabricated from Annona squamosa (L.) peels using a carbonization technique through microwave-assisted hydrothermal digestion at temperatures around 200 °C. Synthesized CDs were detected using a UV transilluminator for the preliminary confirmation of the presence of fluorescence. UV-Vis spectrophotometry (absorbance at 505 nm) analysis, zeta potential measurement (-20.8 mV), nanoparticles tracking analysis (NTA) (average size: 15.4 nm and mode size: 9.26 nm), photoluminescence, and Fourier transform infrared (FT-IR) analysis were used to identify the capping functional groups on the CDs. The total quantum yield exhibited was 8.93%, and the field emission scanning electron microscopy (FESEM) showed the size range up to 40 nm. The germinating mung bean (Vigna radiata (L.)) seeds were incubated with biogenically synthesized CDs to check the absorption of CDs by them. The fluorescence was observed under a UV-transilluminator in the growing parts of seeds, indicating the absorption of CDs during the germination, development, and growth. These fluorescent CDs could be used as a bioimaging agent. This novel method of synthesizing CDs was found to be eco-friendly, rapid, and cost-effective.

Artificial pollination and use of growth regulators in atemoya 'Gefner' fruits

The objective was to study the effectiveness of the growth regulator (ANA + GA3) associated or not to the application of adjuvant and artificial pollination in 'Gefner' atemoya. The experiment was conducted in the experimental orchard at Florida's Tropical Research and Education Center. The experimental design was in a randomized block, with 14 treatments, 10 repetitions and 3 flowers per plot. The highest percentages of fixed fruits were obtained with hand pollination ­ HP and 450 NAA + 1250 GA3 mg L-1 + adjuvant and HP. The use of hand pollination for 'Gefner' atemoya tree proved to be the most efficient method so far. Applying growth regulator without artificial pollination produces parthenocarpic fruits, however with high rate of abortions, and small fruits. Growth regulators together with hand pollination produces small and uneven fruits, and cause reduction in the fruits' titratable acidity. The use of adjuvant caused low fixation and toxicity to fruits, and its use is not recommended.

Inheritance of seedlessness and the molecular characterization of the INO gene in Annonaceae / Herança da ausência de sementes e a caracterização molecular do gene INO em Annonaceae

Abstract The inheritance of the seedless fruit characteristic of Annona squamosa has not yet been explained. Molecular techniques may aid breeding programs, mainly in the assisted selection of the target gene. The INO gene may be related to seed development in these fruits. The objective of the present paper was to investigate the inheritance of seedlessness in the 'Brazilian seedless' sugar apple and INO gene conservation in Annona squamosa and Annona cherimola x Annona squamosa genotypes by assessing their homology with the INO database genes. The F1 generation was obtained by crossing the mutant 'Brazilian seedless' (male genitor) (P1) with the wild-type A. squamosa with seeds (M1 and M2, female genitors). The INO gene was studied in mutant and wild-type A. squamosa (P1, M1, M2 and M3) and in the Gefner atemoya (A. cherimola x A. squamosa) (M4) cultivar. The DNA was extracted from young leaves, and four sets of specific primers flanking the INO gene were amplified. The seedless characteristic was identified as stenospermatic in the fruits of parental P1, suggesting monogenic inheritance with complete dominance. High sequence similarity of the INO gene amplifications in the sugar apple accessions (M1, M2, M3) and the atemoya cultivar Gefner (M4) reinforces the hypothesis of their conservation.

Resumo A herança da característica de fruto sem sementes de Annona squamosa ainda não foi esclarecida. Técnicas moleculares podem auxiliar em programas de melhoramento, principalmente na seleção assistida do gene de interesse. O gene INO pode estar relacionado ao desenvolvimento da semente dessas frutas. O objetivo foi investigar a herança da ausência de sementes em Annona squamosa e a conservação do gene INO nos genótipos Annona squamosa e Annona cherimola x Annona squamosa avaliando sua homologia com banco de dados de genes INO. A geração F1 foi obtida pelo cruzamento do mutante 'Brazilian seedless' (genitor masculino) (P1) com o tipo selvagem com sementes (A. squamosa) (M1 e M2, genitores femininos). O gene INO foi estudado em A. squamosa, mutante e selvagem (P1, M1, M2 e M3) e na cultivar Gefner atemoya (A. cherimola x A. squamosa) (M4). O DNA foi extraído de folhas jovens, e quatro conjuntos de primers específicos flanqueando o gene INO foram amplificados. A característica sem sementes foi identificada como estenospermática nos frutos do parental P1, sugerindo herança monogênica com dominância completa. A alta similaridade de sequência das amplificações do gene INO nos acessos de pinha (M1, M2, M3) e na cultivar de atemóia Gefner (M4) reforça a hipótese de sua conservação.

Inheritance of seedlessness and the molecular characterization of the INO gene in Annonaceae / Herança da ausência de sementes e a caracterização molecular do gene INO em Annonaceae

The inheritance of the seedless fruit characteristic of Annona squamosa has not yet been explained. Molecular techniques may aid breeding programs, mainly in the assisted selection of the target gene. The INO gene may be related to seed development in these fruits. The objective of the present paper was to investigate the inheritance of seedlessness in the 'Brazilian seedless' sugar apple and INO gene conservation in Annona squamosa and Annona cherimola x Annona squamosa genotypes by assessing their homology with the INO database genes. The F1 generation was obtained by crossing the mutant 'Brazilian seedless' (male genitor) (P1) with the wild-type A. squamosa with seeds (M1 and M2, female genitors). The INO gene was studied in mutant and wild-type A. squamosa (P1, M1, M2 and M3) and in the Gefner atemoya (A. cherimola x A. squamosa) (M4) cultivar. The DNA was extracted from young leaves, and four sets of specific primers flanking the INO gene were amplified. The seedless characteristic was identified as stenospermatic in the fruits of parental P1, suggesting monogenic inheritance with complete dominance. High sequence similarity of the INO gene amplifications in the sugar apple accessions (M1, M2, M3) and the atemoya cultivar Gefner (M4) reinforces the hypothesis of their conservation.

A herança da característica de fruto sem sementes de Annona squamosa ainda não foi esclarecida. Técnicas moleculares podem auxiliar em programas de melhoramento, principalmente na seleção assistida do gene de interesse. O gene INO pode estar relacionado ao desenvolvimento da semente dessas frutas. O objetivo foi investigar a herança da ausência de sementes em Annona squamosa e a conservação do gene INO nos genótipos Annona squamosa e Annona cherimola x Annona squamosa avaliando sua homologia com banco de dados de genes INO. A geração F1 foi obtida pelo cruzamento do mutante 'Brazilian seedless' (genitor masculino) (P1) com o tipo selvagem com sementes (A. squamosa) (M1 e M2, genitores femininos). O gene INO foi estudado em A. squamosa, mutante e selvagem (P1, M1, M2 e M3) e na cultivar Gefner atemoya (A. cherimola x A. squamosa) (M4). O DNA foi extraído de folhas jovens, e quatro conjuntos de primers específicos flanqueando o gene INO foram amplificados. A característica sem sementes foi identificada como estenospermática nos frutos do parental P1, sugerindo herança monogênica com dominância completa. A alta similaridade de sequência das amplificações do gene INO nos acessos de pinha (M1, M2, M3) e na cultivar de atemóia Gefner (M4) reforça a hipótese de sua conservação.

Inheritance of seedlessness and the molecular characterization of the INO gene in Annonaceae

Abstract The inheritance of the seedless fruit characteristic of Annona squamosa has not yet been explained. Molecular techniques may aid breeding programs, mainly in the assisted selection of the target gene. The INO gene may be related to seed development in these fruits. The objective of the present paper was to investigate the inheritance of seedlessness in the 'Brazilian seedless' sugar apple and INO gene conservation in Annona squamosa and Annona cherimola x Annona squamosa genotypes by assessing their homology with the INO database genes. The F1 generation was obtained by crossing the mutant 'Brazilian seedless' (male genitor) (P1) with the wild-type A. squamosa with seeds (M1 and M2, female genitors). The INO gene was studied in mutant and wild-type A. squamosa (P1, M1, M2 and M3) and in the Gefner atemoya (A. cherimola x A. squamosa) (M4) cultivar. The DNA was extracted from young leaves, and four sets of specific primers flanking the INO gene were amplified. The seedless characteristic was identified as stenospermatic in the fruits of parental P1, suggesting monogenic inheritance with complete dominance. High sequence similarity of the INO gene amplifications in the sugar apple accessions (M1, M2, M3) and the atemoya cultivar Gefner (M4) reinforces the hypothesis of their conservation.

Resumo A herança da característica de fruto sem sementes de Annona squamosa ainda não foi esclarecida. Técnicas moleculares podem auxiliar em programas de melhoramento, principalmente na seleção assistida do gene de interesse. O gene INO pode estar relacionado ao desenvolvimento da semente dessas frutas. O objetivo foi investigar a herança da ausência de sementes em Annona squamosa e a conservação do gene INO nos genótipos Annona squamosa e Annona cherimola x Annona squamosa avaliando sua homologia com banco de dados de genes INO. A geração F1 foi obtida pelo cruzamento do mutante 'Brazilian seedless' (genitor masculino) (P1) com o tipo selvagem com sementes (A. squamosa) (M1 e M2, genitores femininos). O gene INO foi estudado em A. squamosa, mutante e selvagem (P1, M1, M2 e M3) e na cultivar Gefner atemoya (A. cherimola x A. squamosa) (M4). O DNA foi extraído de folhas jovens, e quatro conjuntos de primers específicos flanqueando o gene INO foram amplificados. A característica sem sementes foi identificada como estenospermática nos frutos do parental P1, sugerindo herança monogênica com dominância completa. A alta similaridade de sequência das amplificações do gene INO nos acessos de pinha (M1, M2, M3) e na cultivar de atemóia Gefner (M4) reforça a hipótese de sua conservação.

Larvicidal property and active compound profiling of Annona squamosa leaf extracts against two species of diptera, Aedes aegypti and Anopheles stephensi.

Background & objectives: Vector control measures are important in lowering the spread of infections spread by mosquito. Synthetic pesticides used to suppress vector populations during the larval stage have had adverse impacts on people and the environment. The early III instar larvae of Aedes aegypti and Anopheles stephensi were the targets of the current experiment, which assessed the larvicidal ability of petroleum ether, chloroform, methanol, and aqueous extracts of Annona squamosa leaves. Methods: Using the standard World Health Organization (WHO) larval bioassay test, leaf extracts were evaluated for their activity against Ae. aegypti and An. stephensi to determine lethal doses. Phytochemical analysis and gas chromatography-mass spectrometry (GC-MS) were carried out to identify larvicidal components in the extract. Further analysis using a scanning electron microscope (SEM) was done to check the extracts toxicity for both mosquito larvae. Results: The larvicidal active components were identified by GC-MS as tetradecanoic acid, cis-vaccenic acid, and 2,4-di-tert-butylphenol etc. Methanol leaf extracts of A. squamosa (ASME) exhibited strong larvicidal activity against the early 3rd instar larvae of Ae. aegypti and An. stephensi with Lethal concentration (LC50) values of 51.450 ppm and 107.121 ppm. Cell damages to the larva post exposure to ASME were examined. Interpretation & conclusion: This finding showed that the ASME has better larvicidal activity and its components that may be used to kill larvae as larvicides. The extracts toxicity towards damage of midgut of larva further suggests that this plant methanol leaf extracts could be effective in larval growth control approaches.

An Integrative Approach to the Flavonoid Profile in Some Plants' Parts of the Annona Genus.

The Annonaceae family is widely distributed in subtropical and tropical regions. Several species of this family are known for their pharmacological and beneficial properties to human health, mainly attributed to flavonoids. The objective of this work was to carry out an integrative review in order to identify the main flavonoids found in some plant parts belonging to the Annona genus: araticum tree (Annona crassiflora Mart.), graviola tree (Annona muricata), atemoya tree (Annona cherimolia Mill × Annona squamosa L.), pinha tree (Annona squamosa), bananinha tree (Annona leptopetala), and marolinho tree (Annona coriacea). Only articles published between the years 2016 to 2021 that answered the guiding question were considered, in order to obtain recent data. Then, search strategies were designated for each database used: Science Direct, CAPES Periodicals, and Scielo. Most of the studies retrieved from the databases are related to fruits. The results showed that the number of flavonoids identified varies according to the analytical methodology used to identify and quantify the compounds. Quercetin was the most commonly found compound in all fruits of the Annona genus studied, and epicatechin, rutin, and kaempferol were also found to a lesser extent. The presence of these compounds in Annona makes the fruit promising, with potential applicability in the pharmaceutical and food industry.

Polyphenol-Rich Leaf of Annona squamosa Stimulates Insulin Release from BRIN-BD11 Cells and Isolated Mouse Islets, Reduces (CH2O)n Digestion and Absorption, and Improves Glucose Tolerance and GLP-1 (7-36) Levels in High-Fat-Fed Rats.

Annona squamosa, commonly known as custard apple, is traditionally used for the treatment of various diseases including diabetes, cardiovascular disease (CVD), and gastritis. This study was undertaken to investigate the effects of an ethanolic (80% v/v) extract of A. squamosa (EEAS) leaves in vitro on insulin secretion from clonal pancreatic BRIN BD11 ß-cells and mouse islets, including mechanistic studies on the effect of EEAS on membrane potential and intracellular calcium ion concentration. Additional in vitro glucose-lowering actions were assessed. For in vivo studies, high-fat-fed (HFF) obese/normal rats were selected. EEAS increased insulin secretion in vitro in a dose-dependent manner. This effect was linked to ß-cell membrane depolarisation and cytoplasmic Ca2+ influx. In the presence of isobutyl methylxanthine (IBMX), tolbutamide, or KCl, the insulin-releasing effect of EEAS was increased, suggesting its effect was also mediated via a KATP-independent pathways. EEAS inhibited insulin glycation, glucose absorption, and DPP-IV enzyme activity in vitro and enhanced glucose uptake and insulin action in 3T3L1 cells. In vivo, gut motility, food intake, glucose tolerance, plasma insulin, and active GLP-1 (7-36) levels were improved, whereas plasma DPP-IV levels were reduced in HFF rats. EEAS attenuated the absorption of sucrose and glucose as well as decreased serum glucose levels after sucrose loading and in situ intestinal perfusion in non-diabetic rats. Rutin, proanthocyanidin, and squafosacin G were putatively identified as the anti-hyperglycaemic phytomolecules in EEAS using HPLC followed by LC-MS analysis. This study illustrates the potential of A. squamosa and its phytoconstituents as a source of potential antidiabetic agents.

Three new cytotoxic annonaceous acetogenins from the seeds of Annona squamosa.

Three new annonaceous acetogenins, annotemoyin L (1), annotemoyin Y (2) and annotemoyin X, (3) were isolated from the seeds of Annona squamosa Linn. Their structures were ascertained by chemical methods and spectral data. The cytotoxic activities of compounds against three multidrug-resistant cancer cell lines were evaluated, and compound 3 exerted strong cytotoxicity against SMMC 7721/ADR (IC50 0.163 µM), A549/T (IC50 0.064 µM) and MCF-7/ADR (IC50 0.057 µM).

Evaluation of the skin protective effects of niosomal-entrapped annona squamosa against UVA irradiation.

Annona squamosa is a medicinal plant that has been used in folk medicine since antiquity. The goal of this study is to see how effective Annona squamosa leaf extract (A.S.L.E) or its niosomal-entrapped preparation is at protecting skin from UVA irradiation. The prepared niosomal-entrapped A.S.L.E has been characterized via spectrophotometry and transmission electron microscopy imaging. Furthermore, the entrapment efficiency and in vitro release of A.S.L.E were determined. In this study, ex vivo and freshly prepared samples from the dorsal region of the rats' skin were used as biological samples, which were divided into five groups: control UVA-unexposed, unprotected UVA-exposed, A.S.L.E-protected UVA-exposed, and niosomal-entrapped A.S.L.E UVA-exposed. UVA irradiation was performed by exposing the skin samples to a UVA-producing lamp for 4 h. Samples from various groups were then examined using FTIR spectroscopy, histopathology, and protein electrophoresis methods. The results showed that A.S.L.E has a skin protective effect against UVA irradiation. The niosomal-entrapped A.S.L.E was more effective than the native plant leaf extract in protecting skin from the damaging effects of UVA. Therefore, the nanotechnologically formulated preparation, niosomal-entrapped A.S.L.E, can be used as an effective photoprotector (sunscreen) against the adverse effects of UVA radiation.

Enhanced Solubility and Antitumor Activity of Annona Squamosa Seed Oil via Nanoparticles Stabilized with TPGS: Preparation and In Vitro and In Vivo Evaluation.

Annona squamosa seed oil (ASSO), which is a waste product in the extraction of annonaceous acetogenins (ACGs), displays good antitumor activity against a variety of tumor cells. However, ASSO is insoluble and has low bioavailability. In order to improve the solubility and application value of ASSO, the seed oil nanoparticles (ASSO-NPs) were successfully prepared only using TPGS as a stabilizer. ASSO-NPs obtained were spherical with a uniform size (less than 200 nm). ASSO-NPs showed the good storage stability at 25 ± 2 °C and were suitable for both oral administration and intravenous injection. The antitumor study in vitro and in vivo demonstrated more enhanced antitumor efficacy of ASSO-NPs than free ASSO. The ASSO-NPs group (15 mg/kg) had the highest tumor inhibition rate (TIR) of 69.8%, greater than the ASSO solution (52.7%, 135 mg/kg, p < 0.05) in 4T1 tumor-bearing mice. The in vivo biodistribution data displayed that the fluorescence intensity of ASSO/DiR-NPs in tumor was similar to that in liver in the presence of the reticuloendothelial system. Besides, the relative tumor-targeting index (RTTI) of (ACGs + ASSO)-NPs was 1.47-fold that of ACGs delivered alone, and there is great potential in ASSO-NPs as tumor-targeted delivery vehicles. In this study, ASSO-NPs were firstly prepared by a very simple method with fewer excipients, which improved the solubility and antitumor activity of the ASSO, displaying a good prospect in the in vivo delivery of natural bioactive compounds.