Annona Muricata Fruit Research Articles

Molecular Docking and Dynamics Study of Acetogenins Targeting Cyclin-dependent Kinase and In vitro Evaluation of Annona Muricata Fruit Extracts using MDA-MB-231 Breast Cancer Cell Line

Background: Overexpressed CDK1 and CDK2 are targeted as potential sites for cancer treatment. Annona muricata fruit has been reported to have more than 100 acetogenins showing cytotoxic activities against cancer cell lines. Hence the study aims to demonstrate the cytotoxicity of ethyl acetate fruit extract, its role in cell cycle progression, and apoptosis using the MDMBA-231 breast cancer cell line. Docking, dynamics, and ADME studies were also demonstrated to generate lead molecules of AM fruit responsible for cancer treatment. Method: Cell viability was quantified by the MTT assay. Cell cycle arrest and apoptotic cells were determined by flow cytometry and PI annexin V-FITC staining by flow cytometry, respectively. Molecular docking, molecular dynamics, and ADME properties of 11 acetogenins were studied using the schrödinger maestro suite 2018-1. Results: The MTT assay revealed IC50 232.9μg/ml with a high degree of cytotoxicity. The extract effectively caused cell cycle arrest at the G2M and S phases; early and late apoptosis was induced at 160 μg/ml and 320 μg/ml. Docking scores of muricin L, J, and annomuricin A complexed with CDK2 and muricin J, K, and L with CDK1 binding energy ranging is mentioned as a molecular dynamic study envisaged muricin j against CDK2 stable hydrogen and hydrophobic interactions with critical residues like ASP-86, GLN-131, HIS-84, LYS-89, PHE80, PHE82, and PHE83 throughout 200 ns (hinge region). ADMET profiling also confirmed that all 11 ligands passed the rule of 5 and 3. The in vitro and in silico studies revealed that these acetogenins could be CDK1 and CDK2 inhibitors for cancer treatment. Conclusion: The in vitro studies presume that the ethyl acetate fruit extract of AM is an excellent cytotoxic agent. In silico studies demonstrated that muricin j could lead molecules to target kinase proteins responsible for cell proliferation. ADME study enlightened us to take 11 acetogenins for the drug discovery process in managing cancer treatment.

Oral Safety Evaluation of the Aqueous Fruit Extract of Annona Muricata in Wistar Rats

Annona muricata fruit (i.e. Soursoup or custard apple a tropical plant species known for its edible fruit)has been attributed with numerous medicinal benefits (including antimicrobial, anti-inflammatory, anti-protozoan, antioxidant, anxiolytic, anti-stress, anti-ulcerogenic, wound healing, hepato-protective, anti-icteric, hepatoprotective, anticancer and antihyperglycemic activities) as well as some toxicological effects (neurotoxicity and neurodegeneration). Despite its ancestral use and wide applications in human health, scientific information on its oral safety remains scanty. In this study, the oral safety of 100 mg/kd/day, 200 mg/kg/day and 400 mg/kg/day of the aqueous fruit extract of Annona Muricata (AFAM) was evaluated in young adult, male and female white albino Wistar rats using standard acute and 42-days sub-chronic oral toxicity testing guidelines on anthropometric, biochemical, hematological and histo-pathological endpoints. In addition, preliminary qualitative and quantitative analyses of AFAM were undertaken using standard procedures. Results of the study showed that the estimated LD50 value for the acute oral toxicity study of AFAM calculated to be greater than 5 g/kg body weight/oral route although the testing was associated with transient but reversible behavioral toxicities. For its sub-chronic oral toxicity testing, AFAM treatment resulted in profound %weight gain, decreases in the serum triglycerides and very low density lipoprotein cholesterol and liver enzymes. Similarly, prolonged oral AFAM treatments caused significant decrease and increase in the differential neutrophils and platelet counts, respectively while the hist-opathological features of hepatic steatos is and renal tubule collapse in the AFAM-treated livers and kidneys, respectively suggested possible increased intrahepatic lipids biosynthesis and nephrotoxicity. The preliminary phytochemical analyses of AFAM showed the presence and relative amount of flavonoids, alkaloids, tannin, glycosides, saponin, and reducing sugars while the Gas Chromatography-Mass spectroscopy showed the relative abundance of thirteen compounds. Composite analyses conducted on the extract showed the presence of carbohydrate (64.65%), protein (2.14%), moisture content (8.07%), ash value (6.73%), lipid (14.22%) and fiber (4.19%). Overall, the study suggested that the prolonged AFAM oral treatments could predispose to the development of fatty liver disease from de novo intrahepatic biosynthesis of triglycerides, nephrotoxicity and hematotoxicity. In conclusion, the results of this study showed that prolonged consumption of AFAM should be with a great caution as it could pose serious health concerns.

Bioactive phytochemicals in Annona muricata fruit juice ethanol extract

Phytochemical contents of Annona muricata fruit juice ethanol extract was determined using gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC). Lyophilized fruit juices were extracted in 10 % v/v aqueous solution of ethanol at 60 0C in a water bath. The GC-MS screening of the extract revealed the concentrations (mg/ml) of thirty-three (33) phytochemicals which included glycerine (9.12), levoglucosenone (5.18), 1,3-propanediol-2-(hydroxymethyl)-2-nitrobenzene (11.83) and D- allose (7.28), benzofuran-2,3-diydro-(1.87), 3,7,11,15-tetramethyl-2-hexadecen-1-ol (1.52), Cis-11,14-Eicosadienoic acid, methyl ester (1.53), 9-Octadecenoic acid, methyl ester (1.68), 2-Methoxy-4-vinylphenol (1.69), which are reported to exhibit various biological activities. The HPLC analyses of the extract revealed various polyphenolic compounds (mg/ml) such as naringenin (12.97), proanthocyanin (0.23), tannin (44.17), coumaric acid (4.12), catechin (39.20), resveratrol (42.27) and kaempferol (29.86). which also possess various health benefits like antibacterial, antifungal, anti-inflammatory, anticancer, antimutagenic, antioxidant, antitumor, and others. It can be concluded that the Annona muricata fruit juice ethanol extract contained bioactive phytochemicals that exhibit promising health-promoting activities.

Histopathological Effect of Annona Muricata Fruit Extract on Methyl nitrosourea -Induced Mammary Gland Carcinoma in Female Albino Mice

The Annona muricata (Family-Annonaceae) fruit contain annonaceous acetogenins which have an effect on cancer cell as reported in many research studies. This study was aimed to evaluate the effect of methanolic fruit extract of Annona muricata (MFEAM) on breast cancer histology and invasive cell of MNU-induced breast cancer mice. Fifty female albino mice were divided into five groups (of ten each): control; MNU-induced breast cancer; MNU-induced breast cancer + (MFEAM) 200 mg/kg, MNU-induced breast cancer + (MFEAM) 300 mg/kg and MNU-induced breast cancer + (MFEAM) 500 mg/kg. The research indicates that breast cancer invasive ductal carcnoma (IDC) developed in the MNU-induced breast cancer group. The control group showed normal duct structure. The (MFEAM) -treated group showed lower invasive (DCIS) compared with the untreated cancer group. We concluded that (MFEAM), that improved the histological changes of breast cancer-induced MNU. Also (MFEAM) reduced proliferative epitheal cell of breast cancer-induced MNU and the most effective dose was 300 mg/kg. The present study concluded that the methanol extracts derived from Annona muricata fruit potentially exhibit antitumor activity. The control group showed normal duct structure. The (MFEAM) -treated group showed lower invasive (DCIS) compared with the untreated cancer group, We concluded (MFEAM) that improved the histological changes of breast cancer-induced MNU. Also (MFEAM) reduced proliferative epitheal cell of breast cancer-induced MNU and the most effective dose in 300 mg/kg.

Green synthesis of selenium nanoparticles using Annona muricata fruit extract and its free radical scavenging activities

Green synthesis of selenium nanoparticles using Annona muricata fruit extract and its free radical scavenging activities

Silver Nanoparticles from Annona muricata Peel and Leaf Extracts as a Potential Potent, Biocompatible and Low Cost Antitumor Tool.

Cancer is one of the most prevalent diseases in the world and requires new therapies for its treatment. In this context, the biosynthesis of silver nanoparticles (AgNPs) has been developed to treat different types of tumors. The Annona muricata plant is known for having anticancer activity. Its main compounds present in the leaves, stems and skin, allowing for its use as reducing agents. In this manuscript, AgNPs with leaf extract (AgNPs-LE) and fruit peel extract (AgNPs-PE) of A. muricata were biosynthesized obtaining an average nanoparticle diameter sizes smaller than 50 nm, being 19.63 ± 3.7 nm and 16.56 ± 4.1 nm, and with a surface plasmonic resonance (SPR) at 447 and 448 nm, respectively. The lactone functional group present in the LE and PE extracts was identified by the FTIR technique. The behavior and antiproliferation activity of AgNPs-LE and AgNPs-PE were evaluated in breast, colon and melanoma cancer cell lines. Our results showed that Annona muricata fruit peel, which is a waste product, has an antitumor effect more potent than leaf extract. This difference is maintained with AgNPs where the destruction of cancer cells was, for the first time, achieved using concentrations that do not exceed 3 μg/mL with a better therapeutic index in the different tumor strains. In conclusion, we present a low-cost one-step experimental setup to generate AgNPs-PE whose in-vitro biocompatibility and powerful therapeutic effect make it a very attractive tool worth exploiting.

Anticancer Activity of Acetogenins from Annona Muricata Fruit

Medicinal plants become very important in our days for their therapeutic benefits to humankind. It sustains human health, and it is commonly known as herbal medicines since ancient times. Annona muricata is a heart-shaped fruit that is consumed raw or as the fruit juice in the tropical area. A. muricata is used in traditional and alternative medicine to treat different ailments such as diabetes, hypertension, respiratory and skin illness, inflammation and cancer. A. muricata contains essential anticancer agents named acetogenins that play the significant role in various cancer types. Acetogenins are strong nicotinamide adenine dinucleotide oxidase inhibitors of the cancer cell's mitochondrial membrane but showed neurotoxic effects in rats. Therefore, acetogenins need to be further investigated to determine the exact mechanisms of action, long-term safety, optimal dosage, and potential side effects. Given the extensive studies on A. muricata, this review focuses on the phytochemistry, medicinal uses, biological activities and the mechanisms of action for the fruit extracts and acetogenins, to stimulate further studies on the fruit pulp used for human consumption.

Evaluating the Anticancer Potentials of Methanol Extracted Annona muricata Fruit Pulp and Seed(s) Phytochemicals

Annona muricata L. has been widely used in traditional medicine for the treatment of various diseases ranging from fever to cancer. In this study, we evaluate the in vitro anticancer potential of methanol extracted A. muricata fruit pulp (AMPM) and seeds (AMSM) phytochemicals against breast (MCF-7), cervical (HeLa), prostate (PC-3) and colorectal (HCT-116) cancer cell lines. Additionally, the in vitro antiinflammatory and antioxidant activities of the extracts have been carried. The findings suggest that the AMSM is the most potent among the either extracts. Notwithstanding, both AMPM and AMSM showed significant dose and cell line-dependent anticancer potential(s).

Solid lipid nanoparticles of Annona muricata fruit extract: formulation, optimization and in vitro cytotoxicity studies

The present study was aimed to develop Annona muricata fruit extract loaded solid lipid nanoparticles (SLNs) and explore its cytotoxic potential in vitro model of breast cancers. Extract loaded SLNs were successfully prepared by high-pressure homogenization followed by ultrasonication method and optimized using 23 full factorial design. The extract loaded SLNs were characterized using different parameters such as particle size (PS), % entrapment efficiency (EE), zeta potential (ZP) and % cumulative drug release (CDR). The SLNs formulation was optimized on the basis of software analysis with an overall desirability factor. The PS and %EE of the optimized formulation were found to be 134.8 nm and 83.26%, respectively. The optimized formulation showed a CDR of 79.83% up to 48 h. In vitro cytotoxicity efficacy of extract loaded SLNs was determined using MTT and Apoptosis assay and compared to that of a free extract. The SLNs showed a notable apoptotic effect and better efficacy to kill MCF7 cancer cells as compared to free extract. Thus, extract loaded SLNs could be an alternative dosage form which possibly controls therapeutic action with reducing side effect.

Annona muricata fruit extract protects against diethylnitrosamine-induced hepatocellular cancer in rats

Objective: To evaluate the anticancer potentials of Annona muricata fruit by in vitro and in vivo methods. Methods: The ethanolic extract of Annona muricata fruit was prepared by Soxhlet extraction method and further fractionated with petroleum ether, ethyl acetate and chloroform. The fractions were tested for cytotoxicity, apoptosis, scratch wound assay, and cell cycle analysis. IC50, apoptotic index and percentage cell migration were determined using HepG2 cells. For the in vivo studies, hepatocellular carcinoma was induced by administering 0.01% diethylnitrosamine (DEN) in drinking water in Wistar rats. In pre-treatment, rats were co-administered 200 mg/kg of fruit extract with DEN for 14 weeks. In post-treatment, the extract was co-administered after 8-weeks of DEN-induction for 14 weeks. Liver function test, haematological test, oxidative stress markers, relative liver weight, number of cancer nodules and histopathological parameters were determined. Results: Annona muricata fruit extract =significantly lowered cell proliferation counts. The chloroform-fraction possessed higher activity [IC50=(53.7±4.3) μg/mL]. The chloroform fraction inhibited cell migration, which was significant compared to curcumin. Further investigations regarding the mode of anticancer activity revealed that the chloroform fraction induced apoptosis. The cell cycle analysis indicated that cells were being arrested at G0/G1. In the in vivo studies, the DEN-control group showed a significant decrease in body weights with increased mortality rate, hepatic nodules, and impairment of liver function compared to normal rats. The rats pre-treated and post-treated with the extract showed positive results with significant improvement in the parameters that were adversely affected by DEN. In addition, other adverse effects of DEN, such as blood dyscrasias and hepatic endogenous antioxidant, were significantly attenuated by Annona muricata fruit extract. Conclusions: The Annona muricata fruit extract has anticancer activity when tested by in vitro and in vivo hepatocellular cancer models.

Protective potentials of Annona muricata fruit pulp on etoposide-induced gastrointestinal toxicity in Wistar rats.

BACKGROUND:Mucositis, one of the devastating consequences of chemotherapy and also limits the efficacy of the treatment. At present, there are no antimucositic agents without side effects. Hence, there is a need for better adjuvant therapy using plant or food sources. Here, we have made an attempt to study the effect of Annona muricata (AM) fruit pulp on etoposide-induced mucositis.MATERIALS AND METHODS:The study was conducted at Central Research Laboratory, Kasturba Medical College, Mangalore. The effect of AM fruit pulp (100 mg and 200 mg/kg body weight) on etoposide-induced mucositis was studied in Wistar rats (n = 36) in comparison with normal and AM controls. Intestinal tissue was collected for histology and estimation of total antioxidants (TAO), glutathione (GSH), myeloperoxidase (MPO), and nitric oxide (NO) levels along with histological changes were studied. Statistical analysis was performed by one-way analysis of variance.RESULTS:TAO and GSH levels were found to be significantly high in the rats which received 200 mg of AM/kg body weight than 100 mg of AM/kg body weight when compared with etoposide control. The levels of inflammatory markers - MPO and NO - were found to be decreased (P < 0.001) in the animals received 200 mg/kg body weight of AM in comparison with etoposide group and lower dosage of AM pulp. Histology of intestine also showed a protective effect of AM (200 mg/kg body weight) against etoposide toxicity.CONCLUSION:The results show that AM fruit pulp has the capacity to act as antimucositic agent and also reduced inflammation.

Isolation of annonacous acetogenins from Annona muricata fruit and their anti proliferative activity on human prostate cancer cell PC-3

The fruit of Annona muricata is an edible and medicinal tropical fruit and commonly available in local markets. The previous work was continued, bioassay-guided fractionation of the fruit powder of A. muricata yielded three more novel bioactive compounds: C-35 annonaceous acetogenins, muricins M and N, and C-37 annonaceous acetogenins, muricenin. They all contain a mono-tetrahydrofuran ring and four hydroxyl groups. The structures were elucidated by spectral methods and chemical modification after isolation via open column chromatographic separation and HPLC purification. Especially, murices M and N demonstrated more potent anti-proliferative activities against human prostate cancer PC-3 cells.