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Annona muricata has been attributed with numerous health benefits – including anticancer properties. The aim of this study was to carry out anticancer. Annona muricata L. (A. muricata) is a species of the Annonaceae family that has been . The increasingly popular use of A. muricata as an anticancer treatment. Extensive anticancer investigations have been conducted on A. muricata due to its reported ethnomedicinal uses against.

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The use of anti-inflammatory natural products to treat inflammatory disorders for cancer prevention and therapy is an appealing area of interest in the last decades. Different parts of A. Some of these experience-based claims on the use of the plant have been transformed into evidence-based information by scientific investigations.

The leaves of the plant have been extensively investigated for its diverse pharmacological aspects and found eminent for anti-inflammatory and anticancer properties.

However, most studies were not on the bioactive isolates which were responsible for the activities but were based on crude extracts of the plant. In this comprehensive review, all significant findings from previous investigations till date on the leaves of A. The toxicology of the plant which has been shown to be due to the presence of neurotoxic annaceous acetogenins and benzyltetrahydro-isoquinoline alkaloids has also been updated to provide recent information on its safety aspects. The present knowledge of the plant has been critically assessed, aimed at providing direction toward improving its prospect as a source of potential anti-inflammatory and anticancer agents.

The analysis will provide a new path for ensuring research on this plant to discover new agents to treat inflammatory diseases and cancer. Further in vitro and in vivo studies should be carried out to explore the molecular mechanisms underlying their anti-inflammatory responses in relation to anticancer activity and more detail toxicity study to ensure they are safe for human consumption.

Sufficient preclinical data and safety data generated will allow clinical trials to be pursued on this plant and its bioactive compounds. Inflammation, owing to central element of innate immunity and inflammatory response serve as a protective mechanism emerged in higher animals in order to defend them against injury and infection. In reaction to any tissue damage, a multifactorial network of chemical signals is initiated in the human body which keep the host body response and repair the impaired tissue.

This multifactorial network encompasses activation and migration of different inflammatory cells i. The coordination of the recruitment of aforementioned inflammatory cells to sites of tissue injury and to the provisional extracellular matrix ECM involves a four-step mechanism. The first step is the activation of adhesion molecules such as L- P- and E-selectin, expedite rolling along the vascular endothelium. Next step is the triggering of signals mediated by leukocyte-activating molecules and cytokines leading to activation and upregulation of leukocyte integrins.

Lastly, the transmigration of the cells to the site of injury through the endothelium is supposedly mediated by extracellular proteases, such as matrix metalloproteinases MMPs Chettibi et al.

In the main, inflammation is segregated as acute inflammation and chronic inflammation. The acute inflammatory phase is characterized by increased in blood flow, aggregation of fluid, different cytokines and leukocytes anticanceg vascular permeability Feghali and Wright, Nonetheless it resides for short time and is usually self-limiting because of the production of anti-inflammatory cytokines followed by pro-inflammatory cytokines ultimately resulting in tissue remodeling and normal tissue homeostasis.

Notwithstanding, if there is unabating inflammation or if the system fails to return to normal homeostasis it eventually leads to chronic inflammation which is identified as a root cause in the development of a variety of chronic inflammatory and immune-related diseases Arshad et al.

Chronic inflammation is correlated to the progression of human diseases such as arthritis, cancer, allergy, infectious diseases, arteriosclerosis, and autoimmune disorders Medzhitov, Most of the immune system disorders are usually described by overactivity of the anticancr cells or abnormally low activity of the immune system.

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The body attacks and damages its own tissues, a condition known as acquired immune system reaction autoimmune diseases in cases of hyperactivity of immune system while immune deficiency diseases decrease the body’s ability to fight invading pathogens, causing vulnerability to infections. Cancer, rheumatoid arthritis, Type 1 diabetes, systemic lupus erythematosus, tuberculosis and atherogenesis, are among the most common diseases due to suppression of the immune functions.

Immunoediting which describes the relation between immune response and tumor development occurs in three phases. During the elimination phase acute inflammatory response induced by innate and adaptive immune system occurs to recognize and eliminate the early-generated tumor cells by induction of apoptosis.

Next, the tumor cells start to resist the strong immune surveillance and shift into the equilibrium phase between the tumor proliferation and apoptosis. In the escape phase, tumor cells become less immunogenic and able to evade the immune control Mohamed et al. Accumulation of bioactive cytokines, chemokines, ROS and growth factors by the immune cells will induce mutation development and transition of the normal cells into abnormal tumor cells Balkwill, The proliferation of normal cells is enhanced during tissue injury associated with wounding, along with the regeneration of tissue, as the invading pathogen is removed, proliferation, and inflammation abated and the repair is completed.

On the other hand, proliferating cells that endure DNA damage continue to proliferate in microenvironments and growth factors support their growth.

Eventually, the tumor microenvironment is said to be largely concentrated with inflammatory cells, which is considered a crucial element in the neoplastic process, further stimulating proliferation, survival, and migration.

Additionally, tumor cells are also assimilated with some of the signaling molecules of the innate immune system, such as chemokines, selectins, and their receptors for invasion, migration, and metastasis Dvorak, Natural products especially plant-derived compounds have been classified as a significant class of novel immunomodulators particularly as potent anti-inflammatory and anticancer agents.

The anti-inflammatory and anticancer properties of plant-based therapeutics have attracted the interest of researchers as they provide alternative strategies to manage several infectious and debilitating diseases. A number of plant extracts have been suggested as potent immunomodulators with promising anti-inflammatory and anticancer properties such as Annona muricata L.

Don, Camptotheca accuminata Decne.

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Lam, Phyllanthus amarus Schumach. Furthermore, phytochemicals such as alkaloids, terpenoids, polysaccharides, lactones, flavonoids, carotenoids, and glycosides as well as essential oils isolated from several plants have also been shown to exhibit potential anti-inflammatory and anticancer effects Jantan et al.

The plant extracts and anticanver active constituents with anti-inflammatory potential anticahcer as natural resources and may provide us with valuable entities to develop novel anti-inflammatory agents to be used as supplements or adjuvants with the present therapeutic modalities for chemotherapy.

This review is to provide an updated overview of the potential anti-inflammatory and anticancer roles of the leaves of Annona anticncer L. In addition, phytochemistry, and toxicological information have also been included to correlate its efficacy and clarify its safety profile. Annona muricata is widely known as soursop due to the sour and sweet taste of its fruit.

It is also known as prickly custard apple due to its taste. The fruit is locally referred as durian belanda. In Indonesia, the plant is called sirsak or nangka belanda, while it is known as graviola in Portuguese and guanabana in Latin American. This plant has the taxonomic classification of the kingdom of Plantae, the division of Angiosperms Magnoliophytathe class of Magnolids, the order of Magnoliales, the family anticanccer Annonaceae, the genus of Annona and the species of A.

The accepted full name of this species is A. The Annonaceae family consists of approximately genera and species, while the genus Annona comprises over 70 species among which A. The tree tends to bloom and fruit most of the year, but there are more defined seasons depending on the altitude Pinto et al. Its fruits are edible, heart-shaped, anticancet in color and 15—20 cm amticancer diameter.

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The flesh is white and creamy with a characteristic aroma and flavor. Each fruit may contain black seeds when fresh qnticancer they turn light brown when dry Awan et al.

Figure 1 refers the various plant parts of A. The natives of Malaysia apply the leaf juice of a mixture of A. The leaves have also been used to treat cystitis, diabetes, headaches, and insomnia Adewole and Caxton-Martins, ; de Souza et al. The decoction of the leaves is applied topically for its anti-rheumatic and neuralgic effects, and to reduce abscesses Adewole and Caxton-Martins, ; de Souza et al. The leaves are used in the bath to cure skin diseases in the Caribbean islands, Indonesia as well as in the South Pacific countries Longuefosse and Nossin, ; Boulogne et al.

The importance of A. Table 2 enlists the traditional medicinal uses that have been reported for the leaves of A. Besides the wide array of the ethnopharmacological values of the leaves of A. In India, the roots, bark and leaves of A. The seeds are used as an anti-anthelmintic against external and internal worms and parasites. The leaves, seeds, unripe fruits and roots of A.

The aqueous extract of A. In addition, the leaves, bark, and roots of A. Besides the traditional medicinal uses, A. Phytochemical studies have been extensively carried out on different parts of A. Thorough investigations have been carried out on the leaves of A. Acetogenins are the most predominant bioactive compounds of Annonaceace family, as well as of A. In the previous phytochemical investigations, more than acetogenins have been reported from the leaves, stems, bark, seeds, pulp, and fruit peel of A.

Annonacin, annonacin A, annonacin B, annonacinone, muricatalicin and muricatalin have been isolated and identified by Yu et al. Further investigation on the A. Further studies led to the isolation of annonacin, annonacinone, annocatalin, cis -corossolone, solamin, and corossolone Liaw et al. Recent investigation conducted by Moghadamtousi et al.

The previously identified acetogenins in A. Annonacin was the most abundant acetogenin isolated from the leaves of A. Alkaloids are a diverse group of naturally occurring secondary compounds derived from amino acids or the process of transamination Dey et al. Till date, around 22 alkaloids have been reported from A. Anomurine and anomuricine, the isoquinoleic alkaloids were isolated and reported by Leboeuf et al.

The chloroform extraction of A.

The nonphenolic fraction afforded aporphine alkaloids identified as anonaine, isolaureline, and xylopine, while the phenolic fraction led to the isolation of coclaurine, the benzyltetrahydroisoquinoline alkaloid Fofana et al.

The alkaloids were eluted by various ratios of benzene and ethanol solvent system Subsequently, Matsushige et al. Based on previous investigations, annona and cureximine annoa the most abundant alkaloids in A. Notably, isoquinoline, aporphine, and protoberberine typed-alkaloids were the most frequently isolated from the A. Thirty-four phenolic compounds have been isolated from the leaves of A. The purification of n-butanol leaf extract of A. Further investigation by Nawwar et al.

Recently, an investigation on the methanol and aqueous leaf extracts of A. Besides all the above mentioned phytochemicals, vitamins, amides, and essential oils have also been identified from the leaves of A. To date, 80 essential oils constituted mainly of sesquiterpenes wnnona have been identified in the leaves of this promising plant. All of the secondary metabolites isolated from the leaves of the A. Murixata secondary metabolites isolated from the leaves of Annona muricata L.

The anti-inflammatory activity of A. The in vitro study conducted by Laksmitawati et al. The study demonstrated the potential of A.