Annona muricata: A comprehensive review on its traditional medicinal uses, phytochemicals, pharmacological activities, mechanisms of action and toxicity

Annona muricata L. (Magnoliales: Annonaceae) is a tropical plant species known for its edible fruit which has some medicinal merits, but also some toxicological effects. This review focuses on the phytochemicals contents, bioactivity, biological actions and toxicological aspects of extracts and isolated compounds, as well as medicinal uses of A. muricata, with the objective of stimulating further studies on extracts and fruit pulp used for human consumption. Traditional medicinal uses of A. muricata have been identified in tropical regions to treat diverse ailments such as fever, pain, respiratory and skin illness, internal and external parasites, bacterial infections, hypertension, inflammation, diabetes and cancer. More than 200 chemical compounds have been identified and isolated from this plant; the most important being alkaloids, phenols and acetogenins. Using in vitro studies, extracts and phytochemicals of A. muricata have been characterized as an antimicrobial, anti-inflammatory, anti-protozoan, antioxidant, insecticide, larvicide, and cytotoxic to tumor cells. In vivo studies of the crude extracts and isolated compounds of A. muricata were shown to possess anxiolytic, anti-stress, anti-inflammatory, contraceptive, anti-tumoral, antiulceric, wound healing, hepato-protective, anti-icteric and hypoglycemic activities. In addition, clinical studies support the hypoglycemic activity of the ethanolic extracts of A. muricata leaves. Mechanisms of action of some pharmacological activities have been elucidated, such as cytotoxic, antioxidant, antimicrobial, antinociception and hypotensive activities. However, some phytochemical compounds isolated from A. muricata have shown a neurotoxic effect in vitro and in vivo, and therefore, these crude extracts and isolated compounds need to be further investigated to define the magnitude of the effects, optimal dosage, mechanisms of action, long-term safety, and potential side effects. Additionally, clinical studies are necessary to support the therapeutic potential of this plant.