Annona muricata: Is the natural therapy to most disease conditions including cancer growing in our backyard? A systematic review of its research history and future prospects.

Annona muricata (A. muricata) is a tropical plant species belonging to family Annonaceae and known for its many medicinal uses. This review focuses on the research history of its traditional uses, phytochemicals, pharmacological activities, toxicological aspects of the extracts and isolated compounds, as well as the in vitro propagation studies with the objective of stimulating further studies on this plant for human consumption and treatment. A. muricata extracts have been identified in tropical regions to traditionally treat diverse conditions ranging from fever to 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, its extracts and phytochemicals have been characterized as antioxidant, anti-microbial, anti-inflammatory, insecticidal, larvicidal, and cytotoxic to cancer cells. In vivo studies have revealed anxiolytic, anti-stress, anti-inflammatory, immunomodulatory, antimalarial, antidepressant, gastro protective, wound healing, hepato-protective, hypoglycemic, anticancer and anti-tumoral activities. In silico studies have also been reported. In addition, clinical studies support the hypoglycemic as well as some anticancer activities. Mechanisms of action of some pharmacological activities have been elucidated. 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, and mechanisms of action, long-term safety, and potential side effects. Additionally, more clinical studies are necessary to support the therapeutic potential of this plant. Some studies were also found to have successfully regenerated the plant in vitro, but with limited success. The reported toxicity notwithstanding, A. muricata extracts seem to be some of the safest and promising therapeutic agents of the 21st century and beyond that need to be studied further for better medicinal formulations and diseases management.