Annonaceous acetogenins isolated from the leaves, bark, and twigs are among the active constituents ⁽³⁵⁾. Graviola-induced cell death inhibited by glucose supplementation suggests energy depletion ⁽²⁰⁾. Graviola has also been shown to stimulate serotonin receptors ⁽²⁴⁾. Cell-stimulating behaviors may occur either by increased mitochondrial turnover or by preparation to leave the G1 phase, possibly through a promitotic stimulus present within the extract which acts like a growth factor ⁽²⁸⁾.

In animal models, antidiabetic effects are due to antioxidant, hypolipidemic, and protective effects in pancreatic beta-cells, which improves glucose metabolism ⁽⁷⁾. Antiulcer effects may occur via increased nitric oxide and prostaglandin E2 activities ⁽⁸⁾. Anti-inflammatory and analgesic actions with a fruit extract occurred via COX-1/2 inhibition and the blocking of opioid receptors ⁽⁵⁾.

Graviola extracts were effective against adriamycin-resistant human mammary adenocarcinoma by blocking ATP access and inhibiting plasma membrane glycoprotein ⁽²⁹⁾. Inhibition of HIF-1α, NF-κB, glucose transporters, and glycolytic enzymes also decreased glucose uptake and ATP production in pancreatic cancer cells ⁽¹⁵⁾. In breast cancer cells, EGFR expression was downregulated ⁽¹⁶⁾ and free-radical scavenging occurred ⁽³⁰⁾. In colon and in lung cancer cell lines, G1 cell-cycle arrest occurred by upregulating Bax and downregulating Bcl-2 proteins ^(12) (13).

In vitro, graviola alkaloids caused movement disorders and myeloneuropathy with symptoms mimicking Parkinson’s disease ^(20) (21). Animal studies suggest that long-term ingestion of graviola juice promotes generation of reactive nitrogen species that may accelerate development of neurodegenerative diseases involving the microtubule-associated protein tau ⁽³⁴⁾.