American Pawpaw

Angiogenesis inhibitory interventions are useful because unlike chemotherapeutic interventions, they can be highly targeted in order to limit damage to the healthy tissue surrounding the tumor; however, angiogenesis inhibition requires long-term administration and management to be effective.³(Qazi 2023). Typically, angiogenesis inhibition is used in combination with chemotherapy or surgery in order to completely remove the tumor.

In a clinical setting, researchers have found that annonaceous acetogenins derived from American pawpaw have been effective in angiogenesis inhibition, making it a promising molecule for further research as a potential intervention against certain cancers, for development as an antiviral medication, or as a pesticide.⁴

Bioactive Alkaloids and Acetogenins

Researchers have also explored the potential applications of different components of pawpaw seed extract (which contains bioactive alkaloids and acetogenins) in managing excessive fat accumulation and symptoms of diabetes.⁵

Implications of Bioactive Alkaloids and Acetogenins on diabetes prevention and management

One study using mouse cell cultures compared the capacity of these cells to metabolize sugars in non-oxygenated conditions with and without the administration of pawpaw seed extract.⁶ As explained above in the section “Annonaceous acetogenins in cancer research,” a lack of oxygen often makes cellular respiration and metabolism less efficient. Nevertheless, cells that were cultivated in the growth medium containing pawpaw seed extract were better able to break down high concentrations of sugars compared to those cultivated without pawpaw seed extract in their growth medium.⁷ This study suggests that the bioactive alkaloids and acetogenins in pawpaw seed extract could help cells to more effectively metabolize sugars, or otherwise help enhance the effects of insulin. Someday this research may lead to the discovery and implementation of specific acetogenins or bioactive alkaloids in the management of blood sugar, particularly among diabetics. It may also lead to research that could help to prevent diabetes in cases where a child in utero is suspected to be at a high risk of developing diabetes.

Implications of Bioactive Alkaloids and Acetogenins in excessive fat cell accumulation

Throughout the lifecourse bodies change. One of the ways bodies change is through the growth of or accumulation of fat cells. Fat cells, also known as adipocytes, are necessary and make up a vital means by which a body stores energy. Throughout childhood and adolescence, people accumulate more adipocytes, and once they reach adulthood, the number of adipocytes in a person’s body tends to become more stable.⁸ Much like with the other cells of the body, each year a number of fat cells die, and in order to maintain a stable condition known as homeostasis, a similar number of fat cells divide; over the course of a year about 10% of adipocytes in the body are replaced in a process called turnover.⁹

Typically, it is not the number of fat cells, but the size of fat cells that changes when a person loses weight due to “burning” fat. Changes to adipocyte number and size during weight gain, however, are a little more complicated. In a book chapter titled “Fat Tissue Growth and Development in Humans,” Peter Arner breaks down the changes very elegantly:

When regaining lost weight, fat cells tend to increase not only in size, but also in number, at which point the new number of adipocytes becomes the person’s baseline number, which is not typically subject to decrease.¹⁰

The Iobe et al. study showed that in low glucose conditions, fewer adipocytes developed than in high glucose conditions in the in vitro cell cultures (2023). However, in the low glucose condition, pawpaw seed extract significantly decreased the number of fat cells that developed over the course of the experiment. This, in combination with the information on adipocyte accumulation over the life course laid out above, suggests that with additional research, bioactive alkaloids and acetogenins may have some clinical applications in the prevention and management of early childhood obesity.

Cautions:

Annonacin, a chemical component found in American pawpaw fruit, seeds, and peels has been demonstrated to exhibit neurotoxic effects when consumed in moderate to high doses.¹¹ In fact, a 2004 study demonstrated that in rats, regular annonacin infusion led to a 44% decrease in ATP levels in the cerebral cortex and a significant reduction in the number of neurons in the basal ganglia, and particularly in the substantia nigra regions of the brain.¹² The substantia nigra and the loss of dopamine-producing neurons therein is significantly associated with Parkinson’s disease. Despite the neuronal loss in the region, however, none of the rats in the study demonstrated any of the tremors or spontaneous movements that are typically associated with the disease.¹³

Nevertheless, animal models are not always perfect representations of effects that drugs may have on humans. A case study involving an 80-year-old man who reportedly ingested about 30 lbs of American pawpaw fruit per year for the five years prior to his death suggests that the neurotoxic effects of annonacin may have been responsible for his symptoms of atypical Parkinson’s disease.¹⁴ His symptoms included difficulty speaking, slowed movement, slight disturbances in balance, and significant neurodegeneration in the midbrain (where the substantia nigra is located) and the cortex. He did not report any improvement in his symptoms when treated with the traditional medication used to manage symptoms of Parkinson’s Disease.¹⁵