Biological Activities of Miracle Berry Supercritical Extracts as Metabolic Regulators in Chronic Diseases

Synsepalum dulcificum (Richardella dulcifica) is a berry fruit from West Africa with the ability to convert the sour taste into a sweet taste, and for this reason, the fruit is also known as the "miracle berry" (MB). The red and bright berry is rich in terpenoids. The fruit's pulp and skin contain mainly phenolic compounds and flavonoids, which correlate with their antioxidant activity. Different polar extracts have been described to inhibit cell proliferation and transformation of cancer cell lines in vitro. In addition, MB has been shown to ameliorate insulin resistance in a preclinical model of diabetes induced by a chow diet enriched in fructose. Herein, we have compared the biological activities of three supercritical extracts obtained from the seed-a subproduct of the fruit-and one supercritical extract obtained from the pulp and the skin of MB. The four extracts have been characterized in terms of total polyphenols content. Moreover, the antioxidant, anti-inflammatory, hypo-lipidemic, and inhibition of colorectal cancer cell bioenergetics have been compared. Non-polar supercritical extracts from the seed are the ones with the highest effects on the inhibition of bioenergetic of colorectal (CRC) cancer cells. At the molecular level, the effects on cell bioenergetics seems to be related to the inhibition of main drivers of the de novo lipogenesis, such as the sterol regulatory element binding transcription factor (SREBF1) and downstream molecular targets fatty acid synthase (FASN) and stearoyl coenzyme desaturase 1 (SCD1). As metabolic reprograming is considered as one of the hallmarks of cancer, natural extracts from plants may provide complementary approaches in the treatment of cancer. Herein, for the first time, supercritical extracts from MB have been obtained, where the seed, a by-product of the fruit, seems to be rich in antitumor bioactive compounds. Based on these results, supercritical extracts from the seed merit further research to be proposed as co-adjuvants in the treatment of cancer.