**3. Conclusion**

Arun et al. carried out a review related to the pharmacological potential of *A. cherimola* and found antidiabetic activity of leaf extract in streptozotocin (STZ)-induced hyperglycemia in rats [57]. The extract effect was evaluated by measuring fasting plasma glucose levels, serum insulin levels, serum lipid profiles, and body weight in normal rats. In addition, the measurement of liver glycogen levels and pancreatic lipid peroxidation levels was considered for diabetic rats [58]. A significant reduction in blood glucose level and a loss of body weight in diabetic rats were observed. Calzada et al. recently evaluated antihyperglycemic activity of *A. cherimola* leaves on alloxan-induced diabetic rats. The effect of ethanol extract at concentrations of 300 mg∙kg−1 was measured through the blood glucose level [59]. A computational molecular docking was also done to show the interaction of flavonoid **5**, **Figure 2**, with enzyme α-glucosidase. Calzada et al. confirm that rutin (5) is the main compound responsible for antihyperglycemic activity of *A. cherimola* leaves. Before this study, Fale et al. found that **5** is the main compound in decoctions of *A. cherimola* leaves, responsible for inhibiting the HMG-CoA reductase activity and decreasing the cholesterol uptake in intestinal cells [60]. HMG-CoA reductase is the dependent enzyme of NADH, which controls the mevalonate

*Annona reticulata* is a small deciduous tree that is grown in diverse parts of the world, including southern and eastern Asia, central and southern America, Australia, and western Africa. It grows up to 10 m in height. The leaves are narrow, lanceolate, alternating, and oblong, measuring approximately 10–20 cm long and 2–5 cm wide with conspicuous veins and a bad odor [61]. Extracts from different parts of *A. reticulata* have shown antioxidant and antimicrobial [62], antihyperglycemic [63, 64], and anticancer [65, 66] activities. Jamkhande et al. (2014) evaluated antioxidant and antimicrobial activity of root extract from *Annona reticulata*. The antioxidant activity was evaluated by DPPH free radical-scavenging assay and antibacterial and antifungal activities by agar cup method and poison plate method, respectively. The results of this study showed that methanol extracts of *A. reticulata* roots have significant antioxidant activity and a wide spectrum antibacterial and antifungal efficacy [61]. Gingine et al. (2016) evaluated the anticancer activity of methanol extract from *Annona reticulata* leaves [64]. This activity was investigated for anticancer potential using sulforhodamine B (SRB) cytotoxicity assay against colon cancer (HCT15), human lung cancer (Hop65), and human hepatoma (HEPG2) cell lines. The extract exhibited a moderate anticancer effect against all the cell lines. Suresh et al. (2011) evaluated the anticancer activity of ethanol extract from *Annona reticulata* roots against melanoma cells in mice and *in vitro* activity on MDA-MB-435 human melanoma cells by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay [65]. The ethanol extract exhibited significant *in vitro* and *in vivo* inhibitory activities against melanoma tumor cells. In both studies, the anticancer activity is attributed to the presence of acetogenins in the extracts used to perform the evaluations. Rahman et al. evaluated antihyperglycemic activity of methanol extract from *A. reticulata* leaves in Swiss albino mice [63]. The extracts were administered at doses of 50, 100, 200, and 400 mg∙kg−1. The results showed lowered blood sugar in mice, and the authors suggest that the responsible compounds are acetogenins. Acetogenins have been reported from the plant seeds [66]. These compounds, including squamone (**31**), solamin (**32**), annomonicin (**33**), and rolliniastatin 2 (**34**), have also been isolated from the leaves (**Figure 11**) [67]. Santos Lima et al.

pathway rate, which produces cholesterol.

**2.5.** *Annona reticulata*

40 Antioxidants in Foods and Its Applications

After analyzing the five most studied species of genus *Annona*, it can be concluded that they have great potential for the treatment of diseases associated with oxidative stress, including diabetes, hyperglycemia, cancer, and gastric ulcers, among others, because they are rich in antioxidant compounds. The most studied species of this genus are *A. muricata* and *A. cherimola*. The stems, trunks, and leaves of the trees are the most frequently studied and used in traditional medicine. Undoubtedly, the most representative bioactive compounds of the genus *Annona* are the acetogenins because they are abundant, mainly in the seeds of the fruit. There are several studies that show the anticancer properties of the genus. In addition, the phenolic compounds found in this genus are capable of inducing antioxidant properties in extracts. It is also possible to find alkaloids and cyclopeptides with properties similar to acetogenins in the species of this genus.

## **Acknowledgements**

The authors thank Carol Ann Hayenga for her English assistance in the preparation of this manuscript. Support was provided by the Universidad Tecnológica de la Mixteca.
