## 4 Biological Properties of _P. avium_ L. By-Products
### Anti-Hyperglycemic Activity
#### 4.2.1 In Vitro and In Vivo Studies
\begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Part of Plant/Compounds** & **Extract** & **Type of Study** & **Main Outcomes** & **References** \\ \hline \multirow{2}{*}{Stems, leaves and flowers} & Ethanol/Water 1:1 (\%/v) & \multirow{2}{*}{_In vitro_} & Inhibition of \(\alpha\)-glucosidase enzyme in & [7] \\  & Aqueous Infusion & & a concentration-dependent manner. & \\ \hline \multirow{2}{*}{Fruits} & Ethanol 70\% & \multirow{2}{*}{_In vitro_} & Inhibition of \(\alpha\)-glucosidase enzyme in & [5; 6] \\  & & & a concentration-dependent manner. & \\ \hline \multirow{2}{*}{Cyanidin-3-rutinoside} & \multirow{2}{*}{n.a.} & \multirow{2}{*}{_In vitro_} & Inhibition of \(\alpha\)-amylase enzyme in a & \\  & & & concentration-dependent manner. & \\ \hline \multirow{4}{*}{Hydrooxcinnamic acids, flavonols, and anthocyanins} & Hydroxycinnamic acid-rich fraction & & \\  & Flavonol-rich fraction & _In vitro_ & Promotion of cellular glucose & \\  & Anthocyanin-rich fraction & & consumption by HepG2 cells. & \\ \hline \multirow{2}{*}{Kaempferol and quercetin} & \multirow{2}{*}{n.a.} & \multirow{2}{*}{_In vitro_} & \(\uparrow\) Insulin-stimulated glucose uptake in & \\  & & & mature 3T3-L1 adipocytes. & [84] \\ \hline \hline \end{tabular}
\end{table} 
Table 5: Anti-hyperglycemic activity of _Pruus avium_ L. fruits and by-products. The biological activities of _P. avium_ cherries and their by-products may be due to the synergistic interactions of several bioactive compounds. [PERSON] et al. [83] evaluated different phenolic fractions (anthocyanin, hydroxycinnamic acid, and flavonol-rich fractions) on the cellular glucose consumption-promotion in HepG2 cells. This study revealed that the hydroxycinnamic acid and flavonoid-rich fractions were able to promote cellular glucose consumption by HepG2 cells [83], acting similarly to the hypoglycemic drugs (e.g., metformin) and insulin. Hydroxycinnamics, particularly caffeoylquinic acids, have been described as effective in blood glucose regulation through different mechanisms: (a) by competitive inhibition of the hydrolysis of glucose-6-phosphate (G6 Pase) in the liver microsome [90], or (b) by induced AMPK phosphorylation, increasing glucose transporter 4 (GLUT4) expression and translocation to the plasma membrane in the muscle cell, and inhibition of hepatic G6 Pase expression and activity [91]. In addition, the flavonoids as quercetin and kaempfer showed similar activities in other experiments [84,85]. Concerning glucose absorption, phenolic compounds such as caffeic and ferulic acids, catechins, quercetin, and naringenin inhibit the sodium-dependent glucose cotransporter 1 (SGLT1) [83]. These compounds have previously been described in the _P. avium_ fruit and its by-products (Table 4); thus, inhibiting this glucose transporter prevents glucose transport to insulin-responsive cells and avoids increased post-prrandial glucose [92]. The anti-hyperglycemic activity of the _P. avium_ fruit and its by-products was also evaluated in animal models. In a study developed by [PERSON] et al. [86], the protective effect of the ethanolic extract of cherry fruit was studied in alloxan-induced diabetic rats for 30 days. At a 200 mg/kg dose, the extract demonstrated a significant reduction of hyperglycemia and urinary microalbumin and an increase in urinary creatinine excretion [86]. Another report demonstrated that certain phenolic compounds such as diacylated anthocyanin, when administered orally, reduce the glycemia value induced by maltose ingestion in normal rats [93]. A study conducted by [PERSON] et al. [87] used obese diabetic (_db/db_) mice fed with a diet supplemented with non-anthocyanin cherry phenolics. The authors demonstrated that these compounds exert protective effects in the liver and prevent hepatic inflammation in diabetic conditions through the decrease of fasting glucose levels [87]. This reduction can improve the pathological complications caused by hyperglycemia, mainly concerning oxidative stress.