# Antidiabetic Potential of Monoterpenes: A Case of Small Molecules Punching above Their Weight
## 4 Antidiabetic Potential of Monoterpenes
### In Vivo Antidiabetic Effects
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\begin{tabular}{c c c c} \hline \hline
**Compound** & **Model** & **Outcome** & **References** \\ \hline Geniposide & Insulin-deficient—APP/PSI transgenic mouse model of [PERSON]’s disease. 5, 10, and 20 mg/kg, intragastric for 4 weeks. & Decrease the phosphorylation of tau protein. & [80] \\ \hline Geniposide & STZ-induced diabetic rats—injection (50 uM, 10 uL) to the lateral ventricle & Prevent spatial learning deficit; reduce tau phosphorylation. & [81] \\ \hline Geniposide & Transgenic mouse model with Streptavidin 5, 10 and 20 mg/kg, intragastric for 4 weeks & Decreased level of \(\beta\)-amyloid peptides (A\(\beta\)1-40 and \(\beta\)1-42); up-regulate the protein levels of \(\beta\)-site APP cleaving enzyme (BACE1) and insulin-degrading enzyme (IDE); decrease the protein levels of ADAM10; enhance the effects of insulin by reducing A\(\beta\)1-42 levels in primary cultured cortical neurons. & [82] \\ \hline Geniposide & STZ-induced diabetic rats—800 mg/kg/day, p.o. for 46 days. & Improve insulin and blood glucose; decrease A\(\beta\)1-42 level; improve the expression of insulin-degrading enzyme. & [83] \\ \hline Geniposide & Spontaneously obese Type 2 diabetic TSOD mice & Suppress body weight, visceral fat and intrahepatic lipid accumulation; alleviate abnormal lipid metabolism; alleviate abnormal glucose tolerance and hyperinsulinemia. & [40] \\ \hline Geniposide & High fat diet—25, 50 or 100 mg/kg, p.o. for six weeks. & Improve liver histology through reducing the elevated liver index (liver weight/body weight), serum alanine aminotransferase and aspartate aminotransferase; decrease total cholesterol, triglycerides and FFA’s in serum and liver; increased serum insulin levels but reduced serum TNF-\(\alpha\) level; suppressed expression of CYP2E1 and increased PPAR\(\alpha\) expression & [84] \\ \hline Geniposide & HFD and STZ-induced diabetic mice \(-\)200 and 400 mg/kg for 2 weeks & Decrease blood glucose, insulin and TG levels; decrease the expression of glycogen phosphorylase and glucose-6-phosphatase at mRNA level and immunoreactive protein levels, as well as enzyme activity. & [84] \\ \hline Geraniol & STZ-induced diabetic rats—100, 200 and 400 mg/kg, p.o. for 45 days & Improve the levels of insulin, hemoglobin and decrease plasma glucose, HbA1c; improve hepatic glycogen content; preserve the normal histological appearance of hepatic cells and pancreatic \(\beta\)-cells. & [85] \\ \hline d-Limonene & STZ-induced diabetic rats—50, 100 and 200 mg/kg, p.o. for 45 days. & Reverse the following diabetic: increased blood glucose and glycosylated hemoglobin levels, increased activity of gluconeogenesis enzymes (glucose 6-phosphate and fructose 1,6-bisphosphatase) and decreased activity of glycolytic enzyme, glucokinase and liver glycogen. & [86] \\ \hline d-Limonene & STZ-induced diabetic rats—50 mg/kg, p.o. for 28 days. & Decrease DNA damage, glutathione reductase enzyme activities and MDA levels; increase GSH levels and CAT, SOD and GSH-Px enzyme activities and altered lipid and liver enzyme parameters in diabetic rats. & [87] \\ \hline Logonin & STZ-induced diabetic mice, 20 mg/kg, p.o. for 12 weeks. & Reduce kidney/body weight ratio, 24 h urine protein levels, serum levels of urea nitrogen and creatinine; improve histology of pancreas and kidney; alleviate structural alterations in endothelial cells, mesangial cells and podocytes in renal cortex; reduce AGE levels in serum and kidney; downregulate mRNA and protein expression of receptors for AGEs in kidney; reduce the levels of MDA; increase the levels of SOD in serum and kidney. & [88] \\ \hline Menthol & STZ-nicotinamide induced diabetes in rats—25, 50, and 100 mg/kg, p.o. for 45 days & Reduce blood glucose and glycosylated hemoglobin levels; increase the total hemoglobin, plasma insulin and liver glycogen levels; protect hepatic and pancreatic islets; modulating glucose metabolizing enzymes, suppression of pancreatic 6-cells apoptosis and altered hepatic, pancreatic morphology & [89] \\ \hline Mytrenal & STZ-induced diabetic rats—80 mg/kg, p.o. for 28 days & Decrease plasma glucose; increase plasma insulin levels; up-regulate IRS2, Akt and GLUT2 in liver; increase IRS2, Akt and GLUT4 protein expression in skeletal muscle. & [90] \\ \hline \hline \end{tabular}
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