# Antidiabetic Potential of Monoterpenes: A Case of Small Molecules Punching above Their Weight
## 4 Antidiabetic Potential of Monoterpenes
### In Vivo Antidiabetic Effects
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Compound** & **Model** & **Outcome** & **References** \\ \hline \multirow{4}{*}{Mytrenal} & \multirow{4}{*}{STZ-induced diabetic and 80 mg/kg, p.o. for 28 days} & Reduce plasma glucose, haemoglobin A1c (HbA1c); increase the levels of insulin and hemoglobin; reverse body weight loss; normalize hexokinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, and hepatic enzymes AST, ALT, and ALP levels; improve hepatic and muscle glycogen content; restore islet cells and liver histology. & [91] \\ \hline \multirow{4}{*}{Mytrenal} & \multirow{4}{*}{STZ-induced diabetic rats—80 mg/kg, p.o. for 28 days} & Improve plasma glucose, pancreatic insulin and lipid profiles (TC, TG, FFAs, phospholipids, LDL, VLDL, atherogenic index); improve histopathological feature of the liver. & [92] \\ \hline \multirow{4}{*}{Paeoniflorin} & \multirow{4}{*}{High-sucrose, HFD rat receiving low dose STZ—15 and 30 mg/kg, p.o. for 4 weeks.} & Reduce brain inflammatory cytokines (IL-1\(\beta\) and TNF-\(\alpha\)), decrease suppressor of cytokine signaling 2 expressions and promote (IRS-1 activity and phosphorylation levels of protein kinase B (Akt) and glycogen synthase kinase-3\(\beta\) (GSK-3\(\beta\)). & [93] \\ \hline \multirow{4}{*}{Paeoniflorin} & \multirow{4}{*}{HFD—induced obese mice—Diet containing 0.05% (_w/w_) of paeoniflorin} & Lower body weight, hyperlipidemia, and insulin resistance; block inflammation; inhibiting lipid ectopic deposition; lower lipid synthesis pathway (de novo pathway, \({}^{3}\)HMC-CoAR), promote fatty acid oxidation & [94] \\  & & (peroxosome proliferatorator-activated receptor-alpha) & [94] \\  & & (PPARa), carnitine palmityltransferase-1); increase cholesterol output (PPARy-liver X receptor-\(\alpha\)-ATP-binding cassette transporter-1); block inflammatory genes activation and reduce gluconeogenesis genes expression (phosphoenolpyruvate carboxykinase and GPGrae). & [95] \\ \hline \multirow{4}{*}{Swertiamarin} & \multirow{4}{*}{STZ-induced diabetic rats—50 mg/kg, i.p. for 6 weeks} & Reduce serum triglycerides, cholesterol and low-density lipoprotein levels; decrease serum fasting glucose; increase insulin sensitivity index. & [94] \\ \hline \multirow{4}{*}{Thymol} & HFD-induced type 2 diabetes in C57 BL/6/6 mice—10, 20 and 40 mg/kg, intragastric for 5 weeks. & Antihyperglycaemic; lower plasma TG, TC, FFAs, LDL and increase HDL cholesterol; lower hepatic lipid contents TG, total cholesterol, FFAs and phospholipids. & [96] \\ \hline \multirow{4}{*}{Thymol} & HFD-induced type 2 diabetes in C57 BL/6/6 mice—40 mg/kg, intragastric for 5 weeks. & Inhib diabetic nephropathy; inhibit the activation of transforming growth factor-\(\beta\)1 and vascular endothelial growth factor; increase level of antioxidants and suppress lipid peroxidation markers in erythrocytes and kidney tissues; downregulate the expression level of sterol regulatory element binding protein-1c and reduce lipid accumulation in the kidney. & [97] \\ \hline \multirow{4}{*}{Thymol} & \multirow{4}{*}{HFD-induced obese C57 BL/6 J mice—20, 40 mg/kg daily} & Reverse body weight gain; ameliorate peripheral insulin resistance; improve cognitive impairments in the Morris Water Maze test; decrease HFD-induced A\(\beta\) deposition and tau hyperphosphorylation in the hippocampus; down-regulate the level of P-Ser307 IRS-1 and enhance the expression of P-Ser473 ART and P-Ser9 GSK3B; up-regulate nuclear respiratory factor /heme oxygenase-1 pathway. & [98] \\ \hline \multirow{4}{*}{Thymol} & \multirow{4}{*}{HFD-fed rats—14 mg/kg, p.o. for 4 weeks.} & Decrease body weight gain, visceral fat -pad weights, lipids, ALT, AST, LDH, blood urea nitrogen, glucose, insulin, and leptin levels; decrease serum lipid peroxidation and increase antioxidant levels. & [97] \\ \hline \hline \end{tabular}
\end{table}