# 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}{*}{Aucubin} & STZ-induced diabetic & Lower blood glucose; reverse lipid peroxidation and the & [66] \\  & rats—5 mg/kg, i.p. twice daily for & decreased in activities of antioxidant enzymes in liver and & [67] \\  & the first 5 days followed by single & kidneys; increase immunoreactive beta cells. & \\  & injections daily for 10 days. & & \\ \hline \multirow{4}{*}{Borneol} & STZ-induced diabetic rats—25 or 50 mg/kg, p.o. for 30 days. & Lower blood glucose and HbA1c; increase blood insulin; & [66] \\  & STZ-induced diabetic rats—25 or 50 mg/kg, p.o. for 30 days. & reverse body weight loss; increase liver glycogen level; & \\  & STZ-induced diabetic rats—25 or 50 mg/kg, p.o. for 30 days. & reverse the diabetes-induced increase in the levels of TC, & [66] \\  & 50 mg/kg, p.o. for 30 days. & TGs LDL-C, VLDL-C; restore urea and ALT and AST levels; increase antioxidant status (SOD, catalase, GSH) in the liver and kidney; reduce MDA level. & [67] \\ \hline \multirow{4}{*}{Carvacrol} & HFD-induced C57 BL/\(\epsilon\)/gl diabetic & Suppress elevated TC, TG, phospholipids and FFAs, & \\  & mice—20 mg/kg p.o. for 35 days. & VLDL-C, LDL-C in plasma and tissues; Suppress liver & [68] \\  & mice—20 mg/kg p.o. for 35 days. & tissue inflammatory cytokines (TNF-\alpha and IL-6); increase & [68] \\  & high density lipoproteins-cholesterol (HDL-C) & & \\ \hline \multirow{4}{*}{Carvacrol} & HFD-induced type 2 diabetic & Ameliorate the increased glucose-6-phosphate and & \\  & C57 BL/\(\epsilon\)/gl mice—20 mg/kg, p.o. & fructose-1,6-bisphosphatase, decreased glucose-6-phosphate dehydrogenase activities; normalize & [69] \\  & for 35 days. & hepatic markers (ASP, ALA, ALP, and \(\gamma\)-glutamyl & \\  & transepeptidase). & & \\ \hline \multirow{4}{*}{Carvacrol} & STZ-induced diabetic rats—25, 50, & Improve diabetes-associated cognitive deficit; suppress & \\  & and 100 mg/kg, p.o. for 7 weeks & oxidative stress (increased MDA level and decreased SOD & [70,71] \\  & or 20, 30 and 40 i.p. & as well as reduced GSH) and inflammatory and apoptosis & [72] \\ \hline \multirow{4}{*}{Carvacrol} & STZ-induced diabetes in & Suppress serum glucose, total cholesterol, ALA, AST and & \\  & rats—25 and 50 mg/kg, p.o. for 7 days. & lactate dehydrogenase; no effect on serum insulin levels, & [72] \\ \hline \multirow{4}{*}{Carvone} & STZ-induced diabetic & Reduce plasma glucose, HbA1c; improve the levels of & \\  & rats—50 mg/kg, p.o. for 30 days. & hemoglobin and insulin. Reverse activities of carbohydrate & \\  & rats—50 mg/kg, p.o. for 30 days. & metabolic enzymes, enzymatic antioxidants and hepatic & [73] \\ \hline \multirow{4}{*}{Catalpol} & STZ-induced diabetic & Improve impaired renal functions; ameliorate pathological & \\  & rats—10 mg/kg, i.p. for 14 days. & changes in kidneys; abolish the diabetes induced elevation & [74] \\  & rats—10 mg/kg, i.p. for 14 days. & of Grb10 expression in the kidneys; increase IGF-1 mRNA & [74] \\ \hline \multirow{4}{*}{Catalpol} & STZ-induced diabetic rats—10, & No effect on body weight; improve fasting glucose and & \\  & STZ-induced diabetic rats—10, & insulin levels, glucose tolerance and insulin tolerance; & \\  & HFD-fed mice receiving & reduce macrophage infiltration into adipose tissue; reduce & \\  & 100 mg/kg, p.o. for 4 weeks & mRNA expressions of MI pro-inflammatory cytokines & [75] \\  & 100 mg/kg, p.o. for 4 weeks & while increasing M2 anti-inflammatory gene expressions & \\  & in adipose tissue; suppress the JNK and NF-\(\kappa\)B signaling & & \\  & pathways in adipose tissue. & & \\ \hline \multirow{4}{*}{Catalpol} & STZ-diabetic rats—0.1 mg/kg, i.p. & Enhance glucose uptake in the isolated soleus muscle of & [76] \\  & STZ-induced diabetic rats—10, & diabetic rats; increase glycogen synthesis. & \\ \hline \multirow{4}{*}{Catalpol} & STZ-induced diabetic rats—10, & Improve neuronal injury and cognitive dysfunction; & \\  & 50 and 100 mg/kg, p.o. for 6 weeks. & increase the nerve growth factor concentration and & [77] \\ \hline \multirow{4}{*}{Citronellol} & STZ-induced diabetic rats—25, 50, & Improve the levels of insulin, hemoglobin and hepatic & \\  & and 100 mg/kg, p.o. for 30 days. & glycerol with significant decrease in glucose and HbA1c & \\  & STZ-induced diabetic rats—25, 50, & levels. Restore altered activities of carbohydrate metabolic & [78] \\  & and 100 mg/kg, p.o. for 30 days. & enzymes and level of hepatic and kidney markers; & [79] \\  & improve morphology of hepatic cells and insulin-positive & \\  & \(\beta\)-cells. & & \\ \hline \multirow{4}{*}{Cymene} & STZ-induced diabetic & Improve HbA1c and nephropathic parameters (like & \\  & rats—20 mg/kg, p.o. for 60 days & albumin excretion rate, serum creatinine and creatinine & [30] \\  & & clearance rate). & \\ \hline \multirow{4}{*}{Genipin} & \multirow{4}{*}{Aging rats—25 mg/kg, i.p. for 12 days} & Ameliorate systemic and hepatic insulin resistance, & \\  & & alleviate hyperinsulinemia, hyperglycaemia and & \\  & & hepatic steatosis, relieve hepatic oxidative stress and & \\  & & mitochondrial dysfunction; improve insulin sensitivity by & \\  & promoting insulin-stimulated glucose consumption and & \\  & glycogen synthesis; inhibit cellular ROS overproduction & \\  & and alleviate the reduction of levels of MMP and ATP. & & \\ \hline \hline \end{tabular}
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