## 6 Therapeutic Actions of Madecassoside and Other Major Compounds in _C. asiatica_
### Diabetes  
Diabetes mellitus (DM) is a widespread disease worldwide, especially in Asia [247]. _Centella asiatica_ has been used as a remedy for DM in Ayurvedic traditional medicine [248; 249]. A study reported that asiaticoside exhibited significant antidiabetic activity in alloxan-induced diabetic mice, most likely by stimulating pancreatic \(\beta\) cells to secrete insulin [247]. In streptozotocin (STZ)-induced diabetic rats, asiatic acid exhibited antihyperlipidemic and antidiabetic effects; here, it decreased blood glucose, increased plasma insulin concentrations and reversed changes in key carbohydrate-metabolizing enzyme levels [250], as well as prevented lipid peroxidation and increased antioxidant status [251; 252]. Asiatic acid was postulated to exert its antihyperglycemic activity by enhancing glucose uptake into skeletal muscle in insulin-deficient STZ diabetic rats via the PI3K-Akt signaling pathway [253]. Asiatic acid also demonstrated lipid and glucose lowering effects in db/db mice via PI3K/Akt/GSK-3\(\beta\) to accelerate glycogen synthesis [254]. Asiatic acid was also proposed to mitigate hyperglycemia by preserving and restoring beta cell mass and function [255], reducing islet fibrosis formation and reversing the over-expression of fibronectin [256]. Madecassic acid was shown to improve glycemic control, lower plasma lipids and attenuate oxidative and inflammatory stress in streptozotocin-induced diabetes in mice [257]. Madecassic acid also reduced insulin resistance and endothelial dysfunction in mice made obese using a high-fat diet [258]. A study conducted recently in our laboratory has demonstrated the efficacy of madecassoside in protecting \(\beta\) cells both in vivo in STZ-diabetic rats and in vitro [259].  
Asiatic acid and asiaticoside may also be effective in ameliorating the complication of diabetes. Asiatic acid could protect against diabetic nephropathy in rats with STZ-induced diabetes [260]. In vitro, asiaticoside was shown to protect cochlear hair cells from high glucose-induced injury by increasing antioxidative activity and suppressing the AGEs/RAGE/NF-\(\kappa\)B pathway [261].  
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Condition** & **Compound** & **Outcome** & **Reference** \\ \hline \multirow{4}{*}{**Skin related conditions**} & \multirow{4}{*}{Asiaticoside} & Promote cell proliferation and collagen synthesis & [79] \\  & & Accelerate wound healing, suppress apoptosis & [85] \\  & & Hinder keloid fibroblast’s invasive growth & [95] \\ \cline{2-4}  & \multirow{2}{*}{Madecassoside} & Anti-oxidative, attenuate mitochondrial damage, promote autophagy & [87] \\  & & Decrease dermal inflammation, reduced keratinocyte proliferation & [89] \\ \hline \multirow{2}{*}{**Rheumatoid arthritis**} & \multirow{2}{*}{Madecassoside} & Increase systemic levels of IL-10 & [106] \\  & & Prevent NF-\(\kappa\)B translocation and phosphorylation & [110] \\ \hline \multirow{4}{*}{**Neurodegenarative diseases**} & \multirow{4}{*}{Protect against GJ25-35 induced tau protein hyperphosphorylation} & \multirow{4}{*}{[125]} \\  & & & \\