## 6 Therapeutic Actions of Madecassoside and Other Major Compounds in _C. asiatica_
### Neurodegenerative Diseases  
Neurodegeneration entails numerous cellular processes whereby neuronal cells gradually deteriorate, lose functionality and eventually die [111]. Neurons are susceptible to ROS-induced oxidative damage resulting from ROS-induced oxidation of various biological macromolecules, causing homeostatic disturbances within neurons leading to cell death. Neuroinflammation is one of the key risk factors of progressive neurodegeneration [112]. The accumulation of ROS and protein misfolding associated with neuroinflammation could be one of several triggers of neurodegeneration [111]. Some studies have implicated neuroinflammation in aggravating Alzheimer's disease (AD) and Parkinson disease (PD), by stimulating excessive production of amyloid \(\beta\) plaques and the destruction of dopaminergic neurons [111]. Several studies have suggested the potential of _C. asiatic_ extract to mitigate symptoms of various neurodegenerative diseases, such as memory impairment, anxiety and locomotive dysfunction [113]. It has been used extensively as a memory-enhancing drug in Asian countries, such as India, China and Malaysia, and has been shown to have some pharmacological activities in the central nervous system [114]. Additionally, _C. asiatic_ extracts were also reported to possess anticonvulsant and central nervous system depressant actions [59]. Purified madecassoside was shown to inhibit in vitro A\(\beta_{1-42}\) fibril formation and to markedly inhibit A\(\beta_{1-42}\) induced apoptosis in SHSY5Y cells [115]. Long-term oral administration of madecassoside protected against spatial memory impairment in A\(\beta_{1-42}\)-infused rats, a model of AD, as well as inhibiting the formation of A\(\beta_{1-42}\) fibrils [116]. Madecassoside also diminished the brain A\(\beta_{1-42}\) burden, oxidative stress, TNF\(\alpha\) and cathepsin D levels, along with a parallel increase in BDNF and postsynaptic density protein (PSD-95) levels in the hippocampus. The interaction of madecassoside with A\(\beta_{1-42}\) by molecular docking was examined to further assess the anti-A\(\beta_{1-42}\) fibrillation effect of madecassoside. Computational modeling studies showed effective molecular docking of madecassoside onto A\(\beta_{1-42}\), consistent with the inhibitory effects of madecassoside on in vitro fibril formation and memory impairment in a rat model of AD [116]. In agreement with these findings, madecassoside was found to markedly improve D-galactose-induced cognitive impairment in mice; this may be mediated by reducing oxidative damage via the inhibition of the NF-kB and ERK/p38 MAPK pathways, and diminishing the deposition of A\(\beta\), thus ameliorating the synaptic plasticity dysfunction with amplified BDNF and PSD-95 expressions in the hippocampus. Furthermore, madecassoside notably enhanced acetylcholine levels while diminishing cholinesterase activity [112]. In another study, madecassoside significantly reduced A\(\beta_{25-35}\)-induced autophagosomes in neural cells and increased neural cell viability, as well as reducing the production of inflammatory cytokines such as TNF-\(\alpha\), IL-10, IL-6 and COX-2, blocking the conversion of light chain 3-I (LC3-I) to light chain 3-II (LC3-II) and decreasing the level of Beclin-I level. All of the above findings suggest that madecassoside could be a potential agent for treating AD [112]. Asiaticoside also has been researched considerably as a therapeutic agent for AD. In an AD rat model induced by intracerebral injection of A\(\beta_{1-42}\) oligomers, asiaticoside diminished learning and memory function impairment, reduced A\(\beta\) build-up in the hippocampus and reinstated subcellular structure damages. Asiaticoside also decreased levels of IL-6 and TNF-\(\alpha\) as well as caspase-3 expression, while amplifying Bcl-2 expression [117].