# Iridoids and Other Monoterpenes in the Alzheimer's Brain: Recent Development and Future Prospects
## 4 Therapeutic Potential for Alzheimer's Disease
### Evidence of Efficacy Demonstrated through In Vivo Studies  
In parallel with the overwhelming in vitro data, animal studies on iridoids and some other monoterenes (Table 2) have shown potential therapeutic effects for treating AD [57; 58; 59; 60; 61; 62; 63; 64; 65; 66; 67; 68; 69; 70; 71; 72; 73; 74; 75; 76; 77; 78; 79; 80; 81; 82]. The neuroprotective effect of carvacrol in vivo was studied by [PERSON] et al. [55] using the intracerebral hemorrhage mouse model, where a significant reduction of the aquaporin-4 (AQP4)-dependent oedema was observed. It is worth noting that AQP4 is a water channel in the brain that plays major role in the development of cerebral oedema. The structural, physiological and pathological significance of ACQ4 has been extensively reviewed [78; 79; 80; 81; 82]. Considering the pathophysiological role of AQP4 in a range of CNS disorders including ischemic stroke [83], neuroinflammation [84] and autoimmune neurodegenerative diseases [85], the reversal of cerebral oedema induced through AQP4 activity by monoterenes is an interesting observation. \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Compound** & **Model** & **Outcome** & **Reference** \\ \hline \hline Carvarcal & Bacterial collagenase-induced intracerebral hemorrhage mouse & Improve neurological deficits reduce cerebral edema and Evans blue leakage; decrease AQP4 mRNA in a model - Single doses of 10, 25, 50 or 100 mg/kg. i.p. & & [57] \\ \hline \multirow{3}{*}{Catalpel} & \multirow{3}{*}{\(\text{D}^{(+)}\)-gallactone mice model—20 mg/kg, intragastric for 30 days} & Reduce the oxidative stress in the cerebral cortex regulate the activities and concentration of SOD, glutathione peroxidase and catalase (MDA level not included); reduce the levels of soluble AQ0 and AQ42 in the cerebral cortex; effects regulated by IDE; improve learning and memory in Morris water maze test. & [58] \\ \hline \multirow{3}{*}{Catalpel} & \multirow{3}{*}{A295-35 injected in rats intrachoreweenwritcularly to establish AD model—5 or 10 mg/kg, i.p. 7 days} & \multirow{3}{*}{More positive neurons (ChAT staining in cerebral cortex) and cells arranged in order; increase CMF activity in dose dependent manner.} & [28] \\ \cline{1-1} \cline{2-3} \cline{5-5} \cline{5  
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Compound** & **Model** & **Outcome** & **Reference** \\ \hline Loganin & Scopolamine-induced AD model in rats—40 mg/kg p.o. & Reverse shortening of step-through latency in the passive avoidance test: reduce the percent alternation in the Y-maze, and increased memory retention in the Morris water maze test. & [45] \\ \hline Loganin & Scopolamine-induced AD model in mice—20 or 40 mg/kg p.o. & Reverse the memory impairment (?-maze test; passive avoidance and the Morris water maze tests); inhibit & [71] \\ \hline Occuprepin & Fullyenetetrazole-induced seizures in male NMR mice—10. & Increased the seizure threshold; anticonvulsant effects reversed by halfrecon (episodic receptor antagonist). & [72] \\ \hline Occuprepin & Coldicine (15 mg/rast) injected into the CA1 area of the hippocampus—10.15 or 20 mg/kg p.o. for 10 days & Improve learning and memory retention (Morris water maze test); attenuate the oxidative damage & [73] \\ \hline Paconifiform & Transgenic mouse model of AD—20 mg/kg i.p. for 24 h. & Improves cognitive function and ameliorate patterns of escape distance and escape latency in AD mice; decrease information (protein expression levels of rs-MS, rs  
A number of studies have targeted the oxidative stress and associated disorders by inducing the pathology with d-(+)-galactose injection into experimental animals. In this model, catalpol has been shown to reduce the level of A\(\beta\) in the cerebral cortex along with improvement of learning and memory; while the level of antioxidant defenses (SOD and GPx) were boosted [58]. In senescent mice treated with d-galactose, [PERSON] et al. [60] also reported neuroprotection by catalpol as evidenced by the increased level and activity of choline acetyltransferase (CHAT).