Loss of neurons, excessive accumulation of beta-amyloid (Aβ) peptides in certain brain regions along with accumulation and excessive stimulation of glutamate receptors in the central nervous system (CNS) are common pathological hallmarks of neurodegenerative disease such as Alzheimer’s disease (AD). Although a number of drugs have been approved for the treatment of AD, most of these synthetic drugs have diverse side effects and yield relatively modest benefits. Marine algae have great potential in pharmaceutical and biomedical applications as they are valuable sources of bioactive properties. Hence, this study aimed to provide an overview of potentials of Malaysian seaweeds (Padina australis, Sargassum polycystum, Turbinaria ornata and Caulerpa racemosa) in inhibiting cholinesterase (ChE) enzymes, Aβ-induced and glutamate-induced toxicity. Cholinesterase inhibitory activity was conducted using Ellman’s colorimetric assay while protective effects against Aβ-induced and glutamate-induced toxicity were assessed by determining percentage of viable cells using MTT assay. C. racemosa and S. polycystum showed the most potent anti-acetylcholinesterase activities with the IC50 values ranging from 0.086-0.115 mg/mL. Moreover, C. racemosa and T. ornata were also found to be active against butyrylcholinesterase with IC50 values ranging from 0.118-0.162 mg/mL. Seaweed with dual anti-cholinergic activity is an important finding in this study, as C. racemosa methanol extract and caulerpin exhibited very potent inhibitory activities against both enzymes. Besides that, methanol extract of C. racemosa and caulerpin showed very good neuroprotective effect against beta-amyloid1-42 induced toxicity. In evaluating glutamate-induced toxicity, T. ornata dichloromethane extract had 143.02% viable cells at 0.00030 mg/mL. Moreover, the cell viability continues to increase in the presence of seaweed extracts for other seaweeds extracts except T. ornata extracts. It is extremely noteworthy that the extracts that gave good ChE inhibition activity also gave best protection against Aβ and glutamate induced toxicity. These findings suggest that Malaysian seaweeds have potential to be used as neuroprotective agents in treatment of AD.

Gradual worsening of type 2 diabetes mellitus is accompanied by progressive deterioration in β cell function and a reduction in the β cell mass. β cells are vulnerable to excess reactive oxygen species (ROS) because of their inherently low expression of antioxidant enzymes. Protection of β cells would provide a valuable approach to treating type 2 diabetes. Madecassoside, is a triterpenoid antioxidant with anti-inflammatory, myocardial-, renal- and neuro-protective effects. This study tests the hypothesis that madecassoside reduces the elevated blood glucose in experimental diabetes by protecting the β-cells. In in vivo study, diabetes was induced in overnight-fasted Sprague-Dawley rats using streptozotocin (60 mg/kg, i.v.) followed by nicotinamide (210 mg/kg, i.p.). Madecassoside (50 mg/kg) was administered orally daily for four weeks. Biochemical parameters such as fasting blood glucose, plasma insulin, HbA1c, liver and lipid parameters were measured, along with enzymatic and nonenzymatic activities, lipid peroxidation, histological iv and immunohistochemical studies. Rat insulinoma (INS-1E) cells was treated with madecassoside (10, 30, 60 μM) in the presence of high glucose (HG), hydrogen peroxide (H2O2), a cytokine cocktail (IL-1β, IFNγ and TNFα) or streptozotocin (STZ). Reactive oxygen species (ROS) measurement and apoptosis studies were also carried out in vitro. Madecassoside potentially normalized the elevated fasting blood glucose levels by increasing plasma insulin concentration, alleviated oxidative stress by improving enzymatic antioxidants and reducing lipid peroxidation in treated diabetic rats. Histopathological examination of the pancreas of madecassoside treated rats showed significant recovery of islet structural degeneration and also increased in area of islets compared to diabetic rats. Increased insulin granules in madecassoside treated rats as evidenced by the immunohistochemical study and improved expressions of GLUT4 also reflects the protective role of madecassoside. Furthermore, in in vitro studies, madecassoside showed non-cytotoxic effect on INS-1E cells, while reversing significant reduction of cell viability caused by HG, cytokine cocktail, H2O2 and STZ. Madecassoside also concentration-dependently reduced ROS production by INS-1E cells in response to these agents. Interestingly, the results demonstrate madecassoside’s capability in protecting the β-cells in vivo and in vitro. Thus, madecassoside may be useful in preserving the β-cells and managing type-2 diabetes mellitus.