Neuroprotective and antineuroinflammatory effects of myrmecodia platytyrea tuber aqueous extract / Nor Ayuni Nordin

Myrmecodia platytyrea (Family: Rubiaceae) is commonly known as the Ant-nest plant and locally as Sarang Semut. It is used in Indonesian traditional medicine for the management of oxidative stress- and inflammation-related diseases such as cancer, diabetes mellitus, cardiovascular diseases and could have potential in treating Alzheimer's disease (AD). Hence, our study aimed to investigate the potential of M. platytyrea tuber aqueous extract (MPAE) in inhibiting neuroinflammation, in vitro and in vivo. The in vitro antineuroinfiammatory effects of MPAE (0.025 - 0.5 mg/ml) were investigated by measuring the cytotoxicity and proinflammatory cytokines (TNF-a, IL 1/3 and IL-6) production in FeSC>4-, H2O2- and LPS-stimulated astrocyte cell line. For the in vivo study, MPAE was assessed in non-LPS mice and LPS-neuroinflammation mice model by Morris water maze (MWM) test. ICR male mice aged 24 weeks were grouped into four and six groups (n=6/group), respectively to each model. For first model, Group 1 was pretreated with distilled water (10 ml/kg, p.o.) while Group 2-4 with MPAE (100, 200 and 400 mg/kg, p.o.). In LPS-model, Group 1 and 2 were pretreated for six days with distilled water, Group 3 with standard nootropic agent, piracetam (400 mg/kg, p.o.) and Group 4-6 with MPAE (100,200 and 400 mg/kg, p.o.). Then, LPS (3 mg/kg; i.p) was administered to the mice of Group 2-6 for 3 days. The mice were subjected to 2 days of training followed by 3 days of MWM test and a day of probe test. Next, the brain was collected for bioassay analysis and molecular works. The antioxidant enzymes (SOD, CAT, GPx), inflammatory cytokines (TNF-a, IL-6, IL 1/3), cholinergic activities (ACh and AChE) and amyloid protein (A/3i-4o and Aj8i-42) assays were conducted using ELISA assay. Meanwhile, inflammatory markers (COX 1, COX-2, PGE2, iNOS and NFK/3) were determined via RT-PCR from the brain homogenate. From the results, MPAE was not cytotoxic on astrocytes with IC50 value of 1.54±0.26 mg/mL. However, MPAE did not protect the astrocytes against Fe2S04, H2O2, or LPS but demonstrated an increment of cell death in the astrocytes in a dose dependent manner. The level of the cytokines was increased dose-dependently. Treatment of MPAE on non-LPS mice significantly (p