Table 1.

The effects of OPP related to neuronal health.

Study Type	Sample/Population	Intervention Dose & Route	Findings	Reference
In vitro	Thioflavin T (ThT) binding assay	300 μL/10 mL of OPP concentration was added to Aβ 1–42 proteins.	ThT fluorescence intensity of the OPP treated assay was decreased compared to control.	[46]
	Familial AD and Wild-type B103 cells.	Both cells were incubated with OPP concentrations (150, 300, 500 μL/10 mL) for protein expression, while incubated with OPP concentration at 150, 300, 500 μL/10 mL for mRNA expression.	Protein expression levels APP In a dose-dependent manner, the APP protein expression in the FAD cells was decreased to the same level as the WT control. Additionally, OPP shows a minor reduction in APP levels even in the WT cells. COX-2 The addition of OPP had significantly decreased the amount of COX-2 protein expression to approximately the same level as the WT control. PARP The addition of OPP had significantly decrease the PARP protein expression in a dose dependent manner. mRNA levels APP There was no significant difference in APP mRNA level between the control and OPP-containing samples in FAD mutant cells. There was statistically significant fold difference in APP expression in WT cells when comparing WT control and WT 150 to WT 300 and WT 600 μL/10 mL samples. COX-2 In FAD cells, only 150 μL/10 mL OPP concentration showed significant difference in COX2 mRNA level while others did not show any changes. This might be related to contamination of the sample. For WT cells, its control and 150 μL/10 mL sample were statistically significant compared to 300 μL/10 mL sample and 600 μL/10 mL sample. In addition, the 300 μL/10 mL sample was statistically significant compared to 600 μL/10 mL sample.
In vitro	Transgenic yeast assay	OPP at a concentration ranges (0–10 µg/mL) were added and incubated with the assay.	For Congo Red dye binding, there were 50% inhibition of Aβ aggregation (IC50) at an OPP concentration of 3.24 μg/mL. For the dynamic light scattering method, there were successive prolongation of the lag phase and a lower slope of exponential fibrillar growth phase at higher OPP concentration. For the mass spectrometry method, only the monomeric Aβ could be observed at concentrations of 90, 900,4500 and 9000 µg/mL OPP. For 2D-IR spectroscopy, beta-sheet signal was absent following 10 h of incubation at 10 µg/mL OPP. In the transgenic yeast assay, the presence of 10 μg/mL OPP rescues the growth of the β-amyloid-producing yeast, Huntingtin-producing yeast and TDP-43-producing yeast ranging from 40–190%.	[50]
In vitro	U87 MG glioma cells	OPP given at 800 µg/mL to the cell line	OPP supplementation had upregulated Phase II antioxidant genes such as PRDX2, HMOX1, XPA, GPX1, HSPB1, MAPK8, SOD1, PRdx1, GSTM4 and HIF1A in the cell line. OPP supplementation demonstrated a mild up-regulation of GSS and GCLC as well as increased the GSH/GSSG ratio of astrocytes in the cell line. OPP supplementation had upregulated HO-1 and nrf2 protein expression in the cell line.	[55]
In vitro	Liposaccharide (LPS) activated BV-2 cell line	OPP added at concentration 50 to 800 µg/mL	OPP had significantly reduced the protein levels of inflammatory enzymes such as iNOS, COX-2 and prostaglandin-2 in the LPS-activated cells. OPP treatment had also significantly reduced the protein levels of NF- κB in the LPS-activated cells.	[55]
In vitro	IL-1β-activated normal human astrocytes	OPP added at concentration ranges at 0, 0.9, 1.8, 3.6 mg/mL.	OPP had significantly reduced level of TNFα, RANTES, and IP-10 in a dose-dependent and time-dependent manner when compared to the control. OPP had significantly reduced ROS production by IL-1β-activated astrocytes. OPP reduced the expression of ICAM and VCAM, both in activated and non-activated human astrocytes in vitro.	[56]
In vivo	Male inbred BALB/c mice	OPP was given as drinking fluid for 6 weeks.	OPP treatment showed a downward trend in latency, mean distance and mean velocity in water maze trials when compared to control. OPP treatment showed an upward trend for average time, average distance travelled and average stopping speed before falling off the rotating drums in rotarod test compared to control. OPP have upregulated genes involved in brain development and activity such as Arc, Cast or D14Ertd171e, Gria3, Kcnb1, Kcnab1, Homer1, Dlgap2, Dlgh4, Sv2b, Stx1a, Gucy1b3, Ncald, Bzrap1 and Pclo. OPP had downregulated genes involved in inflammation such as Spp1, Saa3 and Apod. OPP had also downregulated genes involved in focal adhesion and metabolism of amino acid including alanine, aspartate, valine, leucine, and isoleucine.	[42]
In vivo	32 in-bred aged Brown Norway rats induced with high fat diet for 5 months (23 weeks)	OPP given as 5% purified-diet pellets	From month 1 to month 5, OPP- fed rats showed improvement in escape latency on Morris water maze test. OPP-treated rats revealed few traces of amyloid deposition compared to high-fat control rats in Congo red staining.	[53]
In vivo	32 in-bred aged Brown Norway rats induced with high fat diet for 5 months (23 weeks)	OPP given as 5% purified-diet pellets	OPP-fed rats had a significant improvement in Escape Latency of Morris Water Maze test (p < 0.05) compared to control and high-cholesterol groups OPP-treated group preserved more healthy neurons and demonstrated lower density of plaque deposition in the hippocampal CA-1 and DG areas when compared to high cholesterol fed diet rats in H&E staining. OPP had also significantly lower ß-amyloid 42 level when compared to control and high-cholesterol diet groups. OPP-fed group had also significantly lower plasma, liver and brain MDA level compared to high cholesterol fed group OPP-fed group had significantly lower 3-HOB level compared to high cholesterol group. OPP-fed group showed insignificant difference in IL-6 level compared to high cholesterol group OPP-fed group showed significantly lower gene expression of APP, BACE-1, and ApoE compared to high cholesterol diet group.	[43]