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Fulltext Effects of amyloid precursor protein on pro-apoptotic pathway in neuronal cells

Leong, Yong Qi, Koh, R. Y., Chan, H. H., Leong, C. O.

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):29-29.
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Introduction: Amyloid plaques, mainly comprising of amyloid-beta peptides derived from its precursor protein, are found deposited in hippocampal and entorhinal cortical regions of patients with Alzheimer’s disease (AD). However, none led to a complete understanding of the molecular mechanisms of the AD in order to generate a new therapy that would eradicate the disease effectively. Activation of pro-apoptotic pathway was found to be associated with the accumulation of amyloid precursor protein (APP). The objective of this study is to examine theeffects of APP overexpression on the Bcl-2 family proteins involving in pro-apoptotic pathway in neuronal cells. Methods: The experiment was first performed with the transfection of HEK 293T cells for generation of lentiviral vector system consisting APP plasmid followed by transduction of SH-SY5Y neuronal cells using lentivirus generated. Subsequently, western blot analysis was conducted to validate the APP overexpression in SH-SY5Y cells. Then, expression levels of Bcl-2 family proteins in the APP overexpressed cells were determined by western blot analysis. The statistical analysis was performed by Microsoft Excel with Student’s t-test. Results: APP overexpression in SH-SY5Y cells slightly upregulated the pro-apoptotic proteins including Bad, Bid, Bok and Puma but slightly downregulated Bcl-2, Bim and Bax. Conclusion: Our data suggest that APP overexpression regulated the Bcl-2-mediated pathway by a significant downregulation of Bim protein in neuronal cells.
Fulltext Effects of amyloid precursor protein overexpression on nuclear factor kappa beta pathway in neuronal cells

Pan, M. L., Koh, R. Y., Chan, H. H., Leong, C. O.

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):33-33.
MyJurnal

Introduction: The aging process is the most significant risk factor for developing Alzheimer’s disease (AD). AD is the most common neurodegenerative disease that causes cognitive and memory impairment in the elderly. Excessive build-up of amyloid protein leads to cell death, brain atrophy, and cognitive and functional decline in AD. The nuclear factor kappa beta (NF-κB) is a family of inducible transcription factors composed of NF-κB1, NF-κB2, RelA, RelB and c-Rel. It is activated by genotoxic agents, as well as oxidative and inflammatory stresses. It regulates expression of genes that control apoptosis, cell cycle progression, cell senescence, and inflammation. NF-κB regulates amyloid precursor protein (APP) processing by activating transcription of β and γ secretases, which promotes amyloid dysregulation in AD. In addition, NF-κB activation is linked with many of the known lifespan regulators including insulin/IGF- 1, FOXO, SIRT, and mTOR. Therefore, NF-κB pathway contributes to the pathophysiology of AD. This study aims to evaluate the effects of APP overexpression on NF-κB pathway in neuronal cells. Methods: SH-SY5Y neuronal cells were transduced with APP plasmid. Overexpression of APP in the cells was validated by western blotting. Western blot analysis using antibodies targeting NF-κB signalling pathway was performed using the APP-overexpressed cells. Results: Overexpression of APP in cells caused a significant down-regulation of phosphorylated NF-κB. Overexpression of APP also slightly up-regulated IkappaB-alpha, IKK alpha, and IKK beta. Conclusion: APP overexpression affected NF-κB pathway by down-regulating NF-κB protein.
Antioxidant value and antiproliferative efficacy of mitragynine and a silane reduced analogue

Goh TB, Koh RY, Mordi MN, Mansor SM

Asian Pac J Cancer Prev, 2014;15(14):5659-65.
PMID: 25081682

BACKGROUND: To investigate the antioxidant value and anticancer functions of mitragynine (MTG) and its silane-reduced analogues (SRM) in vitro.
MATERIALS AND METHODS: MTG and SRM was analyzed for their reducing power ability, ABTS radical inhibition and 1,1-diphenyl-2-picryl hydrazylfree radicals scavenging activities. Furthermore, the antiproliferation efficacy was evaluated using MTT assay on K 562 and HCT116 cancer cell lines versus NIH/3T3 and CCD18-Co normal cell lines respectively.
RESULTS: SRM and MTG demonstrate moderate antioxidant value with ABTS assay (Trolox equivalent antioxidant capacity (TEAC): 2.25±0.02 mmol trolox / mmol and 1.96±0.04 mmol trolox / mmol respectively) and DPPH (IC50=3.75±0.04 mg/mL and IC50=2.28±0.02 mg/mL respectively). Both MTG and SRM demonstrate equal potency (IC50=25.20±1.53 and IC50= 22.19±1.06 respectively) towards K 562 cell lines, comparable to control, betulinic acid (BA) (IC5024.40±1.26). Both compounds showed concentration-dependent cytototoxicity effects and exert profound antiproliferative efficacy at concentration > 100 μM towards HCT 116 and K 562 cancer cell lines, comparable to those of BA and 5-FU (5-Fluorouracil). Furthermore, both MTG and SRM exhibit high selectivity towards HCT 116 cell lines with selective indexes of 3.14 and 2.93 respectively compared to 5-FU (SI=0.60).
CONCLUSIONS: These findings revealed that the medicinal and nutitional values of mitragynine obtained from ketum leaves that growth in tropical forest of Southeast Asia and its analogues does not limited to analgesic properties but could be promising antioxidant and anticancer or chemopreventive compounds.
Antidiabetic Potential of Syzygium sp.: An Overview

Zulcafli AS, Lim C, Ling AP, Chye S, Koh R

Yale J Biol Med, 2020 Jun;93(2):307-325.
PMID: 32607091

Diabetes, characterized by hyperglycemia, is one of the most significant metabolic diseases, reaching alarming pandemic proportions. It can be due to the defects in insulin action, or secretion, or both. The global prevalence of diabetes is estimated at 425 million people in 2017, and expected to rise to 629 million by 2045 due to an increasing trend of unhealthy lifestyles, physical inactivity, and obesity. Several treatment options are available to diabetics, however, some of the antidiabetic drugs result in adverse side effects such as hypoglycemia. Hence, there has been a proliferation of studies on natural products with antidiabetic effects, including plants from the Myrtaceae family, such as Psidium guajava, Eucalyptus globulus,Campomanesia xanthocarpa, and more significantly, Syzygium sp. Previous studies have shown that a number of Syzygium species had potent antidiabetic effects and were safe for consumption. This review aims to discuss the antidiabetic potential of Syzygium sp., based on in vitro and in vivo evidence.
Fulltext Melatonin Induced Schwann Cell Proliferation and Dedifferentiation Through NF-ĸB, FAK-Dependent but Src-Independent Pathways

Govindasamy N, Chung Chok K, Ying Ng P, Yian Koh R, Moi Chye S

Rep Biochem Mol Biol, 2022 Apr;11(1):63-73.
PMID: 35765532 DOI: 10.52547/rbmb.11.1.63

BACKGROUND: Peripheral nerve injury (PNI) is a common condition that compromises motor and sensory functions. Peripheral nerves are known to have regenerative capability and the pineal hormone, melatonin, is known to aid nerve regeneration. However, the role of Schwann cells and the pathways involved remain unclear. Thus, the aim of this study is to identify the effects of melatonin on Schwann cell proliferation, dedifferentiation, and the involvement of nuclear factor kappa light chain enhancer of activated B cells (NF-ĸB), focal adhesion kinase (FAK) and proto-oncogene tyrosine-protein kinase, Src pathways in this process.
METHODS: Schwann cells was treated with melatonin and its proliferation and dedifferentiation were identified using MTT assay and immunofluorescence staining for SRY (sex determining region Y)-box 2 (SOX2). Next, the protein expressions of NF-ĸB, FAK and Src pathways were identified by Western blot.
RESULTS: MTT results confirmed increased proliferation of Schwann cells with melatonin treatment, and it was highest at 10 μM melatonin. Immunofluorescent staining revealed an increase in the green fluorescence staining for SOX2 in melatonin-treated cells, showing enhanced dedifferentiation. Western blot assay revealed melatonin increased phospho-NF-ĸB (PNF-ĸB), IKK-α, FAK (D2R2E), phospho-FAK (Tyr 576/577 and Tyr 397) protein expressions as compared with control. However, Src (32G6), Lyn (C13F9), Fyn, Csk (C74C1) protein expressions were not increased as compared with control.
CONCLUSION: Melatonin promotes Schwann cell proliferation and dedifferentiation via NF-ĸB, FAK-dependent but Src-independent pathways.