Publications by authors named "Ammu Radhakrishnan"

69 Publications

Development, Characterization, and Evaluation of α-Mangostin-Loaded Polymeric Nanoparticle Gel for Topical Therapy in Skin Cancer.

Gels 2021 Nov 24;7(4). Epub 2021 Nov 24.

School of Pharmaceutical and population Health Informatics (SoPPHI), DIT University, Dehradun 248009, India.

The aim of this study was to prepare and evaluate α-mangostin-loaded polymeric nanoparticle gel (α-MNG-PLGA) formulation to enhance α-mangostin delivery in an epidermal carcinoma. The poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were developed using the emulsion-diffusion-evaporation technique with a 3-level 3-factor Box-Behnken design. The NPs were characterized and evaluated for particle size distribution, zeta potential (mV), drug release, and skin permeation. The formulated PLGA NPs were converted into a preformed carbopol gel base and were further evaluated for texture analysis, the cytotoxic effect of PLGA NPs against B16-F10 melanoma cells, and in vitro radical scavenging activity. The nanoscale particles were spherical, consistent, and average in size (168.06 ± 17.02 nm), with an entrapment efficiency (EE) of 84.26 ± 8.23% and a zeta potential of -25.3 ± 7.1 mV. Their drug release percentages in phosphate-buffered solution (PBS) at pH 7.4 and pH 6.5 were 87.07 ± 6.95% and 89.50 ± 9.50%, respectively. The release of α-MNG from NPs in vitro demonstrated that the biphasic release system, namely, immediate release in the initial phase, was accompanied by sustained drug release. The texture study of the developed α-MNG-PLGA NPs gel revealed its characteristics, including viscosity, hardness, consistency, and cohesiveness. The drug flux from α-MNG-PLGA NPs gel and α-MNG gel was 79.32 ± 7.91 and 16.88 ± 7.18 µg/cm/h in 24 h, respectively. The confocal study showed that α-MNG-PLGA NPs penetrated up to 230.02 µm deep into the skin layer compared to 15.21 µm by dye solution. MTT assay and radical scavenging potential indicated that α-MNG-PLGA NPs gel had a significant cytotoxic effect and antioxidant effect compared to α-MNG gel ( < 0.05). Thus, using the developed α-MNG-PLGA in treating skin cancer could be a promising approach.
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http://dx.doi.org/10.3390/gels7040230DOI Listing
November 2021

Clinically Relevant Genes and Proteins Modulated by Tocotrienols in Human Colon Cancer Cell Lines: Systematic Scoping Review.

Nutrients 2021 Nov 12;13(11). Epub 2021 Nov 12.

Jeffery Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway 47500, Malaysia.

The last decade has witnessed tremendous growth in tocotrienols (T3s) research, especially in the field of oncology, owing to potent anticancer property. Among the many types of cancers, colorectal cancer (CRC) is growing to become a serious global health threat to humans. Chemoprevention strategies in recent days are open to exploring alternative interventions to inhibit or delay carcinogenesis, especially with the use of bioactive natural compounds, such as tocotrienols. This scoping review aims to distil the large bodies of literature from various databases to identify the genes and their encoded modulations by tocotrienols and to explicate important mechanisms via which T3s combat CRC. For this scoping review, research papers published from 2010 to early 2021 related to T3s and human CRC cells were reviewed in compliance with the PRISMA guidelines. The study included research articles published in English, searchable on four literature databases (Ovid MEDLINE, PubMed, Scopus, and Embase) that reported differential expression of genes and proteins in human CRC cell lines following exposure to T3s. A total of 12 articles that fulfilled the inclusion and exclusion criteria of the study were short-listed for data extraction and analysis. The results from the analysis of these 12 articles showed that T3s, especially its γ and δ analogues, modulated the expression of 16 genes and their encoded proteins that are associated with several important CRC pathways (apoptosis, transcriptional dysregulation in cancer, and cancer progression). Further studies and validation work are required to scrutinize the specific role of T3s on these genes and proteins and to propose the use of T3s to develop adjuvant or multi-targeted therapy for CRC.
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http://dx.doi.org/10.3390/nu13114056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625890PMC
November 2021

Identification of blood-based biomarkers for diagnosis and prognosis of Parkinson's disease: A systematic review of proteomics studies.

Ageing Res Rev 2021 Nov 16;73:101514. Epub 2021 Nov 16.

Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia.

Parkinson's Disease (PD), a neurodegenerative disorder, is characterised by the loss of motor function and dopamine neurons. Therapeutic avenues remain a challenge due to lack of accuracy in early diagnosis, monitoring of disease progression and limited therapeutic options. Proteomic platforms have been utilised to discover biomarkers for numerous diseases, a tool that may benefit the diagnosis and monitoring of disease progression in PD patients. Therefore, this systematic review focuses on analysing blood-based candidate biomarkers (CB) identified via proteomics platforms for PD. This study systematically reviewed articles across six databases (EMBASE, Cochrane, Ovid Medline, Scopus, Science Direct and PubMed) published between 2010 and 2020. Of the 504 articles identified, 12 controlled-PD studies were selected for further analysis. A total of 115 candidate biomarkers (CB) were identified across selected 12-controlled studies, of which 23 CB were found to be replicable in more than two cohorts. Using the PANTHER Go-Slim classification system and STRING network, the gene function and protein interactions between biomarkers were analysed. Our analysis highlights Apolipoprotein A-I (ApoA-I), which is essential in lipid metabolism, oxidative stress, and neuroprotection demonstrates high replicability across five cohorts with consistent downregulation across four cohorts. Since ApoA-I was highly replicable across blood fractions, proteomic platforms and continents, its relationship with cholesterol, statin and oxidative stress as PD biomarker, its role in the pathogenesis of PD is discussed in this paper. The present study identified ApoA-I as a potential biomarker via proteomics analysis of PD for the early diagnosis and prediction of disease progression.
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http://dx.doi.org/10.1016/j.arr.2021.101514DOI Listing
November 2021

Transitioning pre-clinical glioblastoma models to clinical settings with biomarkers identified in 3D cell-based models: A systematic scoping review.

Biomed Pharmacother 2021 Nov 11;145:112396. Epub 2021 Nov 11.

Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor, Malaysia.

Glioblastoma (GBM) remains incurable despite the overwhelming discovery of 2-dimensional (2D) cell-based potential therapeutics since the majority of them have met unsatisfactory results in animal and clinical settings. Incremental empirical evidence has laid the widespread need of transitioning 2D to 3-dimensional (3D) cultures that better mimic GBM's complex and heterogenic nature to allow better translation of pre-clinical results. This systematic scoping review analyses the transcriptomic data involving 3D models of GBM against 2D models from 22 studies identified from four databases (PubMed, ScienceDirect, Medline, and Embase). From a total of 499 genes reported in these studies, 313 (63%) genes were upregulated across 3D models cultured using different scaffolds. Our analysis showed that 4 of the replicable upregulated genes are associated with GBM stemness, epithelial to mesenchymal transition (EMT), hypoxia, and migration-related genes regardless of the type of scaffolds, displaying close resemblances to primitive undifferentiated tumour phenotypes that are associated with decreased overall survival and increased hazard ratio in GBM patients. The upregulation of drug response and drug efflux genes (e.g. cytochrome P450s and ABC transporters) mirrors the GBM genetic landscape that contributes to in vivo and clinical treatment resistance. These upregulated genes displayed strong protein-protein interactions when analysed using an online bioinformatics software (STRING). These findings reinforce the need for widespread transition to 3D GBM models as a relatively inexpensive humanised pre-clinical tool with suitable genetic biomarkers to bridge clinical gaps in potential therapeutic evaluations.
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http://dx.doi.org/10.1016/j.biopha.2021.112396DOI Listing
November 2021

Evaluating Anticancer and Immunomodulatory Effects of (Arthrospira) and Gamma-Tocotrienol Supplementation in a Syngeneic Mouse Model of Breast Cancer.

Nutrients 2021 Jul 6;13(7). Epub 2021 Jul 6.

School of Health Sciences, International Medical University, Kuala Lumpur 57000, Malaysia.

Nutrition can modulate host immune responses as well as promote anticancer effects. In this study, two nutritional supplements, namely gamma-tocotrienol (γT3) and were evaluated for their immune-enhancing and anticancer effects in a syngeneic mouse model of breast cancer (BC). Five-week-old female BALB/c mice were fed , γT3, or a combination of and γT3 ( + γT3) for 56 days. The mice were inoculated with 4T1 cells into their mammary fat pad on day 28 to induce BC. The animals were culled on day 56 for various analyses. A significant reduction ( < 0.05) in tumor volume was only observed on day 37 and 49 in animals fed with the combination of γT3 + . There was a marked increase ( < 0.05) of CD4/CD127 T-cells and decrease ( < 0.05) of T-regulatory cells in peripheral blood from mice fed with either γT3 or The breast tissue of the combined group showed abundant areas of necrosis, but did not prevent metastasis to the liver. Although there was a significant increase ( < 0.05) of MIG-6 and Cadherin 13 expression in tumors from γT3-fed animals, there were no significant ( > 0.05) differences in the expression of MIG-6, Cadherin 13, BIRC5, and Serpine1 upon combined feeding. This showed that combined γT3 + treatment did not show any synergistic anticancer effects in this study model.
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http://dx.doi.org/10.3390/nu13072320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308567PMC
July 2021

Reduced infiltration of regulatory T cells in tumours from mice fed daily with gamma-tocotrienol supplementation.

Clin Exp Immunol 2021 Nov 18;206(2):161-172. Epub 2021 Aug 18.

Pathology Division, School of Medicine, International Medical University, Kuala Lumpur, Malaysia.

Gamma-tocotrienol (γT3) is an analogue of vitamin E with beneficial effects on the immune system, including immune-modulatory properties. This study reports the immune-modulatory effects of daily supplementation of γT3 on host T helper (Th) and T regulatory cell (T ) populations in a syngeneic mouse model of breast cancer. Female BALB/c mice were fed with either γT3 or vehicle (soy oil) for 2 weeks via oral gavage before they were inoculated with syngeneic 4T1 mouse mammary cancer cells (4T1 cells). Supplementation continued until the mice were euthanized. Mice (n = 6) were euthanized at specified time-points for various analysis (blood leucocyte, cytokine production and immunohistochemistry). Tumour volume was measured once every 7 days. Gene expression studies were carried out on tumour-specific T lymphocytes isolated from splenic cultures. Supplementation with γT3 increased CD4 (p < 0.05), CD8 (p < 0.05) T-cells and natural killer cells (p < 0.05) but suppressed T cells (p < 0.05) in peripheral blood when compared to animals fed with the vehicle. Higher interferon (IFN)-γ and lower transforming growth factor (TGF)-ꞵ levels were noted in the γT3 fed mice. Immunohistochemistry findings revealed higher infiltration of CD4 cells, increased expression of interleukin-12 receptor-beta-2 (IL-12ꞵ2R), interleukin (IL)-24 and reduced expression of cells that express the forkhead box P3 (FoxP3) in tumours from the γT3-fed animals. Gene expression studies showed the down-regulation of seven prominent genes in splenic CD4 T cells isolated from γT3-fed mice. Supplementation with γT3 from palm oil-induced T cell-dependent cell-mediated immune responses and suppressed T cells in the tumour microenvironment in a syngeneic mouse model of breast cancer.
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http://dx.doi.org/10.1111/cei.13650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506134PMC
November 2021

Poloxamer 188 (P188), A Potential Polymeric Protective Agent for Central Nervous System Disorders: A Systematic Review.

Curr Neuropharmacol 2021 May 28. Epub 2021 May 28.

Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway 47500, Selangor, Malaysia.

Poloxamer 188 (P188) is an FDA-approved biocompatible block copolymer composed of repeating units of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO). Due to its amphiphilic nature and high hydrophile-lipophile balance (HLB) value of 29, P188 is used as a stabilizer/emulsifier in many cosmetics and pharmaceuticals preparations. While the applications of P188 as an excipient are widely explored, the data on the pharmacological activity of P188 are scarce. Notably, the neuroprotective potential of P188 has gained a lot of interest. Therefore, this systematic review is aimed to review evidence to support the neuroprotective potential of P188 in CNS disorders. The PRISMA model was used, and five databases (Google Scholar, SCOPUS, Wiley Online Library, ScienceDirect, and PubMed) were searched with relevant keywords. The research resulted in 11 articles, which met the inclusion criteria. These articles described the protective effects of P188 on traumatic brain injury or mechanical injury in cells, neurotoxicity, Parkinson's disease, Amyotrophic lateral sclerosis (ALS), and ischemia/ reperfusion injury from stroke. All the articles were original research in experimental or pre-clinical stages using animal models or in vitro systems. The reported activities demonstrated the potential of P188 as a neuroprotective agent in improving CNS conditions such as neurodegeneration.
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http://dx.doi.org/10.2174/1570159X19666210528155801DOI Listing
May 2021

Effects of Probiotics on Anxiety, Stress, Mood and Fitness of Badminton Players.

Nutrients 2021 May 24;13(6). Epub 2021 May 24.

Sports Science Programme, Faculty of Sports Science and Recreation, Universiti Teknologi MARA, Shah Alam 40450, Malaysia.

Background: Reports of probiotic consumption on athletes' performance are debatable due to their equivocal results. There is a need for more evidence on the effects of probiotic intake on psychological state and fitness level. Thus, this study determined the effects of daily probiotic consumption on competitive anxiety, perceived stress and mood among university badminton players, besides their fitness like aerobic capacity, strength, speed, leg power and agility.

Methods: Thirty university badminton players aged from 19 to 22 years old were randomly divided equally into two groups, where the probiotic group (PG; = 15) received a drink that contained Shirota (3 × 10 CFU) and placebo group (CG; = 15) a placebo drink for six weeks. Anxiety, stress and mood levels were determined using the CSAI-2R, PSS and BRUMS questionnaires, respectively. Fitness levels were measured using by subjecting the players to 20-m shuttle runs (aerobic capacity), handgrips (muscular strength), vertical jumps (leg power), 40-m dash (speed) and T-test (agility). The Student's -test ( < 0.05) was used to determine the differences between PG and CG players.

Results: After six weeks, the anxiety and stress levels of PG players significantly decreased by 16% ( < 0.001) and 20% ( < 0.001), respectively, but there were no significant changes detected in CG players. Supplementation of probiotics also improved aerobic capacity in PG players by 5.9% ( < 0.001) but did not influence the speed, strength, leg power and agility.

Conclusions: Probiotics supplementation showed improved aerobic capacity and relieve anxiety and stress. However, further studies need to be carried out to determine the mechanisms through which probiotic intake produces these effects.
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http://dx.doi.org/10.3390/nu13061783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225117PMC
May 2021

Tocotrienols Ameliorate Neurodegeneration and Motor Deficits in the 6-OHDA-Induced Rat Model of Parkinsonism: Behavioural and Immunohistochemistry Analysis.

Nutrients 2021 May 10;13(5). Epub 2021 May 10.

College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia.

Parkinson's disease (PD) is a debilitating neurodegenerative disease, which progresses over time, causing pathological depigmentation of the substantia nigra (SN) in the midbrain due to loss of dopaminergic neurons. Emerging studies revealed the promising effects of some nutrient compounds in reducing the risk of PD. One such nutrient compound that possess neuroprotective effects and prevents neurodegeneration is tocotrienol (T3), a vitamin E family member. In the present study, a single dose intracisternal injection of 250 µg 6-hydroxydopamine (6-OHDA) was used to induce parkinsonism in male Sprague Dawley (SD) rats. Forty-eight hours post injection, the SD rats were orally supplemented with alpha (α)- and gamma (γ)-T3 for 28 days. The neuroprotective effects of α- and γ-T3 were evaluated using behavioural studies and immunohistochemistry (IHC). The findings from this study revealed that supplementation of α- and γ-T3 was able to ameliorate the motor deficits induced by 6-OHDA and improve the neuronal functions by reducing inflammation, reversing the neuronal degradation, and preventing further reduction of dopaminergic neurons in the SN and striatum (STR) fibre density.
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http://dx.doi.org/10.3390/nu13051583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150907PMC
May 2021

Influence of serum concentration in retinoic acid and phorbol ester induced differentiation of SH-SY5Y human neuroblastoma cell line.

Mol Biol Rep 2020 Nov 23;47(11):8775-8788. Epub 2020 Oct 23.

School of Postgraduate Studies, International Medical University, Kuala Lumpur, Malaysia.

Numerous protocols to establish dopaminergic phenotype in SH-SY5Y cells have been reported. In most of these protocols there are variations in concentration of serum used. In this paper, we compared the effects of high (10%), low (3%) and descending (2.5%/1%) serum concentration in differentiation medium containing different proportion of retinoic acid (RA) and 12-O-Tetradecanoylphorbol-13-acetate (TPA) or RA-only on the undifferentiated SH-SY5Y cells with regards to cell morphology, biochemical and gene expression alterations. Cells differentiated in culture medium containing low and descending serum concentrations showed increased number of neurite projections and reduced proliferation rates when compared to undifferentiated cells. The SH-SY5Y cells differentiated in culture medium containing 3% RA and low serum or descending (2.5%/1% RA/TPA) were found to be more susceptible to 6-hydroxydopamine (6-OHDA) induced cytotoxicity. Cells differentiated with RA/TPA or RA differentiated showed increased production of the α-synuclein (SNCA) neuroprotein and dopamine neurotransmitter compared to undifferentiated cells, regardless serum concentrations used. There was no significant difference in the expression of tyrosine hydroxylase (TH) gene between undifferentiated and differentiated SH-SY5Y cells. However, the expression of dopamine receptor D2 (DRD2) gene was markedly increased (p<0.05) in differentiated cells with 3% serum and RA only when compared to undifferentiated cells. In conclusion, to terminally differentiate SH-SY5Y cells to be used as a cell-based model to study Parkinson's disease (PD) to investigate molecular mechanisms and drug discovery, the optimal differentiation medium should contain 3% serum in RA-only.
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http://dx.doi.org/10.1007/s11033-020-05925-2DOI Listing
November 2020

Efficacy of Emu Oil Transfersomes for Local Transdermal Delivery of 4-OH Tamoxifen in the Treatment of Breast Cancer.

Pharmaceutics 2020 Aug 25;12(9). Epub 2020 Aug 25.

Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia.

Oral tamoxifen used in the prevention and treatment of ductal carcinoma in situ (DCIS) (estrogen-positive) patients has limited acceptance, due to its adverse side effects. The efficacy of tamoxifen is related to its major metabolite, 4-hydroxytamoxifen. Local transdermal therapy of 4-hydroxytamoxifen to the breast might avert the toxicity of oral tamoxifen, while maintaining efficacy. We aim to study the skin irritancy, as well as to evaluate the efficacy of the developed transfersome formulations, with/without emu oil, using a syngeneic mouse model of breast cancer. We also quantified tamoxifen/4-hydroxytamoxifen concentrations in blood plasma and performed histopathology. The skin irritancy test showed that the pure emu oil and transfersome formulations with or without the emu oil did not cause skin irritancy in the animals studied. A sensitive and specific LC-MS/MS method for the quantification of tamoxifen and 4-hydroxytamoxifen was developed and validated. Studies on tumor volume and necrosis (histopathology) using the breast cancer mouse model showed that the 4-OHT transfersomal formulations, with and without emu oil, showed comparable efficacy with that of orally administered tamoxifen. However, the transfersomal formulations, with and without emu oil, resulted in significantly lower (10.24 ± 0.07 and 32.45 ± 0.48 ng/mL, respectively) plasma concentrations of 4-hydroxytamoxifen, compared to the oral tamoxifen (TAMX) group (634.42 ± 7.54 ng/mL). This study demonstrated the potential use of emu oil in a local transdermal formulation for the treatment of breast cancer and its reduced adverse effects.
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http://dx.doi.org/10.3390/pharmaceutics12090807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558379PMC
August 2020

Ratite oils for local transdermal therapy of 4-OH tamoxifen: development, characterization, and evaluation.

J Liposome Res 2021 Sep 30;31(3):217-229. Epub 2020 Aug 30.

Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Subang Jaya, Malaysia.

The anti-inflammatory property of ratite oils as well as its ability to act as a penetration enhancer makes it an ideal agent to be used in transdermal formulations. The present study aims to develop an effective transfersomal delivery of 4-hydroxytamoxifen (4-OHT), an anti-cancer drug, using ratite oil as a carrier agent for the treatment of breast cancer (BC). The 4-OHT transfersomes were prepared with and without ratite oils using soy phosphatidylcholine and three different edge activators (EAs) in five different molar ratios using the rotary evaporation-ultrasonication method. Optimal transfersome formulations were selected using physical-chemical characterization and studies. Results from physical-chemical characterization of the developed formulations found sodium taurocholate to be the most suitable EA, which recorded highest entrapment efficiency of 95.1 ± 2.70% with 85:15, (w/w) and lowest vesicle size of 82.3 ± 0.02 nm with 75:25, (w/w) molar ratios. TEM and DSC studies showed that the vesicles were readily identified and present in a nearly perfect spherical shape. In addition, formulations with emu oil had better stability than formulations with ostrich oil. Physical stability studies at 4 °C showed that ratite oil transfersomes were stable up to 4 weeks, while transfersomes without ratite oils were stable for 8 weeks. permeability studies using porcine skin concluded that 4-OHT transfersomal formulations with (85:15, w/w) without emu oil have the potential to be used in transdermal delivery approach to enhance permeation of 4-OHT, which may be beneficial in the treatment of BC.
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http://dx.doi.org/10.1080/08982104.2020.1777155DOI Listing
September 2021

A Novel Method to Identify Autoantibodies against Putative Target Proteins in Serum from beta-Thalassemia Major: A Pilot Study.

Biomedicines 2020 Apr 26;8(5). Epub 2020 Apr 26.

School of Medicine, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia.

Abnormal immune reactivity in patients with beta-thalassemia (beta-thal) major can be associated with poor prognosis. Immunome protein-array analysis represents a powerful approach to identify novel biomarkers. The Sengenics Immunome Protein Array platform was used for high-throughput quantification of autoantibodies in 12 serum samples collected from nine beta-thal major patients and three non-thalassemia controls, which were run together with two pooled normal sera (Sengenics Internal QC samples). To obtain more accurate and reliable results, the evaluation of the biological relevance of the shortlisted biomarkers was analyzed using an Open Target Platform online database. Elevated autoantibodies directed against 23 autoantigens on the immunome array were identified and analyzed using a penetrance fold change-based bioinformatics method. Understanding the autoantibody profile of beta-thal major patients would help to further understand the pathogenesis of the disease. The identified autoantigens may serve as potential biomarkers for the prognosis of beta-thal major.
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http://dx.doi.org/10.3390/biomedicines8050097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277850PMC
April 2020

Nose to brain delivery of rotigotine loaded chitosan nanoparticles in human SH-SY5Y neuroblastoma cells and animal model of Parkinson's disease.

Int J Pharm 2020 Apr 19;579:119148. Epub 2020 Feb 19.

Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address:

Rotigotine, a non-ergoline dopamine agonist, has been shown to be highly effective for the treatment of Parkinson's disease (PD). However, despite its therapeutic potential, its' clinical applications were hindered due to low aqueous solubility, first-pass metabolism and low bioavailability. Therefore, we developed rotigotine-loaded chitosan nanoparticles (RNPs) for nose-to-brain delivery and evaluated its neuronal uptake, antioxidant and neuroprotective effects using cell-based studies. The pharmacological effects of nose-to-brain delivery of the RNPs were also evaluated in an animal model of PD. The average particle size, particle size distribution and entrapment efficiency of the RNPs were found to be satisfactory. Exposure of RNPs for 24 h did not show any cytotoxicity towards SH-SY5Y human neuroblastoma cells. Furthermore, the RNPs caused a decrease in alpha-synuclein (SNCA) and an increase in tyrosine hydroxylase (TH) expression in these cells, suggestion that the exposure alleviated some of the direct neurotoxic effects of 6-OHDA. Behavioral and biochemical testing of RNPs in haloperidol-induced PD rats showed a reversal of catalepsy, akinesia and restoration of swimming ability. A decrease in lactate dehydrogenase (LDH) and an increase in catalase activities were also observed in the brain tissues. The results from the animal model of PD show that intranasally-administered RNPs enhanced brain targeting efficiency and drug bioavailability. Thus, RNPs for nose-to-brain delivery has significant potential to be developed as a treatment approach for PD.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119148DOI Listing
April 2020

Advancing the Role of Gamma-Tocotrienol as Proteasomes Inhibitor: A Quantitative Proteomic Analysis of MDA-MB-231 Human Breast Cancer Cells.

Biomolecules 2019 12 21;10(1). Epub 2019 Dec 21.

Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

Tocotrienol, an analogue of vitamin E has been known for its numerous health benefits and anti-cancer effects. Of the four isoforms of tocotrienols, gamma-tocotrienol (γT3) has been frequently reported for their superior anti-tumorigenic activity in both in vitro and in vivo studies, when compared to its counterparts. In this study, the effect of γT3 treatment in the cytoplasmic and nuclear fraction of MDA-MB-231 human breast cancer cells were assessed using the label-free quantitative proteomics analysis. The cytoplasmic proteome results revealed the ability of γT3 to inhibit a group of proteasome proteins such as PSMA, PSMB, PSMD, and PSME. The inhibition of proteasome proteins is known to induce apoptosis in cancer cells. As such, the findings from this study suggest γT3 as a potential proteasome inhibitor that can overcome deficiencies in growth-inhibitory or pro-apoptotic molecules in breast cancer cells. The nuclear proteome results revealed the involvement of important nuclear protein complexes which hardwire the anti-tumorigenesis mechanism in breast cancer following γT3 treatment. In conclusion, this study uncovered the advancing roles of γT3 as potential proteasomes inhibitor that can be used for the treatment of breast cancer.
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http://dx.doi.org/10.3390/biom10010019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022772PMC
December 2019

Palm Tocotrienol-Adjuvanted Dendritic Cells Decrease Expression of the Gene in Murine Breast Cancer Cells and Tissues.

Vaccines (Basel) 2019 Nov 27;7(4). Epub 2019 Nov 27.

.Pathology Division, School of Medicine, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.

The aim of this study was to evaluate the effectiveness of immunotherapy using dendritic cells (DC) pulsed with tumor lysate (a DC vaccine) in combination with daily supplementation of tocotrienol-rich fraction (TRF) to potentiate anti-tumor immune responses. We had previously reported that DC-vaccine immunotherapy together with TRF supplementation induced protective immunity to tumor challenge. Breast cancer was induced in female BALB/c mice. The mice were randomly assigned into the treatment groups. At autopsy, peripheral blood was collected in heparinized tube and the expression of cell surface molecules (CD40, CD80, CD83, and CD86) that are crucial for T-cell activation and survival were analyzed by flow cytometry. Tumor was excised from each animal and snap-frozen. Total RNA was extracted from each tumor tissue for microarray and gene expression analysis. Total protein was extracted from tumor tissue for protein expression studies using Western blotting. The results show that systemic administration of 1 mg TRF daily in combination with DC-vaccine immunotherapy (DC + TL + TRF) caused a marked reduction ( < 0.05) of tumor size and increased ( < 0.05) the survival rates of the tumor-inoculated mice. The expression of CD40, CD80, CD83, and CD86 were upregulated in peripheral blood from the DC + TL + TRF group compared to other groups. In addition, there was higher expression of FasL in tumor-excised mice from the DC + TL + TRF group compared to other groups. FasL plays an important role in maintaining immune privilege and is required for cytotoxic T-lymphocyte (CTL) activity. Microarray analysis identified several genes involved in the regulation of cancer. In this study, we focused on the special AT rich binding protein 1 gene, which was reported to have dual functions, one of which was to induce aggressive growth in breast cancer cells. Tumors from DC + TL + TRF mice showed lower ( < 0.05) expression of gene. Further study will be conducted to investigate the molecular functions of and the role of in 4T1 mammary cancer cells and DC. In conclusion, TRF supplementation can potentiate the effectiveness of DC-vaccine immunotherapy.
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http://dx.doi.org/10.3390/vaccines7040198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963955PMC
November 2019

Bioactive Compounds: Natural Defense Against Cancer?

Biomolecules 2019 11 21;9(12). Epub 2019 Nov 21.

Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor 47500, Malaysia.

Cancer is a devastating disease that has claimed many lives. Natural bioactive agents from plants are gaining wide attention for their anticancer activities. Several studies have found that natural plant-based bioactive compounds can enhance the efficacy of chemotherapy, and in some cases ameliorate some of the side-effects of drugs used as chemotherapeutic agents. In this paper, we have reviewed the literature on the anticancer effects of four plant-based bioactive compounds namely, curcumin, myricetin, geraniin and tocotrienols (T3) to provide an overview on some of the key findings that are related to this effect. The molecular mechanisms through which the active compounds may exert their anticancer properties in cell and animal-based studies also discussed.
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http://dx.doi.org/10.3390/biom9120758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995630PMC
November 2019

Investigation of the curative effects of palm vitamin E tocotrienols on autoimmune arthritis disease in vivo.

Sci Rep 2019 11 14;9(1):16793. Epub 2019 Nov 14.

Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, 43400, Malaysia.

The tocotrienol-rich fraction (TRF) from palm oil contains vitamin E, which possesses potent antioxidant and anti-inflammatory activities. Rheumatoid arthritis (RA) is a chronic joint inflammatory disease characterised by severe joint pain, cartilage destruction, and bone erosion owing to the effects of various pro-inflammatory mediators and cytokines. Here, we investigated the therapeutic effects of TRF in a rat model of collagen-induced arthritis (CIA). Arthritis was induced by a single intradermal injection of collagen type II in Dark Agouti (DA) rats. Rats were then treated with or without TRF by oral gavage from day 28 after the first collagen injection. Arthritic rats supplemented with TRF showed decreased articular index scores, ankle circumferences, paw volumes, and radiographic scores when compared with untreated rats. The untreated arthritic rats showed higher plasma C-reactive protein levels (p < 0.05) and production of pro-inflammatory cytokines than arthritic rats fed TRF. Moreover, there was a marked reduction in the severity of histopathological changes observed in arthritic rats treated with TRF compared with that in untreated arthritic rats. Overall, the results show that TRF had beneficial effects in this rat model of RA.
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http://dx.doi.org/10.1038/s41598-019-53424-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856359PMC
November 2019

Medical students' orientation toward lifelong learning in an outcome-based curriculum and the lessons learnt.

Med Teach 2021 Jul 13;43(sup1):S6-S11. Epub 2019 Aug 13.

Faculty of Medicine and Health, International Medical University, Kuala Lumpur, Malaysia.

Background: Lifelong learning (LL) is an important outcome of medical training. The objective of this study is to measure the orientation of medical students toward LL and to determine the types of self-directed learning (SDL) activities that contribute toward LL skills.

Methods: The Jefferson Scale of Physician Lifelong Learning for medical student (JeffSPLL-MS) questionnaire was used. Factor analysis was performed, Cronbach's alpha and effect size were calculated. The types of learning activities that contribute to LL skills were identified.

Results: Three-factor structure emerged from the factor analysis and were identified as learning beliefs and motivation, skills in seeking information and attention to learning opportunities. A significant increase ( < .05; ES = 0.27) in orientation toward LL with academic progression was observed. Clinical students improved significantly in the domains of 'skills in seeking information' ( < .001; ES = 0.48) and 'attention to learning opportunities' ( < .001; ES = 0.55). Problem-based learning, flipped classroom, guided reading, projects and experiential learning activities are perceived to be effective for promoting LL.

Conclusions: Medical students' LL skills develop progressively from preclinical to clinical years. Self-directed learning activities are perceived to be effective in promoting LL skills.
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http://dx.doi.org/10.1080/0142159X.2019.1646894DOI Listing
July 2021

Tocotrienols Modulate Breast Cancer Secretomes and Affect Cancer-Signaling Pathways in MDA-MB-231 Cells: A Label-Free Quantitative Proteomic Analysis.

Nutr Cancer 2019 14;71(8):1263-1271. Epub 2019 May 14.

Department of Molecular Medicine, Faculty of Medicine, University of Malaya , Kuala Lumpur , Malaysia.

Tocotrienols (T3), a family of vitamin E, are reported to possess potent anti-cancer effects but the molecular mechanisms behind these effects still remain unclear. The aim of this study was to investigate how T3 exert anti-cancer effects on MDA-MB-231 human breast cancer cells. The MDA-MB-231 cells were chosen for this study as they are triple-negative and highly metastatic cells, which form aggressive tumors in experimental models. The MDA-MB-231 cells were treated with varying concentrations (0-20 µg mL) of gamma (γ) or delta (δ) T3 and the secretome profiles of these cells treated with half maximal inhibitory concentration (IC) of γT3 (5.8 µg mL) or δT3 (4.0 µg mL) were determined using label-free quantitative proteomic strategy. A total of 103, 174 and 141 proteins were identified with ProteinLynx Global Server (PLGS) score of more than 200 and above 25% sequence coverage in the untreated control and T3-treated cell culture supernatant respectively. A total of 18 proteins were dysregulated between untreated control and T3 (δT3 or γT3) treated conditions. The results showed that T3 treatment downregulated the exogenous Cathepsin D and Serpine1 proteins but upregulated Profilin-1 protein, which play a key role in breast cancer in the MDA-MB-231 cells. These findings strongly suggest that T3 may induce differential expression of secreted proteins involved in the cytoskeletal regulation of RHO GTPase signaling pathway.
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http://dx.doi.org/10.1080/01635581.2019.1607407DOI Listing
July 2020

Relationship between various cytokines implicated in asthma.

Hum Immunol 2019 Sep 1;80(9):755-763. Epub 2019 May 1.

Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Asthma is a complex disorder involving immunologic, environmental, genetic and other factors. Today, asthma is the most common disease encountered in clinical medicine in both children and adults worldwide. Asthma is characterized by increased responsiveness of the tracheobronchial tree resulting in chronic swelling and inflammation of the airways recognized to be controlled by the T-helper 2 (Th2) lymphocytes, which secrete cytokines to increase the production of IgE by B cells. There are many cytokines implicated in the development of the chronic inflammatory processes that are often observed in asthma. Ultimately, these cytokines cause the release of mediators such as histamine and leukotrienes (LT), which in turn promote airway remodeling, bronchial hyperresponsiveness and bronchoconstriction. The CD4 T-lymphocytes from the airways of asthmatics express a panel of cytokines that represent the Th2 cells. The knowledge derived from numerous experimental and clinical studies have allowed physicians and scientists to understand the normal functions of these cytokines and their roles in the pathogenesis of asthma. The main focus of this review is to accentuate the relationship between various cytokines implicated in human asthma. However, some key findings from animal models will be highlighted to support the discoveries from clinical studies.
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http://dx.doi.org/10.1016/j.humimm.2019.04.018DOI Listing
September 2019

Fabrication, Optimization, and Evaluation of Rotigotine-Loaded Chitosan Nanoparticles for Nose-To-Brain Delivery.

Pharmaceutics 2019 Jan 10;11(1). Epub 2019 Jan 10.

Department of Pathology, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia.

The objective of the present study was to develop, optimize, and evaluate rotigotine-loaded chitosan nanoparticles (RNPs) for nose-to-brain delivery. Rotigotine-loaded chitosan nanoparticles were prepared by the ionic gelation method and optimized for various parameters such as the effect of chitosan, sodium tripolyphosphate, rotigotine concentration on particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The prepared nanoparticles were characterized using photon correlation spectroscopy, transmission electron microscopy, scanning electron microscopy, atomic force microscopy, fourier-transform infrared spectroscopy, and X-ray diffraction. The developed RNPs showed a small hydrodynamic particle size (75.37 ± 3.37 nm), small PDI (0.368 ± 0.02), satisfactory zeta potential (25.53 ± 0.45 mV), and very high entrapment efficiency (96.08 ± 0.01). The 24-h in vitro release and ex vivo nasal permeation of rotigotine from the nanoparticles were 49.45 ± 2.09% and 92.15 ± 4.74% while rotigotine solution showed corresponding values of 95.96 ± 1.79%and 58.22 ± 1.75%, respectively. The overall improvement ratio for flux and permeability coefficient were found to be 4.88 and 2.67 when compared with rotigotine solution. A histopathological study showed that the nanoparticulate formulation produced no toxicity or structural damage to nasal mucosa. Our results indicated that rotigotine-loaded chitosan nanoparticles provide an efficient carrier for nose-to-brain delivery.
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http://dx.doi.org/10.3390/pharmaceutics11010026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359179PMC
January 2019

Red palm olein supplementation on cytokines, endothelial function and lipid profile in centrally overweight individuals: a randomised controlled trial.

Eur J Clin Nutr 2019 04 26;73(4):609-616. Epub 2018 Jun 26.

Malaysian Palm Oil Board, Bandar Baru Bangi, Kajang, Selangor, 43000, Malaysia.

Background/objectives: The consumption of antioxidant-rich cooking oil such as red palm olein may be cardioprotective from the perspective of subclinical inflammation and endothelial function.

Subjects/methods: Using a crossover design, we conducted a randomised controlled trial in 53 free-living high-risk abdominally overweight subjects, comparing the effects of incorporating red palm olein (with palm olein as control) in a supervised isocaloric 2100 kcal diet of 30% en fat, two-thirds (45 g/day) of which were derived from the test oil for a period of 6 weeks each.

Results: We did not observe a significant change in interleukin-6 (IL-6), in parallel with other pro-inflammatory (tumour necrosis factor-β, interleukin-1β, IL-1β, high sensitivity C-reactive protein, hsCRP) and endothelial function (soluble intercellular adhesion molecules, sICAM, soluble intravascular adhesion molecules, sVCAM) parameters. Interestingly, we observed a significant reduction in oxidised LDL levels (P < 0.0386) while on the red palm olein diet, together with the increase in plasma alpha tocopherol (P < 0.0002), alpha carotene (P < 0.0001) and beta carotene (P < 0.0001) concentrations compared with palm olein diet.

Conclusion: Red palm olein did not improve subclinical inflammation and endothelial function despite profound increase in antioxidant levels. The positive improvement in oxidised LDL merits further attention in this group of subjects at risk of developing cardiovascular disease.
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http://dx.doi.org/10.1038/s41430-018-0236-5DOI Listing
April 2019

Current Concepts of Neurodegenerative Mechanisms in Alzheimer's Disease.

Biomed Res Int 2018 8;2018:3740461. Epub 2018 Mar 8.

College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, QLD, Australia.

Neurodegenerative diseases are hereditary or sporadic conditions that result in the progressive loss of the structure and function of neurons as well as neuronal death. Although a range of diseases lie under this umbrella term, Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases that affect a large population around the globe. Alzheimer's disease is characterized by the abnormal accumulation of extracellular amyloid- plaques and intraneuronal neurofibrillary tangles in brain regions and manifests as a type of dementia in aged individuals that results in memory loss, multiple cognitive abnormalities, and intellectual disabilities that interfere with quality of life. Since the discovery of AD, a wealth of new information has emerged that delineates the causes, mechanisms of disease, and potential therapeutic agents, but an effective remedy to cure the diseases has not been identified yet. This could be because of the complexity of the disease process, as it involves various contributing factors that include environmental factors and genetic predispositions. This review summarizes the current understanding on neurodegenerative mechanisms that lead to the emergence of the pathology of AD.
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http://dx.doi.org/10.1155/2018/3740461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863339PMC
September 2018

Lipid based nanocarriers system for topical delivery of photosensitizers.

Drug Discov Today 2017 08 27;22(8):1274-1283. Epub 2017 Apr 27.

Department of Pharmaceutical Technology, School of Pharmacy, International Medical University (IMU), Kuala Lumpur 57000, Malaysia; Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, UP, 226031 India. Electronic address:

Topical photodynamic therapy (PDT) is a non-invasive technique used in the treatment of malignant and non-malignant skin diseases. It offers great promise because of its simplicity, enhanced patient compliance, localisation of the photosensitizer, as well as the use of light and oxygen to achieve photocytotoxicity. Despite progress in photosensitizer-mediated topical PDT, its clinical application is limited by poor penetration of photosensitizers through the skin. Therefore, much effort has been made to develop nanocarriers that can tackle the challenges of conventional photosensitizer-mediated PDT for topical delivery. This review discusses recent data on the use of different types of lipid-based nanocarriers in delivering photosensitizer for topical PDT.
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http://dx.doi.org/10.1016/j.drudis.2017.04.010DOI Listing
August 2017

Effects of 25-hydroxyvitamin D and vitamin D-binding protein on bone mineral density and disease activity in Malaysian patients with rheumatoid arthritis.

Int J Rheum Dis 2018 May 20;21(5):992-1000. Epub 2017 Feb 20.

Department of Medicine, Subang Jaya Medical Centre, Subang Jaya, Malaysia.

Aim: Vitamin D3 [25(OH)D] has been shown to be important in bone health and can influence rheumatoid arthritis (RA) disease activity. Vitamin D-binding protein (VDBP) levels vary with race and may modulate 'bioavailable' levels of 25(OH)D. The aim of this study was to explore the relationships between 25(OH)D, VDBP and clinical factors on bone mineral density (BMD) in a group of multi-ethnic Malaysian RA patients and healthy controls.

Methods: A cross-sectional study of 77 female RA patients and 29 controls was performed. Serum 25(OH)D was measured using the Elecsys Vitamin D total assay. Serum VDBP was measured using a Quantikine enzyme-linked immunosorbent assay kit. BMD was assessed using dual-energy X-ray absorptiometry (DXA).

Results: Overall, mean 25(OH)D levels were 42.66 ± 21.75 nmol/L with no significant difference between RA patients and controls. 25(OH)D levels were significantly higher in Chinese, compared to Malay/Indian subjects. In RA patients, menopausal status and body mass index (BMI) were significantly associated with BMD but not 25(OH)D or RA Disease Activity Score of 28 joints (DAS28). There was no significant correlation between 25(OH)D and DAS28, even after correction for menopausal status and BMI. VDBP levels were not significantly different between the races and did not significantly correlate with BMD, 25(OH)D overall, or DAS28 in RA patients.

Conclusions: In Malaysian RA patients, menopausal status and BMI were more important influences on BMD than 25(OH)D or RA disease activity. The utility of measuring VDBP levels in this population remains uncertain.
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http://dx.doi.org/10.1111/1756-185X.13048DOI Listing
May 2018

Health-promoting effects of red palm oil: evidence from animal and human studies.

Nutr Rev 2017 Feb;75(2):98-113

Malaysian Palm Oil Board, Kajang, Selangor, Malaysia. Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. University of Malaya Centre for Proteomics Research, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Pathology Division, Faculty of Medicine and Health, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia.

The fruit of the oil palm tree (Elaeis guineesis) is the source of antioxidant-rich red palm oil. Red palm oil is a rich source of phytonutrients such as tocotrienols, tocopherols, carotenoids, phytosterols, squalene, and coenzyme Q10, all of which exhibit nutritional properties and oxidative stability. Mutagenic, nutritional, and toxicological studies have shown that red palm oil contains highly bioavailable β-carotene and vitamin A and is reasonably stable to heat without any adverse effects. This review provides a comprehensive overview of the nutritional properties of red palm oil. The possible antiatherogenic, antihemorrhagic, antihypertensive, anticancer, and anti-infective properties of red palm oil are examined. Moreover, evidence supporting the potential effectiveness of red palm oil to overcome vitamin A deficiency in children and pregnant women, to improve ocular complications of vitamin A deficiency, to protect against ischemic heart disease, to promote normal reproduction in males and females, to aid in the management of diabetes, to ameliorate the adverse effects of chemotherapy, and to aid in managing hypobaric conditions is presented.
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http://dx.doi.org/10.1093/nutrit/nuw054DOI Listing
February 2017

Protective Mechanisms of Flavonoids in Parkinson's Disease.

Oxid Med Cell Longev 2015 20;2015:314560. Epub 2015 Oct 20.

Discipline of Biomedicine, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, QLD 4811, Australia.

Parkinson's disease is a chronic, debilitating neurodegenerative movement disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta region in human midbrain. To date, oxidative stress is the well accepted concept in the etiology and progression of Parkinson's disease. Hence, the therapeutic agent is targeted against suppressing and alleviating the oxidative stress-induced cellular damage. Within the past decades, an explosion of research discoveries has reported on the protective mechanisms of flavonoids, which are plant-based polyphenols, in the treatment of neurodegenerative disease using both in vitro and in vivo models. In this paper, we have reviewed the literature on the neuroprotective mechanisms of flavonoids in protecting the dopaminergic neurons hence reducing the symptoms of this movement disorder. The mechanism reviewed includes effect of flavonoids in activation of endogenous antioxidant enzymes, suppressing the lipid peroxidation, inhibition of inflammatory mediators, flavonoids as a mitochondrial target therapy, and modulation of gene expression in neuronal cells.
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http://dx.doi.org/10.1155/2015/314560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630416PMC
July 2016

Protective effects of quercetin glycosides, rutin, and isoquercetrin against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in rat pheochromocytoma (PC-12) cells.

Int J Immunopathol Pharmacol 2016 Mar 5;29(1):30-9. Epub 2015 Nov 5.

Discipline of Biomedicine, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, QLD, Australia

There is increasing evidence that free radicals induced oxidative stress is a major causative agent in the pathogenesis of neurodegenerative diseases, particularly Parkinson's disease. Quercetin glycosides, namely rutin and isoquercitrin, are flavonoid polyphenol compounds found ubiquitously in fruits and vegetables and have been known to possess antioxidant effects. This study was designed to compare the neuroprotective effects of quercetin glycosides rutin and isoquercitrin in 6-OHDA-induced rat pheochromocytoma (PC-12) cells. The results showed that both rutin and isoquercitrin significantly increased antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase, and glutathione level that were attenuated by 6-OHDA in PC-12 cells. There was no significant difference in the activation of glutathione and glutathione peroxidase enzymes between rutin and isoquercitrin. These two glycosides were equally effective in suppressing lipid peroxidation in 6-OHDA-induced PC-12 cells as both compounds suppressed the malondialdehyde generation and prevented cell damage. In conclusion, quercetin glycosides rutin and isoquercetrin are having a significant neuroprotective effect against 6-OHDA toxicity in PC-12 cells.
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http://dx.doi.org/10.1177/0394632015613039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806739PMC
March 2016
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