Displaying publications 1 - 20 of 23 in total

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  1. Syahmi AR, Vijayarathna S, Sasidharan S, Latha LY, Kwan YP, Lau YL, et al.
    Molecules, 2010 Nov 10;15(11):8111-21.
    PMID: 21072022 DOI: 10.3390/molecules15118111
    Elaeis guineensis (Arecaceae) is widely used in West African traditional medicine for treating various ailments. An evaluation on the toxicity of extracts of this plant is crucial to support the therapeutic claims. The acute oral toxicity and brine shrimp lethality of a methanolic extract of this plant was tested. Oral administration of crude extract at the highest dose of 5,000 mg/kg resulted in no mortalities or evidence of adverse effects, implying that E. guineensis is nontoxic. Normal behavioral pattern, clinical signs and histology of vital organs confirm this evidence. The E. guineensis extracts screened for toxicity against brine shrimp had 50% lethal concentration (LC₅₀) values of more than 1.0 mg/mL (9.00 and 3.87 mg/mL, at 6 and 24 h, respectively), confirming that the extract was not toxic. Maximum mortalities occurred at 100 mg/mL concentration while the least mortalities happened to be at 0.195 mg/mL concentration. The results of both tests confirm that E. guineensis is nontoxic and hence safe for commercial utilization.
  2. Vijayarathna S, Gothai S, Jothy SL, Chen Y, Kanwar JR, Sasidharan S
    Asian Pac J Cancer Prev, 2015;16(17):7435-9.
    PMID: 26625740
    A failure of a cell to self destruct has long been associated with cancer progression and development. The fact that tumour cells may not instigate cell arrest or activate cell death mechanisms upon cancer drug delivery is a major concern. Autophagy is a mechanism whereby cell material can be engulfed and digested while apoptosis is a self-killing mechanism, both capable of hindering multiplication after cell injury. In particular situations, autophagy and apoptosis seem to co-exist simultaneously or interdependently with the aid of mutual proteins. This review covers roles of microRNAs and chemopreventive agents and makes an attempt at outlining possible partnerships in maximizing cancer cell death with minimal normal cell damage.
  3. Vijayarathna S, Sasidharan S
    Asian Pac J Trop Biomed, 2012 Oct;2(10):826-9.
    PMID: 23569855 DOI: 10.1016/S2221-1691(12)60237-8
    To investigate the cytotoxic effect of Elaeis guineensis methanol extract on MCF-7 and Vero cell.
  4. Sumathy V, Zakaria Z, Chen Y, Latha LY, Jothy SL, Vijayarathna S, et al.
    Eur Rev Med Pharmacol Sci, 2013 Jun;17(12):1648-54.
    PMID: 23832733
    Cassia (C.) surattensis Burm. f. (Leguminosae), a medicinal herb native to tropical equatorial Asia, was commonly used in folk medicine to treat various diseases. The aim of the present study is to investigate the effects of methanolic flower extract of C. surattensis against Aspergillus (A.) niger.
  5. Grace-Lynn C, Chen Y, Latha LY, Kanwar JR, Jothy SL, Vijayarathna S, et al.
    Molecules, 2012 Nov 23;17(12):13937-47.
    PMID: 23178309 DOI: 10.3390/molecules171213937
    The aim of the present study was to evaluate the hepatoprotective activity of lantadene A against acetaminophen-induced liver toxicity in mice was studied. Activity was measured by monitoring the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin, along with histo-pathological analysis. Silymarin was used as positive control. A bimodal pattern of behavioural toxicity was exhibited by the lantadene A-treated group at the beginning of the treatment. However, treatment with lantadene A and silymarin resulted in an increase in the liver weight compared with the acetaminophen treated group. The results of the acetaminophen-induced liver toxicity experiments showed that mice treated with lantadene A (500 mg/kg) showed a significant decrease in the activity of ALT, AST and ALP and the level of bilirubin, which were all elevated in the acetaminophen treated group (p < 0.05). Histological studies supported the biochemical findings and a maximum improvement in the histoarchitecture was seen. The lantadene A-treated group showed remarkable protective effects against histopathological alterations, with comparable results to the silymarin treated group. The current study confirmed the hepatoprotective effects of lantadene A against the model hepatotoxicant acetaminophen, which is likely related to its potent antioxidative activity.
  6. Torey A, Vijayarathna S, Jothy SL, Gothai S, Chen Y, Latha LY, et al.
    J Tradit Complement Med, 2016 Jan;6(1):97-104.
    PMID: 26870686 DOI: 10.1016/j.jtcme.2014.11.017
    Candida albicans has become resistant to the commercially available, toxic, and expensive anti-Candida agents that are on the market. These factors force the search for new antifungal agents from natural resources. Cassia spectabilis had been traditionally employed by healers for many generations. The possible mechanisms of the C. spectabilis leaf extract were determined by potassium leakage study and the effect of the extract on the constituents of the cell wall and enzymes as well as the morphological changes on C. albicans cells were studied along with cytotoxicity assays. The cytotoxicity result indicated that the extract is nontoxic as was clearly substantiated by a half maximal inhibitory concentration (IC50) value of 59.10 μg/mL. The treated cells (C. spectabilis extract) demonstrated potassium leakage of 1039 parts per million (ppm) compared to Amphotericin B (AmpB)-treated cells with a released potassium value of 1115 ppm. The effects of the extract on the cell wall proteins illustrated that there were three major types of variations in the expression of treated cell wall proteins: the presence of new proteins, the absence of proteins, and the amount of expressed protein. The activities of two enzymes, α-glucosidase and proteinase, were determined to be significantly high, thereby not fully coinciding with the properties of the antifungal reaction triggered by C. spectabilis. The morphology of C. albicans cells treated with the C. spectabilis extract showed that the cells had abnormalities and were damaged or detached within the microcolonies. Our study verifies C. spectabilis leaf extract as an effective anti-C. albicans agent.
  7. Shanmugapriya, Huda HA, Vijayarathna S, Oon CE, Chen Y, Kanwar JR, et al.
    Adv Exp Med Biol, 2018 9 28;1087:95-105.
    PMID: 30259360 DOI: 10.1007/978-981-13-1426-1_8
    Circular RNAs characterize a class of widespread and diverse endogenous RNAs which are non-coding RNAs that are made by back-splicing events and have covalently closed loops with no polyadenylated tails. Various indications specify that circular RNAs (circRNAs) are plentiful in the human transcriptome. However, their participation in biological processes remains mostly undescribed. To date thousands of circRNAs have been revealed in organisms ranging from Drosophila melanogaster to Homo sapiens. Functional studies specify that these transcripts control expression of protein-coding linear transcripts and thus encompass a key component of gene expression regulation. This chapter provide a comprehensive overview on functional validation of circRNAs. Furthermore, we discuss the recent modern methodologies for the functional validation of circRNAs such as RNA interference (RNAi) gene silencing assay, luciferase reporter assays, circRNA gain-of-function investigation via overexpression of circular transcript assay, RT-q-PCR quantification, and other latest applicable assays. The methods described in this chapter are demonstrated on the cellular model.
  8. Shanmugapriya, Vijayarathna S, Sasidharan S
    Microsc Microanal, 2019 10;25(5):1263-1272.
    PMID: 31383043 DOI: 10.1017/S1431927619014776
    Several microscopy methods have been developed to assess the morphological changes in cells in the investigations of the mode of cell death in response to a stimulus. Our recent finding on the treatment of the IC50 concentration (26.67 μg/mL) of Polyalthia longifolia leaf extract indicated the induction of apoptotic cell death via the regulation of miRNA in HeLa cells. Hence, the current study was conducted to validate the function of these downregulated microRNAs in P. longifolia-treated HeLa cells using microscopic approaches. These include scanning electron microscope (SEM), transmission electron microscope (TEM), and acridine orange/propidium iodide (AO/PI)-based fluorescent microscopy techniques by observing the morphological alterations to cells after transfection with mimic miRNA. Interestingly, the morphological changes observed in this study demonstrated the apoptotic hallmarks, for instance, cell blebbing, cell shrinkage, cytoplasmic and nuclear condensation, vacuolization, cytoplasmic extrusion, and the formation of apoptotic bodies, which proved the role of dysregulated miRNAs in apoptotic HeLa cell death after treatment with the P. longifolia leaf extract. Conclusively, the current study proved the crucial role of downregulated miR-484 and miR-221-5p in the induction of apoptotic cell death in P. longifolia-treated HeLa cells using three approaches-SEM, TEM, and AO/PI-based fluorescent microscope.
  9. Lachumy SJ, Oon CE, Deivanai S, Saravanan D, Vijayarathna S, Choong YS, et al.
    Asian Pac J Cancer Prev, 2013;14(10):5553-65.
    PMID: 24289545
    Plants play important roles in human life not only as suppliers of oxygen but also as a fundamental resource to sustain the human race on this earthly plane. Plants also play a major role in our nutrition by converting energy from the sun during photosynthesis. In addition, plants have been used extensively in traditional medicine since time immemorial. Information in the biomedical literature has indicated that many natural herbs have been investigated for their efficacy against lethal irradiation. Pharmacological studies by various groups of investigators have shown that natural herbs possess significant radioprotective activity. In view of the immense medicinal importance of natural product based radioprotective agents, this review aims at compiling all currently available information on radioprotective agents from medicinal plants and herbs, especially the evaluation methods and mechanisms of action. In this review we particularly emphasize on ethnomedicinal uses, botany, phytochemistry, mechanisms of action and toxicology. We also describe modern techniques for evaluating herbal samples as radioprotective agents. The usage of herbal remedies for combating lethal irradiation is a green anti- irradiation approach for the betterment of human beings without high cost, side effects and toxicity.
  10. Leng KM, Vijayarathna S, Jothy SL, Sasidharan S, Kanwar JR
    Future Sci OA, 2018 Feb;4(2):FSO257.
    PMID: 29379633 DOI: 10.4155/fsoa-2017-0085
    Aim: To study the in vitro and in vivo anticandidal activity of nanocapsulated bovine lactoferrin.

    Materials & methods: In vitro and in vivo antimicrobial activities were conducted to study the anticandidal activities of nanocapsules (NCs).

    Results: The NCs showed good anticandidal activities. The disruption of cell wall and cell membrane was noted via microscopy studies. The NCs changed the normal growth profile of Candida albicans. NCs reduced the colony forming unit in kidney and blood samples. Histopathological examination showed better cell structure and coordination compared with untreated mice kidney. NCs also enhanced the natural killing properties of C. albicans by epithelial cells.

    Conclusion: NCs have effective anticandidal properties and have the potential as a therapeutic agent against candidiasis.

  11. Leng KM, Vijayarathna S, Jothy SL, Sasidharan S, Kanwar JR
    Biomed Pharmacother, 2018 Jan;97:26-37.
    PMID: 29080455 DOI: 10.1016/j.biopha.2017.10.121
    Lactoferrin has been known to have antimicrobial properties. This research was conducted to investigate the toxicity of Alginate/EUDRAGIT® S 100-enclosed chitosan-calcium phosphate-loaded Fe-bLf nanocapsules (NCs) by in vitro and in vivo assays. Brine shrimp lethality assay showed that the LC50 value of NCs was more than 1mg/mL which indicated that NCs was not toxic to Brine shrimp. However, the LC50 values for the positive control potassium dichromate at 24h is 64.15μg/mL, which was demostrated the toxic effect against the brine shrimp. MTT cytotoxicity assay also revealed that NCs was not toxic against non-cancerous Vero cell line with IC50 values of 536μg/mL. Genotoxicity studies by comet assay on Vero cells revealed that NCs exerted no significant genotoxic at 100μg/mL without tail or shorter comet tail. Allium cepa root assay carried out at 125, 250, 500 and 1000μg/mL for 24h revealed that the NCs was destitute of significant genotoxic effect under experimental conditions. The results show that there is no significant difference (p>0.05) in mitotic index between the deionized water and NCs treated Allium cepa root tip cells. In conclusion, no toxicity was observed in NCs in this study. Therefore, nontoxic NCs has the good potential to develop as a therapeutic agent.
  12. Sumathy V, Zakaria Z, Jothy SL, Gothai S, Vijayarathna S, Yoga Latha L, et al.
    Microb Pathog, 2014 Dec;77:7-12.
    PMID: 25457794 DOI: 10.1016/j.micpath.2014.10.004
    Invasive aspergillosis (IA) in immunocompromised host is a major infectious disease leading to reduce the survival rate of world population. Aspergillus niger is a causative agent causing IA. Cassia surattensis plant is commonly used in rural areas to treat various types of disease. C. surattensis flower extract was evaluated against the systemic aspergillosis model in this study. Qualitative measurement of fungal burden suggested a reduction pattern in the colony forming unit (CFU) of lung, liver, spleen and kidney for the extract treated group. Galactomannan assay assessment showed a decrease of fungal load in the treatment and positive control group with galactomannan index (GMI) value of 1.27 and 0.25 on day 28 but the negative control group showed high level of galactomannan in the serum with GMI value of 3.58. Histopathology examinations of the tissues featured major architecture modifications in the tissues of negative control group. Tissue reparation and recovery from infection were detected in extract treated and positive control group. Time killing fungicidal study of A. niger revealed dependence of the concentration of C. surattensis flower extract.
  13. Vijayarathna S, Oon CE, Jothy SL, Chen Y, Kanwar JR, Sasidharan S
    Curr Gene Ther, 2014;14(2):112-20.
    PMID: 24588707
    For years researchers have exerted every effort to improve the influential roles of microRNA (miRNA) in regulating genes that direct mammalian cell development and function. In spite of numerous advancements, many facets of miRNA generation remain unresolved due to the perplexing regulatory networks. The biogenesis of miRNA, eminently endures as a mystery as no universal pathway defines or explicates the variegation in the rise of miRNAs. Early evidence in biogenesis ignited specific steps of being omitted or replaced that eventuate in the individual miRNAs of different mechanisms. Understanding the basic foundation concerning how miRNAs are generated and function will help with diagnostic tools and therapeutic strategies. This review encompasses the canonical and the non-canonical pathways involved in miRNA biogenesis, while elucidating how miRNAs regulate genes at the nuclear level and also the mechanism that lies behind circulating miRNAs.
  14. Kavitha N, Vijayarathna S, Shanmugapriya, Oon CE, Chen Y, Kanwar JR, et al.
    J Ethnopharmacol, 2018 Mar 01;213:118-131.
    PMID: 29154802 DOI: 10.1016/j.jep.2017.11.009
    ETHNOPHARMACOLOGICAL RELEVANCE: Phaleria macrocarpa (Scheff) Boerl, is a famous traditional medicinal plant which exhibited cytotoxicity against various cancerous cells. Traditionally, P. macrocarpa has been used to control cancer, impotency, hemorrhoids, diabetes mellitus, allergies, liver and heart disease, kidney disorders, blood diseases, acne, stroke, migraine, and various skin diseases.

    AIM OF THE STUDY: Recent studies have demonstrated a potent anticancer potential of P. macrocarpa, especially against HeLa cell. The objective of this study was to investigate the regulation of miRNAs on MDA-MB-231 treated with P. macrocarpa ethyl acetate fraction (PMEAF).

    MATERIALS AND METHODS: The regulation of miRNAs on MDA-MB-231 cells treated with PMEAF was studied through IIlumina, Hi-Seq. 2000 platform of Next Generation Sequencing (NGS) and various in silico bioinformatics tools.

    RESULTS: The PMEAF treatment against MDA-MB-231 cells identified 10 upregulated and 10 downregulated miRNAs. A set of 606 target genes of 10 upregulated miRNAs and 517 target genes of 10 downregulated miRNAs were predicted based on computational and validated databases by using miRGate DB Query. Meanwhile, results from DAVID Bioinformatics Resources 6.8 specified the functional annotation of the upregulated miRNAs involvement in cancer pathway by suppressing the oncogenes and downregulating miRNAs by expressing the tumour suppressor genes in the regulation of apoptosis pathway.

    CONCLUSION: In conclusion, the results of this study proved that PMEAF is a promising anticancer agent with high cytotoxicity against MDA-MB-231 breast cancer cells and it induced apoptotic cell death mechanism through the regulation of miRNAs. PMEAF might be the best candidate for developing more potent anticancer drugs or chemo preventive supplements.

  15. Jothy SL, Chen Y, Vijayarathna S, Kanwar JR, Sasidharan S
    Curr Gene Ther, 2015;15(1):15-20.
    PMID: 25478696
    Radiotherapy plays an essential primary role in cancer patients. Regardless of its significant advances in treatment options, tumor recurrence and radio-resistance in cancer cells still occur in a high percentage of patients. Furthermore, the over expression of miRNAs accompanies the development of radio-resistant cancer cells. Consequently, miRNAs might serve as therapeutic targets for the treatment of radio-resistance in cancer cells. The findings of the current research also signify that the use of a natural anti-miRNA substance could inhibit specific miRNAs, and, concurrently, these natural remedies could exhibit radioprotective activity against the healthy cells during radiotherapy. Therefore, in this review, we have reported the association of miRNAs with radio-resistance and the potential uses of natural remedies as green gene therapeutic approaches, as well as radioprotectors against the adverse effects of irradiation on healthy cells during radiotherapy.
  16. Kavitha N, Vijayarathna S, Jothy SL, Oon CE, Chen Y, Kanwar JR, et al.
    Asian Pac J Cancer Prev, 2014;15(18):7489-97.
    PMID: 25292018
    MicroRNAs (miRNAs) are short non-coding RNAs of 20-24 nucleotides that play important roles in carcinogenesis. Accordingly, miRNAs control numerous cancer-relevant biological events such as cell proliferation, cell cycle control, metabolism and apoptosis. In this review, we summarize the current knowledge and concepts concerning the biogenesis of miRNAs, miRNA roles in cancer and their potential as biomarkers for cancer diagnosis and prognosis including the regulation of key cancer-related pathways, such as cell cycle control and miRNA dysregulation. Moreover, microRNA molecules are already receiving the attention of world researchers as therapeutic targets and agents. Therefore, in-depth knowledge of microRNAs has the potential not only to identify their roles in cancer, but also to exploit them as potential biomarkers for cancer diagnosis and identify therapeutic targets for new drug discovery.
  17. Vijayarathna S, Oon CE, Chen Y, Kanwar JR, Sasidharan S
    Biomed Pharmacother, 2017 May;89:499-514.
    PMID: 28249252 DOI: 10.1016/j.biopha.2017.02.075
    Medicinal plants have been accepted as a gold mine, with respect to the diversity of their phytochemicals. Many medicinal plants extracts are potential anticancer agents. Polyalthia longifolia var. angustifolia Thw. (Annonaceae) is one of the most significant native medicinal plants and is found throughout Malaysia. Hence, the present study was intended to assess the anticancer properties of P. longifolia leaf methanolic extract (PLME) and its underlying mechanisms. The Annexin V/PI flow cytometry analysis showed that PLME induces apoptosis in HeLa cells in dose-dependent manner whereas the PI flow cytometric analysis for cell cycle demonstrated the accumulation of cells at sub G0/G1, G0/G1 and G2/M phases. Investigation with JC-1 flow cytometry analysis indicated increase in mitochondria membrane potential depolarisation corresponding to increase in PLME concentrations. PLME was also shown to influence intracellular reactive oxygen species (ROS) by exerting anti-oxidant (half IC50) and pro-oxidant (IC50and double IC50) affect against HeLa cells. PLME treatment also displayed DNA damage in HeLa cells in concentration depended fashion. The proteomic profiling array exposed the expression of pro-apoptotic and anti-apoptotic proteins upon PLME treatment at IC50concentration in HeLa cells. Pro-apoptotic proteins; BAX, BAD, cytochrome c, caspase-3, p21, p27 and p53 were found to be significantly up-regulated while anti-apoptotic proteins; BCL-2 and BCL-w were found to be significantly down-regulated. This investigation postulated the role of p53 into mediating apoptosis, cell cycle arrest and mitochondrial potential depolarisation by modulating the redox status of HeLa cells.
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