MyMedR

Natural pro-oxidants: an alternative remedy to explore as novel cancer therapeutic agents

Jothy SL, Oon CE, Sasidharan S

Asian Pac J Cancer Prev, 2014;15(3):1501.

PMID: 24606490

Regulating Mitochondrial Biogenesis: from Herbal Remedies to Phytomedicine for Cancer Prevention

Jothy SL, Vijayarathna S, Chen Y, Kanwar JR, Sasidharan S

Asian Pac J Cancer Prev, 2015;16(17):8015.

PMID: 26625835

MicroRNAs: association with radioresistant and potential uses of natural remedies as green gene therapeutic approaches

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.

Evaluation of the effect of Cassia surattensis Burm. f., flower methanolic extract on the growth and morphology of Aspergillus niger

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.

Fulltext In vitro, in situ and in vivo studies on the anticandidal activity of Cassia fistula seed extract

Jothy SL, Zakariah Z, Chen Y, Sasidharan S

Molecules, 2012 Jun 07;17(6):6997-7009.

PMID: 22678414 DOI: 10.3390/molecules17066997

Cassia fistula seeds have many therapeutic uses in traditional medicine practice. The present investigation was undertaken to demonstrate the anticandidal activity of the C. fistula seed extract at ultra-structural level through transmission electron microscope (TEM) and scanning electron microscope (SEM) observations. The effect of seed extract on the growth profile of the Candida albicans was examined via time-kill assays and in vivo efficacy of the extract was tested in an animal model. In addition, the anticandidal effect of seed extract was further evaluated by microscopic observations using SEM and TEM to determine any major alterations in the ultrastructure of C. albicans. The complete inhibition of C. albicans growth was shown by C. fistula seed extract at 6.25 mg/mL concentration. The time-kill assay suggested that C. fistula seed extract had completely inhibited the growth of C. albicans and also exhibited prolonged anti-yeast activity. The SEM and TEM observations carried out to distinguish the metamorphosis in the morphology of control and C. fistula seed extract-treated C. albicans cells revealed the notable effect on the outer cell wall and cytoplasmic content of the C. albicans and complete collapse of yeast cell exposed to seed extract at concentration 6.25 mg/mL at 36 h. The in vitro time-kill study performed using the leaf extract at 1/2, 1 or 2 times of the MIC significantly inhibited the yeast growth with a noticeable drop in optical density (OD) of yeast culture, thus confirming the fungicidal effect of the extract on C. albicans. In addition, in vivo antifungal activity studies on candidiasis in mice showed a 6-fold decrease in C. albicans in kidneys and blood samples in the groups of animals treated with the extract (2.5 g/kg body weight). The results suggested that the C. fistula seed extract possessed good anticandidal activity and is a potential candidate for the development of anticandidal agents.

Anti-Cancer Natural Products Inducing Cross-talk between Apoptosis and Autophagy Mutual Proteins to Regulate Cancer Cell Death: Design of Future Green Anticancer Therapies

Vijayarathna S, Jothy SL, Chen Y, Kanwar JR, Sasidharan S

Asian Pac J Cancer Prev, 2015;16(14):6175-6.

PMID: 26320517

Deactivation of Telomerase Enzyme and Telomere Destabilization by Natural Products: a Potential Target for Cancer Green Therapy

Sasidharan S, Jothy SL, Kavitha N, Chen Y, Kanwar JR

Asian Pac J Cancer Prev, 2015;16(18):8671.

PMID: 26745135

Fulltext In vitro and in vivo anticandidal activities of alginate-enclosed chitosan-calcium phosphate-loaded Fe-bovine lactoferrin nanocapsules

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.

In vitro and in vivo toxicity assessment of alginate/eudragit S 100-enclosed chitosan-calcium phosphate-loaded iron saturated bovine lactoferrin nanocapsules (Fe-bLf NCs)

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.

Fulltext Corrigendum to "Evaluation of the Genotoxic Potential against H2O2-Radical-Mediated DNA Damage and Acute Oral Toxicity of Standardized Extract of Polyalthia longifolia Leaf"

Jothy SL, Chen Y, Kanwar JR, Sasidharan S

Evid Based Complement Alternat Med, 2021;2021:9836793.

PMID: 34194528 DOI: 10.1155/2021/9836793

[This corrects the article DOI: 10.1155/2013/925380.].

Fulltext Antioxidant Activity and Hepatoprotective Potential of Polyalthia longifolia and Cassia spectabilis Leaves against Paracetamol-Induced Liver Injury

Jothy SL, Aziz A, Chen Y, Sasidharan S

Evid Based Complement Alternat Med, 2012;2012:561284.

PMID: 23243455 DOI: 10.1155/2012/561284

In the present study, in vitro antioxidant, free radical scavenging capacity, and hepatoprotective activity of methanol extracts from Polyalthia longifolia and Cassia spectabilis were evaluated using established in vitro models such as ferric-reducing antioxidant power (FRAP), 2,2-diphenyl-1-picryl-hydrazyl (DPPH(•)), hydroxyl radical (OH(•)), nitric oxide radical (NO(•)) scavenging, metal chelating, and antilipidperoxidation activities. Interestingly, all the extracts showed considerable in vitro antioxidant and free radical scavenging activities in a dose-dependent manner when compared to the standard antioxidant which verified the presence of strong antioxidant compound in leaf extracts tested. Phenolic and flavonoid content of these extracts is significantly correlated with antioxidant capacity. Since P. longifolia extract was exhibited better in vitro antioxidant activities, it was subjected for in vivo hepatoprotective activity in paracetamol-intoxicated mice. Therapy of P. longifolia showed the liver protective effect on biochemical and histopathological alterations. Moreover, histological studies also supported the biochemical finding, that is, the maximum improvement in the histoarchitecture of the liver. Results revealed that P. longifolia leaf extract could protect the liver against paracetamol-induced oxidative damage by possibly increasing the antioxidant protection mechanism in mice. Our findings indicated that P. longifolia and C. spectabilis have potential as good sources of natural antioxidant/antiaging compounds.

Fulltext Evaluation of the Genotoxic Potential against H2O2-Radical-Mediated DNA Damage and Acute Oral Toxicity of Standardized Extract of Polyalthia longifolia Leaf

Jothy SL, Chen Y, Kanwar JR, Sasidharan S

Evid Based Complement Alternat Med, 2013;2013:925380.

PMID: 23878610 DOI: 10.1155/2013/925380

Medicinal plants have been used in medicoculturally diverse countries around the world, where it is a part of a time-honoured tradition that is respected even today. Polyalthia longifolia leaf extract has been previously reported as an efficient antioxidant in vitro. Hence, the genotoxic effects of P. longifolia leaf were investigated by using plasmid relation, comet, and Allium cepa assay. In the presence of (∙) OH radicals, the DNA in supercoil was start nicked into open circular form, which is the product of the single-stranded cleavage of supercoil DNA and quantified as fragmented separate bands on agarose gel in plasmid relation assay. In the plasmid relation and comet assay, the P. longifolia leaf extract exhibited strong inhibitory effects against H2O2-mediated DNA damage. A dose-dependent increase of chromosome aberrations was also observed in the Allium cepa assay. The abnormalities scored were stickiness, c-mitosis, bridges, and vagrant chromosomes. Micronucleated cells were also observed at the interphase. The results of Allium cepa assay confirmed that the methanol extracts of P. longifolia exerted no significant genotoxic or mitodepressive effects at 100 μ g/mL. Thus, this study demonstrated that P. longifolia leaf extract has a beneficial effect against oxidative DNA damage. This experiment is the first report for the protective effect of P. longifolia on DNA damage-induced by hydroxyl radicals. Additionally in acute oral toxicity study, female rats were treated at 5000 mg/kg body weight of P. longifolia leaf extract and observed for signs of toxicity for 14 days. P. longifolia leaf extract did not produce any treatment-related toxic effects in rats.

Can Cancer Therapy be Achieved by Bridging Apoptosis and Autophagy: a Method Based on microRNA-Dependent Gene Therapy and Phytochemical Targets

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.

In vitro and in vivo antifungal activity of Cassia surattensis flower against Aspergillus niger

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.

MicroRNAs: biogenesis, roles for carcinogenesis and as potential biomarkers for cancer diagnosis and prognosis

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.

MicroRNA pathways: an emerging role in identification of therapeutic strategies

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.

Fulltext Antioxidant activity of methanol extracts of different parts of Lantana camara

Mahdi-Pour B, Jothy SL, Latha LY, Chen Y, Sasidharan S

Asian Pac J Trop Biomed, 2012 Dec;2(12):960-5.

PMID: 23593576 DOI: 10.1016/S2221-1691(13)60007-6

To investigate the antioxidant activity of methanolic extracts of Lantana camara (L. camara) various parts and the determination of their total phenolics content.

Fulltext Acute toxicity impacts of Euphorbia hirta L extract on behavior, organs body weight index and histopathology of organs of the mice and Artemia salina

Rajeh MA, Kwan YP, Zakaria Z, Latha LY, Jothy SL, Sasidharan S

Pharmacognosy Res, 2012 Jul;4(3):170-7.

PMID: 22923956 DOI: 10.4103/0974-8490.99085

The methanol extract of Euphorbia hirta L (Euphorbiaceae), which is used in traditional medicines, was tested for in vivo toxicity.

In vitro antioxidant activity potential of lantadene A, a pentacyclic triterpenoid of Lantana plants

Grace-Lynn C, Darah I, Chen Y, Latha LY, Jothy SL, Sasidharan S

Molecules, 2012 Sep 19;17(9):11185-98.

PMID: 22992785

Lantadenes are pentacyclic triterpenoids present in the leaves of the plant Lantana camara. In the present study, in vitro antioxidant activity and free radical scavenging capacity of lantadene A was evaluated using established in vitro models such as ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picryl-hydrazyl (DPPH•), hydroxyl radical (OH•), nitric oxide radical (NO•), superoxide anion scavenging activities and ferrous ion chelating assay. Interestingly, lantadene A showed considerable in vitro antioxidant, free radical scavenging capacity activities in a dose dependant manner when compared with the standard antioxidant in nitric oxide scavenging, superoxide anion radical scavenging and ferrous ion chelating assay. These findings show that the lantadene A possesses antioxidant activity with different mechanism of actions towards the different free radicals tested. Since lantadene A is a very popular drug in modern medicine, it is a promising candidate for use as an antioxidant and hepatoprotective agent.

Fulltext Bioassay-directed isolation of active compounds with antiyeast activity from a Cassia fistula seed extract

Jothy SL, Zakaria Z, Chen Y, Lau YL, Latha LY, Shin LN, et al.

Molecules, 2011 Sep 05;16(9):7583-92.

PMID: 21894090 DOI: 10.3390/molecules16097583

BACKGROUND AND OBJECTIVE: Cassia fistula L belongs to the family Leguminosae, and it is one of the most popular herbal products in tropical countries. C. fistula seeds have been used as a herbal medicine and have pharmacological activity which includes anti-bacterial, anti-fungal, and antioxidant properties. The goal of this study was to identify compounds from C. fistula seeds which are responsible for anti-Candida albicans activity using bioassay-directed isolation.

RESULTS: The preliminary phytochemical screening of the plant seed revealed the presence of anthraquinones, flavonoids, saponins, tannins and terpenoids. The isolation of active compounds was carried out in four steps: multiple extractions, fractionation using column chromatography and purification using preparative thin-layer chromatography (TLC) and liquid chromatography/mass spectrometry (LC/MS). The structure of separated compounds was determined on the basis of mass spectrometry data. One compound was identified is roseanone.

CONCLUSIONS: The MS analysis on the active fraction from seed extract of C. fistula confirmed the presence of roseanone with antiyeast activity.

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