Displaying publications 1 - 20 of 70 in total

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  1. Kamilla, L., Ramanathan, S., Sasidharan, S., Mansor, S.M.
    MyJurnal
    The Clitoria ternatea (Fabaceae) root, seed, and leaf are commonly used in Ayurvedic medicine in Malaysia and Indonesia. The methanol leaf extracts of C. ternatea was tested for toxicity by means of brine shrimp lethality test and acute oral toxicity assay. In the brine shrimp lethality test, the leaf extract were non-toxic or showed weak lethality (LC50 > 1 mg/ml) at the 6 h, 12 h and 24 h incubation period. Nevertheless, at the 48 h incubation time, the leaf extract exhibited moderate toxicity activity with LC50 values of 0.49 mg/ml. In the acute toxicity study using mice, the median lethal dose (LD50) of the extract was found greater than 2000 mg/kg, and we found no pathological changes by means of macroscopic examination of tissues of mice treated with the extract. We conclude that the C. ternatea leaf extract is not toxic in mice and brine shrimp.
  2. Perumal S, Mahmud R, Ramanathan S
    Nat Prod Res, 2015;29(18):1766-9.
    PMID: 25571920 DOI: 10.1080/14786419.2014.999242
    Euphorbia hirta (L.) plant is traditionally used in Malaysia for the treatment of gastrointestinal, bronchial and respiratory ailments caused by nosocomial infectious agents. Bioactivity-guided fractionation of the methanol extract of the aerial parts of E. hirta and analysis using high-performance liquid chromatography have led to the isolation of two antibacterial compounds. These compounds were identified as caffeic acid (CA) and (-)-epicatechin 3-gallate (ECG) based on spectroscopic analyses and comparison with previously published data. Using broth microdilution method, both ECG and CA had demonstrated significant minimum inhibitory concentration of 15.6 and 31.3 μg/mL respectively, against Pseudomonas aeruginosa. Time-kill assessment of ECG and CA displayed bactericidal effect on P. aeruginosa cells.
  3. Ramanathan S, McCurdy CR
    Curr Opin Psychiatry, 2020 07;33(4):312-318.
    PMID: 32452943 DOI: 10.1097/YCO.0000000000000621
    PURPOSE OF REVIEW: To inform readers about the increasingly popular Western dietary supplement, kratom (Mitragyna speciosa) and how the products are available in the Western world compared with traditional Southeast Asian use. Kratom has been traditionally used for increasing stamina of outdoor laborers (farmers), mood enhancement, pain, and opium addiction. Interestingly, kratom has been reported to have a paradoxical effect in that stimulant feelings, and sedative feelings can be obtained depending on the amount utilized. There are several biologically active alkaloids present in kratom.

    RECENT FINDINGS: Recent studies have been focused on the interactions of mitragynine, the most abundant alkaloid, and opioid-like effects. This has been driven by the harm that kratom products have produced in the Western world, in stark contrast to the lack of harm in Southeast Asian traditional use over centuries. Many users in the Western world ingest kratom for mood enhancement and/or to ween themselves from prescription or illicit opioids. Highly concentrated products and recreational use and misuse have resulted in individuals pushing doses to levels that have not been imagined or ever studied in animal, let alone humans.

    SUMMARY: Kratom, as a preparation and how it is utilized is different around the world.

  4. Kamilla L, Mansor SM, Ramanathan S, Sasidharan S
    Microsc Microanal, 2009 Aug;15(4):366-72.
    PMID: 19575837 DOI: 10.1017/S1431927609090783
    Clitoria ternatea is known for its antimicrobial activity but the antifungal effects of leaf extract on growth and morphogenesis of Aspergillus niger have not been observed. The extract showed a favorable antifungal activity against A. niger with a minimum inhibition concentration 0.8 mg/mL and minimum fungicidal concentration 1.6 mg/mL, respectively. The leaf extract exhibited considerable antifungal activity against filamentous fungi in a dose-dependent manner with 0.4 mg/mL IC50 value on hyphal growth of A. niger. The main changes observed under scanning electron microscopy after C. ternatea extract treatment were loss of cytoplasm in fungal hyphae and the hyphal wall and its diameter became markedly thinner, distorted, and resulted in cell wall disruption. In addition, conidiophore alterations were also observed when A. niger was treated with C. ternatea leaf extract.
  5. Devaraj S, Ismail S, Ramanathan S, Yam MF
    ScientificWorldJournal, 2014;2014:353128.
    PMID: 25133223 DOI: 10.1155/2014/353128
    Curcuma xanthorrhiza (CX) has been used for centuries in traditional system of medicine to treat several diseases such as hepatitis, liver complaints, and diabetes. It has been consumed as food supplement and "jamu" as a remedy for hepatitis. Hence, CX was further explored for its potential as a functional food for liver related diseases. As such, initiative was taken to evaluate the antioxidant and hepatoprotective potential of CX rhizome. Antioxidant activity of the standardized CX fractions was determined using in vitro assays. Hepatoprotective assay was conducted against carbon tetrachloride- (CCl4-) induced hepatic damage in rats at doses of 125, 250, and 500 mg/kg of hexane fraction. Highest antioxidant activity was found in hexane fraction. In the case of hepatoprotective activity, CX hexane fraction showed significant improvement in terms of a biochemical liver function, antioxidative liver enzymes, and lipid peroxidation activity. Good recovery was observed in the treated hepatic tissues histologically. Hence, the results concluded that CX hexane fraction possessed prominent hepatoprotective activities which might be due to its in vitro antioxidant activity. These findings also support the use of CX as a functional food for hepatitis remedy in traditional medicinal system.
  6. Nagaya D, Ramanathan S, Ravichandran M, Navaratnam V
    J Integr Neurosci, 2012 Mar;11(1):117-22.
    PMID: 22744787
    Drug addiction is an important social problem in many countries. Genetic and environmental factors contribute to the predisposition of drug addiction. Genetic variations at the μ opioid receptor (OPRM1) gene locus have been associated with opiate addiction. The present study aims to delineate the frequency of A118G allele of OPRM1 among Malaysian subjects. The frequency of A allele and G allele were 51% and 49%, respectively for addicts and about 73% and 27% respectively for healthy volunteers. The frequency of G allele was 1.77-fold higher in addicts by odds ratio calculation at 95% Cl, which indicate the G allele to be strongly associated with addiction X(2) = 15.31,P < 0.0001; odds ratio 2.51; 95% Cl (1.575-3.994), compared to healthy volunteers. A significant association was observed between A118G polymorphism in μ opioid receptor gene and drug addiction.
  7. Ramanujam TM, Sergius A, Usha V, Ramanathan S
    Pediatr Surg Int, 1998 Nov;14(1-2):134-7.
    PMID: 9880724
    Urethral duplication (UD) is an uncommon malformation. Obstruction rarely occurs in hypospadiac UD. We describe two children with incomplete hypospadiac UD in association with posterior urethral valves, a combination not previously recognised. The embryonic significance of this anomaly is discussed. Keywords Urethral duplication. Hypospadias. Posterior urethral valve. Megalourethra
  8. Ramanathan S, Nair NK, Mansor SM, Navaratnam V
    J. Chromatogr., 1993 Jun 02;615(2):303-7.
    PMID: 8335708
    A rapid and selective high-performance liquid chromatographic assay for simultaneous quantitative determination of a new antifilarial drug (UMF-058, I) and mebendazole (MBZ) is described. After a simple extraction from whole blood, both compounds were analysed using a C18 Nova Pak reversed-phase column and a mobile phase of methanol-0.05 M ammonium dihydrogenphosphate (50:50, v/v) adjusted to pH 4.0, with ultraviolet detection at 291 nm. The average recoveries of I and MBZ over a concentration range of 25-250 ng/ml were 92.0 +/- 7.7 and 84.4 +/- 4.4%, respectively. The minimum detectable concentrations in whole blood for I and MBZ were 7 and 6 ng/ml, respectively. This method was found to be suitable for pharmacokinetic studies.
  9. Kalaiyarasi J, Pandian K, Ramanathan S, Gopinath SCB
    Sci Rep, 2020 07 30;10(1):12860.
    PMID: 32732935 DOI: 10.1038/s41598-020-69578-8
    This research presents a simple, fast and simultaneous electrochemical quantitative determination of nucleobases, for example guanine (G), adenine (A), and thymine (T) in a beef and chicken livers samples to measure the quality of food products based on hybrids of graphitic carbon nitride/Graphene nanoflakes (g-C3N4/GNF) modified electrode. Graphitic carbon nitride (g-C3N4) made of graphite-like covalent link connects nitrogen, nitride, and carbon atoms in the structural design with improved the electrical properties and low band gap semiconductor. The g-C3N4/GNF nanocomposite was synthesized by the hydrothermal treatment to form a porous g-C3N4 interconnected three dimensional (3D) network of g-C3N4 and GNF. The 3D g-C3N4/GNF/GCE was utilized for the detection of nucleic acid bases with a well resolved oxidation peak for the individual analyte. The electrocatalytic current was established to be a linear range from 0.3 × 10-7 to 6.6 × 10-6, 0.3 × 10-7 to 7.3 × 10-6, and 5.3 × 10-6 to 63.3 × 10-4 M for G, A, and T with a detection limit of 4.7, 3.5 and 55 nM, respectively. The diffusion co-efficient and the kinetic parameters were derived from the chronoamperometry technique. The proposed sensing strategy has been effectively used for the application in real sample analysis and observed that the electrode free from the surface fouling.
  10. Ramanathan S, Nair NK, Mansor SM, Navaratnam V
    J Chromatogr B Biomed Appl, 1994 May 13;655(2):269-73.
    PMID: 8081473
    A rapid and selective high-performance liquid chromatographic (HPLC) method for the simultaneous determination of the antifilarial drug UMF-078 (I) and its metabolites UMF-060 (II) and flubendazole (III) is described. After a simple extraction from whole blood, the compounds were determined by HPLC using a C18 Inertsil ODS-2 reversed-phase column with methanol-0.05M ammonium acetate (pH 4.0) as the mobile phase and ultraviolet detection at 291 nm. The average recoveries of I, II and III over the concentration range 20-500 ng ml-1 were 69.9 +/- 4.7, 85.6 +/- 4.4 and 85.1 +/- 6.0%, respectively. The minimum detectable concentrations in whole blood for I, II and III were 10, 7 and 7 ng ml-1, respectively. This method was found to be suitable for pharmacokinetic studies.
  11. Sabetghadam A, Ramanathan S, Mansor SM
    Pharmacognosy Res, 2010 May;2(3):181-5.
    PMID: 21808563 DOI: 10.4103/0974-8490.65514
    Mitragyna speciosa Korth is a medicinal plant indigenous to Thailand and Malaysia and has been known for its narcotic and coca-like effects. Many studies have been performed on the antinociceptive effect of the plant extracts of Thai origin; however, limited studies have been reported till date on M. speciosa extracts of Malaysian origin. Various concentrations of alkaloid (5-20 mg/kg), methanolic (50-200 mg/kg), and aqueous (100-400 mg/kg) extracts of Malaysian M. speciosa leaves were prepared and orally administered to nine groups of rats. Morphine (5 mg/kg, s.c.) and aspirin (300 mg/kg, p.o.) were used as control. Antagonism of the antinociceptive activity was evaluated by pretreatment with naloxone at a dose of 2 mg/kg (i.p.). Results showed that oral administration of the alkaloid (20 mg/kg), methanolic (200 mg/kg), and aqueous (400 mg/kg) extracts significantly prolonged the latency of nociceptive response compared with control groups in both hot plate and tail flick tests (P < 0.05). Antinociceptive action of the alkaloid (20 mg/kg), methanolic (200 mg/kg), and aqueous (400 mg/kg) extracts was significantly blocked by naloxone. In conclusion, these results suggest the presence of antinociceptive effect in various extracts of Malaysian M. speciosa leaves. In addition, the antinociceptive effective doses vary depending on the type of solvents used for extraction.
  12. Hazim AI, Ramanathan S, Parthasarathy S, Muzaimi M, Mansor SM
    J Physiol Sci, 2014 May;64(3):161-9.
    PMID: 24464759 DOI: 10.1007/s12576-014-0304-0
    The effects of mitragynine on anxiety-related behaviours in the open-field and elevated plus-maze tests were evaluated. Male Sprague-Dawley rats were orally treated with mitragynine (10, 20 and 40 mg/kg) or diazepam (10 mg/kg) 60 min before behavioural testing. Mitragynine doses used in this study were selected on the basis of approximately human equivalent doses with reference to our previous literature reports. Acute administration of mitragynine (10, 20 and 40 mg/kg) or diazepam (10 mg/kg) increased central zone and open arms exploration in the open-field and elevated plus-maze tests respectively. These anxiolytic-like effects of mitragynine were effectively antagonized by intraperitoneal administration of naloxone (2 mg/kg), flumazenil (10 mg/kg), sulpiride (0.5 mg/kg) or SCH 23390 (0.02 mg/kg) 15 min before mitragynine treatments. These findings reveal that the acute administration of mitragynine produces anxiolytic-like effects and this could be possibly attributed to the interactions among opioidergic, GABAergic and dopaminergic systems in brain regions involved in anxiety.
  13. Devaraj S, Esfahani AS, Ismail S, Ramanathan S, Yam MF
    Molecules, 2010 Apr;15(4):2925-34.
    PMID: 20428088 DOI: 10.3390/molecules15042925
    Ethanolic extract of Curcuma xanthorrhiza was used to evaluate the analgesic and toxicity effects in vivo. The extract was standardized using GC-MS, which showed that 1 mg of Curcuma xanthorrhiza ethanolic extract contains 0.1238 mg of xanthorrhizol. The analgesic activity was studied in rats using three different models, namely the hot plate test, tail flick test and formalin-induced pain test. The acute oral toxicity was examined by the oral administration of standardized Curcuma xanthorrhiza ethanolic extract in mice at doses ranging from 300-5,000 mg/kg and observation for 14 days. Standardized Curcuma xanthorrhiza ethanolic extract did not show significant analgesic effect in the hot plate and tail flick tests. However, in the formalin-induced pain test, Curcuma xanthorrhiza ethanolic extract significantly (P < 0.05) suppressed the paw licking time of rats in both early and late phases at doses 200 and 400 mg/kg of the extract, respectively. In the acute oral toxicity study, Curcuma xanthorrhiza ethanolic extract did not show any toxic effects in mice at 5 g/kg. These experimental results suggest that the standardized Curcuma xanthorrhiza ethanolic extract showed peripheral and central antinociceptive activity associated with neurogenic pain as well as a relative absence of toxic effects which could compromise the medicinal use of this plant in folk medicine.
  14. Sabetghadam A, Ramanathan S, Sasidharan S, Mansor SM
    J Ethnopharmacol, 2013 Apr 19;146(3):815-23.
    PMID: 23422336 DOI: 10.1016/j.jep.2013.02.008
    ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa is a popular medicinal plant in Southeast Asia which is commonly used for its morphine-like effects. Although the analgesic properties of Mitragyna speciosa and its ability to ameliorate withdrawal signs after abrupt cessation of opioid abuse are well known, information about the long-term safety of the plant's active compounds is lacking. In this work, we evaluated the effects of sub-chronic exposure to mitragynine, the principal alkaloid of Mitragyna speciosa leaves in rats.

    MATERIALS AND METHODS: Male and female Sprague-Dawley rats received three doses of mitragynine (1, 10, 100mg/kg, p.o) for 28 days respectively. Food intake and relative body weight were measured during the experiment. After completion of drug treatment biochemical, hematological, and histological analyses were performed.

    RESULTS: No mortality was observed in any of the treatment groups. The groups of rats treated with the lower and intermediate doses showed no toxic effects during the study. However, the relative body weight of the group of female rats treated with the 100mg/kg dose was decreased significantly. Food intake also tended to decrease in the same group. Only relative liver weight increased after treatment with the high dose of mitragynine (100mg/ kg) in both the male and female treatment groups of rats. Biochemical and hematological parameters were also altered especially in high dose treatment group which corresponds to the histopathological changes.

    CONCLUSIONS: The study demonstrated that mitragynine is relatively safe at lower sub-chronic doses (1-10mg/kg) but exhibited toxicity at a highest dose (sub-chronic 28 days: 100mg/kg). This was confirmed by liver, kidney, and brain histopathological changes, as well as hematological and biochemical changes.

  15. Ponnusamy Y, Chear NJ, Ramanathan S, Lai CS
    J Ethnopharmacol, 2015 Jun 20;168:305-14.
    PMID: 25858509 DOI: 10.1016/j.jep.2015.03.062
    Dicranopteris linearis is a fern used traditionally for the treatment of skin afflictions such as external wounds, boils and ulcers. However, there are no scientific studies to date to demonstrate its ability to induce wound recovery. The objective of the present study was to explore the wound healing properties of an active fraction of D. linearis through several in vitro assays and to determine its chemical profile.
  16. Ramanathan S, Gopinath SCB, Md Arshad MK, Poopalan P
    Biosens Bioelectron, 2019 Sep 15;141:111434.
    PMID: 31238281 DOI: 10.1016/j.bios.2019.111434
    The pragmatic outcome of a lung cancer diagnosis is closely interrelated in reducing the number of fatal death caused by the world's top cancerous disease. Regardless of the advancement made in understanding lung tumor, and its multimodal treatment, in general the percentage of survival remain low. Late diagnosis of a cancerous cell in patients is the major hurdle for the above circumstances. In the new era of a lung cancer diagnosis with low cost, portable and non-invasive clinical sampling, nanotechnology is at its inflection point where current researches focus on the implementation of biosensor conjugated nanomaterials for the generation of the ideal sensing. The present review encloses the superiority of nanomaterials from zero to three-dimensional nanostructures in its discrete and nanocomposites nanotopography on sensing lung cancer biomarkers. Recent researches conducted on definitive nanomaterials and nanocomposites at multiple dimension with distinctive physiochemical property were focused to subside the cases associated with lung cancer through the development of novel biosensors. The hurdles encountered in the recent research and future preference with prognostic clinical lung cancer diagnosis using multidimensional nanomaterials and its composites are presented.
  17. Rajoo A, Ramanathan S, Mansor SM, Sasidharan S
    J Ethnopharmacol, 2021 Feb 10;266:113414.
    PMID: 32980488 DOI: 10.1016/j.jep.2020.113414
    ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants are crucial to healing numerous illnesses. Elaeis guineensis Jacq (family Arecaceae) is a medicinal plant traditionally used for the treatment of wounds.

    AIM OF THE STUDY: However, there are no scientific reports documented on the wound healing activities of this plant against Staphylococcus aureus infections in the Sprague Dawley male rat model. Thus, the present study was conducted to evaluate the wound healing potential of E. guineensis extract leaves.

    MATERIALS AND METHODS: The crude extract was prepared in 10% (w/w) ointment and evaluated for wound healing activity using excision and infected wound models in Sprague Dawley rats. The wound healing activity was evaluated from wound closure rate, CFU reduction, histological analysis of granulation tissue and matrix metalloprotease expression.

    RESULTS: The results show that the E. guineensis extract has potent wound healing ability, as manifest from improved wound closure and tissue regeneration supported by histopathological parameters. Assessment of granulation tissue every fourth day showed a significant reduction in the microbial count. The expression of matrix metalloproteinases was well correlated with the other results, hence confirming E. guineensis wound healing activity's effectiveness.

    CONCLUSIONS: E. guineensis enhanced infected wound healing in rats, thus supporting its traditional use.

  18. Lee MJ, Ramanathan S, Mansor SM, Tan SC
    Anal Biochem, 2020 06 15;599:113733.
    PMID: 32302607 DOI: 10.1016/j.ab.2020.113733
    An enzyme-linked immunosorbent assay for detection of mitragynine, other closely related Kratom alkaloids and metabolites was developed using polyclonal antibodies. Mitragynine was conjugated to a carrier protein, cationized-bovine serum albumin using Mannich reaction. The synthesized antigen was injected into rabbits to elicit specific polyclonal antibodies against mitragynine. An enzyme conjugate was synthesized for evaluating its performance with the antibodies produced. The assay had an IC50 of 7.3 ng/mL with a limit of detection of 15 ng/mL for mitragynine. Antibody produced have high affinity for mitragynine (100%), other closely related Kratom alkaloids such as paynantheine (54%), speciociliatine (63%), 7α-hydroxy-7H-mitragynine (83%) and cross-reacted with metabolites 9-O-demethyl mitragynine (79%), 16-carboxy mitragynine (103%), 9-O-demethyl mitragynine sulfate (263%), 9-O-demethyl mitragynine glucuronide (60%), 16-carboxy mitragynine glucuronide (60%), 9-O-demethyl-16-carboxy mitragynine sulfate (270%) and 17-O-demethyl-16,17-dihydro mitragynine glucuronide (34%). It showed cross-reactivity less than 0.01% to reserpine, codeine, morphine, caffeine, methadone, amphetamine, and cocaine. Ten-fold dilution urine was used in the assay to reduce the matrix effects. The recovery ranged from 83% to 112% with variation coefficients in intraday and interday less than 8% and 6%, respectively. The ELISA turned out to be a convenient tool to diagnose mitragynine, other closely related Kratom alkaloids and metabolites in human urine samples.
  19. Torey A, Sasidharan S, Latha LY, Sudhakaran S, Ramanathan S
    Pharm Biol, 2010 Oct;48(10):1119-23.
    PMID: 20738154 DOI: 10.3109/13880200903490505
    To investigate the in vitro antioxidant activity of methanol extracts of Ixora coccinea L. (Rubiaceae) flower, leaf and stem.
  20. Khaw KY, Kumar P, Yusof SR, Ramanathan S, Murugaiyah V
    Arch Pharm (Weinheim), 2020 Nov;353(11):e2000156.
    PMID: 32716578 DOI: 10.1002/ardp.202000156
    α-Mangostin has been reported to possess a broad range of pharmacological effects including potent cholinesterase inhibition, but the development of α-mangostin as a potential lead compound is impeded by its toxicity. The present study investigated the impact of simple structural modification of α-mangostin on its cholinesterase inhibitory activities and toxicity toward neuroblastoma and liver cancer cells. The dialkylated derivatives retained good acetylcholinesterase (AChE) inhibitory activities with IC50 values between 4.15 and 6.73 µM, but not butyrylcholinesterase (BChE) inhibitory activities, compared with α-mangostin, a dual inhibitor (IC50 : AChE, 2.48 µM; BChE, 5.87 µM). Dialkylation of α-mangostin produced AChE selective inhibitors that formed hydrophobic interactions at the active site of AChE. Interestingly, all four dialkylated derivatives of α-mangostin showed much lower cytotoxicity, being 6.4- to 9.0-fold and 3.8- to 5.5-fold less toxic than their parent compound on neuroblastoma and liver cancer cells, respectively. Likewise, their selectivity index was higher by 1.9- to 4.4-fold; in particular, A2 and A4 showed improved selectivity index compared with α-mangostin. Taken together, modification of the hydroxyl groups of α-mangostin at positions C-3 and C-6 greatly influenced its BChE inhibitory and cytotoxic but not its AChE inhibitory activities. These dialkylated derivatives are viable candidates for further structural modification and refinement, worthy in the search of new AChE inhibitors with higher safety margins.
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