Displaying publications 21 - 40 of 69 in total

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  1. A simple HPLC-DAD method for the detection and quantification of psychotropic mitragynine in Mitragyna speciosa (ketum) and its products for the application in forensic investigation
    Parthasarathy S, Ramanathan S, Murugaiyah V, Hamdan MR, Said MI, Lai CS, et al.
    Forensic Sci Int, 2013 Mar 10;226(1-3):183-7.
    PMID: 23385139 DOI: 10.1016/j.forsciint.2013.01.014
    Mitragyna speciosa, a native plant of Thailand and Malaysia known as 'ketum', is a plant of considerable interest. It exhibits strong antinociceptive effect and yet, acts like a psychostimulant. Due to the affordability and its ease of availability, the abuse of this plant as a substitute for other banned narcotics has become a major concern in many societies. In countries such as Thailand, Myanmar, Australia and Malaysia, the use of ketum is illegal. However, for a person to be charged for possessing or selling ketum, a reliable analytical method is needed in order to detect and identify the plant and its products. Mitragynine is the major alkaloid of ketum. This compound manifests its antinociceptive effects by acting on the opioid receptors. Since M. speciosa contain large quantity of mitragynine and it is exclusive to the species, the present analytical method is developed and validated for the purpose of screening ketum products based on this unique compound as the analytical marker. The method uses a HPLC-DAD system with Inertsil C8 (4.6 mm × 150 mm, 5 μm) as the column and a mixture of acetonitrile and formic acid, 50:50 (v/v), as the mobile phase. This method not only detects mitragynine, it can also be used to quantify the amount of mitragynine in the sample. The limit of detection is 0.25 μg/ml, while the limit of quantification is 0.50 μg/ml. The method is quick, simple and reliable with an accuracy of 97.27-101.74% and coefficient of variations of between 0.91 and 3.96%. The method has been tested and found suitable for the identification and quantification of mitragynine in dried plants, a variety of ketum extracts, as well as ketum drink obtained from the market.
  2. Fulltext Understanding the physicochemical properties of mitragynine, a principal alkaloid of Mitragyna speciosa, for preclinical evaluation
    Ramanathan S, Parthasarathy S, Murugaiyah V, Magosso E, Tan SC, Mansor SM
    Molecules, 2015 Mar 18;20(3):4915-27.
    PMID: 25793541 DOI: 10.3390/molecules20034915
    Varied pharmacological responses have been reported for mitragynine in the literature, but no supportive scientific explanations have been given for this. These studies have been undertaken without a sufficient understanding of the physicochemical properties of mitragynine. In this work a UV spectrophotometer approach and HPLC-UV method were employed to ascertain the physicochemical properties of mitragynine. The pKa of mitragynine measured by conventional UV (8.11 ± 0.11) was in agreement with the microplate reader determination (8.08 ± 0.04). Mitragynine is a lipophilic alkaloid, as indicated by a logP value of 1.73. Mitragynine had poor solubility in water and basic media, and conversely in acidic environments, but it is acid labile. In an in vitro dissolution the total drug release was higher for the simulated gastric fluid but was prolonged and incomplete for the simulated intestinal fluid. The hydrophobicity, poor water solubility, high variability of drug release in simulated biological fluids and acid degradable characteristics of mitragynine probably explain the large variability of its pharmacological responses reported in the literature. The determined physicochemical properties of mitragynine will provide a basis for developing a suitable formulation to further improve its solubility, stability and oral absorption for better assessment of this compound in preclinical studies.
  3. Fulltext Aluminosilicate Nanocomposite on Genosensor: A Prospective Voltammetry Platform for Epidermal Growth Factor Receptor Mutant Analysis in Non-small Cell Lung Cancer
    Ramanathan S, Gopinath SCB, Arshad MKM, Poopalan P, Anbu P, Lakshmipriya T, et al.
    Sci Rep, 2019 11 19;9(1):17013.
    PMID: 31745155 DOI: 10.1038/s41598-019-53573-9
    Lung cancer is one of the most serious threats to human where 85% of lethal death caused by non-small cell lung cancer (NSCLC) induced by epidermal growth factor receptor (EGFR) mutation. The present research focuses in the development of efficient and effortless EGFR mutant detection strategy through high-performance and sensitive genosensor. The current amplified through 250 µm sized fingers between 100 µm aluminium electrodes indicates the voltammetry signal generated by means of the mutant DNA sequence hybridization. To enhance the DNA immobilization and hybridization, ∼25 nm sized aluminosilicate nanocomposite synthesized from the disposed joss fly ash was deposited on the gaps between aluminium electrodes. The probe, mutant (complementary), and wild (single-base pair mismatch) targets were designed precisely from the genomic sequences denote the detection of EGFR mutation. Fourier-transform Infrared Spectroscopy analysis was performed at every step of surface functionalization evidences the relevant chemical bonding of biomolecules on the genosensor as duplex DNA with peak response at 1150 cm-1 to 1650 cm-1. Genosensor depicts a sensitive EGFR mutation as it is able to detect apparently at 100 aM mutant against 1 µM DNA probe. The insignificant voltammetry signal generated with wild type strand emphasizes the specificity of genosensor in the detection of single base pair mismatch. The inefficiency of genosensor in detecting EGFR mutation in the absence of aluminosilicate nanocomposite implies the insensitivity of genosensing DNA hybridization and accentuates the significance of aluminosilicate. Based on the slope of the calibration curve, the attained sensitivity of aluminosilicate modified genosensor was 3.02E-4 A M-1. The detection limit of genosensor computed based on 3σ calculation, relative to the change of current proportional to the logarithm of mutant concentration is at 100 aM.
  4. A DNA based visual and colorimetric aggregation assay for the early growth factor receptor (EGFR) mutation by using unmodified gold nanoparticles
    Ramanathan S, Gopinath SCB, Arshad MKM, Poopalan P, Anbu P
    Mikrochim Acta, 2019 07 18;186(8):546.
    PMID: 31321546 DOI: 10.1007/s00604-019-3696-y
    A genomic DNA-based colorimetric assay is described for the detection of the early growth factor receptor (EGFR) mutation, which is the protruding reason for non-small cell lung cancer. A DNA sequence was designed and immobilized on unmodified gold nanoparticles (GNPs). The formation of the respective duplex indicates the presence of an EGFR mutation. It is accompanied by the aggregation of the GNPs in the presence of monovalent ions, and it indicates the presence of an EGFR mutation. This is accompanied by a color change from red (520 nm) to purple (620 nm). Aggregation was evidenced by transmission electron microscopy, scanning electron microscopy and atomic force microscopy. The limit of detection is 313 nM of the mutant target strand. A similar peak shift was observed for 2.5 μM concentrations of wild type target. No significant peak shift was observed with probe and non-complementary DNA. Graphical abstract Schematic representation of high-specific genomic DNA sequence on gold nanoparticle (GNP) aggregation with sodium chloride (NaCl). It illustrates the detection method for EGFR mutation on lung cancer detection. Red and purple colors of tubes represent dispersed and aggregated GNP, respectively.
  5. Fulltext Accelerated Solvent Extractions (ASE) of Mitragyna speciosa Korth. (Kratom) Leaves: Evaluation of Its Cytotoxicity and Antinociceptive Activity
    Goh YS, Karunakaran T, Murugaiyah V, Santhanam R, Abu Bakar MH, Ramanathan S
    Molecules, 2021 Jun 17;26(12).
    PMID: 34204457 DOI: 10.3390/molecules26123704
    Mitragyna speciosa Korth (kratom) is known for its psychoactive and analgesic properties. Mitragynine is the primary constituent present in kratom leaves. This study highlights the utilisation of the green accelerated solvent extraction technique to produce a better, non-toxic and antinociceptive active botanical extract of kratom. ASE M. speciosa extract had a dry yield (0.53-2.91 g) and showed a constant mitragynine content (6.53-7.19%) when extracted with organic solvents of different polarities. It only requires a shorter extraction time (5 min) and a reduced amount of solvents (less than 100 mL). A substantial amount of total phenolic (407.83 ± 2.50 GAE mg/g and flavonoids (194.00 ± 5.00 QE mg/g) were found in ASE kratom ethanol extract. The MTT test indicated that the ASE kratom ethanolic leaf extract is non-cytotoxic towards HEK-293 and HeLa Chang liver cells. In mice, ASE kratom ethanolic extract (200 mg/kg) demonstrated a better antinociceptive effect compared to methanol and ethyl acetate leaf extracts. The presence of bioactive indole alkaloids and flavonols such as mitragynine, paynantheine, quercetin, and rutin in ASE kratom ethanolic leaf extract was detected using UHPLC-ESI-QTOF-MS/MS analysis supports its antinociceptive properties. ASE ethanolic leaf extract offers a better, safe, and cost-effective choice of test botanical extract for further preclinical studies.
  6. Fulltext Comparative Toxicity Assessment of Kratom Decoction, Mitragynine and Speciociliatine Versus Morphine on Zebrafish (Danio rerio) Embryos
    Damodaran T, Chear NJ, Murugaiyah V, Mordi MN, Ramanathan S
    Front Pharmacol, 2021;12:714918.
    PMID: 34489704 DOI: 10.3389/fphar.2021.714918
    Background: Kratom (Mitragyna speciosa Korth), a popular opioid-like plant holds its therapeutic potential in pain management and opioid dependence. However, there are growing concerns about the safety or potential toxicity risk of kratom after prolonged use. Aim of the study: The study aimed to assess the possible toxic effects of kratom decoction and its major alkaloids, mitragynine, and speciociliatine in comparison to morphine in an embryonic zebrafish model. Methods: The zebrafish embryos were exposed to kratom decoction (1,000-62.5 μg/ml), mitragynine, speciociliatine, and morphine (100-3.125 μg/ml) for 96 h post-fertilization (hpf). The toxicity parameters, namely mortality, hatching rate, heart rate, and morphological malformations were examined at 24, 48, 72, and 96 hpf, respectively. Results: Kratom decoction at a concentration range of ≥500 μg/ml caused 100% mortality of zebrafish embryos and decreased the hatching rate in a concentration-dependent manner. Meanwhile, mitragynine and speciociliatine exposure resulted in 100% mortality of zebrafish embryos at 100 μg/ml. Both alkaloids caused significant alterations in the morphological development of zebrafish embryos including hatching inhibition and spinal curvature (scoliosis) at the highest concentration. While exposure to morphine induced significant morphological malformations such as pericardial oedema, spinal curvature (lordosis), and yolk edema in zebrafish embryos. Conclusion: Our findings provide evidence for embryonic developmental toxicity of kratom decoction and its alkaloids both mitragynine and speciociliatine at the highest concentration, hence suggesting that kratom consumption may have potential teratogenicity risk during pregnancy and thereby warrants further investigations.
  7. Intestinal permeability of mitragynine in rats using in situ absorption model
    Jagabalan JDY, Murugaiyah V, Zainal H, Mansor SM, Ramanathan S
    J Asian Nat Prod Res, 2019 Apr;21(4):351-363.
    PMID: 29667422 DOI: 10.1080/10286020.2018.1461088
    The intestinal permeability of mitragynine was investigated in situ using a single pass intestinal perfusion (SPIP) absorption model, in small intestine of rat using mitragynine in the absence/presence of the permeability markers, P-gp and/or CYP3A4 inhibitors. Mitragynine demonstrated high intestinal permeability (Peff of 1.11 × 10-4 cm/s) that is in the range of highly permeable drugs such as propranolol (Peff of 1.27 × 10-4 cm/s) indicating that it readily crosses the intestine. The addition of azithromycin (P-glycoprotein inhibitor) and ciprofloxacin (CYP3A4 inhibitor) or combination of both has no effect on intestinal permeability of mitragynine across the rat small intestine.
  8. Chemopreventive effects of standardized papaya leaf fraction on oxidatively stressed human liver cells
    Tan SA, Goya L, Ramanathan S, Sulaiman SF, Alam M, Navaratnam V
    Food Res Int, 2014 Oct;64:387-395.
    PMID: 30011665 DOI: 10.1016/j.foodres.2014.06.040
    Extract from papaya leaves, a waste material from fruit farms in Malaysia was previously reported to possess remarkable antioxidative activities. In this study, papaya leaf extract was separated into fractions of different polarities [petroleum ether (PE), ethyl acetate (EA), n-butanol (NB) and water (W) fractions]. The aim of this research was to determine the most active fraction in terms of its chemopreventive effects towards oxidative stress and the chemical constituents involved. The cytoprotective nature of the papaya fractions was observed against t-BOOH-induced oxidative stress on HepG2 liver cell line. ROS assay indicated that only PE and EA effectively reduced the increment of radical due to the pro-oxidant, t-BOOH. Nevertheless, PE was a stronger ROS scavenger by demonstrating ROS reducing activity in a dose-dependent manner to the basal level. This fraction was also found to inhibit cell death caused by t-BOOH toxicity, attenuating lactate dehydrogenase enzyme leakage by more than 90% (p<0.05). In addition, gene expression of phase II antioxidant enzymes (hmox-1 and nqo-1) and their transcription factor (nrf-2) were shown to be upregulated upon PE treatment during a time-course study. A GC-MS fingerprint of the active fraction was subsequently obtained with standardization using the marker compound; α-tocopherol, a well known antioxidant. However, this pure compound was not as effective as its corresponding PE concentrations in ROS reduction. Hence, PE of papaya leaf extract was a strong antioxidant and cytoprotectant with tremendous potential to be harnessed into the next therapeutic remedy against oxidative stress of the liver.
  9. Clitoria ternatea L. root extract ameliorated the cognitive and hippocampal long-term potentiation deficits induced by chronic cerebral hypoperfusion in the rat
    Damodaran T, Tan BWL, Liao P, Ramanathan S, Lim GK, Hassan Z
    J Ethnopharmacol, 2018 Oct 05;224:381-390.
    PMID: 29920356 DOI: 10.1016/j.jep.2018.06.020
    ETHNOPHARMACOLOGICAL RELEVANCE: Clitoria ternatea L. (CT), commonly known as Butterfly pea, is used in Indian Ayurvedic medicine to promote brain function and treat mental disorders. Root of CT has been proven to enhance memory, but its role in an animal model of chronic cerebral hypoperfusion (CCH), which has been considered as a major cause of brain disorders, has yet to be explored.

    AIM OF THE STUDY: To assess the motor and cognitive effects of acute oral administration of CT root methanolic extract and hippocampal long-term plasticity in the CA1 region of the CCH rat model.

    MATERIALS AND METHODS: Male Sprague Dawley rats (200-300 g) were subjected to permanent bilateral occlusion of common carotid arteries (PBOCCA) or sham operation. Then, these rats were given oral administration of CT root extract at doses of 100, 200 or 300 mg/kg on day 28 post-surgery and tested using behavioural tests (open-field test, passive avoidance task, and Morris water maze) and electrophysiological recordings (under urethane anaesthesia).

    RESULTS: Treatment with CT root extract at the doses of 200 and 300 mg/kg resulted in a significant enhancement in memory performance in CCH rats induced by PBOCCA. Furthermore, CCH resulted in inhibition of long-term potentiation (LTP) formation in the hippocampus, and CT root extract rescued the LTP impairment. The CT root extract was confirmed to improve the glutamate-induced calcium increase via calcium imaging using primary cultured rat neurons. No significance difference was found in the CaMKII expression. These results demonstrated that CT root extract ameliorates synaptic function, which may contribute to its improving effect on cognitive behaviour.

    CONCLUSIONS: Our findings demonstrated an improving effect of CT root extract on memory in the CCH rat model suggesting that CT root extract could be a potential therapeutic strategy to prevent the progression of cognitive deterioration in vascular dementia (VaD) and Alzheimer's disease (AD) patients.

  10. Mitragynine (Kratom) impairs spatial learning and hippocampal synaptic transmission in rats
    Hassan Z, Suhaimi FW, Ramanathan S, Ling KH, Effendy MA, Müller CP, et al.
    J. Psychopharmacol. (Oxford), 2019 07;33(7):908-918.
    PMID: 31081443 DOI: 10.1177/0269881119844186
    BACKGROUND: Mitragynine is the major alkaloid of Mitragyna speciosa (Korth.) or Kratom, a psychoactive plant widely abused in Southeast Asia. While addictive effects of the substance are emerging, adverse cognitive effects of this drug and neuropharmacological actions are insufficiently understood.

    AIMS: In the present study, we investigated the effects of mitragynine on spatial learning and synaptic transmission in the CA1 region of the hippocampus.

    METHODS: Male Sprague Dawley rats received daily (for 12 days) training sessions in the Morris water maze, with each session followed by treatment either with mitragynine (1, 5, or 10 mg/kg; intraperitoneally), morphine (5 mg/kg; intraperitoneally) or a vehicle. In the second experiment, we recorded field excitatory postsynaptic potentials in the hippocampal CA1 area in anesthetized rats and assessed the effects of mitragynine on baseline synaptic transmission, paired-pulse facilitation, and long-term potentiation. Gene expression of major memory- and addiction-related genes was investigated and the effects of mitragynine on Ca2+ influx was also examined in cultured primary neurons from E16-E18 rats.

    RESULTS/OUTCOMES: Escape latency results indicate that animals treated with mitragynine displayed a slower rate of acquisition as compared to their control counterparts. Further, mitragynine treatment significantly reduced the amplitude of baseline (i.e. non-potentiated) field excitatory postsynaptic potentials and resulted in a minor suppression of long-term potentiation in CA1. Bdnf and αCaMKII mRNA expressions in the brain were not affected and Ca2+ influx elicited by glutamate application was inhibited in neurons pre-treated with mitragynine.

    CONCLUSIONS/INTERPRETATION: These data suggest that high doses of mitragynine (5 and 10 mg/kg) cause memory deficits, possibly via inhibition of Ca2+ influx and disruption of hippocampal synaptic transmission and long-term potentiation induction.

  11. Combinations of indole based alkaloids from Mitragyna speciosa (Kratom) and cisplatin inhibit cell proliferation and migration of nasopharyngeal carcinoma cell lines
    Domnic G, Jeng-Yeou Chear N, Abdul Rahman SF, Ramanathan S, Lo KW, Singh D, et al.
    J Ethnopharmacol, 2021 Oct 28;279:114391.
    PMID: 34224811 DOI: 10.1016/j.jep.2021.114391
    ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa (Korth.) or kratom is a medicinal plant indigenous to Southeast Asia. The leaf of M. speciosa is used as a remedy in pain management including cancer related pain, in a similar way as opioids and cannabis. Despite its well-known analgesic effect, there is a scarce of information on the cancer-suppressing potential of M. speciosa and its active constituents.

    AIM OF THE STUDY: To assess the potential applicability of M. speciosa alkaloids (mitragynine, speciociliatine or paynantheine) as chemosensitizers for cisplatin in Nasopharyngeal carcinoma (NPC) cell lines.

    MATERIALS AND METHODS: The cytotoxic effects of the extracts, fractions and compounds were determined by conducting in vitro cytotoxicity assays. Based on the cytotoxic screening, the alkaloid extract of M. speciosa exhibited potent inhibitory effect on the NPC cell line NPC/HK1, and therefore, was chosen for further fractionation and purification. NPC cell lines NPC/HK1 and C666-1 were treated with combinations of cisplatin and M. speciosa alkaloids combinations in 2D monolayer culture. The effect of cisplatin and mitragynine as a combination on cell migration was tested using in vitro wound healing and spheroid invasion assays.

    RESULTS: In our bioassay guided isolation, both methanolic and alkaloid extracts showed mild to moderate cytotoxic effect against the NPC/HK1 cell line. Both NPC cell lines (NPC/HK1 and C666-1) were insensitive to single agent and combination treatments of the M. speciosa alkaloids. However, mitragynine and speciociliatine sensitized the NPC/HK1 and C666-1 cells to cisplatin at ~4- and >5-fold, respectively in 2D monolayer culture. The combination of mitragynine and cisplatin also significantly inhibited cell migration of the NPC cell lines. Similarly, the combination also of mitragynine and cisplatin inhibited growth and invasion of NPC/HK1 spheroids in a dose-dependent manner. In addition, the spheroids did not rapidly develop resistance to the drug combinations at higher concentrations over 10 days.

    CONCLUSION: Our data indicate that both mitragynine and speciociliatine could be potential chemosensitizers for cisplatin. Further elucidation focusing on the drug mechanistic studies and in vivo studies are necessary to support delineate the therapeutic applicability of M. speciosa alkaloids for NPC treatment.

  12. Molecularly imprinted polymer amalgamation on narrow-gapped Archimedean-spiral interdigitated electrodes: resistance to electrolyte fouling in acidic medium
    Krishnan H, Gopinath SCB, Md Arshad MK, Zulhaimi HI, Ramanathan S
    Mikrochim Acta, 2021 03 31;188(4):144.
    PMID: 33791872 DOI: 10.1007/s00604-021-04794-1
    A conventional photolithography technique was used to fabricate three types of Archimedean-spiral interdigitated electrodes (AIDEs) containing concentric interlocking electrodes with different electrode and gap sizes, i.e., 150 μm (D1), 100 μm (D2), and 50 μm (D3). The precision of the fabrication was validated by surface topography using scanning electron microscopy, high power microscopy, 3D-nano profilometry, and atomic force microscopy. These AIDEs were fabricated with a tolerance of ± 6 nm in dimensions. The insignificant current variation at the pico-ampere range for all bare AIDEs further proved the reproducibility of the device. The large gap sized AIDE (D1) is insensitive to acidic medium, whereas D2 and D3 are insensitive to alkali medium. D2 was the best with regard to its electrical characterization. Furthermore, uniformly synthesized molecularly imprinted polymer (MIP) nanoparticles prepared with human blood clotting factor IX and its aptamer were in the size range 140 to 160 nm, attached on the sensing surface and characterized. The average thickness of deposited MIP film was 1.7 μm. EDX data shows the prominent peaks for silicon and aluminum substrates as 61.79 and 22.52%, respectively. The MIP nanoparticles-deposited sensor surface was characterized by applying it in electrolyte solutions, and smooth curves with the current flow were observed at pH lower than 8 and discriminated against alkali media. This study provides a new MIP amalgamated AIDE with nano-gapped fingers enabling analysis of other biomaterials due to its operation in an ideal buffer range.
  13. Method validation in quantitative analysis of phase I and phase II metabolites of mitragynine in human urine using liquid chromatography-tandem mass spectrometry
    Lee MJ, Ramanathan S, Mansor SM, Yeong KY, Tan SC
    Anal Biochem, 2018 02 15;543:146-161.
    PMID: 29248503 DOI: 10.1016/j.ab.2017.12.021
    A method using solid phase extraction and liquid chromatography-tandem mass spectrometry to quantitatively detect mitragynine, 16-carboxy mitragynine, and 9-O-demethyl mitragynine in human urine samples was developed and validated. The relevant metabolites were identified using multiple reaction monitoring in positive ionization mode using nalorphine as an internal standard. The method was validated for accuracy, precision, recovery, linearity, and lower limit of quantitation. The intra- and inter-day accuracy and precision were found in the range of 83.6-117.5% with coefficient of variation less than 13%. The percentage of recovery for mitragynine, 16-carboxy mitragynine, and 9-O-demethyl mitragynine was within the range of 80.1-118.9%. The lower limit of quantification was 1 ng/mL for mitragynine, 2 ng/mL for 16-carboxy mitragynine, and 50 ng/mL for 9-O-demethyl mitragynine. The developed method was reproducible, high precision and accuracy with good linearity and recovery for mitragynine, 16-carboxy mitragynine, and 9-O-demethyl mitragynine in human urine.
  14. Severity of Pain and Sleep Problems during Kratom (Mitragyna speciosa Korth.) Cessation among Regular Kratom Users
    Singh D, Narayanan S, Vicknasingam BK, Prozialeck WC, Ramanathan S, Zainal H, et al.
    J Psychoactive Drugs, 2018 03 20;50(3):266-274.
    PMID: 29558272 DOI: 10.1080/02791072.2018.1443234
    Kratom (Mitragyna speciosa Korth.) is traditionally used in Southeast Asia for its medicinal value and psychoactive properties. Nonetheless, cessation from regular kratom use is reported to cause unpleasant dose-dependent withdrawal symptoms. This study aims to evaluate the severity of pain and sleep problems following the cessation of kratom tea/juice consumption among regular kratom users. A total of 170 regular users were recruited through snowball sampling for this cross-sectional study. The Brief Pain Inventory (BPI) and Pittsburgh Sleep Quality Index (PSQI) scales were administered to assess the severity of pain and sleep problems. Most participants experienced moderate pain intensity (84%) and moderate pain interference (70%) during kratom cessation; 46% experienced more sleep problems during kratom cessation. Individuals who consumed ≥4 glasses of kratom tea/juice (about 76-115 mg of mitragynine) daily had higher odds of reporting some pain interference (OR: 2.0; CI: 1.04-3.93: p 
  15. Thrombocyte counts in mice after the administration of papaya leaf suspension
    Sathasivam K, Ramanathan S, Mansor SM, Haris MR, Wernsdorfer WH
    Wien Klin Wochenschr, 2009 Oct;121 Suppl 3:19-22.
    PMID: 19915811 DOI: 10.1007/s00508-009-1229-0
    Following up a popular use of crude leaf preparations from Carica papaya for the treatment of dengue infections, a suspension of powdered Carica papaya leaves in palm oil has been investigated for its effect on thrombocyte counts in mice, administering by gavage 15 mg of powdered leaves per kg body weight to 5 mice. Equal numbers of animals received corresponding volumes of either palm oil alone or physiological saline solution. Thrombocyte counts before and at 1, 2, 4, 8, 10, 12, 24, 48 and 72 hours after dosing revealed significantly higher mean counts at 1, 2, 4, 8, 10 and 12 after dosing with the C. papaya leaf formulation as compared to the mean count at hour 0. There was only a non-significant rise of thrombocyte counts in the group having received saline solution, possibly the expression of a normal circadian rhythm in mice. The group having received palm oil only showed a protracted increase of platelet counts that was significant at hours 8 and 48 and obviously the result of a hitherto unknown stimulation of thrombocyte release. The results call for a dose-response investigation and for extending the studies to the isolation and identification of the C. papaya substances responsible for the release and/or production of thrombocytes.
  16. Fulltext In Vitro antioxidant and xanthine oxidase inhibitory activities of methanolic Swietenia mahagoni seed extracts
    Sahgal G, Ramanathan S, Sasidharan S, Mordi MN, Ismail S, Mansor SM
    Molecules, 2009 Nov 06;14(11):4476-85.
    PMID: 19924080 DOI: 10.3390/molecules14114476
    This study examines the in vitro antioxidant activities of the methanol extract of Swietenia mahagoni seeds (SMCM seed extract). The extract was screened for possible antioxidant activities by free radical scavenging activity (DPPH), xanthine oxidase inhibition (XOI), hydrogen peroxide scavenging activity (HPSA) and ferric-reducing antioxidant power (FRAP) assays. The total phenolic and flavonoid contents were also determined. The extract exhibits antioxidant activity of 23.29% with an IC(50 )value of 2.3 mg/mL in the DPPH radical scavenging method, 47.2% in the XOI assay, 49.5% by the HPSA method, and 0.728 mmol/Fe(II)g in the FRAP method at the concentration tested. The amount of total phenolics and flavonoid contents was 70.83 mg gallic acid equivalent (GAE) and 2.5 +/- 0.15 mg of catechin equivalent per gram of dry extract, respectively. High Performance Thin Layer Chromatography (HPTLC) screening indicates the presence of phenolic compounds in the SMCM seed extract. The results indicate that the extract has both high free radical scavenging and xanthine oxidase inhibition activity. The antioxidant activity of SMCM seed extract is comparable with that of other Malaysian tropical fruits and herbal plants.
  17. A new and simple solid-phase extraction method for LC determination of pyronaridine in human plasma
    Ramanathan S, Karupiah S, Nair NK, Olliaro PL, Navaratnam V, Wernsdorfer WH, et al.
    J Chromatogr B Analyt Technol Biomed Life Sci, 2005 Sep 25;824(1-2):45-50.
    PMID: 16046285
    A new approach using a simple solid-phase extraction technique has been developed for the determination of pyronaridine (PND), an antimalarial drug, in human plasma. After extraction with C18 solid-phase sorbent, PND was analyzed using a reverse phase chromatographic method with fluorescence detection (at lambda(ex)=267 nm and lambda(em)=443 nm). The mean extraction recovery for PND was 95.2%. The coefficient of variation for intra-assay precision, inter-assay precision and accuracy was less than 10%. The quantification limit with fluorescence detection was 0.010 microg/mL plasma. The method described herein has several advantages over other published methods since it is easy to perform and rapid. It also permits reducing both, solvent use and sample preparation time. The method has been used successfully to assay plasma samples from clinical pharmacokinetic studies.
  18. Effects of Mesua ferrea leaf and fruit extracts on growth and morphology of Staphylococcus aureus
    Aruldass CA, Marimuthu MM, Ramanathan S, Mansor SM, Murugaiyah V
    Microsc Microanal, 2013 Feb;19(1):254-60.
    PMID: 23332129 DOI: 10.1017/S1431927612013785
    Mesua ferrea is traditionally used for treating bleeding piles, fever, and renal diseases. It has been reported to have antimircobial activity. In the present study, antibacterial efficacy of leaf and fruit extracts on the growth and morphology of Staphylococcus aureus is evaluated. Both extracts display good antibacterial activity against S. aureus with a minimum inhibition concentration of 0.048 mg/mL. Both extracts are bacteriostatic at a minimum bacteriostatic concentration of 0.39 mg/mL. The bacteriostatic activity lasts for 24 h, and then cells start to grow as normal as shown in time-kill analysis. Scanning electron microscopy study indicated potential detrimental effect of the extracts of leaf and fruits of M. ferrea on the morphology of S. aureus. The treatment with the extracts caused extensive lysis of the cells, leakage of intracellular constituents, and aggregation of cytoplasmic contents forming an open meshwork of the matrix.
  19. Molecular distribution, sources and potential health risks of fine particulate-bound polycyclic aromatic hydrocarbons during high pollution episodes in a subtropical urban city
    Singh A, Banerjee T, Latif MT, Ramanathan S, Suradi H, Othman M, et al.
    Chemosphere, 2023 Nov;340:139943.
    PMID: 37625487 DOI: 10.1016/j.chemosphere.2023.139943
    Abundance of fine particulate-bound 16 priority polycyclic aromatic hydrocarbons (PAHs) was investigated to ascertain its sources and potential carcinogenic health risks in Varanasi, India. The city represents a typical urban settlement of South Asia having particulate exposure manyfold higher than standard with reports of pollution induced mortalities and morbidities. Fine particulates (PM2.5) were monitored from October 2019 to May 2020, with 32% of monitoring days accounting ≥100 μgm-3 of PM2.5 concentration, frequently from November to January (99% of monitoring days). The concentration of 16 priority PAHs varied from 24.1 to 44.6 ngm-3 (mean: 33.1 ± 3.2 ngm-3) without much seasonal deviations. Both low (LMW, 56%) and high molecular weight (HMW, 44%) PAHs were abundant, with Fluoranthene (3.9 ± 0.4ngm-3) and Fluorene (3.5 ± 0.3ngm-3) emerged as most dominating PAHs. Concentration of Benzo(a)pyrene (B(a)P, 0.5 ± 0.1ngm-3) was lower than the national standard as it contributed 13% of total PAHs mass. Diagnostic ratios of PAH isomers indicate predominance of pyrogenic sources including emissions from biomass burning, and both from diesel and petrol-driven vehicles. Source apportionment using receptor model revealed similar observation of major PAHs contribution from biomass burning and fuel combustion (54% of source contribution) followed by coal combustion for residential heating and cooking purposes (44%). Potential toxicity of B[a]P equivalence ranged from 0.003 to 1.365 with cumulative toxicity of 2.13ngm-3. Among the PAH species, dibenzo[h]anthracene contributed maximum toxicity followed by B[a]P, together accounting 86% of PAH induced carcinogenicity. Incremental risk of developing cancer through lifetime exposure (ILCR) of PAHs was higher in children (3.3 × 10-4) with 56% contribution from LMW PAHs, primarily through ingestion and dermal contact. Adults in contrast, were more exposed to inhale airborne PAHs with cumulative ILCR of 2.2 × 10-4. However, ILCR to PM2.5 exposure is probably underestimated considering unaccounted metal abundance thus, require source-specific control measures.
  20. Fulltext Aptasensing nucleocapsid protein on nanodiamond assembled gold interdigitated electrodes for impedimetric SARS-CoV-2 infectious disease assessment
    Ramanathan S, Gopinath SCB, Ismail ZH, Md Arshad MK, Poopalan P
    Biosens Bioelectron, 2022 Feb 01;197:113735.
    PMID: 34736114 DOI: 10.1016/j.bios.2021.113735
    In an aim of developing portable biosensor for SARS-CoV-2 pandemic, which facilitates the point-of-care aptasensing, a strategy using 10 μm gap-sized gold interdigitated electrode (AuIDE) is presented. The silane-modified AuIDE surface was deposited with ∼20 nm diamond and enhanced the detection of SARS-CoV-2 nucleocapsid protein (NCP). The characteristics of chemically modified diamond were evidenced by structural analyses, revealing the cubic crystalline nature at (220) and (111) planes as observed by XRD. XPS analysis denotes a strong interaction of carbon element, composed ∼95% as seen in EDS analysis. The C-C, CC, CO, CN functional groups were well-refuted from XPS spectra of carbon and oxygen elements in diamond. The interrelation between elements through FTIR analysis indicates major intrinsic bondings at 2687-2031 cm-1. The aptasensing was evaluated through electrochemical impedance spectroscopy measurements, using NCP spiked human serum. With a good selectivity the lower detection limit was evidenced as 0.389 fM, at a linear detection range from 1 fM to 100 pM. The stability, and reusability of the aptasensor were demonstrated, showing ∼30% and ∼33% loss of active state, respectively, after ∼11 days. The detection of NCP was evaluated by comparing anti-NCP aptamer and antibody as the bioprobes. The determination coefficients of R2 = 0.9759 and R2 = 0.9772 were obtained for aptamer- and antibody-based sensing, respectively. Moreover, the genuine interaction of NCP aptamer and protein was validated by enzyme linked apta-sorbent assay. The aptasensing strategy proposed with AuIDE/diamond enhanced sensing platform is highly recommended for early diagnosis of SARS-CoV-2 infection.
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