Displaying publications 61 - 80 of 250 in total

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  1. Langmia IM, Apalasamy YD, Omar SZ, Mohamed Z
    Pharmacogenet Genomics, 2015 Apr;25(4):199-204.
    PMID: 25714003 DOI: 10.1097/FPC.0000000000000125
    Angiogenic pathway regulating genes such as vascular endothelial growth factor A (VEGFA) have been implicated in preterm birth (PTB) complications. Research shows that the VEGFA/VEGF receptor system plays an important role in the regulation of circulating progesterone level. Attenuation of VEGFA signaling at mid pregnancy results in onset of labor and parturition because of a reduction in circulating progesterone levels. The aim of this study was to investigate the association of VEGFA gene polymorphisms (rs2010963, rs3025039, rs699947, and rs10434) with spontaneous PTB and VEGFA plasma levels in preterm and term women.
  2. Langmia IM, Apalasamy YD, Omar SZ, Mohamed Z
    Pharmacogenet Genomics, 2016 Nov;26(11):505-509.
    PMID: 27602547
    OBJECTIVE: Genetic factors influence susceptibility to preterm birth (PTB) and the immune pathway of PTB that involves the production of cytokines such as interleukins has been implicated in PTB disease. The aim of this study is to investigate the association of interleukin 1β (IL1B) gene polymorphisms and IL1B levels with spontaneous PTB.

    STUDY DESIGN: Peripheral maternal blood from 495 women was used for extraction of DNA and genotyping was carried out using the Sequenom MassARRAY platform. Maternal plasma was used to measure IL1B levels.

    RESULTS: There was no significant association between the allelic and genotype distribution of IL1B single nucleotide polymorphism (SNP) (rs1143634, rs1143627, rs16944) and the risk of PTB among Malaysian Malay women (rs1143634, P=0.722; rs1143627, P=0.543; rs16944, P=0.615). However, IL1B levels were significantly different between women who delivered preterm compared with those who delivered at term (P=0.030); high mean levels were observed among Malay women who delivered at preterm (mean=32.52) compared with term (mean=21.68). IL1B SNPs were not associated with IL1B plasma levels.

    CONCLUSION: This study indicates a significant association between IL1B levels and reduced risk of PTB among the Malaysian Malay women. This study shows the impact of IL1B levels on susceptibility to PTB disease; however, the high levels of IL1B observed among women in the preterm group are not associated with IL1B SNPs investigated in this study; IL1B high levels may be because of other factors not explored in this study and therefore warrant further investigation.

  3. Sangaran PG, Ibrahim ZA, Chik Z, Mohamed Z, Ahmadiani A
    Front Cell Neurosci, 2020;14:598453.
    PMID: 33551748 DOI: 10.3389/fncel.2020.598453
    Lipopolysacharide (LPS) pre-conditioning (PC), has been shown to exert protective effects against cytotoxic effects. Therefore, we hypothesized, the tolerance produced by LPS PC will be resulted by the alterations and modifications in gene and protein expression. With reference to the results of MTT assays, AO/PI staining, and Annexin V-FITC analyses of LPS concentration (0.7815-50 μg/mL) and time-dependent (12-72 h) experiments, the pre-exposure to 3 μg/mL LPS for 12 h protected the differentiated PC12 cells against 0.75 mg/mL LPS apoptotic concentration. LPS-treated cells secreted more inflammatory cytokines like IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-6, IL-17, IFN-γ, and TNF-α than LPS-PC cells. The production of inflammatory mediators ROS and NO was also higher in the LPS-induced cells compared to LPS-PC cells. Conversely, anti-inflammatory cytokines (like IL-10, IL-13, CNTF, and IL-1Ra) were upregulated in the LPS-PC cells but not in the LPS-induced cells. Meanwhile, the LPS initiated caspase-8 which in turn activates effector caspase 3/7. When the activities of caspases in the LPS-induced cells were inhibited using z-VADfmk and z-DEVDfmk, the expressions of c-MYC and Hsp70 were increased, but p53 was reduced. The potential molecules associated with protective and destructive effect was measured by RT2 Profiler PCR array to elucidate the signaling pathways and suggested inhibition NF-κB/caspase-3 signaling pathway regulates the cytoprotective genes and proto-oncogenes. In conclusion, this study provides a basis for future research to better understand the molecular mechanism underlying LPS pre-conditioning /TLR4 pre-activation and its functional role in offering cytoprotective response in neuronal environment.
  4. Alsalahi A, Alshawsh MA, Chik Z, Mohamed Z
    Exp Anim, 2018 Nov 01;67(4):517-526.
    PMID: 29973470 DOI: 10.1538/expanim.18-0057
    People consume Catha edulis (khat) for its euphoric effect, and type 1 diabetics have claimed that khat could reduce elevated levels of blood sugar. However, khat has been suggested to provoke diabetes mellitus through destruction of pancreatic β-cells. This study investigated the effect of an ethanolic khat extract on pancreatic functions in type 1 diabetes (T1DM)-induced male Sprague-Dawley rats and to assess its in vitro cytotoxicity in rat pancreatic β-cells (RIN-14B). T1DM was induced in a total of 20 rats with a single intraperitoneal injection of 75 mg/kg of streptozotocin. The rats were distributed into four groups (n=5): the diabetic control, 8 IU insulin-treated, 200 mg/kg khat-treated, and 400 mg/kg khat-treated groups. Another 5 rats were included as a nondiabetic control. Body weight, fasting blood sugar, and caloric intake were recorded weekly. Four weeks after treatment, the rats were sacrificed, and blood was collected for insulin, lipid profile, total protein, amylase, and lipase analysis, while pancreases were harvested for histopathology. In vitro, khat exerted moderate cytotoxicity against RIN-14B cells after 24 and 48 h but demonstrated greater inhibition against RIN-14B cells after 72 h. Neither 200 mg/kg nor 400 mg/kg of khat produced any significant reduction in blood sugar; however, 200 mg/kg khat extract provoked more destruction of pancreatic β-cells as compared with the diabetic control. Ultimately, neither 200 mg/kg nor 400 mg/kg of khat extract could produce a hypoglycemic effect in T1DM-induced rats. However, 200 mg/kg of khat caused greater destruction of pancreatic β-cells, implying that khat may cause a direct cytotoxic effect on pancreatic β-cells in vitro.
  5. Lee YJ, Zakaria R, Manaf ZA, Mohamed Z, Lee YY
    Chin Med J (Engl), 2013;126(11):2049-53.
    PMID: 23769556
    There is increasing evidence that CT pulmonary arteriography and venography allow a better diagnostic yield for deep vein thrombosis (DVT) in suspected acute pulmonary embolism (PE). The aim was to investigate the value for using such an approach in a multiracial Asian population.
  6. Alsalahi A, Chik Z, Mohamed Z, Giribabu N, Alshawsh MA
    Saudi J Biol Sci, 2021 Aug;28(8):4633-4643.
    PMID: 34354450 DOI: 10.1016/j.sjbs.2021.04.072
    Cathinone, the main bioactive alkaloid of Catha edulis (khat), slightly increased the blood sugar levels of healthy animals, while its effect on blood sugar levels of diabetic animals has not yet been reported. This study investigated the in vitro inhibition of cathinone on α-amylase and α-glucosidase as well as its in vivo glycemic effects in diabetes-induced rats. Rats were fed on a high fat diet for five weeks, which then intraperitoneally injected with streptozotocin (30 mg/kg). Diabetic rats were distributed randomly into diabetic control (DC, n = 5), 10 mg/kg glibenclamide-treated group (DG, n = 5), and 1.6 mg/kg cathinone-treated group (CAD, n = 5). Additional healthy untreated rats (n = 5) served as a nondiabetic negative control group. Throughout the experiment, fasting blood sugar (FBS), caloric intake and body weight were recorded weekly. By the 28th day of treatment, rats were euthanized to obtain blood samples and pancreases. The results demonstrated that cathinone exerted a significantly less potent in vitro inhibition than α-acarbose against α-amylase and α-glucosidase. As compared to diabetic control group, cathinone significantly increased FBS of diabetic rats, while insulin levels of diabetic rats significantly decreased. In conclusion, cathinone was unable to induce a substantial in vitro inhibition on α-amylase and α-glucosidase, while it exacerbated the hyperglycemia of diabetes-induced rats.
  7. Khang TF, Mohd Puaad NAD, Teh SH, Mohamed Z
    J Forensic Sci, 2021 May;66(3):960-970.
    PMID: 33438785 DOI: 10.1111/1556-4029.14655
    Wing shape variation has been shown to be useful for delineating forensically important fly species in two Diptera families: Calliphoridae and Sarcophagidae. Compared to DNA-based identification, the cost of geometric morphometric data acquisition and analysis is relatively much lower because the tools required are basic, and stable softwares are available. However, to date, an explicit demonstration of using wing geometric morphometric data for species identity prediction in these two families remains lacking. Here, geometric morphometric data from 19 homologous landmarks on the left wing of males from seven species of Calliphoridae (n = 55), and eight species of Sarcophagidae (n = 40) were obtained and processed using Generalized Procrustes Analysis. Allometric effect was removed by regressing centroid size (in log10 ) against the Procrustes coordinates. Subsequently, principal component analysis of the allometry-adjusted Procrustes variables was done, with the first 15 principal components used to train a random forests model for species prediction. Using a real test sample consisting of 33 male fly specimens collected around a human corpse at a crime scene, the estimated percentage of concordance between species identities predicted using the random forests model and those inferred using DNA-based identification was about 80.6% (approximate 95% confidence interval = [68.9%, 92.2%]). In contrast, baseline concordance using naive majority class prediction was 36.4%. The results provide proof of concept that geometric morphometric data has good potential to complement morphological and DNA-based identification of blow flies and flesh flies in forensic work.
  8. Langmia IM, Apalasamy YD, Omar SZ, Mohamed Z
    PMID: 26607028
    Interleukin 1 receptor type 2 (IL1R2) regulates the inflammatory pathway that results in preterm delivery. We aim to investigate the impact of IL1R2 gene polymorphisms on the risk of preterm delivery.
  9. Othman N, Zainudin NS, Mohamed Z, Yahya MM, Leow VM, Noordin R
    Trop Biomed, 2013 Jun;30(2):257-66.
    PMID: 23959491 MyJurnal
    The protein profile of serum samples from patients with amoebic liver abscess (ALA) was compared to those of normal individuals to determine their expression levels and to identify potential surrogate disease markers. Serum samples were resolved by two dimensional electrophoresis (2-DE) followed by image analysis. The up and down-regulated protein spots were excised from the gels and analysed by MS/MS. The concentration of three clusters of proteins i.e. haptoglobin (HP), α1-antitrypsin (AAT) and transferrin in serum samples of ALA patients and healthy controls were compared using competitive ELISA. In addition, serum concentrations of HP and transferrin in samples of patients with ALA and pyogenic liver abscess (PLA) were also compared. The results of the protein 2-DE expression analysis showed that HP cluster, AAT cluster, one spot each from unknown spots no. 1 and 2 were significantly up-regulated and transferrin cluster was significantly down-regulated in ALA patients' sera (p<0.05). The MS/MS analysis identified the unknown protein spot no.1 as human transcript and haptoglobin and spot no. 2 as albumin. Competitive ELISA which compared concentrations of selected proteins in sera of ALA and healthy controls verified the up-regulated expression (p<0.05) of HP and the down-regulated expression (p<0.01) of transferrin in the former, while there was no significant difference in AAT expression (p> 0.05). However, when ALA and PLA samples were compared, competitive ELISA showed significant increased concentration of HP (p<0.05) while transferrin levels were not different. In conclusion, this study showed that HP is a potential surrogate disease marker for ALA.
  10. Riazalhosseini B, Mohamed R, Apalasamy YD, Langmia IM, Mohamed Z
    Rev Soc Bras Med Trop, 2017 Mar-Apr;50(2):161-166.
    PMID: 28562750 DOI: 10.1590/0037-8682-0416-2016
    INTRODUCTION: Hepatitis B virus (HBV) constitutes an important risk factor for cirrhosis and hepatocellular carcinoma (HCC). The link between circulating microRNAs and HBV has been previously reported, although not as a marker of liver disease progression in chronic hepatitis B (CHB). The aim of this study was to characterize miRNA expression profiles between CHB with and without cirrhosis or HCC.

    METHODS:: A total of 12 subjects were recruited in this study. We employed an Affymetrix Gene Chip miRNA 3.0 Array to provide universal miRNA coverage. We compared microRNA expression profiles between CHB with and without cirrhosis/HCC to discover possible prognostic markers associated with the progression of CHB.

    RESULTS:: Our results indicated 8 differently expressed microRNAs, of which miRNA-935, miRNA-342, miRNA-339, miRNA-4508, miRNA-3615, and miRNA-3200 were up-regulated, whereas miRNA-182 and miRNA-4485 were down-regulated in patients with CHB who progressed to cirrhosis/HCC as compared to those without progression.

    CONCLUSIONS:: We demonstrated the differential expression of miRNA-935, miRNA-342, miRNA-339, miRNA-4508, miRNA-3615, miRNA-3200, miRNA-182, and miRNA-4485 between patients with HBV without cirrhosis/HCC and those who had progressed to these more severe conditions. These miRNAs may serve as novel and non-invasive prognostic markers for early detection of CHB-infected patients who are at risk of progression to cirrhosis and/or HCC.
  11. Zambri NDS, Taib NI, Abdul Latif F, Mohamed Z
    Molecules, 2019 Oct 22;24(20).
    PMID: 31652583 DOI: 10.3390/molecules24203803
    The present work reports the successful synthesis of biosynthesized iron oxide nanoparticles (Fe3O4-NPs) with the use of non-toxic leaf extract of Neem (Azadirachta indica) as a reducing and stabilizing agent. The successful synthesis was confirmed by infrared spectra analysis with strong peak observed between 400-600 cm-1 that corresponds to magnetite nanoparticles characteristics. X-ray diffraction (XRD) analysis revealed that iron oxide nanoparticles were of high purity with crystalline cubic structure phases in nature. Besides, the average size of magnetite nanoparticles was observed to be 9-12 nm with mostly irregular shapes using a transmission electron microscope (TEM) and was supported by field emission scanning electron microscope (FESEM). Energy dispersive X-ray analysis shown that the elements iron (Fe) and oxygen (O) were present with atomic percentages of 33.29% and 66.71%, respectively. From the vibrating sample magnetometer (VSM) analysis it was proven that the nanoparticles exhibited superparamagnetic properties with a magnetization value of 73 emu/g and the results showed superparamagnetic behavior at room temperature, suggesting potential applications for a magnetic targeting drug delivery system.
  12. Sanmugavelan R, Teoh TC, Roslan N, Mohamed Z
    Turk J Biol, 2018;42(3):213-223.
    PMID: 30814883 DOI: 10.3906/biy-1710-107
    In this study, transformation of BrCHS var 2 into B. rotunda cell suspension culture, followed by chalcone synthase enzymatic assay and HPLC analysis was conducted to investigate whether the substrate specificity for BrCHS var 2 is either cinnamoyl-CoA or p-coumaroyl-CoA. The HPLC profile showed an increase in the amount of pinocembrin chalcone when cinnamoyl-CoA and malonyl-CoA were added but not p-coumaroyl-CoA. Molecular docking was performed to explore the binding of cinnamoyl-CoA and p-coumaroyl-CoA to BrCHS var 2 receptor and the docking results showed that cinnamoyl-CoA formed numerous hydrogen bonds and more negative docked energy than p-coumaroyl-CoA. Cinnamoyl-CoA showed good interactions with Cys 164 to initiate the subsequent formation of pinocembrin chalcone, whereas the hydroxyl group of p-coumaroyl-CoA formed an unfavorable interaction with Gln 161 that caused steric hindrance to subsequent formation of naringenin chalcone. Docked conformation analysis results also showed that malonyl-CoA formed hydrogen bonding with Cys 164, His 303, and Asn 336 residues in BrCHS var 2. The results show that cinnamoyl-CoA is the preferred substrate for BrCHS var 2.
  13. Koosha S, Mohamed Z, Sinniah A, Alshawsh MA
    Sci Rep, 2019 03 26;9(1):5148.
    PMID: 30914796 DOI: 10.1038/s41598-019-41685-1
    Diosmetin (Dis) is a bioflavonoid with cytotoxicity properties against variety of cancer cells including hepatocarcinoma, breast and colorectal (CRC) cancer. The exact mechanism by which Dis acts against CRC however, still remains unclear, hence in this study, we investigated the possible molecular mechanisms of Dis in CRC cell line, HCT-116. Here, we monitored the viability of HCT-116 cells in the presence of Dis and investigated the underlying mechanism of Dis against HCT-116 cells at the gene and protein levels using NanoString and proteome profiler array technologies. Findings demonstrated that Dis exhibits greater cytotoxic effects towards HCT-116 CRC cells (IC50 = 3.58 ± 0.58 µg/ml) as compared to the normal colon CCD-841 cells (IC50 = 51.95 ± 0.11 µg/ml). Arrests of the cells in G2/M phase confirms the occurrence of mitotic disruption via Dis. Activation of apoptosis factors such as Fas and Bax at the gene and protein levels along with the release of Cytochrome C from mitochondria and cleavage of Caspase cascades indicate the presence of turbulence as a result of apoptosis induction in Dis-treated cells. Moreover, NF-ƙB translocation was inhibited in Dis-treated cells. Our results indicate that Dis can target HCT-116 cells through the mitotic disruption and apoptosis induction.
  14. Hajissa K, Islam MA, Sanyang AM, Mohamed Z
    PLoS Negl Trop Dis, 2022 Feb 11;16(2):e0009971.
    PMID: 35148325 DOI: 10.1371/journal.pntd.0009971
    INTRODUCTION: Parasitic infections, especially intestinal protozoan parasites (IPPs) remain a significant public health issue in Africa, where many conditions favour the transmission and children are the primary victims. This systematic review and meta-analysis was carried out with the objective of assessing the prevalence of IPPs among school children in Africa.

    METHODS: Relevant studies published between January 2000 and December 2020 were identified by systematic online search on PubMed, Web of Science, Embase and Scopus databases without language restriction. Pooled prevalence was estimated using a random-effects model. Heterogeneity of studies were assessed using Cochrane Q test and I2 test, while publication bias was evaluated using Egger's test.

    RESULTS: Of the 1,645 articles identified through our searches, 46 cross-sectional studies matched our inclusion criteria, reported data from 29,968 school children of Africa. The pooled prevalence of intestinal protozoan parasites amongst African school children was 25.8% (95% CI: 21.2%-30.3%) with E. histolytica/ dispar (13.3%; 95% CI: 10.9%-15.9%) and Giardia spp. (12%; 95% CI: 9.8%-14.3%) were the most predominant pathogenic parasites amongst the study participants. While E. coli was the most common non-pathogenic protozoa (17.1%; 95% CI: 10.9%-23.2%).

    CONCLUSIONS: This study revealed a relatively high prevalence of IPPs in school children, especially in northern and western Africa. Thus, poverty reduction, improvement of sanitation and hygiene and attention to preventive control measures will be the key to reducing protozoan parasite transmission.

  15. Apalasamy YD, Ming MF, Rampal S, Bulgiba A, Mohamed Z
    Ann Hum Biol, 2013 Jan;40(1):102-6.
    PMID: 22989167 DOI: 10.3109/03014460.2012.720709
    Melanocortin-4 receptor (MC4R) is an important regulator of body weight and energy intake. Genetic polymorphisms of the MC4R gene have been found to be linked to obesity in many recent studies across the globe.
  16. Seyedan A, Alshawsh MA, Alshagga MA, Mohamed Z
    Planta Med, 2017 May;83(8):684-692.
    PMID: 27992939 DOI: 10.1055/s-0042-121754
    The present study investigated the antiobesity and lipid lowering effects of an ethanolic extract of leaves obtained from Orthosiphon stamineus (200 and 400 mg/kg) and its major compound (rosmarinic acid, 10 mg/kg) in obese mice (C57BL/6) induced by a high-fat diet. Continuous supplementation with O. stamineus extract (200 and 400 mg/kg) for 8 weeks significantly decreased body weight gain (p 
  17. Sangaran PG, Ibrahim ZA, Chik Z, Mohamed Z, Ahmadiani A
    Mol Neurobiol, 2021 May;58(5):2407-2422.
    PMID: 33421016 DOI: 10.1007/s12035-020-02227-3
    Neuroinflammation, an inflammatory response within the nervous system, has been shown to be implicated in the progression of various neurodegenerative diseases. Recent in vivo studies showed that lipopolysaccharide (LPS) preconditioning provides neuroprotection by activating Toll-like receptor 4 (TLR4), one of the members for pattern recognition receptor (PRR) family that play critical role in host response to tissue injury, infection, and inflammation. Pre-exposure to low dose of LPS could confer a protective state against cellular apoptosis following subsequent stimulation with LPS at higher concentration, suggesting a role for TLR4 pre-activation in the signaling pathway of LPS-induced neuroprotection. However, the precise molecular mechanism associated with this protective effect is not well understood. In this article, we provide an overall review of the current state of our knowledge about LPS preconditioning in attenuating apoptosis mechanism and conferring neuroprotection via TLR4 signaling pathway.
  18. Kong WM, Chik Z, Mohamed Z, Alshawsh MA
    PMID: 29076424 DOI: 10.2174/1386207320666171026121820
    AIM AND OBJECTIVE: Mitragynine, a major active alkaloid of Mitragyna speciosa, acts as an agonist on µ-opioid receptors, producing effects similar to morphine and other opioids. It has been traditionally utilized to alleviate opiate withdrawal symptoms. Besides consideration about potency and selectivity, a good drug must possess a suitable pharmacokinetic profile, with suitable absorption, distribution, metabolism, excretion and toxicity (ADME-Tox) profile, in order to have a high chance of success in clinical trials.

    MATERIAL AND METHOD: The purity of mitragynine in a Mitragyna speciosa alkaloid extract (MSAE) was determined using Ultra-Fast Liquid Chromatography (UFLC). In vitro high throughput ADMETox studies such as aqueous solubility, plasma protein binding, metabolic stability, permeability and cytotoxicity tests were carried out to analyze the physicochemical properties of MSAE and mitragynine. The UFLC quantification revealed that the purity of mitragynine in the MSAE was 40.9%.

    RESULTS: MSAE and mitragynine are highly soluble in aqueous solution at pH 4.0 but less soluble at pH 7.4. A parallel artificial membrane permeability assay demonstrated that it is extensively absorbed through the semi-permeable membrane at pH 7.4 but very poorly at pH 4.0. Both are relatively highly bound to plasma proteins (> 85 % bound) and are metabolically stable to liver microsomes (> 84 % remained unchanged). In comparison to MSAE, mitragynine showed higher cytotoxicity against WRL 68, HepG2 and Clone 9 hepatocytes after 72 h treatment.

    CONCLUSION: The obtained ADME and cytotoxicity data demonstrated that both MSAE and mitragynine have poor bioavailability and have the potential to be significantly cytotoxic.

  19. Jamalpour S, Zain SM, Mosavat M, Mohamed Z, Omar SZ
    Gene, 2018 Apr 15;650:34-40.
    PMID: 29410004 DOI: 10.1016/j.gene.2018.01.091
    BACKGROUND: Although the influence of a common variant in the glucokinase regulatory gene (GCKR rs780094) in type 2 diabetes mellitus has been well documented, less data however, is available of its role in gestational diabetes mellitus (GDM). We carried out a case control study to assess the association between GCKR rs780094 and GDM in the Asian, and also a meta-analysis to further assess the strength of the association.

    METHODS: Demographic, clinical and genotype data were determined for 1122 women (267 cases and 855 controls) recruited from the University of Malaya Medical Centre in the Klang Valley, Kuala Lumpur. Relevant articles were identified from Pubmed, Embase, MEDLINE, and Web of Science. Extraction of data was carried out and summary estimates of the association between rs780094 and GDM were examined.

    RESULTS: The frequency of risk allele C was significantly higher in the cases than controls (OR 1.34, 95% CI 1.09-1.66, P = 0.006). The C allele was also associated with increased level of random 2-hour fasting plasma glucose and pregravid body mass index. Meta-analysis further confirmed the association of the GCKR rs780094 with GDM (OR 1.32, 95% CI 1.14-1.52, P = 0.0001).

    CONCLUSION: This study strongly suggests that GCKR rs780094-C is associated with increased risk of GDM.

  20. Kong WM, Mohamed Z, Alshawsh MA, Chik Z
    J Pharm Biomed Anal, 2017 Sep 05;143:43-47.
    PMID: 28551311 DOI: 10.1016/j.jpba.2017.05.020
    A microdialysis system coupled with a sensitive ultra-fast liquid chromatography-mass spectrometry (UFLC-MS) method was developed for the pharmacokinetic analysis of mitragynine in rat blood and striatum. Mitragynine is an active alkaloid of Mitragyna speciosa and has been proposed to be used for opioid withdrawal therapy. In this study, chromatographic separation was performed in a gradient elution mode with 0.1% formic acid and acetonitrile on a Zorbax Eclipse C18 column. The mass spectrometric (MS) analysis was carried out in a positive electrospray mode and mitragynine ion (m/z 399.2) was monitored in extracted ion chromatography. A good linearity range was obtained from 10-1000ng/mL with acceptable accuracy and precision parameters. The microdialysate was collected simultaneously from the striatum and the right jugular vein using microdialysis probes. After a single intravenous administration of 10mg/kg mitragynine, mitragynine showed a two-compartmental drug elimination pattern with half-life (T1/2) of approximately 13h. The percent of AUCbrain/AUCplasma of mitragynine was calculated and shown to be 65.8±4.5%. The results indicated that mitragynine could be a suitable molecule to develop into an opioid replacement drug based on its ideal pharmacokinetic properties, namely, small molecular size, lipophilic in nature and with excellent blood-brain barrier (BBB) permeability.
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