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  1. Fulltext Safety and efficacy of two tacrolimus formulations (Prograf® and Advagraf®) in Malaysian renal transplant patients: a comparative study
    Mac Guad, R., Zaharan, N.L., Wan Md Adnan, W.A.H., Gan, S.H., Chik, Z.,
    JUMMEC, 2019;22(1):20-26.
    MyJurnal
    Aim: A once-daily formulation of tacrolimus, Advagraf®, is increasingly being used in place of twice-daily
    tacrolimus, Prograf®, as a standard immunosuppressive agent for transplant patients. In this study, the
    clinical safety and efficacy of Advagraf® were compared with Prograf®, among multi-ethnic Malaysian renal
    transplanted population.

    Method: This retrospective study identified renal transplant patients who were converted from Prograf® to
    Advagraf® at the University Malaya Medical Centre (UMMC) (n=69). Clinical notes and laboratory records,
    including tacrolimus daily dose and trough levels, were obtained for one-year, pre-and post-conversion. Causality
    assessment of suspected adverse events were based on the WHO-Uppsala Monitoring Center criteria. Renal
    biopsy records were re-evaluated based on the updated Banff 2007 classification for biopsy-confirmed acute
    rejection (BPAR).

    Results: Following conversion to Advagraf®, the mean tacrolimus trough level and daily dose decreased
    significantly (p
  2. Technical aspects of preparing PEG-PLGA nanoparticles as carrier for chemotherapeutic ‎agents by nanoprecipitation method
    Almoustafa HA, Alshawsh MA, Chik Z
    Int J Pharm, 2017 Nov 25;533(1):275-284.
    PMID: 28943210 DOI: 10.1016/j.ijpharm.2017.09.054
    Nanoprecipitation is a simple and increasingly trending method for nanoparticles preparation. The self-assembly feature of poly (ethylene glycol)-poly (lactide-co-glycolic acid) (PEG-PLGA) amphiphilic copolymer into a nanoparticle and its versatile structure makes nanoprecipitation one of the best methods for its preparation. The aim of this study is to review currently available literature for standard preparation of PEG-PLGA nanoparticles using nanoprecipitation technique in order to draw conclusive evidenceto draw conclusive evidence that can guide researchers during formulation development. To achieve this, three databases (Web of Science, Scopus and PubMed) were searched using relevant keywords and the extracted articles were reviewed based on defined inclusion and exclusion criteria. Data extraction and narrative analysis of the obtained literature was performed when appropriate, along with our laboratory observations to support those claims wherever necessary. As a result of this analysis, reports that matched our criteria conformed to the general facts about nanoprecipitation techniques such as simplicity in procedure, low surfactants requirement, narrow size distribution, and low resulting concentrations. However, these reports showed interesting advantages for using PEG-PLGA as they are frequently reported to be freeze-dried and active pharmaceutical ingredients (APIs) with low hydrophobicity were reported to successfully be encapsulated in the particles.
  3. Fulltext Disposal practice and factors associated with unused medicines in Malaysia: a cross-sectional study
    Wang LS, Aziz Z, Chik Z
    BMC Public Health, 2021 Sep 16;21(1):1695.
    PMID: 34530791 DOI: 10.1186/s12889-021-11676-x
    BACKGROUND: The improper disposal of unused medicines is a worldwide concern because of its impact on the environment, economy, and health. This study aims to describe the disposal practice of unused medicine and identify factors associated with unused medicines in Malaysia.

    METHODS: This was a cross-sectional, face to face interview-based survey using a structured questionnaire. We used a convenience sampling method to recruit participants from Kuala Lumpur and Selangor in Malaysia.

    RESULTS: We interviewed 1184 participants, and the response rate was 96%. Out of the total respondents, 995 (84%) reported having unused medicines. About a quarter of respondents kept unused medicines in the cabinet, and another quarter disposed of them into the trash or toilet. Only half of the respondent who used medicines for chronic illnesses had unused medicines compared to about 90% of respondents who used medicines for acute illnesses. The main reason for having unused medicines among those who used medicines for chronic illness was non-adherence (69%, p 

  4. Targeted polymeric nanoparticle for anthracycline delivery in hypoxia-induced drug resistance in metastatic breast cancer cells
    Almoustafa HA, Alshawsh MA, Chik Z
    Anticancer Drugs, 2021 Aug 01;32(7):745-754.
    PMID: 33675612 DOI: 10.1097/CAD.0000000000001065
    Poly lactic-co-glycolic acid (PLGA) nanoparticles are intensively studied nanocarriers in drug delivery because of their biodegradability and biochemical characteristics. Polyethylene glycol (PEG) coating for nanocarriers gives them long circulation time in blood and makes them invisible to the reticuloendothelial system. Breast cancer cells have greater uptake of hyaluronic acid compared to normal cells as it binds to their overexpressed CD44 receptors. Since hypoxia plays an important role in cancer metastasis; we formulated PEG-PLGA nanoparticles coated with hyaluronic acid as targeted delivery system for doxorubicin (DOX) using nanoprecipitation method, and characterized them for chemical composition, size, surface charge, shape, and encapsulation efficiency. Then we tested them in vitro on hypoxia-optimized metastatic breast cancer cells. The nanoparticles were spherical with an average size of about 106 ± 53 nm, a negative surface charge (-15 ± 3 mV), and high encapsulation efficiency (73.3 ± 4.1%). In vitro investigation with hypoxia-elevated CD44 MDA-MB-231 cells showed that hyaluronic acid-targeted nanoparticles maintained their efficacy despite hypoxia-induced drug resistance unlike free DOX and nontargeted nanoparticles. In conclusion, this study revealed a simple third generation nanoparticle formulation for targeted treatment of hypoxia-induced drug resistance in breast cancer metastatic cells. Further, optimization is needed including In vivo efficacy and nanoparticle-specific pharmacokinetic studies.
  5. The pharmacokinetics of 38% silver diamine fluoride in healthy children with dental caries: a quasi-experimental study
    Lim SP, Zainal Aalam N, Chik Z, Musa S
    Eur Arch Paediatr Dent, 2023 Dec;24(6):737-749.
    PMID: 37923916 DOI: 10.1007/s40368-023-00837-8
    PURPOSE: Silver diamine fluoride (SDF) is a medication used for the arrestment of dental caries. This study aims to determine the pharmacokinetics (PK) of silver and fluoride following SDF application in healthy children with dental caries.

    METHODS: A total of 15 subjects, aged 4 to 10 years, with at least one cavity on a primary tooth, were recruited for this study. Urine samples were collected at baseline, first 24 h (F1) and second 24 h (F2) after SDF treatment for analysis of silver and fluoride content. Hair samples were also collected at baseline and at 7, 14, 30, 60, 75, and 90 days after SDF treatment to analyze silver content.

    RESULTS: Participants with under or over-collection of urine, or failure to provide urine collection were excluded for fluoride analysis. As a result, eight subjects' urine samples were eligible for fluoride analysis. Significant correlations were observed between baseline urinary fluoride levels and F1/F2 levels. Pairwise comparisons from Friedman's test showed significant differences between baseline and F1 fluoride levels. For silver analysis, 15 subjects were studied. F1 urinary silver levels were higher than baseline and F2 levels. Subsequent to SDF treatment, hair silver levels displayed fluctuations around the baseline. None of the participants reported adverse effects, and all caries teeth ceased progression within 30 days.

    CONCLUSIONS: The urinary fluoride levels after SDF treatment, although higher, were not clinically significant. Urinary and hair silver levels were negligible. Therefore, SDF appears safe to be used among children.

  6. Analysis of melamine migration from melamine food contact articles
    Chik Z, Haron DE, Ahmad ED, Taha H, Mustafa AM
    Food Addit Contam Part A Chem Anal Control Expo Risk Assess, 2011;28(7):967-73.
    PMID: 21607892 DOI: 10.1080/19440049.2011.576401
    Migration of melamine has been determined for 41 types of retail melamine-ware products in Malaysia. This study was initiated by the Ministry of Health, Malaysia, in the midst of public anxiety on the possibility of melamine leaching into foods that come into contact with the melamine-ware. Thus, the objective of this study was to investigate the level of melamine migration in melamine utensils available on the market. Samples of melamine tableware, including cups and plates, forks and spoons, tumblers, bowls, etc., were collected from various retail outlets. Following the test guidelines for melamine migration set by the European Committee for Standardisation (CEN 2004) with some modifications, the samples were exposed to two types of food simulants (3% acetic acid and distilled water) at three test conditions (25°C (room temperature), 70 and 100°C) for 30 min. Melamine analysis was carried out using LC-MS/MS with a HILIC column and mobile phase consisting of ammonium acetate/formic acid (0.05%) in water and ammonium acetate/formic acid (0.05%) in acetonitrile (95 : 5, v/v). The limit of quantification (LOQ) was 5 ng/ml. Melamine migration was detected from all samples. For the articles tested with distilled water, melamine migration were [median (interquartile range)] 22.2 (32.6), 49.3 (50.9), 84.9 (89.9) ng/ml at room temperature (25°C), 70 and 100°C, respectively. In 3% acetic acid, melamine migration was 31.5 (35.7), 81.5 (76.2), 122.0 (126.7) ng/ml at room temperature (25°C), 70 and 100°C, respectively. This study suggests that excessive heat and acidity may directly affect melamine migration from melamine-ware products. However the results showed that melamine migration in the tested items were well below the specific migration limit (SML) of 30 mg/kg (30,000 ng/ml) set out in European Commission Directive 2002/72/EC.
  7. A bioequivalence comparison of two formulations of rifampicin (300- vs 150-mg capsules): An open-label, randomized, two-treatment, two-way crossover study in healthy volunteers
    Chik Z, Basu RC, Pendek R, Lee TC, Mohamed Z
    Clin Ther, 2010 Sep;32(10):1822-31.
    PMID: 21194606 DOI: 10.1016/j.clinthera.2010.09.006
    Rifampicin is a semisynthetic antibiotic derivative of rifamycin used worldwide for the treatment of various forms of tuberculosis.
  8. Correcting endogenous concentrations of testosterone influences bioequivalence and shows the superiority of TDS(R)-testosterone versus Androgel(R)
    Chik Z, Johnston A, Tucker AT, Kirby K, Alam CA
    Int J Clin Pharmacol Ther, 2009 Apr;47(4):262-8.
    PMID: 19356392
    Circulating concentrations of endogenous compounds such as testosterone, complicate the analysis of pharmacokinetic parameters when these compounds are administered exogenously. This study examines the influence of three correction methods of accounting for endogenous concentrations on the determination of bioequivalence between two testosterone formulations.
  9. Comparative bioavailability study of two salbutamol tablets in healthy adult volunteers
    Chik Z, Basu RC, Pendek R, Lee TC, Mohamed Z
    Int J Clin Pharmacol Ther, 2009 Jun;47(6):413-8.
    PMID: 19473604
    This study was carried out to compare the rate and extent of absorption of a generic salbutamol in oral dosage form (Brethmol, 4 mg) with the proprietary equivalent product (Ventolin, 4 mg), in healthy adult subjects, under fasting conditions. The study was a single dose, randomized, two way crossover study with a four-week washout period. It involved 22 healthy volunteers who received a single dose (4 mg) of the test and the reference products after an overnight fast of at least 10 hours. Blood samples were collected at pre-dose and a serial of 14 samples were collected from each of the subject from 1 h until 48 h post-dose. Plasma concentrations of salbutamol were analyzed using GCMS method. The mean AUC(0-yen) values were 91.26 and 96.45 h.ng/ml for reference and test product, respectively. The mean C(max) values were 12.26 and 12.38 ng/ml and the mean t(max) values were 2.80 and 2.33 hours for reference and test product, respectively. Analysis of variance showed that the 90% confidence intervals on the relative difference of the ratio for the AUC(0-yen) and the C(max) for the test and reference products were contained within the bioequivalence limit (80 - 125%) (C(max): 89.8 - 110.5% and AUC(0-yen): 91.6 - 121.5%). There was no statistically significant difference for the t(max) between the test and reference formulations (p = 0.30). The test formulation was found to be bioequivalent to the reference formulation with regard to AUC(0-yen) and C(max). There was no statistically significant difference in Brethmol and Ventolin t(max). In conclusion, Brethmol and Ventolin are bioequivalent in healthy subjects.
  10. Validation and application of capillary electrophoresis for the analysis of lidocaine in a skin tape stripping study
    Chik Z, Johnston A, Tucker AT, Burn RT, Perrett D
    Biomed Chromatogr, 2007 Aug;21(8):775-9.
    PMID: 17497758
    A fast and simple capillary zone electrophoresis method was developed and validated for the determination of lidocaine in skin using tape samples. Separation was performed in a 350 mm (265 mm to window) x 50 microm i.d. fused silica capillary using a background electrolyte of phosphoric acid-Tris pH 2.5. The extraction of lidocaine from tape samples was achieved using methanol, which was diluted to 50% with water before injection. Procaine was the internal standard. The migration times for procaine and lidocaine were 2.9 and 3.2 min, respectively. The limit of quantification for lidocaine was 50 microg, with signal to noise ratio greater than 10. The calibration curve was linear from 50 to 1000 microg with r(2) greater than 0.99. The CV for both within- and between-assay imprecision and the percentage of inaccuracy for the quality control samples including lower and upper limits of quantitation were 97%. The accuracy and selectivity of this method allowed the measurement of lidocaine in tape samples obtained from a skin tape stripping study of local anesthetics in healthy subjects.
  11. How well does self-reported adherence fare compared to therapeutic drug monitoring in HAART?
    Bulgiba A, Mohammed UY, Chik Z, Lee C, Peramalah D
    Prev Med, 2013;57 Suppl:S34-6.
    PMID: 23313585 DOI: 10.1016/j.ypmed.2013.01.002
    The aim of the study was to determine how well self-reported adherence fares compared to therapeutic drug monitoring in monitoring HAART adherence.
  12. In vitro and in vivo evaluation of a novel testosterone transdermal delivery system (TTDS) using palm oil base
    Haron DE, Chik Z, Noordin MI, Mohamed Z
    Iran J Basic Med Sci, 2015 Dec;18(12):1167-75.
    PMID: 26877845
    Transdermal preparations for testosterone are becoming popular because of their unique advantages such as avoidance of first-pass effect, convenience, improved bioavailability, and reduction of systemic side effects. A novel testosterone transdermal delivery system (TDDS) was developed using a palm oil base called HAMIN™ (a commercial product) and tested using in vitro and in vivo skin permeability test methods.
  13. Fulltext Annexin A1: A Bane or a Boon in Cancer? A Systematic Review
    Ganesan T, Sinniah A, Ibrahim ZA, Chik Z, Alshawsh MA
    Molecules, 2020 Aug 14;25(16).
    PMID: 32823805 DOI: 10.3390/molecules25163700
    Annexin A1 has been extensively investigated as an anti-inflammatory protein, but its role in different types of cancer has not been consolidated in a single systematic review to date. Thus, the aim of this paper is to systematically review and critically analyse 18 studies (in-vivo and in-vitro) to consolidate, in a concerted manner, all the information on differential expression of Annexin A1 in different types of cancer and the role this protein plays in tumorigenesis. Pubmed, Scopus, Web of Science, and ScienceDirect were used for the literature search and the keywords used are "annexin A1," "lipocortin 1," "cancer," "malignancy," "neoplasm," "neoplasia," and "tumor." A total of 1128 articles were retrieved by implementing a standard search strategy subjected to meticulous screening processes and 442 articles were selected for full article screening. A total of 18 articles that adhered to the inclusion criteria were included in the systematic review and these articles possessed low to moderate bias. These studies showed a strong correlation between Annexin A1 expression and cancer progression via modulation of various cancer-associated pathways. Differential expression of Annexin A1 is shown to play a role in cellular proliferation, metastasis, lymphatic invasion, and development of resistance to anti-cancer treatment. Meta-analysis in the future may provide a statistically driven association between Annexin A1 expression and malignancy progression.
  14. Fulltext Punicalagin Regulates Apoptosis-Autophagy Switch via Modulation of Annexin A1 in Colorectal Cancer
    Ganesan T, Sinniah A, Chik Z, Alshawsh MA
    Nutrients, 2020 Aug 13;12(8).
    PMID: 32823596 DOI: 10.3390/nu12082430
    Punicalagin (PU), a polyphenol extracted from pomegranate (Punica granatum) husk is proven to have anti-cancer effects on different types of cancer including colorectal cancer (CRC). Its role in modulating endogenous protein as a means of eliciting its anti-cancer effects, however, has not been explored to date. Hence, this study aimed to investigate the role of PU in modulating the interplay between apoptosis and autophagy by regulating Annexin A1 (Anx-A1) expression in HCT 116 colorectal adenocarcinoma cells. In the study, selective cytotoxicity, pro-apoptotic, autophagic and Anx-A1 downregulating properties of PU were shown which indicate therapeutic potential that this polyphenol has against CRC. Autophagy flux analysis via flow cytometry showed significant autophagosomes degradation in treated cells, proving the involvement of autophagy. Proteome profiling of 35 different proteins in the presence and absence of Anx-A1 antagonists in PU-treated cells demonstrated a complex interplay that happens between apoptosis and autophagy that suggests the possible simultaneous induction and inhibition of these two cell death mechanisms by PU. Overall, this study suggests that PU induces autophagy while maintaining basal level of apoptosis as the main mechanisms of cytotoxicity via the modulation of Anx-A1 expression in HCT 116 cells, and thus has a promising translational potential.
  15. Lipopolysaccharide Pre-conditioning Attenuates Pro-inflammatory Responses and Promotes Cytoprotective Effect in Differentiated PC12 Cell Lines via Pre-activation of Toll-Like Receptor-4 Signaling Pathway Leading to the Inhibition of Caspase-3/Nuclear Factor-κappa B Pathway
    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.
  16. Fulltext Effect of Catha edulis (khat) on pancreatic functions in streptozotocin-induced diabetes in male Sprague-Dawley rats
    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.
  17. Cathinone: An alkaloid of Catha edulis (Khat) exacerbated hyperglycemia in diabetes-induced rats
    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.
  18. In vitro and in vivo Evaluation of New Topical Anaesthetic Cream Formulated with Palm Oil Base
    Khodari SNK, Noordin MI, Chan L, Chik Z
    Curr Drug Deliv, 2017;14(5):690-695.
    PMID: 27480118 DOI: 10.2174/1567201813666160801113302
    BACKGROUND: Topical local anaesthetic cream was reported to be useful for pain relief for cutaneous procedures such as minor surgery and venipuncture.

    OBJECTIVE: The aim of this study was to evaluate the effectiveness of new formulation of lidocaine topical anaesthetic using palm oil base, HAMIN® and to determine how fast this new formulation produces adequate numbness compared to the currently used EMLA cream, in the University of Malaya Medical Centre (UMMC) set-up.

    METHOD: The skin permeation test was conducted by using Franz type diffusion cell and pain assessment was carried out in healthy subject by using Verbal Rating Score (VRS) and Visual Analogue Score (VAS) evaluation.

    RESULT: Result of permeation test demonstrated that the cumulative amount of lidocaine released from HAMIN® cream was increased with time and slightly higher than EMLA cream. The clinical study showed that HAMIN® single lidocaine cream can produces numbness through venepuncture procedure and comparable with EMLA cream which is a combination therapy for local anaesthetic (lidocaine and prilocaine).

    CONCLUSION: It can be concluded that HAMIN® Lidocaine cream is suitable for cream preparation especially for topical application and it can be regarded as an achievement in palm oil and medical industries.

  19. Urine NMR Metabolomic Study on Biochemical Activities to Investigate the Effect of P. betle Extract on Obese Rats
    Abdul Ghani ZDF, Ab Rashid AH, Shaari K, Chik Z
    Appl Biochem Biotechnol, 2019 Oct;189(2):690-708.
    PMID: 31111377 DOI: 10.1007/s12010-019-03042-w
    The present studies are to evaluate the ability of PB to induce weight loss and urine metabolite profile of Piper betle L. (PB) leaf extracts using metabolomics approach. Dried PB leaves were extracted with ethanol 70% and the studies were performed in different groups of rats fed with high fat (HFD) and normal diet (ND). Then, fed with the PB extract with 100, 300, and 500 mg/kg and two negative control groups given water (WTR). The body weights were monitored and evaluated. Urine was collected and 1H NMR-based metabolomics approach was used to detect the metabolite changes. Results showed that PB-treated group demonstrated inhibition of body weight gain. The trajectory of urine metabolites showed that PB-treated group gave the different distribution from week 12 to 16 compared with the control groups. In 1H NMR metabolomic approach analysis, the urine metabolites gave the best separation in principle component 1 and 3, with 40.0% and 9.56% of the total variation. Shared and unique structures (SUS) plot model showed that higher concentration PB-treated group was characterized by high level of indole-3-acetate, aspartate, methanol, histidine, and creatine, thus caused an increased the metabolic function and maintaining the body weight of the animals treated.
  20. LPS Preconditioning Attenuates Apoptosis Mechanism by Inhibiting NF-κB and Caspase-3 Activity: TLR4 Pre-activation in the Signaling Pathway of LPS-Induced Neuroprotection
    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.
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