MyMedR

Displaying all 12 publications

Abstract:

Sort:

Antioxidant, anti-TB activities, phenolic and amide contents of standardised extracts of Piper sarmentosum Roxb

Hussain K, Ismail Z, Sadikun A, Ibrahim P

Nat Prod Res, 2009;23(3):238-49.
PMID: 19235024 DOI: 10.1080/14786410801987597

Ethanol and aqueous extracts of the different parts of Piper sarmentosum were analysed by HPLC for marker compounds to standardise these extracts. The standardised extracts were investigated for antioxidant activity (beta-carotene linoleate model and DPPH model), anti-TB activity (microplate tetrazolium assay), and estimation of total phenolic and amide contents. The extracts of the different parts exhibited different antioxidant activity, phenolic and amide contents (p < 0.01). The ethanol extracts exhibited better antioxidant activity as compared to the aqueous extracts. The leaf ethanol extract was further investigated for dose response relationship and its EC(50) was found to be 38 microg mL(-1). All the extracts have exhibited anti-TB activity with MIC/MBC 12.5 microg mL(-1). The leaf methanol extract was fractionated and the ethyl acetate fraction exhibited anti-TB activity with MIC/MBC 3.12 microg mL(-1) while MIC/MBC of isoniazid (INH) was found to be 0.5 microg mL(-1). A positive correlation was found between antioxidant activity and total polyphenols, flavonoids and amides, in the beta-carotene linoleate model (p = 0.05) and in the DPPH model (p = 0.01). The analytical method was found to have linearity >0.9922, coefficient of variance <5% and accuracy 95.5 +/- 5 to 96.9 +/- 5. This plant possesses promising antioxidant as well as anti-TB properties.
Analysis of differentially expressed proteins in late-stationary growth phase of Mycobacterium tuberculosis H37Rv

Ang KC, Ibrahim P, Gam LH

Biotechnol Appl Biochem, 2014 Mar-Apr;61(2):153-64.
PMID: 23826872 DOI: 10.1002/bab.1137

Mycobacterium tuberculosis is a causative agent of tuberculosis (TB). The ability of M. tuberculosis to be quiescent in the cell has caused the emergence of latent infection. A comprehensive proteomic analysis of M. tuberculosis H37Rv over three growth phases, namely mid-log (14-day culture), early stationary (28-day culture), and late stationary (50-day culture), was performed in order to study the change in proteome from the mid-log phase to late-stationary phase. Combination methods of two-dimensional electrophoresis (2-DE) and tandem mass spectrometry were used to generate proteome maps of M. tuberculosis at different growth phases. Ten proteins were detected differentially expressed in the late-stationary phase compared with the other two phases. These proteins were SucD, TrpD, and Rv2161c, which belong to metabolic pathway proteins; FadE5, AccD5, DesA1, and Rv1139c are proteins involved in cell wall or lipid biosynthesis, whereas TB21.7 and Rv3224 are conserved hypothetical proteins with unknown function. A surface antigen protein, DesA1, was not detectable in the late-stationary phase, although present in both log and early-stationary phases. The changes in the expression levels of these proteins were in line with the growth environment changes of the bacteria from mid-log phase to late-stationary phase. The information gathered may be valuable in the intervention against latent TB infection.
Effects of isoniazid on viability, cell morphologies and acid fastness properties of Mycobacterium avium NCTC 8559 during the growth cycle

Mohamad S, Ibrahim P, Wahab HA

Chemotherapy, 2007;53(4):263-6.
PMID: 17595540

Our previous study demonstrated that the effects of isoniazid (INH) on Mycobacterium tuberculosis at the cellular level varied according to the growth phases. In this study, the variations in the INH action on M. avium strain NCTC 8559 are reported. M. avium cells grown on Middlebrook 7H10 agar were harvested at different stages of their growth cycle, exposed to the minimum inhibitory concentration of INH, stained with acid-fast staining for morphological changes and acid fastness properties, and the number of colonies were evaluated for viability studies. The study demonstrated that M. avium NCTC 8559 cells at the initial and fragmentation stages of the growth cycle were most susceptible to INH.
Comprehension of antibiotic instructions in an outpatient Malaysian practice

Hassan Y, Abd Aziz N, Sarriff A, Darwis Y, Ibrahim P

Hosp Pharm, 1994 Jan;29(1):48-50, 53.
PMID: 10131493

Patients may not comply with antibiotic instructions because they do not understand them. The aim of this study was to assess outpatients' ability to comprehend their antibiotic prescription labels. Two hundred and five subjects on oral antibiotic regimens from an outpatient clinic and pharmacy of a district hospital were selected in this survey. All patients were interviewed by trained clinical pharmacy students. They were asked to read the labels and then how they would take their antibiotics. The results show that 119 (58.1%) patients could interpret the label. Forty-nine (23.9%) patients knew the name of antibiotics and interpreted the directions of use correctly. One hundred sixteen (56.6%) subjects were able to recall the auxiliary information. However, only 44 (21.4%) patients were able to comprehend complete antibiotic instruction. This study demonstrates that a significant proportion of patients could not interpret the labeling instruction. The comprehension level of patients was low and significantly associated (P < 0.05) with the ability of patient to read the label contents. These observations illustrate the need for physicians and pharmacists to provide antibiotic instructions and review these instructions with the patient.

Study site: outpatient clinic and pharmacy of a district hospita
A study of patients' self-interpretation of prescription instructions

Sarriff A, Aziz NA, Hassan Y, Ibrahim P, Darwis Y

J Clin Pharm Ther, 1992 Apr;17(2):125-8.
PMID: 1583080

This study examined out-patients' interpretation of prescription instructions at a community hospital. The results showed a wide range of misinterpretation with respect to drug name, dose schedule, and auxiliary labels. Age level, education and financial status emerged as the most significant variables associated with the patient's response. Therefore, both physicians and pharmacists may wish to review their traditional prescribing and dispensing procedures to help out-patients make better use of potent medication.
Susceptibility of Mycobacterium tuberculosis to isoniazid and its derivative, 1-isonicotinyl-2-nonanoyl hydrazine: investigation at cellular level

Mohamad S, Ibrahim P, Sadikun A

Tuberculosis (Edinb), 2004;84(1-2):56-62.
PMID: 14670346

In this study, the susceptibility of Mycobacterium tuberculosis to isoniazid (INH) was compared with its derivative, 1-isonicotinyl-2-nonanoyl hydrazine (INH-C9), prepared synthetically. The minimum inhibitory concentration (MIC) of the drugs was determined using the 1% proportion method. INH-C9 was found to lower the MIC of INH from 0.05 to 0.025 microg/ml. Further studies on the effects of INH and INH-C9 on M. tuberculosis were assessed by exposing the cells to the above at the MIC level. M. tuberculosis cells grown on Middlebrook 7H10 agar were harvested at different stages of their growth cycle (initial stage, 24 and 72 h), exposed to the MICs of INH and INH-C9, and stained with acid-fast staining. The observations were made for a week. The cellular morphologies and staining characteristics were examined using a Brightfield microscope. The result indicated cells only at the initial stage of growth were most susceptible to the drugs resulting in the loss of acid-fastness and intact cellular morphology in the majority of cells.
Standardization and in vivo antioxidant activity of ethanol extracts of fruit and leaf of Piper sarmentosum

Hussain K, Ismail Z, Sadikun A, Ibrahim P

Planta Med, 2010 Mar;76(5):418-25.
PMID: 19862670 DOI: 10.1055/s-0029-1186279

The present study aimed to investigate standardized ethanol extracts of fruit and leaves of Piper sarmentosum for their in vivo antioxidant activity in rats using a CCl (4)-induced oxidative stress model. The standardization was based on the quantification of the markers pellitorine, sarmentine and sarmentosine by high performance liquid chromatography (HPLC), and determination of total primary and secondary metabolites. The rats, divided into 7 groups each (n = 6), were used as follows: group 1 (CCl (4), negative control), group 2 (untreated, control), groups 3 and 4 (fruit extract 250 and 500 mg/kg, respectively), groups 5 and 6 (leaf extract 250 and 500 mg/kg, respectively) and group 7 (vitamin-E 100 mg/kg, positive control). The doses were administered orally for 14 days; 4 h following the last dose, a single dose of CCl (4) (1.5 mg/kg) was given orally to all the groups except group 2, and after 24 h, blood and liver of each animal were obtained. Analysis of plasma and liver homogenate exhibited significant preservation of markers of antioxidant activity, total plasma antioxidant activity (TPAA), total protein (TP), superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid reactive species (TBARS), in the pretreated groups as compared to the CCl (4) group (p < 0.05). Histology of the liver also evidenced the protection of hepatocytes against CCl (4) metabolites in the pretreated groups. The results of this study indicate the IN VIVO antioxidant activity of both extracts of the plant, which may be valuable to combat diseases involving free radicals.
Fulltext Bioactive Markers Based Pharmacokinetic Evaluation of Extracts of a Traditional Medicinal Plant, Piper sarmentosum

Hussain K, Ismail Z, Sadikun A, Ibrahim P

Evid Based Complement Alternat Med, 2011;2011:980760.
PMID: 19770264 DOI: 10.1093/ecam/nep143

In vitro assays are economical and easy to perform but to establish relevance of their results to real clinical outcome in animals or human, pharmacokinetics is prerequisite. Despite various in vitro pharmacological activities of extracts of Piper sarmentosum, there is no report of pharmacokinetics. Therefore, the present study aimed to evaluate ethanol extract of fruit of the plant in dose of 500 mg kg(-1) orally for pharmacokinetics. Sprague-Dawley rats were randomly divided into groups 1, 2, and 3 (each n = 6) to study absorption, distribution and excretion, respectively. High performance liquid chromatography (HPLC) with ultraviolet detection was applied to quantify pellitorine, sarmentine and sarmentosine in plasma, tissues, feces and urine to calculate pharmacokinetic parameters. Pellitorine exhibited maximum plasma concentration (C(max)) 34.77 ng mL(-1) ± 1.040, time to achieve C(max) (T(max)) 8 h, mean resident time (MRT) 26.00 ± 0.149 h and half life (t(1/2)) 18.64 ± 1.65 h. Sarmentine showed C(max) 191.50 ± 12.69 ng mL(-1), T(max) 6 h, MRT 11.12 ± 0.44 h and t(1/2) 10.30 ± 1.98 h. Sarmentosine exhibited zero oral bioavailability because it was neither detected in plasma nor in tissues, and in urine. Pellitorine was found to be distributed in intestinal wall, liver, lungs, kidney, and heart, whereas sarmentine was found only in intestinal wall and heart. The cumulative excretion of pellitorine, sarmentine and sarmentosine in feces in 72 h was 0.0773, 0.976, and 0.438 μg, respectively. This study shows that pellitorine and sarmentine have good oral bioavailability while sarmentosine is not absorbed from the gastrointestinal tract.
Traditional and complementary medicines: Quality assessment strategies and safe usage

Hussain K, Majeed MT, Ismail Z, Sadikun A, Ibrahim P

South Med Rev, 2009 Apr;2(1):19-23.
PMID: 23093874
Elucidating isoniazid resistance using molecular modeling

Wahab HA, Choong YS, Ibrahim P, Sadikun A, Scior T

J Chem Inf Model, 2009 Jan;49(1):97-107.
PMID: 19067649 DOI: 10.1021/ci8001342

The continuing rise in tuberculosis incidence and the problem of drug resistance strains have prompted the research on new drug candidates and the mechanism of drug resistance. Molecular docking and molecular dynamics simulation (MD) were performed to study the binding of isoniazid onto the active site of Mycobacterium tuberculosis enoyl-acyl carrier protein reductase (InhA) in an attempt to address the mycobacterial resistance against isoniazid. Results show that isonicotinic acyl-NADH (INADH) has an extremely high binding affinity toward the wild type InhA by forming stronger interactions compared to the parent drug (isoniazid) (INH). Due to the increase of hydrophobicity and reduction in the side chain's volume of A94 of mutant type InhA, both INADH and the mutated protein become more mobile. Due to this reason, the molecular interactions of INADH with mutant type are weaker than that observed with the wild type. However, the reduced interaction caused by the fluctuation of INADH and the mutant protein only inflected minor resistance in the mutant strain as inferred from free energy calculation. MD results also showed there exists a water-mediated hydrogen bond between INADH and InhA. However, the bridged water molecule is only present in the INADH-wild type complex, reflecting the putative role of the water molecule in the binding of INADH to the wild type protein. The results support the assumption that the conversion of prodrug isoniazid into its active form INADH is mediated by KatG as a necessary step prior to target binding on InhA. Our findings also contribute to a better understanding of INH resistance in mutant type.
Antituberculosis potential of some ethnobotanically selected Malaysian plants

Mohamad S, Zin NM, Wahab HA, Ibrahim P, Sulaiman SF, Zahariluddin AS, et al.

J Ethnopharmacol, 2011 Feb 16;133(3):1021-6.
PMID: 21094237 DOI: 10.1016/j.jep.2010.11.037

Many local plants are used in Malaysian traditional medicine to treat respiratory diseases including symptoms of tuberculosis. The aim of the study was to screen 78 plant extracts from 70 Malaysian plant species used in traditional medicine to treat respiratory diseases including symptoms of tuberculosis for activity against Mycobacterium tuberculosis H37Rv using a colorimetric microplate-based assay.
Fulltext Antituberculosis activity, phytochemical identification of Costus speciosus (J. Koenig) Sm., Cymbopogon citratus (DC. Ex Nees) Stapf., and Tabernaemontana coronaria (L.) Willd. and their effects on the growth kinetics and cellular integrity of Mycobacterium tuberculosis H37Rv

Mohamad S, Ismail NN, Parumasivam T, Ibrahim P, Osman H, A Wahab H

BMC Complement Altern Med, 2018 Jan 08;18(1):5.
PMID: 29310671 DOI: 10.1186/s12906-017-2077-5

BACKGROUND: Costus speciosus, Cymbopogon citratus, and Tabernaemontana coronaria are herbal plants traditionally used as remedies for symptoms of tuberculosis (TB) including cough. The aims of the present study were to evaluate the in vitro anti-TB activity of different solvent partitions of these plants, to identify the phytochemical compounds, and to assess the effects of the most active partitions on the growth kinetics and cellular integrity of the tubercle organism.
METHODS: The in vitro anti-TB activity of different solvent partitions of the plant materials was determined against M. tuberculosis H37Rv using a tetrazolium colorimetric microdilution assay. The phytochemical compounds in the most active partition of each plant were identified using gas chromatography-mass spectrometry (GC-MS) analysis. The effects of these partitions on the growth kinetics of the mycobacteria were evaluated over 7-day treatment period in a batch culture system. Their effects on the mycobacterial cellular integrity were observed under a scanning electron microscope (SEM).
RESULTS: The respective n-hexane partition of C. speciosus, C. citratus, and T. coronaria exhibited the highest anti-TB activity with minimum inhibitory concentrations (MICs) of 100-200 μg/mL and minimum bactericidal concentration (MBC) of 200 μg/mL. GC-MS phytochemical analysis of these active partitions revealed that majority of the identified compounds belonged to lipophilic fatty acid groups. The active partitions of C. speciosus and T. coronaria exhibited high cidal activity in relation to time, killing more than 99% of the cell population. SEM observations showed that these active plant partitions caused multiple structural changes indicating massive cellular damages.
CONCLUSIONS: The n-hexane partition of the plant materials exhibited promising in vitro anti-TB activity against M. tuberculosis H37Rv. Their anti-TB activity was supported by their destructive effects on the integrity of the mycobacterial cellular structure.