Displaying publications 221 - 240 of 836 in total

Abstract:
Sort:
  1. In vivo effects of stress, ACTH and corticosterone on testicular 11beta-hydroxysteroid dehydrogenase oxidative activity in rats and the possible mechanism of actions
    Nwe KH, Norhazlina AW, Hamid A, Morat PB, Khalid BA
    Exp. Clin. Endocrinol. Diabetes, 2000;108(5):369-77.
    PMID: 10989957
    The effects of stress and corticosterone on testicular 11beta-hydroxysteroid dehydrogenase (11beta-HSD) oxidative activity have been controversial, whilst that of adrenocorticotrophic hormone (ACTH) have not been investigated before. Hence, the aim of the present study was to determine the in vivo effects of stress due to injection and sham operation, ACTH and corticosterone on testicular and hepatic 11beta-HSD oxidative activity and plasma testosterone levels in normal and adrenalectomized (ADX) rats and their possible mechanism of actions. Adrenalectomy reduced both testicular 11beta-HSD oxidative activity and plasma testosterone levels. The effects of injection and sham operation significantly increased plasma corticosterone levels with decreased testicular 11beta-HSD oxidative activity and plasma testosterone levels in normal but not in ADX rats. Likewise. ACTH or corticosterone treatment for 7 days decreased both testicular 11beta-HSD oxidative activity in a dose dependent manner and plasma testosterone levels in normal rats; but the values in ADX rats remained unchanged. However, none of the above values were significantly lower than that of the ADX levels. Corticosterone seems to maintain testicular 11beta-HSD oxidative activity within the range between normal and ADX rats. These changes are not attributable to diurnal rhythms, as the time of sacrifice has been fixed between 8:30 and 10:30 am. In the liver, no significant change in 11beta-HSD oxidative activity was observed with sham operation, ACTH or corticosterone treatment; but adrenalectomy significantly decreased it. In conclusion, in the intact normal rats, stress, ACTH or corticosterone modulates testicular (but not hepatic) 11beta-HSD oxidative activity indirectly through the adrenal glands and the physiological level of corticosterone is ideal for normal reproductive functions.
    Matched MeSH terms: Dose-Response Relationship, Drug
  2. Effect of retinoic acid and palm oil carotenoids on oestrone sulphatase and oestradiol-17beta hydroxysteroid dehydrogenase activities in MCF-7 and MDA-MB-231 breast cancer cell lines
    Ng JH, Nesaretnam K, Reimann K, Lai LC
    Int J Cancer, 2000 Oct 1;88(1):135-8.
    PMID: 10962451
    Oestrogen is important in the development of breast cancer. Oestrogen receptor positive breast cancers are associated with a better prognosis than oestrogen-receptor negative breast cancers since they are more responsive to hormonal treatment. Oestrone sulphate acts as a huge reservoir for oestrogens in the breast. It is converted to the potent oestrogen, oestradiol (E(2)) by the enzymes oestrone sulphatase and oestradiol-17beta hydroxysteroid dehydrogenase (E(2)DH). Retinoic acid and carotenoids have been shown to have chemopreventive activity against some cancers. The aim of our study was to determine and compare the effects of retinoic acid and palm oil carotenoids on growth of and oestrone sulphatase and E(2)DH activities in the oestrogen receptor positive, MCF-7 and oestrogen receptor negative, MDA-MB-231 breast cancer cell lines. Retinoic acid and carotenoids inhibited MCF-7 cell growth but had no effect on MDA-MB-231 cell growth. Both retinoic acid and carotenoids stimulated oestrone sulphatase activity in the MCF-7 cell line. E(1) to E(2) conversion was inhibited by 10(-7) M carotenoids but was stimulated at 10(-6) M in the MCF-7 cell line. Retinoic acid had no effect on E(1) to E(2) conversion at 10(-7) M but stimulated E(1) to E(2) conversion at 10(-6) M. Retinoic acid and carotenoids had no effect on E(2) to E(1) conversion in the MCF-7 cell line. Retinoic acid stimulated E(1) to E(2) conversion in the MDA-MB-231 cell line but had no effect on oestrone sulphatase activity or E(2) to E(1) conversion in this cell line. Both oestrone sulphatase and E(2)DH activity were not affected by carotenoids in the MDA-MB-231 cell line. In conclusion, retinoic acid and carotenoids may prevent the development of hormone-dependent breast cancers since they inhibit the growth of the MCF-7 cell line.
    Matched MeSH terms: Dose-Response Relationship, Drug
  3. Bronchodilator response to inhaled beta-2 agonist and anticholinergic drugs in patients with bronchiectasis
    Hassan JA, Saadiah S, Roslan H, Zainudin BM
    Respirology, 1999 Dec;4(4):423-6.
    PMID: 10612580 DOI: 10.1046/j.1440-1843.1999.00215.x
    OBJECTIVE: An increase in incidence of reversible airflow obstruction and bronchial hyperresponsiveness occurs in patients with bronchiectasis. We conducted a study to assess the efficacy of bronchodilators in the treatment of bronchiectasis.
    METHODOLOGY: Twenty-four patients with confirmed bronchiectasis were studied. Each patient inhaled fenoterol 400 microg administered by metered dose inhaler via a spacer after a baseline lung function and a lung function test was repeated 30 min later. This was followed by a second dose of fenoterol 5 mg via nebulizer and another lung function test 30 min later. A repeat study was done at least 24 h later with ipratropium bromide 40 microg by metered dose inhaler and 500 microg by a nebulizer.
    RESULTS: The results showed a significant improvement from baselines (mean percentage change +/- SD) of peak expiratory flow rate (PEF) by 8.5 +/- 8.72% and 15.3 +/- 11.63%, forced expiratory volume in 1 s (FEV1) by 8.77 +/- 9.69% and 10.2 +/- 12.2% and forced vital capacity (FVC) by 10.25 +/- 11.61% and 10.09 +/- 10.88% after low- and high-dose fenoterol, respectively. The improvements after low- and high-dose ipratropium bromide for PEE FEV1 and FVC were 9.89 +/- 9.35% and 14.39 +/- 12.82%, 9.38 +/- 10.41% and 13.52 +/- 17.09%, and 8.03 +/- 10.85% and 9.63 +/- 13.85%, respectively. Eleven patients (45.8%) responded to one or both bronchodilators significantly (> 15% improvement in FEV1). Five patients (20%) responded to both, three (12%) to fenoterol alone and another three (12%) to ipratropium bromide alone.
    CONCLUSION: There is significant bronchodilator response in a subset of patients with bronchiectasis and patients with bronchiectasis should therefore undergo bronchodilator testing. Skin prick testing against a panel of nine allergens done on each individual yielded a positive result in 13 patients (54.2%).
    Matched MeSH terms: Dose-Response Relationship, Drug
  4. The oral and intratracheal toxicities of ROUNDUP and its components to rats
    Adam A, Marzuki A, Abdul Rahman H, Abdul Aziz M
    Vet Hum Toxicol, 1997 Jun;39(3):147-51.
    PMID: 9167243
    The toxicities of ROUNDUP and its component chemicals, glyphosate (N-phosphonomethylglycine) and polyoxyethyleneamine (POEA), were determined at 0, 1, 3, 6 and 24 h following administration to rats. The intratracheal administration of glyphosate (0.2 g/kg), POEA (0.1 g/kg), a mixture of glyphosate (0.2 g/kg) + POEA (0.1 g/kg), or ROUNDUP (containing 0.2 g/kg glyphosate and 0.1 g/kg POEA) elicited immediate respiratory effects which were more severe and which lasted longer in the groups receiving the POEA-containing preparations than in the glyphosate alone group. By 1 h, all test preparations had caused deaths, but more occurred from the POEA-containing preparations than from glyphosate. The po administration of POEA (1 g/kg), the mixture of glyphosate (2 g/kg) +POEA (1 g/kg), or ROUNDUP (containing 2 g/kg glyphosate and 1 g/kg POEA) produced diarrhea and blood-stained weeping from noses. Death was only seen from POEA at 24 h. Glyphosate (2 g/kg po) produced transient diarrhea without nose bleeds; POEA caused diarrhea at 1 h; and the mixture of POEA + glyphosate produced diarrhea later that increased in severity with time. Bloody nose secretions were seen only with the preparations that contained POEA. No deaths, respiratory effects or bloody nose secretions occurred in controls given saline. Both POEA and glyphosate caused lung hemorrhages and lung epithelial cell damage with po or intratracheal exposures. These results indicate POEA and preparations that contained POEA were more toxic than glyphosate.
    Matched MeSH terms: Dose-Response Relationship, Drug
  5. Determination of naltrexone dosage for narcotic agonist blockade in detoxified Asian addicts
    Navaratnam V, Jamaludin A, Raman N, Mohamed M, Mansor SM
    Drug Alcohol Depend, 1994 Feb;34(3):231-6.
    PMID: 8033761
    Thirty-eight, adult, male, detoxified, Malaysian opiate addicts participated in this double-blind clinical evaluation of naltrexone. Addicts from three ethnic groups: Chinese, Malays, and Indians received a weekly regimen of naltrexone (100 mg on Days 1 and 3, and 150 mg on Day 5). Subjects were randomly assigned to receive intravenous challenge with either 25 mg heroin or placebo 12, 24, 48, and 72 h after the third naltrexone dose. Physiological and subjective parameters were measured at each challenge interval. Results indicated that naltrexone was effective in blocking the physiological and psychological effects of heroin for at least 48 and 72 h, respectively, in detoxified Malaysian opiate addicts. The efficacy of naltrexone did not differ among the three ethnic groups evaluated in this study.
    Matched MeSH terms: Dose-Response Relationship, Drug
  6. Fulltext The use of surgical antibiotic prophylaxis in seven Malaysian hospitals
    Lim VK, Cheong YM, Suleiman AB
    Southeast Asian J. Trop. Med. Public Health, 1994 Dec;25(4):698-701.
    PMID: 7667716
    A survey on the use of antibiotics in surgical prophylaxis was carried out in seven Malaysian hospitals. Details of antibiotic prescriptions were obtained through questionnaires completed by the prescriber. A total of 430 such prescriptions was analysed. A large number of different antibiotic regimens were used for a variety of surgical procedures. The majority of prescriptions (70%) were issued for procedures where such prophylaxis was probably not necessary. Antibiotics were also often prescribed for durations that were longer than necessary. There is an urgent need to educate surgeons and standardize surgical prophylactic regimens in order to reduce cost and combat the emergence of antibiotic resistance.
    Matched MeSH terms: Dose-Response Relationship, Drug
  7. Retinal phlebitis associated with autoimmune hemolytic anemia
    Chew FL, Tajunisah I
    Ocul Immunol Inflamm, 2009 Nov-Dec;17(6):394-5.
    PMID: 20001258 DOI: 10.3109/09273940903260204
    To describe a case of retinal phlebitis associated with autoimmune hemolytic anemia.
    Matched MeSH terms: Dose-Response Relationship, Drug
  8. Fulltext Malaysian Tualang Honey Inhibits Hydrogen Peroxide-Induced Endothelial Hyperpermeability
    Devasvaran K, Tan JJ, Ng CT, Fong LY, Yong YK
    Oxid Med Cell Longev, 2019;2019:1202676.
    PMID: 31531177 DOI: 10.1155/2019/1202676
    Malaysian Tualang honey (TH) is a known therapeutic honey extracted from the honeycombs of the Tualang tree (Koompassia excelsa) and has been reported for its antioxidant, anti-inflammatory, antiproliferative, and wound healing properties. However, the possible vascular protective effect of TH against oxidative stress remains unclear. In this study, the effects of TH on hydrogen peroxide- (H2O2-) elicited vascular hyperpermeability in human umbilical vein endothelial cells (HUVECs) and Balb/c mice were evaluated. Our data showed that TH concentrations ranging from 0.01% to 1.00% showed no cytotoxic effect to HUVECs. Induction with 0.5 mM H2O2 was found to increase HUVEC permeability, but the effect was significantly reversed attenuated by TH (p < 0.05), of which the permeability with the highest inhibition peaked at 0.1%. In Balb/c mice, TH (0.5 g/kg-1.5 g/kg) significantly (p < 0.05) reduced H2O2 (0.3%)-induced albumin-bound Evans blue leak, in a dose-dependent manner. Immunofluorescence staining confirmed that TH reduced actin stress fiber formation while increasing cortical actin formation and colocalization of caveolin-1 and β-catenin in HUVECs. Signaling studies showed that HUVECs pretreated with TH significantly (p < 0.05) decreased intracellular calcium release, while sustaining the level of cAMP when challenged with H2O2. These results suggested that TH could inhibit H2O2-induced vascular hyperpermeability in vitro and in vivo by suppression of adherence junction protein redistribution via calcium and cAMP, which could have a therapeutic potential for diseases related to the increase of both oxidant and vascular permeability.
    Matched MeSH terms: Dose-Response Relationship, Drug
  9. Exploring antidiabetic potential of adamantyl-thiosemicarbazones via aldose reductase (ALR2) inhibition
    Shehzad MT, Hameed A, Al-Rashida M, Imran A, Uroos M, Asari A, et al.
    Bioorg Chem, 2019 11;92:103244.
    PMID: 31541804 DOI: 10.1016/j.bioorg.2019.103244
    The role of aldose reductase (ALR2) in diabetes mellitus is well-established. Our interest in finding ALR2 inhibitors led us to explore the inhibitory potential of new thiosemicarbazones. In this study, we have synthesized adamantyl-thiosemicarbazones and screened them as aldehyde reductase (ALR1) and aldose reductase (ALR2) inhibitors. The compounds bearing phenyl 3a, 2-methylphenyl 3g and 2,6-dimethylphenyl 3m have been identified as most potent ALR2 inhibitors with IC50 values of 3.99 ± 0.38, 3.55 ± 0.26 and 1.37 ± 0.92 µM, respectively, compared with sorbinil (IC50 = 3.14 ± 0.02 μM). The compounds 3a, 3g, and 3m also inhibit ALR1 with IC50 value of 7.75 ± 0.28, 7.26 ± 0.39 and 7.04 ± 2.23 µM, respectively. Molecular docking was also performed for putative binding of potent inhibitors with target enzyme ALR2. The most potent 2,6-dimethylphenyl bearing thiosemicarbazone 3m (IC50 = 1.37 ± 0.92 µM for ALR2) and other two compound 3a and 3g could potentially lead for the development of new therapeutic agents.
    Matched MeSH terms: Dose-Response Relationship, Drug
  10. New triazinoindole bearing thiazole/oxazole analogues: Synthesis, α-amylase inhibitory potential and molecular docking study
    Rahim F, Tariq S, Taha M, Ullah H, Zaman K, Uddin I, et al.
    Bioorg Chem, 2019 11;92:103284.
    PMID: 31546207 DOI: 10.1016/j.bioorg.2019.103284
    New triazinoindole bearing thiazole/oxazole analogues (1-21) were synthesized and characterized through spectroscopic techniques such as HREI-MS, 1H and 13C NMR. The configuration of compound 2i and 2k was confirmed through NOESY. All analogues were evaluated against α-amylase inhibitory potential. Among the synthesized analogues, compound 1h, 1i, 1j, 2a and 2f having IC50 values 1.80 ± 0.20, 1.90 ± 0.30, 1.2 ± 0.30, 1.2 ± 0.01 and 1.30 ± 0.20 μM respectively, showed excellent α-amylase inhibitory potential when compared with acarbose as standard (IC50 = 0.91 ± 0.20 µM). All other analogues showed good to moderate inhibitory potential. Structural activity relationship (SAR) has been established and binding interactions were confirmed through docking studies.
    Matched MeSH terms: Dose-Response Relationship, Drug
  11. Chalcones and bis-chalcones: As potential α-amylase inhibitors; synthesis, in vitro screening, and molecular modelling studies
    Tajudeen Bale A, Mohammed Khan K, Salar U, Chigurupati S, Fasina T, Ali F, et al.
    Bioorg Chem, 2018 09;79:179-189.
    PMID: 29763804 DOI: 10.1016/j.bioorg.2018.05.003
    Despite of a diverse range of biological activities associated with chalcones and bis-chalcones, they are still neglected by the medicinal chemist for their possible α-amylase inhibitory activity. So, the current study is based on the evaluation of this class for the identification of new leads as α-amylase inhibitors. For that purpose, a library of substituted chalcones 1-13 and bis-chalcones 14-18 were synthesized and characterized by spectroscopic techniques EI-MS and 1H NMR. CHN analysis was carried out and found in agreement with the calculated values. All compounds were evaluated for in vitro α-amylase inhibitory activity and demonstrated good activities in the range of IC50 = 1.25 ± 1.05-2.40 ± 0.09 µM as compared to the standard acarbose (IC50 = 1.04 ± 0.3 µM). Limited structure-activity relationship (SAR) was established by considering the effect of different groups attached to aryl rings on varying inhibitory activity. SMe group in chalcones and OMe group in bis-chalcones were found more influential on the activity than other groups. However, in order to predict the involvement of different groups in the binding interactions with the active site of α-amylase enzyme, in silico studies were also conducted.
    Matched MeSH terms: Dose-Response Relationship, Drug
  12. Fulltext Anti-Edematogenic and Anti-Granuloma Activity of a Synthetic Curcuminoid Analog, 5-(3,4-Dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one, in Mouse Models of Inflammation
    Hisamuddin N, Shaik Mossadeq WM, Sulaiman MR, Abas F, Leong SW, Kamarudin N, et al.
    Molecules, 2019 Jul 18;24(14).
    PMID: 31323775 DOI: 10.3390/molecules24142614
    Curcumin, derived from the rhizome Curcuma longa, has been scientifically proven to possess anti-inflammatory activity but is of limited clinical and veterinary use owing to its low bioavailability and poor solubility. Hence, analogs of curcuminoids with improved biological properties have been synthesized to overcome these limitations. This study aims to provide the pharmacological basis for the use of 5-(3,4-dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one (DHHPD), a synthetic curcuminoid analog, as an anti-edematogenic and anti-granuloma agent. The carrageenan-induced paw edema and the cotton pellet-induced granuloma assays were used to assess the anti-inflammatory activity of DHHPD in mice. The effects of DHHPD on the histaminergic, serotonergic, and bradykininergic systems were determined by the histamine-, serotonin-, and bradykinin-induced paw edema tests, respectively. DHHPD (0.1, 0.3, 1, and 3 mg/kg, intraperitoneal) evoked significant reductions (p < 0.05) in carrageenan-induced paw edema at different time intervals and granuloma formation (p < 0.0001) by 22.08, 32.57, 37.20, and 49.25%, respectively. Furthermore, DHHPD significantly reduced paw edema (p < 0.05) induced by histamine, serotonin, and bradykinin. The present study suggests that DHHPD exerts anti-edematogenic activity, possibly by inhibiting the synthesis or release of autacoid mediators of inflammation through the histaminergic, serotonergic, and bradykininergic systems. The anti-granuloma effect may be attributed to the suppression of transudative, exudative, and proliferative activities associated with inflammation.
    Matched MeSH terms: Dose-Response Relationship, Drug
  13. Overcoming barriers to optimal drug dosing during ECMO in critically ill adult patients
    Cheng V, Abdul-Aziz MH, Roberts JA, Shekar K
    Expert Opin Drug Metab Toxicol, 2019 Feb;15(2):103-112.
    PMID: 30582435 DOI: 10.1080/17425255.2019.1563596
    INTRODUCTION: One major challenge to achieving optimal patient outcome in extracorporeal membrane oxygenation (ECMO) is the development of effective dosing strategies in this critically ill patient population. Suboptimal drug dosing impacts on patient outcome as patients on ECMO often require reversal of the underlying pathology with effective pharmacotherapy in order to be liberated of the life-support device. Areas covered: This article provides a concise review of the effective use of antibiotics, analgesics, and sedative by characterizing the specific changes in PK secondary to the introduction of the ECMO support. We also discuss the barriers to achieving optimal pharmacotherapy in patients on ECMO and also the current and potential research that can be undertaken to address these clinical challenges. Expert opinion: Decreased bioavailability due to sequestration of drugs in the ECMO circuit and ECMO induced PK alterations are both significant barriers to optimal drug dosing. Evidence-based drug choices may minimize sequestration in the circuit and would enable safety and efficacy to be maintained. More work to characterize ECMO related pharmacodynamic alterations such as effects of ECMO on hepatic cytochrome system are still needed. Novel techniques to increase target site concentrations should also be explored.
    Matched MeSH terms: Dose-Response Relationship, Drug
  14. Benzoxazinone-thiosemicarbazones as antidiabetic leads via aldose reductase inhibition: Synthesis, biological screening and molecular docking study
    Shehzad MT, Imran A, Njateng GSS, Hameed A, Islam M, Al-Rashida M, et al.
    Bioorg Chem, 2019 06;87:857-866.
    PMID: 30551808 DOI: 10.1016/j.bioorg.2018.12.006
    Aldose reductase is an important enzyme in the polyol pathway, where glucose is converted to fructose, and sorbitol is released. Aldose reductase activity increases in diabetes as the glucose levels increase, resulting in increased sorbitol production. Sorbitol, being less cell permeable tends to accumulate in tissues such as eye lenses, peripheral nerves and glomerulus that are not insulin sensitive. This excessive build-up of sorbitol is responsible for diabetes associated complications such as retinopathy and neuropathy. In continuation of our interest to design and discover potent inhibitors of aldo-keto reductases (AKRs; aldehyde reductase ALR1 or AKR1A, and aldose reductase ALR2 or AKR1B), herein we designed and investigated a series of new benzoxazinone-thiosemicarbazones (3a-r) as ALR2 and ALR1 inhibitors. Most compounds exhibited excellent inhibitory activities with IC50 values in lower micro-molar range. Compounds 3b and 3l were found to be most active ALR2 inhibitors with IC50 values of 0.52 ± 0.04 and 0.19 ± 0.03 μM, respectively, both compounds were more effective inhibitors as compared to the standard ALR2 inhibitor (sorbinil, with IC50 value of 3.14 ± 0.02 μM).
    Matched MeSH terms: Dose-Response Relationship, Drug
  15. Effect of fat supplementation on physiological and reproductive performance of Holstein Friesian bulls during summer
    Butt MA, Bhatti JA, Khalique A, Shahid MQ
    Trop Anim Health Prod, 2019 Nov;51(8):2595-2601.
    PMID: 31230253 DOI: 10.1007/s11250-019-01976-1
    The objective of current study was to determine the effect of fat supplement on physiological and reproductive performance of Holstein Friesian bulls during subtropical summer in Pakistan. Eighteen bulls were randomly divided into 3 treatment groups: (1) CTL, basal diet without fat supplementation; (2) FS100, basal diet with 100 g fat supplementation (Energizer-RP-10®, IFFCO, Johor, Malaysia); (3) FS200, basal diet with 200 g fat supplementation. Basal diet consisted of 50% green fodder (corn silage), 25% wheat straw, and 25% concentrate on dry matter basis. Diets were offered for 14 weeks from May to August 2016. The average daily temperature-humidity index ranged from 85 to 88 for the experimental period. The results indicated that there was no difference in dry matter intake, water intake, rectal temperature, pulse rate, and respiration rate among the treatment groups. Fat supplementation did not influence semen traits including sperm motility, progressive motility, amplitude of lateral head displacement, live-to-dead ratio, normal acrosomal ridge, plasma membrane integrity, and DNA integrity. The interaction of season with fat revealed that FA200 significantly increased post thaw semen motility and progressive motility during hot humid summer (P 
    Matched MeSH terms: Dose-Response Relationship, Drug
  16. Anti-nociceptive mechanisms of flavonoids-rich methanolic extract from Terminalia coriacea (Roxb.) Wight & Arn. leaves
    Ali Khan MS, Ahmed N, Misbah, Arifuddin M, Zakaria ZA, Al-Sanea MM, et al.
    Food Chem Toxicol, 2018 May;115:523-531.
    PMID: 29555329 DOI: 10.1016/j.fct.2018.03.021
    In view of the report on anti-nociceptive activity of Leathery Murdah, Terminalia coriacea {Roxb.} Wight & Arn. (Combretaceae) leaves, the present study was conducted to isolate the active constituents and identify the underlying mechanisms. The methanolic extract of T. coriacea leaves (TCLME) at doses 125, 250 and 500 mg/kg orally, was subjected to various in-vivo assays in acetic acid induced writhing and formalin induced paw-licking tests with aspirin (100 mg/kg) and morphine (5 mg/kg) as reference drugs. Three flavonoids, rutin, robinin and gossypetin 3-glucuronide 8-glucoside were isolated and characterized from TCLME for the first time. The extract showed significant (p dose-dependent anti-nociceptive activity in glutamate induced paw licking in mice. The involvement of opioid pathway was confirmed as naloxone (5 mg/kg, i.p) treatment blocked the analgesic activity of the test extract. Similarly, glibenclamide (an ATP - sensitive potassium channel inhibitor) at dose of 10 mg/kg, i.p increased writhing in acetic acid model. It reversed the inhibitory effects of TCLME when administered in combination. Treatment of TCLME alone and in combination with l-arginine (100 mg/kg, i.p) significantly (p 
    Matched MeSH terms: Dose-Response Relationship, Drug
  17. Anti-inflammatory evaluation of Scurrula ferruginea (jack) danser parasitizing on Tecoma stans (L.) H.B.K. in LPS/IFN-γ-induced RAW 264.7 macrophages
    Hong X, Ajat M, Fakurazi S, Noor AM, Ismail IS
    J Ethnopharmacol, 2021 Mar 25;268:113647.
    PMID: 33271242 DOI: 10.1016/j.jep.2020.113647
    ETHNOPHARMACOLOGICAL RELEVANCE: Scurrula ferruginea (Jack) Danser (locally known as 'Dedalu' or 'dian nan ji sheng' in Malaysia and China) is a hemi-parasitic shrub that is widely used as herbal medicine to treat inflammation, rheumatism, and stroke. However, the scientific basis of its anti-inflammatory function and mechanism remain to be proven.

    AIM OF THE STUDY: To evaluate the anti-inflammatory activity as well as the preliminary mechanism of S. ferruginea parasitizing on Tecoma stans.

    MATERIALS AND METHODS: The anti-inflammatory capability of freeze-dried stem aqueous extract was assessed via inhibition of inflammatory cytokines interleukin- (IL-) 1β, IL-6, IL-10, and tumor necrosis factor-alpha (TNF-α) production in lipopolysaccharide (LPS) and interferon-γ (IFN-γ) stimulated RAW 264.7 macrophages. The underlying anti-inflammatory mechanism was deciphered through reverse transcriptase and real time quantitative polymerase chain reactions (RT-PCR and qPCR) for inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), IL-1β, and TNF-α mRNA expression.

    RESULTS: The results exhibited that aqueous extract of freeze-dried S. ferruginea stem sample concentration-dependently inhibited IL-1β protein production along with the down regulation of iNOS and IL-1β mRNA expression. Moreover, it significantly suppressed the protein release of IL-6 and IL-10 in a concentration-dependent manner. However, it slightly reduced TNF-α at higher sample concentration (250 μg/mL) without affecting the mRNA expression levels of COX-2 and TNF-α.

    CONCLUSIONS: This study suggests that S. ferruginea parasitizing on Tecoma stans exerted anti-inflammatory capability attributed to inhibition of iNOS and IL-1β mRNA expression, NO creation, IL-1β, IL-6, IL-10, and TNF-α protein production, indicating this plant might be a useful plant-derived candidate against inflammation.

    Matched MeSH terms: Dose-Response Relationship, Drug
  18. Toxicology study of vanillin on rats via oral and intra-peritoneal administration
    Ho K, Yazan LS, Ismail N, Ismail M
    Food Chem Toxicol, 2011 Jan;49(1):25-30.
    PMID: 20807560 DOI: 10.1016/j.fct.2010.08.023
    Vanillin is useful as anti-sickle cell anemia, anti-mutagen and anti-bacteria agent. However, vanillin must be administered at high concentration and cannot be oxidized by the upper gastrointestinal track of patients to be medically effective. In this study, we assessed the toxic effect of vanillin when administered in an un-oxidized form at high concentrations (150 and 300 mg/kg) via oral and intra-peritoneal injection. It was found that 300 mg/kg vanillin injection caused the rats to be unconscious without exerting any toxic effect on blood cells, kidney and liver. Besides, it showed blood protective property. Further analysis with GenomeLab GeXP genetic system on brain tissues showed that the expression of most xenobiotic metabolism, cell progression, tumor suppressor, DNA damage and inflammation genes were maintained at normal level. However, the expression of a few xenobiotic metabolism, cell cycle arrest and apoptosis genes were up-regulated by 5% ethanol injection. Nevertheless, when 5% ethanol was injected with the presence of vanillin, the expression was back to normal level. It is postulated that vanillin might have neuro-protective property. In conclusion, vanillin is not toxic at high concentration in both oral and intra-peritoneal injection and could provide blood and brain protective properties.
    Matched MeSH terms: Dose-Response Relationship, Drug
  19. LAT is essential for the mast cell stabilising effect of tHGA in IgE-mediated mast cell activation
    Tan JW, Israf DA, Md Hashim NF, Cheah YK, Harith HH, Shaari K, et al.
    Biochem Pharmacol, 2017 Nov 15;144:132-148.
    PMID: 28813645 DOI: 10.1016/j.bcp.2017.08.010
    Mast cells play a central role in the pathogenesis of allergic reaction. Activation of mast cells by antigens is strictly dependent on the influx of extracellular calcium that involves a complex interaction between signalling molecules located within the cells. We have previously reported that tHGA, an active compound originally isolated from a local shrub known as Melicope ptelefolia, prevented IgE-mediated mast cell activation and passive systemic anaphylaxis by suppressing the release of interleukin-4 (IL-4) and tumour necrosis factor (TNF)-α from activated rat basophilic leukaemia (RBL)-2H3 cells. However, the mechanism of action (MOA) as well as the molecular target underlying the mast cell stabilising effect of tHGA has not been previously investigated. In this study, DNP-IgE-sensitised RBL-2H3 cells were pre-treated with tHGA before challenged with DNP-BSA. To dissect the MOA of tHGA in IgE-mediated mast cell activation, the effect of tHGA on the transcription of IL-4 and TNF-α mRNA was determined using Real Time-Polymerase Chain Reaction (qPCR) followed by Calcium Influx Assay to confirm the involvement of calcium in the activation of mast cells. The protein lysates were analysed by using Western Blot to determine the effect of tHGA on various important signalling molecules in the LAT-PLCγ-MAPK and PI3K-NFκB pathways. In order to identify the molecular target of tHGA in IgE-mediated mast cell activation, the LAT and LAT2 genes in RBL-2H3 cells were knocked-down by using RNA interference to establish a LAT/LAT2 competition model. The results showed that tHGA inhibited the transcription of IL-4 and TNF-α as a result of the suppression of calcium influx in activated RBL-2H3 cells. The results from Western Blot revealed that tHGA primarily inhibited the LAT-PLCγ-MAPK pathway with partial inhibition on the PI3K-p65 pathway without affecting Syk. The results from RNAi further demonstrated that tHGA failed to inhibit the release of mediators associated with mast cell degranulation under the LAT/LAT2 competition model in the absence of LAT. Collectively, this study concluded that the molecular target of tHGA could be LAT and may provide a basis for the development of a mast cell stabiliser which targets LAT.
    Matched MeSH terms: Dose-Response Relationship, Drug
  20. Development of diarylpentadienone analogues as alpha-glucosidase inhibitor: Synthesis, in vitro biological and in vivo toxicity evaluations, and molecular docking analysis
    Abdullah MA, Lee YR, Mastuki SN, Leong SW, Wan Ibrahim WN, Mohammad Latif MA, et al.
    Bioorg Chem, 2020 11;104:104277.
    PMID: 32971414 DOI: 10.1016/j.bioorg.2020.104277
    A series of aminated- (1-9) and sulfonamide-containing diarylpentadienones (10-18) were synthesized, structurally characterized, and evaluated for their in vitro anti-diabetic potential on α-glucosidase and DPP-4 enzymes. It was found that all the new molecules were non-associated PAINS compounds. The sulfonamide-containing series (compounds 10-18) selectively inhibited α-glucosidase over DPP-4, in which compound 18 demonstrated the highest activity with an IC50 value of 5.69 ± 0.5 µM through a competitive inhibition mechanism. Structure-activity relationship (SAR) studies concluded that the introduction of the trifluoromethylbenzene sulfonamide moiety was essential for the suppression of α-glucosidase. The most active compound 18, was then further tested for in vivo toxicities using the zebrafish animal model, with no toxic effects detected in the normal embryonic development, blood vessel formation, and apoptosis of zebrafish. Docking simulation studies were also carried out to better understand the binding interactions of compound 18 towards the homology modeled α -glucosidase and the human lysosomal α -glucosidase enzymes. The overall results suggest that the new sulfonamide-containing diarylpentadienones, compound 18, could be a promising candidate in the search for a new α-glucosidase inhibitor, and can serve as a basis for further studies involving hit-to-lead optimization, in vivo efficacy and safety assessment in an animal model and mechanism of action for the treatment of T2DM patients.
    Matched MeSH terms: Dose-Response Relationship, Drug
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links