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  1. Nur Azlina Mohd. Fahami, Muharani Tajudin
    Kajian ini telah dijalankan untuk menentukan kesan suplimentasi tokotrienol (TT) dan tokoferol (TF) ke atas status oksidatif dan aktiviti enzim antioksidan pada hepar tikus dalam keadaan stres. Sebanyak 24 ekor tikus Sprague-Dawley jantan telah dibahagikan secara rawak kepada empat kumpulan. Dua kumpulan kawalan, kumpulan stres (CS) dan kumpulan tanpa stres (C) serta dua kumpulan rawatan yang diberikan tokotrienol (TTS) atau tokoferol (TFS) secara oral paksaan pada dos 60 mg/kg berat badan selama 28 hari dan didedahkan kepada stres. Setelah tamat tempoh rawatan, tikus-tikus daripada kumpulan CS, TTS dan TFS telah didedahkan kepada stres restain selama dua jam sehari untuk empat hari berturut-turut. Kemudian, darah tikus diambil untuk menentukan aktiviti enzim antioksidan iaitu superoksid dismutas (SOD) dan glutation peroksidase (GPx) manakala hepar diambil untuk menentukan kandungan malondialdehid (MDA) dan tahap glutation. Hasil kajian mendapati kandungan MDA meningkat dan glutation menurun secara signifikan pada tisu hepar pada kumpulan CS setelah diaruh stres, berbanding kumpulan tanpa stres. Walau bagaimanapun, tikus yang diberi suplimentasi tokotrienol dan tokoferol menunjukkan penurunan signifikan kandungan MDA dan peningkatan glutation berbanding kumpulan kawalan. Keputusan kajian ini mencadangkan bahawa tokotrienol dan tokoferol mampu menghalang tekanan oksidatif pada hepar akibat stres. Hasil daripada kajian ini juga menunjukkan peningkatan yang signifikan dalam aktiviti GPx plasma tikus pada kumpulan CS. Kumpulan tikus yang disuplimentasikan dengan tokotrienol menunjukkan penurunan yang signifikan dalam aktiviti GPx berbanding kumpulan CS. Sebagai kesimpulan, tokotrienol dan tokoferol berkesan dalam mengurangkan status oksidatif pada hepar tikus dan ini dapat diperhatikan dengan peningkatan glutation hepar dan penurunan aktiviti GPx plasma tikus yang teraruh stres.
  2. Nur Azlina Mohd Fahami Mail, Naddiah Syafiqah Ramli Mail, Elda Surhaida Latif Mail
    Sains Malaysiana, 2018;47:2411-2419.
    Stres merupakan sebarang gangguan, cabaran atau ancaman kepada seseorang individu yang merangsang perubahan
    respon fizikal, mental dan emosi. Hormon stres dan katekolamin dirembeskan di dalam otak sebagai respon terhadap
    stres. Kajian ini mengenal pasti kesan tokotrienol tulen dan vitamin E sawit ke atas perubahan hormon stres dan
    katekolamin pada tikus yang diaruhkan stres imobilisasi rendaman air. Sebanyak 32 ekor tikus Wistar jantan telah
    dibahagikan secara rawak kepada empat kumpulan kajian. Dua kumpulan kawalan; kumpulan tanpa stres (NS) dan
    kumpulan tanpa stres (CS) serta dua kumpulan rawatan yang diberikan tokotrienol (TTS) atau vitamin E sawit (TFS)
    secara oral paksaan pada dos 60 mg/kg berat badan selama 28 hari. Setelah tamat tempoh rawatan, tikus daripada
    kumpulan CS, TTS dan TFS telah didedahkan kepada stres imobilisasi rendaman air selama tiga setengan jam. Kemudian,
    otak tikus diambil untuk pengukuran hormon pelepasan kotikotrofin (CRH), hormon adenokortikotropik (ACTH),
    norepinefrin, dopamin dan serotonin. Keputusan kajian mendapati peningkatan kandungan CRH, ACTH, norepinefrin
    dan dopamine di dalam otak tikus yang diaruh stres berbanding kumpulan kawalan tanpa stres. Kandungan serotonin
    pula menurun akibat stres. Walau bagaimanapun, tikus yang diberi suplementasi tokotrienol dan vitamin E sawit
    menunjukkan penurunan signifikan kandungan CRH, ACTH, norepinefrin dan dopamin serta peningkatan kandungan
    dan serotonin sehingga hampir ke aras normal. Tiada perbezaan antara pemberian tokotrienol dan vitamin E sawit.
    Sebagai kesimpulan, tokotrienol dan vitamin E sawit berkesan dalam mengawal perubahan hormon stres serta
    katekolamin pada otak tikus yang teraruh stres.
  3. Fazalda A, Quraisiah A, Nur Azlina MF
    PMID: 30105063 DOI: 10.1155/2018/7515692
    Background: Peptic ulcer is a basic term for ulcers on the lower oesophagus, stomach, or jejunum. The specific term for ulcer in the stomach is gastric ulcer. The extensive use of honey around the globe helps researchers to study the usefulness of honey. Many studies had already been conducted and proved the effectiveness of honey in treating gastric ulcer.

    Methods: A systematic review of the literature was conducted to identify relevant studies on honey used as an alternative treatment of gastric ulcer cause by NSAIDs. A comprehensive search was conducted in Medline, SCOPUS, and Ebscohost. The main criteria used were articles published in English and using NSAIDs-induced gastric ulcer in rat's model and those reporting the effectiveness of honey.

    Results: Articles published between 2001 and 2014 were identified to be relevant in studies related to the inclusion criteria. The literature search found 30 potential and closely related articles in this review, but only 5 articles were taken which meet the criteria needed to be fulfilled.

    Conclusions: All studies in this review reported the efficacy of honey for gastric ulcer based on its antioxidant and cytoprotective activities. Most of the studies conducted used different types of honey at various doses on rats. Future studies should be conducted to identify the appropriate dose for humans to achieve similar gastroprotective effects.

  4. Aziz Ibrahim IA, Kamisah Y, Nafeeza MI, Nur Azlina MF
    Arch Med Sci, 2012 Feb 29;8(1):22-9.
    PMID: 22457670 DOI: 10.5114/aoms.2012.27276
    This study examines the effects of palm vitamin E (PVE) or α-tocopherol (α-TF) supplementation on adrenocorticotropin hormone (ACTH), corticosterone and gastric lesions in rats exposed to water-immersion restraint stress (WIRS).
  5. Nur Azlina MF, Qodriyah HMS, Chua KH, Kamisah Y
    World J Gastroenterol, 2017 Aug 28;23(32):5887-5894.
    PMID: 28932080 DOI: 10.3748/wjg.v23.i32.5887
    AIM: To investigate and compare the effects of tocotrienol and omeprazole on gastric growth factors in rats exposed to water-immersion restraint stress (WIRS).

    METHODS: Twenty-eight male Wistar rats were randomly assigned to four groups of seven rats. The two control groups were administered vitamin-free palm oil (vehicle) and the two treatment groups were given omeprazole (20 mg/kg) or tocotrienol (60 mg/kg) by oral gavage. After 28 d of treatment, rats from one control group and both treated groups were subjected to WIRS one time for 3.5 h. Gastric lesions were measured and gastric tissues were obtained to measure vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and transforming growth factor-alpha (TGF-α) mRNA expression.

    RESULTS: Rats exposed to WIRS for 3.5 h demonstrated the presence of considerable ulcers in the form of gastric erosion. The lesion index in the stressed control (S) group was increased (P < 0.001) compared to the tocotrienol treated and omeprazole treated groups. Stress led to a decrease in gastric VEGF (P < 0.001), bFGF (P < 0.001) and TGF-α (P < 0.001) mRNA levels and caused an increase in EGF mRNA (P < 0.001) that was statistically significant compared to the non-stressed control group. Although both treatment agents exerted similar ulcer reducing ability, only treatment with tocotrienol led to increased expression of VEGF (P = 0.008), bFGF (P = 0.001) and TGF-α (P = 0.002) mRNA.

    CONCLUSION: Tocotrienol provides gastroprotective effects in WIRS-induced ulcers. Compared to omeprazole, tocotrienol exerts a similar protective effect, albeit through multiple mechanisms of protection, particularly through up-regulation of growth factors that assist in repair of gastric tissue injuries.

  6. Akmal MN, Abdel Aziz I, Nur Azlina MF
    Front Pharmacol, 2022;13:971443.
    PMID: 36712695 DOI: 10.3389/fphar.2022.971443
    This study investigated the gastroprotective effect of Piper sarmentosum (PS) on stress-induced gastric ulcers in rats by measuring its effect on oxidative stress, gastric mucosal nitric oxide (NO), and inflammatory biomarkers. Twenty-eight male Wistar rats were randomly divided into four groups; two control groups (non-stress and stress) and two treated groups supplemented with either methanolic PS extract (500 mg/kg body weight) or omeprazole (OMZ; 20 mg/kg) orally. After 28 days of treatment, the stress control, PS, and OMZ groups were subjected to water-immersion restrain stress (WIRS) for 3.5 h. Gastric tissue malondialdehyde (MDA), NO, superoxide dismutase (SOD), inducible NO synthase (iNOS), SOD mRNA, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels were measured. WIRS significantly increased gastric MDA, NO, and pro-inflammatory cytokine levels compared to the non-stressed control group. PS and omeprazole supplementation significantly reduced WIRS-exposure-induced gastric ulcers and MDA, iNOS, and IL-1β levels. However, only PS reduced NO, TNF-α, and IL-6 levels, which were upregulated in this ulcer model. In conclusion, the gastroprotection afforded by PS is possibly mediated by gastric mucosal NO normalization through reduced iNOS expression and attenuation of inflammatory cytokines. PS showed a greater protective effect than omeprazole in reducing gastric lesions and NO, TNF-α, and IL-6 levels, and iNOS expression.
  7. Nur Azlina MF, Kamisah Y, Chua KH, Qodriyah HM
    PMID: 23970937 DOI: 10.1155/2013/804796
    The present study aims to distinguish the effect of tocotrienol on an important gastric protective factor, prostaglandin E2 (PGE2), in stress-induced gastric injury. Twenty-eight Wistar rats were divided into four groups of seven rats each. Two control groups were fed commercial rat diet, and two treatment groups were fed the same diet but with additional dose of omeprazole (20 mg/kg) or tocotrienol (60 mg/kg). After 28 days, rats from one control group and both treated groups were subjected to water-immersion restraint stress for 3.5 hours once. The rats were then sacrificed, their stomach isolated and gastric juice collected, lesions examined, and gastric PGE2 content and cyclooxygenase (COX) mRNA expression were determined. Both the regimes significantly attenuated the total lesion area in the stomach compared to the control. Gastric acidity, which was increased in stress, was significantly reduced in rats supplemented with omeprazole and tocotrienol. The PGE2 content was also significantly higher in the rats given tocotrienol supplementation compared to the control followed by an increase in COX-1 mRNA expression. We conclude that tocotrienol supplementation protected rat gastric mucosa against stress-induced lesions possibly by reducing gastric acidity and preserving gastric PGE2 by increasing COX-1 mRNA.
  8. Rodzian MN, Aziz Ibrahim IA, Nur Azlina MF, Nafeeza MI
    Pol J Pathol, 2013 Apr;64(1):52-8.
    PMID: 23625601
    Stress has been implicated as a risk factor of various major health problems, such as stress-induced gastric mucosal injury. This study was performed to investigate the action of a pure preparation of tocotrienol (T3) concentrate, made up of 90% δ-tocotrienol and 10% γ-tocotrienol, on gastric injury of rats induced by water-immersion restraint stress (WIRS). Fourteen male Sprague-Dawley rats (200-250 g) were divided into two equal groups: a control group and a treated group. The treatment group received T3 concentrate at 60 mg/kg body weight daily for 28 days. The body weights of rats were recorded daily before the treatment was given. At the end of the treatment period, all rats were subjected to WIRS for 3.5 hours, following which the rats were euthanized. The stomachs were isolated and opened along the greater curvature for the examination of lesions and measurements of gastric malondialdehyde (MDA) and prostaglandin E₂ (PGE₂) contents. The mean gastric mucosal lesion index in the treated rats was significantly lower than that in the control rats. This suggests that the T3 concentrate has the ability to confer protection to the gastric mucosa against gastric injury induced by acute stress. No significant difference was observed for changes in body weight before and after the treatment. The gastric PGE2 content in both groups was comparable. However, the gastric MDA content was significantly higher in the treated group compared to the control group, indicating that the T3 supplementation was not able to reduce the lipid peroxidation process. This study concludes that the T3 concentrate has the ability to protect the gastric mucosa from stress-induced injury by a non-antioxidant mechanism.
  9. Nur Azlina MF, Kamisah Y, Chua KH, Ibrahim IA, Qodriyah HM
    PLoS One, 2015;10(10):e0139348.
    PMID: 26465592 DOI: 10.1371/journal.pone.0139348
    This study aimed to investigate the possible gastroprotective effect of tocotrienol against water-immersion restraint stress (WIRS) induced gastric ulcers in rats by measuring its effect on gastric mucosal nitric oxide (NO), oxidative stress, and inflammatory biomarkers. Twenty-eight male Wistar rats were randomly assigned to four groups of seven rats. The two control groups were administered vitamin-free palm oil (vehicle) and the two treatment groups were given omeprazole (20 mg/kg) or tocotrienol (60 mg/kg) orally. After 28 days, rats from one control group and both treated groups were subjected to WIRS for 3.5 hours once. Malondialdehyde (MDA), NO content, and superoxide dismutase (SOD) activity were assayed in gastric tissue homogenates. Gastric tissue SOD, iNOS, TNF-α and IL1-β expression were measured. WIRS increased the gastric MDA, NO, and pro-inflammatory cytokines levels significantly when compared to the non-stressed control group. Administration of tocotrienol and omeprazole displayed significant protection against gastric ulcers induced by exposure to WIRS by correction of both ulcer score and MDA content. Tissue content of TNF-α and SOD activity were markedly reduced by the treatment with tocotrienol but not omeprazole. Tocotrienol significantly corrected nitrite to near normal levels and attenuated iNOS gene expression, which was upregulated in this ulcer model. In conclusion, oral supplementation with tocotrienol provides a gastroprotective effect in WIRS-induced ulcers. Gastroprotection is mediated through 1) free radical scavenging activity, 2) the increase in gastric mucosal antioxidant enzyme activity, 3) normalisation of gastric mucosal NO through reduction of iNOS expression, and 4) attenuation of inflammatory cytokines. In comparison to omeprazole, it exerts similar effectiveness but has a more diverse mechanism of protection, particularly through its effect on NO, SOD activity, and TNF-α.
  10. Ekeuku SO, Thong BKS, Quraisiah A, Annuar F, Hanafiah A, Nur Azlina MF, et al.
    Drug Des Devel Ther, 2020;14:5359-5366.
    PMID: 33324037 DOI: 10.2147/DDDT.S287239
    Purpose: Triple therapy is the standard therapy to eradicate Helicobacter pylori (H.pylori) infection. Chronic use of proton pump inhibitors (PPIs), a component of triple therapy, is associated with osteoporosis. However, the skeletal effects of short-term triple therapy containing PPI remain elusive. This study aims to determine the skeletal effect of short-term triple therapy in a rat model of gastric ulcer induced by H. pylori.

    Methods: Three-month-old male Sprague Dawley rats were assigned to normal control, H. pylori-inoculated group (negative control) and H. pylori-inoculated group receiving triple therapy consisting of omeprazole [2.035 mg/kg body weight (b.w)], amoxicillin (102.80 mg/kg b.w) and clarithromycin (51.37 mg/kg b.w) (n=6/group). H. pylori infection developed for four weeks after inoculation, followed by two-week triple therapy. At the end of the treatment period, femoral bones of the rats were harvested for analysis. Bone mineral density and content of the femurs were determined using dual-energy X-ray absorptiometry, while bone strength was measured with a universal mechanical tester.

    Results: Bone mineral content was significantly lower in the negative control group compared to the triple therapy group (p=0.014). Triple therapy decreased strain (vs negative control, p=0.002) and displacement of the femur (vs normal control, p=0.004; vs untreated control, p=0.005). No significant difference was observed in other parameters among the study groups (p>0.05).

    Conclusion: Short-term triple therapy increases bone mineral content but decreases bone strength of rats. Skeletal prophylaxis should be considered for patients on short-term triple therapy containing PPI.

  11. Ibrahim IAA, Alzahrani AR, Alanazi IM, Shahzad N, Shahid I, Falemban AH, et al.
    Int J Nanomedicine, 2024;19:1109-1124.
    PMID: 38344441 DOI: 10.2147/IJN.S445206
    BACKGROUND: Liver cancer is the sixth most prevalent form of cancer and the second major cause of cancer-associated mortalities worldwide. Cancer nanotechnology has the ability to fundamentally alter cancer treatment, diagnosis, and detection.

    OBJECTIVE: In this study, we explained the development of graphene oxide/polyethylene glycol/folic acid/brucine nanocomposites (GO/PEG/Bru-FA NCs) and evaluated their antimicrobial and anticancer effect on the liver cancer HepG2 cells.

    METHODOLOGY: The GO/PEG/Bru-FA NCs were prepared using the co-precipitation technique and characterized using various techniques. The cytotoxicity of the GO/PEG/Bru-FA NCs was tested against both liver cancer HepG2 and non-malignant Vero cells using an MTT assay. The antimicrobial activity of the GO/PEG/Bru-FA NCs was tested against several pathogens using the well diffusion technique. The effects of GO/PEG/Bru-FA NCs on endogenous ROS accumulation, apoptosis, and MMP levels were examined using corresponding fluorescent staining assays, respectively. The apoptotic protein expressions, such as Bax, Bcl-2, and caspases, were studied using the corresponding kits.

    RESULTS: The findings of various characterization assays revealed the development of GO/PEG/Bru-FA NCs with face-centered spherical morphology and an agglomerated appearance with an average size of 197.40 nm. The GO/PEG/Bru-FA NCs treatment remarkably inhibited the growth of the tested pathogens. The findings of the MTT assay evidenced that the GO/PEG/Bru-FA NCs effectively reduced the HepG2 cell growth while not showing toxicity to the Vero cells. The findings of the fluorescent assay proved that the GO/PEG/Bru-FA NCs increased ROS generation, reduced MMP levels, and promoted apoptosis in the HepG2 cells. The levels of Bax, caspase-9, and -3 were increased, and Bcl-2 was reduced in the GO/PEG/Bru-FA NCs-treated HepG2 cells.

    CONCLUSION: The results of this work demonstrate that GO/PEG/Bru-FA NCs suppress viability and induce apoptosis in HepG2 cells, indicating their potential as an anticancer candidate.

  12. Kamisah Y, Shamil S, Nabillah MJ, Kong SY, Hamizah NA, Qodriyah HM, et al.
    Malays J Med Sci, 2012 Oct;19(4):57-62.
    PMID: 23613649
    BACKGROUND: This study was performed to compare the oxidative quality of repeatedly heated palm and soybean oils, which were used to fry keropok lekors and potato chips.

    METHODS: A kilogramme of keropok lekors or potato chips was fried in 2.5 L of palm or soybean oil at 180 °C for 10 minutes. The frying process was repeated once and four times to obtain twice-heated and five-times-heated oils. The peroxide value and fatty acid composition of the oils were measured.

    RESULTS: Frequent heating significantly increased the peroxide values in both oils, with the five-times-heated oils having the highest peroxide values [five-times-heated palm: 14.26 ± 0.41 and 11.29 ± 0.58 meq/kg vs fresh: 2.13 ± 0.00, F (3,12) = 346.80, P < 0.001; five-times-heated soybean: 16.95 ± 0.39 and 12.90 ± 0.21 meq/kg vs fresh: 2.53 ± 0.00 oils, F (3,12) = 1755, P < 0.001, when used to fry keropok lekors and potato chips, respectively]. Overall, both oils showed significantly higher peroxide values when keropok lekors were fried in them compared with when potato chips were fried. In general, the heated soybean oil had significantly higher peroxide values than the heated palm oil. Fatty acid composition in the oils remained mostly unaltered by the heating frequency.

    CONCLUSION: keropok lekors, when used as the frying material, increased the peroxide values of the palm and soybean oils. Fatty acid composition was not much affected by the frequency of frying or the fried item used.

  13. Banerjee S, Mukherjee S, Mohsin Kazi, Sen KK, Das A, Hasan R, et al.
    Cell Mol Biol (Noisy-le-grand), 2024 Sep 08;70(8):39-49.
    PMID: 39262264 DOI: 10.14715/cmb/2024.70.8.5
    The present study deals with the in-silico analyses of several flavonoid derivatives to explore COVID-19 through pharmacophore modelling, molecular docking, molecular dynamics, drug-likeness, and ADME properties. The initial literature study revealed that many flavonoids, including luteolin, quercetin, kaempferol, and baicalin may be useful against SARS β-coronaviruses, prompting the selection of their potential derivatives to investigate their abilities as inhibitors of COVID-19. The findings were streamlined using in silico molecular docking, which revealed promising energy-binding interactions between all flavonoid derivatives and the targeted protein. Notably, compounds 8, 9, 13, and 15 demonstrated higher potency against the coronavirus Mpro protein (PDB ID 6M2N). Compound 8 has a -7.2 Kcal/mol affinity for the protein and binds to it by hydrogen bonding with Gln192 and π-sulfur bonding with Met-165. Compound 9 exhibited a significant interaction with the main protease, demonstrating an affinity of -7.9 kcal/mol. Gln-192, Glu-189, Pro-168, and His-41 were the principle amino acid residues involved in this interaction. The docking score for compound 13 is -7.5 Kcal/mol, and it binds to the protease enzyme by making interactions with Leu-41, π-sigma, and Gln-189. These interactions include hydrogen bonding and π-sulfur. The major protease and compound 15 were found to bind with a favourable affinity of -6.8 Kcal/mol. This finding was further validated through molecular dynamic simulation for 1ns, analysing parameters such as RMSD, RMSF, and RoG profiles. The RoG values for all four of the compounds varied significantly (35.2-36.4). The results demonstrated the stability of the selected compounds during the simulation. After passing the stability testing, the compounds underwent screening for ADME and drug-likeness properties, fulfilling all the necessary criteria. The findings of the study may support further efforts for the discovery and development of safe drugs to treat COVID-19.
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