Displaying publications 41 - 60 of 377 in total

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  1. Fulltext 3',4'-dihydroxyflavonol ameliorates endoplasmic reticulum stress-induced apoptosis and endothelial dysfunction in mice
    Lau YS, Mustafa MR, Choy KW, Chan SMH, Potocnik S, Herbert TP, et al.
    Sci Rep, 2018 01 29;8(1):1818.
    PMID: 29379034 DOI: 10.1038/s41598-018-19584-8
    Endoplasmic reticulum (ER) stress has been implicated in the development of hypertension 3 through the induction of endothelial impairment. As 3',4'-dihydroxyflavonol (DiOHF) 4 reduces vascular injury caused by ischaemia/reperfusion or diabetes, and flavonols have been demonstrated to attenuate ER stress, we investigated whether DiOHF can protect mice from ER stress-induced endothelial dysfunction. Male C57BLK/6 J mice were injected with tunicamycin to induce ER stress in the presence or absence of either DiOHF or tauroursodeoxycholic acid (TUDCA), an inhibitor of ER stress. Tunicamycin elevated blood pressure and impaired endothelium-dependent relaxation. Moreover, in aortae there was evidence of ER stress, oxidative stress and reduced NO production. This was coincident with increased NOX2 expression and reduced phosphorylation of endothelial nitric oxide synthase (eNOS) on Ser1176. Importantly, the effects of tunicamycin were significantly ameliorated by DiOHF or TUDCA. DiOHF also inhibited tunicamycin-induced ER stress and apoptosis in cultured human endothelial cells (HUVEC). These results provide evidence that ER stress is likely an important initiator of endothelial dysfunction through the induction of oxidative stress and a reduction in NO synthesis and that DiOHF directly protects against ER stress- induced injury. DiOHF may be useful to prevent ER and oxidative stress to preserve endothelial function, for example in hypertension.
    Matched MeSH terms: Nitric Oxide/metabolism; Nitric Oxide Synthase Type III/metabolism
  2. Fulltext Epigallocatechin gallate (EGCG) alleviates vascular dysfunction in angiotensin II-infused hypertensive mice by modulating oxidative stress and eNOS
    Mohd Sabri NA, Lee SK, Murugan DD, Ling WC
    Sci Rep, 2022 Oct 21;12(1):17633.
    PMID: 36271015 DOI: 10.1038/s41598-022-21107-5
    Epigallocatechin gallate (EGCG) has been shown to have antihypertensive activity. However, the role of epigallocatechin gallate (EGCG) in improving vascular function via modulation of endothelial nitric oxide synthase (eNOS) in hypertensive subjects is not well researched. Angiotensin II-infused hypertensive mice (8-10 weeks old) received EGCG (50 mg/kg/day) for 14 days via oral gavage. The arterial systolic blood pressure (SBP) was measured using the tail-cuff method every three days. At the end of the treatment, the vascular reactivity of the isolated aortae was studied using wire myographs. The level of nitric oxide (NO), cyclic guanosine monophosphate (cGMP) and tetrahydrobiopterine (BH4) were determined using assay kits while the presence of proteins (NOS, p-eNOS and NOx-2) were determined using by Western blotting. In vivo treatment with EGCG for 14 days significantly attenuated the increase in SBP, alleviated the vascular dysfunction, increased the vascular cGMP and BH4 level as well as the expression of p-eNOS and decreased elevated ROS level and NOx-2 protein in angiotensin II-infused hypertensive mice. Collectively, treatment with EGCG in hypertensive mice exerts a blood pressure lowering effect which is partly attributed to the improvement in the vascular function due to its ability to reduce vascular oxidative stress in the aortic tissue leading to a decrease in eNOS uncoupling thus increasing NO bioavailability.
    Matched MeSH terms: Nitric Oxide/metabolism
  3. Fulltext The effect and action mechanism of resveratrol on the vascular endothelial cell by high glucose treatment
    Liu X, Tian J, Bai Q, Ashraf MA, Sarfraz M, Zhao B
    Saudi J Biol Sci, 2016 Jan;23(1):S16-21.
    PMID: 26858561 DOI: 10.1016/j.sjbs.2015.06.021
    To investigate the effect and action mechanism of resveratrol on the vascular endothelial cell by high glucose treatment. Primarily cultured human umbilical vein endothelial cells (HUVECs) were pretreated by resveratrol (0.2 μmol/L) and holding for 6 h, and then cultured in Dulbecco Modified Eagle Medium (DMEM) within 0.45 mmol/L of palmimte acid and 32.8 mmol/L of glucose, which is holding for 12 h. The cells were collected to analyze the expression of E-selected element. Supernatant of cultured cells, induced by 100 nmol/L insulin for 30 min, was used to analyze the nitric oxide content. Compared with normal control cells, the secretion of nitric oxide is stimulated by insulin decrease, however, the expression of E-selected element increased in HUVEC. Resveratrol treatment increased the secretion of nitric oxide stimulated by insulin and decreased the expression of E-selected element and partly counteracts the impairment of high glucose and palmitate acid on the function of endothelial cells. Resveratrol can improve and protect the function of high glucose and fatty acid cultured endothelial cell, and therefore may be a promising medicine in the prevention or therapy of diabetic macrovascular diseases.
    Matched MeSH terms: Nitric Oxide
  4. Fulltext The stingless bee honey protects against hydrogen peroxide-induced oxidative damage and lipopolysaccharide-induced inflammation in vitro
    Ooi TC, Yaacob M, Rajab NF, Shahar S, Sharif R
    Saudi J Biol Sci, 2021 May;28(5):2987-2994.
    PMID: 34025176 DOI: 10.1016/j.sjbs.2021.02.039
    Oxidative stress, DNA damage, and unresolved inflammation are the predisposing factors of many chronic and degenerative diseases, including cancer. Stingless bee honey (SBH) is recognized to have high medicinal value by traditional medicine practitioners and has been used to treat various illnesses traditionally. This study aimed to determine the antioxidant, anti-inflammatory, and genoprotective effects of SBH by using in vitro cell culture models. The sugar content, total phenolic content, radical scavenging activity, and ferric reducing antioxidant power (FRAP) of SBH were determined in this study. Then, the protective effect of SBH against hydrogen peroxide (H2O2)-induced cell death and DNA damage was studied by using WIL2-NS human lymphoblastoid cell line, while the lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages cell line was used to study the anti-inflammatory effects of SBH. Results from this present study showed that the major sugar contents of SBH were fructose (19.39 + 0.01%) and glucose (14.03 ± 0.03%). Besides, the total phenolic content, the radical scavenging activity, and the FRAP value of SBH were 15.38 ± 0.02 mg GAE/100 g of honey, 34.04 ± 0.21%, and 206.77 + 1.76 μM AAE/100 g honey respectively. Pretreatment with SBH protected WIL2-NS cells from H2O2-induced cell death and DNA damage (p nitric oxide by inhibiting the expression of inducible nitric oxide synthase in LPS-induced RAW 264.7 cells (p 
    Matched MeSH terms: Nitric Oxide; Nitric Oxide Synthase Type II
  5. Discharge based processing systems for nitric oxide remediation
    Hashim S, Wong C, Abas M, Dahlan K
    Sains Malaysiana, 2010;39.
    An electron beam (EB) flue gas test rig and a dielectric barrier discharge (DBD) reactor were tested for the removal of nitric oxide (NO) from gas stream in separate experiments. In both systems, energised electrons were used to produce radicals that reacted with the pollutants. The EB system was a laboratory scale test rig used to treat emission from a diesel run generator. At 1.0 MeV and 10 mA more than 90% NO removal from flue gases flowing at 120 Nm3/h can be achieved. For higher removal percentage, higher beam current was required. In a related effort, a table top, two tubes DBD reactor was used to process bottled gases containing 106 ppm NO. Total removal (>99%) was achieved when the inlet gas contained only NO and N2. Additional SO2 in the in let gas stream lowered the removal rate but was overcame by scaling up the system to 10 DBD tubes. The system was operated with input AC voltage of 35 kV peak to peak. In the EB treatment system, the amount of NO2 increased at high beam current, showing that the NO was also oxidised in the process. Whereas in the DBD reactor, the amount of NO2 remained insignificant throughout the process. This leads to the conclusion that the DBD reactor is capable of producing total removal of NO. This is highly desirable as post treatment will not be necessary.
    Matched MeSH terms: Nitric Oxide
  6. Nitric oxide increases Pb tolerance by lowering Pb uptake and translocation as well as phytohormonal changes in Cowpea (Vigna Unguiculata (L.) Walp.)
    Sadeghipour O
    Sains Malaysiana, 2017;46:189-195.
    Lead (Pb) is one of the most abundant toxic heavy metals which adversely affected growth and yield of crop plants. Nitric oxide (NO), an endogenous signaling molecule, has been suggested to be involved in defense responses to biotic and abiotic stresses in plants. The present study was done to induce Pb tolerance in cowpea plants by exogenous NO application using two levels of Pb, 0 and 200 mg Pb (NO3)2 kg-1 soil and three NO levels, 0, 0.5 and 1 mM sodium nitroprusside (SNP), as NO donor. The results showed that Pb treatment caused a significant increase in Pb concentration in all plant parts. Roots had higher levels of Pb than the stems, leaves and seeds. Furthermore, lead toxicity reduced auxin (IAA), cytokinin and gibberellic acid (GA3) content but increased abscisic acid (ABA) level. Moreover Pb stress decreased stomatal conductance, leaf area and consequently seed yield of cowpea. Exogenous application of NO at 0.5 mM noticeably alleviated the lead toxicity by improving the leaf area, stomatal conductance and seed yield. NO increased Pb tolerance by lowering Pb uptake and translocation, enhancing the promoting phytohormone (IAA, cytokinin and GA3) level and reducing ABA content.
    Matched MeSH terms: Nitric Oxide; Nitric Oxide Donors
  7. Nitric oxide accelerates mycorrhizal effects on plant growth and root development of trifoliate orange
    Li Tian, Xiao-yun Huang, Qiang-sheng Wu, Nasrullah
    Sains Malaysiana, 2017;46:1687-1691.
    Arbuscular mycorrhizal fungi (AMF) actively colonize plant roots and thus enhance plant growth through different mechanisms. In the present study, trifoliate orange (Poncirus trifoliata) seedlings inoculated with Diversispora versiformis were subjected to 0 and 0.2 mmol/L sodium nitroprusside (SNP, a nitric oxide donor) treatments. After eight weeks, exogenous SNP considerably increased root mycorrhizal colonization by 25%, showing a positive stimulating effect of NO on mycorrhizal formation. Mycorrhizal inoculation significantly increased plant growth performance (height, stem diameter, leaf number and shoot and root dry weight) and root traits (length, projected area, surface area, volume and number of 2nd and 3rd order lateral roots) than non-mycorrhizal treatment and NO (exogenous SNP treatment) heavily strengthened the mycorrhizal effects. Moreover, NO and mycorrhization induced more fine root (0-0.5 cm) formation. There was an opposite changed trend in root sucrose and leaf and root glucose contents by SNP in AMF versus non-AMF seedlings. All these results implied that NO plays important roles in mycorrhizal formation and development and also accelerates mycorrhizal effects on plant growth and root development of trifoliate orange.
    Matched MeSH terms: Nitric Oxide Donors
  8. Fulltext Expression of Endothelin-1 and Endothelial Nitric Oxide Synthase in Normal and Preeclamptic Placentae
    Khaing A, Swe AT, Aung CL, Thwin MM, Sein MT
    Rev Bras Ginecol Obstet, 2022 Feb;44(2):125-132.
    PMID: 35213910 DOI: 10.1055/s-0042-1742317
    OBJECTIVE:  To investigate the expression of endothelin-1 (ET-1) and endothelial nitric oxide (NO) synthase (eNOS) in normal and preeclamptic (PE) placentae.

    METHODS:  The present cross-sectional analytical study was performed in normal and PE primigravidae (n = 10 in each group) who were admitted to the North Okkalapa General and Teaching Hospital from February 2019 to February 2020. Serum samples were collected immediately before delivery, and placental tissues were collected immediately after emergency or elective cesarean section. The expression of placental eNOS was measured by western blot, and the levels of ET-1 in placental tissue homogenates and in the serum were measured by enzyme-linked immunosorbent assay (ELISA).

    RESULTS:  The PE group had significantly higher serum levels of ET-1 (median: 116.56 pg/mL; IQR: 89.14-159.62 pg/mL) than the normal group (median: 60.02 pg/mL; IQR: 50.89-94.37 pg/mL) (p 

    Matched MeSH terms: Nitric Oxide Synthase Type III
  9. The effects of tempol on renal function and hemodynamics in cyclosporine-induced renal insufficiency rats
    Chia TY, Sattar MA, Abdulla MH, Rathore HA, Ahmad Fu, Kaur G, et al.
    Ren Fail, 2013 Aug;35(7):978-88.
    PMID: 23822648 DOI: 10.3109/0886022X.2013.809563
    This study investigated the effects of tempol, a superoxide dismutase (SOD) mimetic and L-NAME, a nitric oxide (NO) synthase inhibitor on the renal function and hemodynamics in cyclosporine A (CsA) induced renal insufficiency rats. Male Sprague-Dawley rats were treated with either vehicle (C), tempol (T, 1 mmol/L in drinking fluid), L-NAME (L, 1 mmol/L in drinking fluid), CsA (Cs, 25 mg/kg/day via gavage), CsA plus tempol (TCs), CsA plus L-NAME (LCs) or CsA plus a combination of tempol and L-NAME (TLCs) for 21 consecutive days. At the end of treatment regimen, the renal responses to noradrenaline (NA), phenylephrine (PE), methoxamine and angiotensin II (Ang II) were determined. Cs and LCs rats had lower creatinine clearance (0.7 ± 0.1 and 0.6 ± 0.5 vs. 1.3 ± 0.2 mL/min/kg) and fractional excretion of sodium (0.12 ± 0.02 and 0.17 ± 0.01 vs. 0.67 ± 0.04%) but higher systolic blood pressure (145 ± 2 and 178 ± 4 vs. 116 ± 2) compared to the control (all p 
    Matched MeSH terms: Nitric Oxide/antagonists & inhibitors; Nitric Oxide/metabolism
  10. Fulltext Nitrogen management is essential to prevent tropical oil palm plantations from causing ground-level ozone pollution
    Hewitt CN, MacKenzie AR, Di Carlo P, Di Marco CF, Dorsey JR, Evans M, et al.
    Proc Natl Acad Sci U S A, 2009 Nov 3;106(44):18447-51.
    PMID: 19841269 DOI: 10.1073/pnas.0907541106
    More than half the world's rainforest has been lost to agriculture since the Industrial Revolution. Among the most widespread tropical crops is oil palm (Elaeis guineensis): global production now exceeds 35 million tonnes per year. In Malaysia, for example, 13% of land area is now oil palm plantation, compared with 1% in 1974. There are enormous pressures to increase palm oil production for food, domestic products, and, especially, biofuels. Greater use of palm oil for biofuel production is predicated on the assumption that palm oil is an "environmentally friendly" fuel feedstock. Here we show, using measurements and models, that oil palm plantations in Malaysia directly emit more oxides of nitrogen and volatile organic compounds than rainforest. These compounds lead to the production of ground-level ozone (O(3)), an air pollutant that damages human health, plants, and materials, reduces crop productivity, and has effects on the Earth's climate. Our measurements show that, at present, O(3) concentrations do not differ significantly over rainforest and adjacent oil palm plantation landscapes. However, our model calculations predict that if concentrations of oxides of nitrogen in Borneo are allowed to reach those currently seen over rural North America and Europe, ground-level O(3) concentrations will reach 100 parts per billion (10(9)) volume (ppbv) and exceed levels known to be harmful to human health. Our study provides an early warning of the urgent need to develop policies that manage nitrogen emissions if the detrimental effects of palm oil production on air quality and climate are to be avoided.
    Matched MeSH terms: Nitric Oxide/analysis
  11. Fulltext Supplementation of 100% Flesh Watermelon [Citrullus lanatus (Thunb.) Matsum. and Nakai] Juice Improves Swimming Performance in Rats
    Ridwan R, Razak HRA, Adenan MI, Saad WMM
    Prev Nutr Food Sci, 2019 Mar;24(1):41-48.
    PMID: 31008095 DOI: 10.3746/pnf.2019.24.1.41
    Nutritional intervention of fruit juice supplementation is able to maximize exercise performance. Watermelon [Citrullus lanatus (Thunb.) Matsum. and Nakai] contains high L-citrulline content and consumption of watermelon juice may promote ergogenic effects. The aim of the present study was to investigate the role of 100% flesh watermelon juice and 100% rind watermelon juice supplementation for 14 days on swimming performance in rats. Twenty four male Sprague-Dawley rats were randomly divided into four groups: Cx group of rats supplemented with filtered tap water (negative control), L-cit group of rats supplemented with L-citrulline (positive control), FR group of rats supplemented with 100% flesh watermelon juice, and RR group of rats supplemented with 100% rind watermelon juice. Each group was supplemented for 14 days ad libitum prior to swimming exercise protocol. The rats were performed swimming exercise for 3 days and swimming time until exhaustion was measured. Plasma samples were collected to measure lactate concentration, ammonia concentration, and nitric oxide production. Rats supplemented with 100% flesh watermelon juice demonstrated significantly prolonged of swimming time until exhaustion, reduction of lactate and ammonia concentrations, and increased of nitric oxide production compared to Cx and L-cit groups (P<0.05). These findings postulate that supplementation with 100% flesh watermelon juice improves endurance in swimming performance.
    Matched MeSH terms: Nitric Oxide
  12. Fulltext Antioxidant Activities of 4-Methylumbelliferone Derivatives
    Al-Majedy YK, Al-Amiery AA, Kadhum AA, Mohamad AB
    PLoS One, 2016;11(5):e0156625.
    PMID: 27243231 DOI: 10.1371/journal.pone.0156625
    The synthesis of derivatives of 4-Methylumbelliferone (4-MUs), which are structurally interesting antioxidants, was performed in this study. The modification of 4-Methylumbelliferone (4-MU) by different reaction steps was performed to yield the target compounds, the 4-MUs. The 4-MUs were characterized by different spectroscopic techniques (Fourier transform infrared; FT-IR and Nuclear magnetic resonance; NMR) and micro-elemental analysis (CHNS). The in vitro antioxidant activity of the 4-MUs was evaluated in terms of their free radical scavenging activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH), Nitric oxide radical scavenging activity assay, chelating activity and their (FRAP) ferric-reducing antioxidant power, which were compared with a standard antioxidant. Our results reveal that the 4-MUs exhibit excellent radical scavenging activities. The antioxidant mechanisms of the 4-MUs were also studied. Density Function Theory (DFT)-based quantum chemical studies were performed with the basis set at 3-21G. Molecular models of the synthesized compounds were studied to understand the antioxidant activity. The electron levels, namely HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital), for these synthesized antioxidants were also studied.
    Matched MeSH terms: Nitric Oxide/chemistry
  13. Fulltext Angiotensin 1-7 Protects against Angiotensin II-Induced Endoplasmic Reticulum Stress and Endothelial Dysfunction via Mas Receptor
    Murugan D, Lau YS, Lau CW, Lau WC, Mustafa MR, Huang Y
    PLoS One, 2015;10(12):e0145413.
    PMID: 26709511 DOI: 10.1371/journal.pone.0145413
    Angiotensin 1-7 (Ang 1-7) counter-regulates the cardiovascular actions of angiotensin II (Ang II). The present study investigated the protective effect of Ang 1-7 against Ang II-induced endoplasmic reticulum (ER) stress and endothelial dysfunction. Ex vivo treatment with Ang II (0.5 μM, 24 hours) impaired endothelium-dependent relaxation in mouse aortas; this harmful effect of Ang II was reversed by co-treatment with ER stress inhibitors, l4-phenylbutyric acid (PBA) and tauroursodeoxycholic acid (TUDCA) as well as Ang 1-7. The Mas receptor antagonist, A779, antagonized the effect of Ang 1-7. The elevated mRNA expression of CHOP, Grp78 and ATF4 or protein expression of p-eIF2α and ATF6 (ER stress markers) in Ang II-treated human umbilical vein endothelial cells (HUVECs) and mouse aortas were blunted by co-treatment with Ang 1-7 and the latter effect was reversed by A779. Furthermore, Ang II-induced reduction in both eNOS phosphorylation and NO production was inhibited by Ang 1-7. In addition, Ang 1-7 decreased the levels of ER stress markers and augmented NO production in HUVECs treated with ER stress inducer, tunicamycin. The present study provides new evidence for functional antagonism between the two arms of the renin-angiotensin system in endothelial cells by demonstrating that Ang 1-7 ameliorates Ang II-stimulated ER stress to raise NO bioavailability, and subsequently preserves endothelial function.
    Matched MeSH terms: Nitric Oxide/biosynthesis; Nitric Oxide Synthase Type III/metabolism
  14. Fulltext Chemopreventive efficacy of Andrographis paniculata on azoxymethane-induced aberrant colon crypt foci in vivo
    Al-Henhena N, Ying RP, Ismail S, Najm W, Najm W, Khalifa SA, et al.
    PLoS One, 2014;9(11):e111118.
    PMID: 25390042 DOI: 10.1371/journal.pone.0111118
    Andrographis paniculata is a grass-shaped medicinal herb, traditionally used in Southeast Asia. The aim of this study was to evaluate the chemoprotective effects of A. paniculata on colorectal cancer. A. paniculata ethanol extract was tested on azoxymethane (AOM)-induced aberrant crypt foci (ACF) in vivo and in vitro. A. paniculata treated groups showed a significant reduction in the number of ACF of the treated rats. Microscopically, ACF showed remarkably elongated and stratified cells, and depletion of the submucosal glands of AOM group compared to the treated groups. Histologically, staining showed slightly elevated masses above the surrounding mucosa with oval or slit-like orifices. Immunohistochemically, expression of proliferating cell nuclear antigen (PCNA) and β-catenin protein were down-regulated in the A. paniculata treated groups compared to the AOM group. When colon tissue was homogenized, malondialdehyde (MDA) and nitric oxide (NO) levels were significantly decreased, whereas superoxide dismutase (SOD) activity was increased in the treated groups compared to the AOM group. A. paniculata ethanol extract showed antioxidant and free radical scavenging activity, as elucidated by the measure of oxidative stress markers. Further, the active fractions were assessed against cell lines of CCD841 and HT29 colon cancer cells.
    Matched MeSH terms: Nitric Oxide/metabolism
  15. Fulltext Gastroprotection studies of Schiff base zinc (II) derivative complex against acute superficial hemorrhagic mucosal lesions in rats
    Golbabapour S, Gwaram NS, Hassandarvish P, Hajrezaie M, Kamalidehghan B, Abdulla MA, et al.
    PLoS One, 2013;8(9):e75036.
    PMID: 24058648 DOI: 10.1371/journal.pone.0075036
    The study was carried out to assess the gastroprotective effect of the zinc (II) complex against ethanol-induced acute hemorrhagic lesions in rats.
    Matched MeSH terms: Nitric Oxide/metabolism
  16. Fulltext In vitro and in vivo anti-inflammatory activity of 17-O-acetylacuminolide through the inhibition of cytokines, NF-κB translocation and IKKβ activity
    Achoui M, Appleton D, Abdulla MA, Awang K, Mohd MA, Mustafa MR
    PLoS One, 2010;5(12):e15105.
    PMID: 21152019 DOI: 10.1371/journal.pone.0015105
    17-O-acetylacuminolide (AA), a diterpenoid labdane, was isolated for the first time from the plant species Neouvaria foetida. The anti-inflammatory effects of this compound were studied both in vitro and in vivo.
    Matched MeSH terms: Nitric Oxide/metabolism; Nitric Oxide Synthase Type II/metabolism
  17. Fulltext Preventive Effects of Tocotrienol on Stress-Induced Gastric Mucosal Lesions and Its Relation to Oxidative and Inflammatory Biomarkers
    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.
    Matched MeSH terms: Nitric Oxide/metabolism
  18. Fulltext Attenuation of Inflammatory Mediators (TNF-α and Nitric Oxide) and Up-Regulation of IL-10 by Wild and Domesticated Basidiocarps of Amauroderma rugosum (Blume & T. Nees) Torrend in LPS-Stimulated RAW264.7 Cells
    Chan PM, Tan YS, Chua KH, Sabaratnam V, Kuppusamy UR
    PLoS One, 2015;10(10):e0139593.
    PMID: 26427053 DOI: 10.1371/journal.pone.0139593
    Amauroderma rugosum, commonly known as "Jiǎzī" in China, is a wild mushroom traditionally used by the Chinese to reduce inflammation, to treat diuretic and upset stomach, and to prevent cancer. It is also used by the indigenous communities in Malaysia to prevent epileptic episodes and incessant crying by babies. The aim of this study was to compare the wild and domesticated basidiocarps of A. rugosum for antioxidant and in vitro anti-inflammatory effects in LPS-stimulated RAW264.7 cells. The wild basidiocarps of A. rugosum were collected from the Belum Forest, Perak, Malaysia and the domesticated basidiocarps of A. rugosum were cultivated in the mushroom house located in the University of Malaya, Kuala Lumpur, Malaysia. Both the wild and domesticated basidiocarps were subjected to ethanolic extraction and the extracts were tested for antioxidant and anti-inflammatory activities. In this study, the crude ethanolic extract of wild (WB) and domesticated (DB) basidiocarps of A. rugosum had comparable total phenolic content and DPPH scavenging activity. However, WB (EC50 = 222.90 μg/mL) displayed a better ABTS cation radical scavenging activity than DB (EC50 = 469.60 μg/mL). Both WB and DB were able to scavenge nitric oxide (NO) radical and suppress the NO production in LPS-stimulated RAW264.7 cells and this effect was mediated through the down-regulation of inducible nitric oxide synthase (iNOS) gene. In addition, both WB and DB caused down-regulation of the inflammatory gene TNF-α and the up-regulation of the anti-inflammatory gene IL-10. There was no inhibitory effect of WB and DB on nuclear translocation of NF-κB p65. In conclusion, the wild and domesticated basidiocarps of A. rugosum possessed antioxidant and in vitro anti-inflammatory properties. WB and DB inhibited downstream inflammatory mediators (TNF-α and NO) and induced anti-inflammatory cytokine IL-10 production. No inhibitory effects shown on upstream nuclear translocation of NF-κB p65. WB and DB exhibited antioxidant activity and attenuation of proinflammatory mediators and therefore, A. rugosum may serve as a potential therapeutic agent in the management of inflammation.
    Matched MeSH terms: Nitric Oxide/metabolism*
  19. Fulltext Cystathione gamma lyase/Hydrogen Sulphide Pathway Up Regulation Enhances the Responsiveness of α1A and α1B-Adrenoreceptors in the Kidney of Rats with Left Ventricular Hypertrophy
    Ahmad A, Sattar MA, Azam M, Abdulla MH, Khan SA, Hashmi F, et al.
    PLoS One, 2016;11(5):e0154995.
    PMID: 27191852 DOI: 10.1371/journal.pone.0154995
    The purpose of the present study was to investigate the interaction between H2S and NO (nitric oxide) in the kidney and to evaluate its impact on the functional contribution of α1A and α1B-adrenoreceptors subtypes mediating the renal vasoconstriction in the kidney of rats with left ventricular hypertrophy (LVH). In rats the LVH induction was by isoprenaline administration and caffeine in the drinking water together with intraperitoneal administration of H2S. The responsiveness of α1A and α1B to exogenous noradrenaline, phenylephrine and methoxaminein the absence and presence of 5-methylurapidil (5-MeU) and chloroethylclonidine (CEC) was studied. Cystathione gamma lyase (CSE), cystathione β synthase (CBS), 3-mercaptopyruvate sulphar transferase (3-MST) and endothelial nitric oxide synthase (eNOS) were quantified. There was significant up regulation of CSE and eNOS in the LVH-H2S compared to the LVH group (P<0.05). Baseline renal cortical blood perfusion (RCBP) was increased (P<0.05) in the LVH-H2S compared to the LVH group. The responsiveness of α1A-adrenergic receptors to adrenergic agonists was increased (P<0.05) after administration of low dose 5-Methylurapidil in the LVH-H2S group while α1B-adrenergic receptors responsiveness to adrenergic agonists were increased (P<0.05) by both low and high dose chloroethylclonidine in the LVH-H2S group. Treatment of LVH with H2S resulted in up-regulation of CSE/H2S, CBS, and 3-MST and eNOS/NO/cGMP pathways in the kidney. These up regulation of CSE/H2S, CBS, and 3-MST and eNOS/NO/cGMP pathways enhanced the responsiveness of α1A and α1B-adrenoreceptors subtypes to adrenergic agonists in LVH-H2S. These findings indicate an important role for H2S in modulating deranged signalling in the renal vasculature resulting from LVH development.
    Matched MeSH terms: Nitric Oxide/metabolism; Nitric Oxide Synthase Type III/metabolism
  20. Fulltext Chronic treatment with paeonol improves endothelial function in mice through inhibition of endoplasmic reticulum stress-mediated oxidative stress
    Choy KW, Lau YS, Murugan D, Mustafa MR
    PLoS One, 2017;12(5):e0178365.
    PMID: 28562691 DOI: 10.1371/journal.pone.0178365
    Endoplasmic reticulum (ER) stress leads to endothelial dysfunction which is commonly associated in the pathogenesis of several cardiovascular diseases. We explored the vascular protective effects of chronic treatment with paeonol (2'-hydroxy-4'-methoxyacetophenone), the major compound from the root bark of Paeonia suffruticosa on ER stress-induced endothelial dysfunction in mice. Male C57BL/6J mice were injected intraperitoneally with ER stress inducer, tunicamycin (1 mg/kg/week) for 2 weeks to induce ER stress. The animals were co-administered with or without paeonol (20 mg/kg/oral gavage), reactive oxygen species (ROS) scavenger, tempol (20 mg/kg/day) or ER stress inhibitor, tauroursodeoxycholic acid (TUDCA, 150 mg/kg/day) respectively. Blood pressure and body weight were monitored weekly and at the end of treatment, the aorta was isolated for isometric force measurement. Protein associated with ER stress (GRP78, ATF6 and p-eIF2α) and oxidative stress (NOX2 and nitrotyrosine) were evaluated using Western blotting. Nitric oxide (NO) bioavailability were determined using total nitrate/nitrite assay and western blotting (phosphorylation of eNOS protein). ROS production was assessed by en face dihydroethidium staining and lucigenin-enhanced chemiluminescence assay, respectively. Our results revealed that mice treated with tunicamycin showed an increased blood pressure, reduction in body weight and impairment of endothelium-dependent relaxations (EDRs) of aorta, which were ameliorated by co-treatment with either paeonol, TUDCA and tempol. Furthermore, paeonol reduced the ROS level in the mouse aorta and improved NO bioavailability in tunicamycin treated mice. These beneficial effects of paeonol observed were comparable to those produced by TUDCA and tempol, suggesting that the actions of paeonol may involve inhibition of ER stress-mediated oxidative stress pathway. Taken together, the present results suggest that chronic treatment with paeonol preserved endothelial function and normalized blood pressure in mice induced by tunicamycin in vivo through the inhibition of ER stress-associated ROS.
    Matched MeSH terms: Nitric Oxide/metabolism
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