Displaying publications 41 - 60 of 831 in total

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  1. Fulltext Alpha-tomatine induces apoptosis and inhibits nuclear factor-kappa B activation on human prostatic adenocarcinoma PC-3 cells
    Lee ST, Wong PF, Cheah SC, Mustafa MR
    PLoS One, 2011;6(4):e18915.
    PMID: 21541327 DOI: 10.1371/journal.pone.0018915
    Alpha-tomatine (α-tomatine) is the major saponin in tomato (Lycopersicon esculentum). This study investigates the chemopreventive potential of α-tomatine on androgen-independent human prostatic adenocarcinoma PC-3 cells.
    Matched MeSH terms: Dose-Response Relationship, Drug
  2. Alpha1A- and alpha1D-adrenoceptors are the major functional subtypes of renal alpha1-adrenoceptors in streptozotocin-induced diabetic and normal Sprague-Dawley rats
    Armenia, Sattar MA, Abdullah NA, Khan MA, Johns EJ
    Auton Autacoid Pharmacol, 2008 Jan;28(1):1-10.
    PMID: 18257746 DOI: 10.1111/j.1474-8673.2007.00412.x
    1 The present study investigated the effect of streptozotocin-induced diabetes on alpha(1)-adrenoceptor subtypes in rat renal resistance vessels. 2 Studies on renal haemodynamics were carried out 7 days after the last streptozotocin. Changes in renal blood flow were recorded in response to electrical stimulation of the renal nerve (RNS) and a range of adrenergic agonists; noradrenaline (NA), phenylephrine (PE) and methoxamine (MTX), either in the absence or the presence of nitrendipine (Nit), 5-methylurapidil (MEU), chlorethylclonidine (CEC) or BMY 7378. 3 In non-diabetic animals, Nit, MEU and BMY 7378 significantly attenuated renal vasoconstriction induced by adrenergic agonists, while CEC showed a significant accentuation in RNS-induced responses without having a significant effect on responses to adrenergic agonists. In diabetic rats, renal vasoconstriction was also significantly reduced in Nit-, MEU- and BMY 7378-treated groups and CEC potentiated RNS-induced contractions caused a change similar to that observed in non-diabetic rats. BMY 7378 significantly (P < 0.05) attenuated the PE- and MTX-induced vasoconstrictions but did not cause any significant (P > 0.05) alteration in the RNS- and NA-induced responses. 4 The results showed functional co-existence of alpha(1A)- and alpha(1D)-adrenoceptors in the renal vasculature of SD rats irrespective of the presence of diabetes. A possible minor contribution of prejunctional alpha-adrenoceptor subtype has also been suggested in either experimental group, particularly possible functional involvement of alpha(1B)-adrenoceptor subtypes in non-diabetic SD rats.
    Matched MeSH terms: Dose-Response Relationship, Drug
  3. Alstoscholactine and Alstolaxepine, Monoterpenoid Indole Alkaloids with γ-Lactone-Bridged Cycloheptane and Oxepane Moieties from Alstonia scholaris
    Krishnan P, Lee FK, Chong KW, Mai CW, Muhamad A, Lim SH, et al.
    Org. Lett., 2018 12 21;20(24):8014-8018.
    PMID: 30543301 DOI: 10.1021/acs.orglett.8b03592
    Two new monoterpenoid indole alkaloids, alstoscholactine (1) and alstolaxepine (2), were isolated from Alstonia scholaris. Compound 1 represents a rearranged stemmadenine alkaloid with an unprecedented C-6-C-19 connectivity, whereas compound 2 represents a 6,7- seco-angustilobine B-type alkaloid incorporating a rare γ-lactone-bridged oxepane ring system. Their structures and absolute configurations were determined by spectroscopic analyses. Compound 1 was successfully semisynthesized from 19 E-vallesamine. Compound 2 induced marked vasorelaxation in rat isolated aortic rings precontracted with phenylephrine.
    Matched MeSH terms: Dose-Response Relationship, Drug
  4. Fulltext Alterations of microRNA expression patterns in human cervical carcinoma cells (Ca Ski) toward 1'S-1'-acetoxychavicol acetate and cisplatin
    Phuah NH, In LL, Azmi MN, Ibrahim H, Awang K, Nagoor NH
    Reprod Sci, 2013 May;20(5):567-78.
    PMID: 23012319 DOI: 10.1177/1933719112459220
    The aims of this study were to investigate the combined effects of a natural compound 1'S-1'-acetoxychavicol acetate (ACA) with cisplatin (CDDP) on HPV-positive human cervical carcinoma cell lines (Ca Ski-low cisplatin sensitivity and HeLa-high cisplatin sensitivity), and to identify microRNAs (miRNAs) modulated in response toward ACA and/or CDDP. It was revealed that both ACA and CDDP induced dose- and time-dependent cytotoxicity when used as a stand-alone agent, while synergistic effects were observed when used in combination with a combination index (CI) value of 0.74 ± 0.01 and 0.85 ± 0.01 in Ca Ski and HeLa cells, respectively. A total of 25 miRNAs were found to be significantly differentially expressed in response to ACA and/or CDDP. These include hsa-miR-138, hsa-miR-210, and hsa-miR-744 with predicted gene targets involved in signaling pathways regulating apoptosis and cell cycle progression. In conclusion, ACA acts as a chemosensitizer which synergistically potentiates the cytotoxic effect of CDDP in cervical cancer cells. The altered miRNA expression upon administration of ACA and/or CDDP suggests that miRNAs play an important role in anticancer drug responses, which can be manipulated for therapeutic purposes.
    Matched MeSH terms: Dose-Response Relationship, Drug
  5. Amplifying the manganese scavenging potential of Streptococcus zooepidemicus to reactive oxygen species during production of hyaluronic acid
    Mashitah MD, Masitah H, Ramachandran KB
    Med J Malaysia, 2004 May;59 Suppl B:59-60.
    PMID: 15468818
    Streptococcus zooepidemicus (SZ) is an aerotolerant bacteria and its ability to survive under reactive oxidant challenge raises the question of the existence of a defense system. Thus growth, hyaluronic acid (HA) and hydrogen peroxide (H2O2) production by SZ in the presence of increasing concentration of Mn2+ were studied. The results suggested that the tested strain supported growth and HA production in cultures treated with 1 and 10 mM of Mn2+ regardless of H2O2 presence in the medium. This showed that SZ have acquired elaborate defense mechanisms to scavenge oxygen toxicity and thus protect cells from direct and indirect effect of this radical. In contrast, cells treated with 25 mM Mn2+ were sensitive, in which, the HA production was reduced considerably. Thus showing that the oxygen scavenger systems of the cells may be fully saturated at this concentration.
    Matched MeSH terms: Dose-Response Relationship, Drug
  6. An expedient, ionic liquid mediated multi-component synthesis of novel piperidone grafted cholinesterase enzymes inhibitors and their molecular modeling study
    Basiri A, Murugaiyah V, Osman H, Kumar RS, Kia Y, Awang KB, et al.
    Eur J Med Chem, 2013 Sep;67:221-9.
    PMID: 23871902 DOI: 10.1016/j.ejmech.2013.06.054
    Series of hitherto unreported piperidone grafted pyridopyrimidines synthesized through ionic liquid mediated multi-component reaction. These compounds were evaluated for their inhibitory activities against AChE and BChE enzymes. All the compounds displayed considerable potency against AChE with IC50 values ranging from 0.92 to 9.11 μM, therein compounds 6a, 6h and 6i displayed superior enzyme inhibitory activities compared to standard drug with IC50 values of 0.92, 1.29 and 2.07 μM. Remarkably, all the compounds displayed higher BChE inhibitory activity compared to galantamine with IC50 values of 1.89-8.13 μM. Molecular modeling, performed for the most active compounds using three dimensional crystal structures of TcAChE and hBChE, disclosed binding template of these inhibitors into the active site of their respective enzymes.
    Matched MeSH terms: Dose-Response Relationship, Drug
  7. Anaerobic respiration: In vitro efficacy of Nitazoxanide against mitochondriate Acanthamoeba castellanii of the T4 genotype
    Aqeel Y, Siddiqui R, Farooq M, Khan NA
    Exp Parasitol, 2015 Oct;157:170-6.
    PMID: 26297676 DOI: 10.1016/j.exppara.2015.08.007
    Acanthamoeba is an opportunistic protist pathogen that is responsible for serious human and animal infection. Being one of the most frequently isolated protists from the environment, it is likely that it readily encounters microaerophilic environments. For respiration under anaerobic or low oxygen conditions in several amitochondriate protists, decarboxylation of pyruvate is catalyzed by pyruvate ferredoxin oxidoreductase instead of pyruvate dehydrogenase. In support, Nitazoxanide, an inhibitor of pyruvate ferredoxin oxidoreductase, is effective and non-mutagenic clinically against a range of amitochondriate protists, Giardia intestinalis, Entamoeba histolytica and Trichomonas vaginalis. The overall aim of the present study was to determine in vitro efficacy of Nitazoxanide against Acanthamoeba castellanii. At micromolar concentrations, the findings revealed that Nitazoxanide neither affected A. castellanii growth or viability nor amoeba-mediated host cell monolayer damage in vitro or extracellular proteolytic activities. Similarly, microaerophilic conditions alone had no significant effects. In contrast, microaerophilic conditions together with Nitazoxanide showed amoebicidal effects and inhibited A. castellanii-mediated host cell monolayer damage as well as extracellular proteases. Using encystation assays, it was observed that Nitazoxanide inhibited trophozoite transformation into cysts both under aerophilic and microaerophilic conditions. Furthermore, pre-treatment of cysts with Nitazoxanide inhibited A. castellanii excystation. These findings are important in the identification of potential targets that could be useful against parasite-specific respiration as well as to understand the basic biology of the life cycle of Acanthamoeba.
    Matched MeSH terms: Dose-Response Relationship, Drug
  8. Analgesic and antipyretic effects of Sansevieria trifasciata leaves
    Anbu JS, Jayaraj P, Varatharajan R, Thomas J, Jisha J, Muthappan M
    Afr J Tradit Complement Altern Med, 2009 Jul 03;6(4):529-33.
    PMID: 20606773
    The ethanol and water extracts of Sansevieria trifasciata leaves showed dose-dependent and significant (P < 0.05) increase in pain threshold in tail-immersion test. Moreover, both the extracts (100 - 200 mg/kg) exhibited a dose-dependent inhibition of writhing and also showed a significant (P < 0.001) inhibition of both phases of the formalin pain test. The ethanol extract (200 mg/kg) significantly (P < 0.01) reversed yeast-induced fever. Preliminary phytochemical screening of the extracts showed the presence of alkaloids, flavonoids, saponins, glycosides, terpenoids, tannins, proteins and carbohydrates.
    Matched MeSH terms: Dose-Response Relationship, Drug
  9. Analgesic use and chronic renal disease in patients with headache
    Rahman A, Segasothy M, Samad SA, Zulfiqar A, Rani M
    Headache, 1993 Sep;33(8):442-5.
    PMID: 8262786
    The pattern of analgesic use, abuse and incidence of analgesic-associated nephropathy in 79 patients with chronic headache was studied. Sixty-eight of these patients had migraine. Most patients had consumed a combination of analgesics (81%) while 19% had taken single analgesics for their headache. Nonsteroidal anti-inflammatory drugs were the most commonly used analgesics (96.2%) followed by paracetamol (70.9%) and aspirin, phenacetin and caffeine compounds (5.1%). Mefenamic acid was the commonest nonsteroidal anti-inflammatory drug consumed (97.4%). Analgesic abuse which was defined as a minimum total of 1 kg of analgesics such as paracetamol or aspirin, phenacetin and caffeine compounds or 400 capsules/tablets of nonsteroidal anti-inflammatory drugs was noted in 65 patients. Nonsteroidal anti-inflammatory drugs were the most commonly abused analgesics (89.2%) followed by paracetamol (38.5%). Forty-five of the 65 analgesic abusers had an intravenous urogram or ultrasound performed and renal papillary necrosis was documented in one patient. Three (4.6%) of the analgesic abusers had mildly raised serum creatinine levels. Mild proteinuria of less than 1 gm/litre was present in 27.7% of abusers. In conclusion, although analgesic use and abuse is common in patients with chronic headache, the short term incidence of analgesic-associated nephropathy (2.2%) and renal impairment (4.6%) was low. Prolonged observations will be necessary to ascertain the safety of these drugs for long term use.
    Matched MeSH terms: Dose-Response Relationship, Drug
  10. Fulltext Analogues of 2'-hydroxychalcone with modified C4-substituents as the inhibitors against human acetylcholinesterase
    Sukumaran SD, Nasir SB, Tee JT, Buckle MJC, Othman R, Rahman NA, et al.
    J Enzyme Inhib Med Chem, 2021 Dec;36(1):130-137.
    PMID: 33243025 DOI: 10.1080/14756366.2020.1847100
    A series of C4-substituted tertiary nitrogen-bearing 2'-hydroxychalcones were designed and synthesised based on a previous mixed type acetylcholinesterase inhibitor. Majority of the 2'-hydroxychalcone analogues displayed a better inhibition against acetylcholinesterase (AChE) than butyrylcholinesterase (BuChE). Among them, compound 4c was identified as the most potent AChE inhibitor (IC50: 3.3 µM) and showed the highest selectivity for AChE over BuChE (ratio >30:1). Molecular docking studies suggested that compound 4c interacts with both the peripheral anionic site (PAS) and catalytic anionic site (CAS) regions of AChE. ADMET analysis confirmed the therapeutic potential of compound 4c based on its blood-brain barrier penetrating. Overall, the results suggest that this 2'-hydroxychalcone deserves further investigation into the therapeutic lead for Alzheimer's disease (AD).
    Matched MeSH terms: Dose-Response Relationship, Drug
  11. Andrographis paniculata ameliorates carbon tetrachloride (CCl(4))-dependent hepatic damage and toxicity: diminution of oxidative stress
    Koh PH, Mokhtar RA, Iqbal M
    Redox Rep., 2011;16(3):134-43.
    PMID: 21801496 DOI: 10.1179/1351000211Y.0000000003
    Andrographis paniculata (hempedu bumi) is a plant that possesses many medicinal values in treating several diseases and for health care maintenance. However, its hepatoprotective activity and mechanism of action have not been fully investigated. Therefore, this study aimed to evaluate the hepatoprotective effects of A. paniculata and its mechanism of action in rats. Carbon tetrachloride (CCl(4)) challenge of rats at a dose of 1.2 ml/kg body weight-induced oxidative stress in the liver. This was evidenced by augmentation in lipid peroxidation, which was accompanied by a decrease in the activities of antioxidant enzymes and depletion in the level of reduced glutathione (P < 0.05). Parrallel to these changes, CCl(4) challenge too, enhanced hepatic damage as evidenced by sharp increase in serum transaminases (e.g. alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase) (P < 0.05). Additionally, the impairment of liver function corresponded to histolopathological changes. However, most of these changes were reversed in a dose-dependent fashion by pre-treatment of animals with A. paniculata (P < 0.05). The ability of A. paniculata to scavenge the 2,2-Diphenyl-2-picrylhydrazyl radical was determined through its EC(50) value. The EC(50) value of A. paniculata was 583.60 ± 4.25 µg/ml. In addition, A. paniculata was found to contain 65.37 ± 1.20 mg/g total phenolics expressed as gallic acid equivalent. From these studies, it is concluded that A. paniculata could be used as a hepatoprotective agent and possesses the potential to treat or prevent degenerative diseases where oxidative stress is implicated.
    Matched MeSH terms: Dose-Response Relationship, Drug
  12. Andrographolide and 14-deoxy-11, 12-didehydroandrographolide inhibit cytochrome P450s in HepG2 hepatoma cells
    Ooi JP, Kuroyanagi M, Sulaiman SF, Muhammad TS, Tan ML
    Life Sci, 2011 Feb 28;88(9-10):447-54.
    PMID: 21219911 DOI: 10.1016/j.lfs.2010.12.019
    Cytochrome P450 (CYP) enzymes have been implicated in a large number of preventable drug-herb interactions. Andrographis paniculata Nees, a tropical herb widely used for various health conditions contains two major diterpenoids, andrographolide and 14-Deoxy-11, 12-Didehydroandrographolide. These compounds were evaluated systematically for their effects on CYP1A2, CYP2D6 and CYP3A4 expressions in HepG2 cells.
    Matched MeSH terms: Dose-Response Relationship, Drug
  13. Andrographolide inhibits growth of acute promyelocytic leukaemia cells by inducing retinoic acid receptor-independent cell differentiation and apoptosis
    Manikam SD, Manikam ST, Stanslas J
    J Pharm Pharmacol, 2009 Jan;61(1):69-78.
    PMID: 19126299 DOI: 10.1211/jpp/61.01.0010
    The growth inhibiting potential of andrographolide was evaluated in three acute promyelocytic leukaemia cell line models (HL-60, NB4 and all-trans retinoic acid (ATRA)-resistant NB4-R2).
    Matched MeSH terms: Dose-Response Relationship, Drug
  14. Angiotensin-I Converting Enzyme (ACE) Inhibitory and Anti-Hypertensive Effect of Protein Hydrolysate from Actinopyga lecanora (Sea Cucumber) in Rats
    Sadegh Vishkaei M, Ebrahimpour A, Abdul-Hamid A, Ismail A, Saari N
    Mar Drugs, 2016 Sep 30;14(10).
    PMID: 27706040
    Food protein hydrolysates are known to exhibit angiotensin converting enzyme (ACE) inhibitory properties and can be used as a novel functional food for prevention of hypertension. This study evaluated the ACE inhibitory potentials of Actinopyga lecanora proteolysate (ALP) in vivo. The pre-fed rats with ALP at various doses (200, 400, 800 mg/kg body weight) exhibited a significant (p ≤ 0.05) suppression effect after inducing hypertension. To determine the optimum effective dose that will produce maximal reduction in blood pressure, ALP at three doses was fed to the rats after inducing hypertension. The results showed that the 800 mg/kg body weight dose significantly reduced blood pressure without noticeable negative physiological effect. In addition, there were no observable changes in the rats' heart rate after oral administration of the ALP. It was concluded that Actinopyga lecanora proteolysate could potentially be used for the development of functional foods and nutraceuticals for prevention and treatment of hypertension.
    Matched MeSH terms: Dose-Response Relationship, Drug
  15. Fulltext Annatto-Derived Tocotrienol Promotes Mineralization of MC3T3-E1 Cells by Enhancing BMP-2 Protein Expression via Inhibiting RhoA Activation and HMG-CoA Reductase Gene Expression
    Wan Hasan WN, Chin KY, Abd Ghafar N, Soelaiman IN
    Drug Des Devel Ther, 2020;14:969-976.
    PMID: 32184566 DOI: 10.2147/DDDT.S224941
    PURPOSE: Annatto-derived tocotrienol (AnTT) has been shown to improve bone formation in animal models of osteoporosis and promote differentiation of pre-osteoblastic cells. However, the mechanism of action of AnTT in achieving these effects is unclear. This study aims to investigate the mechanism of action of AnTT on MC3T3-E1 pre-osteoblasts via the mevalonate pathway.

    METHODS: Murine pre-osteoblastic cells, MC3T3-E1, were cultured with the density of 1 × 104 cells/mL and treated with 4 concentrations of AnTT (0.001-1 µg/mL). Expression of HMG-CoA reductase (HMGR) gene was carried out using qPCR after treatment with AnTT for 21 days. RhoA activation and bone morphogenetic protein-2 (BMP-2) were measured using immunoassay after 9 and 15 days of AnTT treatment. Lovastatin was used as the positive control. Mineralized nodules were detected using Von Kossa staining after 21 days of AnTT treatment.

    RESULTS: The results showed that HMGR was up-regulated in the lovastatin group on day 9 and 21 compared to the control. Lovastatin also inhibited RhoA activation (day 9 and 15) and increased BMP-2 protein (day 15). On the other hand, AnTT at 0.001 μg/mL (day 3) and 0.1 μg/mL (day 21) significantly down-regulated HMGR gene expression compared to the control. On day 21, HMGR gene expression was significantly reduced in all groups compared to day 15. AnTT at 0.1 μg/mL significantly decreased RhoA activation on day 9 compared to the control. AnTT at 1 μg/mL significantly increased BMP-2 protein on day 15 compared to the control (P<0.05). Mineralized calcium nodules were more abundant in AnTT treated groups compared to the control on day 21.

    CONCLUSION: AnTT suppresses the mevalonate pathway by downregulating HMGR gene expression and inhibiting RhoA activation, leading to increased BMP-2 protein in MC3T3-E1 cells. This explains the stimulating effects of AnTT on osteoblast mineralization.

    Matched MeSH terms: Dose-Response Relationship, Drug
  16. Fulltext Annatto-derived tocotrienol stimulates osteogenic activity in preosteoblastic MC3T3-E1 cells: a temporal sequential study
    Wan Hasan WN, Abd Ghafar N, Chin KY, Ima-Nirwana S
    Drug Des Devel Ther, 2018;12:1715-1726.
    PMID: 29942115 DOI: 10.2147/DDDT.S168935
    PURPOSE: Annatto-derived tocotrienol (AnTT) has been shown to improve bone formation in animal models of osteoporosis. However, detailed studies of the effects of AnTT on preosteoblastic cells were limited. This study was conducted to investigate the osteogenic effect of AnTT on preosteoblast MC3T3-E1 cells in a time-dependent manner.

    MATERIALS AND METHODS: Murine MC3T3-E1 preosteoblastic cells were cultured in the different concentrations of AnTT (0.001-1 µg/mL) up to 24 days. Expression of osteoblastic differentiation markers was measured by qPCR (osterix [OSX], collagen 1 alpha 1 [COL1α1], alkaline phosphatase [ALP], and osteocalcin [OCN]) and by fluorometric assay for ALP activity. Detection of collagen and mineralized nodules was done via Direct Red staining and Alizarin Red staining, respectively.

    RESULTS: The results showed that osteoblastic differentiation-related genes, such as OSX, COL1α1, ALP, and OCN, were significantly increased in the AnTT-treated groups compared to the vehicle group in a time-dependent manner (P<0.05). Type 1 collagen level was increased from day 3 to day 15 in the AnTT-treated groups, while ALP activity was increased from day 9 to day 21 in the AnTT-treated groups (P<0.05). Enhanced mineralization was observed in the AnTT-treated groups via increasing Alizarin Red staining from day 3 to day 21 (P<0.05).

    CONCLUSION: Our results suggest that AnTT enhances the osteogenic activity by promoting the bone formation-related genes and proteins in a temporal and sequential manner.

    Matched MeSH terms: Dose-Response Relationship, Drug
  17. 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
  18. Anti-allergic activity of 2,4,6-trihydroxy-3-geranylacetophenone (tHGA) via attenuation of IgE-mediated mast cell activation and inhibition of passive systemic anaphylaxis
    Tan JW, Israf DA, Harith HH, Md Hashim NF, Ng CH, Shaari K, et al.
    Toxicol Appl Pharmacol, 2017 03 15;319:47-58.
    PMID: 28167223 DOI: 10.1016/j.taap.2017.02.002
    tHGA, a geranyl acetophenone compound originally isolated from a local shrub called Melicope ptelefolia, has been previously reported to prevent ovalbumin-induced allergic airway inflammation in a murine model of allergic asthma by targeting cysteinyl leukotriene synthesis. Mast cells are immune effector cells involved in the pathogenesis of allergic diseases including asthma by releasing cysteinyl leukotrienes. The anti-asthmatic properties of tHGA could be attributed to its inhibitory effect on mast cell degranulation. As mast cell degranulation is an important event in allergic responses, this study aimed to investigate the anti-allergic effects of tHGA in cellular and animal models of IgE-mediated mast cell degranulation. For in vitro model of IgE-mediated mast cell degranulation, DNP-IgE-sensitized RBL-2H3 cells were pre-treated with tHGA before challenged with DNP-BSA to induce degranulation. For IgE-mediated passive systemic anaphylaxis, Sprague Dawley rats were sensitized by intraperitoneal injection of DNP-IgE before challenged with DNP-BSA. Both in vitro and in vivo models showed that tHGA significantly inhibited the release of preformed mediators (β-hexosaminidase and histamine) as well as de novo mediators (interleukin-4, tumour necrosis factor-α, prostaglandin D2 and leukotriene C4). Pre-treatment of tHGA also prevented IgE-challenged RBL-2H3 cells and peritoneal mast cells from undergoing morphological changes associated with mast cell degranulation. These findings indicate that tHGA possesses potent anti-allergic activity via attenuation of IgE-mediated mast cell degranulation and inhibition of IgE-mediated passive systemic anaphylaxis. Thus, tHGA may have the potential to be developed as a mast cell stabilizer for the treatment of allergic diseases in the future.
    Matched MeSH terms: Dose-Response Relationship, Drug
  19. Anti-angiogenic quassinoid-rich fraction from Eurycoma longifolia modulates endothelial cell function
    Al-Salahi OS, Kit-Lam C, Majid AM, Al-Suede FS, Mohammed Saghir SA, Abdullah WZ, et al.
    Microvasc Res, 2013 Nov;90:30-9.
    PMID: 23899415 DOI: 10.1016/j.mvr.2013.07.007
    Targeting angiogenesis could be an excellent strategy to combat angiogenesis-dependent pathophysiological conditions such as cancer, rheumatoid arthritis, obesity, systemic lupus erythematosus, psoriasis, proliferative retinopathy and atherosclerosis. Recently a number of clinical investigations are being undertaken to assess the potential therapeutic application of various anti-angiogenic agents. Many of these angiogenesis inhibitors are directed against the functions of endothelial cells, which are considered as the building blocks of blood vessels. Similarly, roots of a traditional medicinal plant, Eurycoma longifolia, can be used as an alternative treatment to prevent and treat the angiogenesis-related diseases. In the present study, antiangiogenic potential of partially purified quassinoid-rich fraction (TAF273) of E. longifolia root extract was evaluated using ex vivo and in vivo angiogenesis models and the anti-angiogenic efficacy of TAF273 was investigated in human umbilical vein endothelial cells (HUVEC). TAF273 caused significant suppression in sprouting of microvessels in rat aorta with IC50 11.5μg/ml. TAF273 (50μg/ml) showed remarkable inhibition (63.13%) of neovascularization in chorioallantoic membrane of chick embryo. Tumor histology also revealed marked reduction in extent of vascularization. In vitro, TAF273 significantly inhibited the major angiogenesis steps such as proliferation, migration and differentiation of HUVECs. Phytochemical analysis revealed high content of quassinoids in TAF273. Specially, HPLC characterization showed that TAF273 is enriched with eurycomanone, 13α(21)-epoxyeurycomanone and eurycomanol. These results demonstrated that the antiangiogenic activity of TAF273 may be due to its inhibitory effect on endothelial cell proliferation, differentiation and migration which could be attributed to the high content of quassinoids in E. longifolia.
    Matched MeSH terms: Dose-Response Relationship, Drug
  20. Anti-hyperglycemic potential of Hyptis verticillata jacq in streptozotocin-induced diabetic rats
    Ogar I, Egbung GE, Nna VU, Iwara IA, Itam E
    Biomed Pharmacother, 2018 Nov;107:1268-1276.
    PMID: 30257341 DOI: 10.1016/j.biopha.2018.08.115
    Uncontrolled hyperglycaemia and oxidative stress have been implicated in the pathophysiology of diabetes mellitus. Hyptis verticillata is reportedly explored traditionally for its therapeutic benefits. Resulting from the paucity of information on the anti-hyperglycaemic potential of this plant, the present study assessed the anti-hyperglycaemic activity of H. verticillata leaf extract. Fifty-four albino Wistar rats were divided into two main groups consisting of diabetic and non-diabetic rats. The diabetic and non-diabetic rats were either treated with oral doses of metformin (500 mg/kg b.w.), quercetin (10 mg/kg b.w.), ethanol extract of H. verticillata leaf (low dose: 250 mg/kg b.w.) or H. verticillata (high dose: 500 mg/kg b.w.) for 28 days. Results showed significantly decreased body weight, increased fasting blood glucose (FBG) and glycated haemoglobin (HbA1c) levels, decreased pancreatic islet area and β-cell number in the diabetic untreated group, relative to normal control. H. verticillata - treated diabetic rats showed decreased FBG and HbA1c, increased body weight, pancreatic islet area and β-cell number, comparable to the effects of metformin. GCMS analysis of H. verticillata showed the presence of ten bioactive volatile compounds, with squalene which possess strong antioxidant, hypoglycaemic and hypotriglyceridemic effects, as the most abundant. We therefore conclude that H. verticillata has anti-hyperglycaemic properties.
    Matched MeSH terms: Dose-Response Relationship, Drug
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