Displaying publications 21 - 40 of 155 in total

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  1. Fulltext Possible participation of nitric oxide/cyclic guanosine monophosphate/protein kinase C/ATP-sensitive K(+) channels pathway in the systemic antinociception of flavokawin B
    Mohamad AS, Akhtar MN, Khalivulla SI, Perimal EK, Khalid MH, Ong HM, et al.
    Basic Clin Pharmacol Toxicol, 2011 Jun;108(6):400-5.
    PMID: 21214864 DOI: 10.1111/j.1742-7843.2010.00670.x
    The possible mechanisms of action in the antinociceptive activity induced by systemic administration (intraperitoneal, i.p.) of flavokawin B (FKB) were analysed using chemical models of nociception in mice. It was demonstrated that i.p. administration of FKB to the mice at 0.3, 1.0, 3.0 and 10 mg/kg produced significant dose-related reduction in the number of abdominal constrictions. The antinociception induced by FKB in the acetic acid test was significantly attenuated by i.p. pre-treatment of mice with L-arginine, the substrate for nitric oxide synthase or glibenclamide, the ATP-sensitive K(+) channel inhibitor, but was enhanced by methylene blue, the non-specific guanylyl cyclase inhibitor. FKB also produced dose-dependent inhibition of licking response caused by intraplantar injection of phorbol 12-myristate 13-acetate, a protein kinase C activator (PKC). Together, these data indicate that the NO/cyclic guanosine monophosphate/PKC/ATP-sensitive K(+) channel pathway possibly participated in the antinociceptive action induced by FKB.
    Matched MeSH terms: Mice, Inbred ICR
  2. The Effect of a Polyvalent Antivenom on the Serum Venom Antigen Levels of Naja sputatrix (Javan Spitting Cobra) Venom in Experimentally Envenomed Rabbits
    Yap MK, Tan NH, Sim SM, Fung SY, Tan CH
    Basic Clin Pharmacol Toxicol, 2015 Oct;117(4):274-9.
    PMID: 25819552 DOI: 10.1111/bcpt.12398
    The treatment protocol of antivenom in snake envenomation remains largely empirical, partly due to the insufficient knowledge of the pharmacokinetics of snake venoms and the effects of antivenoms on the blood venom levels in victims. In this study, we investigated the effect of a polyvalent antivenom on the serum venom antigen levels of Naja sputatrix (Javan spitting cobra) venom in experimentally envenomed rabbits. Intravenous infusion of 4 ml of Neuro Polyvalent Snake Antivenom [NPAV, F(ab')2 ] at 1 hr after envenomation caused a sharp decline of the serum venom antigen levels, followed by transient resurgence an hour later. The venom antigen resurgence was unlikely to be due to the mismatch of pharmacokinetics between the F(ab')2 and venom antigens, as the terminal half-life and volume of distribution of the F(ab')2 in serum were comparable to that of venom antigens (p > 0.05). Infusion of an additional 2 ml of NPAV was able to prevent resurgence of the serum venom antigen level, resulting in a substantial decrease (67.1%) of the total amount of circulating venom antigens over time course of envenomation. Our results showed that the neutralization potency of NPAV determined by neutralization assay in mice may not be an adequate indicator of its capability to modulate venom kinetics in relation to its in vivo efficacy to neutralize venom toxicity. The findings also support the recommendation of giving high initial dose of NPAV in cobra envenomation, with repeated doses as clinically indicated in the presence of rebound antigenemia and symptom recurrence.
    Matched MeSH terms: Mice, Inbred ICR
  3. Fulltext Watermelon (Citrullus lanatus (Thunb.) Matsum. and Nakai) juice modulates oxidative damage induced by low dose X-ray in mice
    Mohammad MK, Mohamed MI, Zakaria AM, Abdul Razak HR, Saad WM
    Biomed Res Int, 2014;2014:512834.
    PMID: 24877107 DOI: 10.1155/2014/512834
    Watermelon is a natural product that contains high level of antioxidants and may prevent oxidative damage in tissues due to free radical generation following an exposure to ionizing radiation. The present study aimed to investigate the radioprotective effects of watermelon (Citrullus lanatus (Thunb.) Matsum. and Nakai) juice against oxidative damage induced by low dose X-ray exposure in mice. Twelve adult male ICR mice were randomly divided into two groups consisting of radiation (Rx) and supplementation (Tx) groups. Rx received filtered tap water, while Tx was supplemented with 50% (v/v) watermelon juice for 28 days ad libitum prior to total body irradiation by 100 μGy X-ray on day 29. Brain, lung, and liver tissues were assessed for the levels of malondialdehyde (MDA), apurinic/apyrimidinic (AP) sites, glutathione (GSH), and superoxide dismutase (SOD) inhibition activities. Results showed significant reduction of MDA levels and AP sites formation of Tx compared to Rx (P < 0.05). Mice supplemented with 50% watermelon juice restore the intracellular antioxidant activities by significantly increased SOD inhibition activities and GSH levels compared to Rx. These findings may postulate that supplementation of 50% watermelon (Citrullus lanatus (Thunb.) Matsum. and Nakai) juice could modulate oxidative damage induced by low dose X-ray exposure.
    Matched MeSH terms: Mice, Inbred ICR
  4. Mechanisms of α-mangostin-induced antinociception in a rodent model
    Sani MH, Taher M, Susanti D, Kek TL, Salleh MZ, Zakaria ZA
    Biol Res Nurs, 2015 Jan;17(1):68-77.
    PMID: 25504952 DOI: 10.1177/1099800414529648
    Elucidate the antinociceptive mechanisms of α-mangostin isolated from Garcinia malaccensis Linn.
    Matched MeSH terms: Mice, Inbred ICR
  5. Methanolic extract of Morinda citrifolia Linn. unripe fruit attenuates methamphetamine-induced conditioned place preferences in mice
    Pandy V, Wai YC, Amira Roslan NF, Sajat A, Abdulla Jallb AH, Vijeepallam K
    Biomed Pharmacother, 2018 Nov;107:368-373.
    PMID: 30099340 DOI: 10.1016/j.biopha.2018.08.008
    The first objective of the present study was to determine the appropriate dose of methamphetamine (Meth) to induce a successful conditioned place preference (CPP) in mice. The next objective was to examine the effect of a methanolic extract of M. citrifolia unripe fruit (MMC) against Meth-induced CPP in mice. In answering to the first objective, following the preconditioning test, an intraperitoneal injection of a fixed dose of Meth (0.5 or 1 or 2 mg/kg, i.p.) or saline (10 ml/kg, i.p.) was given on alternate days during the 10 days conditioning period followed by a postconditioning test conducted in Meth-free state. The first experiment revealed that 0.5 mg/kg of Meth could be an appropriate fixed low dose to induce CPP in mice. Meanwhile, in other experiments, the effect of MMC and bupropion (BUPR) against the expression, extinction, and reinstatement of Meth (0.5 mg/kg)-induced CPP in mice, respectively, was investigated. In a separate set of studies on each phase, an oral administration of MMC (1, 3 and 5 g/kg, p.o.) or BUPR (20 mg/kg, p.o.) was given 60 min prior to CPP postconditioning testing or extinction testing or reinstatement testing in mice. Extinction trials were conducted in Meth-free state to weaken CPP over the next 5 days. Reinstatement test was conducted by a single low dose priming injection of Meth (0.1 mg/kg, i.p.). The present study, however, failed to establish a successful extinction and reinstatement of Meth-CPP in mice. Further studies using other doses of Meth are warranted for a successful establishment of all phases of Meth CPP in mice. This study also demonstrates that MMC (3 and 5 g/kg, p.o.) and BUPR (20 mg/kg, p.o.) could attenuate the expression of Meth-induced CPP in mice.
    Matched MeSH terms: Mice, Inbred ICR
  6. Fulltext Protective effect of α-asarone against nicotine-induced seizures in mice, but not by its interaction with nicotinic acetylcholine receptors
    Chellian R, Pandy V
    Biomed Pharmacother, 2018 Dec;108:1591-1595.
    PMID: 30372861 DOI: 10.1016/j.biopha.2018.09.137
    Alpha-asarone is one of the bioactive phytochemicals present in the rhizomes of Acorus species and demonstrated its anticonvulsant activity in rodents. Alpha-asarone protected mice from the gamma-aminobutyric acid (GABA) type A receptor antagonist or N-methyl-d-aspartate (NMDA) receptor agonist-induced seizures. In our recent study, α-asarone attenuated the nicotine withdrawal-induced depression-like behavior in mice. The seizures induced by nicotine is mediated through the activation of nicotinic acetylcholine receptors (nAChRs) and stimulation of NMDA receptors. Therefore, we hypothesized that α-asarone might be effective against nicotine-induced seizures. Also, the interaction of α-asarone with nAChRs is unknown. In this study, we investigated the effect of α-asarone on the locomotor activity and body temperature in mice. In addition, we studied the effect of α-asarone on nicotine-induced seizures in mice. Finally, we assessed in vivo pharmacodynamic interaction of α-asarone with nAChRs using nicotine-induced hypomotility and hypothermia tests in mice. The results of this study showed that the α-asarone (50-200 mg/kg, i.p.) and diazepam (5 mg/kg, i.p.) treatment significantly decreased the locomotor activity and body temperature in mice. Furthermore, α-asarone (50-200 mg/kg, i.p.) and diazepam (5 mg/kg, i.p.) pretreatment significantly prolonged the onset time of nicotine-induced seizures in mice. However, α-asarone (30 and 50 mg/kg, i.p.) pretreatment did not inhibit the nicotine-induced hypomotility or hypothermia in mice. Conversely, mecamylamine (1 mg/kg, s.c.) pretreatment completely blocked the nicotine-induced seizures and significantly prevents the nicotine-induced hypomotility and hypothermia in mice. Overall, these results suggest that the protective effect of α-asarone against nicotine-induced seizures did not mediate through the antagonism of nAChRs. We also postulated that the GABAergic and glutamatergic activities of α-asarone could be involved in its protective effect against nicotine-induced seizures and based on this aspect further studies are required.
    Matched MeSH terms: Mice, Inbred ICR
  7. Fulltext Mangosteen xanthone γ-mangostin exerts lowering blood glucose effect with potentiating insulin sensitivity through the mediation of AMPK/PPARγ
    Chen SP, Lin SR, Chen TH, Ng HS, Yim HS, Leong MK, et al.
    Biomed Pharmacother, 2021 Dec;144:112333.
    PMID: 34678724 DOI: 10.1016/j.biopha.2021.112333
    Diabetes mellitus (DM) is concomitant with significant morbidity and mortality and its prevalence is accumulative in worldwide. The conventional antidiabetic agents are known to mitigate the symptoms of diabetes; however, they may also cause side and adverse effects. There is an imperative necessity to conduct preclinical and clinical trials for the discovery of alternative therapeutic agents that can overcome the drawbacks of current synthetic antidiabetic drugs. This study aimed to investigate the efficacy of lowering blood glucose and underlined mechanism of γ-mangostin, mangosteen (Garcinia mangostana) xanthones. The results showed γ-Mangostin had a antihyperglycemic ability in short (2 h)- and long-term (28 days) administrations to diet-induced diabetic mice. The long-term administration of γ-mangostin attenuated fasting blood glucose of diabetic mice and exhibited no hepatotoxicity and nephrotoxicity. Moreover, AMPK, PPARγ, α-amylase, and α-glucosidase were found to be the potential targets for simulating binds with γ-mangostin after molecular docking. To validate the docking results, the inhibitory potency of γ-mangostin againstα-amylase/α-glucosidase was higher than Acarbose via enzymatic assay. Interestingly, an allosteric relationship between γ-mangostin and insulin was also found in the glucose uptake of VSMC, FL83B, C2C12, and 3T3-L1 cells. Taken together, the results showed that γ-mangostin exerts anti-hyperglycemic activity through promoting glucose uptake and reducing saccharide digestion by inhibition of α-amylase/α-glucosidase with insulin sensitization, suggesting that γ-mangostin could be a new clue for drug discovery and development to treat diabetes.
    Matched MeSH terms: Mice, Inbred ICR
  8. Annona muricata leaves extracts prevent DMBA/TPA-induced skin tumorigenesis via modulating antioxidants enzymes system in ICR mice
    Md Roduan MR, Hamid RA, Sulaiman H, Mohtarrudin N
    Biomed Pharmacother, 2017 Oct;94:481-488.
    PMID: 28779710 DOI: 10.1016/j.biopha.2017.07.133
    Annona muricata, locally known as soursop has been reported to exhibit antiproliferative activities against various cancer cell lines. In this current study, we have investigated the antitumor promotion of various fractions of Annona muricata leaves (AML); hexane (AMLH), dichloromethane (AMLD) and methanol (AMLM) fraction respectively on 7, 12-dimethylbenz[α]anthracene (DMBA) induced and 12-0-tetradecaboylphorbol-13-acetate (TPA) promoted skin tumorigenesis in mice via morphological assessment, biochemical analysis and histopathological evaluation. The results of the study revealed significant inhibition in tumor incidence, tumor burden and tumor volume in the groups received AMLH and AMLD, respectively, and suppressive effects in group received AMLM compared with carcinogen control group at week 21. Superoxide dismutase, catalase, and lipid peroxidation levels were returned to near normal by administration of AML to DMBA/TPA-induced mice. The above findings were supported by histopathological studies, in which the extensive epidermal hyperplasia in carcinogen control group was restored to normal in AML treated groups. Whilst, annonacin, a major annaonaceous acetogenin was found to be the highest in AMLH and AMLD. From the present study, it can be inferred that AML supressed DMBA/TPA-induced skin tumor and this antitumor-promoting activity may be linked to the antioxidant/free radical-scavenging constituents of the extract and annonacin contained in the extracts.
    Matched MeSH terms: Mice, Inbred ICR
  9. Zerumbone alleviates chronic constriction injury-induced allodynia and hyperalgesia through serotonin 5-HT receptors
    Chia JSM, Omar Farouk AA, Mohamad AS, Sulaiman MR, Perimal EK
    Biomed Pharmacother, 2016 Oct;83:1303-1310.
    PMID: 27570173 DOI: 10.1016/j.biopha.2016.08.052
    Zerumbone, a bioactive sesquiterpene isolated from Zingiber zerumbet (Smith), has shown to exert antiallodynic and antihyperalgesic effects in neuropathic pain mice model in our recent study. The mechanism through which zerumbone alleviates neuropathic pain has yet to be elucidated. Thus, this study aimed to determine whether the serotonergic system, part of the descending pain modulation pathway, contributes to the antineuropathic effect of zerumbone. Participation of the serotonergic system in zerumbone-induced antiallodynia and antihyperalgesia was assessed using Dynamic Plantar Aesthesiometer von Frey test and Hargreaves plantar test respectively in chronic-constriction injury mice model. Administration of ρ-chlorophenylalanine (PCPA, 100mg/kg, i.p.) for four consecutive days to deplete serotonin (5-HT) prior to zerumbone administration blocked the antiallodynic and antihyperalgesic effects of zerumbone. Further investigation with 5-HT receptor antagonists methiothepin (5-HT1/6/7 receptor antagonist, 0.1mg/kg), WAY-100635 (5-HT1A receptor antagonist, 1mg/kg), isamoltane (5-HT1B receptor antagonist, 2.5mg/kg), ketanserin (5-HT2A receptor antagonist, 0.3mg/kg) and ondansetron (5-HT3 receptor antagonist, 0.5mg/kg) managed to significantly attenuate antiallodynic and antihyperalgesic effects of zerumbone (10mg/kg). These findings demonstrate that zerumbone alleviates mechanical allodynia and thermal hyperalgesia through the descending serotonergic system via 5-HT receptors 1A, 1B, 2A, 3, 6 and 7 in chronic constriction injury neuropathic pain mice.
    Matched MeSH terms: Mice, Inbred ICR
  10. Fulltext Methanol Extract of Dicranopteris linearis Leaves Attenuate Pain via the Modulation of Opioid/NO-Mediated Pathway
    Zakaria ZA, Roosli RAJ, Marmaya NH, Omar MH, Basir R, Somchit MN
    Biomolecules, 2020 02 12;10(2).
    PMID: 32059475 DOI: 10.3390/biom10020280
    Dicranopteris linearis leaf has been reported to exert antinociceptive activity. The present study elucidates the possible mechanisms of antinociception modulated by the methanol extract of D. linearis leaves (MEDL) using various mouse models. The extract (25, 150, and 300 mg/kg) was administered orally to mice for 30 min priot to subjection to the acetic acid-induced writhing-, hot plate- or formalin-test to establish the antinociceptive profile of MEDL. The most effective dose was then used in the elucidation of possible mechanisms of action stage. The extract was also subjected to the phytochemical analyses. The results confirmed that MEDL exerted significant (p < 0.05) antinociceptive activity in those pain models as well as the capsaicin-, glutamate-, bradykinin- and phorbol 12-myristate 13-acetate (PMA)-induced paw licking model. Pretreatment with naloxone (a non-selective opioid antagonist) significantly (p < 0.05) reversed MEDL effect on thermal nociception. Only l-arginine (a nitric oxide (NO) donor) but not N(ω)-nitro-l-arginine methyl ester (l-NAME; a NO inhibitor) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; a specific soluble guanylyl cyclase inhibitor) significantly (p < 0.05) modified MEDL effect on the writhing test. Several polyphenolics and volatile antinociceptive compounds were detected in MEDL. In conclusion, MEDL exerted the opioid/NO-mediated antinociceptive activity, thus, justify D. linearis as a potential source for new analgesic agents development.
    Matched MeSH terms: Mice, Inbred ICR
  11. Characterization of secreted recombinant Toxoplasma gondii surface antigen 2 (SAG2) heterologously expressed by the yeast Pichia pastoris
    Fong MY, Lau YL, Zulqarnain M
    Biotechnol Lett, 2008 Apr;30(4):611-8.
    PMID: 18043869
    The surface antigen 2 (SAG2) gene of the protozoan parasite, Toxoplasma gondii, was cloned and extracellularly expressed in the yeast Pichia pastoris. The effectiveness of the secreted recombinant SAG2 (rSAG2-S) as a serodiagnosis reagent was assessed by western blots and ELISA. In the western blot assay, rSAG2-S reacted with all Toxoplasma-antibody positive human serum samples but not with Toxoplasma-negative samples. In the ELISA, rSAG2-S yielded sensitivity rates ranging from 80% (IgG negative, IgM positive) to 100% (IgG positive, IgM negative). In vivo experiments showed that serum from mice immunized with rSAG2-S reacted specifically with the native SAG2 of T. gondii. These mice were protected when challenged with live cells of T. gondii.
    Matched MeSH terms: Mice, Inbred ICR
  12. Fulltext CNS neurotoxicity of bacterial cellulose-poly(acrylamide-sodium acrylate) hydrogel: a future therapeutic carrier
    Pandey M, Mohd Amin MC
    CNS Neurosci Ther, 2014 Apr;20(4):377-8.
    PMID: 24588895 DOI: 10.1111/cns.12237
    Matched MeSH terms: Mice, Inbred ICR
  13. Sunitinib DDI with paracetamol, diclofenac, mefenamic acid and ibuprofen shows sex-divergent effects on the tissue uptake and distribution pattern of sunitinib in mice
    Tan SY, Wong MM, Tiew AL, Choo YW, Lim SH, Ooi IH, et al.
    Cancer Chemother Pharmacol, 2016 10;78(4):709-18.
    PMID: 27495788 DOI: 10.1007/s00280-016-3120-9
    PURPOSE: Pharmacokinetic interaction of sunitinib with diclofenac, paracetamol, mefenamic acid and ibuprofen was evaluated due to their P450 mediated metabolism and OATP1B1, OATP1B3, ABCB1, ABCG2 transporters overlapping features.

    METHODS: Male and female mice were administered 6 sunitinib doses (60 mg/kg) PO every 12 h and 30 min before the last dose were administered vehicle (control groups), 250 mg/kg paracetamol, 30 mg/kg diclofenac, 50 mg/kg mefenamic acid or 30 mg/kg ibuprofen (study groups), euthanized 6 h post last administration and sunitinib plasma, liver, kidney, brain concentrations analyzed.

    RESULTS: Ibuprofen halved sunitinib plasma concentration in female mice (p mice (p mice showed 45 and 25 % higher plasma concentrations than male mice which were 27 % lower in mefenamic acid female mice. Paracetamol increased 2.2 (p mice that were lower in female mice (p mice that were higher than in female mice (p mice had 35 % higher sunitinib brain concentration than male mice but the concentration decreased 37, 33, 10 and 57 % in the diclofenac, paracetamol, mefenamic acid and ibuprofen (p mice (liver, brain) and female mice (liver, kidney).

    CONCLUSIONS: These results portray gender-based sunitinib pharmacokinetic differences and NSAIDs selective effects on male or female mice, with potential clinical translatability.

    Matched MeSH terms: Mice, Inbred ICR
  14. Amino acid and fatty acid composition of an aqueous extract of Channa striatus (Haruan) that exhibits antinociceptive activity
    Zakaria ZA, Mat Jais AM, Goh YM, Sulaiman MR, Somchit MN
    Clin Exp Pharmacol Physiol, 2007 Mar;34(3):198-204.
    PMID: 17250639
    1. The present study was performed in order to determine the amino acid and fatty acid composition of an aqueous extract of the freshwater fish Channa striatus, obtained by soaking (1:2, w/v) fresh fillets overnight in a chloroform:methanol (2:1, v/v) solvent, to elucidate the mechanism responsible for its antinociceptive activity and to clarify the relationship between the presence of the amino and fatty acids and the expected activity. 2. The aqueous extract was found to contain all amino acids with the major amino acids glycine, alanine, lysine, aspartic acid and proline making up 35.77 +/- 0.58, 10.19 +/- 1.27, 9.44 +/- 0.56, 8.53 +/- 1.15 and 6.86 +/- 0.78% of the total protein, respectively. 3. In addition, the aqueous extract was found to have a high palmitic acid (C16:0) content, which contributed approximately 35.93 +/- 0.63% to total fatty acids. The other major fatty acids in the aqueous extract were oleic acid (C18:1), stearic acid (C18:0), linoleic acid (C18:2) and arachidonic acid (C20:4), contributing 22.96 +/- 0.40, 15.31 +/- 0.33, 11.45 +/- 0.31 and 7.44 +/- 0.83% of total fatty acids, respectively. 4. Furthermore, the aqueous extract was demonstrated to possess concentration-dependent antinociceptive activity, as expected, when assessed using the abdominal constriction test in mice. 5. It is concluded that the aqueous extract of C. striatus contains all the important amino acids, but only some of the important fatty acids, which are suggested to play a key role in the observed antinociceptive activity of the extract, as well as in the traditionally claimed wound healing properties of the extract.
    Matched MeSH terms: Mice, Inbred ICR
  15. Geographical venom variations of the Southeast Asian monocled cobra (Naja kaouthia): venom-induced neuromuscular depression and antivenom neutralization
    Tan KY, Tan CH, Sim SM, Fung SY, Tan NH
    Comp Biochem Physiol C Toxicol Pharmacol, 2016 Jul-Aug;185-186:77-86.
    PMID: 26972756 DOI: 10.1016/j.cbpc.2016.03.005
    The Southeast Asian monocled cobras (Naja kaouthia) exhibit geographical variations in their venom proteomes, especially on the composition of neurotoxins. This study compared the neuromuscular depressant activity of the venoms of N. kaouthia from Malaysia (NK-M), Thailand (NK-T) and Vietnam (NK-V), and the neutralization of neurotoxicity by a monospecific antivenom. On chick biventer cervicis nerve-muscle preparation, all venoms abolished the indirect twitches, with NK-T venom being the most potent (shortest t90, time to 90% twitch inhibition), followed by NK-V and NK-M. Acetylcholine and carbachol failed to reverse the blockade, indicating irreversible/pseudo-irreversible post-synaptic neuromuscular blockade. KCl restored the twitches variably (NK-M preparation being the least responsive), consistent with different degree of muscle damage. The findings support that NK-T venom has the most abundant curarimimetic alpha-neurotoxins, while NK-M venom contains more tissue-damaging cytotoxins. Pre-incubation of tissue with N. kaouthia monovalent antivenom (NKMAV) prevented venom-induced twitch depression, with the NK-T preparation needing the largest antivenom dose. NKMAV added after the onset of neuromuscular depression could only halt the inhibitory progression but failed to restore full contraction. The findings highlight the urgency of early antivenom administration to sequester as much circulating neurotoxins as possible, thereby hastening toxin elimination from the circulation. In envenomed mice, NKMAV administered upon the first neurological sign neutralized the neurotoxic effect, with the slowest full recovery noticed in the NK-T group. This is consistent with the high abundance of neurotoxins in the NK-T venom, implying that a larger amount or repeated dosing of NKMAV may be required in NK-T envenomation.
    Matched MeSH terms: Mice, Inbred ICR
  16. Isolation and characterisation of acetylcholinesterase inhibitors from Aquilaria subintegra for the treatment of Alzheimer's disease (AD)
    Bahrani H, Mohamad J, Paydar MJ, Rothan HA
    Curr Alzheimer Res, 2014 Feb;11(2):206-14.
    PMID: 24479629
    Aquilaria subintegra, locally known as "Gaharu", belongs to the Thymelaeceae family. This plant's leaves have been claimed to be effective for the treatment of Alzheimer's disease (AD) by Malay traditional practitioner in Malaysia. In this research, the chloroform extracts of the leaves and stem of A. subintegra were tested for acetylcholinesterase (AChE) inhibitory activity. The Thin Layer Chromatography (TLC) results indicated the presence of phenols, flavonoids, terpenoids, and alkaloids compounds in the extracts. Analysis of the stem chloroform extracts with LCMS/MS displayed that it contains kaempferol 3,4,7-trimethyl ether. The AChE inhibitory activity of leaves and stem chloroform extracts and kaempferol were 80%, 93% and 85.8%, respectively. The Brine Shrimp Lethality Assay (BSLA) exhibited low to moderate toxicity of the chloroform extract from leaves (LC50=531.18 ± 49.53 μg/ml), the stem chloroform extract (LC50=407.34 ± 68.05 μg/ml) and kaempferol (LC50=762.41 ± 45.09 μg/ml). The extracts and kaempferol were not cytotoxic to human umbilical vein endothelial cells (HUVEC), human normal gastric epithelial cell line (GES-1) and human normal hepatic cell line (WRL-68). The effect of leaf and stem chloroform extracts and kaempferol were determined in the Radial Arm Maze (RAM) after administration by oral gavage to ICR male and female mice with valium-impaired memory. Administration of kaempferol to the mice significantly reduced the number of repeated entries into the arms of maze in males and females. In conclusion, the inhibition of AChE by leaf and stem chloroform extracts of A. subintegra could be due to the presence of kaempferol. This extract is safe for use as a natural AChE inhibitor as an alternative to berberine for the treatment of AD.
    Matched MeSH terms: Mice, Inbred ICR
  17. Fulltext Development of Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions
    Minayoshi Y, Maeda H, Yanagisawa H, Hamasaki K, Mizuta Y, Nishida K, et al.
    Drug Deliv, 2018 Nov;25(1):1067-1077.
    PMID: 29688069 DOI: 10.1080/10717544.2018.1464083
    Because of its multifaceted anti-inflammatory and immunomodulatory effects, delivering type-I interferon to Kupffer cells has the potential to function as a novel type of therapy for the treatment of various types of hepatitis. We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis. The presence of this unique oligosaccharide permits the protein to be efficiently, rapidly and preferentially distributed to Kupffer cells. Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor. These data indicate that Man-HSA(D494N)-IFNα2b retained the biological activities of type-I interferon. Man-HSA(D494N)-IFNα2b significantly inhibited liver injury in Concanavalin A (Con-A)-induced hepatitis model mice, and consequently improved their survival rate. Moreover, the post-administration of Man-HSA(D494N)-IFNα2b at 2 h after the Con-A challenge also exerted hepato-protective effects. In conclusion, this proof-of-concept study demonstrates the therapeutic effectiveness and utility of Kupffer cell targeting type-I interferon against hepatitis via its anti-inflammatory and immunomodulatory actions.
    Matched MeSH terms: Mice, Inbred ICR
  18. Fulltext Methanol leaf extract ofActinodaphne sesquipedalis(Lauraceae) enhances gastric defense against ethanol-induced ulcer in rats
    Omar H, Nordin N, Hassandarvish P, Hajrezaie M, Azizan AHS, Fadaeinasab M, et al.
    Drug Des Devel Ther, 2017;11:1353-1365.
    PMID: 28496305 DOI: 10.2147/DDDT.S120564
    Actinodaphne sesquipedalis
    Hook. F. Var. Glabra (Kochummen), also known as "Medang payung" by the Malay people, belongs to the Lauraceae family. In this study, methanol leaf extract ofA. sesquipedaliswas investigated for their acute toxicity and gastroprotective effects to reduce ulcers in rat stomachs induced by ethanol. The rats were assigned to one of five groups: normal group (group 1), ulcer group (group 2), control positive drug group (group 3) and two experimental groups treated with 150 mg/kg (group 4) and 300 mg/kg (group 5) of leaf extract. The rats were sacrificed an hour after pretreatment with extracts, and their stomach homogenates and tissues were collected for further evaluation. Macroscopic and histological analyses showed that gastric ulcers in rats pretreated with the extract were significantly reduced to an extent that it allowed leukocytes penetration of the gastric walls compared with the ulcer group. In addition, an ulcer inhibition rate of >70% was detected in rats treated with both doses ofA. sesquipedalisextract, showing a notable protection of gastric layer. Severe destruction of gastric mucosa was prevented with a high production of mucus and pH gastric contents in both omeprazole-treated and extract-treated groups. Meanwhile, an increase in glycoprotein uptake was observed in pretreated rats through accumulation of magenta color in Periodic Acid Schiff staining assay. Analysis of gastric homogenate from pretreated rats showed a reduction of malondialdehyde and elevation of nitric oxide, glutathione, prostaglandin E2, superoxide dismutase and protein concentration levels in comparison with group 2. Suppression of apoptosis in gastric tissues by upregulation of Hsp70 protein and downregulation of Bax protein was also observed in rats pretreated with extract. Consistent results of a reduction of gastric ulcer and the protection of gastric wall were obtained for rats pretreated withA. sesquipedalisextract, which showed its prominent gastroprotective potential in rats' stomach against ethanol-induced ulcer.
    Matched MeSH terms: Mice, Inbred ICR
  19. Fulltext Gancidin W, a potential low-toxicity antimalarial agent isolated from an endophytic Streptomyces SUK10
    Zin NM, Baba MS, Zainal-Abidin AH, Latip J, Mazlan NW, Edrada-Ebel R
    Drug Des Devel Ther, 2017;11:351-363.
    PMID: 28223778 DOI: 10.2147/DDDT.S121283
    Endophytic Streptomyces strains are potential sources for novel bioactive molecules. In this study, the diketopiperazine gancidin W (GW) was isolated from the endophytic actinobacterial genus Streptomyces, SUK10, obtained from the bark of Shorea ovalis tree, and it was tested in vivo against Plasmodium berghei PZZ1/100. GW exhibited an inhibition rate of nearly 80% at 6.25 and 3.125 μg kg-1 body weight on day four using the 4-day suppression test method on male ICR strain mice. Comparing GW at both concentrations with quinine hydrochloride and normal saline as positive and negative controls, respectively, 50% of the mice treated with 3.125 μg kg-1 body weight managed to survive for more than 11 months after infection, which almost reached the life span of normal mice. Biochemical tests of selected enzymes and proteins in blood samples of mice treated with GW were also within normal levels; in addition, no abnormalities or injuries were found on internal vital organs. These findings indicated that this isolated bioactive compound from Streptomyces SUK10 exhibits very low toxicity and is a good candidate for potential use as an antimalarial agent in an animal model.
    Matched MeSH terms: Mice, Inbred ICR
  20. Antinociceptive activity of a synthetic chalcone, flavokawin B on chemical and thermal models of nociception in mice
    Mohamad AS, Akhtar MN, Zakaria ZA, Perimal EK, Khalid S, Mohd PA, et al.
    Eur J Pharmacol, 2010 Nov 25;647(1-3):103-9.
    PMID: 20826146 DOI: 10.1016/j.ejphar.2010.08.030
    The present study examined the potential antinociceptive activity of flavokawin B (6'-hydroxy-2',4'-dimethoxychalcone), a synthetic chalcone using chemical- and thermal-induced nociception models in mice. It was demonstrated that flavokawin B (FKB; 0.3, 1, 3 and 10 mg/kg) administered via both oral (p.o.) and intraperitoneal (i.p.) routes produced significant and dose-dependent inhibition in the abdominal constrictions induced by acetic acid, with the i.p. route producing antinociception of approximately 7-fold more potent than the p.o. route. It was also demonstrated that FKB produced significant inhibition in the two phases of the formalin-induced paw licking test. In addition, the same treatment of flavokawin B (FKB) exhibited significant inhibition of the neurogenic nociceptive induced by intraplantar injections of glutamate and capsaicin. Likewise, this compound also induced a significant increase in the response latency period to thermal stimuli in the hot plate test and its antinociceptive effect was not related to muscle relaxant or sedative action. Moreover, the antinociception effect of the FKB in the formalin-induced paw licking test and the hot plate test was not affected by pretreatment of non-selective opioid receptor antagonist, naloxone. The present results indicate that FKB produced pronounced antinociception effect against both chemical and thermal models of pain in mice that exhibited both peripheral and central analgesic activity.
    Matched MeSH terms: Mice, Inbred ICR
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