Displaying publications 41 - 60 of 90 in total

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  1. 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.
  2. Fulltext Cardamonin Modulates Neuropathic Pain through the Possible Involvement of Serotonergic 5-HT1A Receptor Pathway in CCI-Induced Neuropathic Pain Mice Model
    Kaswan NK, Mohammed Izham NAB, Tengku Mohamad TAS, Sulaiman MR, Perimal EK
    Molecules, 2021 Jun 16;26(12).
    PMID: 34208700 DOI: 10.3390/molecules26123677
    Cardamonin, a naturally occurring chalcone isolated from Alpinia species has shown to possess strong anti-inflammatory and anti-nociceptive activities. Previous studies have demonstrated that cardamonin exerts antihyperalgesic and antiallodynic properties in chronic constriction injury (CCI)-induced neuropathic pain animal model. However, the mechanisms underlying cardamonin's effect have yet to be fully understood. The present study aims to investigate the involvement of the serotonergic system in cardamonin induced antihyperalgesic and antiallodynic effects in CCI-induced neuropathic pain mice model. The neuropathic pain symptoms in the CCI mice model were assessed using Hargreaves Plantar test and von-Frey filament test on day 14 post-surgery. Central depletion of serotonin along the descending serotonergic pathway was done using ρ-chlorophenylalanine (PCPA, 100 mg/kg, i.p.), an inhibitor of serotonin synthesis for four consecutive days before cardamonin treatment, and was found to reverse the antihyperalgesic and antiallodynic effect produced by cardamonin. Pretreatment of the mice with several 5-HT receptor subtypes antagonists: methiothepin (5-HT1/6/77 receptor antagonist, 0.1 mg/kg), WAY 100635 (5-HT1A receptor antagonist, 1 mg/kg), isamoltane (5-HT1B receptor antagonist, 2.5 mg/kg), ketanserin (5-HT2A receptor antagonist, 0.3 mg/kg), and ondansetron (5-HT3 receptor antagonist, 0.5 mg/kg) were shown to abolish the effect of cardamonin induced antihyperalgesic and antiallodynic effects. Further evaluation of the 5-HT1A receptor subtype protein expressions reveals that cardamonin significantly upregulated its expression in the brainstem and spinal cord. Our results suggest that the serotonergic pathway is essential for cardamonin to exert its antineuropathic effect in CCI mice through the involvement of the 5-HT1A receptor subtype in the central nervous system.
  3. Fulltext Zerumbone Ameliorates Neuropathic Pain Symptoms via Cannabinoid and PPAR Receptors Using In Vivo and In Silico Models
    Chia JSM, Farouk AAO, Mohamad TAST, Sulaiman MR, Zakaria H, Hassan NI, et al.
    Molecules, 2021 Jun 24;26(13).
    PMID: 34202590 DOI: 10.3390/molecules26133849
    Neuropathic pain is a chronic pain condition persisting past the presence of any noxious stimulus or inflammation. Zerumbone, of the Zingiber zerumbet ginger plant, has exhibited anti-allodynic and antihyperalgesic effects in a neuropathic pain animal model, amongst other pharmacological properties. This study was conducted to further elucidate the mechanisms underlying zerumbone's antineuropathic actions. Research on therapeutic agents involving cannabinoid (CB) and peroxisome proliferator-activated receptors (PPARs) is rising. These receptor systems have shown importance in causing a synergistic effect in suppressing nociceptive processing. Behavioural responses were assessed using the von Frey filament test (mechanical allodynia) and Hargreaves plantar test (thermal hyperalgesia), in chronic constriction injury (CCI) neuropathic pain mice. Antagonists SR141716 (CB1 receptor), SR144528 (CB2 receptor), GW6471 (PPARα receptor) and GW9662 (PPARγ receptor) were pre-administered before the zerumbone treatment. Our findings indicated the involvement of CB1, PPARα and PPARγ in zerumbone's action against mechanical allodynia, whereas only CB1 and PPARα were involved against thermal hyperalgesia. Molecular docking studies also suggest that zerumbone has a comparable and favourable binding affinity against the respective agonist on the CB and PPAR receptors studied. This finding will contribute to advance our knowledge on zerumbone and its significance in treating neuropathic pain.
  4. Hepatotoxicity induced by antifungal drugs itraconazole and fluconazole in rats: a comparative in vivo study
    Somchit N, Norshahida AR, Hasiah AH, Zuraini A, Sulaiman MR, Noordin MM
    Hum Exp Toxicol, 2004 Nov;23(11):519-25.
    PMID: 15625777
    Itraconazole and fluconazole are oral antifungal drugs, which have a wide spectrum antifungal activity and better efficacy than the older drugs. However, both drugs have been associated with hepatotoxicity in susceptible patients. The mechanism of antifungal drug-induced hepatotoxicity is largely unknown. Therefore, the aim of this present study was to investigate and compare the hepatotoxicity induced by these drugs in vivo. Rats were treated intraperitoneally with itraconazole or fluconazole either single (0, 10, 100 and 200 mg/kg) or subchronic (0, 10, 50 and 100 mg/kg per day for 14 days) doses. Plasma and liver samples were taken at the end of the study. A statistically significant and dose dependent increase of plasma alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities were detected in the subchronic itraconazole-treated group. In addition, dose-dependent hepatocellular necrosis, degeneration of periacinar and mizonal hepatocytes, bile duct hyperplasia and biliary cirrhosis and giant cell granuloma were observed histologically in the same group. Interestingly, fluconazole treated rats had no significant increase in transaminases for both single and subchronic groups. In the subchronic fluconazole treated rats, only mild degenerative changes of centrilobular hepatocytes were observed. These results demonstrated that itraconazole was a more potent hepatotoxicant than fluconazole in vivo in rats.
  5. Atrovirinone inhibits pro-inflammatory mediator release from murine macrophages and human whole blood
    Syahida A, Israf DA, Permana D, Lajis NH, Khozirah S, Afiza AW, et al.
    Immunol Cell Biol, 2006 Jun;84(3):250-8.
    PMID: 16509831
    Many plant-derived natural compounds have been reported previously to inhibit the production of important pro-inflammatory mediators such as nitric oxide, prostaglandin E2, TNF-alpha and reactive oxygen species by suppressing inducible enzyme expression via inhibition of the mitogen-activated protein kinase pathway and nuclear translocation of critical transcription factors. This study evaluates the effects of atrovirinone [2-(1-methoxycarbonyl-4,6-dihydroxyphenoxy)-3-methoxy-5,6-di-(3-methyl-2-butenyl)-1,4-benzoquinone)], a benzoquinone that we have previously isolated from Garcinia atroviridis, on two cellular systems that are repeatedly used in the analysis of anti-inflammatory bioactive compounds, namely, RAW 264.7 macrophage cells and whole blood. Atrovirinone inhibited the production of both nitric oxide and prostaglandin E2 from LPS-induced and IFN-gamma-induced RAW 264.7 cells and whole blood, with inhibitory concentration (IC)50 values of 4.62 +/- 0.65 and 9.33 +/- 1.47 micromol/L, respectively. Analysis of thromboxane B2 (TXB2) secretion from whole blood stimulated by either the cyclooxygenase (COX)-1 or the COX-2 pathway showed that atrovirinone inhibits the generation of TXB2 by both pathways, with IC50 values of 7.41 +/- 0.92 and 2.10 +/- 0.48 micromol/L, respectively. Analysis of IC50 ratios showed that atrovirinone was more COX-2 selective in its inhibition of TXB2, with a ratio of 0.32. Atrovirinone also inhibited the generation of intracellular reactive oxygen species and the secretion of TNF-alpha from RAW 264.7 cells in a dose-responsive manner, with IC50 values of 5.99 +/- 0.62 and 11.56 +/- 0.04 micromol/L, respectively. Lipoxygenase activity was also moderately inhibited by atrovirinone. Our results suggest that atrovirinone acts on important pro-inflammatory mediators possibly by the inhibition of the nuclear factor-kappaB pathway and also by the inhibition of the COX/lipoxygenase enzyme activity.
  6. Fulltext Comparative Study of The Yield and Physicochemical Properties of Collagen from Sea Cucumber (Holothuria scabra), Obtained through Dialysis and the Ultrafiltration Membrane
    Saallah S, Roslan J, Julius FS, Saallah S, Mohamad Razali UH, Pindi W, et al.
    Molecules, 2021 Apr 28;26(9).
    PMID: 33924820 DOI: 10.3390/molecules26092564
    Collagen was extracted from the body wall of sea cucumber (Holothuria scabra) using the pepsin-solubilized collagen method followed by isolation using dialysis and the ultrafiltration membrane. The yield and physicochemical properties of the collagen obtained from both isolation methods, denoted as D-PSC and UF-PSC, were compared. The ultrafiltration method affords a higher yield of collagen (11.39%) than that of the dialysis (5.15%). The isolated collagens have almost the same amino acid composition, while their functional groups, referred to as amide A, B, I, II, and III bands, were in accordance with commercial collagen, as verified by Fourier Transform Infrared (FT-IR) spectroscopy. The UV-Vis absorption peaks at 240 nm and 220 nm, respectively, indicated that the collagens produced are type-I collagen. The D-PSC showed interconnecting sheet-like fibrils, while the UF-PSC exhibited a flaky structure with flat-sheets arranged very close to each other. The higher yield and comparable physicochemical properties of the collagen obtained by ultrafiltration as compared with dialysis indicate that the membrane process has high potential to be used in large-scale collagen production for food and pharmaceutical applications.
  7. Antinociceptive and antiinflammatory activities of the aqueous extract of Trigonopleura malayana resin in experimental animal models
    Sulaiman MR, Zakaria ZA, Kamaruddin A, Meng TF, Ali DI, Moin S
    Methods Find Exp Clin Pharmacol, 2008 Nov;30(9):691-6.
    PMID: 19229377 DOI: 10.1358/mf.2008.30.9.1305824
    Trigonopleura malayana L. (Euphorbiaceae) resin, locally known as Gambir Sarawak, has been used traditionally to alleviate pain associated with insect bites, muscle ache, toothache and minor injuries. The present study was carried out using various animal models to determine the antinociceptive and antiinflammatory activities of the T. malayana resin aqueous extract. Antinociceptive activity was measured using the abdominal constriction, hot plate and formalin tests, while antiinflammatory activity was measured using the carrageenan-induced paw edema test. The extract, obtained after 24 h of soaking the dried resin in distilled water, was prepared in doses of 0.3, 3 and 10 mg/kg and administered subcutaneously 30 min prior to the assays. The mechanism of action was also determined by prechallenging with naloxone (10 mg/kg), a nonselective opioid antagonist. The extract was found to exhibit significant (P < 0.05) and dose-dependent antinociceptive and antiinflammatory activities; naloxone failed to inhibit the former activity. In conclusion, the aqueous extract of T. malayana resin possesses nonopioid antinociceptive and antiinflammatory activities, thus supporting previous claims regarding its traditional use by the Malays to treat various ailments, particularly those related to pain.
  8. Antinociceptive effect of Melastoma malabathricum ethanolic extract in mice
    Sulaiman MR, Somchit MN, Israf DA, Ahmad Z, Moin S
    Fitoterapia, 2004 Dec;75(7-8):667-72.
    PMID: 15567242
    The antinociceptive effect of the ethanolic extract of Melastoma malabathricum (MME) was investigated using acetic acid-induced abdominal writhing test and hot-plate test in mice. It was demonstrated that the extract (30-300 mg/kg, i.p.) strongly and dose-dependently inhibited the acetic acid-induced writhing with an ED(50) of 100 (78-160) mg/kg i.p. It also significantly increased the response latency period to thermal stimuli. Furthermore, the nonselective opioid receptor antagonist, naloxone blocked the antinociceptive effect of the extract in both tests, suggesting that M. malabathricum may act both at peripheral and central levels.
  9. Fulltext Evaluation of Antinociceptive Profile of Chalcone Derivative (3-(2,5-dimethoxyphenyl)-1-(5-methylfuran-2-yl) prop-2-en-1-one (DMPF-1) in vivo
    Abu Bakar NA, Sulaiman MR, Lajis N, Akhtar MN, Mohamad AS
    J Pharm Bioallied Sci, 2020 Nov;12(Suppl 2):S711-S717.
    PMID: 33828366 DOI: 10.4103/jpbs.JPBS_344_19
    Introduction: Pain is a major global health issue, where its pharmacotherapy prompts unwanted side effects; hence, the development of effective alternative compounds from natural derivatives with lesser side effects is clinically needed. Chalcone; the precursors of flavonoid, and its derivatives have been widely investigated due to its pharmacological properties.

    Objective: This study addressed the therapeutic effect of 3-(2,5-dimethoxyphenyl)-1-(5-methyl furan-2-yl) prop-2-en-1-one (DMPF-1); synthetic chalcone derivative, on antinociceptive activity in vivo.

    Materials and Methods: The antinociceptive profile was evaluated using acetic-acid-induced abdominal writhing, hot plate, and formalin-induced paw licking test. Capsaicin, phorbol 12-myristate 12 acetate (PMA), and glutamate-induced paw licking test were carried out to evaluate their potential effects toward different targets.

    Results: It was shown that the doses of 0.1, 0.5, 1, and 5 mg/kg of DMPF-1 given via intraperitoneal injection showed significant reduction in writhing responses and increased the latency time in hot-plate test where reduced time spent on licking the injected paw in formalin and dose contingency inhibition was observed. The similar results were observed in capsaicin, PMA, and glutamate-induced paw licking test. In addition, the challenge with nonselective opioid receptor antagonist (naloxone) aimed to evaluate the involvement of the opioidergic system, which showed no reversion in analgesic profile in formalin and hot-plate test.

    Conclusion: Collectively, this study showed that DMPF-1 markedly inhibits both peripheral and central nociception through the mechanism involving an interaction with vanilloid and glutamatergic system regardless of the activation of the opioidergic system.

  10. Cardamonin (2',4'-dihydroxy-6'-methoxychalcone) isolated from Boesenbergia rotunda (L.) Mansf. inhibits CFA-induced rheumatoid arthritis in rats
    Voon FL, Sulaiman MR, Akhtar MN, Idris MF, Akira A, Perimal EK, et al.
    Eur J Pharmacol, 2017 Jan 05;794:127-134.
    PMID: 27845065 DOI: 10.1016/j.ejphar.2016.11.009
    Boesenbergia rotunda (L.) Mansf. had been traditionally used as herbs to treat pain and rheumatism. Cardamonin (2',4'-dihydroxy-6'-methoxychalcone) is a compound isolated from Boesenbergia rotunda (L.) Mansf.. Previous study had shown the potential of cardamonin in inhibiting the release of pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in vitro. Thus, the possible therapeutic effect of cardamonin in the rheumatoid arthritis (RA) joints is postulated. This study was performed to investigate the anti-arthritic properties of cardamonin in rat model of induced RA, particularly on the inflammatory and pain response of RA. Rheumatoid arthritis paw inflammation was induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA) in Sprague Dawley rats. Using four doses of cardamonin (0.625, 1.25, 2.5, and 5.0mg/kg), anti-arthritic activity was evaluated through the paw edema, mechanical allodynia and thermal hyperalgesia responses. Enzyme-linked immunosorbent assay (ELISA) was carried out to evaluate the plasma level of TNF-α, IL-1β, and IL-6. Histological slides were prepared from the harvested rat paws to observe the arthritic changes in the joints. Behavioral, biochemical, and histological studies showed that cardamonin demonstrated significant inhibition on RA-induced inflammatory and pain responses as well as progression of joint destruction in rats. ELISA results showed that there was significant inhibition in TNF-α, IL-1β, and IL-6 levels in plasma of the cardamonin-treated RA rats. Overall, cardamonin possesses potential anti-arthritic properties in CFA-induced RA rat model.
  11. The influences of temperature and naloxone on the antinociceptive activity of Corchorus olitorius L. in mice
    Zakaria ZA, Safarul M, Valsala R, Sulaiman MR, Fatimah CA, Somchit MN, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2005 Jul;372(1):55-62.
    PMID: 16133487
    A series of preliminary studies was carried out to evaluate the antinociceptive (pain relief) activity of the aqueous extract of Corchorus olitorius L. leaves (COAE) and to determine the influence of temperature and opioid receptors on COAE activity using the abdominal constriction and hot plate tests in mice. COAE, at concentrations of 10, 25, 50, 75, and 100%, showed both peripheral and central antinociception that are non-concentration- and concentration-dependent respectively. The peripheral activity was clearly observed at a concentration of 25% and diminished at a concentration of 100%, while the central activity was observed at all the concentrations of COAE used. Furthermore, the insignificant results obtained indicated that this peripheral activity (at concentrations of 25 and 50%) was comparable to that of morphine (0.8 mg/kg). Pre-heating COAE at a temperature of 80 degrees C and 100 degrees C, or 60 degrees C and 80 degrees C was found to enhance its peripheral and central antinociception respectively. Pre-treatment with naloxone (10 mg/kg), a general opioid receptor antagonist, for 5 min, followed by COAE, was found to completely block its peripheral, but not central, antinociceptive activity. Based on this observation, we conclude that the antinociceptive activity exhibited by C. olitorius is enhanced by the increase in temperature and may be mediated peripherally, but not centrally, at least in part, via an opioid receptor.
  12. Fulltext Hepatoprotective activity of dried- and fermented-processed virgin coconut oil
    Zakaria ZA, Rofiee MS, Somchit MN, Zuraini A, Sulaiman MR, Teh LK, et al.
    Evid Based Complement Alternat Med, 2011;2011:142739.
    PMID: 21318140 DOI: 10.1155/2011/142739
    The present study aims to determine the hepatoprotective effect of MARDI-produced virgin coconut oils, prepared by dried- or fermented-processed methods, using the paracetamol-induced liver damage in rats. Liver injury induced by 3 g/kg paracetamol increased the liver weight per 100 g bodyweight indicating liver damage. Histological observation also confirms liver damage indicated by the presence of inflammations and necrosis on the respective liver section. Interestingly, pretreatment of the rats with 10, but not 1 and 5, mL/kg of both VCOs significantly (P < .05) reduced the liver damage caused by the administration of paracetamol, which is further confirmed by the histological findings. In conclusion, VCO possessed hepatoprotective effect that requires further in-depth study.
  13. Antinociceptive activity of the essential oil of Zingiber zerumbet
    Sulaiman MR, Tengku Mohamad TA, Shaik Mossadeq WM, Moin S, Yusof M, Mokhtar AF, et al.
    Planta Med, 2010 Feb;76(2):107-12.
    PMID: 19637111 DOI: 10.1055/s-0029-1185950
    In the present study, the rhizome essential oil from Zingiber zerumbet (Zingiberaceae) was evaluated for antinociceptive activity using chemical and thermal models of nociception, namely, the acetic acid-induced abdominal writhing test, the hot-plate test and the formalin-induced paw licking test. It was demonstrated that intraperitoneal administration of the essential oil of Z. zerumbet (EOZZ) at the doses of 30, 100 and 300 mg/kg produced significant dose-dependent inhibition of acetic acid-induced abdominal writhing, comparable to that of obtained with acetylsalicylic acid (100 mg/kg). At the same doses, the EOZZ produced significant dose-dependent increases in the latency time in the hot-plate test with respect to controls, and in the formalin-induced paw licking test, the EOZZ also significantly reduced the painful stimulus in both neurogenic and inflammatory phase of the test. In addition, the antinociceptive effect of the EOZZ in the formalin-induced paw licking test as well as hot-plate test was reversed by the nonselective opioid receptor antagonist, naloxone suggesting that the opioid system was involved in its analgesic mechanism of action. On the basis of these data, we concluded that the EOZZ possessed both central and peripheral antinociceptive activities which justifying its popular folkloric use to relieve some pain conditions.
  14. Fulltext Antinociceptive activity of Melicope ptelefolia ethanolic extract in experimental animals
    Sulaiman MR, Mohd Padzil A, Shaari K, Khalid S, Shaik Mossadeq WM, Mohamad AS, et al.
    J Biomed Biotechnol, 2010;2010:937642.
    PMID: 21274262 DOI: 10.1155/2010/937642
    Melicope ptelefolia is a medicinal herb commonly used in Malaysia to treat fever, pain, wounds, and itches. The present study was conducted to evaluate the antinociceptive activity of the Melicope ptelefolia ethanolic extract (MPEE) using animal models of nociception. The antinociceptive activity of the extract was assessed using acetic acid-induced abdominal writhing, hot-plate, and formalin-induced paw licking tests. Oral administration of MPEE produced significant dose-dependent antinociceptive effects when tested in mice and rats using acetic acid-induced abdominal constriction test and on the second phase of the formalin-induced paw licking test, respectively. It was also demonstrated that MPEE had no effect on the response latency time to the heat stimulus in the thermal model of the hot-plate test. In addition, the antinociception produced by MPEE was not blocked by naloxone. Furthermore, oral administration of MPEE did not produce any effect in motor performance of the rota-rod test and in acute toxicity study no abnormal behaviors as well as mortality were observed up to a dose level of the extract of 5 g/kg. These results indicated that MPEE at all doses investigated which did not produce any sedative and toxic effects exerted pronounce antinociceptive activity that acts peripherally in experimental animals.
  15. Antinociceptive, anti-inflammatory and antipyretic effects of Solanum nigrum aqueous extract in animal models
    Zakaria ZA, Sulaiman MR, Morsid NA, Aris A, Zainal H, Pojan NH, et al.
    Methods Find Exp Clin Pharmacol, 2009 Mar;31(2):81-8.
    PMID: 19455262 DOI: 10.1358/mf.2009.31.2.1353876
    The present study was carried out to evaluate the antinociceptive, anti-inflammatory and antipyretic effects of the aqueous extract of Solanum nigrum leaves using various animal models. The extract, at concentrations of 10, 50 and 100%, was prepared by soaking (1:20; w/v) air-dried powdered leaves (20 g) in distilled water (dH2O) for 72 h. The extract solutions were administered subcutaneously in mice/rats 30 min prior to the tests. The extract exhibited significant (P < 0.05) antinociceptive activity when assessed using the abdominal constriction, hot plate and formalin tests. The extract also produced significant (P < 0.05) anti-inflammatory and antipyretic activities when assessed using the carrageenan-induced paw edema and brewer's yeast-induced pyrexia tests, respectively. Overall, these activities occurred in a concentration-dependent manner, except for the 50% concentration of the extract, which was not effective in the abdominal constriction test. In conclusion, the present study demonstrated that S. nigrum leaves possessed antinociceptive, anti-inflammatory and antipyretic effects and thus supported traditional claims of its medicinal uses.
  16. A geranyl acetophenone targeting cysteinyl leukotriene synthesis prevents allergic airway inflammation in ovalbumin-sensitized mice
    Ismail N, Jambari NN, Zareen S, Akhtar MN, Shaari K, Zamri-Saad M, et al.
    Toxicol Appl Pharmacol, 2012 Mar 1;259(2):257-62.
    PMID: 22266348 DOI: 10.1016/j.taap.2012.01.003
    Asthma is associated with increased pulmonary inflammation and airway hyperresponsiveness. The current use of corticosteroids in the management of asthma has recently raised issues regarding safety and lack of responsiveness in 5-10% of asthmatic individuals. The aim of the present study was to investigate the therapeutic effect of a non-steroidal small molecule that has cysteinyl leukotriene (cysLT) inhibitory activity, upon attenuation of allergic lung inflammation in an acute murine model. Mice were sensitized with ovalbumin (OVA) and treated with several intraperitoneal doses (100, 20, 2 and 0.2mg/kg) of 2,4,6,-trihydroxy-3-geranylacetophenone (tHGA). Bronchoalveolar lavage was performed, blood and lung samples were obtained and respiratory function was measured. OVA sensitization increased pulmonary inflammation and pulmonary allergic inflammation was significantly reduced at doses of 100, 20 and 2mg/kg with no effect at the lowest dose of 0.2mg/kg. The beneficial effects in the lung were associated with reduced eosinophilic infiltration and reduced secretion of Th2 cytokines and cysLTs. Peripheral blood reduction of total IgE was also a prominent feature. Treatment with tHGA significantly attenuated altered airway hyperresponsiveness as measured by the enhanced pause (Penh) response to incremental doses of methacholine. These data demonstrate that tHGA, a synthetic non-steroidal small molecule, can prevent acute allergic inflammation. This proof of concept opens further avenues of research and development of tHGA as an additional option to the current armamentarium of anti-asthma therapeutics.
  17. Anti-inflammatory effect of zerumbone on acute and chronic inflammation models in mice
    Sulaiman MR, Perimal EK, Akhtar MN, Mohamad AS, Khalid MH, Tasrip NA, et al.
    Fitoterapia, 2010 Oct;81(7):855-8.
    PMID: 20546845 DOI: 10.1016/j.fitote.2010.05.009
    The anti-inflammatory activity of zerumbone (1), a natural cyclic sesquiterpene isolated from Zingiber zerumbet Smith was investigated using carrageenan-induced paw edema and cotton pellet-induced granuloma tissue formation test in mice. It was demonstrated that intraperitoneal administration of 1 at a dose of 5, 10, 50 and 100 mg/kg produced significant dose-dependent inhibition of paw edema induced by carrageenan. It was also demonstrated that 1 at similar doses significantly suppressed granulomatous tissue formation in cotton pellet-induced granuloma test.
  18. The effects of a synthetic curcuminoid analogue, 2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone on proinflammatory signaling pathways and CLP-induced lethal sepsis in mice
    Tham CL, Lam KW, Rajajendram R, Cheah YK, Sulaiman MR, Lajis NH, et al.
    Eur J Pharmacol, 2011 Feb 10;652(1-3):136-44.
    PMID: 21114991 DOI: 10.1016/j.ejphar.2010.10.092
    We previously showed that 2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone (BHMC), suppressed the synthesis of various proinflammatory mediators. In this study we explain the mechanism of action of BHMC in lipopolysaccharide (LPS)-induced U937 monocytes and further show that BHMC prevents lethality of CLP-induced sepsis. BHMC showed dose-dependent inhibitory effects on p38, JNK and ERK 1/2 activity as determined by inhibition of phosphorylation of downstream transcription factors ATF-2, c-Jun and Elk-1 respectively. Inhibition of these transcription factors subsequently caused total abolishment of AP-1-DNA binding. BHMC inhibited p65 NF-κB nuclear translocation and DNA binding of p65 NF-κB only at the highest concentration used (12.5μM) but failed to alter phosphorylation of JNK, ERK1/2 and STAT-1. Since the inhibition of p38 activity was more pronounced we evaluated the possibility that BHMC may bind to p38. Molecular docking experiments confirmed that BHMC fits well in the highly conserved hydrophobic pocket of p38 MAP kinase. We also show that BHMC was able to improve survival from lethal sepsis in a murine caecal-ligation and puncture (CLP) model.
  19. Preliminary analysis of the antinociceptive activity of zerumbone
    Sulaiman MR, Perimal EK, Zakaria ZA, Mokhtar F, Akhtar MN, Lajis NH, et al.
    Fitoterapia, 2009 Jun;80(4):230-2.
    PMID: 19535012 DOI: 10.1016/j.fitote.2009.02.002
    We have investigated the antinociceptive activity of zerumbone (1), a natural cyclic sesquiterpene isolated from Zingiber zerumbet Smith, in acetic acid-induced abdominal writhing test and hot plate test in mice. 1 given by intraperitoneal route produced significant dose-dependent antinociceptive effect in all the test models used. In addition, the antinociceptive effect of 1 in the hot plate test was reversed by the non-selective opioid receptor antagonist naloxone, suggesting that the opioid system is involved in its analgesic mechanism of action.
  20. Antinociceptive and antiedematogenic activities of andrographolide isolated from Andrographis paniculata in animal models
    Sulaiman MR, Zakaria ZA, Abdul Rahman A, Mohamad AS, Desa MN, Stanslas J, et al.
    Biol Res Nurs, 2010 Jan;11(3):293-301.
    PMID: 19689990 DOI: 10.1177/1099800409343311
    The current study was performed to evaluate the antinociceptive and antiedematogenic properties of andrographolide isolated from the leaves of Andrographis paniculata using two animal models. Antinociceptive activity was evaluated using the acetic acid- induced writhing and the hot-plate tests, while antiedematogenic activity was measured using the carrageenan-induced paw edema test. Subcutaneous (s.c.) administration of andrographolide (10, 25, and 50 mg/kg) did not affect the motor coordination of the experimental animals but produced significant (p < .05) antinociceptive activity when assessed using both tests. However, 2 mg/kg naloxone failed to affect the 25 mg/kg andrographolide activity in both tests, indicating that the activity was modulated via nonopioid mechanisms. Furthermore, andrographolide showed significant (p < .05) antiedematogenic activity. In conclusion, the results obtained suggest that andrographolide has antinociceptive and antiedematogenic activities; it may be useful for treating pain and inflammation once human studies are conducted.
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