Displaying publications 1 - 20 of 31 in total

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  1. Israf DA, Tham CL, Syahida A, Lajis NH, Sulaiman MR, Mohamad AS, et al.
    Phytomedicine, 2010 Aug;17(10):732-9.
    PMID: 20378317 DOI: 10.1016/j.phymed.2010.02.006
    In a previous communication we showed that atrovirinone, a 1,4-benzoquinone isolated from the roots of Garcinia atroviridis, was able to inhibit several major proinflammatory mediators of inflammation. In this report we show that atrovirinone inhibits NO and PGE(2) synthesis through inhibition of iNOS and COX-2 expression. We also show that atrovirinone inhibits the secretion of IL-1beta and IL-6 in a dose dependent fashion whereas the secretion of IL-10, the anti-inflammatory cytokine, was enhanced. Subsequently we determined that the inhibition of proinflammatory cytokine synthesis and inducible enzyme expression was due to a dose-dependent inhibition of phosphorylation of p38 and ERK1/2. We also showed that atrovirinone prevented phosphorylation of I-kappaBalpha, which resulted in a reduction of p65NF-kappaB nuclear translocation as demonstrated by expression analysis. We conclude that atrovirinone is a potential anti-inflammatory drug lead that targets both the MAPK and NF-kappaB pathway.
  2. Saha K, Lajis NH, Israf DA, Hamzah AS, Khozirah S, Khamis S, et al.
    J Ethnopharmacol, 2004 Jun;92(2-3):263-7.
    PMID: 15138010
    Methanol extracts of seven Malaysian medicinal plants were screened for antioxidant and nitric oxide inhibitory activities. Antioxidant activity was measured by using FTC, TBA and DPPH free radical scavenging methods and Griess assay was used for the measurement of nitric oxide inhibition in lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma)-treated RAW 264.7 cells. All the extracts showed strong antioxidant activity comparable to or higher than that of alpha-tocopherol, BHT and quercetin in FTC and TBA methods. The extracts from Leea indica and Spermacoce articularis showed strong DPPH free radical scavenging activity comparable with quercetin, BHT and Vit C. Spermacoce exilis showed only moderate activity but other species were weak as compared to the standards. In the Griess assay Lasianthus oblongus, Chasalia chartacea, Hedyotis verticillata, Spermacoce articularis and Leea indica showed strong inhibitory activity on nitric oxide production in LPS and IFN-gamma-induced RAW 264.7 cells. Extracts from Psychotria rostrata and Spermacoce exilis also inhibited NO production but this was due to their cytotoxic effects upon cells during culture.
  3. Zakaria ZA, Mohamad AS, Ahmad MS, Mokhtar AF, Israf DA, Lajis NH, et al.
    Biol Res Nurs, 2011 Oct;13(4):425-32.
    PMID: 21112917 DOI: 10.1177/1099800410386590
    Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used for the treatment of inflammation. However, despite their effectiveness, most NSAIDs cause various side effects that negatively affect the management of inflammation and, in part, pain. Thus, there is a need to search for new anti-inflammatory agents with few, or no, side effects. Natural products of plant, animal, or microorganism origin have been good sources of new bioactive compounds. The present study was carried out to evaluate the acute and chronic anti-inflammatory activities of the essential oil of the rhizomes of Zingiber zerumbet (Zingiberaceae) using the carrageenan-induced paw edema and cotton pellet-induced granuloma tests, respectively. The effect of the essential oil on inflammatory- and noninflammatory-mediated pain was also assessed using the formalin test. Essential oil of Z. zerumbet, at doses of 30, 100, and 300 mg/kg, was administered intraperitoneally to rats. The substance exhibited significant anti-inflammatory activity both in acute and chronic animal models. The essential oil also inhibited inflammatory- and noninflammatory-mediated pain when assessed using the formalin test. In conclusion, the essential oil of Z. zerumbet possessed anti-inflammatory activity, in addition to its antinociceptive activity, which may explain its traditional uses to treat inflammatory-related ailments.
  4. 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.
  5. Khalid S, Shaik Mossadeq WM, Israf DA, Hashim P, Rejab S, Shaberi AM, et al.
    Med Princ Pract, 2010;19(4):255-9.
    PMID: 20516700 DOI: 10.1159/000312710
    To study the effects of Tamarindus indica L. aqueous fruit extract on the antinociceptive activities in rodent models.
  6. Zakaria ZA, Patahuddin H, Mohamad AS, Israf DA, Sulaiman MR
    J Ethnopharmacol, 2010 Mar 2;128(1):42-8.
    PMID: 20035852 DOI: 10.1016/j.jep.2009.12.021
    Ethnopharmacological relevance: Piper sarmentosum (Piperaceae) is a medicinal plant traditionally used by the Malays to treat headaches, toothaches, coughs, asthma and fever.

    Aim of the study: In order to establish the pharmacological properties of the leaf of this plant, studies were performed on anti-nociceptive and anti-inflammatory activities.

    Materials and methods: The aqueous extract of Piper sarmentosum (AEPS) was prepared in the doses of 30, 100 and 300 mg/kg. Anti-nociceptive activity of AEPS was evaluated by abdominal constriction and hot-plate tests. AEPS was also pre-challenged with 5mg/kg naloxone to determine the involvement of opioid receptors. Anti-inflammatory activity was evaluated using carrageenan-induced paw edema assay.

    Results: Subcutaneous administration of AEPS exhibited anti-nociceptive activity (P<0.05) in a dose-dependent manner in the abdominal constriction and hot-plate tests. Pre-treatment with naloxone completely (P<0.05) diminished the extract anti-nociceptive activity in both tests. The AEPS, at all doses used, exerted significant (P<0.05) anti-inflammatory activity in a dose-dependent manner.

    Conclusions: The AEPS exhibits opioid-mediated anti-nociceptive activity at the peripheral and central levels, as well as anti-inflammatory activity, which confirmed the traditional uses of the plant in the treatment of pain- and inflammatory-related ailments.
  7. Israf DA, Lajis NH, Somchit MN, Sulaiman MR
    Life Sci, 2004 Jun 11;75(4):397-406.
    PMID: 15147827
    An experiment was conducted with the objective to enhance mucosal immunity against ovalbumin (OVA) by co-administration of OVA with an aqueous extract from the fruit of Solanum torvum (STE). Five groups of female ICR mice aged approximately 8 weeks at the commencement of the experiment were caged in groups of eight and received various treatments. The treatments included OVA alone, OVA with cholera toxin (CT), and OVA with various doses of STE. Mice were primed intraperitoneally with 500 microg of OVA alone or co-administered with 0.1 microg CT, or with 1 microg STE. All mice were boosted orally via gastric intubation 14 days after priming with 10 mg OVA alone, or co-administered with 10 microg CT or with 10 mg, 1 mg or 0.1 mg STE. One week later all mice were killed and organs obtained for analysis of the immune response. Intestinal, faecal and pulmonary OVA-specific sIgA concentration was significantly increased (p<0.05) in mice that received booster combinations of OVA/CT and OVA with all extract doses (p<0.05). Specific serum IgG titres did not differ significantly between groups. It is concluded that STE can significantly enhance secretory immunity in the intestine to OVA with mucosal homing to the lungs. The adjuvant effect of STE is comparable to that of CT.
  8. Zakaria ZA, Mohamad AS, Chear CT, Wong YY, Israf DA, Sulaiman MR
    Med Princ Pract, 2010;19(4):287-94.
    PMID: 20516705 DOI: 10.1159/000312715
    OBJECTIVE: The present study was carried out to determine the antiinflammatory and antinociceptive activities of a methanol extract of Zingiber zerumbet rhizomes (MEZZ) using various experimental model systems.

    MATERIALS AND METHODS: The MEZZ was prepared by macerating oven-dried (50 degrees C) powdered rhizomes (1.2 kg) of Z. zerumbet in 80% methanol in a ratio of 1:20 (w/v) for 48 h. The supernatant was collected, filtered and evaporated to dryness under reduced pressure (50 degrees C) yielding approximately 21.0 g of the crude dried extract. The crude dried extract was stored at -20 degrees C prior to use and was dissolved in normal saline (0.9% NaCl) immediately before administration at concentrations required to produce doses of 25, 50 and 100 mg/kg.

    RESULTS: All dosages of MEZZ showed significant (p < 0.05) antiedema activity when assessed using the carrageenan-induced paw edema test and the cotton-pellet-induced granuloma test. The MEZZ exhibited significant (p < 0.05) antinociceptive activity when assessed by the writhing, hot plate and formalin tests. Pretreatment with naloxone (5 mg/kg) significantly decreased the latency of discomfort produced by the 100 mg/kg dose of MEZZ in the hot plate test.

    CONCLUSION: MEZZ produced antiinflammatory and antinociceptive activities which may involve the inhibition of bradykinin-, prostaglandin-, histamine- and opioid-mediated processes.

  9. Al-Haddawi MH, Jasni S, Israf DA, Zamri-Saad M, Mutalib AR, Sheikh-Omar AR
    Res Vet Sci, 2001 Jun;70(3):191-7.
    PMID: 11676614
    Sixteen 8- to 9-week-old Pasteurella multocida-free New Zealand White rabbits were divided into two equal groups. The first group was inoculated intranasally with P multocida serotype D:1 strain and the second group that was inoculated with phosphate-buffered saline (PBS) only was used as a control group. Pasteurella multocida was isolated from the nasal cavity of all infected rabbits in group 1 and from tracheal swabs of seven rabbits in this group. Four rabbits in group 1 died with clinical signs of septicaemia, two rabbits had mucopurulent nasal discharge and pneumonic lesions and the other two did not show any clinical signs or gross lesions. The ultrastructural changes detected were deciliation or clumping of cilia of ciliated epithelium, cellular swelling, vacuolation and sloughing. The subepithelial capillaries showed congestion, intravascular fibrin deposition, platelets aggregation and endothelial injury. Pasteurella multocida was observed attached to the injured endothelial cells. Heterophils, mast cells, vacuolated monocytes and macrophages infiltrated the lamina propria and between the degenerated epithelial cells.
  10. Zulkifli I, Che Norma MT, Israf DA, Omar AR
    Poult Sci, 2000 Oct;79(10):1401-7.
    PMID: 11055844
    This study was conducted to determine whether early age feed restriction improves heat tolerance in female broiler chickens. Chicks were brooded for 3 wk and then maintained at 24+/-1 C. On Day 0, chicks were assigned to one of four feeding regimens; each regimen was applied to four cages of chicks. The feeding regimens were 1) ad libitum feeding (ALF); 2) 40% feed restriction at 4, 5, and 6 d of age (F40); 3) 60% feed restriction at 4, 5, and 6 d of age (F60); and (4) 80% feed restriction at 4, 5, and 6 d of age (F80). From 35 to 41 d of age, all birds were exposed to 38+/-1 C for 2 h/d. Serum concentrations of glucose were elevated by the heat challenge, but were not affected by the feeding regimen. The heat treatment resulted in hypocholesteremia among ALF and F80 chicks, whereas the concentrations increased and remained constant in the F60 and F40 birds, respectively. Subjecting chicks to F60 improved growth and survivability and reduced heterophil to lymphocyte ratios (H/L) in response to the heat treatment as compared with the ALF and F80 regimens. The survivability rate and H/L of F40 chicks were similar to those attained by chicks on other regimens. Newcastle disease antibody titer of ALF birds declined with duration of heat treatment. It is concluded that the F60 regimen is beneficial for alleviating, at least in part, the detrimental effects of heat stress in female broiler chickens.
  11. Zulkifli I, Che Norma MT, Israf DA, Omar AR
    Br Poult Sci, 2002 Mar;43(1):141-5.
    PMID: 12003331
    1. This study was conducted to determine the effect of early-age food restriction on heat shock protein (hsp) 70 synthesis in the brains of female broiler chickens exposed to high ambient temperatures. 2. Chicks were brooded for 3 weeks and then maintained at 24+/-1 degrees C. 3. On d 0, chicks were assigned to one of 4 feeding regimens; each regimen was applied to 4 cages of chicks. The regimens were: (1) ad libitum feeding (AL); (2) 80% food restriction at 4, 5 and 6 d of age (F80); (3) 60% food restriction at 4, 5, and 6 d of age (F60); and (4) 40% food restriction at 4, 5 and 6 d of age (F40). From d 35 to d 41, all chicks were subjected to 38+/-1 degrees C for 2 h/d. 4. One day following food restriction (d 7), hsp 70 expression in the brain samples of F60 and F40 chicks was augmented but not those fed AL and F80. 5. Prior to the heat challenge (d 35), all chicks had similar hsp 70 response. Irrespective of feeding regimen, there was a marked increase in hsp 70 expression after 4 d of heat treatment (d 38). Following 7 d of heat exposure (d 41), except for the F60 chicks, the augmented hsp 70 expression in the brains of AL, F80 and F40 birds was not maintained. 6. Enhancement of hsp 70 expression was noted in birds subjected to F60, but not AL, F80 or F40, throughout the period of heat exposure.
  12. Israf DA, Zainal MJ, Ben-Gheshir MA, Rasedee A, Sani RA, Noordin MM
    J. Helminthol., 1998 Jun;72(2):143-6.
    PMID: 9687595
    The influence of dietary protein supplementation upon resistance to haemonchosis was examined in Dorsimal (Polled Dorset x Malin) lambs offered two levels of protein. Lambs were offered either a complete basal ruminant diet (15% crude protein (CP)) or the same diet supplemented with fish meal as a source of rumen bypass protein (19% CP). Lambs from each dietary treatment group were given either a 7-week trickle infection with Haemonchus contortus infective larvae (L3) or remained uninfected. All lambs were drenched with anthelmintic at week 8 post-infection (PI), challenged with a single dose of 5000 H. contortus L3 one week later, and killed 14 days post-challenge (PC). Lambs on the supplemented diet that were trickle infected showed a significant reduction in egg output. Supplementation and previous infection did not affect either growth rate, worm burden, worm development or haematological parameters. There was a trend for enhanced growth among supplemented non-infected lambs in comparison to lambs which received the basal ration.
  13. Sabri MY, Zamri-Saad M, Mutalib AR, Israf DA, Muniandy N
    Vet Microbiol, 2000 Apr 04;73(1):13-23.
    PMID: 10731614
    The outer membrane proteins (OMP) were extracted from the P. haemolytica A2, A7 and A9 to determine their potential as immunogens and their capability for cross-protection. Sixty lambs of approximately 9 months old were divided into four main groups. Animals in Group 1 were vaccinated with 2ml vaccine containing 100microg/ml of the outer membrane proteins of P. haemolytica A2. Animals in Group 2 were similarly vaccinated with the OMPs of P. haemolytica A7 while Group 3 with OMPs of P. haemolytica A9. Animals in Group 4 were unvaccinated control. During the course of the study, serum was collected to evaluate the antibody levels toward each OMP. There appeared to be good immune responses. However, high antibody levels did not necessarily result in good protection of the animals, particularly against cross-infection with P. haemolytica A9 in animals vaccinated with the OMPs of P. haemolytica A2. It seemed that the antibody responses were more specific toward the homologous challenge but generally did not cross-protect against heterologous serotype challenge. However, the OMPs of P. haemolytica A7 produced good in vivo cross-protection and excellent correlations when good antibody responses against all serotypes led to successful reductions of the extent of lung lesions following homologous and heterologous challenge exposures. Thus, the OMPs of P. haemolytica A7 was effective in protecting animals against homologous and heterologous infection by live P. haemolytica A2, A7 and A9.
  14. 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.
  15. Abas F, Hui LS, Ahmad S, Stanslas J, Israf DA, Shaari K, et al.
    Z Naturforsch C J Biosci, 2006 12 2;61(9-10):625-31.
    PMID: 17137104
    Nine derivatives of three natural diarylheptanoids, curcumin, demethoxycurcumin and bisdemethoxycurcumin, were prepared. Their antioxidant, free radical scavenging, nitric oxide (NO) inhibitory and cytotoxic activities were evaluated and compared with those of the respective natural compounds. Curcumin (1), demethoxycurcumin (2), demethyldemethoxy-curcumin (C3), diacetyldemethoxycurcumin (AC2) and triacetyldemethylcurcumin (AC5) exhibited higher antioxidant activity than quercetin while products from demethylation of 1 and 2 exhibited higher free radical scavenging activity. Compounds AC2 and AC5 were found to be most active in inhibiting breast cancer cells (MCF-7) proliferation with IC50 values of 6.7 and 3.6 microM, respectively. The activity of AC2 is almost doubled and of AC5 almost tripled as compared to curcumin. Their selectivity towards different cell lines is also more noticeable. Compounds AC2 and AC5 also showed increased activity against a human prostate cancer cell line (DU-145) and non-small lung cancer cell line (NCI-H460) with IC50 values of 20.4, 16.3 and 18.3, 10.7 microM, respectively.
  16. 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.
  17. Israf DA, Khaizurin TA, Syahida A, Lajis NH, Khozirah S
    Mol Immunol, 2007 Feb;44(5):673-9.
    PMID: 16777230
    Cardamonin, a chalcone isolated from the fruits of a local plant Alpinia rafflesiana, has demonstrated anti-inflammatory activity in cellular models of inflammation. In this report, we evaluated the ability of cardamonin to suppress both NO and PGE2 synthesis, iNOS and COX-2 expression and enzymatic activity, and key molecules in the NF-kappaB pathway in order to determine its molecular target. Cardamonin suppressed the production of NO and PGE2 in interferon-gamma (IFN-gamma)- and lipopolysaccharide (LPS)-induced RAW 264.7 cells. This inhibition was demonstrated to be caused by a dose-dependent down-regulation of both inducible enzymes, iNOS and COX-2, without direct effect upon iNOS or COX-2 enzyme activity. Subsequently we determined that the inhibition of inducible enzyme expression was due to a dose-dependent inhibition of phosphorylation and degradation of I-kappaBalpha, which resulted in a reduction of p65NF-kappaB nuclear translocation. We conclude that cardamonin is a potential anti-inflammatory drug lead that targets the NF-kappaB pathway.
  18. 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.
  19. 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. 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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