Displaying publications 1 - 20 of 90 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. Adam Y, Somchit MN, Sulaiman MR, Nasaruddin AA, Zuraini A, Bustamam AA, et al.
    J Ethnopharmacol, 2009 Jul 6;124(1):154-8.
    PMID: 19375494 DOI: 10.1016/j.jep.2009.04.014
    Orthosiphon stamineus has been used in traditional medicine for centuries especially to treat diseases of the urinary system.
  3. Lee YZ, Ming-Tatt L, Lajis NH, Sulaiman MR, Israf DA, Tham CL
    Molecules, 2012 Dec 07;17(12):14555-64.
    PMID: 23222902 DOI: 10.3390/molecules171214555
    A sensitive and accurate high performance liquid chromatography with ultraviolet/visible light detection (HPLC-UV/VIS) method for the quantification of 2,6-bis-(4-hydroxy-3-methoxybenzylidene)-cyclohexanone (BHMC) in rat plasma was developed and validated. BHMC and the internal standard, harmaline, were extracted from plasma samples by a simple liquid-liquid extraction using 95% ethyl acetate and 5% methanol. Plasma concentration of BHMC and internal standard were analyzed by reversed phase chromatography using a C₁₈ column (150 × 4.6 mm I.D., particle size 5 µm) and elution with a gradient mobile phase of water and methanol at a flow rate of 1.0 mL/min. Detection of BHMC and internal standard was done at a wavelength of 380 nm. The limit of quantification was 0.02 µg/mL. The calibration curves was linear (R² > 0.999) over the concentration range of 0.02-2.5 µg/mL. Intra- and inter-day precision were less than 2% coefficient of variation. The validated method was then applied to a pharmacokinetic study in rats by intravenous administration of BHMC at a single dose of 10 mg/kg. Pharmacokinetic parameters such as half-life, maximum plasma concentration, volume of distribution, clearance and elimination rate constant for BHMC were calculated.
  4. Hisamuddin N, Shaik Mossadeq WM, Sulaiman MR, Abas F, Leong SW, Kamarudin N, et al.
    Molecules, 2019 Jul 18;24(14).
    PMID: 31323775 DOI: 10.3390/molecules24142614
    Curcumin, derived from the rhizome Curcuma longa, has been scientifically proven to possess anti-inflammatory activity but is of limited clinical and veterinary use owing to its low bioavailability and poor solubility. Hence, analogs of curcuminoids with improved biological properties have been synthesized to overcome these limitations. This study aims to provide the pharmacological basis for the use of 5-(3,4-dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one (DHHPD), a synthetic curcuminoid analog, as an anti-edematogenic and anti-granuloma agent. The carrageenan-induced paw edema and the cotton pellet-induced granuloma assays were used to assess the anti-inflammatory activity of DHHPD in mice. The effects of DHHPD on the histaminergic, serotonergic, and bradykininergic systems were determined by the histamine-, serotonin-, and bradykinin-induced paw edema tests, respectively. DHHPD (0.1, 0.3, 1, and 3 mg/kg, intraperitoneal) evoked significant reductions (p < 0.05) in carrageenan-induced paw edema at different time intervals and granuloma formation (p < 0.0001) by 22.08, 32.57, 37.20, and 49.25%, respectively. Furthermore, DHHPD significantly reduced paw edema (p < 0.05) induced by histamine, serotonin, and bradykinin. The present study suggests that DHHPD exerts anti-edematogenic activity, possibly by inhibiting the synthesis or release of autacoid mediators of inflammation through the histaminergic, serotonergic, and bradykininergic systems. The anti-granuloma effect may be attributed to the suppression of transudative, exudative, and proliferative activities associated with inflammation.
  5. Ming-Tatt L, Khalivulla SI, Akhtar MN, Lajis N, Perimal EK, Akira A, et al.
    Pharmacol. Biochem. Behav., 2013 Dec;114-115:58-63.
    PMID: 24201054 DOI: 10.1016/j.pbb.2013.10.019
    The present study investigated the analgesic effect of a novel synthetic cyclohexanone derivative, 2,6-bis-4-(hydroxyl-3-methoxybenzilidine)-cyclohexanone or BHMC in a mouse model of chronic constriction injury-induced neuropathic pain. It was demonstrated that intraperitoneal administration of BHMC (0.03, 0.1, 0.3 and 1.0mg/kg) exhibited dose-dependent inhibition of chronic constriction injury-induced neuropathic pain in mice, when evaluated using Randall-Selitto mechanical analgesiometer. It was also demonstrated that pretreatment of naloxone (non-selective opioid receptor blocker), nor-binaltorphimine (nor-BNI, selective κ-opioid receptor blocker), but not β-funaltrexamine (β-FN, selective μ-opioid receptor blocker) and naltrindole hydrochloride (NTI, selective δ-opioid receptor blocker), reversed the anti-nociceptive effect of BHMC. In addition, the analgesic effect of BHMC was also reverted by pretreatment of 1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one (ODQ, soluble guanosyl cyclase blocker) and glibenclamide (ATP-sensitive potassium channel blocker) but not Nω-nitro-l-arginine (l-NAME, a nitric oxide synthase blocker). Taken together, the present study demonstrated that the systemic administration of BHMC attenuated chronic constriction, injury-induced neuropathic pain. We also suggested that the possible mechanisms include κ-opioid receptor activation and nitric oxide-independent cyclic guanosine monophosphate activation of ATP-sensitive potassium channel opening.
  6. Kamaldin MN, Akhtar MN, Mohamad AS, Lajis N, Perimal EK, Akira A, et al.
    Molecules, 2013 Apr 10;18(4):4209-20.
    PMID: 23612473 DOI: 10.3390/molecules18044209
    Previous studies have shown that systemic administration of 6'-hydroxy-2',4'-dimethoxychalcone (flavokawin B, FKB) exerts significant peripheral and central antinociceptive effects in laboratory animals. However, the mechanisms underlying these peripheral and central antinociceptive effects have yet to be elucidated. Therefore, the objective of the present study was to evaluate the participation of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/potassium (K+) channels pathway in the peripheral antinociception induced by FKB. It was demonstrated that intraplantar (i.pl.) administration of FKB (150, 250, 375 and 500 µg/paw) resulted in dose-dependent peripheral antinociception against mechanical hyperalgesia in carrageenan-induced hyperalgesia test model in rats. The possibility of FKB having either a central or a systemic effect was excluded since administration of FKB into the right paw did not elicit antinociception in the contralateral paw. Furthermore, peripheral antinociception induced by FKB (500 µg/paw) was significantly reduced when L-arginine (25 µg/paw, i.pl.), Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 50 µg/paw, i.pl.), glibenclamide (300 µg/paw, i.pl.), tetraethylammonium (300 µg/paw, i.pl.) and charybdotoxin (3 µg/paw, i.pl.) were injected before treatment. Taken together, our present data suggest that FKB elicits peripheral antinociception when assessed in the mechanical hyperalgesia induced by carrageenan. In addition, it was also demonstrated that this effect was mediated through interaction of the NO/cGMP/K+ channels signaling pathway.
  7. Ming-Tatt L, Khalivulla SI, Akhtar MN, Mohamad AS, Perimal EK, Khalid MH, et al.
    Basic Clin Pharmacol Toxicol, 2012 Mar;110(3):275-82.
    PMID: 21967232 DOI: 10.1111/j.1742-7843.2011.00804.x
    This study investigated the potential antinociceptive efficacy of a novel synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)cyclohexanone (BHMC), using chemical- and thermal-induced nociception test models in mice. BHMC (0.03, 0.1, 0.3 and 1.0 mg/kg) administered via intraperitoneal route (i.p.) produced significant dose-related inhibition in the acetic acid-induced abdominal constriction test in mice with an ID(50) of 0.15 (0.13-0.18) mg/kg. It was also demonstrated that BHMC produced significant inhibition in both neurogenic (first phase) and inflammatory phases (second phase) of the formalin-induced paw licking test with an ID(50) of 0.35 (0.27-0.46) mg/kg and 0.07 (0.06-0.08) mg/kg, respectively. Similarly, BHMC also exerted significant increase in the response latency period in the hot-plate test. Moreover, the antinociceptive effect of the BHMC in the formalin-induced paw licking test and the hot-plate test was antagonized by pre-treatment with the non-selective opioid receptor antagonist, naloxone. Together, these results indicate that the compound acts both centrally and peripherally. In addition, administration of BHMC exhibited significant inhibition of the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin with ID(50) of 0.66 (0.41-1.07) mg/kg and 0.42 (0.38-0.51) mg/kg, respectively. Finally, it was also shown that BHMC-induced antinociception was devoid of toxic effects and its antinociceptive effect was associated with neither muscle relaxant nor sedative action. In conclusion, BHMC at all doses investigated did not cause any toxic and sedative effects and produced pronounced central and peripheral antinociceptive activities. The central antinociceptive activity of BHMC was possibly mediated through activation of the opioid system as well as inhibition of the glutamatergic system and TRPV1 receptors, while the peripheral antinociceptive activity was perhaps mediated through inhibition of various inflammatory mediators.
  8. Perimal EK, Akhtar MN, Mohamad AS, Khalid MH, Ming OH, Khalid S, et al.
    Basic Clin Pharmacol Toxicol, 2011 Mar;108(3):155-62.
    PMID: 20955360 DOI: 10.1111/j.1742-7843.2010.00635.x
    This study investigated the antinociceptive effects of zerumbone in chemical behavioural models of nociception in mice. Zerumbone given through intraperitoneal route (i.p.) produced dose-related antinociception when assessed on acetic acid-induced abdominal writhing test in mice. In addition, the i.p. administration of zerumbone exhibited significant inhibition of the neurogenic pain induced by intraplantar (i.pl.) injection of capsaicin and bradykinin. Likewise, zerumbone given by i.p. route reduced the nociception produced by i.pl. injection of glutamate and phorbol myristate acetate (PMA). The antinociception caused by zerumbone in the acetic acid test was significantly attenuated by i.p. pre-treatment of mice with l-arginine (nitric oxide precursor) and glibenclamide (ATP-sensitive K(+) channel inhibitor). However, the antinociception of zerumbone was enhanced by methylene blue (non-specific gyanylyl cyclase inhibitor). Together, these results indicate that zerumbone produces pronounced antinociception against chemical models of nociception in mice. It also strongly suggests that the l-arginine-nitric oxide-cGMP-PKC-K(+) ATP channel pathways, the TRPV1 and kinin B2 receptors play an important role in the zerumbone-induced antinociception.
  9. 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.
  10. Ong HM, Mohamad AS, Makhtar N', Khalid MH, Khalid S, Perimal EK, et al.
    J Ethnopharmacol, 2011 Jan 7;133(1):227-33.
    PMID: 20920570 DOI: 10.1016/j.jep.2010.09.030
    Acmella uliginosa (Sw.) Cass. is a medicinal herbaceous plant that is commonly used by the Malay community in Malaysia to relieve pain often associated with mouth ulcers, toothache, sore throat, and stomach ache.
  11. Zakaria ZA, Hussain MK, Mohamad AS, Abdullah FC, Sulaiman MR
    Biol Res Nurs, 2012 Jan;14(1):90-7.
    PMID: 21278166 DOI: 10.1177/1099800410395378
    Ficus deltoidea (Family Moraceae) leaves have been used traditionally by the Malays to treat ailments such as wounds, sores, and rheumatism. The aim of the present study was to determine the anti-inflammatory activity of the aqueous extract of F. deltoidea leaf (FDA) using acute and chronic inflammatory models. FDA, in the doses of 30, 100, and 300 mg/kg, was administered intraperitoneally in rats (n = 6) before the animals were subjected to the carrageenan-induced paw edema test, cotton pellet-induced granuloma test, and formalin test. The first two tests represent acute and chronic models of inflammation, respectively. The first and second phases of the formalin test represent neurogenic pain and inflammatory-mediated pain, respectively; thus, only the second phase was measured in the present study. Results showed that FDA exerted significant (p < .05) anti-inflammatory activity in all assays, with dose-response effects seen in the paw edema and formalin tests. In conclusion, the leaf of F. deltoidea possesses anti-inflammatory activity against acute and chronic inflammatory responses and against pain-associated inflammatory response. These findings justify the traditional uses of F. deltoidea leaves for treatment of inflammatory-mediated ailments.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. Zakaria ZA, Gopalan HK, Zainal H, Mohd Pojan NH, Morsid NA, Aris A, et al.
    Yakugaku Zasshi, 2006 Nov;126(11):1171-8.
    PMID: 17077618
    AIM: The present study was carried out to evaluate the antinociceptive, anti-inflammatory and antipyretic effects of chloroform extract of Solanum nigrum leaves using various animal models.

    METHODS: The extract was prepared by soaking (1:20; w/v) the air-dried powdered leaves (20 g) in chloroform for 72 hrs followed by evaporation (40 degrees C) under reduced pressure to dryness (1.26 g) and then dissolved (1:50; w/v) in dimethylsulfoxide (DMSO). The supernatant, considered as the stock solution with dose of 200 mg/kg, was diluted using DMSO to 20 and 100 mg/kg, and all doses were administered (s.c.; 10 ml/kg) in mice/rats 30 min prior to tests.

    RESULTS: 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. Overall, the activities occurred in a dose-independent manner.

    CONCLUSION: The present study demonstrated that the lipid-soluble extract of S. nigrum leaves possessed antinociceptive, anti-inflammatory and anti-pyretic properties and confirmed the traditional claims.

  17. Pariyani R, Ismail IS, Azam AA, Abas F, Shaari K, Sulaiman MR
    Biomed Res Int, 2015;2015:742420.
    PMID: 26819955 DOI: 10.1155/2015/742420
    The term Java tea refers to the decoction of Orthosiphon stamineus (OS) Benth (Lamiaceae) leaves, which are widely consumed by the people in Europe and South East Asian countries. The OS leaves are known for their use in traditional medicinal systems as a prophylactic and curative agent for urinary stone, diabetes, and hypertension and also as a diuretic agent. The present study was aimed at evaluating its possible toxicity. Herein, the major phytochemical constituents of microwave dried OS leaf, which is the common drying process for tea sachets in the market, were also identified. The acute oral toxicity test of aqueous, 50% aqueous ethanolic, and ethanolic extracts of OS was performed at a dose of 5000 mg/Kg body weight of Sprague-Dawley rats. During the 14-day study, the animals were observed for any mortality, behavioral, motor-neuronal abnormalities, body weight, and feed-water consumption pattern. The hematological and serum biochemical parameters to assess the kidney and liver functions were carried out, along with the histological analysis of these organs. It was found that all microwave dried OS leaf extracts did not cause any toxic effects or mortality at the administered dose. No abnormality was noticed in all selected parameters in rats of both sexes as compared with their respective control groups. Thus, the possible oral lethal dose for microwave dried Java tea leaves is more than 5000 mg/Kg body weight.
  18. 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.
  19. Pui Ping C, Akhtar MN, Israf DA, Perimal EK, Sulaiman MR
    Molecules, 2020 Nov 18;25(22).
    PMID: 33217904 DOI: 10.3390/molecules25225385
    The perception of pain caused by inflammation serves as a warning sign to avoid further injury. The generation and transmission of pain impulses involves various pathways and receptors. Cardamonin isolated from Boesenbergia rotunda (L.) Mansf. has been reported to exert antinociceptive effects in thermal and mechanical pain models; however, the precise mechanism has yet to be examined. The present study investigated the possible mechanisms involved in the antinociceptive activity of cardamonin on protein kinase C, N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptors, l-arginine/cyclic guanosine monophosphate (cGMP) mechanism, as well as the ATP-sensitive potassium (K+) channel. Cardamonin was administered to the animals intra-peritoneally. Present findings showed that cardamonin significantly inhibited pain elicited by intraplantar injection of phorbol 12-myristate 13-acetate (PMA, a protein kinase C activator) with calculated mean ED50 of 2.0 mg/kg (0.9-4.5 mg/kg). The study presented that pre-treatment with MK-801 (NMDA receptor antagonist) and NBQX (non-NMDA receptor antagonist) significantly modulates the antinociceptive activity of cardamonin at 3 mg/kg when tested with glutamate-induced paw licking test. Pre-treatment with l-arginine (a nitric oxide precursor), ODQ (selective inhibitor of soluble guanylyl cyclase) and glibenclamide (ATP-sensitive K+ channel inhibitor) significantly enhanced the antinociception produced by cardamonin. In conclusion, the present findings showed that the antinociceptive activity of cardamonin might involve the modulation of PKC activity, NMDA and non-NMDA glutamate receptors, l-arginine/nitric oxide/cGMP pathway and ATP-sensitive K+ channel.
  20. Ismail NI, Ming-Tatt L, Lajis N, Akhtar MN, Akira A, Perimal EK, et al.
    Molecules, 2016 Aug 22;21(8).
    PMID: 27556438 DOI: 10.3390/molecules21081077
    The antinociceptive effects produced by intraperitoneal administration of a novel synthetic chalcone, 3-(2,3-dimethoxyphenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one (DMFP), were investigated in several mouse models of induced nociception. The administration of DMFP (0.1, 0.5, 1.0 and 5.0 mg/kg) produced significant attenuation on the acetic acid-induced abdominal-writhing test. It also produced a significant increase in response latency time in the hot-plate test and a marked reduction in time spent licking the injected paw in both phases of the formalin-induced paw-licking test. In addition, it was also demonstrated that DMFP exhibited significant inhibition of the neurogenic nociceptive response induced by intraplantar injections of capsaicin and glutamate. Moreover, the antinociceptive effect of DMFP in the acetic acid-induced abdominal-writhing test and the hot-plate test was not antagonized by pretreatment with a non-selective opioid receptor antagonist, naloxone. Finally, DMFP did not show any toxic effects and/or mortality in a study of acute toxicity and did not interfere with motor coordination during the Rota-rod test. Our present results show that DMFP exhibits both peripheral and central antinociceptive effects. It was suggested that its peripheral antinociceptive activity is associated with attenuated production and/or release of NO and various pro-inflammatory mediators, while central antinociceptive activity seems to be unrelated to the opioidergic system, but could involve, at least in part, an interaction with the inhibition of capsaicin-sensitive fibers and the glutamatergic system.
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