Displaying publications 1 - 20 of 29 in total

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  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. Khalid MH, Akhtar MN, Mohamad AS, Perimal EK, Akira A, Israf DA, et al.
    J Ethnopharmacol, 2011 Sep 01;137(1):345-51.
    PMID: 21664960 DOI: 10.1016/j.jep.2011.05.043
    ETHNOPHARMACOLOGICAL RELEVANCE: Zingiber zerumbet (L.) Smith, a wild edible ginger species or locally known as "lempoyang", commonly used in the Malays traditional medicine as an appetizer or to treat stomachache, toothache, muscle sprain and as a cure for swelling sores and cuts.

    AIM: The present study was conducted to investigate the possible mechanism of actions underlying the systemic antinociception activity of the essential oil of Zingiber zerumbet (EOZZ) in chemical-induced nociception tests in mice.

    MATERIALS AND METHODS: Acetic acid-induced abdominal constriction, capsaicin-, glutamate- and phorbol 12-myristate 13-acetate-induced paw licking tests in mice were employed in the study. In all experiments, EOZZ was administered systemically at the doses of 50, 100, 200 and 300 mg/kg.

    RESULTS: It was shown that EOZZ given to mice via intraperitoneal and oral routes at 50, 100, 200 and 300 mg/kg produced significant dose dependent antinociception when assessed using acetic acid-induced abdominal writing test with calculated mean ID(50) values of 88.84 mg/kg (80.88-97.57 mg/kg) and 118.8 mg/kg (102.5-137.8 mg/kg), respectively. Likewise, intraperitoneal administration of EOZZ at similar doses produced significant dose dependent inhibition of neurogenic pain induced by intraplantar injection of capsaicin (1.6 μg/paw), glutamate (10 μmol/paw) and phorbol 12-myristate 13-acetate (1.6μg/paw) with calculated mean ID(50) of 128.8 mg/kg (118.6-139.9 mg/kg), 124.8 mg/kg (111.4-139.7 mg/kg) and 40.29 (35.39-45.86) mg/kg, respectively. It was also demonstrated that pretreatment with l-arginine (100mg/kg, i.p.), a nitric oxide precursor significantly reversed antinociception produced by EOZZ suggesting the involvement of l-arginine/nitric oxide pathway. In addition, methylene blue (20mg/kg, i.p.) significantly enhanced antinociception produced by EOZZ. Administration of glibenclamide (10mg/kg, i.p.), an ATP-sensitive K(+) channel antagonist significantly reversed antinociceptive activity induced by EOZZ.

    CONCLUSION: Together, the present results suggested that EOZZ-induced antinociceptive activity was possibly related to its ability to inhibit glutamatergic system, TRPV1 receptors as well as through activation of l-arginine/nitric oxide/cGMP/protein kinase C/ATP-sensitive K(+) channel pathway.

  8. 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.
  9. 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.
  10. 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.
  11. Bharatham BH, Abu Bakar MZ, Perimal EK, Yusof LM, Hamid M
    Biomed Res Int, 2014;2014:146723.
    PMID: 25110655 DOI: 10.1155/2014/146723
    A novel porous three-dimensional bone scaffold was developed using a natural polymer (alginate/Alg) in combination with a naturally obtained biomineral (nano cockle shell powder/nCP) through lyophilization techniques. The scaffold was developed in varying composition mixture of Alg-nCP and characterized using various evaluation techniques as well as preliminary in vitro studies on MG63 human osteoblast cells. Morphological observations using SEM revealed variations in structures with the use of different Alg-nCP composition ratios. All the developed scaffolds showed a porous structure with pore sizes ideal for facilitating new bone growth; however, not all combination mixtures showed subsequent favorable characteristics to be used for biological applications. Scaffolds produced using the combination mixture of 40% Alg and 60% nCP produced significantly promising results in terms of mechanical strength, degradation rate, and increased cell proliferation rates making it potentially the optimum composition mixture of Alg-nCP with future application prospects.
  12. Zulazmi NA, Gopalsamy B, Farouk AA, Sulaiman MR, Bharatham BH, Perimal EK
    Fitoterapia, 2015 Sep;105:215-21.
    PMID: 26205045 DOI: 10.1016/j.fitote.2015.07.011
    Neuropathic pain is a chronic condition that is difficult to be treated. Current therapies available are either ineffective or non-specific thus requiring newer treatment approaches. In this study, we investigated the antiallodynic and antihyperalgesic effects of zerumbone, a bioactive sesquiterpene from Zingiber zerumbet in chronic constriction injury (CCI)-induced neuropathic pain animal model. Our findings showed that single and repeated dose of intra-peritoneal administration of zerumbone (5, 10, 50, 100 mg/kg) significantly attenuated the CCI-induced neuropathic pain when evaluated using the electronic von Frey anesthesiometer, cold plate, Randall-Selitto analgesiometer and the Hargreaves plantar test. Zerumbone significantly alleviated tactile and cold allodynia as well as mechanical and thermal hyperalgesia. Our findings are in comparison to the positive control drugs thatused gabapentin (20 mg/kgi.p.) and morphine (1 mg/kgi.p.). Together, these results showed that the systemic administration of zerumbone produced marked antiallodynic and antihyperalgesic effects in the CCI-induced neuropathic pain in mice and may serve as a potential lead compound for further analysis.
  13. 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.
  14. 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.
  15. 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.
  16. Sambasevam Y, Omar Farouk AA, Tengku Mohamad TA, Sulaiman MR, Bharatham BH, Perimal EK
    Eur J Pharmacol, 2017 Feb 05;796:32-38.
    PMID: 27988285 DOI: 10.1016/j.ejphar.2016.12.020
    Neuropathic pain arises from the injury of nervous system. The condition is extremely difficult to be treated due to the ineffectiveness and presence of various adverse effects of the currently available drugs. In the present study, we investigated the antiallodynic and antihyperlagesic properties of cardamonin, a naturally occurring chalcone in chronic constriction injury (CCI)-induced neuropathic pain mice model. Our findings showed that single and repeated dose of intra-peritoneal administration of cardamonin (3, 10, 30mg/kg) significantly inhibited (P<0.001) the chronic constriction injury-induced neuropathic pain using the Hargreaves plantar test, Randall-Selitto analgesiometer test, dynamic plantar anesthesiometer test and the cold plate test in comparison with the positive control drug used (amitriptyline hydrochloride, 20mg/kg, i.p.). Pre-treatment with naloxone hydrochloride (1mg/kg, i.p.) and naloxone methiodide (1mg/kg, s.c) significantly reversed the antiallodynic and antihyperalgesic effects of cardamonin in dynamic plantar anesthesiometer test and Hargreaves plantar test, respectively. In conclusion, the current findings demonstrated novel antiallodynic and antihyperalgesic effects of cardamonin through the activation of the opioidergic system both peripherally and centrally and may prove to be a potent lead compound for the development of neuropathic pain drugs in the future.
  17. Zulazmi NA, Gopalsamy B, Min JC, Farouk AA, Sulaiman MR, Bharatham BH, et al.
    Molecules, 2017 Mar 30;22(4).
    PMID: 28358309 DOI: 10.3390/molecules22040555
    The present study investigates the involvement of the l-arginine-Nitric Oxide-cGMP-K⁺ ATP pathways responsible for the action of anti-allodynic and antihyperalgesic activities of zerumbone in chronic constriction injury (CCI) induced neuropathic pain in mice. The role of l-arginine-NO-cGMP-K⁺ was assessed by the von Frey and the Randall-Selitto tests. Both allodynia and hyperalgesia assessments were carried out on the 14th day post CCI, 30 min after treatments were given for each respective pathway. Anti-allodynic and antihyperalgesic effects of zerumbone (10 mg/kg, i.p) were significantly reversed by the pre-treatment of l-arginine (10 mg/kg), 1H [1,2,4]Oxadiazole[4,3a]quinoxalin-1-one (ODQ), a soluble guanosyl cyclase blocker (2 mg/kg i.p.) and glibenclamide (ATP-sensitive potassium channel blocker) (10 mg/kg i.p.) (p < 0.05). Taken together, these results indicate that systemic administration of zerumbone produces significant anti-allodynic and antihyperalgesic activities in neuropathic pain in mice possibly due to involvement of the l-arginine-NO-cGMP-PKG-K⁺ ATP channel pathways in CCI model.
  18. Gopalsamy B, Farouk AAO, Tengku Mohamad TAS, Sulaiman MR, Perimal EK
    J Pain Res, 2017;10:2605-2619.
    PMID: 29184437 DOI: 10.2147/JPR.S143024
    Background: Neuropathic pain is a debilitating condition that severely affects the quality of life for those with this pain condition, and treatment for pain relief is greatly sought-after. Zerumbone (Zer), a sesquiterpene compound isolated from the rhizomes of a Southeast Asian ginger plant, Zingiber zerumbet (L.) Roscoe ex Smith. (Zingiberaceae), showed antinociceptive and antiinflammatory properties when previously tested on models of nociception and inflammation.

    Objective: This study investigated the effects of prophylactic administration of zerumbone on allodynia and hyperalgesia in a mouse model of chronic constriction injury (CCI)-induced neuropathic pain.

    Methods: Intraperitoneal administration of Zer (5-50 mg/kg) from day 1 post-surgery was carried out to identify the onset and progression of the pain condition. Responses toward mechanical and cold allodynia, and mechanical and thermal hyperalgesia were assessed on days 3, 5, 7, 9, 11, and 14 post-surgery. Blood plasma and spinal cord levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and IL-10 were screened using enzyme-linked immunosorbent assay on day 15.

    Results: Zer (10 and 50 mg/kg) attenuated pain symptoms on all days of behavioral testing without any signs of sedation in the rotarod test. ED50 values for mechanical allodynia, cold allodynia, thermal hyperalgesia, and mechanical hyperalgesia were 9.25, 9.507, 8.289, and 9.801 mg/kg, respectively. Blood plasma and spinal levels of IL-1β, IL-6, and tumor necrosis factor-α but not IL-10 were significantly (p<0.05) suppressed by zer treatment.

    Discussion and conclusion: Zer exhibits its antiallodynic and antihyperalgesic properties via reduced sensitization at nociceptor neurons possibly through the suppression of inflammatory mediators. Zer may prove to be a novel and beneficial alternative for the management of neuropathic pain.

  19. Ping CP, Tengku Mohamad TAS, Akhtar MN, Perimal EK, Akira A, Israf Ali DA, et al.
    Molecules, 2018 Sep 03;23(9).
    PMID: 30177603 DOI: 10.3390/molecules23092237
    Pain is one of the most common cause for hospital visits. It plays an important role in inflammation and serves as a warning sign to avoid further injury. Analgesics are used to manage pain and provide comfort to patients. However, prolonged usage of pain treatments like opioids and NSAIDs are accompanied with undesirable side effects. Therefore, research to identify novel compounds that produce analgesia with lesser side effects are necessary. The present study investigated the antinociceptive potentials of a natural compound, cardamonin, isolated from Boesenbergia rotunda (L) Mansf. using chemical and thermal models of nociception. Our findings showed that intraperitoneal and oral administration of cardamonin (0.3, 1, 3, and 10 mg/kg) produced significant and dose-dependent inhibition of pain in abdominal writhing responses induced by acetic acid. The present study also demonstrated that cardamonin produced significant analgesia in formalin-, capsaicin-, and glutamate-induced paw licking tests. In the thermal-induced nociception model, cardamonin exhibited significant increase in response latency time of animals subjected to hot-plate thermal stimuli. The rota-rod assessment confirmed that the antinociceptive activities elicited by cardamonin was not related to muscle relaxant or sedative effects of the compound. In conclusion, the present findings showed that cardamonin exerted significant peripheral and central antinociception through chemical- and thermal-induced nociception in mice through the involvement of TRPV₁, glutamate, and opioid receptors.
  20. Sithravel R, Ibrahim R, Lye MS, Perimal EK, Ibrahim N, Dahlan ND
    PLoS One, 2018;13(11):e0207488.
    PMID: 30496193 DOI: 10.1371/journal.pone.0207488
    Workplace architectural lighting conditions that are biologically dim during the day are causing healthy individuals to experience light-induced health and performance-related problems. Dynamic lighting was reported beneficial in supporting individuals' psychological behavior and physiological responses during work period in Europe. It has yet to be investigated in workplaces with minimal/no natural daylight contribution in tropical Malaysia. Hence, an exploratory experimental study was initiated in an experimental windowless open-plan workplace in Universiti Putra Malaysia, Serdang. The aim was to identify dynamic lighting configurations that were more supportive of a morning boosting effect than the control constant lighting, to support dayshift individuals' psychophysiological wellbeing indicators during the peak morning work period. The immediate impact of a 2-hour morning exposure to overhead white LED (6500 K) with different horizontal illuminance levels and oscillations (lighting patterns) were investigated on physiological indicator limited to urinary 6-sulfatoxymelatonin, and psychological indicators for alertness, mood, visual comfort, cognitive and visual task performance. Not all of the investigated dynamic lighting configurations were supportive of a morning boost. Only configurations 500increased to750 and 500increased to1000 lx therapeutically supported most of the indicators. Both these configurations suppressed urinary 6-sulfatoxymelatonin, and improved alertness, cognitive performance, positive affect, and visual comfort better than 'visit 1: 500constant500' lx (control). The increasing oscillation was observed more beneficial for the morning boost in tropical Malaysia, which is in reverse to that specified in the human rhythmic dynamic lighting protocol developed by researchers from the Netherlands for application during winter. The findings from this study present the feasibility of dynamic architectural lighting acting as an environmental therapeutic solution in supporting the individuals' psychophysiological wellbeing indicators in windowless open-plan workplace in tropical Malaysia. Further investigations on the two prospective configurations are recommended to determine the better supportive one for the morning boosting effect in Malaysia.
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