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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.
Antinociceptive and anti-inflammatory properties of Corchorus capsularis leaves chloroform extract in experimental animal models

Zakaria ZA, Sulaiman MR, Gopalan HK, Abdul Ghani ZD, Raden Mohd Nor RN, Mat Jais AM, et al.

Yakugaku Zasshi, 2007 Feb;127(2):359-65.
PMID: 17268156

The antinociceptive and anti-inflammatory properties of Corchorus capsularis leaves chloroform extract were investigated in experimental animal models. The antinociceptive activity was measured using the writhing, hot plate and formalin tests, while the anti-inflammatory activity was measured using the carrageenan-induced paw edema test. The extract, obtained after 72 h soaking of the air-dried leaves in chloroform followed by in vacuo evaporation to dryness, was weighed and prepared by serial dilution in DMSO in the doses of 20, 100 and 200 mg/kg. The extract was administered (s.c.) 30 min prior to subjection to the respective assays. The extract was found to exhibit significant (p < 0.05) antinociceptive and anti-inflammatory activities. As a conclusion, the present study confirmed the traditional claims of using C. capsularis to treat various ailments related to inflammation and pain.
Antinociceptive and anti-inflammatory effects of the ethanol extract of Alpinia conchigera rhizomes in various animal models

Sulaiman MR, Zakaria ZA, Mohamad AS, Ismail M, Hidayat MT, Israf DA, et al.

Pharm Biol, 2010 Aug;48(8):861-8.
PMID: 20673172 DOI: 10.3109/13880200903302820

Alpinia conchigera Griff. (Zingiberaceae), locally known to the Malays as "lengkuas ranting", is native to Peninsular Malaysia. The Malays traditionally used it to treat infection and rashes, and as a health drink. This study evaluated the analgesic and anti-inflammatory activities of the ethanol extract of A. conchigera rhizomes in mice and rats, respectively. The analgesic activity was elucidated using the acetic acid-induced writhing test, hot plate test, and formalin test, while the anti-inflammatory activity was determined using carrageenan-induced paw edema. The extract (30, 100, and 300 mg/kg) given intraperitoneally (i.p.) exhibited antinociceptive and anti-inflammatory activities in all tests used. The range of percentage of analgesia obtained for all doses of extract in the writhing test was 50-92%, and in the early and late phases of the formalin test was 25-62% and 63-98%, respectively. In addition, naloxone (5 mg/kg) given subcutaneously (s.c.) was found to reverse the extract (300 mg/kg)-induced antinociceptive activity in the writhing, hot plate, and formalin tests. Based on the results obtained, it can be concluded that the ethanol extract of A. conchigera rhizomes possessed a peripheral and central antinociceptive activity that was mediated, in part, via the opioid receptor, as well as anti-inflammatory activity.
Antinociceptive and anti-inflammatory effects of the ethanol extract of Alpinia conchigera Griff. leaves in various animal models

Sulaiman MR, Zakaria ZA, Adilius M, Mohamad AS, Ismail M, Israf DA

Methods Find Exp Clin Pharmacol, 2009 May;31(4):241-7.
PMID: 19557202 DOI: 10.1358/mf.2009.31.4.1371198

The ethanolic extract of Alpinia conchigera Griff. leaves (EACL) was evaluated for its antinociceptive and anti-inflammatory activities in several in vivo experimental models. Antinociceptive activity was determined using the acetic acid-induced abdominal writhing test, the hot plate test and the formalin test. Anti-inflammatory activity was determined using the carrageenan-induced paw edema test. The extract (30, 100 and 300 mg/kg i.p.) was found to possess significant, dose-dependent inhibitory activity in all test models. In addition, the antinociceptive effect of the extract in the acetic acid-induced writhing and hot plate tests was reversed by naloxone, suggesting that this activity is mediated through activation of the opioid system. These findings suggest that EACL presents notable analgesic and anti-inflammatory activities, which support its folkloric use for painful and inflammatory conditions.
Fulltext Antinociceptive and anti-inflammatory effects of Stachytarpheta jamaicensis (L.) Vahl (Verbenaceae) in experimental animal models

Sulaiman MR, Zakaria ZA, Chiong HS, Lai SK, Israf DA, Azam Shah TM

Med Princ Pract, 2009;18(4):272-9.
PMID: 19494533 DOI: 10.1159/000215723

The present study was carried out to explore the antinociceptive as well as the anti-inflammatory effects of an ethanol extract of Stachytarpheta jamaicensis (L.) Vahl (EESJ) using 3 models of nociception and 2 models of inflammation in experimental animals.
Antinociceptive and anti-inflammatory activities of the aqueous extract of Kaempferia galanga leaves in animal models

Sulaiman MR, Zakaria ZA, Daud IA, Ng FN, Ng YC, Hidayat MT

J Nat Med, 2008 Apr;62(2):221-7.
PMID: 18404328 DOI: 10.1007/s11418-007-0210-3

This study was performed to determine the antinociceptive and anti-inflammatory activities of aqueous extract of Kaempferia galanga leaves using various animal models. The extract, in the doses of 30, 100, and 300 mg/kg, was prepared by soaking (1:10; w/v) the air-dried powdered leaves (40 g) in distilled water (dH(2)O) for 72 h and 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, with activity observed in all tests occurring in a dose-dependent manner. Furthermore, the antinociceptive activity of K. galanga extract was significantly (P < 0.05) reversed when prechallenged with 10 mg/kg naloxone. The extract also produced a significantly (P < 0.05) dose-dependent anti-inflammatory activity when assessed using the carrageenan-induced paw-edema test. In conclusion, this study demonstrated that K. galanga leaves possessed antinociceptive and anti-inflammatory activities and thus supports the Malay's traditional uses of the plant for treatments of mouth ulcer, headache, sore throat, etc.
Antinociceptive and anti-inflammatory activities of Dicranopteris linearis leaves chloroform extract in experimental animals

Zakaria ZA, Abdul Ghani ZD, Raden Mohd Nor RN, Gopalan HK, Sulaiman MR, Abdullah FC

Yakugaku Zasshi, 2006 Nov;126(11):1197-203.
PMID: 17077622

The present study was carried out to establish the antinociceptive and anti-inflammatory properties of Dicranopteris linearis leaves chloroform extract in experimental animals. The antinociceptive activity was measured using the abdominal constriction, formalin and hot plate tests, while the anti-inflammatory activity was measured using the carrageenan-induced paw edema. The extract, obtained after 72 h soaking of the air-dried leaves in chloroform followed by evaporation under vacuo (40 degrees C) to dryness, was dissolved in dimethyl sulfoxide to the doses of 20, 100 and 200 mg/kg and administered subcutaneously 30 min prior to subjection to the above mentioned assays. The extract, at all doses used, was found to exhibit significant (p<0.05) antinociceptive activity in a dose-dependent manner. However, the significant (p<0.05) anti-inflammatory activity observed occur in a dose-independent manner. As a conclusion, the chloroform extract of D. linearis possesses antinociceptive and anti-inflammatory activity and thus justify its traditional uses by the Malays to treat various ailments.
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.
Antinociceptive activity of methanolic extract of Acmella uliginosa (Sw.) Cass

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.
Fulltext Antinociceptive activity of a synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)cyclohexanone, on nociception-induced models in mice

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.
Antinociceptive activity of a synthetic chalcone, flavokawin B on chemical and thermal models of nociception in mice

Mohamad AS, Akhtar MN, Zakaria ZA, Perimal EK, Khalid S, Mohd PA, et al.

Eur J Pharmacol, 2010 Nov 25;647(1-3):103-9.
PMID: 20826146 DOI: 10.1016/j.ejphar.2010.08.030

The present study examined the potential antinociceptive activity of flavokawin B (6'-hydroxy-2',4'-dimethoxychalcone), a synthetic chalcone using chemical- and thermal-induced nociception models in mice. It was demonstrated that flavokawin B (FKB; 0.3, 1, 3 and 10 mg/kg) administered via both oral (p.o.) and intraperitoneal (i.p.) routes produced significant and dose-dependent inhibition in the abdominal constrictions induced by acetic acid, with the i.p. route producing antinociception of approximately 7-fold more potent than the p.o. route. It was also demonstrated that FKB produced significant inhibition in the two phases of the formalin-induced paw licking test. In addition, the same treatment of flavokawin B (FKB) exhibited significant inhibition of the neurogenic nociceptive induced by intraplantar injections of glutamate and capsaicin. Likewise, this compound also induced a significant increase in the response latency period to thermal stimuli in the hot plate test and its antinociceptive effect was not related to muscle relaxant or sedative action. Moreover, the antinociception effect of the FKB in the formalin-induced paw licking test and the hot plate test was not affected by pretreatment of non-selective opioid receptor antagonist, naloxone. The present results indicate that FKB produced pronounced antinociception effect against both chemical and thermal models of pain in mice that exhibited both peripheral and central analgesic activity.
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.
Fulltext Antinociceptive activities of a novel diarylpentanoid analogue, 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol, and its possible mechanisms of action in mice

Ong HM, Azmi AFA, Leong SW, Abas F, Perimal EK, Farouk AAO, et al.

Sci Rep, 2021 12 16;11(1):24121.
PMID: 34916536 DOI: 10.1038/s41598-021-02961-1

A novel synthetic compound from the 2-benzoyl-6-benzylidenecyclohexanone analogue, namely 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol (BBHC), showed pronounced nitric oxide inhibition in IFN-γ/LPS-induced RAW 264.7 cells. Based on this previous finding, our present study aimed to investigate the antinociceptive effects of BBHC via chemical and thermal stimuli in vivo. The investigation of the antinociceptive activity of BBHC (0.1, 0.3, 1.0 and 3.0 mg/kg, i.p.) was initiated with 3 preliminary screening tests, then BBHC was subjected to investigate its possible involvement with excitatory neurotransmitters and opioid receptors. The potential acute toxicity of BBHC administration was also studied. Administration of BBHC significantly inhibited acetic acid-induced abdominal constrictions, formalin-induced paw licking activity and developed notable increment in the latency time. BBHC's ability to suppress capsaicin- and glutamate-induced paw licking activities, as well as to antagonise the effect of naloxone, had indicated the possible involvement of its antinociception with TRPV1, glutamate and opioid receptors, respectively. The antinociceptive activities of BBHC was not related to any sedative action and no evidence of acute toxic effect was detected. The present study showed that BBHC possessed significant peripheral and central antinociceptive activities via chemical- and thermal-induced nociceptive murine models without any locomotor alteration and acute toxicity.
Fulltext Antinociceptive Effects of Cardamonin in Mice: Possible Involvement of TRPV₁, Glutamate, and Opioid Receptors

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.
Fulltext Antinociceptive Effect of 3-(2,3-Dimethoxyphenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one in Mice Models of Induced Nociception

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.
Fulltext Antiinflammatory and antinociceptive activities of Zingiber zerumbet methanol extract in experimental model systems

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.
Antidepressant-like effect of aqueous extract of Channa striatus fillet in mice models of depression

Saleem AM, Taufik Hidayat M, Mat Jais AM, Fakurazi S, Moklas M, Sulaiman MR, et al.

Eur Rev Med Pharmacol Sci, 2011 Jul;15(7):795-802.
PMID: 21780549

Channa (C.) striatus (Malay-Haruan), is a fresh water snakehead fish, consumed as a rejuvenating diet in post-parturition period in local Malay population. The aqueous extract of C. striatus fillet (AECSF) was reported to act through serotonergic receptor system in a previous study. There is no scientific report on neuropharmacological effects of C. striatus. Based on these data, the antidepressant-like effect of C. striatus was evaluated in mice models of depression.
Antiallodynic and antihyperalgesic effects of zerumbone on a mouse model of chronic constriction injury-induced neuropathic pain

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.
Fulltext Antiallodynic and antihyperalgesic activities of zerumbone via the suppression of IL-1β, IL-6, and TNF-α in a mouse model of neuropathic pain

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.
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.

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