Preliminary study on antinociceptove effect of aqueous extract of Boesenbergia pandurata in formalin-induced nociception test in mice

Pain is an unpleasant sensation associated with body state dysfunction that negatively affects the productivity of patients. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used as over-the-counter pain reliever medication due to its cost effectiveness. However, prolonged usage of NSAIDs usually accompanied with adverse side effects such as ulcer, nausea and even kidney failure. Hence, researchers are now focused on traditional herbal research to search for potential analgesic substances that are with minimal or no adverse effects. Boesenbergia pandurata，it is also known as temu kunci in Malaysia is a perennial herb that belongs to Zingiberaceae family. Boesenbergia pandurata is widely distributed in Southeast Asia and its rhizomes are commonly used as food ingredients or as traditional medicine to treat diseases conditions such as inflammation, cancer, and fungal infection. The aim of this study is to evaluate the inhibitory effect of aqueous extract of Boesenbergia pandurata (AEBP) on formalin-induced nociception test in mice. Mice were pre-treated with AEBP via intraperitoneal injection 30 min before challenged with intraplantar injection of formalin. It was demonstrated that intraperitoneal administration of AEBP at doses (0.3, 1, 3 and 10 mg/kg) produced significant antinociceptive response in both neurogenic and inflammatory phases of pain response induced by formalin. The findings indicated preliminary study on antinociceptive effect of AEBP, but further study should be conducted to explore the exact mechanism of pain inhibition by AEBP

Effects of Melicope ptelifolia aqueous extract on sperm parameters and testosterone level in Sprague-Dawley rats

The increasing number of prevalence infertility cases is becoming a major public health problem in developing countries due to changes in diet and lifestyle. Melicope ptelefolia is known for its health benefit as a sex enhancing effect among the Malays folk however there is no clinical data to prove it until these days. The main aim of the present study is to identify the effects of Melicope ptelifolia Aqueous extract (MPAE) on Sperm Parameters and Testosterone Level . A total of 30 male Sprague Dawley rats were divided equally into five different groups. MPAE was given by orally gavage for 28 days at a dose of 100mg/kg, 200 mg/kg and 500 mg/kg body weight to the animals of group II (n=6), III (n=6) and IV (n=6), respectively. The animals of group I (control, n=6) had distilled water and group V had sildenafil citrate. Results were analyzed using one way ANOVA test and the data were significant at p<0.05. Oral administration of MPAE extract showed an increased sperm count and sperm viability. Oral administration of the MPAE resulted a significant increased (p<0.05) for Group II, III and IV in sperm count and sperm morphology. A significant increased increased was recorded for Group I, II, III and IV in sperm viability. However, sperm vitality remained normal in all the groups. From our present experimental findings we are tempted to suggest that the MPAE could be a potential male fertility agent

Activity of cardamonin on chemical model of nociception in mice

Non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are among the most widely used medication in reducing pain. Prolonged usage of these drugs leads to undesirable side effects such as gastrointestinal bleeding, respiratory depression and tolerance. Thus, there is a demand to search for new pharmacologically potent analgesic compounds with fewer or no adverse effects. Cardamonin is a naturally occurring chalcone, which are commonly found in plant kingdom. Previous reports showed that cardamonin has anti-inflammatory effects and inhibit generation of nitric oxide and prostaglandin E2 via interruption of NF-κB pathway. In the present study, we evaluated the antinociceptive property of cardamonin using acetic acid-induced abdominal writhing test in mice. Cardamonin (0.3, 1, 3 and 10 mg/kg), vehicle (10 ml/kg) or indomethacin (10 mg/kg) was administered either intraperitoneally or orally, 30 minutes or 60 minutes respectively before injection of 0.8% acetic acid. The number of abdominal writhes was recorded for 30 minutes, starting from 5 minutes after acetic acid injection. Cardamonin showed significant reduction in abdominal writhes. These findings suggested that cardamonin exerted pronounced antinociceptive activity when assessed in chemical model of nociception in mice

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

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. Zerum-bone (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 car-ried 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-αbut 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

Zerumbone alleviates chronic constriction injury-induced allodynia and hyperalgesia through serotonin 5-HT receptors

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, 100 mg/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-HT 1/6/7 receptor antagonist, 0.1 mg/kg), WAY-100635 (5-HT 1A receptor antagonist, 1 mg/kg), isamoltane (5-HT 1B receptor antagonist, 2.5 mg/kg), ketanserin (5-HT 2A receptor antagonist, 0.3 mg/kg) and ondansetron (5-HT 3 receptor antagonist, 0.5 mg/kg) managed to significantly attenuate antiallodynic and antihyperalgesic effects of zerumbone (10 mg/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

Antinociceptive effect of the essential oil of Zingiber zerumbet in mice : possible mechanisms

Abstract 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 ID50 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 (1.6 μg/paw) with calculated mean ID50 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 (100 mg/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 (20 mg/kg, i.p.) significantly enhanced antinociception produced by EOZZ. Administration of glibenclamide (10 mg/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

The involvement of L-arginine-nitric ox-ide-cGMP-ATP-sensitive K+ channel pathway in antinocicep-tion of BBHC, a novel diarylpentanoid analogue, in mice model

The present study focuses on the possible involvement of l-arginine-nitric oxide-cGMP-ATP-sensitive K+ channel pathway in the antinociceptive activity of a novel diarylpentanoid analogue, 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol (BBHC) via a chemical nociceptive model in mice. The antinociceptive action of BBHC (1 mg/kg, i.p.) was attenuated by the intraperitoneal pre-treatment of l-arginine (a nitric oxide synthase precursor) and glibenclamide (an ATP-sensitive K+ channel blocker) in acetic acid-induced abdominal constriction tests. Interestingly, BBHC’s antinociception was significantly enhanced by the i.p. pre-treatment of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a selective inhibitor of soluble guanylyl cyclase (p < 0.05). Altogether, these findings suggest that the systemic administration of BBHC is able to establish a significant antinociceptive effect in a mice model of chemically induced pain. BBHC’s antinociception is shown to be mediated by the involvement of l-arginine-nitric oxide-cGMP-ATP-sensitive K+ channel pathway, without any potential sedative or muscle relaxant concerns

Cardamonin attenuates hyperalgesia and allodynia in a mouse model of chronic constriction injury-induced neuropathic pain: possible involvement of the opioid system

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, 30 mg/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, 20 mg/kg, i.p.). Pre-treatment with naloxone hydrochloride (1 mg/kg, i.p.) and naloxone methiodide (1 mg/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

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

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 ID50 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 ID50 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 ID50 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

Boesenbergia rotunda ethanolic extract inhibits compound action potentials via opioid receptors

Boesenbergia rotunda, traditionally used to relieve stomach, abdomen, joint, muscle, and rheumatic pain was also reported for its antinociceptive effect on a mouse model. However, the possible pain relief effect of Boesenbergia rotunda ethanolic extract (BREE) via the inhibition to the neural pain pathway remains to be elucidated. This study investigated the inhibitory effect of BREE on compound action potentials (CAPs) and the possible involvement of the opioid receptors. The changes in the CAPs amplitudes of the frog’s sciatic nerves were evaluated following the exposure to three different dosages of BREE (1, 3 and 10 mg/ml and morphine (3 mg/ml). In another set of experiment, the nerves were pretreated with a non-selective opioid receptor antagonist, naloxone (0.1 mg/ml), before exposing the nerve to BREE (1 mg/ml) to investigate the involvement of opioid receptors in the CAPs inhibitory mechanism. The outcome showed a reduction in the CAPs amplitudes when treated with BREE (1, 3 and 10 mg/ml) whereby the effect was reversible. The CAPs inhibition by BREE was absent when the opioid receptors were blocked. Taken together, these findings suggest that BREE-induced CAPs amplitude reduction involves the activation of opioid receptors