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Fulltext Watermelon (Citrullus lanatus (Thunb.) Matsum. and Nakai) juice modulates oxidative damage induced by low dose X-ray in mice

Mohammad MK, Mohamed MI, Zakaria AM, Abdul Razak HR, Saad WM

Biomed Res Int, 2014;2014:512834.
PMID: 24877107 DOI: 10.1155/2014/512834

Watermelon is a natural product that contains high level of antioxidants and may prevent oxidative damage in tissues due to free radical generation following an exposure to ionizing radiation. The present study aimed to investigate the radioprotective effects of watermelon (Citrullus lanatus (Thunb.) Matsum. and Nakai) juice against oxidative damage induced by low dose X-ray exposure in mice. Twelve adult male ICR mice were randomly divided into two groups consisting of radiation (Rx) and supplementation (Tx) groups. Rx received filtered tap water, while Tx was supplemented with 50% (v/v) watermelon juice for 28 days ad libitum prior to total body irradiation by 100 μGy X-ray on day 29. Brain, lung, and liver tissues were assessed for the levels of malondialdehyde (MDA), apurinic/apyrimidinic (AP) sites, glutathione (GSH), and superoxide dismutase (SOD) inhibition activities. Results showed significant reduction of MDA levels and AP sites formation of Tx compared to Rx (P < 0.05). Mice supplemented with 50% watermelon juice restore the intracellular antioxidant activities by significantly increased SOD inhibition activities and GSH levels compared to Rx. These findings may postulate that supplementation of 50% watermelon (Citrullus lanatus (Thunb.) Matsum. and Nakai) juice could modulate oxidative damage induced by low dose X-ray exposure.

Matched MeSH terms: Mice, Inbred ICR
Isolation and characterisation of acetylcholinesterase inhibitors from Aquilaria subintegra for the treatment of Alzheimer's disease (AD)

Bahrani H, Mohamad J, Paydar MJ, Rothan HA

Curr Alzheimer Res, 2014 Feb;11(2):206-14.
PMID: 24479629

Aquilaria subintegra, locally known as "Gaharu", belongs to the Thymelaeceae family. This plant's leaves have been claimed to be effective for the treatment of Alzheimer's disease (AD) by Malay traditional practitioner in Malaysia. In this research, the chloroform extracts of the leaves and stem of A. subintegra were tested for acetylcholinesterase (AChE) inhibitory activity. The Thin Layer Chromatography (TLC) results indicated the presence of phenols, flavonoids, terpenoids, and alkaloids compounds in the extracts. Analysis of the stem chloroform extracts with LCMS/MS displayed that it contains kaempferol 3,4,7-trimethyl ether. The AChE inhibitory activity of leaves and stem chloroform extracts and kaempferol were 80%, 93% and 85.8%, respectively. The Brine Shrimp Lethality Assay (BSLA) exhibited low to moderate toxicity of the chloroform extract from leaves (LC50=531.18 ± 49.53 μg/ml), the stem chloroform extract (LC50=407.34 ± 68.05 μg/ml) and kaempferol (LC50=762.41 ± 45.09 μg/ml). The extracts and kaempferol were not cytotoxic to human umbilical vein endothelial cells (HUVEC), human normal gastric epithelial cell line (GES-1) and human normal hepatic cell line (WRL-68). The effect of leaf and stem chloroform extracts and kaempferol were determined in the Radial Arm Maze (RAM) after administration by oral gavage to ICR male and female mice with valium-impaired memory. Administration of kaempferol to the mice significantly reduced the number of repeated entries into the arms of maze in males and females. In conclusion, the inhibition of AChE by leaf and stem chloroform extracts of A. subintegra could be due to the presence of kaempferol. This extract is safe for use as a natural AChE inhibitor as an alternative to berberine for the treatment of AD.

Matched MeSH terms: Mice, Inbred ICR
Evaluation of neutralizing antibodies produced by papaya mosaic virus nanoparticles fused to the E2EP3 peptide epitope of Chikungunya envelope

Nor Rashid N, Teoh TC, Al-Harbi SJ, Yusof R, Rothan HA

Trop Biomed, 2021 Mar 01;38(1):36-41.
PMID: 33797522 DOI: 10.47665/tb.38.1.007

Chikungunya virus (CHIKV) infection is the cause of acute symptoms and chronic symmetrical polyarthritis associated with long-term morbidity and mortality. Currently, there is no available licensed vaccine or particularly useful drug for human use against CHIKV infection. This study was conducted to evaluate the efficacy of antibodies produced by papaya mosaic virus (PapMV) nanoparticles fused to E2EP3 peptide of CHIKV envelope as a recombinant CHIKV vaccine. PapMV, PapMV-C- E2EP3, and E2EP3-N-PapMV were produced in E. coli with an approximate size of 27 to 30 kDa. ICR mice (5 to 6 weeks of age) were injected subcutaneously with 25 micrograms of vaccine construct, and ELISA measured the titer of CHIKV specific IgG antibodies. The results showed that both recombinant proteins E2EP3-N-PapMV and PapMVC-E2EP3 were able to induce IgG antibodies production in immunized mice against CHIKV while immunization with recombinant PapMV showed no IgG antibodies induction. The neutralizing activity of the antibodies generated by either E2EP3-N-PapMV or PapMV-C-E2EP3 exhibited similar inhibition to CHIKV replication in Vero cells using the cells based antibody neutralizing assay and analyzed by plaque formation assay. This study showed the effectiveness of nanoparticles vaccine generated by fusing epitope peptide of CHIKV envelope to papaya mosaic virus envelope in inducing a robust immune response in mice against CHIKV. The data showed that levels of neutralizing antibodies correlate with a protective immune response CHIKV replication.

Matched MeSH terms: Mice, Inbred ICR
Lactobacilli-fermented cow's milk attenuated lipopolysaccharide-induced neuroinflammation and memory impairment in vitro and in vivo

Musa NH, Mani V, Lim SM, Vidyadaran S, Abdul Majeed AB, Ramasamy K

J Dairy Res, 2017 Nov;84(4):488-495.
PMID: 29154736 DOI: 10.1017/S0022029917000620

Nutritional interventions are now recommended as strategies to delay Alzheimer's disease (AD) progression. The present study evaluated the neuroprotective effect (anti-inflammation) of lactic acid bacteria (either Lactobacillus fermentum LAB9 or L. casei LABPC) fermented cow's milk (CM) against lipopolysaccharide (LPS)-activated microglial BV2 cells in vitro. The ability of CM-LAB in attenuating memory deficit in LPS-induced mice was also investigated. ICR mice were orally administered with CM-LAB for 28 d before induction of neuroinflammation by LPS. Learning and memory behaviour were assessed using the Morris Water Maze Test. Brain tissues were homogenised for measurement of acetylcholinesterase (AChE), antioxidative, lipid peroxidation (malondialdehyde (MDA)) and nitrosative stress (NO) parameters. Serum was collected for cytokine analysis. CM-LAB9 and CM-LABPC significantly (P < 0·05) decreased NO level but did not affect CD40 expression in vitro. CM-LAB attenuated LPS-induced memory deficit in mice. This was accompanied by significant (P < 0·05) increment of antioxidants (SOD, GSH, GPx) and reduction of MDA, AChE and also pro-inflammatory cytokines. Unfermented cow's milk (UCM) yielded greater cytokine lowering effect than CM-LAB. The present findings suggest that attenuation of LPS-induced neuroinflamation and memory deficit by CM-LAB could be mediated via anti-inflammation through inhibition of AChE and antioxidative activities.

Matched MeSH terms: Mice, Inbred ICR
Lineage-related cytotoxicity and clonogenic profile of 1,4-benzoquinone-exposed hematopoietic stem and progenitor cells

Chow PW, Abdul Hamid Z, Chan KM, Inayat-Hussain SH, Rajab NF

Toxicol Appl Pharmacol, 2015 Apr 1;284(1):8-15.
PMID: 25645895 DOI: 10.1016/j.taap.2015.01.016

Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) are sensitive targets for benzene-induced hematotoxicity and leukemogenesis. The impact of benzene exposure on the complex microenvironment of HSCs and HPCs remains elusive. This study aims to investigate the mechanism linking benzene exposure to targeting HSCs and HPCs using phenotypic and clonogenic analyses. Mouse bone marrow (BM) cells were exposed ex vivo to the benzene metabolite, 1,4-benzoquinone (1,4-BQ), for 24h. Expression of cellular surface antigens for HSC (Sca-1), myeloid (Gr-1, CD11b), and lymphoid (CD45, CD3e) populations were confirmed by flow cytometry. The clonogenicity of cells was studied using the colony-forming unit (CFU) assay for multilineage (CFU-GM and CFU-GEMM) and single-lineage (CFU-E, BFU-E, CFU-G, and CFU-M) progenitors. 1,4-BQ demonstrated concentration-dependent cytotoxicity in mouse BM cells. The percentage of apoptotic cells increased (p < 0.05) following 1,4-BQ exposure. Exposure to 1,4-BQ showed no significant effect on CD3e(+) cells but reduced the total counts of Sca-1(+), CD11b(+), Gr-1(+), and CD45(+) cells at 7 and 12 μM (p < 0.05). Furthermore, the CFU assay showed reduced (p < 0.05) clonogenicity in 1,4-BQ-treated cells. 1,4-BQ induced CFU-dependent cytotoxicity by significantly inhibiting colony growth for CFU-E, BFU-E, CFU-G, and CFU-M starting at a low concentration of exposure (5μM); whereas for the CFU-GM and CFU-GEMM, the inhibition of colony growth was remarkable only at 7 and 12μM of 1,4-BQ, respectively. Taken together, 1,4-BQ caused lineage-related cytotoxicity in mouse HPCs, demonstrating greater toxicity in single-lineage progenitors than in those of multi-lineage.

Matched MeSH terms: Mice, Inbred ICR
Zinc intake during pregnancy increases the proliferation at ventricular zone of the newborn brain

Azman MS, Wan Saudi WS, Ilhami M, Mutalib MS, Rahman MT

Nutr Neurosci, 2009 Feb;12(1):9-12.
PMID: 19178786 DOI: 10.1179/147683009X388904

Neurogenesis involves cell proliferation, cell cycle arrest, differentiation, migration and the natural developmental death of the neural precursors. These processes are highly co-ordinated and governed by cell-cycle genes and neural transcription factors. Zn plays a crucial role as a functional and structural component of enzymes and transcription factors and components of the intracellular signaling pathway associated with the regulation of cell proliferation. The influence of additional Zn intake during pregnancy on the neuronal proliferation at ventricular zone of the developing fetus has been studied. Pups delivered by the group of mice provided with drinking water with 4.0 mM Zn supplement throughout pregnancy contained an increased number of proliferating neurons in the ventricular zone at P0 compared to those delivered by the mice provided with drinking water without any Zn supplement. This finding provides direct evidence to support the notion that maternal Zn levels influence the development of the nervous system of the offspring.

Matched MeSH terms: Mice, Inbred ICR
Effect of green and ripe Carica papaya epicarp extracts on wound healing and during pregnancy

Anuar NS, Zahari SS, Taib IA, Rahman MT

Food Chem Toxicol, 2008 Jul;46(7):2384-9.
PMID: 18468758 DOI: 10.1016/j.fct.2008.03.025

The traditional use of papaya to treat many diseases, especially skin conditions and its prohibition for consumption during pregnancy has prompted us to determine whether papaya extracts both from green and ripe fruits improve wound healing and also produce foetal toxicity. Aqueous extracts of green papaya epicarp (GPE) and ripe papaya epicarp (RPE) were applied on induced wounds on mice. GPE treatment induced complete healing in shorter periods (13 days) than that required while using RPE (17 days), sterile water (18 days) and Solcoseryl ointment (21 days). Extracts were administered orally (1 mg/g body weight/day) to pregnant mice from day 10 and onwards after conception. 3 (n=7) mice and 1 (n=6) mice given RPE and misoprostol, an abortive drug, respectively experienced embryonic resorption while this effect was observed in none of the mice given GPE (n=5) and water (n=5). The average body weight of live pups delivered by mice given GPE (1.12+/-0.04 g) was significantly lower than those delivered by mice given water (1.38+/-0.02 g). In SDS-PAGE, proteins were distributed in three bands (Mr range approximately 8-29 kDa). Band intensity at Mr approximately 28-29 kDa was higher in GPE than in RPE. In contrast, band intensity at low Mr (approximately 8 kDa) was found to be higher in RPE than in GPE. Notably, the band corresponding to Mr approximately 23-25 kDa was absent in RPE. These differences in composition may have contributed to the different wound healing and abortive effects of green and ripe papaya.

Matched MeSH terms: Mice, Inbred ICR
Effect of fluoxetine on maximal electroshock seizures in mice: acute vs chronic administration

Raju SS, Noor AR, Gurthu S, Giriyappanavar CR, Acharya SB, Low HC, et al.

Pharmacol Res, 1999 Jun;39(6):451-4.
PMID: 10373242

There are no definite reports regarding the effects of chronic fluoxetine on animal models of epilepsy. Since chronically administered fluoxetine, in comparison to acutely administered fluoxetine has different effects on CNS, the present study was undertaken to investigate the effect of acute and chronic fluoxetine pretreatment, on a median anticonvulsant dose (ED50) of phenytoin in male ICR albino mice. Additionally, the effects of fluoxetine pretreatment on median convulsive current (CC50) in the presence and absence of phenytoin were investigated and results were compared. The maximal electroshock seizure (MES) test was used to estimate the ED50of phenytoin. The electroshock threshold test was used to estimate CC50. ED50and CC50values were calculated by probit analysis. The effects of the chronic and acute fluoxetine groups on the ED50of phenytoin were significantly different (P<0.05), and on CC50this difference was not statistically significant. Chronic fluoxetine insignificantly increased the ED50of phenytoin and decreased the CC50while acute fluoxetine decreased the ED50of phenytoin and increased the CC50. Our results indicate that chronic fluoxetine does not have an antiepileptic property and it may have dubious proconvulsant properties, contrary to acute fluoxetine.

Matched MeSH terms: Mice, Inbred ICR
Molecular mechanism of L-SP40 peptide and in vivo efficacy against EV-A71 in neonatal mice

Lalani S, Tan SH, Tan KO, Lim HX, Ong KC, Wong KT, et al.

Life Sci, 2021 Dec 15;287:120097.
PMID: 34715144 DOI: 10.1016/j.lfs.2021.120097

AIMS: Enterovirus A71 (EV-A71) is an etiological agent of hand foot and mouth disease (HFMD) and has the potential to cause severe neurological infections in children. L-SP40 peptide was previously known to inhibit EV-A71 by prophylactic action. This study aimed to identify the mechanism of inhibition in Rhabdomyosarcoma (RD) cells and in vivo therapeutic potential of L-SP40 peptide in a murine model.
MAIN METHODS: A pull-down assay was performed to identify the binding partner of the L-SP40 peptide. Co-immunoprecipitation and co-localization assays with the L-SP40 peptide were employed to confirm the receptor partner in RD cells. The outcomes were validated using receptor knockdown and antibody blocking assays. The L-SP40 peptide was further evaluated for the protection of neonatal mice against lethal challenge by mouse-adapted EV-A71.
KEY FINDINGS: The L-SP40 peptide was found to interact and co-localize with nucleolin, the key attachment receptor of Enteroviruses A species, as demonstrated in the pull-down, co-immunoprecipitation and co-localization assays. Knockdown of nucleolin from RD cells led to a significant reduction of 3.5 logs of viral titer of EV-A71. The L-SP40 peptide demonstrated 80% protection of neonatal mice against lethal challenge by the mouse-adapted virus with a drastic reduction in the viral loads in the blood (~4.5 logs), skeletal muscles (1.5 logs) and brain stem (1.5 logs).
SIGNIFICANCE: L-SP40 peptide prevented severe hind limb paralysis and death in suckling mice and could serve as a potential broad-spectrum antiviral candidate to be further evaluated for safety and potency in future clinical trials against EV-A71.

Matched MeSH terms: Mice, Inbred ICR
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.

Matched MeSH terms: Mice, Inbred ICR
Fulltext Zerumbone-Induced Analgesia Modulated via Potassium Channels and Opioid Receptors in Chronic Constriction Injury-Induced Neuropathic Pain

Gopalsamy B, Chia JSM, Farouk AAO, Sulaiman MR, Perimal EK

Molecules, 2020 Aug 26;25(17).
PMID: 32858809 DOI: 10.3390/molecules25173880

Zerumbone, a monocyclic sesquiterpene from the wild ginger plant Zingiber zerumbet (L.) Smith, attenuates allodynia and hyperalgesia. Currently, its mechanisms of action in neuropathic pain conditions remain unclear. This study examines the involvement of potassium channels and opioid receptors in zerumbone-induced analgesia in a chronic constriction injury (CCI) neuropathic pain mice model. Male Institute of Cancer Research (ICR) mice were subjected to CCI and behavioral responses were tested on day 14. Responses toward mechanical allodynia and thermal hyperalgesia were tested with von Frey's filament and Hargreaves' tests, respectively. Symptoms of neuropathic pain were significantly alleviated following treatment with zerumbone (10 mg/kg; intraperitoneal, i.p.). However, when the voltage-dependent K+ channel blocker tetraethylammonium (TEA, 4 mg/kg; i.p.), ATP-sensitive K+ channel blocker, glibenclamide (GLIB, 10 mg/kg; i.p.); small-conductance Ca2+-activated K+ channel inhibitor apamin (APA, 0.04 mg/kg; i.p.), or large-conductance Ca2+-activated K+ channel inhibitor charybdotoxin (CHAR, 0.02 mg/kg; i.p.) was administered prior to zerumbone (10 mg/kg; i.p.), the antiallodynic and antihyperalgesic effects of zerumbone were significantly reversed. Additionally, non-specific opioid receptors antagonist, naloxone (NAL, 10 mg/kg; i.p.), selective µ-, δ- and κ-opioid receptor antagonists; β-funaltrexamine (β-FN, 40 mg/kg; i.p.), naltrindole (20 mg/kg; s.c.), nor-binaltorphamine (10 mg/kg; s.c.) respectively attenuated the antiallodynic and antihyperalgesic effects of zerumbone. This outcome clearly demonstrates the participation of potassium channels and opioid receptors in the antineuropathic properties of zerumbone. As various clinically used neuropathic pain drugs also share this similar mechanism, this compound is, therefore, a highly potential substitute to these therapeutic options.

Matched MeSH terms: Mice, Inbred ICR
Experimental Characterization of the Chronic Constriction Injury-Induced Neuropathic Pain Model in Mice

Gopalsamy B, Sambasevam Y, Zulazmi NA, Chia JSM, Omar Farouk AA, Sulaiman MR, et al.

Neurochem Res, 2019 Sep;44(9):2123-2138.
PMID: 31376053 DOI: 10.1007/s11064-019-02850-0

Number of ligations made in the chronic constriction injury (CCI) neuropathic pain model has raised serious concerns. We compared behavioural responses, nerve morphology and expression of pain marker, c-fos among CCI models developed with one, two, three and four ligations. The numbers of ligation(s) on sciatic nerve shows no significant difference in displaying mechanical and cold allodynia, and mechanical and thermal hyperalgesia throughout 84 days. All groups underwent similar levels of nerve degeneration post-surgery. Similar c-fos level in brain cingulate cortex, parafascicular nuclei and amygdala were observed in all CCI models compared to sham-operated group. Therefore, number of ligations does not impact intensity of pain symptoms, pathogenesis and neuronal activation. A single ligation is sufficient to develop neuropathic pain, in contrast to the established model of four ligations. This study dissects and characterises the CCI model, ascertaining a more uniform animal model to surrogate actual neuropathic pain condition.

Matched MeSH terms: Mice, Inbred ICR*
Zerumbone alleviates chronic constriction injury-induced allodynia and hyperalgesia through serotonin 5-HT receptors

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.

Matched MeSH terms: Mice, Inbred ICR
Fulltext Cardamonin Modulates Neuropathic Pain through the Possible Involvement of Serotonergic 5-HT1A Receptor Pathway in CCI-Induced Neuropathic Pain Mice Model

Kaswan NK, Mohammed Izham NAB, Tengku Mohamad TAS, Sulaiman MR, Perimal EK

Molecules, 2021 Jun 16;26(12).
PMID: 34208700 DOI: 10.3390/molecules26123677

Cardamonin, a naturally occurring chalcone isolated from Alpinia species has shown to possess strong anti-inflammatory and anti-nociceptive activities. Previous studies have demonstrated that cardamonin exerts antihyperalgesic and antiallodynic properties in chronic constriction injury (CCI)-induced neuropathic pain animal model. However, the mechanisms underlying cardamonin's effect have yet to be fully understood. The present study aims to investigate the involvement of the serotonergic system in cardamonin induced antihyperalgesic and antiallodynic effects in CCI-induced neuropathic pain mice model. The neuropathic pain symptoms in the CCI mice model were assessed using Hargreaves Plantar test and von-Frey filament test on day 14 post-surgery. Central depletion of serotonin along the descending serotonergic pathway was done using ρ-chlorophenylalanine (PCPA, 100 mg/kg, i.p.), an inhibitor of serotonin synthesis for four consecutive days before cardamonin treatment, and was found to reverse the antihyperalgesic and antiallodynic effect produced by cardamonin. Pretreatment of the mice with several 5-HT receptor subtypes antagonists: methiothepin (5-HT1/6/77 receptor antagonist, 0.1 mg/kg), WAY 100635 (5-HT1A receptor antagonist, 1 mg/kg), isamoltane (5-HT1B receptor antagonist, 2.5 mg/kg), ketanserin (5-HT2A receptor antagonist, 0.3 mg/kg), and ondansetron (5-HT3 receptor antagonist, 0.5 mg/kg) were shown to abolish the effect of cardamonin induced antihyperalgesic and antiallodynic effects. Further evaluation of the 5-HT1A receptor subtype protein expressions reveals that cardamonin significantly upregulated its expression in the brainstem and spinal cord. Our results suggest that the serotonergic pathway is essential for cardamonin to exert its antineuropathic effect in CCI mice through the involvement of the 5-HT1A receptor subtype in the central nervous system.

Matched MeSH terms: Mice, Inbred ICR
Fulltext Zerumbone Ameliorates Neuropathic Pain Symptoms via Cannabinoid and PPAR Receptors Using In Vivo and In Silico Models

Chia JSM, Farouk AAO, Mohamad TAST, Sulaiman MR, Zakaria H, Hassan NI, et al.

Molecules, 2021 Jun 24;26(13).
PMID: 34202590 DOI: 10.3390/molecules26133849

Neuropathic pain is a chronic pain condition persisting past the presence of any noxious stimulus or inflammation. Zerumbone, of the Zingiber zerumbet ginger plant, has exhibited anti-allodynic and antihyperalgesic effects in a neuropathic pain animal model, amongst other pharmacological properties. This study was conducted to further elucidate the mechanisms underlying zerumbone's antineuropathic actions. Research on therapeutic agents involving cannabinoid (CB) and peroxisome proliferator-activated receptors (PPARs) is rising. These receptor systems have shown importance in causing a synergistic effect in suppressing nociceptive processing. Behavioural responses were assessed using the von Frey filament test (mechanical allodynia) and Hargreaves plantar test (thermal hyperalgesia), in chronic constriction injury (CCI) neuropathic pain mice. Antagonists SR141716 (CB1 receptor), SR144528 (CB2 receptor), GW6471 (PPARα receptor) and GW9662 (PPARγ receptor) were pre-administered before the zerumbone treatment. Our findings indicated the involvement of CB1, PPARα and PPARγ in zerumbone's action against mechanical allodynia, whereas only CB1 and PPARα were involved against thermal hyperalgesia. Molecular docking studies also suggest that zerumbone has a comparable and favourable binding affinity against the respective agonist on the CB and PPAR receptors studied. This finding will contribute to advance our knowledge on zerumbone and its significance in treating neuropathic pain.

Matched MeSH terms: Mice, Inbred ICR
Heat-killed Salmonella typhi induces the release of prostaglandins and leukotrienes from mouse macrophages

Pang T, Devi S, Puthucheary S, Pawlowski N

Microbiol. Immunol., 1991;35(3):267-71.
PMID: 1870442

Mouse macrophages pre-labeled with [3H]arachidonic acid (20:4) were shown to release metabolites generated by the lipoxygenase and cyclo-oxygenase pathways following in vitro addition of heat-killed Salmonella typhi. These metabolites were maximally released after 60-90 min of incubation and consisted of prostaglandins (85%), leukotriene C (6%), di-HETEs, leukotrienes D and E (4%), mono-HETEs (2%) and other metabolites (3%). Of the metabolites generated by the cyclo-oxygenase pathway (prostaglandins), 6-keto PGF1 alpha and PGE2 were generated at a ratio of 1.2 to 1. The significance and importance of these results are discussed.

Matched MeSH terms: Mice, Inbred ICR
Fulltext Protective effect of α-asarone against nicotine-induced seizures in mice, but not by its interaction with nicotinic acetylcholine receptors

Chellian R, Pandy V

Biomed Pharmacother, 2018 Dec;108:1591-1595.
PMID: 30372861 DOI: 10.1016/j.biopha.2018.09.137

Alpha-asarone is one of the bioactive phytochemicals present in the rhizomes of Acorus species and demonstrated its anticonvulsant activity in rodents. Alpha-asarone protected mice from the gamma-aminobutyric acid (GABA) type A receptor antagonist or N-methyl-d-aspartate (NMDA) receptor agonist-induced seizures. In our recent study, α-asarone attenuated the nicotine withdrawal-induced depression-like behavior in mice. The seizures induced by nicotine is mediated through the activation of nicotinic acetylcholine receptors (nAChRs) and stimulation of NMDA receptors. Therefore, we hypothesized that α-asarone might be effective against nicotine-induced seizures. Also, the interaction of α-asarone with nAChRs is unknown. In this study, we investigated the effect of α-asarone on the locomotor activity and body temperature in mice. In addition, we studied the effect of α-asarone on nicotine-induced seizures in mice. Finally, we assessed in vivo pharmacodynamic interaction of α-asarone with nAChRs using nicotine-induced hypomotility and hypothermia tests in mice. The results of this study showed that the α-asarone (50-200 mg/kg, i.p.) and diazepam (5 mg/kg, i.p.) treatment significantly decreased the locomotor activity and body temperature in mice. Furthermore, α-asarone (50-200 mg/kg, i.p.) and diazepam (5 mg/kg, i.p.) pretreatment significantly prolonged the onset time of nicotine-induced seizures in mice. However, α-asarone (30 and 50 mg/kg, i.p.) pretreatment did not inhibit the nicotine-induced hypomotility or hypothermia in mice. Conversely, mecamylamine (1 mg/kg, s.c.) pretreatment completely blocked the nicotine-induced seizures and significantly prevents the nicotine-induced hypomotility and hypothermia in mice. Overall, these results suggest that the protective effect of α-asarone against nicotine-induced seizures did not mediate through the antagonism of nAChRs. We also postulated that the GABAergic and glutamatergic activities of α-asarone could be involved in its protective effect against nicotine-induced seizures and based on this aspect further studies are required.

Matched MeSH terms: Mice, Inbred ICR
Fulltext Anti-tumor effect of Ardisia crispa hexane fraction on 7, 12-dimethylbenz[α]anthracene-induced mouse skin papillomagenesis

Sulaiman H, Hamid RA, Ting YL, Othman F

J Cancer Res Ther, 2012 Jul-Sep;8(3):404-10.
PMID: 23174723 DOI: 10.4103/0973-1482.103521

CONTEXT: Ardisia crispa Thunb. A. DC (Myrsinaceae) or locally known as hen's eyes has been used in local folk medicine as a remedy in various illnesses. Previously, it has been reported to inhibit various inflammatory diseases. However, research done on this plant is still limited.
AIMS: In the present study, the hexane fraction of the A. crispa root (ACRH) was evaluated on the peri-initiation and promotion phases of skin carcinogenesis.
MATERIALS AND METHODS: This two-stage skin carcinogenesis was induced by a single topical application of 7,12-dimethylbenz(α)anthracene (DMBA) and promoted by repeated treatment with croton oil for 10 weeks in Imprinting Control Region (ICR) mice. Morphological observation would be conducted to measure tumor incidence, tumor burden, and tumor volume. Histological evaluation on the skin tissue would also be done.
RESULTS: The carcinogen control group exhibited 66.67% of tumor incidence. Although, in the ACRH-treated groups, at 30 mg/kg, the mice showed only 10% of tumor incidence with a significant reduction (P < 0.05) in the values of tumor burden and tumor volume of 2.00 and 0.52 mm(3), respectively. Furthermore, the result was significantly lower than that of the carcinogen and curcumin control. At 100 mg/kg, ACRH showed a comparable result to carcinogen control. On the contrary, at 300 mg/kg, ACRH exhibited 100% tumor incidence and showed a significant elevated (P < 0.05) value of tumor burden (3.80) and tumor volume (14.67 ± 2.48 mm(3)).
CONCLUSIONS: The present study thus demonstrates that the anti-tumor effect of the chemopreventive potential of ACRH is at a lower dosage (30 mg/kg bwt) in both the initiating and promotion period, yet it exhibits a promoting effect at a higher dosage (300 mg/kg bwt).

Matched MeSH terms: Mice, Inbred ICR
Constituents of the Edible Leaves of Melicope pteleifolia with Potential Analgesic Activity

Lee BW, Park JG, Ha TKQ, Pham HTT, An JP, Noh JR, et al.

J Nat Prod, 2019 08 23;82(8):2201-2210.
PMID: 31393125 DOI: 10.1021/acs.jnatprod.9b00224

Melicope pteleifolia has long been consumed as a popular vegetable and tea in Southeast Asian countries, including Malaysia and southern mainland China, and is effective in the treatment of colds and inflammation. In the search for active metabolites that can explain its traditional use as an antipyretic, six new phloroacetophenone derivatives (3-8) along with seven known compounds (1, 2, and 9-13) were isolated from the leaves of M. pteleifolia. Their chemical structures were confirmed by extensive spectroscopic analysis including NMR, IR, ECD, and HRMS. All compounds isolated from the leaves of M. pteleifolia (1-13) have a phloroacetophenone skeleton. Notably, the new compound 8 contains an additional cyclobutane moiety in its structure. The bioactivities of the isolated compounds were evaluated, and compounds 1, 6, and 7 inhibited tumor necrosis factor-α-induced prostaglandin E2. Moreover, the major constituent, 3,5-di-C-β-d-glucopyranosyl phloroacetophenone (1), was found to be responsible for the antipyretic activity of M. pteleifolia based on in vivo experiments.

Matched MeSH terms: Mice, Inbred ICR
Diabetes alters the mRNA expression of insulin-like growth factors and their receptors in the mouse fallopian tube and uterus during the preimplantation stages

Zakaria R, Rajikin MH, Yaacob NS, Nor NM

Reprod Biol, 2007 Mar;7(1):41-53.
PMID: 17435832

The possible role of insulin-like growth factors (IGFs) and their receptors (IGFRs) in the pathogenesis of diabetic embryopathy was investigated. Sexually mature female ICR mice of 6-8 weeks old were made diabetic by a single intraperitoneal injection with 200 mg/kg streptozotocin ten days prior to mating. Fallopian tubes and uterine tissues were obtained from the superovulated diabetic and normal mice 48, 72 and 96 hours following human chorionic gonadotropin (hCG) injection. The mRNA expression of IGF-1 and IGF-2 as well as their receptors was determined in the tissues using Real-time Polymerase Chain Reaction (Real-time PCR). The mRNA expression of IGF-1 in the fallopian tube and uterus of the diabetic mice was significantly lower 72 and 96 hours after hCG treatment, respectively, as compared to the controls. The mRNA expression of IGF-1R at 96 hours post-hCG treatment was significantly higher in the fallopian tube and lower in the uterus of the diabetic mice as compared to the controls. The mRNA expression IGF-2 in the fallopian tube was significantly higher 48 and 96 hours after hCG treatment, but was lower in the uterus of diabetic mice 96 hours after hCG treatment as compared to controls. The mRNA expression of IGF-2R in the diabetic mice was significantly higher 48 and 96 hours (the fallopian tube) and 48 hours (uterus) after hCG treatments as compared to the controls. In conclusion, an alteration in mRNA expression of IGFs and their receptors in the diabetic mice as observed in this study could possibly result in diabetic embryopathy.

Matched MeSH terms: Mice, Inbred ICR

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