Displaying publications 21 - 40 of 2084 in total

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  1. Ooi TC, Chan KM, Sharif R
    Biol Trace Elem Res, 2016 Aug;172(2):458-464.
    PMID: 26749414 DOI: 10.1007/s12011-015-0615-x
    This study aimed to investigate the role of the mitogen-activated protein kinases (MAPKs) signaling pathway in the anti-inflammatory effects of zinc carnosine (ZnC) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Cells were pretreated with ZnC (0-100 μM) for 2 h prior to the addition of LPS (1 μg/ml). Following 24 h of treatment, ZnC was found not to be cytotoxic to RAW 264.7 cells up to the concentration of 100 μM. Our current findings showed that ZnC did not protect RAW 264.7 cells from LPS-induced "respiratory burst". Significant increment in intracellular glutathione (GSH) level and reduction in thiobarbituric acid reactive substances (TBARS) concentration can only be observed in cell pretreated with high doses of ZnC only (50 and 100 μM for GSH and 100 μM only for TBARS). On the other hand, pretreatment of cells with ZnC was able to inhibit LPS-induced inducible nitric oxide synthase and cyclooxygenase-2 expression significantly. Furthermore, results from immunoblotting showed that ZnC was able to suppress nuclear factor-kappaB (NF-κB) activation, and highest suppression can be observed at 100 μM of ZnC pretreatment. However, pretreatment of ZnC did not inhibit the early activation of MAPKs. In conclusion, pretreatment with ZnC was able to inhibit the expression of inflammatory mediators in LPS-induced RAW 264.7 cells, mainly via suppression of NF-κB activation, and is independent of the MAPKs signaling pathway.
    Matched MeSH terms: Mice
  2. 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.
    Matched MeSH terms: Mice, Inbred ICR; Mice
  3. 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; Mice
  4. Paudel KR, Clarence DD, Panth N, Manandhar B, De Rubis G, Devkota HP, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2024 Apr;397(4):2465-2483.
    PMID: 37851060 DOI: 10.1007/s00210-023-02760-7
    The purpose of this study was to evaluate the potential of zerumbone-loaded liquid crystalline nanoparticles (ZER-LCNs) in the protection of broncho-epithelial cells and alveolar macrophages against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro. The effect of the treatment of ZER-LCNs on in vitro cell models of cigarette smoke extract (CSE)-treated mouse RAW264.7 and human BCi-NS1.1 basal epithelial cell lines was evaluated for their anti-inflammatory, antioxidant and anti-senescence activities using colorimetric and fluorescence-based assays, fluorescence imaging, RT-qPCR and proteome profiler kit. The ZER-LCNs successfully reduced the expression of pro-inflammatory markers including Il-6, Il-1β and Tnf-α, as well as the production of nitric oxide in RAW 264.7 cells. Additionally, ZER-LCNs successfully inhibited oxidative stress through reduction of reactive oxygen species (ROS) levels and regulation of genes, namely GPX2 and GCLC in BCi-NS1.1 cells. Anti-senescence activity of ZER-LCNs was also observed in BCi-NS1.1 cells, with significant reductions in the expression of SIRT1, CDKN1A and CDKN2A. This study demonstrates strong in vitro anti-inflammatory, antioxidative and anti-senescence activities of ZER-LCNs paving the path for this formulation to be translated into a promising therapeutic agent for chronic respiratory inflammatory conditions including COPD and asthma.
    Matched MeSH terms: Mice
  5. Jantan I, Haque MA, Ilangkovan M, Arshad L
    Int Immunopharmacol, 2019 Aug;73:552-559.
    PMID: 31177081 DOI: 10.1016/j.intimp.2019.05.035
    Zerumbone exhibited various biological properties including in vitro immunosuppressive effects. However, its modulatory activity on the immune responses in experimental animal model is largely unknown. This investigation was conducted to explore the effects of daily treatment of zerumbone (25, 50, and 100 mg/kg) isolated from Zingiber zerumbet rhizomes for 14 days on various cellular and humoral immune responses in Balb/C mice. For measurement of adaptive immunity, sheep red blood cells (sRBC) were used to immunize the mice on day 0 and orally fed with similar doses of zerumbone for 14 days. The effects of zerumbone on phagocytosis, nitric oxide (NO) release, myeloperoxidase (MPO) activity, proliferation of T and B cells, lymphocyte phenotyping, cytokines release in serum by activated T cells, delayed type hypersensitivity (DTH) and immunoglobulins production (IgG and IgM) were investigated. Zerumbone downregulated the engulfment of E. coli by peritoneal macrophages and the release of NO and MPO in a concentration-dependent manner. Zerumbone showed significant and concentration-dependent suppression of T and B lymphocytes proliferation and inhibition of the Th1 and Th2 cytokines release. At higher concentrations of zerumbone, the % expression of CD4+ and CD8+ in splenocytes was significantly inhibited. Zerumbone also concentration-dependently demonstrated strong suppression on sRBC-triggered swelling of mice paw in DTH. Substantial suppression of anti-sRBC immunoglobulins antibody titer was noted in immunized and zerumbone-treated mice in a concentration-dependent manner. The potent suppressive effects of zerumbone on the immune responses suggest that zerumbone can be a potential candidate for development of immunosuppressive agent.
    Matched MeSH terms: Mice, Inbred BALB C
  6. 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; Mice
  7. Chia JSM, Izham NAM, Farouk AAO, Sulaiman MR, Mustafa S, Hutchinson MR, et al.
    Front Pharmacol, 2020;11:92.
    PMID: 32194397 DOI: 10.3389/fphar.2020.00092
    Zerumbone has shown great potential in various pathophysiological models of diseases, particularly in neuropathic pain conditions. Further understanding the mechanisms of action is important to develop zerumbone as a potential anti-nociceptive agent. Numerous receptors and pathways function to inhibit and modulate transmission of pain signals. Previously, we demonstrated involvement of the serotonergic system in zerumbone's anti-neuropathic effects. The present study was conducted to determine zerumbone's modulatory potential involving noradrenergic, transient receptor potential vanilloid type 1 (TRPV1) and N-methyl-D-aspartate (NMDA) receptors in chronic constriction injury (CCI)-induced in vitro and lipopolysaccharide (LPS)-induced SH-SY5Y in vitro neuroinflammatory models. von Frey filament and Hargreaves plantar tests were used to assess allodynia and hyperalgesia in the chronic constriction injury-induced neuropathic pain mouse model. Involvement of specific adrenoceptors were investigated using antagonists- prazosin (α1-adrenoceptor antagonist), idazoxan (α2-adrenoceptor antagonist), metoprolol (β1-adrenoceptor antagonist), ICI 118,551 (β2-adrenoceptor antagonist), and SR 59230 A (β3-adrenoceptor antagonist), co-administered with zerumbone (10 mg/kg). Involvement of excitatory receptors; TRPV and NMDA were conducted using antagonists capsazepine (TRPV1 antagonist) and memantine (NMDA antagonist). Western blot was conducted to investigate the effect of zerumbone on the expression of α2A-adrenoceptor, TRPV1 and NMDA NR2B receptors in CCI-induced whole brain samples of mice as well as in LPS-induced SH-SY5Y neuroblastoma cells. Pre-treatment with α1- and α2-adrenoceptor antagonists significantly attenuated both anti-allodynic and anti-hyperalgesic effects of zerumbone. For β-adrenoceptors, only β2-adrenoceptor antagonist significantly reversed the anti-allodynic and anti-hyperalgesic effects of zerumbone. β1-adrenoceptor antagonist only reversed the anti-allodynic effect of zerumbone. The anti-allodynic and anti-hyperalgesic effects of zerumbone were both absent when TRPV1 and NMDA receptors were antagonized in both nociceptive assays. Zerumbone treatment markedly decreased the expression of α2A-adrenoceptor, while an up-regulation was observed of NMDA NR2B receptors. Expression of TRPV1 receptors however did not significantly change. The in vitro study, representing a peripheral model, demonstrated the reduction of both NMDA NR2B and TRPV1 receptors while significantly increasing α2A-adrenoceptor expression in contrast to the brain samples. Our current findings suggest that the α1-, α2-, β1- and β2-adrenoceptors, TRPV1 and NMDA NR2B are essential for the anti-allodynic and antihyperalgesic effects of zerumbone. Alternatively, we demonstrated the plasticity of these receptors through their response to zerumbone's administration.
    Matched MeSH terms: Mice
  8. 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; Mice
  9. 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.
    Matched MeSH terms: Mice
  10. Zhang X, Zhao L, Xiang S, Sun Y, Wang P, Chen JJ, et al.
    J Ethnopharmacol, 2023 May 10;307:116243.
    PMID: 36791927 DOI: 10.1016/j.jep.2023.116243
    ETHNOPHARMACOLOGICAL RELEVANCE: Yishen Tongluo formula (YSTLF) is formulated based on traditional Chinese medicine theory for the treatment of Diabetic kidney disease (DKD) and has been shown to be effective in improving the symptoms of DKD according to the clinical observation.

    AIM OF THE STUDY: To explore the effect of YSTLF on DKD and figure out whether its effects were due to the regulation Sirt6/TGF-β1/Smad2/3 pathway and promoting degradation of TGF-β1.

    MATERIALS AND METHODS: The extract of YSTLF at 1, 2.5 and 5 g/kg was orally administered to C57BLKS/J (db/db) mice for 8 weeks and db/db mice were given valsartan as a positive control. The littermate db/m and db/db mice were given vehicle as the control and model group, respectively. Blood urea nitrogen and serum creatinine were detected and the urinary albumin excretion, urea albumin creatinine ratio was calculated. The histopathological change of renal tissues in each group was determined. Simultaneously, the levels of fibrosis-related proteins and messenger RNA (mRNA) in kidney and high glucose (HG)-induced SV40-MES-13 cells were detected. The roles of YSTLF in regulating of Sirt6/TGF-β1/Smad2/3 signaling pathway were investigated in HG-stimulated SV40-MES-13 cells and validated in db/db mice. Furthermore, the effect of YSTLF on TGF-β1 degradation was investigated in HG-stimulated SV40-MES-13 cells.

    RESULTS: YSTLF significantly improved the renal function in DKD mice. YSTLF dose-dependently attenuated pathological changes and suppressed the expression of type I collagen, alpha smooth muscle actin, type IV collagen, and fibronectin in vitro and in vivo, resulting in ameliorating of renal fibrosis. YSTLF positively regulated Sirt6 expression, while inhibited the activating of TGF-β1/Smad2/3 signaling pathway. TGF-β1 was steady expressed in HG-stimulated SV40-MES-13 cells, whereas was continuously degraded under YSTLF treatment.

    CONCLUSIONS: YSTLF significantly ameliorates renal damages and fibrosis may via regulating Sirt6/TGF-β1/Smad2/3 signaling pathway as well as promoting the degradation of TGF-β1.

    Matched MeSH terms: Mice
  11. Gordon Smith CE, Turner LH, Armitage P
    Bull World Health Organ, 1962;27:717-27.
    PMID: 13993152
    Because of the risk of introduction of yellow fever to South-East Asia, comparative studies were made of yellow fever vaccination in Malayans who had a high prevalence of antibody to related viruses and in volunteers without related antibody. The proportions of positive neutralizing antibody responses to subcutaneous vaccination with 17D vaccine were not significantly different between volunteers with and without heterologous antibody but the degree of antibody response was greater in those without. The ID(50) of 17D in both groups was about 5 mouse intracerebral LD(50). Multiple puncture vaccination with 17D gave a much lower response rate than subcutaneous vaccination in volunteers with heterologous antibody. In both groups subcutaneous doses of about 50 mouse intracerebral LD(50) gave larger antibody responses than higher doses. The neutralizing indices and analysis of results were calculated by a method based on the survival time of the mice. This method, which has advantages over that of Reed & Muench, is fully described in an annex to this paper.
    Matched MeSH terms: Mice
  12. Gordon Smith CE, McMahon DA, Turner LH
    Bull World Health Organ, 1963;29:75-80.
    PMID: 14043754
    In view of the risk of introduction of yellow fever into South-East Asia, comparative studies have been made of yellow fever vaccination in Malayan volunteers with a high prevalence of antibody to related viruses and in volunteers without related antibody. In a previous paper the neutralizing antibody responses of these volunteers were reported. The present paper describes the haemagglutinin-inhibiting (HI) antibody responses of the same groups of volunteers and discusses the relationship of these responses to the neutralizing antibody responses.The HI responses to yellow fever following vaccination closely paralleled the neutralizing antibody responses whether vaccination was subcutaneous or by multiple puncture. Volunteers with a high level of YF HI antibody due to infection with other group B viruses were found to be less likely to show a significant YF HI response than those without antibody. 90% of HI responses could be detected by the 21st day after vaccination.As with neutralizing antibody responses, volunteers given vaccine doses of 50-500 mouse intracerebral LD(50) subcutaneously gave greater responses than those given higher doses.
    Matched MeSH terms: Mice
  13. Laila L, Febriyenti F, Salhimi SM, Baie S
    Int Wound J, 2011 Oct;8(5):484-91.
    PMID: 21722317 DOI: 10.1111/j.1742-481X.2011.00820.x
    Haruan (Channa striatus) is a type of fresh water fish in Malaysia that is known to promote wound healing. Haruan water extract has been formulated in an aerosol system which can produce a film for wound dressing. As topical preparation, Haruan spray needs to be evaluated in terms of the possibility to cause irritation reaction or toxic response. Three experiments were carried out to evaluate the safety of Haruan spray which are Primary Skin Irritation test, Intracutaneous test and Systemic Injection test. The result shows that Haruan spray gave no significant responses to all the above tests. The investigation of the effect of Haruan spray as wound dressing in the healing process was performed in Sprague-Dawley rats where 6-cm long full-thickness incision wound and burn wound were made on the back of the animals. Haruan spray was tested and compared with blank formula as control. Tensile strength test of treated wound was carried out at the 3rd, 6th, 9th and 12th day after wounding and treatment. The burn wounds contraction was measured daily for 21 days. Results showed that haruan water extract spray formula is not only effective but also safe for application to both incision and burn wounds.
    Matched MeSH terms: Mice
  14. Kalantari K, Mostafavi E, Afifi AM, Izadiyan Z, Jahangirian H, Rafiee-Moghaddam R, et al.
    Nanoscale, 2020 Jan 28;12(4):2268-2291.
    PMID: 31942896 DOI: 10.1039/c9nr08234d
    Infections are the main reason why most people die from burns and diabetic wounds. The clinical challenge for treating wound infections through traditional antibiotics has been growing steadily and has now reached a critical status requiring a paradigm shift for improved chronic wound care. The US Centers for Disease Control have predicted more deaths from antimicrobial-resistant bacteria than from all types of cancers combined by 2050. Thus, the development of new wound dressing materials that do not rely on antibiotics is of paramount importance. Currently, incorporating nanoparticles into scaffolds represents a new concept of 'nanoparticle dressing' which has gained considerable attention for wound healing. Silver nanoparticles (Ag-NPs) have been categorized as metal-based nanoparticles and are intriguing materials for wound healing because of their excellent antimicrobial properties. Ag-NPs embedded in wound dressing polymers promote wound healing and control microorganism growth. However, there have been several recent disadvantages of using Ag-NPs to fight infections, such as bacterial resistance. This review highlights the therapeutic approaches of using wound dressings functionalized with Ag-NPs and their potential role in revolutionizing wound healing. Moreover, the physiology of the skin and wounds is discussed to place the use of Ag-NPs in wound care into perspective.
    Matched MeSH terms: Mice
  15. Ibrahim N', Wong SK, Mohamed IN, Mohamed N, Chin KY, Ima-Nirwana S, et al.
    PMID: 30366427 DOI: 10.3390/ijerph15112360
    Wound healing is a complex process of recovering the forms and functions of injured tissues. The process is tightly regulated by multiple growth factors and cytokines released at the wound site. Any alterations that disrupt the healing processes would worsen the tissue damage and prolong repair process. Various conditions may contribute to impaired wound healing, including infections, underlying diseases and medications. Numerous studies on the potential of natural products with anti-inflammatory, antioxidant, antibacterial and pro-collagen synthesis properties as wound healing agents have been performed. Their medicinal properties can be contributed by the content of bioactive phytochemical constituents such as alkaloids, essential oils, flavonoids, tannins, saponins, and phenolic compounds in the natural products. This review highlights the in vitro, in vivo and clinical studies on wound healing promotions by the selected natural products and the mechanisms involved.
    Matched MeSH terms: Mice
  16. Hung TH, Hsu SC, Cheng CY, Choo KB, Tseng CP, Chen TC, et al.
    Oncotarget, 2014 Dec 15;5(23):12273-90.
    PMID: 25401518
    Multidrug resistance in cancer cells arises from altered drug permeability of the cell. We previously reported activation of the Wnt pathway in ABCB1-overexpressed human uterus sarcoma drug-resistant MES-SA/Dx5 cells through active β-catenin and associated transactivation activities, and upregulation of Wnt-targeting genes. In this study, Wnt5A was found to be significantly upregulated in MES-SA/Dx5 and MCF7/ADR2 cells, suggesting an important role for the Wnt5A signaling pathway in cancer drug resistance. Higher cAMP response elements and Tcf/Lef transcription activities were shown in the drug-resistant cancer cells. However, expression of Wnt target genes and CRE activities was downregulated in Wnt5A shRNA stably-transfected MES-SA/Dx5 cells. Cell viability of the drug-resistant cancer cells was also reduced by doxorubicin treatment and Wnt5A shRNA transfection, or by Wnt5A depletion. The in vitro data were supported by immunohistochemical analysis of 24 paired breast cancer biopsies obtained pre- and post-chemotherapeutic treatment. Wnt5A, VEGF and/or ABCB1 were significantly overexpressed after treatment, consistent with clinical chemoresistance. Taken together, the Wnt5A signaling pathway was shown to contribute to regulating the drug-resistance protein ABCB1 and β-catenin-related genes in antagonizing the toxic effects of doxorubicin in the MDR cell lines and in clinical breast cancer samples.
    Matched MeSH terms: Mice, Nude; Mice
  17. Khalilpourfarshbafi M, Devi Murugan D, Abdul Sattar MZ, Sucedaram Y, Abdullah NA
    PLoS One, 2019;14(6):e0218792.
    PMID: 31226166 DOI: 10.1371/journal.pone.0218792
    The increased prevalence of obesity and associated insulin resistance calls for effective therapeutic treatment of metabolic diseases. The current PPARγ-targeting antidiabetic drugs have undesirable side effects. The present study investigated the anti-diabetic and anti-obesity effects of withaferin A (WFA) in diet-induced obese (DIO) C57BL/6J mice and also the anti-adipogenic effect of WFA in differentiating 3T3- F442A cells. DIO mice were treated with WFA (6 mg/kg) or rosiglitazone (10 mg/kg) for 8 weeks. At the end of the treatment period, metabolic profile, liver function and inflammatory parameters were obtained. Expression of selective genes controlling insulin signaling, inflammation, adipogenesis, energy expenditure and PPARγ phosphorylation-regulated genes in epididymal fats were analyzed. Furthermore, the anti-adipogenic effect of WFA was evaluated in 3T3- F442A cell line. WFA treatment prevented weight gain without affecting food or caloric intake in DIO mice. WFA-treated group also exhibited lower epididymal and mesenteric fat pad mass, an improvement in lipid profile and hepatic steatosis and a reduction in serum inflammatory cytokines. Insulin resistance was reduced as shown by an improvement in glucose and insulin tolerance and serum adiponectin. WFA treatment upregulated selective insulin signaling (insr, irs1, slc2a4 and pi3k) and PPARγ phosphorylation-regulated (car3, selenbp1, aplp2, txnip, and adipoq) genes, downregulated inflammatory (tnf-α and il-6) genes and altered energy expenditure controlling (tph2 and adrb3) genes. In 3T3- F442A cell line, withaferin A inhibited adipogenesis as indicated by a decrease in lipid accumulation in differentiating adipocytes and protein expression of PPARγ and C/EBPα. The effect of rosiglitazone on physiological and lipid profiles, insulin resistance, some genes expression and differentiating adipocytes were markedly different. Our data suggest that WFA is a promising therapeutic agent for both diabetes and obesity.
    Matched MeSH terms: Mice, Inbred C57BL; Mice, Obese; Mice
  18. Abu Bakar MH, Azmi MN, Shariff KA, Tan JS
    Appl Biochem Biotechnol, 2019 May;188(1):241-259.
    PMID: 30417321 DOI: 10.1007/s12010-018-2920-2
    Withaferin A (WA), a bioactive constituent derived from Withania somnifera plant, has been shown to exhibit many qualifying properties in attenuating several metabolic diseases. The current investigation sought to elucidate the protective mechanisms of WA (1.25 mg/kg/day) on pre-existing obese mice mediated by high-fat diet (HFD) for 12 weeks. Following dietary administration of WA, significant metabolic improvements in hepatic insulin sensitivity, adipocytokines with enhanced glucose tolerance were observed. The hepatic oxidative functions of obese mice treated with WA were improved via augmented antioxidant enzyme activities. The levels of serum pro-inflammatory cytokines and hepatic mRNA expressions of toll-like receptor (TLR4), nuclear factor κB (NF-κB), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand-receptor, and cyclooxygenase 2 (COX2) in HFD-induced obese mice were reduced. Mechanistically, WA increased hepatic mRNA expression of peroxisome proliferator-activated receptors (PPARs), cluster of differentiation 36 (CD36), fatty acid synthase (FAS), carnitine palmitoyltransferase 1 (CPT1), glucokinase (GCK), phosphofructokinase (PFK), and phosphoenolpyruvate carboxykinase (PCK1) that were associated with enhanced lipid and glucose metabolism. Taken together, these results indicate that WA exhibits protective effects against HFD-induced obesity through attenuation of hepatic inflammation, oxidative stress, and insulin resistance in mice.
    Matched MeSH terms: Mice, Inbred C57BL; Mice
  19. Razali WA, Sreenivasan VK, Bradac C, Connor M, Goldys EM, Zvyagin AV
    J Biophotonics, 2016 08;9(8):848-58.
    PMID: 27264934 DOI: 10.1002/jbio.201600050
    Fluorescence microscopy is a fundamental technique for the life sciences, where biocompatible and photostable photoluminescence probes in combination with fast and sensitive imaging systems are continually transforming this field. A wide-field time-gated photoluminescence microscopy system customised for ultrasensitive imaging of unique nanoruby probes with long photoluminescence lifetime is described. The detection sensitivity derived from the long photoluminescence lifetime of the nanoruby makes it possible to discriminate signals from unwanted autofluorescence background and laser backscatter by employing a time-gated image acquisition mode. This mode enabled several-fold improvement of the photoluminescence imaging contrast of discrete nanorubies dispersed on a coverslip. It enabled recovery of the photoluminescence signal emanating from discrete nanorubies when covered by a layer of an organic fluorescent dye, which were otherwise invisible without the use of spectral filtering approaches. Time-gated imaging also facilitated high sensitivity detection of nanorubies in a biological environment of cultured cells. Finally, we monitor the binding kinetics of nanorubies to a functionalised substrate, which exemplified a real-time assay in biological fluids. 3D-pseudo colour images of nanorubies immersed in a highly fluorescent dye solution. Nanoruby photoluminescence is subdued by that of the dye in continuous excitation/imaging (left), however it can be recovered by time-gated imaging (right). At the bottom is schematic diagram of nanoruby assay in a biological fluid.
    Matched MeSH terms: Mice
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