Methods - Experimental animal models to induce cardiac arrhythmias

Cardiac arrhythmias are of different types based on their mechanism and origin. The information gathered from animal studies has been instrumental in devising diagnostic and therapeutic strategies; so different animal models are needed for different types of arrhythmias. The origin and mechanism underlying clinical arrhythmias are of considerable significance, since knowledge of these processes may provide a basis for successful therapy. Various animal models that encompass different types of arrhythmias are reviewed. This review classifies various experimental models according to their origin, which are mainly supraventricular and ventricular. Also included are various transgenic animal models for arrhythmias

Neonatal streptozotocin-induced rat model of Type 2 diabetes mellitus: A glance

Diabetes mellitus is a group of syndromes characterized by hyperglycemia, altered metabolism of lipids, carbohydrates and protein and an increased risk of complication of vascular diseases. Type 2 diabetes mellitus is characterized by derangement of insulin secretion and an inability of the peripheral tissues to respond to insulin. In spite of the availability of many animal models for Type 2 diabetes mellitus including genetic and chemically induced, none of them simulate human Type 2 diabetes mellitus. An attempt has been made in the present review, to evaluate the neonatal streptozotocin-induced rat (n-STZ rats) model of Type 2 diabetes mellitus, for its potential advantages as a suitable model over the others. The n-STZ model (with alteration of dose and day of STZ injection) exhibits various stages of Type 2 diabetes mellitus such as impaired glucose tolerance, and mild, moderate and severe glycemia. The cells in n-STZ rats bear a resemblance to insulin secretory characteristics found in patients with Type 2 diabetes mellitus. Thus the n-STZ model can be considered as one of the suitable animal models of Type 2 diabetes mellitus

Investigations of Sapindus trifoliatus in dopaminergic and serotonergic systems: Putative antimigraine mechanisms

OBJECTIVE: To evaluate the potential dopaminergic and serotonergic receptor-mediated modulatory effect of the aqueous extract of Sapindus trifoliatus [(ST), (family: Sapindaceae)], a traditional phytomedicine used in the treatment of hemicrania (migraine), using animal models and receptor assays. MATERIALS AND METHODS: ST (at 20 and 100 mg/kg, i.p. doses) was evaluated for its effect on apomorphine-induced climbing behavior, 5-hydroxytryptophan (l-5-HTP)-induced serotonin syndrome, and MK-801-induced hyperactivity in mice. The radioligand binding studies for various receptors and enzymes were carried out (outsourced) using standard procedures at 250 µg/ml concentration of ST. RESULTS: ST significantly inhibited the apomorphine-induced climbing behavior, the l-5-HTP-induced serotonin syndrome and MK-801-induced hyperactivity in mice. In the receptor radioligand binding studies, ST exhibited affinity towards dopamine D2, 5-HT2A receptors. CONCLUSION: The results of the behavioral studies in mice indicate that ST modulated D2 and 5-HT2A receptor-mediated paradigms. The radioligand binding studies supported these observations, suggesting the possible involvement of dopaminergic and serotonergic mechanisms in the antimigraine activity of ST

Polyphenols, Promising Therapeutics For Inflammatory Diseases?

[No abstract available]421430Arts, I.C., Hollman, P.C., Polyphenols and disease risk in epidemiologic studies (2005) American Journal of Clinical Nutrition, 81, pp. 317S-325SAzazieh, H., Saad, B., Cooper, E., Said, O., Traditional Arabic and Islamic medicine, a re-emerging health aid (2008) Evidence-Based Complementary and Alternative Medicine, 7, pp. 419-424Balasubramanian, S., Efimova, T., Eckert, R.L., Green tea polyphenol stimulates a Ras, MEKK1, MEK3, and p38 cascade to increase activator protein 1 factor-dependent involucrin gene expression in normal human keratinocytes (2002) Journal of Biological Chemistry, 277, pp. 1828-1836Balick, J.M., Cox, P.A., (1996) Plants, People and Culture: The Science of Ethnobotany, , Scientific American Library, New YorkBelcaro, G., Cesarone, M.R., Dugall, M., Efficacy and safety of Meriva®, a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients (2010) Alternative Medicine Review, 15 (4), pp. 337-344Bereswill, S., Muñoz, M., Fischer, A., Anti-inflammatory effects of resveratrol, curcumin and simvastatin in acute small intestinal inflammation (2010) PLoS One, 5 (12), pp. e15099Bravo, L., Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance (1998) Nutrition Reviews, 56, pp. 317-333Butt, M.S., Sultan, M.T., Green tea: nature's defense against malignancies (2009) Critical Reviews in Food Science and Nutrition, 49, pp. 463-473Calixto, J.B., Otuki, M.F., Santos, A.R., Anti-inflammatory compounds of plant origin. Part I. Action on arachidonic acid pathway, nitric oxide and nuclear factor kappa B (NF-kappaB) (2003) Planta Medica, 69 (11), pp. 973-983Cho, S.Y., Park, S.J., Kwon, M.J., Quercetin suppresses proinflammatory cytokines production through MAP kinases and NF-kappaB pathway in lipopolysaccharide stimulated macrophage (2003) Molecular and Cellular Biochemistry, 243, pp. 153-160Giday, M., Asfaw, Z., Elmqvist, T., Woldu, Z., An ethnobotanical study of medicinal plants used by the Zay people in Ethiopia (2003) Journal of Ethnopharmacology, 85, pp. 43-52Hill, A.F., (1989) Economic Botany: A Text Book of Useful Plants and Plant Products, , McGraw Hill Book Company, New York, 560ppJang, M., Pezzuto, J.M., Effects of resveratrol on 12-O-tetradecanoylphorbol 13-acetate-induced oxidative events and gene expression in mouse skin (1998) Cancer Letters, 134, pp. 81-89Kim, O.K., Murakami, A., Nakamura, Y., Screening of edible Japanese plants for nitric oxide generation inhibitory activities in RAW 2647 cells (1998) Cancer Letters, 125, pp. 199-207Kostyuk, V.A., Potapovich, A.I., Suhan, T.O., de Luca, C., Korkina, L.G., Antioxidant and signal modulation properties of plant polyphenols in controlling vascular inflammation (2011) European Journal of Pharmacology, 658, pp. 248-256Lanzilli, G., Cottarelli, A., Nicotera, G., Anti-inflammatory effect of resveratrol and polydatin by in vitro IL-17 modulation (2011) Inflammation, 35, pp. 240-248Levine, J.D., Reichling, D.B., Peripheral mechanisms of inflammatory pain (1999) Textbook of Pain, pp. 59-84. , Churchill Livingstone, London, P.D. Wall, R. Melzack (Eds.)Liang, Y.C., Huang, Y.T., Tsai, S.H., Suppression of inducible cyclooxygenase and inducible nitric oxide synthase by apigenin and related flavonoids in mouse macrophages (1999) Carcinogenesis, 20, pp. 1945-1952MacCarrone, M., Lorenzon, T., Guerrieri, P., Agro, A.F., Resveratrol prevents apoptosis in K562 cells by inhibiting lipoxygenase and cyclooxygenase activity (1999) European Journal of Biochemistry, 265, pp. 27-34Manach, C., Scalbert, A., Morand, C., Polyphenols: food sources and bioavailability (2004) American Journal of Clinical Nutrition, 79, pp. 727-747Mann, G.E., Rowlands, D.J., Li, F.Y., Activation of endothelial nitric oxide synthase by dietary isoflavones: role of NO in Nrf2-mediated antioxidant gene expression (2007) Cardiovascular Research, 75, pp. 261-274Masella, R., Di Benedetto, R., Vari, R., Novel mechanisms of natural antioxidant compounds in biological systems: involvement of glutathione and glutathione-related enzymes (2005) Journal of Nutritional Biochemistry, 16, pp. 577-586Middleton, E., Kandaswami, C., Theoharides, T.C., The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer (2000) Pharmacological Reviews, 52, pp. 673-751Nichols, J.A., Katiyar, S.K., Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms (2010) Archives for Dermatological Research, 302 (2), pp. 71-83Noreen, Y., Serrano, G., Perera, P., Flavan-3-ols isolated from some medicinal plants inhibiting COX-1 and COX-2 catalysed prostaglandin biosynthesis (1998) Planta Medica, 64, pp. 520-524Peterson, J., Dwyer, J., Flavonoids: dietary occurrence and biochemical activity (1998) Nutrition Research, 18, pp. 1995-2018Rahman, I., Biswas, S.K., Kirkham, P.A., Regulation of inflammation and redox signaling by dietary polyphenols (2006) Biochemical Pharmacology, 72, pp. 1439-1452Ramos, S., Cancer chemoprevention and chemotherapy: dietary polyphenols and signalling pathways (2008) Molecular Nutrition and Food Research, 52, pp. 507-526Samy, R.P., Gopalakrishnakone, P., Therapeutic potential of plants as anti-microbials for drug discovery (2008) Evidence-Based Complementary and Alternative Medicine, 7, pp. 283-294Santangelo, C., Varì, R., Scazzocchio, B., Polyphenols, intracellular signalling and inflammation (2007) Annali dell'Istituto Superiore di Sanità, 43, pp. 394-405Schmitt, C.A., Heiss, E.H., Dirsch, V.M., Effect of resveratrol on endothelial cell function: molecular mechanisms (2010) Biofactors, 36 (5), pp. 342-349Serafini, M., Bugianesi, R., Salucci, M., Effect of acute ingestion of fresh and stored lettuce (Lactuca sativa) on plasma total antioxidant capacity and antioxidant levels in human subjects (2002) British Journal of Nutrition, 88, pp. 615-623Serafini, M., Testa, M.F., Villano, D., Antioxidant activity of blueberry fruit is impaired by association with milk (2009) Free Radical Biology and Medicine, 46, pp. 769-774Subbaramaiah, K., Chung, W.J., Michaluart, P., Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells (1998) Journal of Biological Chemistry, 273, pp. 21875-21882Surh, Y.J., Chun, K.S., Cha, H.H., Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation (2001) Mutation Research, 480-481, pp. 43-68Taubert, D., Roesen, R., Lehmann, C., Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial (2007) Journal of the American Medical Association, 298, pp. 49-60Wadsworth, T.L., Koop, D.R., Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced release of nitric oxide (2001) Chemico-Biological Interactions, 137, pp. 43-58Wadsworth, T.L., McDonald, T.L., Koop, D.R., Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced signaling pathways involved in the release of tumor necrosis factor-alpha (2001) Biochemical Pharmacology, 62, pp. 963-974Welton, A.F., Tobias, L.D., Fiedler-Nagy, C., Effect of flavonoids on arachidonic acid metabolism (1986) Plant Flavonoids in Biology and Medicine, pp. 231-242. , Alan R. Liss, New York, V. Cody, E. Middleton, J.B. Harborne (Eds.)Wilken, R., Veena, M.S., Wang, M.B., Srivatsan, E.S., Curcumin: a review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma (2011) Molecular Cancer, 10 (1), p. 12Wondimu, T., Asfaw, Z., Kelbessa, E., Ethnobotanical study of medicinal plants around 'Dheera' town, Arsi zone, Ethiopia (2007) Journal of Ethnopharmacology, 112, pp. 152-161Zern, T.L., Fernandez, M.L., Cardioprotective effects of dietary polyphenols (2005) Journal of Nutrition, 135, pp. 2291-2294Zhong, F., Chen, H., Han, L., Jin, Y., Wang, W., Curcumin attenuates lipopolysaccharide-induced renal inflammation (2011) Biological and Pharmaceutical Bulletin, 34 (2), pp. 226-23

Pharmacological investigations of Sapindus trifoliatus in various in vitro and in vivo models of inflammation

OBJECTIVE: To investigate the effect of lyophilized aqueous extract of pericarps of Sapindus trifoliatus (ST) in various in vitro and in vivo inflammatory models. METHODS: ST was studied for its in vitro inhibitory activity against 5-lipoxygenase (5-LO), cyclo-oxygenase (COX), leukotriene B4 (LTB4) and nitric oxide synthase (NOS). At doses 20 and 100 mg/kg, i.p. ST was evaluated in acute pedal inflammation induced by carrageenan, histamine, serotonin and zymosan in rats and mice. Further, the effect of topical application of the extract (1 mg and 5 mg) on ear inflammation induced by various inflammatory agents like -O-tetradecanoyl-phorbol 13-acetate (TPA) or capsaicin or arachidonic oxazolone or dinitrofluorobenzene (DNFB) was also investigated. RESULTS: In vitro evaluation of the extract revealed its inhibitory activity against the major inflammatory mediators 5-LO, COX, LTB4 and NOS. The extract significantly inhibited the pedal inflammation produced by carrageenan, histamine, serotonin and zymosan. Further, topical application of ST significantly inhibited the ear inflammation induced by acute and multiple applications of TPA and acute application of capsaicin or arachidonic acid. However, the extract failed to inhibit ear inflammation induced by oxazolone or DNFB. CONCLUSION: ST has antiinflammatory activity possibly mediated through 5-LO and COX pathways

Anti-inflammatory Benefits Of Pentacyclic Triterpenes

[No abstract available]413419Abe, F., Yamauchi, T., Nagao, T., Ursolic acid as a trypanocidal constituent in rosemary (2002) Biological and Pharmaceutical Bulletin, 25, pp. 1485-1487Allouche, Y., Jimenez, A., Uceda, M., Aguilera, M.P., Gaforio, J.J., Beltran, G., Triterpenic content and chemometric analysis of virgin olive oils from forty olive cultivars (2009) Journal of Agricultural and Food Chemistry, 57, pp. 3604-3610Allouche, Y., Warleta, F., Campos, M., Antioxidant, antiproliferative, and pro-apoptotic capacities of pentacyclic triterpenes found in the skin of olives on MCF-7 human breast cancer cells and their effects on DNA damage (2011) Journal of Agricultural and Food Chemistry, 59 (1), pp. 121-130Chaturvedi, P.K., Bhui, K., Shukla, Y., Lupeol: connotations for chemoprevention (2008) Cancer Letters, 263, pp. 1-13De Clercq, E., Novel compounds in preclinical/early clinical development for the treatment of HIV infections (2000) Reviews in Medical Virology, 10, pp. 255-277. , Erratum in: 2000. Reviews in Medical Virology 10, 349Fernandez, M.A., de las Heras, B., Garcia, M.D., Saenz, M.T., Villar, A., New insights into the mechanism of action of the anti-inflammatory triterpene lupeol (2001) Journal of Pharmacy and Pharmacology, 53, pp. 1533-1539Fulda, S., Betulinic acid for cancer treatment and prevention (2008) International Journal of Molecular Sciences, 9, pp. 1096-1107Fulda, S., Susin, S.A., Kroemer, G., Debatin, K.M., Molecular ordering of apoptosis induced by anticancer drugs in neuroblastoma cells (1999) Cancer Research, 58, pp. 4453-4460Geetha, T., Varalaxmi, P., Anti-inflammatory activity of lupeol and lupeol linoleate in adjuvant-induced arthritis (1998) Fitoterapia, 69, pp. 13-19Giday, M., Asfaw, Z., Elmqvist, T., Woldu, Z., An ethnobotanical study of medicinal plants used by the Zay People in Ethiopia (2003) Journal of Ethnopharmacology, 85, pp. 43-52Guo, M., Zhang, S., Song, F., Wang, D., Liu, Z., Liu, S., Studies on the non-covalent complexes between oleanolic acid and cyclodextrins using electrospray ionization tandem mass spectrometry (2003) Journal of Mass Spectrometry, 38, pp. 723-731Hill, A.F., (1989) Economic Botany: A Text Book of Useful Plants and Plant Products, , McGraw Hill Book Company, Inc., New York, p. 560Ikeda, Y., Murakami, A., Ohigashi, H., Ursolic acid: an anti- and pro-inflammatory triterpenoid (2008) Molecular Nutrition & Food Research, 52 (1), pp. 26-42Kang, S.Y., Yoon, S.Y., Roh, D.H., The anti-arthritic effect of ursolic acid on zymosan-induced acute inflammation and adjuvant-induced chronic arthritis models (2008) Journal of Pharmacy and Pharmacology, 60 (10), pp. 1347-1354Kweifio-Okai, G., de Munk, F., Macrides, T.A., Smith, P., Rumble, B.A., Anti-arthritic mechanisms of lupeol triterpenes (1995) Drug Develop Research, 36, pp. 20-24Levine, J.D., Reichling, D.B., Peripheral mechanisms of inflammatory pain (1999) Textbook of Pain, pp. 59-84. , Churchill Livingstone, London, P.D. Wall, R. Melzack (Eds.)Liu, J., Oleanolic acid and ursolic acid: research perspectives (2005) Journal of Ethnopharmacology, 100, pp. 92-94Manez, S., Recio, M.C., Giner, R.M., Rios, J.L., Effect of selected triterpenoids on chronic dermal inflammation (1997) European Journal of Pharmacology, 334, pp. 103-105Pisha, E., Chai, H., Lee, I.S., Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis (1995) Nature Medicine, 1, pp. 1046-1051Recio, M.C., Giner, R.M., Manez, S., Rios, J.L., Structural requirements for the anti-inflammatory activity of natural triterpenoids (1995) Planta Medica, 61, pp. 182-185Ringbom, T., Huss, U., Stenholm, A., COX-2 inhibitory effects of naturally occurring and modified fatty acids (2001) Journal of Natural Products, 64, pp. 745-749Ringbom, T., Segura, L., Noreen, Y., Perera, P., Bohlin, L., Ursolic acid from Plantago major, a selective inhibitor of cyclooxygenase-2 catalyzed prostaglandin biosynthesis (1998) Journal of Natural Products, 61, pp. 1212-1215Safayhi, H., Sailer, E.R., Anti-inflammatory actions of pentacyclic triterpenes (1997) Planta Medica, 63, pp. 487-493Saleem, M., Lupeol, a novel anti-inflammatory and anti-cancer dietary triterpene (2009) Cancer Letters, 285 (2), pp. 109-115Samy, R.P., Gopalakrishnakone, P., Therapeutic potential of plants as anti-microbials for drug discovery (2008) Evidence-Based Complementary and Alternative Medicine, 5, pp. 1-12Son, L.B., Kaplun, A.P., Symon, A.V., Shpilevsky, A.A., Grigoriev, V.B., Shvets VI Liposomal form of betulinic acid, a selective apoptosis inducing in melanoma cells substance (1998) Journal of Liposome Research, 8, p. 78Subbaramaiah, K., Michaluart, P., Sporn, M.B., Dannenberg, A.J., Ursolic acid inhibits cyclooxygenase-2 transcription in human mammary epithelial cells (2000) Cancer Research, 60, pp. 2399-2404Subhadhirasakul, S., Takayama, H., Kitajima, F.M., Aimi, N.F., Triterpenoids from Thai medicinal plant, Willughbeia firma (2000) Natural Medicines, 54, pp. 155-157Suh, N., Honda, T., Finlay, H.J., Novel triterpenoids suppress inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2) in mouse macrophages (1998) Cancer Research, 58, pp. 717-723Tan, Y., Yu, R., Pezzuto, J.M., Betulinic acid-induced programmed cell death in human melanoma cells involves mitogen-activated protein kinase activation (2003) Clinical Cancer Research, 9 (7), pp. 2866-2875Wondimu, T., Asfaw, Z., Kelbessa, E., Ethnobotanical study of medicinal plants around 'Dheera' town, Arsi zone, Ethiopia (2007) Journal of Ethnopharmacology, 112, pp. 152-161Zuco, V., Supino, R., Righetti, S.C., Selective cytotoxicity of betulinic acid on tumor cell lines, but not on normal cells (2002) Cancer Letters, 175, pp. 17-2

Monoamine oxidase-A is an important source of oxidative stress and promotes cardiac dysfunction, apoptosis, and fibrosis in diabetic cardiomyopathy

AbstractOxidative stress is closely associated with the pathophysiology of diabetic cardiomyopathy (DCM). The mitochondrial flavoenzyme monoamine oxidase A (MAO-A) is an important source of oxidative stress in the myocardium. We sought to determine whether MAO-A plays a major role in modulating DCM. Diabetes was induced in Wistar rats by single intraperitoneal injection of streptozotocin (STZ). To investigate the role of MAO-A in the development of pathophysiological features of DCM, hyperglycemic and age-matched control rats were treated with or without the MAO-A-specific inhibitor clorgyline (CLG) at 1mg/kg/day for 8 weeks. Diabetes upregulated MAO-A activity; elevated markers of oxidative stress such as cardiac lipid peroxidation, superoxide dismutase activity, and UCP3 protein expression; enhanced apoptotic cell death; and increased fibrosis. All these parameters were significantly attenuated by CLG treatment. In addition, treatment with CLG substantially prevented diabetes-induced cardiac contractile dysfunction as evidenced by decreased QRS, QT, and corrected QT intervals, measured by ECG, and LV systolic and LV end-diastolic pressure measured by microtip pressure transducer. These beneficial effects of CLG were seen despite the persistent hyperglycemic and hyperlipidemic environments in STZ-induced experimental diabetes. In summary, this study provides strong evidence that MAO-A is an important source of oxidative stress in the heart and that MAO-A-derived reactive oxygen species contribute to DCM