Change of pathways in organ damage

• Project/Area Number: 26460239
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Nigata University of Phermacy and Applied Life Sciences
• Principal Investigator: WATANABE KENICHI 新潟薬科大学, 薬学部, 教授 (70175090)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 医療薬剤学 / 標識脂肪酸 / 糖尿病 / 潰瘍性大腸炎 / アトピー皮膚炎 / 酸化ストレス / 心不全 / モデル動物 / 臓器障害 / アポト－シス

Outline of Final Research Achievements

Oxidative stress is important in many diseases. A majority of hospitalizations for complications of diabetes are linked to nephrotic diseases (Diabetic Nephropathy) and cardiovascular diseases (Diabetic Cardiomyopathy, Myocardial Infarction etc.). We determined cardiac function, left ventricular remodeling, and cardiac sympathetic nerve function with iodine-125;labeled metaiodobenzylguanidine. Long-chain fatty acids are major cardiac energy substrates, and decreased myocardial fatty acid metabolism using I-labeled 9- pentadecanoic acid has been demonstrated in diabetic cardiomyopathy and failing heart. Long-term drug treatment not only prevented left ventricular remodeling and improved cardiac function in rat with diabetic and dilated cardiomyopathy, but also restored cardiac sympathetic tone to hold norepinephrine in the heart. It is important that protective food function as underpinning strategy for disease prevention.

Research Products

• [Journal Article] Comparative effects of torasemide and furosemide on gap junction proteins and cardiac fibrosis in a rat model of dilated cardiomyopathy. (2017)
  • Author(s): Watanabe K, Sreedhar R, Thandavarayan RA, Karuppagounder V, Giridharan VV, Antony S, Harima M, Nakamura M, Suzuki K, Suzuki H, Sone H, Arumugam S.
  • Journal Title: Biofactors. Volume: 43 Issue: 2 Pages: 187-194
  • DOI: 10.1002/biof.1332
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The senescence accelerated mouse prone 8 (SAMP8): A novel murine model for cardiac aging (2017)
  • Author(s): Karuppagounder V, Arumugam S, Babu SS, Palaniyandi SS, Watanabe K, Cooke JP, Thandavarayan RA.
  • Journal Title: Ageing Res Rev. Volume: 35 Pages: 291-296
  • DOI: 10.1016/j.arr.2016.10.006
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Curcumin ameliorates liver damage and progression of NASH in NASH-HCC mouse model possibly by modulating HMGB1-NF-κB translocation. (2017)
  • Author(s): Afrin R, Arumugam S, Rahman A, Wahed MI, Karuppagounder V, Harima M, Suzuki H, Miyashita S, Suzuki K, Yoneyama H, Ueno K, Watanabe K.
  • Journal Title: Int Immunopharmacol Volume: 44 Pages: 174-182
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Le Carbone, a charcoal supplement, modulates DSS-induced acute colitis in mice through activation of AMPKα and downregulation of STAT3 and caspase 3 dependent apoptotic pathways. (2017)
  • Author(s): Afrin MR, Arumugam S, Rahman MA, Karuppagounder V, Sreedhar R, Harima M, Suzuki H, Nakamura T, Miyashita S, Suzuki K, Ueno K, Watanabe K.
  • Journal Title: Int Immunopharmacol. Volume: 43 Pages: 70-78
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Tiny molecule, big power: Multi-target approach for curcumin in diabetic cardiomyopathy. (2017)
  • Author(s): Karuppagounder V, Arumugam S, Giridharan VV, Sreedhar R, Bose RJ, Vanama J, Palaniyandi SS, Konishi T, Watanabe K,
  • Journal Title: Nutrition Volume: 34 Pages: 47-54
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Curcumin alleviates renal dysfunction and suppresses inflammation by shifting from M1 to M2 macrophage polarization in daunorubicin induced nephrotoxicity in rats. (2016)
  • Author(s): Karuppagounder V, Arumugam S, Thandavarayan RA, Sreedhar R, Giridharan VV, Afrin R, Harima M, Miyashita S, Hara M, Suzuki K, Nakamura M, Ueno K, Watanabe K.
  • Journal Title: Cytokine. Volume: 84 Pages: 1-9
  • DOI: 10.1016/j.cyto.2016.05.001
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Pivotal Role of Carbohydrate Sulfotransferase 15 in Fibrosis and Mucosal Healing in Mouse Colitis. (2016)
  • Author(s): Suzuki K, Arumugam S, Yokoyama J, Kawauchi Y, Honda Y, Sato H, Aoyagi Y, Terai S, Okazaki K, Suzuki Y, Mizumoto S, Sugahara K, Atreya R, Neurath MF, Watanabe K, Hashiguchi T, Yoneyama H, Asakura H.
  • Journal Title: PLoS One Volume: 13
  • NAID: 120005906913
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fasting time duration modulates the onset of insulin-induced hypoglycemic seizures in mice. (2016)
  • Author(s): Pitchaimani V, Arumugam S, Thandavarayan RA, Karuppagounder V, Afrin MR, Sreedhar R, Harima M, Suzuki H, Miyashita S, Nakamura T, Suzuki K, Nakamura M, Ueno K, Watanabe K.
  • Journal Title: Epilepsy Res Volume: 125 Pages: 47-51
  • DOI: 10.1016/j.eplepsyres.2016.06.009
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Targeting fatty acid metabolism in heart failure: is it a suitable therapeutic approach? (2016)
  • Author(s): Arumugam S, Sreedhar R, Thandavarayan RA, Karuppagounder V, Watanabe K.
  • Journal Title: Drug Discov Today Volume: 21 Issue: 6 Pages: 1003-1008
  • DOI: 10.1016/j.drudis.2016.02.010
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Curcumin as a therapeutic agent in the chemoprevention of inflammatory bowel disease. (2016)
  • Author(s): Sreedhar R, Arumugam S, Thandavarayan RA, Karuppagounder V, Watanabe K.
  • Journal Title: Drug Discov Today Volume: 21 Issue: 5 Pages: 843-849
  • DOI: 10.1016/j.drudis.2016.03.007
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Molecular targets of quercetin with anti-inflammatory properties in atopic dermatitis. (2016)
  • Author(s): Karuppagounder V, Arumugam S, Thandavarayan RA, Sreedhar R, Giridharan VV, Watanabe K.
  • Journal Title: Drug Discov Today Volume: 21 Issue: 4 Pages: 632-639
  • DOI: 10.1016/j.drudis.2016.02.011
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Modulation of Macrophage Polarization and HMGB1-TLR2/TLR4 Cascade Plays a Crucial Role for Cardiac Remodeling in Senescence-Accelerated Prone Mice. (2016)
  • Author(s): Karuppagounder V, Giridharan VV, Arumugam S, Sreedhar R, Palaniyandi SS, Krishnamurthy P, Quevedo J, Watanabe K, Konishi T, Thandavarayan RA.
  • Journal Title: PLoS One. Volume: 12
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Angiotensin receptor blockers: Focus on cardiac and renal injury. (2016)
  • Author(s): Arumugam S, Sreedhar R, Thandavarayan RA, Karuppagounder V, Krishnamurthy P, Suzuki K, Nakamura M, Watanabe K.
  • Journal Title: Trends Cardiovasc Med. Volume: 26 Issue: 3 Pages: 221-228
  • DOI: 10.1016/j.tcm.2015.06.004
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Role of MAPK-mediated endoplasmic reticulum stress signaling in the heart during aging in senescence-accelerated prone mice. (2016)
  • Author(s): Sreedhar R, Giridharan VV, Arumugam S, Karuppagounder V, Palaniyandi SS, Krishnamurthy P, Quevedo J, Watanabe K, Konishi T, Thandavarayan RA.
  • Journal Title: Biofactors. Volume: 42 Issue: 4 Pages: 368-375
  • DOI: 10.1002/biof.1280
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Naringenin ameliorates skin inflammation and accelerates phenotypic reprogramming from M1 to M2 macrophage polarization in atopic dermatitis NC/Nga mouse model. (2016)
  • Author(s): Karuppagounder V, Arumugam S, Thandavarayan RA, Sreedhar R, Giridharan VV, Pitchaimani V, Afrin R, Harima M, Krishnamurthy P, Suzuki K, Nakamura M, Ueno K, Watanabe K.
  • Journal Title: Exp Dermatol. Volume: 25 Issue: 5 Pages: 404-407
  • DOI: 10.1111/exd.12962
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Attenuation of Endoplasmic Reticulum Stress-Mediated Liver Damage by Mulberry Leaf Diet in Streptozotocin-Induced Diabetic Rats. (2016)
  • Author(s): .Afrin R, Arumugam S, Wahed MI, Pitchaimani V, Karuppagounder V, Sreedhar R, Harima M, Suzuki H, Miyashita S, Nakamura T, Suzuki K, Nakamura M, Ueno K, Watanabe K.
  • Journal Title: Am J Chin Med. Volume: 44 Issue: 01 Pages: 87-101
  • DOI: 10.1142/s0192415x16500063
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Depletion of cardiac 14-3-3η protein adversely influences pathologic cardiac remodeling during myocardial infarction after coronary artery ligation in mice. (2016)
  • Author(s): Sreedhar R, Arumugam S, Thandavarayan RA, Giridharan VV, Karuppagounder V, Pitchaimani V, Afrin R, Harima M, Nakamura M, Suzuki K, Gurusamy N, Krishnamurthy P, Watanabe K.
  • Journal Title: Int J Cardiol. Volume: 202 Pages: 146-153
  • DOI: 10.1016/j.ijcard.2015.08.142
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Jumihaidokuto effectively inhibits colon inflammation and apoptosis in mice with acute colitis. (2015)
  • Author(s): Remya S, Somasundaram A, Vengadeshprabhu K, Rajarajan A. T, Vijayasree V G, Vigneshwaran P, Mst. Rejina A, M Harima, T Nakamura, M Nakamura, K Suzuki, K Watanabe.
  • Journal Title: International Immunopharmacology. Volume: 29 Pages: 957-963
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Schisandrin B Ameliorates ICV-Infused Amyloid β Induced Oxidative stress and Neuronal Dysfunction through Inhibiting RAGE/NF-κB/MAPK and Up-regulating HSP/beclin Expression. (2015)
  • Author(s): Vijayasree V. Giridharan, Rajarajan A. Thandavarayan, Somasundaram Arumugam, Makoto Mizuno, Hiroyuki Nawa, Kenji Suzuki, Kam M. Ko, Prasanna Krishnamurthy, Kenichi Watanabe, T Konish.
  • Journal Title: Pros One Volume: 15 Issue: 11 Pages: 1-17
  • DOI: 10.1371/journal.pone.0142483
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Toki-shakuyaku-san, a Japanese kampo medicine, reduces colon inflammation in a mouse model of acute colitis. (2015)
  • Author(s): Remya S, , Watanabe KSomasundaram A, Vengadeshprabhu K, Rajarajan A. T, Vijayasree V G, Vigneshwaran P, Mst. Rejina A, M Harima, T Nakamura, K Ueno, M Nakamura, K Suzuki, K Watanabe.
  • Journal Title: International Immunopharmacology. Volume: 29 Pages: 869-875
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Tannic acid modulates NF<kappa>B signaling pathway and skin inflammation in NC/Nga transgenic mice through PPAR<gamma> expression. (2015)
  • Author(s): Vengadeshprabhu Karuppagounder; Somasundaram Arumugam; Rajarajan A Thandavarayan; Vigneshwaran Pitchaimani; Remya Sreedhar; Rejina Afrin; Meilei Harima; Hiroshi Suzuki; Mayumi Nomoto; Shizuka Miyashita; Kenji Suzuki; Masahiko Nakamura; Kazuyuki Ueno, Watanabe K.
  • Journal Title: Cytokine. Volume: 76 Pages: 206-213
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Effect of carvedilol against myocardial injury due to ischemia&#8211;reperfusion of the brain in rats. (2015)
  • Author(s): Harima M, Somasundaram A, Wen J, Vengadeshprabhu K, , Rajarajan A T, Vigneshwaran P, Remya S, Rejina A, Watanabe K.
  • Journal Title: Exp Molec Path Volume: 98 Pages: 558-562
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Telmisartan treatment targets inflammatory cytokines to suppress the pathogenesis of acute colitis induced by dextran sulphate sodium in mice. (2015)
  • Author(s): Somasundaram Arumugam; Remya Sreedhar; Rajarajan A Thandavarayan; Vijayasree V Giridharan; Vengadeshprabhu Karuppagounder; Vigneshwaran Pitchaimani; Mst Rejina Afrin; Shizuka Miyashita; Mayumi Nomoto; Meilei Harima; Hiroshi Suzuki; Takashi Nakamura; Masahiko Nakamura; Kenji Suzuki. Watanabe K.
  • Journal Title: Cytokine. Volume: 74 Pages: 305-312
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Schisandrin B prevents doxorubicin induced cardiac dysfunction by modulation of DNA damage, oxidative stress and inflammation through inhibition of MAPK/p53 signaling. (2015)
  • Author(s): Thandavarayan RA, Giridharan VV, Arumugam S, Suzuki K, Ko KM, Krishnamurthy P, Watanabe K, Konishi T.
  • Journal Title: PLoS One Volume: 2015 Issue: 3 Pages: 1-18
  • DOI: 10.1371/journal.pone.0119214
  • Peer Reviewed / Open Access
• [Journal Article] Myocardial 14-3-3η protein protects against mitochondria mediated apoptosis. (2015)
  • Author(s): Remya Sreedhar, Somasundaram Arumugam, Rajarajan A. Thandavarayan, Vijayasree V. Giridharan, Vengadeshprabhu Karuppagounder, Vigneshwaran Pitchaimani, Rejina Afrin, Shizuka Miyashita, Mayumi Nomoto, Meilei Harima, Narasimman Gurusamy, Kenji Suzuki, Kenichi Watanabe.
  • Journal Title: Cellular Signalling. Volume: 27 Pages: 770-776
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Myocardial 14-3-3η protein protects against mitochondria mediated apoptosis (2015)
  • Author(s): Remya Sreedhar, Somasundaram Arumugam, Rajarajan A. Thandavarayan, Vijayasree V. Giridharan, Vengadeshprabhu Karuppagounder, Vigneshwaran Pitchaimani, Rejina Afrin, Shizuka Miyashita, Mayumi Nomoto, Meilei Harima, Narasimman Gurusamy, Kenji Suzuki, Kenichi Watanabe.
  • Journal Title: Cellular Signalling. Volume: ２７ Pages: 770-776
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Prevention of DSS induced acute colitis by Petit Vert, a newly developed function improved vegetable, in mice (2014)
  • Author(s): Somasundaram A, Rajarajan A. T, Vigneshwaran P,Vengadeshprabhu K, Harima M, Nishizawa Y, Sasaki K, Suzuki K, Konishi T, Watanabe K.
  • Journal Title: Pharma Nutrition Volume: ２ Pages: 129-134
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Resveratrol attenuates HMGB1 signaling and inflammation in house dust mite-induced atopic dermatitis in mice. (2014)
  • Author(s): Vengadeshprabhu K, Somasundaram A, Rajarajan A T, Vigneshwaran P, Remya S, Rejina A, Harima M, Suzuki H, Nomoto M, Miyashita S, Suzuki K, Watanabe K.
  • Journal Title: Int Imunopharmacol Volume: ２３ Pages: 617-623
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comparative evaluation of torasemide and furosemide on rats with streptozotocin-induced diabetic nephropathy. (2014)
  • Author(s): Somasundaram A, Remya S, Vengadesh K, Rajarajan A. T, Vijayasree V, Vigneshwaran P, Rejina A, Harima M, Suzuki K, , K Watanabe.
  • Journal Title: Experimental and Molecular Pathology Volume: ９７ Pages: 137-143
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Fasting mediated increase in p-BADser155 and p-AKTser473 in the prefrontal cortex of mice. (2014)
  • Author(s): Vigneshwaran Pitchaimani, Somasundaram Arumugam, Rajarajan Amirthalingam, Thandavarayan, Vengadeshprabhu Karuppagounder, Remya Sreedhar, Rejina Afrin, Meilei Harima, Hiroshi Suzuki, Shizuka Miyashita, Mayumi Nomoto, Hirohito Sone, Kenji Suzuki, Kenichi Watanabe.
  • Journal Title: Neuroscience Letters. Volume: 579 Pages: 134-139
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Curcumin Effectively Inhibits CXCL10 Associated Pathogenesis in the Liver of NASH-HCC Mice Model (2016)
  • Author(s): Mst. Rejina Afrin, kenichi Watanabe
  • Organizer: the 25th Conference of the Asian Pacific Association for the Study of the Liver
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2016-02-20
  • Int'l Joint Research
• [Presentation] Naringenin ameliorates skin inflammation and promotes polarization towards M1 like macrophages in atopic dermatitis NC/Nga mouse model (2015)
  • Author(s): Vengadeshprabhu Karuppagounder, kenichi Watanabe
  • Organizer: the 5th Euro-India International Conference on Holistic Medicine (ICHM-2015),
  • Place of Presentation: Kerala, India
  • Year and Date: 2015-09-11
  • Int'l Joint Research
• [Presentation] Antioxidant therapy against dilated cardiomyopathy following experimental autoimmune myocarditis in rats (2015)
  • Author(s): Somasundaram Arumuga, kenichi Watanabe
  • Organizer: 1st Annual International Heart Failure Conference,
  • Place of Presentation: Abu Dhabi,
  • Year and Date: 2015-05-26
  • Int'l Joint Research
• [Presentation] Depletion of cardiac 14-3-3η protein adversely influences pathologic cardiac remodeling during myocardial infarction after coronary artery ligation in mice (2015)
  • Author(s): Remya Sreedha, kenichi Watanabe
  • Organizer: the 1st Annual International Heart Failure Conference,
  • Place of Presentation: Abu Dhabi
  • Year and Date: 2015-05-26
  • Int'l Joint Research
• [Presentation] Glucose transporter expression in cortex and hippocampus of fasting, moderate and severe hypoglycemia of mice. (2014)
  • Author(s): Vigneshwaran Pitchaimani, Somasundaran Arumugam, Rajarajan A Thandavarayan, Vengadeshprabhu Karuppa Gounder, Remya Sreeedhar, Meilei Harima, Hiroshi Suzuki, Shizuka Miyashita, Mayumi Nomoto, Kenji Suzuki, Kenichi Watanabe
  • Organizer: DIABETIC AND METABOLIC SYNDROME
  • Place of Presentation: Haryana, India
  • Year and Date: 2014-11-24 – 2014-11-29
• [Presentation] Dominant Negative 14-3-3 Protein Exacerbates Cardiac Dysfunction by Suppressing Cardiac Regeneration After Coronary Artery ligation in mice. (2014)
  • Author(s): Rajarajan Amirthalingam Thandavarayan , Somasundaram Arumugam, Vigneshwaran Pitchaimani, Vengadeshprabhu Karuppa Gounder, Vijayasree Vayalanellore, Remya Sreedhar, Meilei Harima, Darukeshwara Joladarashi, Kenji Suzuki, Kenichi Watanabe
  • Organizer: American heart Association
  • Place of Presentation: Chicago. USA
  • Year and Date: 2014-11-15 – 2014-11-19