title: Tongxinluo Protects against Hypertensive Kidney Injury in Spontaneously-Hypertensive Rats by Inhibiting Oxidative Stress and Activating Forkhead Box O1 Signaling.
abstract: Hypertension is an independent risk factor for the progression of chronic renal failure, and oxidative stress plays a critical role in hypertensive renal damage. Forkbox O1(FoxO1) signaling protects cells against oxidative stress and may be a useful target for treating oxidative stress-induced hypertension. Tongxinluo is a traditional Chinese medicine with cardioprotective and renoprotective functions. Therefore, this study aimed to determine the effects of Tongxinluo in hypertensive renal damage in spontaneously hypertensive rats(SHRs)and elucidate the possible involvement of oxidative stress and FoxO1 signaling in its molecular mechanisms. SHRs treated with Tongxinluo for 12 weeks showed a reduction in systolic blood pressure. In addition to increasing creatinine clearance, Tongxinluo decreased urinary albumin excretion, oxidative stress injury markers including malondialdehyde and protein carbonyls, and expression of nicotinamide adenine dinucleotide phosphate oxidase subunits and its activity in SHR kidneys. While decreasing phosphorylation of FoxO1, Tongxinluo also inhibited the phosphorylation of extracellular signal-regulated kinase1/2 and p38 and enhanced manganese superoxide dismutase and catalase activities in SHR kidneys. Furthermore, histology revealed attenuation of glomerulosclerosis and renal podocyte injury, while Tongxinluo decreased the expression of α-smooth muscle actin, extracellular matrixprotein, transforming growth factor β1 and small mothers against decapentaplegic homolog 3,and improved tubulointerstitial fibrosis in SHR kidneys. Finally, Tongxinluo inhibited inflammatory cell infiltration as well as expression of tumor necrosis factor-α and interleukin-6. In conclusion, Tongxinluo protected SHRs against hypertension-induced renal injury by exerting antioxidant, antifibrotic, and anti-inflammatory activities. Moreover, the underlying mechanisms of these effects may involve inhibition of oxidative stress and functional activation of FoxO1 signaling.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, Shandong, China.|Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Luo
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Kong
authors.affiliation: Department of Magnetic Resonance Imaging, Jinan hospital of infectious diseases, Jinan, Shandong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Xiao-Qiong
authors.initials: XQ
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Rui-Xue
authors.initials: RX
authors.lastname: Yang
authors.affiliation: Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Yu-Xia
authors.initials: YX
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D002374:Catalase / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006977:Hypertension, Renal / Q000188:drug therapy*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D011507:Proteinuria / Q000188:drug therapy; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000071161:Forkhead Box Protein O1
chemical_list: D000975:Antioxidants; D002374:Catalase; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D051858:Forkhead Transcription Factors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D009419:Nerve Tissue Proteins; D013482:Superoxide Dismutase; D048051:p38 Mitogen-Activated Protein Kinases; C513941:tongxinluo; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1