title: Qian Yang Yu Yin Granule-containing serum inhibits angiotensin II-induced proliferation, reactive oxygen species production, and inflammation in human mesangial cells via an NADPH oxidase 4-dependent pathway.
abstract: BACKGROUND
  Qian Yang Yu Yin Granule (QYYYG), a traditional Chinese herbal medicine, has been indicated for renal damage in hypertension for decades in China, but little remains known regarding its underlying molecular mechanism. Therefore, we performed the current study in order to investigate the underlying molecular mechanism of QYYYG in the treatment of hypertensive renal damage.
  
  
  METHODS
  We hypothesize that QYYYG relieves hypertensive renal injury through an angiotensin II (Ang II)-nicotinamide adenine dinucleotide phosphate (NAPDH)-oxidase (NOX)-reactive oxygen species (ROS) pathway. In this study, we investigated the effects of QYYYG-containing serum (QYGS) in human mesangial cells (HMCs) against Ang II-induced cell proliferation, ROS production, and inflammation through the seropharmacological method.
  
  
  RESULTS
  We found that QYGS could inhibit cell proliferation in Ang II-treated HMCs. In addition, QYGS considerably suppressed production of ROS, decreased mRNA and protein expression of NAPDH-oxidase 4 (NOX4), p22 (phox) , and activated Ras-related C3 botulinum toxin substrate 1 (GTP-Rac1); as well as counteracted the up-regulation of inflammatory markers including tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB) p65, and interleukin 6 (IL-6). These effects were further confirmed in HMCs transfected with specific small interfering RNA (siRNA) targeting NOX4.
  
  
  CONCLUSIONS
  Taken together, these results suggest that a NOX4-dependent pathway plays an important role in regulating the inhibitory effect of QYGS. Our findings provide new insights into the molecular mechanisms of QYYYG and their role in the treatment of hypertensive nephropathy.
authors.affiliation: First College of Clinical Medicine, Nanjing University of Traditional Chinese Medicine, Nanjing, 210046, China. zh_cb2013@163.com.|Nanjing Hospital of Traditional Chinese Medicine, Nanjing, 210001, China. zh_cb2013@163.com.
authors.forename: Kang
authors.initials: K
authors.lastname: Ding
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, China. hy_nf2013@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Jiangsu Province Hospital of Traditional Chinese Medicine, No.155 Hanzhong Road, Nanjing, 210029, China. ct_dg2013@sohu.com.
authors.forename: Weimin
authors.initials: W
authors.lastname: Jiang
authors.affiliation: College of Pharmacy, Nanjing University of Traditional Chinese Medicine, Nanjing, 210029, China. fr_gh2013@sohu.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, China. yinhongping@cpu.edu.cn.
authors.forename: Hongping
authors.initials: H
authors.lastname: Yin
authors.affiliation: Jiangsu Province Hospital of Traditional Chinese Medicine, No.155 Hanzhong Road, Nanjing, 210029, China. zhuyuan_fang@163.com.
authors.forename: Zhuyuan
authors.initials: Z
authors.lastname: Fang
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002681:China; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006977:Hypertension, Renal / Q000188:drug therapy / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D008517:Phytotherapy; D028502:Polygonum; D034741:RNA, Small Interfering / Q000494:pharmacology; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D019255:NADPH Oxidases