title: Huangkui capsule, an extract from Abelmoschus manihot (L.) medic, ameliorates adriamycin-induced renal inflammation and glomerular injury via inhibiting p38MAPK signaling pathway activity in rats.
abstract: BACKGROUND
  Abelmoschus manihot (L.) medic (AM) is a natural medicinal plant used for the treatment of inflammatory diseases in China. Huangkui capsule (HKC), an extract from AM, has been proved clinically effective in improving renal inflammation and glomerular injury in chronic kidney disease (CKD). However, the dose-effects and the mechanisms involved in vivo are still unclear.
  
  
  OBJECTIVE
  This study was performed to examine the dose-effects of HKC on renal inflammation and glomerular lesion in adriamycin-induced nephropathy (ADRN), then to clarify the mechanisms in vivo of HKC by investigating its actions on modulating the activation of p38 mitogen-activated protein kinase (p38MAPK) signaling pathway.
  
  
  METHODS
  The rats with chronic ADRN, created by the unilateral nephrectomy and twice adriamycin injections (ADR, 4 mg/kg and 2mg/kg) within 4 weeks, were divided into four groups, a Sham group, a Vehicle group, a high-dose HKC group, and a low-dose HKC group, and that, sacrificed at the end of the 4th week after the administration. The rat's general status, renal morphological appearance, proteinuria, blood biochemical parameters, glomerular morphological changes, podocyte shape, and macrophage (ED1(+) and ED3(+) cells) infiltration in glomeruli were examined, respectively. The protein expressions of inflammatory cytokines including tumor necrosis factor (TNF)-α and interleukin (IL)-2, as well as p38MAPK signaling molecules such as transforming growth factor (TGF)-β1, p38MAPK, and phosphorylated-p38MAPK (p-p38MAPK), were also evaluated individually.
  
  
  RESULTS
  HKC at high dose of 2g/kg/d not only significantly ameliorated the rat's general status, renal morphological appearance, proteinuria, albumin, and glomerulosclerosis, but also obviously reduced the infiltrated ED1(+) and ED3(+) macrophages in glomeruli and TNF-α protein expression in the kidney, in addition to these, evidently down-regulated TGF-β1 and p-p38MAPK protein expressions in ADRN rats, but had no influence on podocyte shape and renal function.
  
  
  CONCLUSIONS
  HKC could dose-dependently ameliorate renal inflammation and glomerular injury in ADRN rats, by way of reducing the infiltration and the activation of macrophages in glomeruli, and TNF-α protein expression in the kidney, as well as inhibiting p38MAPK signaling pathway activity via the down-regulation of p-p38MAPK and TGF-β1 protein expressions in vivo.
authors.affiliation: Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Tu
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.forename: Yi-Gang
authors.initials: YG
authors.lastname: Wan
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Che
authors.forename: Hong-Ping
authors.initials: HP
authors.lastname: Pu
authors.forename: Xue-Jiao
authors.initials: XJ
authors.lastname: Yin
authors.forename: Hao-Li
authors.initials: HL
authors.lastname: Chen
authors.forename: Xian-Jie
authors.initials: XJ
authors.lastname: Meng
authors.forename: Yan-Ru
authors.initials: YR
authors.lastname: Huang
authors.forename: Xi-Miao
authors.initials: XM
authors.lastname: Shi
mesh_terms: D028483:Abelmoschus; D000818:Animals; D002214:Capsules; D004317:Doxorubicin; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D007376:Interleukin-2 / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002214:Capsules; D004365:Drugs, Chinese Herbal; D007376:Interleukin-2; D047428:Protein Kinase Inhibitors; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D004317:Doxorubicin; D048051:p38 Mitogen-Activated Protein Kinases