PMID- 29207360
OWN - NLM
STAT- MEDLINE
DCOM- 20180820
LR  - 20231201
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 55
DP  - 2018 Feb
TI  - Oridonin protects against the inflammatory response in diabetic nephropathy by 
      inhibiting the TLR4/p38-MAPK and TLR4/NF-kappaB signaling pathways.
PG  - 9-19
LID - S1567-5769(17)30460-5 [pii]
LID - 10.1016/j.intimp.2017.11.040 [doi]
AB  - Inflammation plays a pivotal role in the development and progression of diabetic 
      nephropathy (DN). Oridonin (Ori), a component isolated from Rabdosia rubescens, 
      possesses remarkable anti-inflammatory, immunoregulatory and antitumor 
      properties. However, the renoprotective effects of Ori and the underlying 
      molecular mechanisms have not been explored in DN. In this study, we aimed to 
      investigate the protective effects and potential mechanisms responsible for the 
      anti-inflammatory effects of Ori in diabetes-induced renal injury in vivo and in 
      vitro. Our results showed that Ori significantly attenuated diabetes-induced 
      renal injury and markedly decreased urinary protein excretion levels, serum 
      creatinine concentrations and blood urea nitrogen concentrations in rats. Ori 
      also significantly alleviated infiltration of inflammatory cells (cluster of 
      differentiation (CD)68) in kidney tissues and reduced the levels of 
      pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), 
      interleukin-6 (IL-6), IL-1beta and monocyte chemotactic protein 1 (MCP-1), both in 
      vivo and in vitro. TLR4 is a principal mediator of innate immune and inflammatory 
      responses and participates in the development of DN. Our molecular studies 
      indicated that Ori administration significantly down-regulated TLR4 
      overexpression in DN. Additional studies were conducted to investigate the effect 
      of Ori on the p38-mitogen-activated protein kinase (p38-MAPK) and nuclear factor 
      (NF)-kappaB pathways. The results showed that Ori inhibited IkappaBalpha, p65, and p38 
      phosphorylation, as well as NF-kappaB DNA-binding activity. In conclusion, these 
      results demonstrated that Ori exerts protective effects in diabetes-induced renal 
      injury in vivo and in vitro. These effects may be ascribed to its 
      anti-inflammatory and modulatory effects on the TLR4/p38-MAPK and TLR4/NF-kappaB 
      signaling pathways.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Li, Jushuang
AU  - Li J
AD  - Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan 430071, 
      China.
FAU - Bao, Liping
AU  - Bao L
AD  - Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan 430071, 
      China.
FAU - Zha, Dongqing
AU  - Zha D
AD  - Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan 430071, 
      China.
FAU - Zhang, Lian
AU  - Zhang L
AD  - Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan 430071, 
      China.
FAU - Gao, Ping
AU  - Gao P
AD  - Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan 430071, 
      China.
FAU - Zhang, Juan
AU  - Zhang J
AD  - Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan 430071, 
      China.
FAU - Wu, Xiaoyan
AU  - Wu X
AD  - Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan 430071, 
      China. Electronic address: ZN000081@whu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20171205
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (Diterpenes, Kaurane)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 0 (Tlr4 protein, rat)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0APJ98UCLQ (oridonin)
RN  - AYI8EX34EU (Creatinine)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
EIN - Int Immunopharmacol. 2024 Jan 5;126:111252. PMID: 38040552
MH  - Animals
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Cells, Cultured
MH  - Creatinine/blood
MH  - Cytokines/metabolism
MH  - Diabetes Mellitus, Experimental/*drug therapy
MH  - Diabetic Nephropathies/*drug therapy
MH  - Disease Models, Animal
MH  - Diterpenes, Kaurane/*therapeutic use
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Isodon/immunology
MH  - Kidney/*drug effects/metabolism/pathology
MH  - Male
MH  - NF-kappa B/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
MH  - Toll-Like Receptor 4/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
OTO - NOTNLM
OT  - Diabetic nephropathy
OT  - Inflammatory response
OT  - NF-kappaB
OT  - Oridonin
OT  - TLR4
OT  - p38-MAPK
EDAT- 2017/12/06 06:00
MHDA- 2018/08/21 06:00
CRDT- 2017/12/06 06:00
PHST- 2017/09/24 00:00 [received]
PHST- 2017/11/22 00:00 [revised]
PHST- 2017/11/28 00:00 [accepted]
PHST- 2017/12/06 06:00 [pubmed]
PHST- 2018/08/21 06:00 [medline]
PHST- 2017/12/06 06:00 [entrez]
AID - S1567-5769(17)30460-5 [pii]
AID - 10.1016/j.intimp.2017.11.040 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2018 Feb;55:9-19. doi: 10.1016/j.intimp.2017.11.040. Epub 
      2017 Dec 5.