PMID- 37017270
OWN - NLM
STAT- MEDLINE
DCOM- 20230406
LR  - 20230411
IS  - 1525-6049 (Electronic)
IS  - 0886-022X (Print)
IS  - 0886-022X (Linking)
VI  - 45
IP  - 1
DP  - 2023 Dec
TI  - Ginsenoside Rg1 treatment alleviates renal fibrosis by inhibiting the NOX4-MAPK 
      pathway in T2DM mice.
PG  - 2197075
LID - 10.1080/0886022X.2023.2197075 [doi]
LID - 2197075
AB  - Diabetic kidney disease (DKD) is a severe complication of type 2 diabetes 
      mellitus (T2DM). However, the pathogenesis of DKD remains unclear, and effective 
      treatment strategies are still lacking. Ginsenoside Rg1 (Rg1) has been reported 
      to improve DKD, but the mechanism is unclear. NADPH oxidase 4 (NOX4) is an 
      essential reactive oxygen species (ROS) source in the kidney. The 
      mitogen-activated protein kinase (MAPK) signaling may exacerbate renal fibrosis. 
      Therefore, we hypothesized that Rg1 might alleviate renal injury and fibrosis by 
      inhibiting NOX4 and MAPK signaling in T2DM-induced DKD. We found that Rg1 
      significantly improves lipid deposition, fibrosis, and ROS production and reduces 
      NOX4, p22phox, p47phox, p-ERK, p-JNK, and p-P38 MAPK expressions in the T2DM mice 
      kidneys. We also found that the high-fat diet treatment in mice and the palmitate 
      (PA) and PA + HG (high glucose) exposure in human mesangial cells could 
      significantly induce lipid deposition, ROS production, fibrosis, and the 
      activation of NOX4-MAPK signaling. The results suggest that high lipid and 
      glucose may play a significant role in DKD progression, while Rg1 may attenuate 
      renal fibrosis by inhibiting NOX4-MAPK signaling.
FAU - Ji, Pengmin
AU  - Ji P
AD  - Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of 
      Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical 
      University, Hefei, China.
FAU - Shi, Qifeng
AU  - Shi Q
AD  - Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of 
      Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical 
      University, Hefei, China.
FAU - Liu, Yan
AU  - Liu Y
AD  - Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of 
      Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical 
      University, Hefei, China.
FAU - Han, Min
AU  - Han M
AD  - Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of 
      Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical 
      University, Hefei, China.
FAU - Su, Yong
AU  - Su Y
AD  - Department of Pharmacy, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
FAU - Sun, Ran
AU  - Sun R
AD  - Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of 
      Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical 
      University, Hefei, China.
FAU - Zhou, Huimin
AU  - Zhou H
AD  - Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of 
      Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical 
      University, Hefei, China.
FAU - Li, Weizu
AU  - Li W
AD  - Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of 
      Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical 
      University, Hefei, China.
FAU - Li, Weiping
AU  - Li W
AD  - Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of 
      Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical 
      University, Hefei, China.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Ren Fail
JT  - Renal failure
JID - 8701128
RN  - EC 1.6.3.- (NADPH Oxidase 4)
RN  - 0 (Reactive Oxygen Species)
RN  - PJ788634QY (ginsenoside Rg1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
RN  - 0 (Lipids)
RN  - EC 1.6.3.- (NOX4 protein, human)
RN  - EC 1.6.3.- (Nox4 protein, mouse)
SB  - IM
MH  - Mice
MH  - Humans
MH  - Animals
MH  - NADPH Oxidase 4/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - *Mitogen-Activated Protein Kinases
MH  - *Diabetes Mellitus, Type 2/complications/drug therapy
MH  - Fibrosis
MH  - Glucose/pharmacology
MH  - Lipids
PMC - PMC10078147
OTO - NOTNLM
OT  - MAPK
OT  - NOX4
OT  - Type 2 diabetes mellitus
OT  - diabetic kidney disease
OT  - ginsenoside Rg1
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2023/04/06 06:00
MHDA- 2023/04/06 06:41
PMCR- 2023/04/05
CRDT- 2023/04/05 07:23
PHST- 2023/04/06 06:41 [medline]
PHST- 2023/04/05 07:23 [entrez]
PHST- 2023/04/06 06:00 [pubmed]
PHST- 2023/04/05 00:00 [pmc-release]
AID - 2197075 [pii]
AID - 10.1080/0886022X.2023.2197075 [doi]
PST - ppublish
SO  - Ren Fail. 2023 Dec;45(1):2197075. doi: 10.1080/0886022X.2023.2197075.