PMID- 37189016
OWN - NLM
STAT- MEDLINE
DCOM- 20230907
LR  - 20230907
IS  - 1099-1573 (Electronic)
IS  - 0951-418X (Linking)
VI  - 37
IP  - 9
DP  - 2023 Sep
TI  - Astragaloside IV attenuates high glucose-induced NF-kappaB-mediated inflammation 
      through activation of PI3K/AKT-ERK-dependent Nrf2/ARE signaling pathway in 
      glomerular mesangial cells.
PG  - 4133-4148
LID - 10.1002/ptr.7875 [doi]
AB  - Inflammation is a key contributor to diabetic kidney disease pathogenesis, 
      including reactive oxidation stress (ROS)-mediated nuclear factor-kappaB (NF-kappaB) 
      signaling pathway. In this study, we examined the effect of Astragaloside IV 
      (AS-IV) on anti-inflammatory and anti-oxidative properties under high glucose 
      (HG) condition and the potential mechanism in glomerular mesangial cells (GMCs). 
      We showed that AS-IV concentration-dependently reduced GMCs proliferation, 
      restrained ROS release and hydrogen peroxide content, and suppressed 
      pro-inflammatory cytokines as well as pro-fibrotic factors expression, which were 
      associated with the inhibition of NF-kappaB and nuclear factor-erythroid 2-related 
      factor 2 (Nrf2) signaling activation. Accordingly, both NF-kappaB overexpression by 
      using RNA plasmid and Nrf2 gene silencing by using RNA interference weakened the 
      ability of AS-IV to ameliorate HG-induced oxidative stress, inflammation, and 
      cell proliferation. Furthermore, phosphatidylinositide 3-kinases 
      (PI3K)/serine/threonine protein kinase (Akt) and extracellular regulated protein 
      kinases (ERK) signaling pathway regulated the process of AS-IV-induced Nrf2 
      activation and antioxidant capacity, which evidenced by using PI3K inhibitor 
      LY294002 or ERK inhibitor PD98059 that largely abolished the AS-IV efficacy. 
      Taken together, these results indicated that AS-IV protected against HG-induced 
      GMCs damage by inhibiting ROS/NF-kB-induced increases of inflammatory cytokines, 
      fibrosis biomarkers, and cell proliferation via up-regulation of Nrf2-dependent 
      antioxidant enzyme expression, which were mediated by PI3K/Akt and ERK signaling 
      pathway activation.
CI  - (c) 2023 John Wiley & Sons Ltd.
FAU - Su, Xue
AU  - Su X
AD  - Department of Nephrology, Putuo Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, China.
FAU - Guo, Hengjiang
AU  - Guo H
AD  - Department of Anesthesiology, Shanghai Children's Hospital, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Zhou, Yuying
AU  - Zhou Y
AD  - Department of Nephrology, Putuo Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, China.
FAU - Cao, Aili
AU  - Cao A
AD  - Department of Nephrology, Shanghai Sixth People's Hospital Affiliated to Shanghai 
      Jiao Tong University School of Medicine, Shanghai, China.
FAU - Shen, Qian
AU  - Shen Q
AD  - Department of Nephrology, Putuo Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, China.
FAU - Zhu, Bingbing
AU  - Zhu B
AD  - Department of Nephrology, Putuo Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, China.
FAU - Yao, Xingmei
AU  - Yao X
AD  - Department of Nephrology, Putuo Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, China.
FAU - Wang, Yunman
AU  - Wang Y
AD  - Department of Nephrology, Putuo Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, China.
FAU - Wang, Hao
AU  - Wang H
AD  - Department of Nephrology, Putuo Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, China.
AD  - Shanghai Putuo Central School of Clinical Medicine, Anhui Medical University, 
      Hefei, China.
FAU - Wang, Li
AU  - Wang L
AUID- ORCID: 0000-0003-4337-3547
AD  - Department of Nephrology, Putuo Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, China.
AD  - Shanghai Putuo Central School of Clinical Medicine, Anhui Medical University, 
      Hefei, China.
AD  - Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese 
      Medicine, Shanghai, China.
LA  - eng
GR  - 2021tszk02/Clinical specialty of Shanghai Putuo District Health System/
GR  - 2020360A/Innovation Program of Talent Project of Putuo District/
GR  - 81903996/National Science Foundation of China/
GR  - ptkwws202001/Science and Technology Innovation Project of Putuo District Health 
      System/
GR  - 21PJ1412400/Shanghai Pujiang Program/
PT  - Journal Article
DEP - 20230515
PL  - England
TA  - Phytother Res
JT  - Phytotherapy research : PTR
JID - 8904486
RN  - 0 (NF-kappa B)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - 3A592W8XKE (astragaloside A)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Antioxidants)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - 0 (Cytokines)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Humans
MH  - *NF-kappa B/metabolism
MH  - *Proto-Oncogene Proteins c-akt/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - NF-E2-Related Factor 2/metabolism
MH  - Antioxidants/pharmacology
MH  - Mesangial Cells/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - Oxidative Stress
MH  - Cytokines/metabolism
MH  - Glucose/metabolism
MH  - Inflammation/metabolism
OTO - NOTNLM
OT  - Astragaloside IV
OT  - diabetic kidney disease
OT  - glomerular mesangial cells
OT  - inflammation
OT  - oxidative stress
EDAT- 2023/05/16 01:09
MHDA- 2023/09/07 06:43
CRDT- 2023/05/15 23:32
PHST- 2023/04/16 00:00 [revised]
PHST- 2022/11/28 00:00 [received]
PHST- 2023/05/07 00:00 [accepted]
PHST- 2023/09/07 06:43 [medline]
PHST- 2023/05/16 01:09 [pubmed]
PHST- 2023/05/15 23:32 [entrez]
AID - 10.1002/ptr.7875 [doi]
PST - ppublish
SO  - Phytother Res. 2023 Sep;37(9):4133-4148. doi: 10.1002/ptr.7875. Epub 2023 May 15.