PMID- 38456329
OWN - NLM
STAT- Publisher
LR  - 20240308
IS  - 1522-7278 (Electronic)
IS  - 1520-4081 (Linking)
DP  - 2024 Mar 8
TI  - Qi-dan-dihuang decoction ameliorates renal fibrosis in diabetic rats via 
      p38MAPK/AKT/mTOR signaling pathway.
LID - 10.1002/tox.24179 [doi]
AB  - CONTEXT: Qi-dan-dihuang decoction (QDD) has been used to treat diabetic kidney 
      disease (DKD), but the underlying mechanisms are poorly understood. OBJECTIVE: 
      This study reveals the mechanism by which QDD ameliorates DKD. MATERIALS AND 
      METHODS: The compounds in QDD were identified by high-performance liquid 
      chromatography and quadrupole-time-of-flight tandem mass spectrometry 
      (HPLC-Q-TOF-MS). Key targets and signaling pathways were screened through 
      bioinformatics. Nondiabetic Lepr db/m mice were used as control group, while Lepr 
      db/db mice were divided into model group, dapagliflozin group, 1% QDD-low 
      (QDD-L), and 2% QDD-high (QDD-H) group. After 12 weeks of administration, 24 h 
      urinary protein, serum creatinine, and blood urea nitrogen levels were detected. 
      Kidney tissues damage and fibrosis were evaluated by pathological staining. In 
      addition, 30 mmol/L glucose-treated HK-2 and NRK-52E cells to induce DKD model. 
      Cell activity and migration capacity as well as protein expression levels were 
      evaluated. RESULTS: A total of 46 key target genes were identified. Functional 
      enrichment analyses showed that key target genes were significantly enriched in 
      the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and 
      mitogen-activated protein kinase (MAPK) signaling pathways. In addition, in vivo 
      and in vitro experiments confirmed that QDD ameliorated renal fibrosis in 
      diabetic mice by resolving inflammation and inhibiting the epithelial-mesenchymal 
      transition (EMT) via the p38MAPK and AKT-mammalian target of rapamycin (mTOR) 
      pathways. DISCUSSION AND CONCLUSION: QDD inhibits EMT and the inflammatory 
      response through the p38MAPK and AKT/mTOR signaling pathways, thereby playing a 
      protective role in renal fibrosis in DKD.
CI  - (c) 2024 Wiley Periodicals LLC.
FAU - Kuang, Liuyan
AU  - Kuang L
AD  - Endocrinology Department, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong, China.
AD  - School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 
      China.
FAU - You, Yanting
AU  - You Y
AD  - Endocrinology Department, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong, China.
AD  - School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 
      China.
AD  - Taishan People's Hospital, Postdoctoral Innovation Practice Base of Southern 
      Medical University, Taishan, Guangdong, China.
FAU - Qi, Jieying
AU  - Qi J
AD  - School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 
      China.
FAU - Chen, Jieyu
AU  - Chen J
AD  - School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 
      China.
FAU - Zhou, Xinghong
AU  - Zhou X
AD  - School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 
      China.
FAU - Ji, Shuai
AU  - Ji S
AD  - School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 
      China.
FAU - Cheng, Jingru
AU  - Cheng J
AD  - Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Kwan, Hiu Yee
AU  - Kwan HY
AD  - School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
FAU - Jiang, Pingping
AU  - Jiang P
AD  - Department of Traditional Chinese Medicine, The First Affiliated Hospital of 
      Guangdong Pharmaceutical University, Guangzhou, China.
FAU - Sun, Xiaomin
AU  - Sun X
AD  - School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 
      China.
FAU - Su, Mengting
AU  - Su M
AD  - Cellular and Molecular Diagnostics Center, Sun Yat-sen Memorial Hospital, Sun 
      Yat-sen University, Guangzhou, China.
FAU - Wang, Ming
AU  - Wang M
AD  - Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical 
      University, Guangzhou, Guangdong, China.
FAU - Chen, Wenxiao
AU  - Chen W
AD  - Taishan People's Hospital, Postdoctoral Innovation Practice Base of Southern 
      Medical University, Taishan, Guangdong, China.
FAU - Luo, Ren
AU  - Luo R
AUID- ORCID: 0000-0003-2952-6543
AD  - School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 
      China.
FAU - Zhao, Xiaoshan
AU  - Zhao X
AD  - School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 
      China.
FAU - Zhou, Lin
AU  - Zhou L
AD  - Endocrinology Department, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong, China.
LA  - eng
GR  - 2018A0303130320/Natural Science Foundation of Guangdong Province, China/
GR  - 2018030310451/Natural Science Foundation of Guangdong Province, China/
GR  - ZYYCXTD-C-202001/Innovation Team and Talents Cultivation Program of National 
      Administration of Traditional Chinese Medicine/
GR  - 201903010069/Science and Technical Plan of Guangzhou, Guangdong, China/
GR  - 81830117/Key Project of National Natural Science Foundation of China/
GR  - 81774212/National Science Foundation of China/
PT  - Journal Article
DEP - 20240308
PL  - United States
TA  - Environ Toxicol
JT  - Environmental toxicology
JID - 100885357
SB  - IM
OTO - NOTNLM
OT  - Qi-dan-dihuang decoction
OT  - diabetic kidney disease
OT  - epithelial-mesenchymal transition
OT  - inflammatory response
OT  - network pharmacology
OT  - renal fibrosis
EDAT- 2024/03/08 06:43
MHDA- 2024/03/08 06:43
CRDT- 2024/03/08 05:30
PHST- 2023/12/25 00:00 [revised]
PHST- 2023/10/17 00:00 [received]
PHST- 2024/01/06 00:00 [accepted]
PHST- 2024/03/08 06:43 [medline]
PHST- 2024/03/08 06:43 [pubmed]
PHST- 2024/03/08 05:30 [entrez]
AID - 10.1002/tox.24179 [doi]
PST - aheadofprint
SO  - Environ Toxicol. 2024 Mar 8. doi: 10.1002/tox.24179.