PMID- 36341817
OWN - NLM
STAT- MEDLINE
DCOM- 20221201
LR  - 20221201
IS  - 1872-7573 (Electronic)
IS  - 0378-8741 (Linking)
VI  - 302
IP  - Pt A
DP  - 2023 Feb 10
TI  - Anti-apoptotic effect of HeidihuangWan in renal tubular epithelial cells via 
      PI3K/Akt/mTOR signaling pathway.
PG  - 115882
LID - S0378-8741(22)00921-7 [pii]
LID - 10.1016/j.jep.2022.115882 [doi]
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Heidihuang Wan (HDHW) is a classic Chinese herbal 
      formula, which was first recorded in the "Suwen Bingji Qiyi Baoming Collection" 
      written by Liu Wansu during the Jin Dynasty (1115-1234 AD). It is commonly used 
      clinically for the treatment of kidney diseases and its curative effect is 
      stable. Previous animal experiments have confirmed that HDHW can effectively 
      improve renal fibrosis. However, the underlying pharmacological mechanism remains 
      unclear. AIMS OF THIS STUDY: Renal tubular epithelial cell (RTEC) apoptosis is 
      one of the main pathological features of renal fibrosis. This study aimed to 
      observe the effect and underlying mechanism of HDHW on the apoptosis of RTECs to 
      further explore the pathological mechanism of HDHW against renal fibrosis. 
      MATERIALS AND METHODS: We examined the HDHW composition in rat serum. In vitro, 
      we first screened out the optimal intervention concentration of HDHW on RTECs 
      using the MTT assay. Hypoxia/reoxygenation was then used to induce apoptosis of 
      RTECs (H/R-RTECs), which were divided into H/R-RTEC, astragaloside IV (positive 
      control), HDHW, and RTECs groups. After 48 h of drug intervention, apoptosis of 
      RTECs was detected using flow cytometry and protein expression was detected by 
      western blotting. The 5/6 nephrectomy rat model was constructed and divided into 
      the normal control, 5/6 nephrectomy, HDHW, and astragaloside IV groups. After 8 
      weeks of treatment, TUNEL staining was used to detect cell apoptosis, and western 
      blotting was used to detect protein expression. RESULTS: HDHW downregulated the 
      expression of pro-apoptotic proteins Bax and Caspase3, up-regulated the 
      expression of anti-apoptotic protein Bcl-2, activated the PI3K/Akt/mTOR signaling 
      pathway, and reversed the early apoptosis of RTECs, thereby resisting the 
      apoptosis of RTECs. CONCLUSION: HDHW inhibits apoptosis of RTECs by modulating 
      the PI3K/Akt/mTOR signaling pathway. This study provides experimental evidence 
      for the anti-fibrotic effect of HDHW on the kidneys and partially elucidates its 
      pharmacological mechanism of action.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Li, Ying-Ying
AU  - Li YY
AD  - College of First Clinical Medical, Shandong University of Traditional Chinese 
      Medicine, Jinan, China.
FAU - Tian, Zeng-Hui
AU  - Tian ZH
AD  - College of First Clinical Medical, Shandong University of Traditional Chinese 
      Medicine, Jinan, China.
FAU - Su, Shan-Shan
AU  - Su SS
AD  - Department of Nephrology, Affiliated Hospital of Shandong University of 
      Traditional Chinese Medicine, Jinan, China.
FAU - Shi, Jing-Jing
AU  - Shi JJ
AD  - College of First Clinical Medical, Shandong University of Traditional Chinese 
      Medicine, Jinan, China.
FAU - Zhou, Chao
AU  - Zhou C
AD  - Department of Oncology, Weifang Hospital of Traditional Chinese Medicine, 
      Weifang, China.
FAU - Zhang, Li-Hua
AU  - Zhang LH
AD  - Department of Geriatrics, Weifang Hospital of Traditional Chinese Medicine, 
      Weifang, China.
FAU - Zhang, Fa-Rong
AU  - Zhang FR
AD  - Department of Nephrology, Affiliated Hospital of Shandong University of 
      Traditional Chinese Medicine, Jinan, China. Electronic address: 
      71000162@sdutcm.edu.cn.
FAU - Hao, Yan-Ke
AU  - Hao YK
AD  - Department of Spine Orthopedics, Affiliated Hospital of Shandong University of 
      Traditional Chinese Medicine, Jinan, China. Electronic address: 
      71000331@sdutcm.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20221029
PL  - Ireland
TA  - J Ethnopharmacol
JT  - Journal of ethnopharmacology
JID - 7903310
RN  - 3A592W8XKE (astragaloside A)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - EC 2.7.1.1 (mTOR protein, rat)
SB  - IM
MH  - Rats
MH  - Animals
MH  - *Proto-Oncogene Proteins c-akt/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Apoptosis
MH  - Epithelial Cells
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - *Kidney Diseases/pathology
MH  - Fibrosis
OTO - NOTNLM
OT  - Apoptosis
OT  - HeidihuangWan
OT  - PI3K/Akt/mTOR signaling pathway
OT  - Renal tubular epithelial cells
COIS- Declaration of competing interest The authors declare no con fl icts of interest.
EDAT- 2022/11/08 06:00
MHDA- 2022/12/02 06:00
CRDT- 2022/11/07 06:17
PHST- 2022/09/04 00:00 [received]
PHST- 2022/10/23 00:00 [revised]
PHST- 2022/10/25 00:00 [accepted]
PHST- 2022/11/08 06:00 [pubmed]
PHST- 2022/12/02 06:00 [medline]
PHST- 2022/11/07 06:17 [entrez]
AID - S0378-8741(22)00921-7 [pii]
AID - 10.1016/j.jep.2022.115882 [doi]
PST - ppublish
SO  - J Ethnopharmacol. 2023 Feb 10;302(Pt A):115882. doi: 10.1016/j.jep.2022.115882. 
      Epub 2022 Oct 29.