PMID- 37579922
OWN - NLM
STAT- MEDLINE
DCOM- 20230918
LR  - 20230918
IS  - 1872-7573 (Electronic)
IS  - 0378-8741 (Linking)
VI  - 318
IP  - Pt B
DP  - 2024 Jan 10
TI  - Rehmannia glutinosa Libosch and Cornus officinalis Sieb herb couple ameliorates 
      renal interstitial fibrosis in CKD rats by inhibiting the TGF-beta1/MAPK signaling 
      pathway.
PG  - 117039
LID - S0378-8741(23)00907-8 [pii]
LID - 10.1016/j.jep.2023.117039 [doi]
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Herb couple Rehmannia glutinosa Libosch and 
      Cornus officinalis Sieb (RC), originated from "Liuwei Dihuang Pill" which 
      recorded in Key to Therapeutics of Children's Diseases. Traditionally, they have 
      been used widely for their ability to nourish yin and energize the kidneys. Our 
      previous study indicated that the RC could protect against adenine induced 
      Chronic kidney disease (CKD) rats. Nevertheless, there is still no clear 
      explanation of the mechanisms by which RC affects renal interstitial fibrosis in 
      CKD rats. AIM OF THE STUDY: Current Work aims to explore the amelioration and 
      potential mechanism of RC on renal interstitial fibrosis in CKD rats. MATERIALS 
      AND METHODS: CKD rats were induced by adenine. Two weeks after administration, 
      blood, urine, and kidney tissue were collected for biochemical analysis. 
      Observing the physiological state of rats through the changes of rat body weight 
      and renal index. The pro-inflammatory cytokines were measured by enzyme linked 
      immunosorbent assay (ELISA), while renal tissue damage and fibrosis were assessed 
      with Hematoxylin-eosin staining (H&E) and Masson's trichrome staining. In order 
      to determine the levels of indicators and proteins associated with fibrosis 
      signaling pathways, real time PCR (Rt-PCR), Western blot (WB), and 
      immunofluorescence were employed. RESULTS: The renal interstitial fibrosis led to 
      impaired cellular functions with increased the levels of Blood Urea Nitrogen 
      (BUN), Urine protein (UP), Interleukin-1beta (IL-1beta), Interleukin-6 (IL-6), and 
      Tumor Necrosis Factor alpha (TNF-alpha). and simultaneous up-regulated 
      collagenⅠ(COL-1), fibronection (FN), alpha-smooth muscle actin (a-SMA), transforming 
      growth factor-beta1 (TGF-beta1), c-Jun N-terminal kinase (JNK), p38 and extracellular 
      regulated protein kinases (ERK), down-regulated the expression of the E-cadherin 
      proteins. RC notably improved renal dysfunction in CKD rats as indicated by 
      decreases in BUN, UP, and renal index. In addition, consistent with the 
      morphological changes of renal tissue, renal interstitial fibrosis in CKD rats 
      after RC intervention was significantly improved, mainly manifested by a decrease 
      in the positive expression of COL-1, FN, and a-SMA, and increased levels of 
      E-cadherin protein. Meanwhile, RC reduced the classical pro-inflammatory 
      cytokines IL-1beta, IL-6, and TNF-alpha in adenine-induced CKD rats. Additionally, RC 
      administration also down-regulated TGF-beta1, JNK, p38 and ERK. CONCLUSION: In 
      conclusion, RC may reduce inflammation in adenine induced CKD rats, improve 
      extracellular matrix (ECM) components deposition, and diminish 
      epithelial-mesenchymal transition (EMT) marker protein levels. Furthermore, RC 
      intervention significantly reduces the release of inflammatory cytokines and 
      inhibits the TGF-beta1/MAPK signaling pathway. Based on the results, RC might be 
      useful in the treatment of adenine induced renal fibrosis.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Zhu, Jin-Hui
AU  - Zhu JH
AD  - School of Public Health, Nantong University, 19 Qixiu Road, Nantong, China; 
      School of Pharmacy, Nantong University, 9 Seyuan Road, Nantong, China.
FAU - Wang, Ling
AU  - Wang L
AD  - School of Pharmacy, Nantong University, 9 Seyuan Road, Nantong, China.
FAU - Ma, Zhen-Xiang
AU  - Ma ZX
AD  - School of Public Health, Nantong University, 19 Qixiu Road, Nantong, China.
FAU - Duan, Jin-Ao
AU  - Duan JA
AD  - Collaborative Innovation Center of Chinese Medicine Resources, Nanjing University 
      of Chinese Medicine, 138 Xianlin Road, Nanjing, China.
FAU - Tao, Jin-Hua
AU  - Tao JH
AD  - School of Public Health, Nantong University, 19 Qixiu Road, Nantong, China; 
      School of Pharmacy, Nantong University, 9 Seyuan Road, Nantong, China. Electronic 
      address: taojinhua2000@ntu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230812
PL  - Ireland
TA  - J Ethnopharmacol
JT  - Journal of ethnopharmacology
JID - 7903310
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Cytokines)
RN  - 0 (Cadherins)
SB  - IM
MH  - Rats
MH  - Animals
MH  - Transforming Growth Factor beta1/metabolism
MH  - *Cornus
MH  - *Rehmannia
MH  - Interleukin-6/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Kidney/pathology
MH  - Signal Transduction
MH  - *Renal Insufficiency, Chronic/metabolism
MH  - Cytokines/metabolism
MH  - Fibrosis
MH  - Cadherins/metabolism
OTO - NOTNLM
OT  - CKD
OT  - Cornus officinalis Sieb
OT  - EMT
OT  - Rehmannia glutinosa Libosch
OT  - Renal interstitial fibrosis
OT  - TGF-beta1/MAPK
COIS- Declaration of competing interest We declare that the results presented in this 
      paper have not been published previously, either in whole or part. The authors 
      have declared that no competing interest exists.
EDAT- 2023/08/15 00:42
MHDA- 2023/09/18 12:44
CRDT- 2023/08/14 19:23
PHST- 2023/06/04 00:00 [received]
PHST- 2023/07/09 00:00 [revised]
PHST- 2023/08/11 00:00 [accepted]
PHST- 2023/09/18 12:44 [medline]
PHST- 2023/08/15 00:42 [pubmed]
PHST- 2023/08/14 19:23 [entrez]
AID - S0378-8741(23)00907-8 [pii]
AID - 10.1016/j.jep.2023.117039 [doi]
PST - ppublish
SO  - J Ethnopharmacol. 2024 Jan 10;318(Pt B):117039. doi: 10.1016/j.jep.2023.117039. 
      Epub 2023 Aug 12.