PMID- 38044666
OWN - NLM
STAT- MEDLINE
DCOM- 20231205
LR  - 20240121
IS  - 1521-0499 (Electronic)
IS  - 0190-2148 (Linking)
VI  - 49
IP  - 1
DP  - 2023 Nov 20
TI  - Stevioside attenuates bleomycin-induced pulmonary fibrosis by activating the Nrf2 
      pathway and inhibiting the NF-kappaB and TGF-beta1/Smad2/3 pathways.
PG  - 205-219
LID - 10.1080/01902148.2023.2286465 [doi]
AB  - Objective: This study aimed to investigate the effects of stevioside (STE) on 
      pulmonary fibrosis (PF) and the potential mechanisms. Methods: In this study, a 
      mouse model of PF was established by a single intratracheal injection of 
      bleomycin (BLM, 3 mg/kg). The experiment consisted of four groups: control group, 
      BLM group, and STE treatment groups (STE 50 and 100 mg/kg). ELISA and biochemical 
      tests were conducted to determine the levels of TNF-alpha, IL-1beta, IL-6, NO, 
      hydroxyproline (HYP), SOD, GSH, and MDA. Histopathological changes and collagen 
      deposition in lung tissues were observed by HE and Masson staining. 
      Immunohistochemistry was performed to determine the levels of collagen I-, 
      collagen III-, TGF-beta1- and p-Smad2/3-positive cells. Western blot analysis was 
      used to measure the expression of epithelial-mesenchymal transition (EMT) 
      markers, including alpha-SMA, vimentin, E-cadherin, and ZO-1, as well as proteins 
      related to the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, 
      nuclear transcription factor-kappaB (NF-kappaB) pathway, and TGF-beta1/Smad2/3 pathway in 
      lung tissues. Results: STE significantly alleviated BLM-induced body weight loss 
      and lung injury in mice, decreased HYP levels, and reduced the levels of collagen 
      I- and collagen III-positive cells, thereby decreasing extracellular matrix (ECM) 
      deposition. Moreover, STE markedly improved oxidative stress (MDA levels were 
      decreased, while SOD and GSH activity were enhanced), the inflammatory response 
      (the levels of TNF-alpha, IL-1beta, IL-6, and NO were reduced), and EMT (the expression 
      of alpha-SMA and vimentin was downregulated, and the expression of E-cadherin and 
      ZO-1 was upregulated). Further mechanistic analysis revealed that STE could 
      activate the Nrf2 pathway and inhibit the NF-kappaB and TGF-beta1/Smad2/3 pathways. 
      Conclusion: STE may alleviate oxidative stress by activating the Nrf2 pathway, 
      suppress the inflammatory response by downregulating the NF-kappaB pathway, and 
      inhibit EMT progression by blocking the TGF-beta1/Smad2/3 pathway, thereby improving 
      BLM-induced PF.
FAU - Hao, Wei
AU  - Hao W
AD  - Department of Functional Experimental Training Center, Basic Medical College, 
      Wannan Medical College, Wuhu, China.
FAU - Yu, Ting-Ting
AU  - Yu TT
AD  - Department of Functional Experimental Training Center, Basic Medical College, 
      Wannan Medical College, Wuhu, China.
FAU - Zuo, Dong-Ze
AU  - Zuo DZ
AD  - Department of Pharmacy, Second People's Hospital of Hefei, Hefei, China.
FAU - Hu, Heng-Zhao
AU  - Hu HZ
AD  - School of Anesthesiology, Wannan Medical College, Wuhu, China.
FAU - Zhou, Ping-Ping
AU  - Zhou PP
AD  - Department of Physiology, Basic Medical College, Wannan Medical College, Wuhu, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231203
PL  - England
TA  - Exp Lung Res
JT  - Experimental lung research
JID - 8004944
RN  - 0 (NF-kappa B)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 11056-06-7 (Bleomycin)
RN  - 0YON5MXJ9P (stevioside)
RN  - 0 (Vimentin)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Interleukin-6)
RN  - 9007-34-5 (Collagen)
RN  - 0 (Collagen Type I)
RN  - 0 (Cadherins)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Pulmonary Fibrosis/chemically induced/drug therapy/metabolism
MH  - NF-kappa B
MH  - Transforming Growth Factor beta1/metabolism
MH  - Bleomycin/adverse effects
MH  - Vimentin
MH  - NF-E2-Related Factor 2
MH  - Tumor Necrosis Factor-alpha
MH  - Interleukin-6
MH  - Collagen/metabolism
MH  - Collagen Type I/metabolism
MH  - Cadherins
MH  - Superoxide Dismutase
OTO - NOTNLM
OT  - Stevioside
OT  - epithelial-mesenchymal transition
OT  - inflammatory response
OT  - oxidative stress
OT  - pulmonary fibrosis
EDAT- 2023/12/04 06:42
MHDA- 2023/12/05 12:43
CRDT- 2023/12/04 03:40
PHST- 2023/12/05 12:43 [medline]
PHST- 2023/12/04 06:42 [pubmed]
PHST- 2023/12/04 03:40 [entrez]
AID - 10.1080/01902148.2023.2286465 [doi]
PST - ppublish
SO  - Exp Lung Res. 2023 Nov 20;49(1):205-219. doi: 10.1080/01902148.2023.2286465. Epub 
      2023 Dec 3.