PMID- 37837833
OWN - NLM
STAT- MEDLINE
DCOM- 20231201
LR  - 20231216
IS  - 1618-0372 (Electronic)
IS  - 0065-1281 (Linking)
VI  - 125
IP  - 8
DP  - 2023 Dec
TI  - Saikosaponin-d regulates angiogenesis in idiopathic pulmonary fibrosis through 
      angiopoietin/Tie-2 pathway.
PG  - 152100
LID - S0065-1281(23)00107-1 [pii]
LID - 10.1016/j.acthis.2023.152100 [doi]
AB  - OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is considered as a chronic 
      interstitial lung disease with underlying mechanism of IPF remaining unclear, 
      while there are no definitive treatment options. In recent years, scientists have 
      gradually paid attention to the influence of angiogenesis on IPF. Because IPF is 
      a progressive with microvascular remodeling disorder, scientists have postulated 
      that angiogenesis may also be one of the initiating and contributing factors of 
      the disease. Bupleurum is a common natural Chinese herbal medicine with 
      antibacterial, anti-inflammatory, anti-tumor and other pharmacological effects. 
      As the most important active monomer of Bupleurum, Saikosaponin-d (SSd) is a new 
      discovery with anti-pulmonary fibrosis (PF) activity. This study attempts to 
      investigate the role of SSd in the interference of PF through regulation of 
      angiogenesis in IPF through Angiopoietin (Angpt) /Tie receptor 2 (Tie2) pathway. 
      METHODS: Randomly, we allocated C57BL/6 mice into four groups (n = 20 in each 
      group). Afterwards, establishment of IPF model was accomplished via intratracheal 
      administration of bleomycin (BLM, 5 mg/kg), while corresponding drug intervention 
      was given accordingly. On 3rd, 7th, 14th and 28th days after modeling, we 
      performed histopathological examination through staining. Meanwhile, 
      immunohistochemistry (IHC) of PF and the expression of related factors were 
      observed, while Ang/Tie2 pathway was assessed by ELISA with the effect of SSd on 
      angiogenesis related proteins in IPF being explored with IHC and Western Blot 
      technique. RESULTS: Our results showed that SSd could reduce inflammation and PF 
      levels in lung tissue of experimental mice, while levels of angiogenesis-related 
      factors, namely Tie-2, Ang-1 and ANGPT2 (Ang-2), fibrosis- associated factors 
      like Alpha-smooth muscle actin (alpha-SMA), collagen-I and hydroxyproline in SSd and 
      dexamethasone (DXM) mice were significantly reduced at each time point compared 
      to BLM (p < 0.01). Additionally, we discovered substantial decreased expressions 
      of Ang-1, Ang-2, Tie-2, alpha-SMA and collagen-I at protein level in SSd and DXM mice 
      at each time point compared to BLM (p < 0.05). Besides, insignificant differences 
      were observed between SSd and DXM groups (p > 0.05). CONCLUSION: This study has 
      demonstrated that SSd could down-regulate the expression of ANG-1, Ang-2 and Tie2 
      in the Ang/Tie2 pathway, and may reduce lung inflammation and PF in BLM-induced 
      mice via inhibition of angiogenesis.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.
FAU - Wu, Yan
AU  - Wu Y
AD  - Department of Respiratory and Critical Care Medicine, Affiliated Hospital of 
      Jiangnan University, 1000 Hefeng Road, Binhu District, Wuxi City, Jiangsu 214122, 
      China.
FAU - Zhang, Jun
AU  - Zhang J
AD  - Department of Respiratory and Critical Care Medicine, Aoyang Hospital Affiliated 
      to Jiangsu University, 279 Jingang Dadao, Zhangjiagang City, Jiangsu 215631, 
      China.
FAU - Wang, Xintian
AU  - Wang X
AD  - Department of Respiratory and Critical Care Medicine, Affiliated Hospital of 
      Jiangsu University, 438 Jiefang Road, Jingkou District, Zhenjiang City, Jiangsu 
      212000, China.
FAU - Xu, Yuncong
AU  - Xu Y
AD  - Department of Respiratory and Critical Care Medicine, Affiliated Hospital of 
      Jiangsu University, 438 Jiefang Road, Jingkou District, Zhenjiang City, Jiangsu 
      212000, China.
FAU - Zheng, Jinxu
AU  - Zheng J
AD  - Department of Respiratory and Critical Care Medicine, Affiliated Hospital of 
      Jiangsu University, 438 Jiefang Road, Jingkou District, Zhenjiang City, Jiangsu 
      212000, China. Electronic address: zhengjxu@ujs.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20231012
PL  - Germany
TA  - Acta Histochem
JT  - Acta histochemica
JID - 0370320
RN  - UR635J3F00 (saikosaponin D)
RN  - 0 (Angiopoietins)
RN  - 0 (Collagen Type I)
RN  - 11056-06-7 (Bleomycin)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Angiopoietins/metabolism/pharmacology
MH  - Mice, Inbred C57BL
MH  - Lung/metabolism
MH  - *Idiopathic Pulmonary Fibrosis/drug therapy/metabolism/pathology
MH  - Collagen Type I/metabolism
MH  - Bleomycin/pharmacology/metabolism
OTO - NOTNLM
OT  - Ang/Tie-2 pathway
OT  - Angiogenesis
OT  - Idiopathic pulmonary fibrosis
OT  - Saikosaponin‑d
COIS- Declaration of Competing Interest The authors declared no conflict of interests.
EDAT- 2023/10/15 05:46
MHDA- 2023/12/01 06:43
CRDT- 2023/10/14 18:06
PHST- 2023/04/12 00:00 [received]
PHST- 2023/09/06 00:00 [revised]
PHST- 2023/09/30 00:00 [accepted]
PHST- 2023/12/01 06:43 [medline]
PHST- 2023/10/15 05:46 [pubmed]
PHST- 2023/10/14 18:06 [entrez]
AID - S0065-1281(23)00107-1 [pii]
AID - 10.1016/j.acthis.2023.152100 [doi]
PST - ppublish
SO  - Acta Histochem. 2023 Dec;125(8):152100. doi: 10.1016/j.acthis.2023.152100. Epub 
      2023 Oct 12.