PMID- 37414198
OWN - NLM
STAT- MEDLINE
DCOM- 20230918
LR  - 20230918
IS  - 1872-7573 (Electronic)
IS  - 0378-8741 (Linking)
VI  - 318
IP  - Pt A
DP  - 2024 Jan 10
TI  - Integration of network pharmacology and proteomics to elucidate the mechanism and 
      targets of traditional Chinese medicine Biyuan Tongqiao granule against allergic 
      rhinitis in an ovalbumin-induced mice model.
PG  - 116816
LID - S0378-8741(23)00684-0 [pii]
LID - 10.1016/j.jep.2023.116816 [doi]
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Biyuan Tongqiao granule (BYTQ) is a traditional 
      Chinese medicine that has been used in China to clinically treat patients with 
      allergic rhinitis (AR), yet its underlying mechanism and targets remains unclear. 
      AIM OF THE STUDY: The study aimed to investigate the potential mechanism of BYTQ 
      against AR using the ovalbumin (OVA) -induced AR mice model. Integrating network 
      pharmacology and proteomics to investigate possible targets of BYTQ for AR. 
      MATERIALS AND METHODS: The compounds in BYTQ were analyzed using 
      UHPLC-ESI-QE-Orbitrap-MS. The OVA/Al(OH)(3) were used to induce the AR mice 
      model. The nasal symptoms, histopathology, immune subsets, inflammatory factors, 
      and differentially expressed proteins were examined. Proteomics analysis 
      elucidated the potential mechanisms of BYTQ to improve AR, which was further 
      validated by Western blot (WB) assay. The compounds and potential targets of BYTQ 
      were systematically elucidated by integrating network pharmacology and proteomics 
      analysis to explore the mechanism. The binding affinity between key potential 
      targets and corresponding compounds was then validated using molecular docking. 
      Molecular docking results were verified by a western blotting and cellular 
      thermal shift assay (CETSA). RESULTS: A total of 58 compounds were identified 
      from BYTQ. BYTQ significantly suppressed AR symptoms by inhibiting the release of 
      OVA-specific immunoglobulin E (IgE) and histamine, improving the pathological 
      injury of nasal mucosal tissue, and regulating the proportions of lymphocytes to 
      maintain immune balance. Proteomics analysis showed that the cell adhesion 
      factors and focal adhesion pathway might be potential mechanism of BYTQ against 
      AR. The levels of E-selectin, vascular endothelial cell adhesion molecule-1 
      (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) proteins in the nasal 
      mucosal tissue were significantly downregulated in the BYTQ-H group compared to 
      the AR group. Integrating network pharmacology and proteomics analysis identified 
      that SRC, PIK3R1, HSP90AA1, GRB2, AKT1, MAPK3, MAPK1, TP53, PIK3CA, and STAT3 may 
      be potential protein targets for BYTQ to treat AR. Molecular docking analysis 
      indicated that the active compounds of BYTQ could bind tightly to these key 
      targets. In addition, BYTQ could inhibit OVA-induced phosphorylation levels of 
      PI3K, AKT1, STAT3 and ERK1/2. The CETSA data suggested that BYTQ could improve 
      the heat stability of PI3K, AKT1, STAT3 and ERK1/2. CONCLUSIONS: BYTQ suppresses 
      E-selectin and VCAM-1 and ICAM1 expression by regulating PI3K/AKT and STAT3/MAPK 
      signaling pathways, thus alleviating inflammation in AR mice. BYTQ is the 
      aggressive treatment for AR.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Wang, Ruikun
AU  - Wang R
AD  - Department of Otolaryngology, Head and Neck Surgery, Children's Hospital Capital 
      Institute of Pediatrics, Beijing, 100020, China.
FAU - Yang, Tianye
AU  - Yang T
AD  - State Key Laboratory of Integration and Innovation of Classic Formula and Modern 
      Chinese Medicine, Lunan Pharmaceutical Group Co. LTD., Linyi, 276005, China.
FAU - Feng, Qun
AU  - Feng Q
AD  - State Key Laboratory of Integration and Innovation of Classic Formula and Modern 
      Chinese Medicine, Lunan Pharmaceutical Group Co. LTD., Linyi, 276005, China.
FAU - Jiang, Yujun
AU  - Jiang Y
AD  - State Key Laboratory of Integration and Innovation of Classic Formula and Modern 
      Chinese Medicine, Lunan Pharmaceutical Group Co. LTD., Linyi, 276005, China.
FAU - Yuan, Xiaomei
AU  - Yuan X
AD  - State Key Laboratory of Integration and Innovation of Classic Formula and Modern 
      Chinese Medicine, Lunan Pharmaceutical Group Co. LTD., Linyi, 276005, China.
FAU - Zhao, Lizhi
AU  - Zhao L
AD  - State Key Laboratory of Integration and Innovation of Classic Formula and Modern 
      Chinese Medicine, Lunan Pharmaceutical Group Co. LTD., Linyi, 276005, China.
FAU - Liu, Ning
AU  - Liu N
AD  - State Key Laboratory of Integration and Innovation of Classic Formula and Modern 
      Chinese Medicine, Lunan Pharmaceutical Group Co. LTD., Linyi, 276005, China.
FAU - Liu, Zhong
AU  - Liu Z
AD  - State Key Laboratory of Integration and Innovation of Classic Formula and Modern 
      Chinese Medicine, Lunan Pharmaceutical Group Co. LTD., Linyi, 276005, China.
FAU - Zhang, Yongkang
AU  - Zhang Y
AD  - College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 
      250355, China.
FAU - Wang, Luyao
AU  - Wang L
AD  - State Key Laboratory of Integration and Innovation of Classic Formula and Modern 
      Chinese Medicine, Lunan Pharmaceutical Group Co. LTD., Linyi, 276005, China.
FAU - Cheng, Guoliang
AU  - Cheng G
AD  - College of Traditional Chinese Medicine, Beijing University of Traditional 
      Chinese Medicine, Beijing, 100029, China.
FAU - Yao, Jingchun
AU  - Yao J
AD  - State Key Laboratory of Integration and Innovation of Classic Formula and Modern 
      Chinese Medicine, Lunan Pharmaceutical Group Co. LTD., Linyi, 276005, China.
FAU - Sun, Chenghong
AU  - Sun C
AD  - State Key Laboratory of Integration and Innovation of Classic Formula and Modern 
      Chinese Medicine, Lunan Pharmaceutical Group Co. LTD., Linyi, 276005, China. 
      Electronic address: sch658@163.com.
FAU - Zhang, Guimin
AU  - Zhang G
AD  - State Key Laboratory of Integration and Innovation of Classic Formula and Modern 
      Chinese Medicine, Lunan Pharmaceutical Group Co. LTD., Linyi, 276005, China. 
      Electronic address: lunanzhangguimin@yeah.net.
FAU - Gu, Qinglong
AU  - Gu Q
AD  - Department of Otolaryngology, Head and Neck Surgery, Children's Hospital Capital 
      Institute of Pediatrics, Beijing, 100020, China. Electronic address: 
      gql13146836613@163.com.
LA  - eng
PT  - Journal Article
DEP - 20230704
PL  - Ireland
TA  - J Ethnopharmacol
JT  - Journal of ethnopharmacology
JID - 7903310
RN  - 9006-59-1 (Ovalbumin)
RN  - 0 (E-Selectin)
RN  - 0 (Cytokines)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Ovalbumin/pharmacology
MH  - *E-Selectin
MH  - Cytokines/metabolism
MH  - Medicine, Chinese Traditional
MH  - Vascular Cell Adhesion Molecule-1
MH  - Molecular Docking Simulation
MH  - Network Pharmacology
MH  - Phosphatidylinositol 3-Kinases
MH  - Proteomics
MH  - *Rhinitis, Allergic/chemically induced/drug therapy
MH  - Mice, Inbred BALB C
OTO - NOTNLM
OT  - Allergic rhinitis
OT  - Biyuan Tongqiao granule
OT  - Cell adhesion factor
OT  - Focal adhesion
OT  - Inflammation
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/07/07 01:05
MHDA- 2023/09/18 12:42
CRDT- 2023/07/06 19:25
PHST- 2023/04/11 00:00 [received]
PHST- 2023/06/16 00:00 [revised]
PHST- 2023/06/17 00:00 [accepted]
PHST- 2023/09/18 12:42 [medline]
PHST- 2023/07/07 01:05 [pubmed]
PHST- 2023/07/06 19:25 [entrez]
AID - S0378-8741(23)00684-0 [pii]
AID - 10.1016/j.jep.2023.116816 [doi]
PST - ppublish
SO  - J Ethnopharmacol. 2024 Jan 10;318(Pt A):116816. doi: 10.1016/j.jep.2023.116816. 
      Epub 2023 Jul 4.