PMID- 37586441
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  - An integrated RNA-Seq and network pharmacology approach for exploring the 
      preventive effect of Corydalis bungeana Turcz. Extract and Acetylcorynoline on 
      LPS-induced acute lung injury.
PG  - 117048
LID - S0378-8741(23)00916-9 [pii]
LID - 10.1016/j.jep.2023.117048 [doi]
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis bungeana Turcz. (KDD) is a Chinese 
      herbal medicine with anti-inflammatory, lung cleansing, detoxification and other 
      functions. Clinically, it is commonly used to treat respiratory infections. This 
      study uses ALI as the research model, which is consistent with the clinical use 
      of KDD. Acetylcorynoline (AC) is the main alkaloid component of the KDD extracts, 
      and network pharmacology studies suggest that it may be the main active 
      ingredient in the prevention of ALI. AIM OF THE STUDY: The aim of this study is 
      to explore the underlying mechanisms and to study the efficacy material basis of 
      KDD in anti-ALI effect by LPS-induced mice and using a combination of RNA 
      sequencing (RNA-Seq) technology and network pharmacology. MATERIALS AND METHODS: 
      Establish a mouse model of ALI by intraperitoneal injection of LPS (5 mg/kg). The 
      main active ingredients of KDD were identified and analyzed by high performance 
      liquid chromatography with quadrupole time-of-flight mass spectrometry 
      (HPLC-QTOF-MS) and network pharmacology. IL-18, IL-1beta, and IL-6 levels in serum 
      and bronchoalveolar lavage fluid (BALF), lung histopathological changes, and lung 
      myeloperoxidase (MPO) activity were assessed. We investigated the possible 
      molecular mechanisms of KDD and AC in an LPS-induced mouse ALI models with 
      RNA-Seq technology. In addition, the anti-inflammatory effect of AC was verified 
      in vitro by establishing an LPS-stimulated RAW264.7 inflammation model. Molecular 
      docking further validated AC as the efficacy material basis of KDD in anti-ALI. 
      RESULTS: Based on HPLC-QTOF-MS technology and network pharmacology, KDD is more 
      strongly associated with lung tissue, and that AC may be the main active 
      ingredient of KDD. Subsequently, in vivo experiments results showed that KDD and 
      AC reduced the levels of pro-inflammatory cytokines in serum and BALF, reduced 
      MPO levels and reduced inflammatory damage in the lungs. To elucidate its 
      underlying mechanism, based on RNA-Seq analysis techniques performed in lung 
      tissue, enrichment analysis showed that KDD and AC intervened through the NLR 
      signaling pathway, thereby mitigating LPS-induced ALI. Then, RT-qPCR, IF, WB and 
      other technologies were used to verify the anti-ALI core difference genes of KDD 
      and AC from the gene transcription and protein expression levels of the NLR 
      signaling pathway, and confirmed the anti-ALI. In vitro experimental results also 
      showed that AC has anti-inflammatory effects in RAW264.7. Finally, the 
      biotransformation and molecular docking results also further indicated that AC is 
      the active ingredient of KDD in anti-ALI. CONCLUSIONS: Studies have shown that 
      KDD has a good therapeutic effect on ALI, and AC is the main pharmacodynamic 
      material basis for its therapeutic effect in ALI.
CI  - Copyright (c) 2023. Published by Elsevier B.V.
FAU - Li, Qinning
AU  - Li Q
AD  - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, 
      Nanjing University of Chinese Medicine, Nanjing, 210028, China; Key Laboratory of 
      New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Province Academy of 
      Traditional Chinese Medicine, Nanjing, 210028, China.
FAU - Xiang, Yan
AU  - Xiang Y
AD  - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, 
      Nanjing University of Chinese Medicine, Nanjing, 210028, China; Key Laboratory of 
      New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Province Academy of 
      Traditional Chinese Medicine, Nanjing, 210028, China.
FAU - Zhang, Zhenxu
AU  - Zhang Z
AD  - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, 
      Nanjing University of Chinese Medicine, Nanjing, 210028, China; Key Laboratory of 
      New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Province Academy of 
      Traditional Chinese Medicine, Nanjing, 210028, China.
FAU - Qu, Xiaoyang
AU  - Qu X
AD  - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, 
      Nanjing University of Chinese Medicine, Nanjing, 210028, China; Key Laboratory of 
      New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Province Academy of 
      Traditional Chinese Medicine, Nanjing, 210028, China.
FAU - Wu, Jie
AU  - Wu J
AD  - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, 
      Nanjing University of Chinese Medicine, Nanjing, 210028, China; Key Laboratory of 
      New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Province Academy of 
      Traditional Chinese Medicine, Nanjing, 210028, China.
FAU - Fu, Jun
AU  - Fu J
AD  - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, 
      Nanjing University of Chinese Medicine, Nanjing, 210028, China; Key Laboratory of 
      New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Province Academy of 
      Traditional Chinese Medicine, Nanjing, 210028, China.
FAU - Zhu, Fenxia
AU  - Zhu F
AD  - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, 
      Nanjing University of Chinese Medicine, Nanjing, 210028, China; Key Laboratory of 
      New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Province Academy of 
      Traditional Chinese Medicine, Nanjing, 210028, China. Electronic address: 
      zfxcjq@126.com.
FAU - Tang, Hao
AU  - Tang H
AD  - Department of Pharmacy, Jinling Hospital, Nanjing, 210002, China. Electronic 
      address: tang_hao0518@sina.com.
LA  - eng
PT  - Journal Article
DEP - 20230815
PL  - Ireland
TA  - J Ethnopharmacol
JT  - Journal of ethnopharmacology
JID - 7903310
RN  - 0 (acetylcorynoline)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Plant Extracts)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (NF-kappa B)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Corydalis/chemistry
MH  - Lipopolysaccharides/pharmacology
MH  - Molecular Docking Simulation
MH  - Network Pharmacology
MH  - RNA-Seq
MH  - *Acute Lung Injury/chemically induced/drug therapy/prevention & control
MH  - Lung
MH  - Plant Extracts/adverse effects
MH  - Anti-Inflammatory Agents/adverse effects
MH  - NF-kappa B/metabolism
OTO - NOTNLM
OT  - Acetylcorynoline
OT  - Acute lung injury
OT  - Corydalis bungeana Turcz.
OT  - Network pharmacology
OT  - RNA-Seq
COIS- Declaration of competing interest The authors declare that they have no conflicts 
      of interest.
EDAT- 2023/08/17 00:42
MHDA- 2023/09/18 12:42
CRDT- 2023/08/16 19:21
PHST- 2023/04/13 00:00 [received]
PHST- 2023/08/10 00:00 [revised]
PHST- 2023/08/13 00:00 [accepted]
PHST- 2023/09/18 12:42 [medline]
PHST- 2023/08/17 00:42 [pubmed]
PHST- 2023/08/16 19:21 [entrez]
AID - S0378-8741(23)00916-9 [pii]
AID - 10.1016/j.jep.2023.117048 [doi]
PST - ppublish
SO  - J Ethnopharmacol. 2024 Jan 10;318(Pt B):117048. doi: 10.1016/j.jep.2023.117048. 
      Epub 2023 Aug 15.