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  2. TMT-based quantitative proteomics reveals the protective mechanism of tenuigenin after experimental intracerebral hemorrhage in mice

TMT-based quantitative proteomics reveals the protective mechanism of tenuigenin after experimental intracerebral hemorrhage in mice

  • J Ethnopharmacol. 2023 Sep 20;117213. doi: 10.1016/j.jep.2023.117213.
Peng Wang 1 YiQing Shen 1 Anatol Manaenko 1 FangYu Liu 1 WenSong Yang 1 ZhongSong Xiao 1 PeiZheng Li 1 YuXin Ran 1 RuoZhi Dang 1 Yong He 1 QingYuan Wu 2 Peng Xie 3 Qi Li 4
Affiliations

Affiliations

  • 1 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
  • 2 NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; Department of Neurology, Chongqing University Three Gorges Hospital, Chongqing, China.
  • 3 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. Electronic address: [email protected].
  • 4 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. Electronic address: [email protected].
Abstract

Ethnopharmacological relevance: Tenuigenin (TNG) is an extract obtained from Polygalae Radix. It possesses anti-inflammatory, antioxidant, and neuroprotective properties. However, the potential mechanism of TNG in intracerebral hemorrhage (ICH) has not been well studied.

Aim of the study: In the present study, we aimed to identify the prospective mechanism of TNG in treating ICH.

Materials and methods: A total of 120 mice were divided into five groups: Sham group, ICH + vehicle group, ICH + TNG(8 mg/kg), ICH + TNG(16 mg/kg), and ICH + TNG(32 mg/kg). The modified Garcia test and beam walking test were carried out at 24 h and 72 h after ICH. Brain water content, haematoma volume and hemoglobin content examinations were performed at 72 h after ICH. TMT-based quantitative proteomics combined with bioinformatics analysis methods was used to distinguish differentially expressed proteins (DEPs) to explore potential pharmacological mechanisms. Western blotting was performed to validate representative proteins.

Results: Our results showed that the optimal dose of TNG was 16 mg/kg, which could markedly improve neurological functions, and reduce cerebral oedema, haematoma volume and hemoglobin levels 72 h after ICH. A total of 404 DEPs (353 up-and 51 downregulated) were identified in the ICH + vehicle vs. sham group, while 342 DEPs (306 up-and 36 downregulated) and 76 DEPs (28 up-and 48 downregulated) were quantified in the TNG vs. sham group and TNG vs. ICH + vehicle group, respectively. In addition, a total of 26 DEPs were selected according to strict criteria. Complement and coagulation cascades were the most significantly enriched pathways, and two proteins (MBL-C and Car1) were further validated as hub molecules.

Conclusions: Our results suggested that the therapeutic effects of TNG on ICH were closely associated with the Complement System, and that MBL-C and Car1 might be potential targets of TNG for the treatment of ICH.

Keywords

Complement system; Inflammation; Intracerebral hemorrhage; TMT-based proteomics; Tenuigenin.

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