Journal of ethnopharmacology · 2023
TMT-based quantitative proteomics reveals the protective mechanism of tenuigenin after experimental intracerebral hemorrhage in mice.
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Wang Peng, Shen YiQing, Manaenko Anatol, Liu FangYu, Yang WenSong, Xiao ZhongSong, Li PeiZheng, Ran YuXin, Dang RuoZhi, He Yong, Wu QingYuan, Xie Peng, Li Qi
Аннотация
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.
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.