Modified Sijunzi Granules Exhibit Hemostatic Effect by Activating Akt and Erk Signal Pathways via Regulating 5-HT and Its Receptors Levels.
10.1007/s11655-023-3567-6
- Author:
Jun WANG
1
;
Xue-Ying ZHANG
2
;
Yan-Hong KANG
2
;
Yun ZHANG
1
;
Xin-Yi CHEN
2
;
Jia-Li ZHOU
3
;
Wei MA
4
,
5
Author Information
1. Department of Hematology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China.
2. Department of Hemato-Oncology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
3. Hunter Biotechnology, Inc., Hangzhou, 310051, China.
4. Department of Hemato-Oncology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China. doctormawei@
5. com.
- Publication Type:Journal Article
- Keywords:
5-hydroxytryptamine;
5-hydroxytryptamine receptor;
Chinese medicine;
mitogen-activated protein kinase/extracellular regulated protein kinases signal pathway;
modified Sijunzi Granules;
phosphoinositide3-kinases/protein kinase B signal pathway;
primary immune thrombocytopenia;
zebrafish
- MeSH:
Animals;
Zebrafish;
Serotonin/metabolism*;
Proto-Oncogene Proteins c-akt/metabolism*;
Drugs, Chinese Herbal/pharmacology*;
Hemostatics/pharmacology*;
MAP Kinase Signaling System/drug effects*;
Receptors, Serotonin/genetics*;
Extracellular Signal-Regulated MAP Kinases/metabolism*;
Signal Transduction/drug effects*;
Hemostasis/drug effects*
- From:
Chinese journal of integrative medicine
2024;30(12):1121-1127
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To investigate the hemostatic effect of modified Sijunzi Granules (MSG) in primary immune thrombocytopenia (ITP) zebrafish model and explore the potential mechanism.
METHODS:AB strain wild type zebrafish were treated with simvastatin (6 µmol/L) for 24 h to establish the hemorrhage model (model control group). The zebrafish were treated with MSG at different doses (55.6, 167, and 500 µg/mL), respectively. The hemostatic effect was assessed by examining the intestinal bleeding and hemostatic rate. 5-Hydroxytryptamine (5-HT) content was determined using enzyme-linked immunosorbent assay (ELISA) assay. The expressions of 5-HT2aR, 5-HT2bR, and SERT genes were detected by quantitative real-time polymerase chain reaction(PCR). The protein expressions of protein kinase B (Akt), p-Akt, extracellular regulated protein kinases (Erk), and p-Erk were examined using Western blot analysis.
RESULTS:The intestinal bleeding rate was 37%, 40%, and 80% in the 55.6, 167, and 500 µg/mL dose of MSG, respectively, in which 55.6 and 167 µg/mL MSG dose groups were associated with significantly decreased intestinal bleeding rate when compared with the model control group (70%, P<0.05). Significantly higher hemostatic rates were also observed in the 55.6 (54%) and 167 (52%) µg/mL MSG dose groups (P<0.05). MSG increased the 5-HT content and mRNA expression levels of 5-HT2aR, 5-HT2bR, and SERT (P<0.05). In addition, caspase3/7 activity was inhibited (P<0.05). Significant increase in p-Akt and p-Erk was also detected after treatment with MSG (P<0.05).
CONCLUSIONS:MSG could reduce the incidence and severity of intestinal bleeding in zebrafish by activating MAPK/Erk and PI3K/Akt signal pathways through regulating the levels of 5-HT and its receptors, which may provide evidence for the treatment of ITP.
