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| Status |
Public on Nov 13, 2021 |
| Title |
Tormentic Acid Ameliorates Hepatic Fibrosis in vivo by Inhibiting Glycerophospholipids Metabolism and PI3K/Akt/mTOR and NF-κB Pathways: Based on Transcriptomics and Metabolomics |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
This study aimed to investigate the effects and underlying mechanisms of tormentic acid (TA) on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. The rats were intragastrically administered with 50% CCl4 for 9 weeks to induce hepatic fibrosis, followed by various agents for 6 weeks. Transcriptomic analysis was carried out to predict the potential targets, and then multiple examinations were performed to verify the prediction. The results showed that TA significantly alleviated liver injury and fibrosis, as evidenced by the ameliorative pathological tissue, low transaminase activity, and decreased collagen accumulation. Besides, TA markedly reduced hepatocyte apoptosis by regulating the expression of caspase-3 and Bcl-2 families. The transcriptomic analysis revealed 2,173 differentially expressed genes (DEGs) between the TA and model groups, which could be enriched in the metabolic pathways and the PI3K/Akt and NF-κB signaling pathways. The metabolomics analysis showed that TA could regulate the glycerophospholipid metabolism pathway by regulating the synthesis of phosphatidylserines, phosphatidylethanolamines and phosphatidylcholines. Moreover, the integrative analysis of the transcriptomics and metabolomics data indicated that TA inhibited the glycerophospholipid metabolism pathway by inhibiting the expression of LPCAT4, PTDSS2, PLA2G2A and CEPT1. In addition, the relevant signaling pathways analysis confirmed that TA inhibited HSCs activation by blocking the PI3K/Akt/mTOR pathway and ameliorated inflammatory injury by inhibiting the NF-κB pathway. In conclusion, TA significantly alleviates liver fibrosis in vivo by inhibiting the glycerophospholipid metabolism pathway and the PI3K/Akt/mTOR and NF-κB signaling pathways.
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| Overall design |
Male Sprague–Dawley (SD) rats were intragastrically administered with 2 ml/kg CCl4 (50% oil solution) twice a week for 9 weeks to induce liver fibrosis, followed by Tormentic acid (TA) treatment for 6 weeks. At the end of the treatment, all animals were fasted for 12 h and then anesthetized by intraperitoneal injection of 3% sodium pentobarbital (1.0 ml/kg). The liver samples were collected immediately. The samples for the analysis were obtained from the normal group, model group, and SCL group (3.0 mg/kg TA group; SCL means the special concentration of liver homogenate (<1μg/mL) from the 3.0 mg/kg TA-treated group).
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| Web link |
https://www.frontiersin.org/articles/10.3389/fphar.2022.801982/full
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| Contributor(s) |
Lin X, Wei Y, Li Y, Xiong Y |
| Citation(s) |
35359829 |
| Submission date |
Nov 11, 2021 |
| Last update date |
Apr 07, 2022 |
| Contact name |
xing lin |
| Organization name |
Guangxi medical university
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| Street address |
Shuangyong Road
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| City |
Nanning |
| ZIP/Postal code |
530001 |
| Country |
China |
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| Platforms (1) |
| GPL14844 |
Illumina HiSeq 2000 (Rattus norvegicus) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA779615 |
| SRA |
SRP345602 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE188604_wyy_AVSwyy_B.All.txt.gz |
1.9 Mb |
(ftp)(http) |
TXT |
| GSE188604_wyy_CVSwyy_B.All.txt.gz |
1.9 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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