التفاصيل البيبلوغرافية
| العنوان: |
Rosmarinic acid alleviates toosendanin-induced liver injury through restoration of autophagic flux and lysosomal function by activating JAK2/STAT3/CTSC pathway. |
| المؤلفون: |
Luo, Li1 (AUTHOR), Lin, Jinxian1 (AUTHOR), Chen, Sixin1 (AUTHOR), Ni, Jiajie1 (AUTHOR), Peng, Hongjie1 (AUTHOR), Shen, Feihai1,2 (AUTHOR) tobyshum12@163.com, Huang, Zhiying1 (AUTHOR) hzhiying@mail.sysu.edu.cn |
| المصدر: |
Journal of Ethnopharmacology. Aug2024, Vol. 330, pN.PAG-N.PAG. 1p. |
| مصطلحات موضوعية: |
*LIVER injuries, *LIVER disease prevention, *LYSOSOMES, *AUTOPHAGY, *ROSMARINIC acid, *CHOLECYSTOKININ, *ELECTRON microscopy, *CELLULAR signal transduction, *LACTATE dehydrogenase, *IMMUNODIAGNOSIS, *REVERSE transcriptase polymerase chain reaction, *PLANT extracts, *LIVER diseases, *JANUS kinases, *MICE, *GENE expression, *IMMUNOHISTOCHEMISTRY, *MESSENGER RNA, *LIVER cells, *MEDICINAL plants, *ANIMAL experimentation, *WESTERN immunoblotting, *OXIDOREDUCTASES, *GENE expression profiling, *ORGANIC compounds, *STAT proteins, *BIOLOGICAL assay, *STAINS & staining (Microscopy), *POLYPHENOLS, *CELL surface antigens |
| مستخلص: |
Rosmarinic acid (RA), a natural polyphenol abundant in numerous herbal remedies, has been attracting growing interest owing to its exceptional ability to protect the liver. Toosendanin (TSN), a prominent bioactive compound derived from Melia toosendan Siebold & Zucc., boasts diverse pharmacological properties. Nevertheless, TSN possesses remarkable hepatotoxicity. Intriguingly, the potential of RA to counteract TSN-induced liver damage and its probable mechanisms remain unexplored. This study is aimed at exploring whether RA can alleviate TSN-induced liver injury and the potential mechanisms involved autophagy. CCK-8 and LDH leakage rate assay were used to evaluate cytotoxicity. Balb/c mice were intraperitoneally administered TSN (20 mg/kg) for 24 h after pretreatment with RA (0, 40, 80 mg/kg) by gavage for 5 days. The autophagic proteins P62 and LC3B expressions were detected using western blot and immunohistochemistry. RFP-GFP-LC3B and transmission electron microscopy were applied to observe the accumulation levels of autophagosomes and autolysosomes. LysoTracker Red and DQ-BSA staining were used to evaluate the lysosomal acidity and degradation ability respectively. Western blot, immunohistochemistry and immunofluorescence staining were employed to measure the expressions of JAK2/STAT3/CTSC pathway proteins. Dual-luciferase reporter gene was used to measure the transcriptional activity of CTSC and RT-PCR was used to detect its mRNA level. H&E staining and serum biochemical assay were employed to determine the degree of damage to the liver. TSN-induced damage to hepatocytes and livers was significantly alleviated by RA. RA markedly diminished the autophagic flux blockade and lysosomal dysfunction caused by TSN. Mechanically, RA alleviated TSN-induced down-regulation of CTSC by activating JAK2/STAT3 signaling pathway. RA could protect against TSN-induced liver injury by activating the JAK2/STAT3/CTSC pathway-mediated autophagy and lysosomal function. [Display omitted] • TSN suppressed JAK2/STAT3/CTSC pathway-mediated autophagy. • RA alleviated TSN-induced hepatotoxicity by activating JAK2/STAT3/CTSC pathway. • STAT3 participated in the transcriptional activation of CTSC. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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