scholarly journals Gambogic acid suppresses inflammation in rheumatoid arthritis rats via PI3K/Akt/mTOR signaling pathway

2017 ◽  
Vol 16 (5) ◽  
pp. 7112-7118 ◽  
Author(s):  
Xiaodan Wu ◽  
Li Long ◽  
Jian Liu ◽  
Jin Zhang ◽  
Tong Wu ◽  
...  
2020 ◽  
Vol 10 (8) ◽  
pp. 1176-1183
Author(s):  
Juan Ni ◽  
Zhe Hao

Background and Objectives: Rheumatoid arthritis (RA) is an autoimmune arthropathy characterised by chronic synovitis, joint cartilage breakdown and bone erosions. The life quality of RA patients has been substantially effected by the disease and it is of great significance to search for more efficacious and novel therapeutic agents. Methods: In this study, mRNA levels of miR-34a in HFLS and RA-FLS were examined by RT-PCR. CCK8 assay was applied to detect the viability of RA-FLS transfected with miR-34a mimic or inhibitor. Furthermore, TUNEL assay and Hoechest-33342 assay was applied to detect the apoptosis of RA-FLS transfected with miR-34a mimic or inhibitor. The expressions of proteins related to AMPK/Akt/mTOR and autophagy were also detected by western blot. Results: The RT-PCR result showed that miR-34a mRNA levels was markedly downregulated in RA-FLS compared to HFLS. CCK8 assay results demonstrated that miR-34a overexpression significantly suppressed RA-FLS proliferation and miR-34a interference had the opposite effect. TUNEL assay and Hoechest-33342 assay demonstrated that miR-34a overexpression significantly promoted RA-FLS apoptosis and miR-34a interference had the opposite effect. The western blot results revealed that miR-34a can affect autophagy via AMPK/Akt/mTOR signaling pathway. Conclusion: This study suggested that miR-34a can regulate proliferation and apoptosis in RA-FLS by affecting autophagy through AMPK/Akt/mTOR signaling pathway.


2020 ◽  
Vol 20 (6) ◽  
pp. 3361-3372 ◽  
Author(s):  
Guoxuan Luo ◽  
Shengqiang Jiang ◽  
Xu Zhang ◽  
Yunzhi Ling ◽  
Hengshan Luo ◽  
...  

Gambogic acid (GA) is a natural compound with a polyprenylated xanthone structure that has antiinflammatory, antioxidant, and neuroprotective properties and acts as a chemopreventive agent. GA exhibits anti-tumor, antimicrobial, and anti-proliferative effects on cancer cells. In the current study, the effect of GA on phosphoinositide kinase-3 (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway was examined in human U251 glioma cells. Cell viability and apoptosis were evaluated by MTT and Annexin V/PI Double Staining. The expressions of P38, AKT, and mTOR were evaluated by western blot and qRT-PCR, respectively. MagBeads Total RNA Extraction Kit was used to isolate cell tissue RNA. GA decreased the phosphorylation of P38, AKT, and mTOR. Inhibitors of PI3K (LY294002) enhanced the phosphorylation of P38, AKT, and mTOR. GA reduced the phosphorylation of ribosomal protein precursors (Pre) and upstream binding factor (UBF), and insulin-like growth factor I (IGF-1) further enhanced the cell proliferation and expression of Pre and UBF. These results suggested that downregulation of PI3K/AKT/mTOR signaling pathway may be an important mediator in GA-affected ribosomal occurrence in glioma cells.


2020 ◽  
Author(s):  
Minfen Zhang ◽  
Hui Chen ◽  
Ping Qin ◽  
Tonghui Cai ◽  
Lingjun Li ◽  
...  

2020 ◽  
Vol 27 ◽  
Author(s):  
Naser-Aldin Lashgari ◽  
Nazanin Momeni Roudsari ◽  
Saeideh Momtaz ◽  
Negar Ghanaatian ◽  
Parichehr Kohansal ◽  
...  

: Inflammatory bowel disease (IBD) is a general term for a group of chronic and progressive disorders. Several cellular and biomolecular pathways are implicated in the pathogenesis of IBD, yet the etiology is unclear. Activation of the mammalian target of rapamycin (mTOR) pathway in the intestinal epithelial cells was also shown to induce inflammation. This review focuses on the inhibition of the mTOR signaling pathway and its potential application in treating IBD. We also provide an overview on plant-derived compounds that are beneficial for the IBD management through modulation of the mTOR pathway. Data were extracted from clinical, in vitro and in vivo studies published in English between 1995 and May 2019, which were collected from PubMed, Google Scholar, Scopus and Cochrane library databases. Results of various studies implied that inhibition of the mTOR signaling pathway downregulates the inflammatory processes and cytokines involved in IBD. In this context, a number of natural products might reverse the pathological features of the disease. Furthermore, mTOR provides a novel drug target for IBD. Comprehensive clinical studies are required to confirm the efficacy of mTOR inhibitors in treating IBD.


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