Abstract
Background: Fangchinoline (Fan) is extracted from traditional Chinese medicine (called Fangji), or the root of Stephania tetrandra Moore. Fangji is well-known in Chinese medical literature for treating rheumatic diseases. Sjogren's syndrome (SS) is a rheumatic disease whose progression can be mediated via CD4+ T cell infiltration.
Objective: This study identifies the potential role of Fan in inducing apoptosis in Jurkat T cells.
Methods: First, we explored the biological process (BP) associated with SS development by performing a gene ontology analysis of SS salivary gland-related mRNA microarray data. The effect of Fan on Jurkat cells was investigated by analyzing the viability, proliferation, apoptosis, reactive oxygen species (ROS) production, and DNA damage.
Results: Biological process analysis showed that T cells played a role in salivary gland lesions in patients with SS, indicating the significance of T cell inhibition in SS treatment. Viability assays revealed that the half-maximal inhibitory concentration of Fan was 2.49 μM in Jurkat T cells, while the proliferation assay revealed that Fan had an inhibitory effect on the proliferation of Jurkat T cells. The results of the apoptotic, ROS, agarose gel electrophoresis, and immunofluorescence assays showed that Fan induced oxidative stress-induced apoptosis and DNA damage in a dosedependent manner.
Conclusion: These results indicate that Fan could significantly induce oxidative stress-induced apoptosis and DNA damage and inhibit the proliferation of Jurkat T cells. Moreover, Fan further enhanced the inhibitory effect on DNA damage and apoptosis by inhibiting the pro-survival Akt signal.
Keywords: Fangchinoline, Reactive, Oxygen species, DNA damage, Apoptosis, Akt.
[http://dx.doi.org/10.1002/art.39859] [PMID: 27785888]
[http://dx.doi.org/10.1111/bjh.13192] [PMID: 25316606]
[http://dx.doi.org/10.1016/j.jaci.2016.01.024] [PMID: 27045581]
[http://dx.doi.org/10.1111/j.1365-2249.2012.04606.x] [PMID: 22774983]
[http://dx.doi.org/10.1155/2022/3210200] [PMID: 35211629]
[http://dx.doi.org/10.1016/j.jaut.2019.102358] [PMID: 31757716]
[http://dx.doi.org/10.1016/j.jep.2020.112995] [PMID: 32497674]
[http://dx.doi.org/10.1016/j.bioorg.2019.103431] [PMID: 31759658]
[http://dx.doi.org/10.3390/molecules24061154] [PMID: 30909541]
[http://dx.doi.org/10.1124/mol.60.5.1083] [PMID: 11641437]
[http://dx.doi.org/10.2174/1874467215666220217103233] [PMID: 35176991]
[http://dx.doi.org/10.1016/j.intimp.2014.05.021] [PMID: 24877754]
[http://dx.doi.org/10.7150/thno.43441] [PMID: 32194859]
[http://dx.doi.org/10.1016/j.biopha.2018.12.043] [PMID: 30579253]
[http://dx.doi.org/10.1055/s-2003-40647] [PMID: 12865967]
[http://dx.doi.org/10.1016/j.jare.2021.03.008] [PMID: 35024200]
[PMID: 12147592]
[PMID: 6600176]
[http://dx.doi.org/10.1038/nri1330] [PMID: 15057788]
[http://dx.doi.org/10.1016/S0378-8741(97)00092-5] [PMID: 9406900]
[http://dx.doi.org/10.1016/j.jhazmat.2021.125903] [PMID: 34492839]
[http://dx.doi.org/10.1016/j.dnarep.2021.103142] [PMID: 34102579]
[http://dx.doi.org/10.1016/j.bmc.2021.116113] [PMID: 33744825]
[http://dx.doi.org/10.1007/s12602-019-09576-z] [PMID: 31332650]
[http://dx.doi.org/10.1016/j.biocel.2015.11.009] [PMID: 26589722]
[http://dx.doi.org/10.3892/ijmm.2018.3746] [PMID: 29956734]
[http://dx.doi.org/10.1038/s41419-018-0667-x] [PMID: 29855474]
[http://dx.doi.org/10.1172/JCI129479] [PMID: 32750040]
[http://dx.doi.org/10.1038/s41584-021-00741-9] [PMID: 35075294]