Lobetyolin, a Q-marker isolated from Radix Platycodi, exerts protective effects on cisplatin-induced cytotoxicity in HEK293 cells.
Yun-Yi HouSi-Min QiJing LengQiong ShenShan TangJing-Tian ZhangJun-Nan HuShuang JiangWei LiPublished in: Journal of natural medicines (2023)
This study investigated the protective effect of lobetyolin (LBT), a Q-marker isolated from the roots of Platycodon grandiflorum (Radix Platycodi), against cisplatin-induced cytotoxicity in human embryonic kidney (HEK293) cells. Results showed that LBT at 20 μM significantly prevented cisplatin-induced cytotoxicity by improving the viability of HEK293 cells, decreasing levels of MDA, and decreasing GSH content triggered by cisplatin. It also suppressed reactive oxygen species (ROS) levels. Molecular docking analysis revealed a strong binding affinity between LBT and the NF-κB protein, with a docking fraction of - 6.5 kcal/mol. These results provide compelling evidence suggesting a potential link between the visualization analysis of LBT and its protective mechanism, specifically implicating the NF-κB signaling pathway. LBT also reduced the expression level of tumor necrosis factor-alpha (TNF-α), phosphorylation NF-κB and IκBα in HEK293 cells which were increased by cisplatin exposure, leading to inhibition of inflammation. Furthermore, western blotting showed that LBT antagonized the up-regulation of Bax, cleaved caspase 3, 8, and 9 expression and inhibited the MAPK signaling pathway by down-regulating phosphorylation JNK, ERK, and p38, partially ameliorating cisplatin-induced cytotoxicity in HEK293 cells. Therefore, these results indicate that LBT has potentially protected renal function by inhibiting inflammation and apoptosis.
Keyphrases
- signaling pathway
- induced apoptosis
- cell cycle arrest
- pi k akt
- oxidative stress
- endoplasmic reticulum stress
- cell death
- epithelial mesenchymal transition
- molecular docking
- rheumatoid arthritis
- reactive oxygen species
- endothelial cells
- poor prognosis
- small molecule
- molecular dynamics simulations
- binding protein
- toll like receptor
- breast cancer cells
- dna damage
- climate change
- mass spectrometry
- induced pluripotent stem cells
- pluripotent stem cells