Physcion alleviates cisplatin-induced apo in HK-2 cells by activating the apo signaling for treating acute kidney injury: Integrating network pharmacology and informatics.

Abstract

This research leverages the traditional Chinese medicine systems pharmacology (TCMSP) and Encyclopedia of traditional Chinese medicine (ETCM) to identify Chinese herbal remedies for (AKI) treatment. Lycii Fructus was found to be a potential candidate, and its pharmacological effects and molecular mechanisms were explored. Key targets of Lycii Fructus for AKI were identified and integrated into a "Herb-Ingredient-Target-Disease" (HITD) network. Through network pharmacology (NP) and literature review, physcion (PHY), a compound found in Lycii Fructus, was identified as a potential active ingredient targeting the Bcl2 gene, with apoptosis (Apo) proposed as the mechanism for its effects on AKI. To investigate this, a cisplatin-induced Apo model in human renal tubular epithelial cells (HK-2) was established. The study revealed that dose-dependent PHY administration substantially reduced cisplatin-induced Apo in HK-2 cells, as shown by CCK-8 assays and flow cytometry. We treated HK-2 with cisplatin at 5 mg L^-1, treatment is carried out with different concentrations of PHY, to investigate the effect of PHY on the survival rates, the apoptosis rates and expressions of Bcl2/Bax protein of cells. CCK-8 assays showed, the survival rates of the cells in the groups with PHY therapeutic concentrations of 20 μmol L^-1,40 μmol L^-1 and 60 μmol L^-1, the increase value compared with the cisplatin group were 8.40%, 31.67% and 37.19% respectively (P < 0.01) as well as apoptosis rates of the cells in the groups with PHY therapeutic concentrations of 40 μmol L^-1 and 60 μmol L^-1, the decrease in compared with the cisplatin group were 14.20% and 26.28% respectively (P < 0.01). Overall, PHY alleviated cisplatin-induced Apo in HK-2 cells by activating the Apo signaling.