Exploring the potential of oxymatrine in preventing CHIKV-induced acute kidney injury based on multi-dimensional computational analysis and in vitro experiments

Chikungunya virus (CHIKV) infection can induce acute kidney injury (AKI) and may be fatal in severe cases, yet effective therapeutic strategies remain unclear. This study integrated computational analysis (network pharmacology and molecular docking) with in vitro experiments to evaluate the protective potential of oxymatrine against CHIKV-induced AKI and to explore its underlying mechanisms. Network pharmacology analysis identified 605 overlapping targets between CHIKV- and AKI-related genes, with core targets including TNF, AKT1, IL6, IL1B, and TP53, which were primarily enriched in the PI3K/AKT signaling pathway. RT-qPCR analysis and molecular docking further indicated that oxymatrine may interact with 18 targets, such as BAX, BCL2, and TLR4, thereby modulating CHIKV-associated PI3K/AKT signaling. In vitro experiments showed that oxymatrine at concentrations of 250–2,000 μM significantly increased the viability of HEK293T cells infected with CHIKV at a MOI of 0.01 for 24 h, with an average increase of approximately 25.8%. At these concentrations, oxymatrine reduced the expression of the CHIKV entry factor TIM-1 and regulated the PI3K/AKT, NF-κB, and TNF signaling pathways, which may contribute to the inhibition of viral replication. Further analysis revealed that CHIKV-induced AKI involved 75 ferroptosis-related targets and was closely associated with inflammatory responses. Oxymatrine may attenuate these effects through the regulation of targets such as SIRT3, AR, and FURIN. Consistently, ELISA results demonstrated that 1,000 μM oxymatrine significantly decreased the levels of IL-1β, TNF-α, and IL-6 in HEK293T cells infected with CHIKV. In conclusion, these findings suggest that oxymatrine may protect against CHIKV-induced AKI by limiting viral replication, modulating PI3K/AKT and NF-κB/TNF signaling pathways, suppressing inflammation, and regulating ferroptosis-related processes.