The preventative effect of Baihe Gujin Pill on cisplatin-induced acute kidney injury by activating the PI3K/AKT and suppressing the NF-κB/MAPK pathways

Ethnopharmacological relevance: Baihe Gujin Pill (BHGJP) is a traditional Chinese medicine (TCM) derived from the "Collection of Medical Formulas". BHGJP is applied to treat lung and kidney deficiency by nourishing yin and clearing heat. However, the role and preventative mechanism of BHGJP in cisplatin induced acute kidney injury (CIAKI) are poorly understood.

Aim of the study: The preventative effect of BHGJP on CIAKI by the in vitro and in vivo experiments based on network pharmacology was investigated.

Methods: Network pharmacology was used to predict the protective effect of BHGJP on CIAKI. The effect and mechanism of BHGJP against CIAKI were detected and verified by the in vitro kidney cells 293T and HK-2 as well as the in vivo mice model established by a single injection of cisplatin.

Results: Network pharmacology predicted that BHGJP prevented CIAKI by regulating PI3K/Akt and NF-κB/MAPK signaling pathways. BHGJP could reverse the reduced cell viability of HK-2 and 293T cells caused by cisplatin without decreasing its cytotoxic effects on H460, H1299, and A549 cells. Meanwhile, BHGJP effectively controlled kidney injury in the CIAKI model. Moreover, cisplatin induced cell Apoptosis and accumulation of Reactive Oxygen Species (ROS) were downregulated after treatment with BHGJP. The changes of oxidative stress indexes of GSH, MDA, and SOD as well as the inflammatory factors of TNF-α, IL-6, and IL-1β in the CIAKI model were recovered to normal state when BHGJP treatment. Furthermore, BHGJP activated PI3K/Akt pathway and suppressed the NF-κB/MAPK pathway in the CIAKI model.

Conclusion: The study found that BHGJP prevented CIAKI by inhibiting Apoptosis, oxidative stress, and inflammation via regulating PI3K/Akt and NF-κB/MAPK pathways, providing new efficacy and clinical applications for BHGJP.

Acute kidney injury; Cisplatin; Mechanism; Network pharmacology; Traditional Chinese medicine.