Salvia miltiorrhiza Bunge (Danshen) and Bioactive Compound Tanshinone IIA Alleviates Cisplatin-Induced Acute Kidney Injury Through Regulating PXR/NF-κB Signaling

Abstract

Objective: The present study aims to provide evidence on the potential protective role of Salvia miltiorrhiza Bunge (Danshen) and its bioactive compound Tanshinone IIA (TanIIA) in AKI and to reveal the specific regulatory function of PXR/NF-κB signaling in AKI-induced renal inflammation.Methods: A network pharmacological analysis was used to study target genes and regulatory networks in the treatment of Salvia miltiorrhiza on AKI. Further experiments with in vivo AKI mouse model and in vitro studies were applied to investigate the renal protective effect of TanIIA in AKI. The mechanisms of TanIIA regulating PXR/NF-κB signaling in renal inflammation were also studied.Results: Network pharmacology had suggested the nuclear receptor family as new therapeutic targets of Salvia miltiorrhiza in AKI treatment. The in vivo studies had demonstrated that TanIIA improved renal function and inflammation by reducing necrosis and promoting the proliferation of tubular epithelial cells. Improved renal arterial perfusion in AKI mice with TanIIA treatment was also recorded by ultrasonography. In vitro studies had shown that TanIIA ameliorated renal inflammation by activating the PXR while inhibiting PXR-mediated NF-κB signaling. The results had suggested a role of PXR activation against AKI-induced renal inflammation.Conclusion:Salvia miltiorrhiza Bunge (Danshen) may protect the kidneys against AKI by regulating nuclear receptors. TanIIA improved cell necrosis proliferation and reduced renal inflammation by upregulating the expression of the PXR and inhibiting NF-κB signaling in a PXR-dependent manner. The PXR may be a potential therapeutic target for AKI treatment.

Research Progress on Regulation of Immune Response by Tanshinones and Salvianolic Acids of Danshen (Salvia miltiorrhiza Bunge)

“…Sustained-release preparations can markedly prolong the in vivo coexistence of tanshinone IIA, tanshinol, protocatechuic aldehyde, and salvianolic acid B in Danshen compared to the commercial Danshen capsules to enhance their overall effects [ 20 ]. Tanshinone IIA isolated from Danshen can alleviate cisplatin-induced acute kidney injury through the regulation of PXR/NF-κB signaling [ 21 ].…”

In Silico Analysis of Pyeongwi-San Involved in Inflammatory Bowel Disease Treatment Using Network Pharmacology, Molecular Docking, and Molecular Dynamics

“…Since traditional formulae in traditional Korean medicine are used in combination with various medicinal substances, network pharmacology from a holistic perspective plays an important role in understanding the effects and mechanisms of herbal medicines. For example, using network pharmacological analysis, Zhou and Wu showed that the mitogen-activated protein kinase pathway is a potential pharmacological pathway of Eucommiae cortex against osteoporosis [ 3 ], and Dou et al reported the protective effect of tanshinone II in Salvia miltiorrhiza Bunge in an acute kidney injury model through pregnane X receptor activation [ 4 ].…”