Transcriptomic Analysis Reveals the Potential Mechanism of Cardamine circaeoides Hook.f. & Thomson in Lowering Serum Uric Acid by Reducing Inflammatory State Through CCR7 Target

Abstract

Cardamine circaeoides Hook.f. & Thomson (CC) is a traditional medicinal herb with multiple biological activities. In previous studies, we have identified its serum uric acid (SUA) lowering effects and speculated that Cardamine circaeoides water extract (CCE) may exert anti-hyperuricemia effects related to its anti-inflammatory activity. This study aims to further investigate the molecular mechanism underlying these effects at the mRNA level through transcriptomic analysis, quantitative reverse transcription polymerase chain reaction (RT-qPCR), molecular docking, and Western blotting. CCE effectively reduced SUA and improved renal function in a dose-dependent manner in hyperuricemia rats. Cytokine–cytokine receptor interaction pathway was significantly altered by CCE. An additional study identified a number of genes (IL27, Inhbe, CCR7, CXCR3, IL12RB1, CXCR5, Mstn, and GDF5) as regulators of the inflammatory response. Meanwhile, three key targets (IL27, Inhbe, and CCR7) were found to be significantly expressed at the mRNA level and have strong binding affinity with 22 components, among which Kaempferol 3-sophoroside 7-glucoside, Kaempferol-3-O-sophoroside, and Quercetin 3-sophoroside 7-glucoside have strong binding activities. Following this, Western blotting showed a significant increase in CCR7 expression. Our findings indicated that CCE regulated the cytokine–cytokine receptor interaction pathway through CCR7 to reduce the inflammatory state and exert an SUA-lowering effect.