Baicalin-Geniposide combination modulates microglia polarization against chronic cerebral ischemia and concomitant kidney injury via the HIF-1α/EPO/NF-κB pathway

Abstract

Background

Baicalin and geniposide combination (BC/GD), a traditional Chinese medicine pairing, is beneficial for chronic cerebral ischemia (CCI) and kidney injury, but the underlying mechanism remains unknown.

Methods

Using network pharmacology, we identified targets and pathways of BC/GD in CCI and kidney injury. Using molecular docking, we discovered the affinity between BC/GD and the key targets HIF-1α, EPOR, and TNF-α. Then, these were verified in SD rats and transwell co-cultures of HMC3 and HK-2 cells.

Results

Experimental validation demonstrated that BC/GD ameliorated cerebral and kidney pathological injury, cognitive impairment, and kidney dysfunction, increased cerebral blood flow, inhibited microglia activation and polarization of pro-inflammatory phenotypes, increased the expression of HIF-1α and EPOR, and reduced the phosphorylation of NF-κB and the level of pro-inflammatory factors in CCI rats. Then, in vitro validation experiments, we found that 12.5 μM and 25 μM BC/GD significantly increased the levels of anti-inflammatory factors and modulated the HIF-1α/EPO/NF-κB pathway in oxygen-glucose-deprived HMC3 and HK-2 cells, which was partially antagonized by PX-478, an inhibitor of HIF-1α.

Conclusion

BC/GD alleviated cerebral and kidney inflammatory injury, and its mechanism may be related to the modulation of microglia polarization through HIF-1α/EPO/NF-κB.