Awei-5 protects against posterior circulation ischemic vertigo by modulating oxidative stress and the HIF-1α/VEGF

Awei-5 (AW-5) is a classic Traditional Mongolian Medicine formula with a centuries-long history. It has traditional functions of activating blood circulation and treating 'Head Heyi' (Wind-stroke). Clinically, it is widely used for vertigo and posterior circulation ischemic vertigo (PCIV), though its molecular mechanisms remain elusive.

This study aimed to identify the bioactive components of AW-5 and investigate its neuroprotective effects and underlying molecular mechanisms against PCIV using an integrated pharmacological strategy.

UPLC-Q-TOF/MS analysis and Network pharmacology were employed to screen active components and predict core targets. A rat PCIV model was established to evaluate neuroprotection via behavioral tests, Nissl staining, and oxidative stress assays. The regulation of the HIF-1α/VEGF pathway was assessed through immunohistochemistry, qRT-PCR, and Western blotting, followed by molecular docking verification.

Network analysis identified the HIF-1 signaling pathway as a core therapeutic target. In vivo, AW-5 significantly alleviated behavioral deficits and neuronal damage. It effectively mitigated oxidative stress by reducing MDA levels and restoring SOD and GSH-PX activities. Furthermore, AW-5 significantly upregulated the mRNA and protein expressions of HIF-1α and VEGF, promoting an adaptive angiogenic response. Molecular docking confirmed strong binding affinities between key AW-5 ingredients and HIF-1α.

AW-5 exhibits significant neuroprotective potential against PCIV by suppressing oxidative stress and activating the HIF-1α/VEGF pathway to facilitate angiogenic repair and neuronal survival. This study provides a solid scientific basis for its traditional clinical application, offering promising avenues for novel therapeutic strategies and drug discovery.