Pachyman Relieved the BPPV Progression in Slc26a4 loop/loop Mutant Mice Through Regulating the TLR2-mediated NF-κB Pathway

BACKGROUND: Benign paroxysmal positional vertigo (BPPV) is a peripheral vestibular disorder characterized by brief episodes of vertigo triggered by changes in head position. Pachyman, a bioactive polysaccharide derived from the medicinal mushroom Poria cocos (also known as Fu Ling), exhibits diverse biological activities and shows promising applications in pharmaceutical development and functional foods. This study aimed to explore the therapeutic potential of pachyman in BPPV progression. METHODS: Slc26a4loop/loop mutant mice were used to simulate the BPPV progression in vivo. The mice were orally administered of pachyman, injected with TLR2 overexpression vector and BAY-11-7082. The air righting reflex accuracy, contact righting reflex evaluation, time of contact righting reflex, and the scores of head tilt and swimming behavior were recorded. In addition, the TLR2 expression and NF-κB pathway were detected by RT-qPCR and western blot assays. RESULTS: Pachyman treatment increased the accuracy rate of contact righting reflex, decreased the time of contact righting reflex and the scores of head tilt and swimming behavior. TLR2 was increased in the BPPV patients and Slc26a4loop/loop mutant mice, while pachyman treatment decreased it. In addition, TLR2 overexpression reversed the role of pachyman in Slc26a4loop/loop mutant mice. Furthermore, TLR2 overexpression activated NF-κB pathway. After BAY-11-7082 treatment, the role of TLR2 overexpression vector in pachyman-treated Slc26a4loop/loop mutant mice was reversed. CONCLUSION: Pachyman relieved the BPPV-related vestibular deficits in Slc26a4loop/loop mutant mice through inhibiting the TLR2-mediated NF-κB pathway.