Ameliorative Effects of Citrus Unshiu Peel Extract in Cellular and Mouse Models of Pelizaeus-Merzbacher Disease.

Hypomyelinating leukodystrophy 1 (HLD1), also known as Pelizaeus-Merzbacher disease (PMD), is a severe X-linked hereditary hypomyelinating/demyelinating disorder caused primarily by genomic duplications or multiplications that lead to the increased expression of proteolipid protein 1 (PLP1). Aberrant PLP1 expression impairs oligodendrocyte differentiation and disrupts myelin formation in the central nervous system (CNS). Despite decades of research, effective disease-modifying therapies remain unavailable. In the present study, we investigated the potential of Chinpi, the Citrus Unshiu Peel extract commonly utilized in traditional herbal medicine and reported to protect cells from various cellular stresses, using both in vitro cellular and in vivo animal models of PMD. Using an FBD-102b oligodendrocyte precursor model cell line engineered to overexpress PLP1, we demonstrated that treatment with Chinpi significantly ameliorates critical defects in morphological differentiation and successfully restores the expression of major myelin proteins. Furthermore, oral administration of Chinpi to PLP1 transgenic mice improves myelin protein expression in the brain and significantly alleviates progressive motor incoordination, as assessed by behavioral tests. Taken together, these findings suggest that Chinpi exerts protective effects against PLP1-induced morphological differentiation defects and subsequent reductions in myelin protein expression, highlighting its potential as a recovery approach for PMD.