4.7 Article

Quassinoids from Twigs of Harrisonia perforata (Blanco) Merr and Their Anti-Parkinson's Disease Effect

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Publisher

MDPI
DOI: 10.3390/ijms242216196

Keywords

Harrisonia perforata; quassinoid; simarubaceae; neuroprotection; PC12 cells; PINK1(B9) flies

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In this study, six new C-20 and one new C-19 quassinoids were isolated and identified from the twigs of Harrisonia perforata. Two of these compounds showed significant anti-Parkinson's disease potential in both cell and Drosophila models.
Six new C-20 and one new C-19 quassinoids, named perforalactones F-L (1-7), were isolated from twigs of Harrisonia perforata. Spectroscopic and X-ray crystallographic experiments were conducted to identify their structures. Through oxidative degradation of perforalactone B to perforaqussin A, the biogenetic process from C-25 quassinoid to C-20 via Baeyer-Villiger oxidation was proposed. Furthermore, the study evaluated the anti-Parkinson's disease potential of these C-20 quassinoids for the first time on 6-OHDA-induced PC12 cells and a Drosophila Parkinson's disease model of PINK1(B9). Perforalactones G and I (2 and 4) showed a 10-15% increase in cell viability of the model cells at 50 mu M, while compounds 2 and 4 (100 mu M) significantly improved the climbing ability of PINK1(B9) flies and increased the dopamine level in the brains and ATP content in the thoraces of the flies.

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