Abstract
Autophagy is a crucial process for maintaining cellular homeostasis by degrading and recycling unnecessary or damaged cellular components. In the process of exploring autophagy regulators in plants, unique nine oligomeric flavonoids linked by the bonding of C-3 and C-4, consisting of three pairs of biflavonoids, linderanidins A–C [(+)-1/(−)-1, (+)-2/(−)-2, and (+)-3/(−)-3], and three trimeric A-type proanthocyanidins, linderanidins D–F (4–6), were isolated from the roots of Lindera erythrocarpa. The structures and absolute configurations of these compounds were determined using various techniques, such as 1D and 2D NMR, mass spectrometry, X-ray crystallography, and electronic circular dichroism. All isolates were evaluated for their ability to regulate autophagy, and compounds (±)-1–(±)-3, (−)-1–(−)-3, (+)-1–(+)-3 and 4 were found to inhibit autophagy by blocking the fusion process between autophagosome and lysosome in HEK293 cells. This study suggests that unique oligomeric flavonoids possessing a C-3–C-4 linkage derived from the roots of L. erythrocarpa are potent autophagy inhibitors.
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