Scubardins A−K, Aromatic Abietane Diterpenoids from Scutellaria barbata and Their Cardiomyocyte Mitophagy-Promoting Activity

Scutellaria barbata D. Don (Lamiaceae), a traditional Chinese medicinal herb, has been reported to possess genes involved in abietane-type diterpenoid biosynthesis, although no such compounds have been isolated previously. In this study, systematic phytochemical investigation of the whole herb of S. barbata led to the discovery of 14 aromatic abietane diterpenoids (1−14), including 11 new compounds (scubardins A−K, 1−11), one new natural product (12), and two known compounds (13 and 14). Among them, scubardins A (1) and B (2) are the first aromatic abietane diterpenoids obtained, wherein a five-membered oxacyclic ring is constructed via an oxygen bridge between C-4 and C-10. Their planar structures were elucidated on the basis of HRESIMS, 1D/2D NMR, UV, and IR data. The absolute configurations were determined using Mosher′s method and electronic circular dichroism (ECD) calculations. Among the isolates, compound 3 emerged as a significant activator of PINK1-dependent mitophagy. This activity enabled it to rescue doxorubicin-impaired mitochondrial function in vitro, as further evidenced by its modulation of mitophagy-related proteins in vivo.