Isolation and target identification of anti-renal fibrosis compounds from Cordyceps militaris

Four undescribed compounds including one aromatic glucoside derivative, cordyceglycoside A (1), one new isoleucine derivative inner salt, cordycepisosalt A (2), a rare four-membered lactam, cinerealactam B (3), and one sesquiterpene derivative, cordycepsetp A (4), together with six known compounds were isolated from Cordyceps militaris. The structures including absolute configurations of these new compounds, were unambiguously elucidated by spectroscopic data analysis and single crystal X-ray diffraction. Biological evaluation of compounds 1–4 showed that 3 displays anti-renal fibrotic activities in TGF-β1 induced NRK-52e cells. Furthermore, DARTS coupled with LC-MS/MS analysis was used to identify candidate target proteins for 3. Subsequently, C1qbp knockdown using siRNA allowed us to validate the target protein of 3.