Alstoniaschines A‒I, nine undescribed alkaloids from Alstonia scholaris and their potential medicinal effects on diabetic nephropathy

Alstoniaschines A‒I (1–9), nine previously alkaloids sharing five different skeletons were obtained from the leaves of Alstonia scholaris. The structures and absolute configurations were established by their extensive spectroscopic data analyses, including NMR, HRESIMS, X-ray crystallography data, and theoretical ECD calculations. Compounds 1, 2, 3, and 9 exerted significant protective effect against oxidative stress and inflammatory damage of podocytes induced by high glucose, manifesting as the increase of superoxide dismutase, catalase, glutathione peroxidase, alongside the reductions of malondialdehyde, nitric oxide, lactate dehydrogenase. Moreover, the bioactive compounds might intervene in diabetic nephropathy through JAK2/STAT3 signaling pathway by suppressing gene expressions of jak2, stat3, and il-6 in high glucose-induced MPC5 cells.