Madecassoside alleviates acute kidney injury by regulating JNK-mediated oxidative stress and programmed cell death.

BACKGROUND: Acute kidney injury (AKI) has high morbidity and mortality, which is manifested by inflammation and apoptosis. Effective treatment methods for AKI are currently lacking. OBJECTIVE: This study demonstrated the protecting effects of Madecassoside (MA) in the cisplatin- and hypoxia-reoxygenation-induced renal tubular epithelial cells in vitro and AKI mice in vivo. METHODS: In vivo AKI mouse models were established by inducing them with cisplatin and renal ischemia-reperfusion. In vitro injury models of mouse renal tubular epithelial cells were established by inducing them with cisplatin and hypoxia and reoxygenation, respectively. The mechanism of MA effects was further explored using molecular docking and RNA-sequencing. RESULTS: MA could significantly reduce kidney injury in the cisplatin-and renal ischemia-reperfusion (IRI)-induced AKI. Further validation in the two cellular models also showed that MA had protect effects. MA can alleviate AKI in vitro and in vivo by inhibiting inflammation, cell apoptosis, and oxidative stress. MA exhibited high permeability across the Caco-2 cell, can enter cells directly. Through RNA-seq and molecular docking analysis, this study further demonstrated that MA inhibits its activity by directly binding to JNK kinase, thereby inhibiting c-JUN mediated cell apoptosis and improving AKI. In addition, MA has better renal protective effects compared to curcumin and JNK inhibitor SP600125. CONCLUSION: The results demonstrate that MA might be a potential drug for the treatment of AKI and act through the JNK/c-JUN signaling pathway.

Preparative Isolation of Piceatannol Derivatives from Passion Fruit (Passiflora edulis) Seeds by High-Speed Countercurrent Chromatography Combined with High-Performance Liquid Chromatography and Screening for α-Glucosidase Inhibitory Activities.

Passiflora edulis Sims (passion fruit) seeds are often discarded as byproducts during juice processing. In fact, the seeds are of considerable commercial value in the food and cosmetics industry because of their rich polyphenols, especially piceatannol. In this study, high-speed countercurrent chromatography (HSCCC) was applied for the separation of stilbene polyphenols from passion fruit seeds. The n-hexane-ethyl acetate-methanol-water (1:2:1:2.8, v/v) was found to be the optimum two-phase solvent for the preparation of two major stilbenes, scirpusin B (8) and piceatannol (9) with purities of 90.2% and 94.8%, respectively. In addition, a continuous semipreparative HPLC was applied to further purify the HSCCC fractions containing minor stilbenes and obtain four new piceatannol derivatives (1-4) along with three known ones (5-7). The structures of these new compounds were determined using spectroscopic methods, including NMR, high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and circular dichroism (CD). The isolated compounds were evaluated for α-glucosidase inhibitory activities in vitro. The result suggested that all of them exhibited more significant activity than acarbose, and passiflorinol B (2) had the strongest activity, with a IC50 value of 1.7 µM.