isoxanthohumol and kurarinone

Diabetic retinopathy (DR) is one of the most serious complications of diabetic microangiopathy. Recent studies have shown its close association with high glucose-induced oxidative stress and autophagy disorder. Previous studies showed that various compounds of flavonoids of Sophora flavescens Aiton extracted using ethyl acetate (SFE) could cross the blood-retinal barrier, exerting favorable effects on retinal tissue disorders and angiogenesis in rats with DR. However, the mechanism and the specific material basis for SFE are still unclear. Here, we established the in vitro DR model of human retinal microvascular endothelial cell (HRMECs) induced by high glucose and hypoxia (HGY), screened out the potential pharmacodynamic components of SFE viz. norkurarinone (NKR) and isoxanthohumol (IXM), and proved that they could improve the pathological features of angiogenesis. Further, we explored the mechanism of action of NKR and IXM, investigating their effects on cellular oxidative stress and autophagy levels under HGY conditions. Finally, the role of the PI3K/AKT/mTOR signaling pathway in the regulation of cell autophagy by NKR and IXM was evaluated. Collectively, NKR and IXM could improve cellular oxidative stress state and activate PI3K/AKT/mTOR signaling pathway to regulate autophagy dysregulation, thus playing a significant role in protecting HRMECs from HGY-caused angiogenesis.

Topics: Animals; Autophagy; Diabetic Retinopathy; Endothelial Cells; Flavonoids; Glucose; Humans; Hypoxia; Neovascularization, Pathologic; Oxidative Stress; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; TOR Serine-Threonine Kinases

Radix Sophorae Flavescentis is a traditional Chinese medicine, which is the roots of Sophora flavescens and is used to treat abscess, dysentery, eczema and skin itch. The main active compounds of the roots of Sophora flavescens are alkaloids and flavonoids. To provide reference compounds for HPLC-DAD qualitification analysis of flavanonoids and for study on the bioactivities of flavanonoids, six main flavanonoids were isolated from the roots of Sophora flavescens. They are 5-methoxy-7, 2', 4'-trihydroxy-8-[3,3-dimethylallyl] -flavanone (1), isoxanthohumol (2), 3/beta, 7, 4'-trihydroxy-5-methoxy-8-[3,3-dimethylallyl] -flavanone (3), nor-kurarinone [(2S) -sophoraflavanone G] (4), kurarinone (5) and kushenol I (6). Compound 1 is a new compound, and compound 3 is obtained from Sophora flavecens for the first time. The 13C NMR data of compounds 3 and 5 are reported for the first time.

Topics: Flavanones; Flavonoids; Molecular Structure; Plant Roots; Plants, Medicinal; Sophora; Xanthones