α-Mangostin reduces hypertension in spontaneously hypertensive rats and inhibits EMT and fibrosis in Ang II-induced HK-2 cells

Hypertension affects a large number of individuals globally and is a common cause of nephropathy, stroke, ischaemic heart disease and other vascular diseases. While many anti-hypertensive medications are used safely and effectively in clinic practice, controlling hypertensive complications solely by reducing blood pressure (BP) can be challenging. alpha-Mangostin, a xanthone molecule extracted from the pericarp of Garcinia mangostana L., has shown various beneficial effects such as anti-tumor, anti-hyperuricemia, and anti-inflammatory properties. However, the effects of alpha-Mangostin on hypertension remain unknown. In this study, we observed that alpha-Mangostin significantly decreased systolic and diastolic blood pressure in spontaneously hypertensive rats (SHR), possibly through the down-regulation of angiotensin II (Ang II). We also identified early markers of hypertensive nephropathy, including urinary N-acetyl-(3-D-glucosaminidase (NAG) and (32-microglobulin ((32-MG), which were reduced by alpha-Mangostin treatment. Mechanistic studies suggested that alpha-Mangostin may inhibit renal tubular epithelial-to-mesenchymal transformation (EMT) by down-regulating the TGF-(3 signaling pathway, thus potentially offering a new therapeutic approach for hypertension and hypertensive nephropathy.