Abstract
Neuroinflammation in the hypothalamic paraventricular nucleus (PVN) can contribute to sympathetic excitation and hypertension. We evaluated a Styphnolobium japonicum bud extract (SJBE; historically Sophora japonica) quantified for rutin and quercetin by targeted high-performance liquid chromatography (HPLC). The extract was tested in angiotensin II (Ang II)-stimulated BV-2 microglia, BV-2/mHypoA-2/10 soluble-factor co-cultures, an in vitro high-sodium neuronal-stress condition, and rats with Nω-nitro-L-arginine methyl ester (L-NAME)-induced nitric-oxide-deficiency hypertension. At non-cytotoxic working concentrations, SJBE reduced inflammatory and oxidative-stress endpoints in BV-2 cells and was associated with higher angiotensin-converting enzyme 2 (ACE2), Mas receptor (MasR), and angiotensin-(1-7) [Ang-(1-7)] markers. In co-culture, SJBE reduced inflammatory transfer and neuronal stress. Oral SJBE lowered tail-cuff blood-pressure measurements and was associated with higher PVN ACE2/MasR and Ang-(1-7), lower Iba-1 and c-Fos staining, and lower circulating norepinephrine and cytokines. MLN-4760 provided in vitro functional support for ACE2 involvement, but no in vivo pathway blockade or brain-exposure pharmacokinetics were performed. The results therefore support an association between SJBE treatment, reduced neuroinflammatory signaling, and lower blood pressure, without establishing central-pathway causality.