Cardiovasc Toxicol. 2026 Jun 25;26(7):66. doi: 10.1007/s12012-026-10139-2.
ABSTRACT
Hypertension increases the risk for cardiovascular and cerebrovascular diseases and both its preventive and current therapeutics measures require extensive investigations. Despite that Gastrodin, a neuroprotective compound extracted from a Traditional Chinese medicine (TCM), reportedly has preventive and curative potentials in hypertensive patients, its molecular mechanisms in lowering blood pressure still remain obscure. This study was designed to test the hypothesis that gastrodin lowers blood pressure by targeting the PPAR-γ/NF-κB/NLRP3 signaling axis in the hypothalamic paraventricular (PVN). Gastrodin or vehicle (artificial cerebrospinal fluid, aCSF) was directly infused into the PVN through a mini osmotic pump for 28 days to Spontaneous hypertensive rats (SHRs) and Wistar Kyoto (WKY). Four groups of rats were set: WKY + PVN vehicle; WKY + PVN Gastrodin; SHR + PVN vehicle; and SHR + PVN Gastrodin. Blood pressure was monitored and at the conclusion of experiment, plasma and PVN samples were collected and processed for ELISA, PCR, Western blotting and Immunofluorescence analyses. SHRs had elevated blood pressure (BP), heart rate (HR) and plasmatic norepinephrine (NE) validating their hypertensive status. PVN micro-infusion of gastrodin markedly reversed these hypertensive features in SHRs. At molecular level, gastrodin attenuated the local production of reactive oxygen species (ROS), reduced NADPH Oxidases (NOX)2 and NOX4 messenger RNA (mRNA) level and attenuated the activation of PPAR-γ in the PVN. In addition, gastrodin reduced the inflammasome activation and the expression of interleukin-1β (IL-1β). Furthermore, pretreatment with gastrodin reduced the expression of caspase-1 p10 and inflammation (IL-1β and MCP-1), the ratio of phosphorylated kappa B kinase (p-IKK)/IKK, and that of p-p65/p65 in the PVN of SHRs. In conclusion, gastrodin-lowered blood pressure is associated with balanced PPAR-γ/NF-κB/NLRP3 signaling axis within the PVN local highlighting its promising properties in the management of hypertension.
PMID:42348022 | DOI:10.1007/s12012-026-10139-2