{Reference Type}: Journal Article {Title}: Antihypertensive Potential of Pistacia lentiscus var. Chia: Molecular Insights and Therapeutic Implications. {Author}: Efentakis P;Symeonidi L;Gianniou DD;Mikropoulou EV;Giardoglou P;Valakos D;Vatsellas G;Tsota M;Kostomitsopoulos N;Smyrnioudis I;Trougakos IP;Halabalaki M;Dedoussis GV;Andreadou I; {Journal}: Nutrients {Volume}: 16 {Issue}: 13 {Year}: 2024 Jul 5 {Factor}: 6.706 {DOI}: 10.3390/nu16132152 {Abstract}: Background: Hypertension poses a significant global health burden and is associated with cardiovascular morbidity. Chios mastic gum (CMG), derived from Pistacia lentiscus var. Chia, shows potential as a phytotherapeutic agent, due to its multifaceted beneficial effects. However, its anti-hypertensive effects and vascular, circulatory, and renal-related dysfunction, have not been thoroughly investigated. Herein, we aimed to explore the antihypertensive potential of CMG, focusing on vascular and renal endothelium, in vivo. Methods: Two models of hypertension in male rats, induced by Angiotensin II and Deoxycorticosterone acetate (DOCA)-high-salt administration, were utilized. CMG was administered at 220 mg/kg daily for four weeks after hypertension onset and blood pressure was measured non-invasively. Whole blood RNA sequencing, metabolomics, real-time PCR, and Western blot analyses of kidney and aorta tissues were additionally performed. Results: CMG significantly lowered systolic, diastolic, and mean blood pressure in both models. RNA sequencing revealed that CMG modulated immunity in the Angiotensin II model and metabolism in the DOCA-HS model. CMG downregulated genes related to oxidative stress and endothelial dysfunction and upregulated endothelial markers such as Vegfa. Metabolomic analysis indicated improved endothelial homeostasis via lysophosphatidylinositol upregulation. Conclusions: CMG emerges as a potent natural antihypertensive therapy, demonstrating beneficial effects on blood pressure and renal endothelial function.