Curcumin attenuates NMDA Receptor Phosphorylation on Glutamatergic Terminals and Lowers Blood Pressure in Obese
Kevin John1, Tatiana Bunge1, Kallie Crowl1
1Biochemistry and Nutrition Department, Des Moines University, West Des Moines, IA, United States.
Background:
Obesity significantly increases the risk of hypertension in postmenopausal females, presenting a major cardiovascular health challenge in this population. Conventional antihypertensive therapies exhibit diminished efficacy in these females compared with age-matched males, highlighting a critical gap in current treatment strategies. Curcumin, a bioactive compound with documented antihypertensive properties, represents a promising therapeutic candidate. However, its effectiveness and the underlying mechanisms in the context of obesity and estrogen deficiency remain poorly understood.
Objectives:
This study aimed to determine whether curcumin attenuates hypertension progression in an obese postmenopausal model by modulating glutamatergic signaling through suppression of NMDAR phosphorylation.
Methods:
Eight-week-old male and female C57/BL mice were randomly divided into 3 groups (n = 24/group) and given ad libitum access to their respective diets [low-fat piperine (10% kcal from fat); high-fat piperine (60% kcal from fat); high-fat curcumin (60% kcal from fat)] for 17 wk. Piperine (200 μL of a 10% solution of piperine) or curcumin (300mg of curcumin per 200 μL + 10% piperine solution) was administered to animals daily, via gavage, during the last 4 wk of the study. The female mice were further divided into groups identified as sham-operated (SHAM; ovaries intact - estrogen replete) and ovariectomized (OVX; ovaries removed - estrogen depleted). Food and body weight were measured weekly. At the end of the study, glucose, retroperitoneal fat pads, and systolic blood pressure were measured. The hypothalamus was extracted from a subpopulation of mice to conduct Western blot analysis. The remaining animals in the study were transcardially perfused for histological analysis.
Results:
Curcumin treatment significantly attenuated the hypertension (P < 0.0162) and the weight gain (P < 0.0001) observed in OVX mice fed a high-fat diet. Western blot analysis of hypothalamic tissue revealed a marked reduction in NMDAR phosphorylation (pNMDAR) after curcumin administration (P = 0.001) compared with controls. Consistent with these findings, histological analysis demonstrated decreased pNMDAR expression within the PVN and the rostral ventrolateral medulla, mirroring the biochemical results. Notably, curcumin exerted no effect on NMDAR phosphorylation in lean or obese male mice (P = 0.3431) and SHAM females (P = 0.2804).
Conclusions:
Collectively, these findings highlight a potential mechanism in which curcumin targets to lower blood pressure specifically under conditions of obesity and estrogen deficiency. However, additional studies are warranted to determine whether this mechanism is a direct or indirect effect of curcumin.
