Beta-caryophyllene restores blood pressure, heart rate, and electrocardiographic alterations while mitigating cardiometabolic biomarkers in a rat model of metabolic syndrome: Implications for non-communicable disease prevention.

Background: Metabolic Syndrome (MS) is an escalating non-communicable disease (NCD) and public health crisis heavily driven by modern high-calorie dietary transitions. MS is closely linked to catastrophic cardiovascular dysfunction (CVD). Conventional CVD medications are frequently constrained by high financial costs, system-wide adverse effects, and poor population-level accessibility in lower-middle-income countries (LMICs). This underscores an urgent public health need to evaluate safe, scalable, and low-cost dietary nutraceuticals for primary prevention. This study evaluated the cardioprotective and preventative effects of Beta-caryophyllene (BCP)--an affordable, widely accessible, and GRAS-designated dietary cannabinoid--in a lifestyle-mimicking rodent model of MS. Methods: Seventy-two male Wistar rats (10 weeks old) were divided into six groups (n=12/group). Groups I and II served as controls given Normal Diet (ND) alone and ND+{beta}-caryophyllene (50 mg/kg p.o.), respectively. Metabolic Syndrome was induced in Groups III-VI using a High-Fat High-Fructose Diet (HF/HFD) for 16 weeks. For the subsequent 4 weeks, Group III continued on HF/HFD, Group IV received HF/HFD + BCP (50 mg/kg p.o.), Group V underwent dietary withdrawal (returned to a normal diet [ND]), and Group VI received ND + BCP. Conscious hemodynamic variables and electrocardiograms (ECG) were recorded via telemetry. Plasma apolipoprotein-B (Apo-B) and C-reactive protein (CRP) were quantified using ELISA. Lipid profiles, oxidative stress parameters, and organ histopathology were evaluated using standard biochemical and staining methods, with data analysed using ANOVA at = 0.05. Results: In Group II, BCP decreased SBP (145.00{+/-}12.13 vs 120.30{+/-}2.15 mmHg), DBP (105.70{+/-}10.80 vs 94.00{+/-}17.20 mmHg), heart rate (448.00{+/-}11.90 vs 280.00{+/-}18.70 beats/min), and PR-interval (49.50{+/-}3.53 vs 45.00{+/-}12.70 ms) compared with Group I. Group IV significantly decreased SBP (129.00{+/-}1.28 vs 125.5{+/-}11.1 mmHg) and heart rate (380.00{+/-}16.20 vs 351.00{+/-}3.00 beats/min) compared with Group III. Furthermore, BCP significantly increased HDL-cholesterol (10.80{+/-}1.70 vs 15.40{+/-}1.00 mg/dl), SOD (0.35{+/-}0.07 vs 0.76{+/-}0.30 U/mg protein), and GSH (1.64{+/-}0.02 vs 3.60{+/-}0.13 mM) in Group IV compared with Group III. Conversely, BCP significantly decreased total cholesterol (166{+/-}31.00 vs 113{+/-}18.50 mg/dl), Apo-B (26.70{+/-}1.68 vs 19.00{+/-}1.30 mg/dl), leptin (5.10{+/-}0.03 vs 2.18{+/-}0.01 ng/ml), NO (6.30{+/-}0.40 vs 4.30{+/-}2.61 M), and malondialdehyde (11.80{+/-}4.10 vs 9.90{+/-}2.30 M) in Group IV. BCP significantly decreased triglycerides (64.90{+/-}1.30 vs 55.90{+/-}1.30 mg/dl) in Group VI compared with Group IV, while lowering CRP across all groups. Distortion of the cytoarchitecture of the heart, liver, and pancreas observed in Group III was completely reversed by BCP treatment in Group IV. Conclusion: Beta-caryophyllene effectively ameliorates diet-induced metabolic syndrome and associated cardiovascular dysfunction via potent anti-atherogenic, anti-inflammatory, and antioxidant mechanisms. These findings suggest that integrating affordable, culturally accepted, BCP-rich indigenous functional ingredients into regional nutrition frameworks represents a highly scalable, low-cost public health strategy for global NCD prevention. Keywords: Cardiovascular dysfunction, Metabolic Syndrome, Beta-caryophyllene, High-fat-high-fructose diet, Public Health Nutrition, NCD Prevention.