Beta‑caryophyllene improves blood pressure, ECG, and cardiometabolic markers in a rat metabolic sy

Introduction and Rationale

Metabolic syndrome (MS) is an increasing global non‑communicable disease driven in part by high‑calorie dietary patterns and is closely associated with cardiovascular dysfunction. The cost, side effects, and limited access to conventional cardiovascular drugs, especially in lower‑middle‑income countries, motivate evaluation of safe, affordable dietary nutraceuticals for primary prevention. This preclinical study assessed the cardioprotective and preventive potential of beta‑caryophyllene (BCP), a widely available, Generally Recognized As Safe (GRAS) dietary cannabinoid, in a rodent model designed to mimic lifestyle‑related MS.

Study Design and Animal Groups

Seventy‑two male Wistar rats (10 weeks old) were allocated to six groups (n = 12 per group). Groups I and II were normal diet (ND) controls, with Group II receiving BCP (50 mg/kg orally). Metabolic syndrome was induced in Groups III–VI by feeding a High‑Fat High‑Fructose Diet (HF/HFD) for 16 weeks. Following induction, a 4‑week intervention phase assigned the HF/HFD groups to: continued HF/HFD (Group III), HF/HFD + BCP 50 mg/kg p.o. (Group IV), dietary withdrawal to ND (Group V), and ND + BCP (Group VI).

Interventions and Dosing

BCP was administered orally at 50 mg/kg in the designated groups. The HF/HFD protocol lasted 16 weeks to induce MS prior to the 4‑week treatment or withdrawal phase. The source provides dosing and timing but does not report pharmacokinetic or long‑term safety data in this document.

Physiologic and Biochemical Measurements

Conscious hemodynamic variables and electrocardiograms (ECG) were recorded via telemetry. Plasma apolipoprotein‑B (Apo‑B) and C‑reactive protein (CRP) were quantified by ELISA. Standard biochemical assays evaluated lipid profiles and oxidative stress parameters including superoxide dismutase (SOD), reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO). Leptin levels were measured and histopathology of heart, liver, and pancreas was performed using routine staining methods. Statistical analyses used ANOVA with α = 0.05.

Key Hemodynamic and ECG Findings

• In normal‑diet rats, BCP reduced systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, and PR interval when compared with untreated normal‑diet controls.
• In HF/HFD animals, addition of BCP (Group IV) produced significant reductions in SBP and heart rate relative to untreated HF/HFD controls (Group III).

These telemetry‑derived results indicate that BCP modified both resting arterial pressure and cardiac electrical timing in this rodent model.

Lipid, Inflammatory, and Oxidative Stress Results

• BCP increased HDL‑cholesterol and antioxidant markers SOD and GSH in HF/HFD + BCP animals versus HF/HFD alone.
• BCP decreased total cholesterol, Apo‑B, leptin, NO, and MDA in the treated HF/HFD group compared with untreated HF/HFD.
• Triglycerides were reported to decrease in one comparison (Group VI vs Group IV).
• CRP was lowered across all groups receiving BCP when compared with their respective controls.

Collectively, these biochemical changes suggest an anti‑atherogenic, anti‑inflammatory, and antioxidant effect associated with BCP treatment in this model.

Histopathology Findings

HF/HFD‑induced distortion of tissue architecture in the heart, liver, and pancreas observed in untreated MS animals was reported to be completely reversed in HF/HFD animals treated with BCP. The source reports restoration of cytoarchitecture but does not provide detailed quantitative scoring data or representative photomicrographs in this summary.

Interpretation and Mechanisms

The data presented support a multi‑modal effect of BCP in this rodent MS model: improvement in hemodynamic parameters and ECG intervals, favorable modulation of lipid and apolipoprotein profiles, reduction in systemic inflammation (CRP, leptin) and oxidative stress (MDA down; SOD and GSH up), and reversal of organ structural damage. The authors interpret these findings as evidence that BCP exerts anti‑atherogenic, anti‑inflammatory, and antioxidant activities that can ameliorate diet‑induced metabolic and cardiovascular derangements.

Public health implications and Recommendations

The authors propose that integrating BCP‑rich, culturally accepted functional ingredients into regional diets could represent a low‑cost, scalable strategy for non‑communicable disease (NCD) prevention, particularly in resource‑limited settings. The source frames BCP as affordable and widely accessible, suggesting potential for primary prevention via dietary approaches.

Limitations and Preprint Status

This report is a preprint and has not been peer reviewed; the source explicitly states this. Important limitations based on the source text include: the data derive from an animal model and cannot be directly extrapolated to humans without further studies; the preprint does not report human safety, long‑term effects, or clinical dosing guidance; detailed histopathology scoring, full statistical tables, and broader mechanistic experiments are not provided in the abstract text. These gaps should be addressed by peer review and follow‑up studies before clinical recommendations can be made.

Overall, the source documents reproducible preclinical evidence that oral beta‑caryophyllene at 50 mg/kg mitigated several key features of diet‑induced metabolic syndrome and associated cardiovascular dysfunction in rats, supporting further investigation into its translational potential for NCD prevention.