Brucea javanica (L.) Merr Seed Extract Exerts Antihypertensive and Renoprotective Activity in Renovascular Hypertensive Mice Model
Abstract
BACKGROUND: Renovascular hypertension (RVH) drives excessive renin-angiotensin-aldosterone system (RAAS) activation, oxidative stress, and vascular remodelling, but most of current RVH therapies may not fully prevent the disease progression. Brucea javanica seed is known to contain bioactive compound that modulate RAAS and regulate blood pressure, but their effects on RVH remain unclear. This study was conducted to evaluate the potential of B. javanica seed extract (BJSE) as antihypertensive and renoprotective effects.
METHODS: BJSE were profiled using liquid chromatography–high resolution mass spectrometry (LC-HRMS) and antioxidant activity was assessed. Network pharmacology and molecular docking were conducted to identify compound–protein targets. Male BALB/c mice was RVH-induced by renal blood flow restriction surgery and received either: no treatment, captopril, or, 10, 20, 30 mg/kg BW BJSE. Healthy mice were also included as control. Blood pressure, urinalysis, haematology, renal function, gross pathology, and kidney-heart histology were evaluated.
RESULTS: Ten major metabolites were identified, including flavonoids, phenolic acids, and terpenoids. Antioxidant assays showed IC50 values of 71.81±0.35 ppm (DPPH), 76.30±0.29 ppm (FRAP), and 49.45±0.26 ppm (ABTS). Network pharmacology revealed five hub genes (matrix metallopeptidase 9 (MMP9), peroxisome proliferator-activated receptor gamma (PPARG), nitric oxide synthase 3 (NOS3), angiotensin-converting enzyme (ACE), estrogen receptor 1 (ESR1)), further molecular docking showed phloretin has the highest potential binding with ACE mapped to RAAS. BJSE dose-dependently reduced systolic blood pressure, proteinuria, blood urea nitrogen (BUN), and creatinine, improved erythrocyte parameters and leukocyte counts, and attenuated renal atrophy, cardiac hypertrophy, and histopathological lesions.
CONCLUSION: BJSE significantly reduced blood pressure and improved cardiac and renal histopathological profiles, as well as hematological and urinary parameters associated with renoprotective activity. These effects are achieved suggested due to its antioxidant activity and multi-targeted mechanisms.
KEYWORDS: polycystic ovary syndrome, Brucea javanica, network pharmacology, renin-angiotensin-aldosterone system, renovascular hypertension, two-kidney-one-clip
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DOI: https://doi.org/10.18585/inabj.v18i5.4431
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