Development and pharmacological evaluation of Evodia rutaecarpa extract-based transdermal gels: a novel approach for hypertension management

Objective Alkaloids from Evodia rutaecarpa exhibit strong antihypertensive and antioxidant effects, but oral administration suffers from low bioavailability. This study aimed to develop and optimize a transdermal gel patch containing a vinegar–water extract of E. rutaecarpa to enhance therapeutic efficacy.Methods Gel formulations were optimized using single-factor tests and a Box–Behnken design (BBD), with adhesion and organoleptic properties as evaluation indices. In vitro permeation and kinetic modeling were used to characterize drug release, while antihypertensive effects were assessed in L-NAME-induced hypertensive rats. Serum lactate dehydrogenase (LDH), atrial natriuretic peptide (ANP), estradiol (E2), testosterone (T), and interleukin-6 (IL-6) were quantified by ELISA. Histopathological evaluation of the heart, kidney, and aorta was also performed.Results Optimized formulation: NP-700 (6.8 g), DAA (0.15 g), PVP K-90 (0.1 g), tartaric acid (0.15 g), glycerol (25 g), and distilled water (60 g). In vitro, the 72 h cumulative permeation of dehydroevodiamine, evodiamine, and rutaecarpine was 302.64 ± 0.74, 129.11 ± 0.41, and 41.50 ± 0.14 μg·cm−2, respectively. The release kinetics fitted the Weibull model. In the L-NAME–induced hypertensive rats, patch treatment reduced systolic blood pressure (SBP) from 158.5 ± 4.9 to 122.5 ± 2.5 mmHg (p < 0.001) and significantly restored serum LDH, ANP, IL-6, E2, and T (p < 0.05). Histological analysis showed attenuation of myocardial hypertrophy and fibrosis, endothelial injury and smooth muscle proliferation, and reduced renal edema, tubular atrophy, and inflammatory infiltration.Conclusions The E. rutaecarpa vinegar–water extract gel patch exhibited marked antihypertensive activity and protection against target organ damage, highlighting its promise as a novel transdermal therapy for hypertension.