A Novel Herbal Combination of Cistus ladaniferus, Petroselinum crispum, and Rosmarinus officinalis (CCPR) for Managing Hypertension: Enhanced Efficacy through Synergistic Antioxidant and Hypotensive Effects

Abstract

Herbal formulations offer an intriguing option for managing various health concerns, including hypertension. This study investigated the pharmacological and safety profiles of a newly designed combination product (CCPR), which includes extracts of Cistus ladaniferus (CLE), Petroselinum crispum (PCE), and Rosmarinus officinalis (ROE). Additionally, the pharmacokinetic potential of the CCPR components was analyzed using in silico methods. The study screened in vitro antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, while its efficacy was further validated through a non-invasive hypotensive test. Synergistic interactions among the extracts were evaluated using an interaction index. Based on these results, the optimized combination CCPR underwent acute toxicity and antihypertensive testing. Pharmacokinetic parameters were predicted using the SwissADME platform. The results demonstrated that CCPR exhibited the highest antioxidant activity, correlating with its hypotensive effect. The administration of CCPR at a dose of 250 mg/kg/day significantly reduced systolic blood pressure (SBP) compared to other combinations. Furthermore, interaction index analysis confirmed the synergistic effects of the extracts within CCPR. The antihypertensive tests indicated that CCPR, at doses of 125 and 250 mg/kg, significantly lowered SBP and improved oxidative stress markers compared to both the standard antihypertensive drug “Enalapril” (15 mg/kg/day) and the hypertensive model group treated with L-NAME (40 mg/kg/day). The acute toxicity test confirmed the safety of CCPR, showing no abnormalities at a single dose of 2 g/kg. In silico pharmacokinetic analysis revealed favorable properties for the major compounds in CCPR, including high absorption and minimal adverse effects, supporting its suitability for long-term use. In conclusion, the findings of this study indicate that CCPR has the potential to be an effective formulation for managing hypertension. This formulation presents a valuable approach for the pharmaceutical industry, particularly for developing dietary supplements or as adjunctive therapy