Andaliman fruit (Zanthoxylum acanthopodium DC.) Improves Physiological Condition in Preeclamptic Rat through Angiotensin II Receptor Type 1 Inhibition

Background: Preeclampsia (PE) is a severe pregnancy complication involving the AT1R overactivation. Andaliman fruit showed potential for managing preeclampsia, but their effects on the renin-angiotensin system are not well-known. This study aimed to virtually analyze angiotensin II type 1 receptor (AT1R) inhibition by Andaliman Fruit (Zanthoxylum acanthopodium DC.) bioactive compounds and evaluated the effect through an in vivo approach. Methods: The AT1R protein structure was modeled from the AT1R gene, and computational analysis was performed to identify potential molecules to inhibit AT1R. Wistar rats (n=25) were divided into five groups: normal pregnancy, PE pregnancy, PE + candesartan 5 mg/ kg, PE + Andaliman 100 mg/ kg BW, and PE + Andaliman 200 mg/ kg BW. Blood pressure and proteinuria levels were measured on days 5, 13, and 21 of pregnancy. Serum and kidney Angiotensin-Converting Enzyme (ACE) levels were measured by ELISA, and kidney TNF-alpha levels by dot blotting. Results: Kaempferol was indicated as the most potential compound to inhibit AT1R. In the late gestation period, Andaliman treatment significantly improved the blood pressure (124.5 mmHg) compared to the PE group (174.1 mmHg) (P < 0.01). Proteinuria level showed improvement in a dose-dependent manner. Serum and kidney ACE levels were downregulated significantly (P < 0.05) at the highest dose of Andaliman (17.6 and 19.9 ng/mL), as well as the kidney TNF-alpha expression (12,503,447 INT/mm²). Conclusion: The study result found bioactive compounds from Andaliman possibly inhibited AT1R to return the blood pressure to normal level, improved proteinuria condition, and lowered the ACE and TNF-alpha protein levels.