Pharmacological Characteristics of the Hydroethanolic Extract of Acmella oleracea (L) R. K. Jansen Flowers: ADME/Tox In Silico and In Vivo Antihypertensive and Chronic Toxicity Evaluation

Emanuelle T Rodrigues; Paulo Peretti; Roberto M Bezerra; Manoel F Biancardi; Francisco F O Sousa; Elizabeth P Mendes; João B R Dutra; Carla C R Silveira; Carlos H Castro; Jorddy N Cruz; Cleydson B R Santos; Fernanda C A Santos; Mayara T Pinheiro

doi:10.1155/2023/1278720

Pharmacological Characteristics of the Hydroethanolic Extract of Acmella oleracea (L) R. K. Jansen Flowers: ADME/Tox In Silico and In Vivo Antihypertensive and Chronic Toxicity Evaluation

Evid Based Complement Alternat Med. 2023 Apr 29:2023:1278720. doi: 10.1155/2023/1278720. eCollection 2023.

Authors

Emanuelle T Rodrigues^{1

2}, Paulo Peretti^{1

2}, Roberto M Bezerra^{2

3}, Manoel F Biancardi⁴, Francisco F O Sousa⁵, Elizabeth P Mendes⁶, João B R Dutra^{6

7}, Carla C R Silveira^{6

7}, Carlos H Castro^{6

7}, Jorddy N Cruz¹, Cleydson B R Santos^{1

8}, Fernanda C A Santos³, Mayara T Pinheiro^{1

2}

Affiliations

¹ Laboratory of Biotechnology in Natural Products, Faculty of Pharmacy, Department of Biological and Health Sciences, Federal University of Amapá, Macapá, Amapá, Brazil.
² Graduate Program in Health Sciences, Department of Biological and Health Sciences, Federal University of Amapá, Macapá, Amapá, Brazil.
³ Laboratory of Atomic Absorption and Bioprospecting, Department of Biological and Health Sciences, Federal University of Amapá, Macapá, Amapá, Brazil.
⁴ Department of Histology, Embryology and Cell Biology, Laboratory of Microscopy Applied to Reproduction, Institute of Biological Sciences, Federal University of Goiás, Goiânia, Goiás, Brazil.
⁵ Laboratory of Quality Control and Bromatology, Faculty of Pharmacy, Department of Biological and Health Sciences, Federal University of Amapá, Macapá, Amapá, Brazil.
⁶ Department of Physiological Sciences, Institute of Biological Sciences, Federal University of Goiás, Goiânia, Goiás, Brazil.
⁷ Integrated Laboratory of Cardiovascular and Neurological Pathophysiology, Federal University of Goiás, Goiânia, Goiás, Brazil.
⁸ Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapá, Amapá, Brazil.

Abstract

Acmella oleracea (L.) R. K. Jansen, popularly known as jambu in Northern Brazil, is widely used in folk medicine and local cuisine. Its consumption in different ways reinforces the need for safety assessments. In this study, the major compounds found in the hydroethanolic extract of A. oleracea flowers (EHFAO) were characterized by ultra-performance liquid mass spectrometry (UHPLC-ESI-QTOF-MS/MS). The effects of oral administration of 100/mg/kg of EHFAO extract over 60 days in male spontaneously hypertensive (SHR) and Wistar (WR) rats and the in silico ADME/Tox predictions, lipophilicity, and water solubility were accomplished for the compounds identified. Spilanthol was detected as the foremost major compound at a concentration of 97.7%, followed by 1.53% scopoletin and 0.77% d-limonene. The treatment with EHFAO did not alter the animals´ weight over the studied period. Moderate alterations were observed solely in the hepatic enzymes AST (WR = 97 UI/L and SHR = 150 UI/L ^∗ p < 0.05) and ALT (WR = 55 UI/L and SHR = 95 UI/L ^∗ p < 0.05), while no relevant histopathological alterations were found. The in-silico study confirmed the in vivo findings, as the identified compounds were considered highly bioactive orally, due to their drug similarity profiles, adequate lipid solubility, bioavailability, and pharmacokinetics. Therefore, the chronic treatment with EHFAO was found safe at the concentration of 100/mg/kg, with no interference in the blood pressure levels neither appreciable toxic effects.