Bioassay-guided identification of antithrombotic compounds from Cnidoscolus aconitifolius (Mill.) I. M. Jhonst.: molecular docking, bioavailability, and toxicity prediction

Abstract

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Conventional antithrombotic therapy has reported hemorrhagic accidents. Ethnobotanical and scientific reports point to Cnidoscolus aconitifolius as an antithrombotic adjuvant. Previously, C. aconitifolius leaves ethanolic extract displayed antiplatelet, anticoagulant, and fibrinolytic activities. This work aimed to identify compounds from C. aconitifolius with in vitro antithrombotic activity through a bioassay-guided study. Antiplatelet, anticoagulant, and fibrinolytic tests guided the fractionation. Ethanolic extract was subjected to a liquid–liquid partitioning, followed by vacuum liquid, and size exclusion chromatography to obtain the bioactive JP10B fraction. The compounds were identified through UHPLC-QTOF-MS, and their molecular docking, bioavailability, and toxicological parameters were determined computationally. Kaempferol-3-O-glucorhamnoside and 15(S)-HPETE were identified; both showed affinity for antithrombotic targets, low absorption, and safety for human consumption. Further in vitro and in vivo evaluations will better understand their antithrombotic mechanism. This bioassay-guided fractionation demonstrated that C. aconitifolius ethanolic extract has antithrombotic compounds.

Communicated by Ramaswamy H. Sarma

Keywords:

• Bioassay-guided fractionation
• antiplatelet
• anticoagulant
• fibrinolytic
• antithrombotic
• Cnidoscolus aconitifolius
• flavonoid
• eicosanoid
• bioactive compound

Acknowledgments

The authors thank to CONACYT for national scholarship 861074 and project 316633.

Authors’ contributions

Juan Pablo Quintal Martínez: Methodology, Formal Analysis, Investigation, Wrting—Original Draft, Writing—Review & Editing, Visualization. Irma Guadalupe Quintal Ortiz: Methodology, Writing—Reviewing & Editing. Ligia Gabriela Alonzo Salomón: Methodology, Writing—Reviewing & Editing. Karlina García Sosa: Methodology. Luis Manuel Peña Rodríguez: Methodology, Writing—Reviewing & Editing. José Antonio Guerrero Analco: Methodology, Writing—Reviewing & Editing. Juan Luis Monribot Villanueva: Methodology, Writing—Reviewing & Editing. Abraham Vidal Limon: Methodology, Writing—Reviewing & Editing. Maira Rubi Segura Campos: Conceptualization, Formal Analysis, Investigation, Resources, Writing—Original Draft, Writing—Review & Editing, Visualization, Supervision, Project Administration. This work has been approved by all authors.

Data availability statement

The data presented in this study are available on request from the corresponding author.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Consejo Nacional de Ciencia y Tecnología the under grant 316633.