Work

Predicting the Toxicity In Silico of the Aqueous Extract of Chiranthodendron pentadactylon Flowers. Experimental Evaluation In Vivo

Year: 2026

Type: article

Abstract: Chiranthodendron pentadactylon Larreat (“flor de manita”) is traditionally used for gastrointestinal, cardiovascular, and neurological disorders. Objective: This study comprehensively integrated phytochemical characterization, in silico toxicological profiling, an exposure-informed Integrative Toxicity Prediction Model (ITPM), uncertainty analysis, and acute testing of a fresh flower aqueous extract (FFAE). Methods: Thirty-six phytochemicals were screened for hepatotoxicity, nephrotoxicity, Ames mutagenicity, carcinogenicity, hERG inhibition, reproductive-effects alerts, and acute oral toxicity. Five organ- or effect-specific endpoints were integrated into an exploratory Toxicological Alert Score (TAS), whereas reproductive alerts and predicted LD50 were reported separately. Seventeen compounds quantified in the FFAE were compared with a 20-compound literature-informed profile through 50,000 Monte Carlo iterations. Male CD-1 mice received a single FFAE dose of 300–5000 mg/kg and were observed for 14 days. Results: Positive predictions occurred for hERG inhibition in 33 compounds (91.7%), hepatotoxicity in 29 (80.6%), nephrotoxicity and carcinogenicity in 28 each (77.8%), and mutagenicity in 21 (58.3%). Six compounds had predicted LD50 values ≤ 1000 mg/kg. The proportional ITPM toxicity-evidence index was 6.91% for the experimental profile and 19.34% for the literature-informed profile. Monte Carlo means were 6.98% (95% uncertainty interval, 5.65–8.44%) and 19.32% (16.76–22.37%), respectively. No mortality, overt clinical signs, or treatment-related body weight differences occurred up to 5000 mg/kg. Conclusions: Compound-level predictions identified priorities for confirmatory testing, while the extract-specific model yielded a lower comparative toxicity-evidence proportion, and the animal study showed low overall acute toxicity under the evaluated conditions. These findings do not establish general or long-term safety, calibrated risk probabilities, or biological neutralization of toxicological liabilities.

Source: Pharmaceuticals

DOI: 10.3390/ph19091354

Authors: Oscar Salvador Barrera-Vázquez, Gil Alfonso Magos-Guerrero, Juan Luis Escobar-Ramírez, Rubén San Miguel-Chávez, Maira Huerta-Reyes

Institutions: Universidad Nacional Autónoma de México, Colegio de Postgraduados, Mexican Social Security Institute, Centro Medico Nacional Siglo XXI

Language: English

Topic: Phytochemistry Medicinal Plant Applications

Subfield: Plant Science

Field: Agricultural and Biological Sciences

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499