Ethnobotanical Uses and Phytochemical, Pharmacological, Behavioral, and Toxicological Effects of Montanoa Species Used by Pre-Columbian Mesoamerican Cultures for Anxiety and Depression.

Ancient cultures have long studied plants for medicinal use. Today, multidisciplinary research focuses on re-evaluating these plants to discover drugs for treating various diseases, including psychiatric disorders. Pre-Columbian Mesoamerican cultures described three plants (Montanoa tomentosa, Montanoa frutescens, and Montanoa grandiflora) for treating both anxiety and depression disorders, which were called cihuapahtli in Nahuatl. This narrative review describes and analyzes the ethnobotanical use and phytochemical, pharmacological, behavioral, and toxicological effects of cihuapahtli, which can contribute to the discovery of anxiolytic and antidepressant drugs. The results show a significant advance in identifying bioactive phytochemicals, including triterpenes, diterpenes, monoterpenes, and sesquiterpenes, as well as sterols, flavonoids, and alkaloids. In particular, the mechanism of action underlying their anxiolytic and antidepressant effects involves the activation of oxytocinergic neurons in the paraventricular nucleus of the hypothalamus, as well as that of the GABAergic system by targeting GABAA receptors. The three Montanoa species have the potential to help us develop anxiolytic and antidepressant drugs; however, future studies are still required to evaluate toxicity, dose standardization, possible variability in plant-derived compounds, pharmacokinetic parameters, and pharmacological interactions. Only then will preclinical evidence be sufficiently robust to justify translational studies evaluating the safety and efficacy of these plant extracts for the development of anxiolytic and antidepressant phytomedicines.