Antidepressant Potential of Species from the Piperaceae Family: A Comprehensive Review of Preclinical Studies

The Piperaceae family is recognized for its ethnopharmacological relevance and diversity of secondary metabolites. Several species, such as Piper nigrum, Piper methysticum and Piper longum, have been traditionally used for their effects on the central nervous system, sparking growing scientific interest regarding their therapeutic potential. Thus, the present study aims to review published works on natural and synthetic compounds from the Piperaceae family with proven antidepressant activity. Methods: A bibliographic survey was conducted covering the period from 2000 to 2025 in the Web of Science, PubMed, and Science Direct databases. The descriptors “Piperaceae” and “depression” (Portuguese and English terms) were used. After title and abstract screening, 43 articles were initially selected, and following eligibility criteria, 18 articles were retained for full-text review. Results: Piper nigrum, Piper longum and Piper sarmentosum were the most investigated species regarding their potential antidepressant effects, acting on several systems such as serotonergic, GABAergic, and monoamine oxidase enzymes. All studies were conducted in animal models of depression, employing isolated substances, extracts, and essential oils. Conclusion: Preclinical studies highlight species of the Piperaceae family as promising alternatives for antidepressant treatment, given their abundance in nature. However, further studies in other species, as well as clinical trials, are warranted.