Kalanchoe pinnata Phytochemistry and Preclinical Pharmacology with an Appraisal of Safety and Clinical Evidence

Background: Kalanchoe pinnata (Lam.) Pers. is a medicinal species of the Crassulaceae family with a long history of ethnomedicinal use and a chemically diverse profile comprising flavonoids, bufadienolides, phenolic acids, triterpenes, and other secondary metabolites. Experimental studies have reported multiple biological effects of K. pinnata extracts and isolated constituents; however, the strength and clinical relevance of this evidence vary substantially among investigated applications. This review critically summarizes the phytochemical composition of K. pinnata, the proposed mechanisms underlying its biological activities, and the current level of experimental and clinical evidence relevant to its potential therapeutic use. Methods: A narrative review of the scientific literature was conducted using publications identified in PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Studies addressing the phytochemical composition of K. pinnata, identification and characterization of its metabolites, biological mechanisms, pharmacological activity, safety, and available experimental and clinical evidence were considered. Particular attention was given to differences in study design, extract composition, experimental models, and the level of evidence supporting individual biological effects. Results: Phytochemical studies have identified flavonoids, bufadienolides, phenolic acids, triterpenes, and other secondary metabolites in K. pinnata, several of which have been associated with biological effects observed in experimental models. Quercetin glycosides, particularly quercetin 3-O-α-L-arabinopyranosyl-(1 → 2)-α-L-rhamnopyranoside (QAR), represent important bioactive constituents associated with anti-inflammatory, antioxidant, and wound-healing activities, whereas bufadienolides have demonstrated cytotoxic and antiproliferative effects in experimental cancer models but also represent an important toxicological concern. Preclinical evidence is most extensive for wound-healing, anti-inflammatory, antioxidant, antimicrobial, metabolic, and cytotoxic effects, whereas evidence for cardioprotective, hepatoprotective, nephroprotective, and other systemic applications remains predominantly experimental. However, differences in plant origin, phytochemical composition, extraction procedures, and experimental methodologies, together with the predominance of in vitro and animal studies, limit the direct translation of current findings into clinical practice. Conclusions: Current evidence supports the biological activity of several Kalanchoe pinnata extracts and isolated constituents under experimental conditions, but the extent to which these findings translate into clinically relevant therapeutic effects remains uncertain. The limited number of human studies, substantial variability in extract composition, incomplete pharmacokinetic characterization, and safety concerns related particularly to bufadienolides currently restrict broader clinical interpretation. Further research should prioritize standardized preparations, clearly characterized phytochemical profiles, dose–response relationships, long-term safety assessment, and well-designed controlled clinical trials.