From Traditional Use to Molecular Mechanisms: A Bioinformatic and Pharmacological Review of the Genus Kalanchoe with In Silico Evidence

The genus <i>Kalanchoe</i> (Crassulaceae) comprises approximately 125 species of succulents distributed across Madagascar, Africa, Arabia, Australia, Southeast Asia, and tropical America. Traditionally regarded as "miracle plants", <i>Kalanchoe</i> species are employed for treating inflammatory, infectious, metabolic, and cardiovascular conditions; this is associated with their abundant content of polyphenols, including phenolic acids and flavonoids such as quercetin, kaempferol, luteolin, rutin, and patuletin. However, robust clinical evidence remains limited. This review integrates pharmacological and bioinformatic perspectives by analyzing more than 70 studies published since 2000 on 15 species, including <i>Bryophyllum</i>. As an in silico complement, the genome of <i>Kalanchoe fedtschenkoi</i> was used to predict genes (AUGUSTUS), perform homology searches against <i>Arabidopsis thaliana</i>, and model three key enzymes: CHS, CYP90, and VEP1. The AlphaFold2/ColabFold models showed conserved catalytic motifs, and molecular docking with representative ligands supported the plausibility of biosynthetic pathways for flavonoids, brassinosteroids, and bufadienolides. The available evidence highlights chemopreventive, antibacterial, anti-inflammatory, antiviral, antioxidant, and cytotoxic activities, primarily associated with flavonoids and bufadienolides. Significant gaps remain, such as the lack of gene-metabolite correlations and the absence of standardized clinical trials. Overall, <i>Kalanchoe</i> represents a promising model that requires multi-omics approaches to enhance its phytopharmaceutical potential.