Neuroprotective and Immunomodulatory Efficacy of Selected Caribbean Medicinal Plants: A Systematic Review

The three Caribbean medicinal plants Momordica charantia (cerasee/bitter melon), Annona muricata (soursop/graviola), and Petiveria alliacea (Guinea hen weed/anamu) have been traditionally used to treat inflammatory, metabolic, and neurological disorders. Although research in plant phytochemistry has increased, the evidence base in preclinical settings regarding neuroprotective and immunomodulating effects remains underexplored. This systematic review aimed to synthesize published preclinical evidence on the neuroprotective, immunomodulatory, and anti-inflammatory mechanisms of M. charantia, A. muricata, and P. alliacea and to assess their translational and public health relevance within Caribbean and resource-limited contexts. An exhaustive literature search was performed in PubMed, Scopus, Web of Science, and Cochrane Library through specific Boolean search strategies. Relevant articles were selected based on predefined inclusion criteria by one independent reviewer. Articles that met the inclusion criteria were defined as those consisting of original experimental studies (in vitro, in vivo, or both) involving mechanistic immunomodulatory, anti-inflammatory, and neuroprotective mechanisms. Systematic reviews and articles not containing any mechanistic information were ruled out. The methodological quality of the included papers was evaluated using the MMAT (McGill University, Montreal, Canada) and the JBI critical appraisal tool (JBI, Adelaide, Australia). Since the included studies were diverse, results were described descriptively. Out of a total of 1,182 sources, 13 articles were found to fulfill the criteria: nine on M. charantia, two on A. muricata, and two on P. alliacea. All three medicinal plants demonstrated similar anti-inflammatory effects: downregulation of pro-inflammatory cytokines, inhibition of ROS production, and regulation of key signaling cascades, including PI3K/AKT/NF-κB, MAPK, Nrf2/HO-1, and SIRT1/β-catenin. Neuroprotection included inhibition of neuronal apoptosis, promotion of neural stem cell differentiation, and increased permeability of the blood-brain barrier. Additionally, microbiome alteration and miRNA modulation were recognized as promising mechanisms. Dose-dependent cytotoxic effects were reported for certain compounds, while significant methodology heterogeneity hampered comparability between studies. The reviewed literature supports significant neuroprotective and immunomodulatory effects of these Caribbean medicinal herbs in preclinical settings. Nevertheless, translational research is needed to develop recommendations for the clinical use of these herbs, including pharmacological research and clinical trials.