Abstract
Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of abnormal plasma cells, with marked heterogeneity and therapeutic refractoriness. Despite the introduction of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies (mAbs), and chimeric antigen receptor T-cell (CAR-T) therapy, relapse and drug resistance remain major challenges that urgently need to be addressed. Plant-derived natural products have attracted increasing attention in recent years due to their multi-target synergistic effects, demonstrating unique potential in inducing MM cell apoptosis, reversing drug resistance, and modulating the immune microenvironment-making them a rising focus in translational medicine research. In this structured narrative review, we systematically summarize the anti-myeloma mechanisms of fourteen plant-derived natural products, including plant-derived monomeric compounds (baicalein, artemisinin, curcumin, celastrol, gambogic acid, resveratrol, ginsenosides, icariin, oridonin, plumbagin, formononetin) and standardized plant extracts (Strychnos nux-vomica root extract, dandelion flavonoids, Hedyotis diffusa polysaccharides). This review highlights their multi-target regulatory effects on signaling pathways, cell cycle modulation, and immune regulation, and further discusses their potential translational value in overcoming drug resistance and optimizing combination treatment strategies. Literature was retrieved from PubMed, Web of Science, and CNKI databases, covering studies published up to January 2025. Although plant-derived natural products exhibit promising multi-target regulatory mechanisms in MM therapy, their clinical translation remains limited by poor bioavailability of single compounds and the lack of standardized extracts. Future research should integrate systems pharmacology with clinical studies to elucidate multi-component synergistic networks and develop novel targeted formulations, thereby accelerating the efficient translation of phytochemicals from bench to bedside.