Natural extract–derived compounds for the treatment of hematological diseases through modulation of the bone marrow microenvironment

The bone marrow microenvironment comprises a complex network of hematopoietic stem cells, immune cells, stromal cells, and non-cellular components such as the extracellular matrix and soluble factors, collectively maintaining the homeostasis of hematopoietic stem and progenitor cells. It is highly vulnerable to pathological perturbations induced by hematologic malignancies, solid tumors, inflammatory stress, and therapeutic exposure, which collectively destabilize microenvironmental homeostasis and promote hematopoietic failure, malignant progression, and immune dysregulation. Natural products exhibit unique advantages in modulating the blood microenvironment due to their structural diversity, multitarget effects, and low toxicity. Their biological activities span multiple mechanistic dimensions, including redox regulation, metal ion homeostasis, signaling inhibition, and microenvironment remodeling. However, the intrinsic relationships between their chemical structures and biological functions have not yet been systematically elucidated. Therefore, from a translational medicine perspective, this review focuses on elucidating the pharmacological mechanisms by which natural products regulate the hematopoietic microenvironment. We systematically summarize their chemical basis and structure-activity relationships, together with recent advances in extraction techniques, chemical modification, and targeted delivery strategies. The aim is to bridge the gap between chemical research on natural products and their clinical therapeutic applications, providing a framework and innovative directions for drug development targeting hematological diseases.