Plant protoberberine alkaloids: structural diversity, biosynthesis, synthesis, biological activity, structure-activity relationships and clinical applications of berberine.

Protoberberine alkaloids are a class of organic heterocyclic compounds categorized within the isoquinoline alkaloids, exhibiting significant therapeutic potential due to their potent biological activities. With advancements natural product chemistry, synthetic organic chemistry, biochemistry, and molecular biology, novel insights into their biosynthetic pathways, chemical synthesis pathways, mechanisms of action, and clinical applications have been elucidated. A comprehensive understanding of protoberberine alkaloids is instrumental in enhancing their commercial value and utilization of medicinal plant resources. Among these alkaloids, berberine stands out as a well-studied compound with broad-spectrum bioactivities. In this review, we summarized the progress in the study of protoberberine alkaloids, focusing on the recent advances in the biosynthetic pathway, the regulatory mechanism of biosynthesis, chemical synthesis, clinical applications and structure-activity relationship analysis of berberine. It is anticipated that this review will offer valuable insights for researchers in the fields of synthesis, medicinal chemistry, and bactericidal chemistry, who are engaged in exploring the chemistry and biology of protoberberine alkaloids.