Panax notoginseng is a famous perennial herb widely used as material for medicine and health-care food. Due to its various therapeutic effects, research work on P. notoginseng has rapidly increased in recent years, urging a comprehensive review of research progress on this important medicinal plant. Here, we summarize the latest studies on the representative bioactive constituents of P. notoginseng and their multiple pharmacological effects, like cardiovascular protection, anti-tumor, and immunomodulatory activities. More importantly, we emphasize the biosynthesis and regulation of ginsenosides, which are the main bioactive ingredients of P. notoginseng. Key enzymes and transcription factors (TFs) involved in the biosynthesis of ginsenosides are reviewed, including diverse CYP450s, UGTs, bHLH, and ERF TFs. We also construct a transcriptional regulatory network based on multi-omics data and predicted candidate TFs mediating the biosynthesis of ginsenosides. Finally, the current three major biotechnological approaches for ginsenoside production are highlighted. This review covers advances in the past decades, providing insights into quality evaluation and perspectives for the rational utilization and development of P. notoginseng resources. Modern omics technologies facilitate the exploration of the molecular mechanisms of ginsenoside biosynthesis, which is crucial to the breeding of novel P. notoginseng varieties. The identification of functional enzymes for biosynthesizing ginsenosides will lead to the formulation of potential strategies for the efficient and large-scale production of specific ginsenosides.

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