Research Progress of Diterpenoids with Potential Antidiabetic Activity

Introduction: Diabetes mellitus has become a global epidemic. Diterpenoids have complex and variable structures and are widely distributed in nature. They play a crucial role in disease treatment due to their versatile bioactivities, including antidiabetic activities. Objective: This review aims to systematically summarize the antidiabetic activity of diterpenoids and recognize the potential antidiabetic candidates from diterpenoids for researchers. Methods: By searching the literature from 1999 to 2025 in scientific search engines with diterpenoids and antidiabetes, and other related words as keywords, more than 100 references were included. Results: A total of 175 diterpenoids with antidiabetic activity were outlined according to their structural classification, including acyclic-, monocyclic-, bicyclic-, tricyclic-, tetracyclic-, and macrocyclic diterpenoids, in which bicyclic and tricyclic diterpenoids have the most potent antidiabetic activity. Particularly, a bicyclic diterpenoid, andrographolide, and its derivatives exhibit superb effects in diabetic animals. Meanwhile, the isolation or synthesis methods of these diterpenoids were also briefly introduced. Discussion: The underlying antidiabetic mechanisms of these diterpenoids were diverse, with PTP1B inhibition being the most common mechanism. However, most of the diterpenoids remain to be investigated for their in vivo antidiabetic activity. Conclusion: Diterpenoids, especially andrographolide and its analogs, are promising candidates, and this review is helpful for researchers in the discovery of novel drugs based on diterpenoid skeletons in the treatment of diabetes and its complications