Anti-HIV active diterpenoids identified in Daphne pseudomezereum

A research group led by Professor Wei Li from the Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Toho University, in collaboration with the Duke University Medical Center in the United States, has discovered for the first time that Daphne pseudomezereum (commonly known as Onishibari) contains a substance inhibiting replication of human immunodeficiency virus (HIV). The plants were cultivated at the Medicinal Plant Garden of the Faculty of Pharmaceutical Sciences, Toho University. This finding is expected to lead to the discovery of drug seeds for novel drugs with superior anti-HIV activity.

A paper reporting this study was published in the scientific journal Phytochemistry on December 16, 2024.

Key findings

• Daphnane diterpenoid were isolated from D. pseudomezereum (Thymelaeaceae) and their potent anti-HIV activity was demonstrated.
• This is the first report of anti-HIV active diterpenoids identified in D. pseudomezereum.
• Further elucidation of the anti-HIV diterpenoids in plants of Thymelaeaceae is expected to contribute to the discovery of new anti-HIV drugs.

Research overview

The Thymelaeaceae family consists of over 53 genera and 800 species distributed worldwide, except in polar and desert regions. These plants contain diterpenoids, which exhibit significant biological activities, including anticancer, anti-HIV, and analgesic effect. Daphne pseudomezereum (commonly known as Onishibari) is a deciduous shrub of the Thymelaeaceae family found in Japan, China, and Korea. Its bark has been traditionally used in medicine to treat chronic skin diseases and rheumatism due to its anti-inflammatory properties. Additionally, this fiber-rich bark has been utilized as an additive in Japanese paper production.

In the present study, a research group isolated ten daphnane diterpenoids, including three previously undescribed compounds, from the fruits of D. pseudomezereum (Figure 1). Among the isolated compounds, three exhibited potent anti-HIV activity, with EC₅₀ values around 1 nM and cytotoxicity at IC50 > 5 μM. The findings of this study not only underscore the promising anti-HIV potential of daphnane diterpenoids but also provide a foundation for future research aimed at optimizing their activity through strategic structural modifications.