Potential HIV latency-reversing agents with STAT1-activating activity from the leaves of Wikstroemia chamaedaphne

  • Phytochemistry. 2022 Nov;203:113395. doi: 10.1016/j.phytochem.2022.113395.
Shi-Fei Li  1 ,  Xiu-Yi Wang  2 ,  Gong-Lu Li  3 ,  Ying-Ying Jiao  4 ,  Wen-Hao Wang  4 ,  Xing-Kang Wu  4 ,  Li-Wei Zhang  5
Affiliations
  • 1. Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Institute of Molecular Science, Shanxi University, Taiyuan, 030006, People's Republic of China. Electronic address: [email protected].
  • 2. Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Institute of Molecular Science, Shanxi University, Taiyuan, 030006, People's Republic of China; Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, 030006, People's Republic of China.
  • 3. Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, 030006, People's Republic of China.
  • 4. Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Institute of Molecular Science, Shanxi University, Taiyuan, 030006, People's Republic of China.
  • 5. Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Institute of Molecular Science, Shanxi University, Taiyuan, 030006, People's Republic of China. Electronic address: [email protected].
PMID: 36027969 DOI: 10.1016/j.phytochem.2022.113395
Abstract

Developing highly effective HIV latency-reversing agent is an inportmant approach for the treatment of AIDS via the "shock and kill" of latent HIV. In this study, two unreported modified daphnane-type diterpenes (chamaedaphnelide A and epi-chamaedaphnelide A) and one unreported tigliane-type diterpene (chamaedaphnelide B), along with four known daphnane-type diterpenes and one known tigliane-type diterpene were obtained from the leaves of Wikstroemia chamaedaphne. Chamaedaphnelide A and epi-chamaedaphnelide A represents the first A ring cleavage daphnane-type backbone. Chamaedaphnelide A, epi-chamaedaphnelide A, chamaedaphnelide B, and 6α,7α-epoxy-5β-hydroxy-12-deoxyphorbol-13-decanoate showed HIV latency-reversing activity, especially chamaedaphnelide B and 6α,7α-epoxy-5β-hydroxy-12-deoxyphorbol-13-decanoate displayed equally potential to positive drugs prostratin with reversing latent HIV on more than 100-fold compared to unstimulated cells. Furthermore, the activation of STAT1 was involved in the HIV latency-reversing activity of these diterpenes, firstly demonstrating that daphnane- and tigliane-type diterpenes can rapidly activate STAT1 activity. Indeed, these results also supported that activating STAT1 activity is a pathway for reversing latent HIV.

Keywords
Daphnane-type diterpene; HIV latency-Reversing agent; STAT1; Thymelaeaceae; Tigliane-type diterpene; Wikstroemia chamaedaphne.
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