Hyperelatolides A–D, Antineuroinflammatory Constituents with Unusual Carbon Skeletons from Hypericum elatoides

• Published in: Journal of natural products (Washington, D.C.) Vol. 86; no. 8; pp. 1910 - 1918
• Main Authors: Xie, Jin-Yan, Wang, Zi-Xuan, Liu, Wu-Yang, Liu, Han-Wu, Li, Ding, Sang, Yi-Fan, Yang, Zhi, Gao, Jin-Ming, Yan, Xi-Tao
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society and American Society of Pharmacognosy 25.08.2023
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.3c00226

Four new δ- and γ-lactone derivatives, hyperelatolides A–D (1–4, respectively), were discovered from the aerial portions of Hypericum elatoides R. Keller. Their structures were elucidated by analysis of NMR spectra, HRESIMS, quantum chemical calculations of NMR and ECD spectra, and X-ray crystallographic data. Hyperelatolides A (1) and B (2) represent the first examples of δ-lactone derivatives characterized by a (Z)-(5,5-dimethyl-2-(2-oxopropyl)­cyclohexylidene)­methyl moiety and a benzoyloxy group attached to the β- and γ-positions of the δ-lactone core, respectively, while hyperelatolides C (3) and D (4) are unprecedented γ-lactone derivatives featuring substituents similar to those of 1 and 2. All compounds were tested for their inhibitory effects on NO production in LPS-activated BV-2 cells. Lactones 1 and 2 exhibited considerable antineuroinflammatory activity, with IC50 values of 5.74 ± 0.27 and 7.35 ± 0.26 μM, respectively. Moreover, the mechanistic study revealed that lactone 1 significantly suppressed nuclear factor kappa B signaling and downregulated the expression of inducible nitric oxide synthase and cyclooxygenase-2 in LPS-induced cells, which may contribute to its antineuroinflammatory activity.