Rare Chlorinated C19 Steroids Hocarnoids A and B from Hoya carnosa: Isolation, Semisynthesis, and Anti-inflammation

Steroids have consistently drawn scientific attention due to their diverse structures and exceptional pharmacological activities. However, halogenated natural steroids remain relatively rare, especially for those derived from plants. In this study, two chlorinated C₁₉ steroids hocarnoids A (1) and B (2) were identified from the folk medicinal plant Hoya carnosa, representing the first examples of plant derived C-16 chlorinated steroids. Semisynthesis of compounds 1 and 2 was completed in 4 and 5 linear steps with 28.2% and 25.3% overall yields through a modified approach, corroborating further their structures. A total collection of 11 C₁₉ steroids, including intermediates obtained during the synthesis, were evaluated for the anti-inflammatory activity against lipopolysaccharide (LPS)-induced inflammation-related RAW 264.7 macrophages. Among them, the natural product hocarnoid A (1) displayed the strongest anti-inflammatory activity with an IC₅₀ value of 3.62 ± 0.08 μM, which also attenuated the mRNA levels of proinflammatory cytokines IL-1β, IL-6, IL-10, and TNF-α.