New steroidal saponins from Physochlainae Radix: Structures and anti-inflammatory efficacy

Physochlainae Radix (PR), a crucial herbal medicine, has been widely utilized in the treatment of pulmonary disorders, such as asthma and bronchitis. In the present study, nine previously undescribed steroidal saponins, designated as infundilides A-I (1-9), were isolated from PR. These compounds exhibit unique structural features characterized by the presence of unusual hydroxymethyl or carboxyl substituents at the C-20 position. Additionally, five new analogues, infundilides J-N (10-14), were also obtained. Their planar structures were elucidated based on analysis of MS and NMR spectroscopy data, and the absolute configurations were determined by single-crystal X-ray diffraction and comparisons of spectroscopic data. In vitro anti-inflammatory activity assays revealed that infundilide A (1), infundilide E (5), and infundilide K (11) exhibited pronounced inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Subsequently, to further explore the anti-inflammatory efficacy of steroidal saponins in PR, the therapeutic potential of infundilide A (1) was evaluated in a mouse model of acute lung injury (ALI). The results demonstrated that infundilide A effectively alleviated ALI-associated pathological changes, reduced inflammatory cytokines levels (IL-1β, TNF-α, IL-6, and COX-2) in the lung tissues, and modulated the TLR4/MyD88/NF-κB signaling pathway. To sum up, infundilide A holds promise as a potential anti-inflammatory lead compound. These discoveries emphasize the prospective therapeutic uses of steroidal saponins from PR in the treatment of inflammatory disorders.