Novel β-γ′ type lignans from cultivated Notopterygium incisum and their potential anti-inflammatory activity

Two novel β-γ′ type lignans, notolignan A ( 2 ) and notolignan B ( 3 ) were isolated from the 80 % EtOH extract of cultivated Notopterygium incisum along with one known analogue ( 1 ) by normal and reverse phase column chromatography. The structures of the undescribed compounds were characterized by extensive spectroscopic data. This study aimed to evaluate the potential protective effects of a novel compound on acute lung injury (ALI) in mice via the NLRP3 inflammasome. The model of ALI was established with lipopolysaccharide (LPS) in C57BL/6 mice by intraperitoneal injection. LPS was also used to stimulate RAW264.7 cells that detected the anti-inflammatory activity of compound 2 . The NLRP3 inflammasome was activated by LPS + Nig in iBMDMs. Our data noted that compound 2 could effectively inhibit the NO production with safe concentration and which effect was superior to positive control (30, 40 and 50 μM). Furthermore, compound 2 dramatically suppresses the activation of NLRP3 inflammasome and production of IL-1β, blocking NEK7-NLRP3 and NLRP3-ASC interactions. The DFT calculations, docking, and MDs have demonstrated that compound 2 interacts with NLRP3 to form a stable complex. In addition, pre-treated with compound 2 could obviously alleviated the lung pathological symptoms in ALI mice, and significantly down regulate the expression of NLRP3 and IL-1β in lung tissues. These findings suggest that the isolated compounds may serve as potential anti-inflammatory agents or lead compounds for drug development. • Two novel β-γ′ type lignans lignans were isolated from Notopterygium incisum . • Notolignan A alleviated symptoms in ALI mice. • Notolignan A suppressed the activation of NLRP3 inflammasomes in DSS mice. • Notolignan A inhibited inflammasome activation in iBMDMs.