A sesquiterpene isolated from the stems and leaves of Dioscorea opposita thunb. Transforms the composition of immune cells through ERβ in a mouse model of LPS-induced lung injury

Abstract

Acute lung injury (ALI) is a common critical disease with a high mortality rate. Natural products have marked efficacy in the prevention and treatment of ALI, in addition, estrogen and its receptors are involved in the pathogenesis and development of lung injury. Our previous research shows that sesquiterpenes isolated from the stems and leaves of Dioscorea opposita Thunb. have anti-inflammatory and estrogenic-like activity. In the present study, sesquiterpene (A1) is a natural extract from the stems and leaves of Dioscorea opposita Thunb. with a view to determining whether A1 can improve lung function in a mouse model of LPS-induced ALI and exploring the involvement of the estrogen receptor β (ERβ) pathway. A1 (20 or 40 mg/kg, i. g., 2 times/day) was administered for 3 d, followed by the induction of ALI via an intratracheal LPS drip (5 mg/kg/2 h). The lung function and levels of inflammation, immune cells, apoptosis, and ERβ expression were examined. The antagonistic activity of specific ERβ blocker (THC, 1 μM) against A1 (20 μM) in co-cultured BEAS-2B cells and splenic lymphocytes induced with LPS (1 μg/mL, 24 h) was also investigated to assess whether the observed effects of A1 were mediated by ERβ. A1 improved lung function, regulated the immune system, and decreased inflammation and apoptosis. Moreover, A1 increased the expression of ERβ in LPS-induced mice, and antagonism of ERβ decreased the protective effects of A1 in a co-culture system. A1 had anti-ALI effects that might partially mediated through ERβ signaling. Our data provide molecular justification for the use of A1 in the treatment of ALI.