Therapeutic effects of mangiferin on sepsis-associated acute lung and kidney injuries via the downregulation of vascular permeability and protection of inflammatory and oxidative damages

Abstract

Background: Sepsis is a serious systemic inflammatory response that primarily affects the lungs and kidneys. Moreover, a few drugs can effectively treat this disease. Mangiferin (MF) is a xanthone glucoside that possesses many pharmacological effects. This study aims to assess the effects of MF on capillary endothelial permeability and inflammatory responses and oxidative damages in mice with sepsis-associated lung and kidney injuries.

Methods: Mice were randomly divided into the control, lipopolysaccharide (LPS), and MF+LPS (20, 50, and 100 mg/kg) groups (n = 8). Mice in the MF+LPS group were treated with MF via oral administration once a day for 7 days before injection of LPS. Mice in the LPS and MF+LPS groups were treated with LPS (1 mg/kg body weight, tail vein injection) to establish a sepsis model. Six hours after LPS administration, lung, kidney, blood, and urine samples were further analyzed.

Results: Pathological results revealed that MF reduced the pathological injuries of the lung and kidney in LPS-induced sepsis. Immunofluorescence and ELISA results showed that MF reduced the permeability of capillary to albumin of the lung and kidney in LPS-induced sepsis. Further analysis indicated that the protective effects of MF on the permeability of capillary to albumin was associated with the upregulation of occludin expression and protection of syndecan-1 (SDC-1) damage. MF was also involved in the inhibition of matrix metalloproteinase-9 expression, which is an SDC-1-degrading factor. MF might relieve oxidative damages by inhibiting the production of reactive oxygen species and malondialdehyde, and boosting the superoxide dismutase activity to increase the total antioxidant capacity of the lung and kidney in LPS-induced sepsis. Western blot analysis results further revealed that MF can inhibit the activation of NF-κB and high-mobility group box 1 inflammatory signaling of the lung and kidney in LPS-induced sepsis.

Conclusions: The downregulation of vascular permeability and protection of inflammatory and oxidative damages by MF may be used as treatment targets for sepsis-associated acute lung and kidney injuries.

Keywords: HMGB1; NF-κB; Occludin; Sepsis; Syndecan-1.