Genipin attenuates mitochondrial-dependent apoptosis, endoplasmic reticulum stress, and inflammation via the PI3K/AKT pathway in acute lung injury.

Genipin attenuates mitochondrial-dependent apoptosis, endoplasmic reticulum stress, and inflammation via the PI3K/AKT pathway in acute lung injury. Int Immunopharmacol. 2019 Aug 26;76:105842 Authors: Luo X, Lin B, Gao Y, Lei X, Wang X, Li Y, Li T Abstract The protective effects of genipin against lipopolysaccharide (LPS)-induced acute lung injury (ALI) have been reported; however, the mechanism is unclear. Genipin performs its pharmacological effects via activation of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. In the present study, we aimed to determine whether the PI3K/AKT pathway is involved in the protective effects of genipin against mitochondrial-dependent apoptosis, endoplasmic reticulum stress (ERS), and inflammation in ALI. We constructed in vivo and in vitro models of LPS-induced ALI. PI3K/AKT signaling was inhibited using LY294002. Pretreatment with genipin increased AKT phosphorylation, indicating that PI3K/AKT signaling was upregulated. Genipin pretreatment prevented LPS-induced histopathological deterioration, increased pulmonary edema, and decreased oxygenation index, all of which were inhibited using LY294002. In addition, genipin pretreatment attenuated LPS-mediated mitochondrial apoptosis, as indicated by improved mitochondrial dysfunction, downregulation of BAX (BCL2 associated X, apoptosis regulator), upregulation of BCL2 (BCL2 apoptosis regulator), inhibited...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research