Protective Effects of Kirenol against Lipopolysaccharide-Induced Acute Lung Injury through the Modulation of the Proinflammatory NFκB Pathway and the AMPK2-/Nrf2-Mediated HO-1/AOE Pathway

Acute lung injury (ALI) is an acute and life-threatening inflammatory disease of the lung parenchyma that is associated with high mortality worldwide. No therapeutic strategies have been developed for the mitigation of the proinflammatory response that characterizes ALI. Kirenol has anti-inflammatory, antiarthritic, and immunoregulatory effects. In the present study, we investigated the protective effects of kirenol against lipopolysaccharides (LPS)-induced ALI in mice. Kirenol reduced the LPS-induced histopathology changes involving edema and thickening of the interstitial or alveolar walls, infiltration of leukocytes, formation of hyaline membrane. Pretreatment with kirenol reduced leukocytes infiltration in bronchoalveolar lavage fluid (BALF), the alveolar-capillary barrier disruption and lipid peroxidation in lung tissues induced by LPS. Kirenol significantly inhibited the secretion of cytokines, IL-1β, IL6, and TNFα, into the BALF of the mice with LPS-induced ALI through NFκB activation. Moreover, kirenol attenuated the downregulation of the antioxidant enzymes, superoxide dismutase, glutathione peroxidase, and catalase that was induced by LPS. HO-1 expression and the phosphorylation of Nrf2 and AMPK2 were also induced by kirenol. The results indicate that kirenol can be developed as a treatment strategy for ALI, and its effects are induced through the inhibition of the NF-κB proinflammatory pathway and promotion of AMPK2/Nrf2-mediated HO-1 and antioxidant enzymes (AOE) activation.

Isolation and characterization of mitochondria and lysosome from isoproterenol induced cardiotoxic rats

Mitochondrial and lysosomal membranes are prominent membranes of cardiac cells and are the factors that determine membrane function in myocardial ischemia. In this study, isolation of mitochondria and lysosome from heart tissue under the control, isoproterenol (ISO) (8.5mg/100g) induced cardiotoxic rats and oral pretreatment with Z. armatum fruit (200, 400mg/kg body weight) treated rats. Further characterization of marker enzymes was done. A decreased in the activity of all the mitochondrial and lysosomal marker enzymes in ISO administered cardiotoxic rats when compared to control rats which indicate ISO decreased the stability of the membrane. Pretreatment with hydroethanolic extract of Z. armatum fruit to ISO induced rats significantly reverted these biochemical alterations near to normal. The possible mechanism for the protection of heart mitochondria and lysosome against oxidative damage induced by ISO might be due to quenching of free radicals and enhancing the action of marker enzymes.