Investigation on the mechanisms of biochanin A alleviate PM10-induced acute pulmonary cell injury

Abstract

Epidemiological studies have shown that the elevated concentration of particulate matter with aerodynamic diameter less than 10 µm (PM10) is closely related to the increased risk of heart and lung diseases in the population. Natural isoflavone compound biochanin A (BCA) has anti-inflammatory and antioxidant activities, and has efficacy in alleviating lung injury. The objective of this study was to investigate the inhibitory effect of BCA on PM10 induced acute human bronchial epithelial cells injury. The results showed that PM10 decreased intracellular catalase level to 1.19 ± 0.01 nmol/min/mg prot and induce a surge of reactive oxygen species (ROS). It also increased lactate dehydrogenase (LDH) activity by 428.89% and caused the lipid peroxidation phenomenon. PM10 exposure also upregulates the expression of inflammatory cytokines and mediators. However, BCA could interfere with the above changes caused by PM10, inhibit the LDH level to 8.22 ± 0.03 u/mL, and show anti-inflammatory and antioxidant activities. In addition, the phosphatidylinositol 3-kimase (PI3K) /protein kinase B (PKB/Akt) is a key signal pathway in response to PM10 exposure. In this study, PI3K/Akt signaling pathway is seriously affected by PM10 exposure. PI3K/Akt signaling pathway, PI3K, AKT, tensin homolog deleted on chromosome 10 (PTEN), mechanistic target of rapamycin (mTOR) and p53 protein were all inhibited by PM10 exposure, and PI3K/Akt signaling pathway was inactivated. BCA exert anti-damage function by regulating the activation process of PI3K protein, intervening the regulation process of PI3K/Akt by PTEN, and intervening the expression and phosphorylation of downstream Akt protein.

Keywords

• Biochanin A
• PM10
• Acute pulmonary cell injury
• PI3K/Akt