Inhibitory effects of compounds isolated from Dioscorea batatas Decne peel on particulate matter-induced pulmonary injury in mice

ABSTRACT

Particulate matter 2.5 (PM_2.5), with an aerodynamic diameter of ≤2.5 μm, is the primary air pollutant that plays a key role associated with lung injury produced by loss of vascular barrier integrity. Dioscorea batatas Decne (Chinese yam), a perennial plant belonging to Dioscoreaceae family, is widely cultivated in tropical and subtropical regions across Asia. Both aerial parts and root of D. batatas are consumed for nutritional and medicinal purposes. The aim of this study was to (1) identify the bioactive compounds present in D. batatas peel which may be responsible for inhibition of PM_2.5-induced pulmonary inflammation in mice and (2) examine in vitro mechanisms underlying the observed effects of these compounds on mouse lung microvascular endothelial cells. The measured parameters include permeability, leukocyte migration, proinflammatory protein activation, reactive oxygen species (ROS) generation, and histology. Two phenanthrene compounds, 2,7-dihydroxy-4,6-dimethoxyphenanthrene (1) and 6,7-dihydroxy-2,4-dimethoxyphenanthrene (2) were isolated from D. batatas peels. Both these phenanthrene compounds exhibited significant scavenging activity against PM_2.5-induced ROS and inhibited ROS-induced activation of p38 mitogen-activated protein kinase. In addition, enhancement of Akt pathway, involved in the maintenance of endothelial integrity, was noted. These phenanthrene compounds also reduced vascular protein leakage, leukocyte infiltration, and proinflammatory cytokine release in the bronchoalveolar lavage fluid obtained from PM_2.5-induced lung tissues. Evidence thus indicates that phenanthrene compounds derived from D. batatas may exhibit protective effects against PM_2.5-induced inflammatory lung injury and vascular hyperpermeability in mice.

KEYWORDS:

• Akt
• Dioscorea batatas Decne peel
• particulate matter
• vascular permeability
• pulmonary injury

Author contributions

W.L., S.Y.J., and M.J.G. performed the experiments; W.L and S.Y.J. wrote the manuscript; E.K.P., M.-C.B., D.H., and J.-S.B. analyzed the data; J.S.L and J.S.K. contributed materials; J.S.B. designed the research; and D.H. and J.S.B. reviewed the manuscript.

Conflict of interest statement

The authors declare no conflicts of interest.

Supporting information

Supporting Information is available from Wiley Online Library or from the author.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2017R1A5A2015391, 2017M3A9G8083382).