Metabonomic approaches investigate diosbulbin B-induced pulmonary toxicity and elucidate its underling mechanism in male mice

Hainan Ji; Chang Liu; Na Tong; Naining Song; Baoliang Xu; Chan Zhao; Haishan Li; Guolin Shen; Hua Li

doi:10.1093/toxres/tfab014

Metabonomic approaches investigate diosbulbin B-induced pulmonary toxicity and elucidate its underling mechanism in male mice

Toxicol Res (Camb). 2021 Mar 23;10(2):272-276. doi: 10.1093/toxres/tfab014. eCollection 2021 Mar.

Authors

Hainan Ji¹, Chang Liu², Na Tong³, Naining Song¹, Baoliang Xu¹, Chan Zhao¹, Haishan Li¹, Guolin Shen¹, Hua Li⁴

Affiliations

¹ Institute of Chemicals Safety, Chinese Academy of Inspection and Quarantine, No. 11 Rong Hua middle road, Economic-Technological Development Area, 100176 Beijing, China.
² The Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, No. 151 malianwa North Road, Haidian District, 100193 Beijing, China.
³ Center for Food Evaluation, State Administration for Market Regulation, Building 15, area 11, 188 South Fourth Ring Road West, Fengtai District, 100070 Beijing, China.
⁴ Beijing Institute of Pharmacology\remvoliss and Toxicology, No. 27 Taiping Road, Haidian District, 100850 Beijing, China.

Abstract

Air Potato Yam is widely used in the treatment of many conditions such as cancer, inflammation, and goiter. Diosbulbin B (DIOB) is the primary active component of Air Potato Yam, and it exhibits anti-tumor and anti-inflammatory properties. The main purpose of this study was to determine the mechanism by which DIOB induces lung toxicity, using metabonomics and molecular biology techniques. The results showed that the lung toxicity induced by DIOB may occur because of a DIOB-induced increase in the plasma levels of long-chain free fatty acids and endogenous metabolites related to inflammation. In addition, treatment with DIOB increases the expression of the cyp3a13 enzyme, which leads to enhanced toxicity in a dose-dependent manner. The molecular mechanism underlying toxicity in mouse lung cells is the DIOB-mediated inhibition of fatty acid β-oxidation, partial glycolysis, and the TCA cycle, but DIOB treatment can also compensate for the low Adenosine triphosphate (ATP) supply levels by improving the efficiency of the last step of the glycolysis reaction and by increasing the rate of anaerobic glycolysis. Using metabonomics and other methods, we identified the toxic effects of DIOB on the lung and clarified the underlying molecular mechanism.

Keywords: DIOB; glycolysis; metabonomics; β-oxidation.