Biochemometric approach combined with 1D CSSF-TOCSY for the identification of sensitization agents in Curcuma longa L. and prediction of their action mechanisms

• Published in: Microchemical journal Vol. 181; p. 107727
• Main Authors: Li, Fei-Fei, Zhang, Yan-Li, Guo, Dong-Xiao, Zhao, Chang-Jun, Yao, Yun-Feng, Lin, Yong-Qiang, Wang, Shu-Qi
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2022
• Subjects: 1D CSSF-TOCSY; 1H NMR; Curcuma longa L; OPLS-DA; Sensitization agents; Sensitization agents; 1H NMR; Curcuma longa L; 1D CSSF-TOCSY; OPLS-DA
• ISSN: 0026-265X; 1095-9149
• DOI: 10.1016/j.microc.2022.107727

[Display omitted] •A biochemometric method for rapid screening of sensitizing agents of 5-FU in Curcuma longa L., and prediction of their action mechanisms was established.•Three sensitization agents, including curcumin, demethoxycurcumin and bisdemethoxycurcumin in Curcuma longa L, were identified using 1D CSSF-TOCSY spectra according to the biochemometric analysis.•The role of curcumnoids in regulating multi-drug resistance related transporters and lactate transporter MCT1 was revealed. Herbal medicines are valuable resources of clinical anticancer drugs. However, due to the complicated composition of the medicines, the process of searching for anticancer components is laborious. In current study, we proved the sensitization effects of total extract of Curcuma longa L. on 5-FU against HCT8/FU, a 5-FU resistant colorectal cancer cell line. A biochemometric analytical method using orthogonal partial least squares-discriminant analysis (OPLS-DA) model was established to identify the potential sensitization agents in Curcuma longa L. and predict their possible action mechanisms simultaneously before the agents were obtained. By correlating the 1H NMR-based metabolic profiles of Curcuma longa L. extract with its specific biological functions, we screened out the proton signals being responsible for the effects. According to the 1D CSSF-TOCSY spectra, the proton signals were attributed to three compounds, including curcumin, demethoxycurcumin, and bisdemethoxycurcumin, respectively. Moreover, two mechanisms, including reversal of drug resistance and disruption in lactate excretion, were revealed to be possible explanations for the activity enhancement. To validate the method, the three compounds were obtained and evaluated for their combined effects with 5-FU against HCT8/FU cells. The results confirmed that all the compounds significantly enhanced the sensitivity of HCT8/FU cells to 5-FU treatment. Furthermore, downregulation of the drug resistance related transporters ABCG2, MRP1 and P-gp, and lactate membrane transporter MCT1 in the cells following combination treatments, corroborated the previous predictions about the action mechanisms obtained from the methods. This work may provide a method for the fast identification of active agents in the mixture, and, meanwhile, prediction of their possible action mechanisms before the process of isolation.