Rapid discovery of potentially vasodilative compounds from Uncaria by UHPLC/Q-Orbitrap-MS based metabolomics and correlation analysis.

• The metabolites between U. rhynchophylla (Miq.) Miq. ex Havil. and U. hirsuta Havil. by LC-MS based metabolomics were investigated. • Utilizing chemometrics including PCA and OPLS-DA to identify 16 distinguished compounds between URM and UHH. • By combining multivariate statistical analysis and correlation analysis, the potential anti-hypertension compounds were discovered. • The activities of the potential compounds were fully validated. The genus Uncaria belongs to the family of Rubiaceae, which contains approximately 34 species. It has been widely used as a traditional Chinese medicine (TCM) in China to treat hypertension, fevers, headaches, gastrointestinal illness, epilepsy, wounds, and ulcers. Uncaria rhynchophylla. (Miq.) Miq. ex Hvail.(URM) and Uncaria hirsuta Havil.(UHH) are mainly used as remedies for hypertension, which both belong to the resource of "Gou-teng" in the Chinese Pharmacopoeia. However, the authentic antihypertensive components of Uncaria still have not been fully elucidated until now. In this work, we firstly explored and compared the vasorelaxation effect of URM and UHH on the isolated rat mesenteric artery ring. Then, the variations of metabolite profiles between URM and UHH samples were investigated by UHPLC/Q-Orbitrap-MS, and 16 different metabolites have been found through multivariate statistical analysis. Further, the potential vasodilative compounds which include corynoxeine, isocorynoxeine, isorhynchophylline, rhynchophylline, hirsuteine and hirsutine were screened through the correlation analysis between metabolites and anti-hypertension activities. And the relaxation effects of the six compounds on the mesenteric artery have verified. The results indicated that metabolomics combined with correlation analysis could be effective strategies to rapid explore the active compounds from TCM. [ABSTRACT FROM AUTHOR]