Dissecting the Metabolic Phenotype of the Antihypertensive Effects of Five Uncaria Species on Spontaneously Hypertensive Rats.

Zijin Feng,Wenyong Wu,Linlin Zhang,Wanying Wu,Haijuan Zhi,Yang Yu,Yanping Deng,Jinjun Hou,Xia Wang,De-An Guo

doi:10.3389/fphar.2019.00845

Abstract

The sourcing of plants from multiple botanical origins is a common phenomenon in traditional Chinese medicines. Uncaria Stem with Hooks (UHs) are approved for using five botanical origins in the Chinese Pharmacopoeia (2015 Edition). All five UHs are commonly used for treating hypertension even though the plants have different chromatographic fingerprints based on our previous study. However, their hypotensive effects and metabolic phenotypes have not been fully studied. In the present study, spontaneously hypertensive rats (SHRs) were orally administered five aqueous extracts (4 g crude drug/kg) prepared from the different UHs over a 6-week period. Systolic blood pressure (SBP) was measured every week, and urine was collected after SBP measurement. Untargeted metabonomics was performed using ultra performance liquid chromatography (UPLC) coupled with an LTQ-Orbitrap mass spectrometer. Bidirectional orthogonal projection to latent structures discriminant analysis (O2PLS-DA), Student’s t test, and correlation analysis were used for pattern recognition and the selection of significant metabolites. A similar and prolonged reduction in SBP was observed in each of the groups given the five different UHs, while the metabolic profiles were perturbed slightly compared with that of SHR. Further analysis has shown that only a few common, different components were observed within the five groups, which showed the similar antihypertensive effect in spite of the distinct metabolic pathways due to their different alkaloid composition. These results help in understanding the mechanisms of the phenomenon “different species, same effect” of UHs.

Highlights

Traditional Chinese medicines (TCMs) are important alternative therapeutics for chronic diseases because of their significant biological effects in disease prevention and treatment (Yim et al, 2000; Chen et al, 2008; Lee et al, 2013)
Miq. ex Havil. (URM), 9 and 10 in Uncaria macrophylla Wall. (UMW), and 13 and 14 in Uncaria hirsuta Havil. (UHH). These results confirmed that the chromatographic fingerprints and the main components of the five individual Uncaria species were quite different
Treatments were stopped, and all Uncaria Stem with Hooks (UHs)-treated groups remained at a lower systolic blood pressure (SBP) than the spontaneously hypertensive rats (SHRs) model groups (p < 0.05). These results demonstrated that all five different UHs had similar effects on decreasing SBP

Summary

Introduction

Traditional Chinese medicines (TCMs) are important alternative therapeutics for chronic diseases because of their significant biological effects in disease prevention and treatment (Yim et al, 2000; Chen et al, 2008; Lee et al, 2013). The Metabolic Phenotype of Five Different Uncaria phenomenon of multiple botanical origins (one-to-multiple) is common. It means that one recommended constituent in a remedy may be derived from multiple botanical species, instead of assigned individual plant for the remedy (Wu et al, 2007; Tian et al, 2009; Da et al, 2012). TCM materials derived from different plant species usually differ in morphology, as well as their microscopic and chemical characteristics. They can have similar clinical applications and effects (Zheng et al, 2010; Ashfaq et al, 2011). It is urgent to understand how similar clinical effects could be produced by TCMs with quite different chemical profiles

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