Emerging Applications of Metabolomics in Traditional Chinese Medicine Treating Hypertension: Biomarkers, Pathways and More

Abstract

Hypertension is a prevalent, complex, and polygenic cardiovascular disease, which is associated with increased mortality and morbidity. Across the world, traditional Chinese medicine (TCM) constituted by herbal medicine and non-pharmacological therapies is used to assist blood pressure management. Though widely accepted in daily practice, its mechanism remains largely unknown. Recent years saw a number of studies utilizing metabolomics technologies to elucidate the biological foundation of the antihypertensive effect of TCM. Metabolomics is a relatively "young" omics approach that has gained enormous attention recently in cardiovascular drug discovery and pharmacology studies of natural products. In this review, we described the use of metabolomics in deciphering TCM diagnostic codes for hypertension and in revealing molecular events that drive the antihypertensive effect. By corroborating the diagnostic rules, there's accumulating evidence showing that metabolic profile could be the signature of different syndromes/patterns of hypertension, which offers new perspectives for disease diagnosis and efficacy optimization. Moreover, TCM treatment significantly altered the metabolic perturbations associated with hypertension, which could be a crucial mechanism of the therapeutic effect of TCM. Not only significantly rebalances the dynamics of metabolic flux, TCM but also elicits metabolic network reorganization through restoring the functions of key metabolites, and metabolic pathways. The role of TCM in regulating metabolic perturbations will be informative to researchers seeking new leads for drug discovery. This review further envisioned the promises of employing metabolomics to explore network pharmacology, host-gut microbiota interactions and metabolic reprogramming in TCM, and possible herb-drug interactions in this field in future.

Keywords: hypertension; metabolic regulation; metabolome; metabolomics; traditional Chinese medicine.

Figure 1

The antihypertensive herbal drug/formula- metabolic pathway map. Present metabolomics studies showed that antihypertensive herbal drugs/formulas are connected with carbohydrate metabolism, lipid metabolism, amino acid metabolism, and other major metabolic pathways, indicating the potential role of metabolic alternations induced by traditional Chinese medicine in treating hypertension. The interconnected network revealed that the two most prominent substance metabolisms activated by traditional Chinese medicine could be lipid and amino acid, as they have more frequent and concurrent biological information communications denoted by connecting lines.

Figure 2

The antihypertensive herbal drug/formula- metabolic pathway map. Traditional Chinese medicine administrated by human for the purpose of treating hypertension and other cardiovascular diseases may take effect through two major paths: (1) though regulating genetic predispositions to module the enzymatic activities and consequently fluctuate the metabolome, which in turn changes the biological phenotype of a patient; (2) though rejuvenating the gut and restoring the intestinal hemostasis to reshape the composition and function of the gut microbiota, which will results in an increased production of blood pressure-benefit metabolites entering circulation to improve the clinical outcome.