1H NMR-Based Metabolomics Reveals Refined-Huang-Lian-Jie-Du-Decoction (BBG) as a Potential Ischemic Stroke Treatment Drug With Efficacy and a Favorable Therapeutic Window.

Yan Lv,Shanting Liao,Xiaowei Fu,Dingqiao Xu,Junsong Wang,Lingyi Kong,Minghua Yang

doi:10.3389/fphar.2019.00337

Abstract

Huang-Lian-Jie-Du-Decoction (HLJDD) is a traditional Chinese medicine (TCM) used to treat ischemic stroke. However, the complexity of its chemical composition makes quality control difficult. Berberine, baicalin, and geniposide are the three main ingredients in HLJDD. Here, a formula of BBG comprised of berberine, baicalin, and geniposide, known as Refined-Huang-Lian-Jie-Du-Decoction, was investigated for its efficacy, therapeutic window, and mechanisms of action. BBG was assessed on two major types of ischemic stroke, cerebral ischemia-reperfusion (I/R) injury, and continuous ischemia injury, respectively. BBG showed efficacy comparable to HLJDD in the treatment of cerebral I/R injury within 5 h after injury initiation but did poorly in treating continuous ischemia injury. BBG exhibited neuroprotective effects on cerebral I/R injury by regaining the balance in energy metabolism, oxidative stress, amino acid metabolism, inflammation, and nucleic acid metabolism. These results suggested that BBG could be a good alternative to HLJDD, with high efficacy and a long therapeutic window, which shows great potential for drug development to treat stroke.

Highlights

Stroke remains a global health problem, in undeveloped countries (O’donnell et al, 2016)
There was no significant difference in the infarct volumes between the HLJDD and BBG groups (Figure S3)
Treatments with each BBG component individually could obviously reduce infarct volumes when compared to transient middle cerebral artery occlusion (TMCAO) group, but not as prominently as with BBG (P < 0.05)

Summary

Introduction

Stroke remains a global health problem, in undeveloped countries (O’donnell et al, 2016). It is the second cause of death clinically (Lozano et al, 2012), making its prevention and treatment a worldwide health concern. Only tissue plasminogen activator (t-PA) has been approved by the Food and Drug Administration (FDA, USA). It only benefits about 5% of patients due to its high risk-to-benefit ratio and narrow therapeutic window (Mozaffarian et al, 2016). A high priority in the field is to seek other therapies with good efficacy and safety

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Conclusion