Abstract
Berberine, baicalin, and jasminoidin were major active ingredients of Huang-Lian-Jie-Du-Decoction (HLJDD), a famous prescription of traditional Chinese medicine (TCM), which has been used for the treatment of ischemic stroke. The aim of the present study was to classify their roles in the treatment effects of ischemic stroke. A rat model of middle cerebral artery occlusion (MCAO) was constructed to mimic ischemic stroke and treatment effects of berberine, baicalin, and jasminoidin, and HLJDD was assessed by neurologic deficit scoring, infarct volume, histopathology, immunohistochemistry, biochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. In addition, the 1H NMR metabolomics approach was used to assess the metabolic profiles, which combined with correlation network analysis successfully revealed metabolic disorders in ischemic stroke concerning the treatment of the three principal compounds from HLJDD for the first time. The combined results suggested that berberine, baicalin, and jasminoidin are responsible for the effectiveness of HLJDD on the treatment of ischemic stroke by amelioration of abnormal metabolism and regulation of oxidative stress, neuron autophagy, and inflammatory response. This integrated metabolomics approach showed its potential in understanding the function of complex formulae and clarifying the role of its components in the overall treatment effects.
Highlights
Stroke is one of the leading causes of death and disability worldwide, of which ischemic stroke accounts for approximately 85% [1, 2]
The results demonstrated that HLJDD, berberine, baicalin, and jasminoidin-induced neuroprotections were effective on 1 d, 3 d, and 7 d after ischemia
The optimized HPLC method was subsequently applied to the simultaneous quantitative analysis of berberine, baicalin, and jasminoidin in HLJDD extract (Figures 1(a) and 1(b) and Supplementary Figure S3), and their contents were determined to be 5.32%, 2.51%, and 2.09%, respectively
Summary
Stroke is one of the leading causes of death and disability worldwide, of which ischemic stroke accounts for approximately 85% [1, 2]. Over the past few years, the pharmaceutical industry has seen a shift from the search for “magic bullets” that target a single disease-causing molecule to the pursuit of combination therapies that comprise more than one active ingredients to treat complex illnesses such as ischemic stroke. This shift coincides with the tested advocacy of traditional Chinese medicine (TCM) to utilize combinatorial therapeutic strategies [3]. Our previous study showcased good efficacy of HLJDD in the treatment of ischemic stroke [10, 11]. The role of its principals in the treatment of stroke remains largely unknown
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