4.4 Article

Metabolomics coupled with integrative pharmacology reveals the therapeutic effect of l-borneolum against cerebral ischaemia in rats

Journal

JOURNAL OF PHARMACY AND PHARMACOLOGY
Volume 72, Issue 9, Pages 1256-1268

Publisher

OXFORD UNIV PRESS
DOI: 10.1111/jphp.13294

Keywords

cerebral ischaemia; energy metabolism; l-borneolum; metabolomics; permanent MCAO

Funding

  1. National Natural Science Foundation of China [81703725]
  2. Chengdu University of TCM Foundation [QNXZ2018025, CXTD2018004]

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Objectives This study aimed to investigate metabolic biomarker changes and related metabolic pathways before and after treatment with l-borneolum in cerebral ischaemic rats. Methods Rats were subjected to pMCAO surgery. The Zea-Longa scoring method was used to evaluate neurological deficits. TTC staining was used to observe cerebral infarction. HE staining was used to observe the pathological changes in brain tissue. The metabolomics method was used to analyse the changes in metabolism. Results The pharmacology changes of the H-B group were significantly different from those of the vehicle group. Moreover, according to the metabolomics method, identification of potential biomarkers in cerebral ischaemia treatment showed that the levels of l-valine and l-arginine were increased while the levels of N-succinyl-L,L-2,6-diaminopimelate and LysoPC (18 : 1(9Z)) were reduced, which were related to energy metabolism. Simultaneously, thermogenesis and bile secretion levels were inhibited by l-borneolum. Furthermore, elevated level of methotrexate might be related to an anti-inflammatory effect. Conclusions The therapeutic effect of l-borneolum on cerebral ischaemia might be associated with the regulation of energy metabolism, thermogenesis and bile secretion. These metabolic changes and the core target changes, as well as the metabolic-target pathway network, help to elucidate the mechanisms governing the effect of l-borneolum on cerebral ischaemia.

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