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Protective Effects of 28-O-Caffeoyl Betulin (B-CA) on the Cerebral Cortex of Ischemic Rats Revealed by a NMR-Based Metabolomics Analysis

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A Correction to this article was published on 16 January 2021

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Abstract

28-O-caffeoyl betulin (B-CA) has been demonstrated to reduce the cerebral infarct volume caused by transient middle cerebral artery occlusion (MCAO) injury. B-CA is a novel derivative of naturally occurring caffeoyl triterpene with little information associated with its pharmacological target(s). To date no data is available regarding the effect of B-CA on brain metabolism. In the present study, a 1H-NMR-based metabolomics approach was applied to investigate the therapeutic effects of B-CA on brain metabolism following MCAO in rats. Global metabolic profiles of the cortex in acute period (9 h after focal ischemia onset) after MCAO were compared between the groups (sham; MCAO + vehicle; MCAO + B-CA). MCAO induced several changes in the ipsilateral cortex of ischemic rats, which consequently led to the neuronal damage featured with the downregulation of NAA, including energy metabolism dysfunctions, oxidative stress, and neurotransmitter metabolism. Treatment with B-CA showed statistically significant rescue effects on the ischemic cortex of MCAO rats. Specifically, treatment with B-CA ameliorated the energy metabolism dysfunctions (back-regulating the levels of succinate, lactate, BCAAs, and carnitine), oxidative stress (upregulating the level of glutathione), and neurotransmitter metabolism disturbances (back-regulating the levels of γ-aminobutyric acid and acetylcholine) associated with the progression of ischemic stroke. With the administration of B-CA, the levels of three phospholipid related metabolites (O-phosphocholine, O-phosphoethanolamine, sn-glycero-3-phosphocholine) and NAA improved significantly. Overall, our findings suggest that treatment with B-CA may provide neuroprotection by augmenting the metabolic changes observed in the cortex following MCAO in rats.

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Acknowledgements

The NMR data was recorded in the Institutional Technological Service Center of Shanghai Institute of Materia Medica, Chinese Academy of Sciences. This work was financially supported by the National Natural Science Foundation of China (Grant Nos. 21877119, 81872859, 21778061), and the National Science & Technology Major Project “Key New Drug Creation and Manufacturing Program” of China (Grant Nos. 2018ZX09711002, 2018ZX09711002-002-014).

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  1. Xia Liu, Zhi Ruan, and Xing-cheng Shao contribute equally to this work.

Authors and Affiliations

  1. Department of Analytical Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

    Xia Liu & Nai-xia Zhang

  2. CAS Key Laboratory of Receptor Research, Department of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

    Zhi Ruan, Hong-xuan Feng, Lei Wu, Wei Wang & Hai-yan Zhang

  3. Department of Natural Product Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

    Xing-cheng Shao, Hong-min Wang, Hong-yan Mu, Ru-jun Zhang & Wei-min Zhao

  4. University of Chinese Academy of Sciences, Beijing, 100049, China

    Xing-cheng Shao & Hong-yan Mu

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  1. Xia Liu
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Contributions

H-yZ, N-xZ and W-mZ designed the study. XL, RZ, H-yZ and N-xZ wrote the manuscript. XL, RZ, X-cS, H-xF, LW, WW, H-mW, H-yM, R-jZ performed the experiments.

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Correspondence to Wei-min Zhao, Hai-yan Zhang or Nai-xia Zhang.

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Liu, X., Ruan, Z., Shao, Xc. et al. Protective Effects of 28-O-Caffeoyl Betulin (B-CA) on the Cerebral Cortex of Ischemic Rats Revealed by a NMR-Based Metabolomics Analysis. Neurochem Res 46, 686–698 (2021). https://doi.org/10.1007/s11064-020-03202-z

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