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Therapeutic effects of a standardized-flavonoid Diospyros kaki L.f. leaf extract on transient focal cerebral ischemia-induced brain injury in mice

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Abstract

This study aimed to investigate the neuroprotective and therapeutic effects of Diospyros kaki L.f. leaves (DK) on transient focal cerebral ischemic injury and underlying mechanisms using a middle cerebral artery occlusion (MCAO) model of mice. The animals received the MCAO operation on day 0. The daily administrations of DK (50 and 100 mg/kg, p.o) and edaravone (6 mg/kg, i.v), a reference drug with radical scavenging activity, were started 7 days before (pre-treatment) or immediately after the MCAO operation (post-treatment) and continued during the experimental period. Histochemical, biochemical, and neurological changes and cognitive performance were evaluated. MCAO caused cerebral infarction and neuronal cell loss in the cortex, striatum, and hippocampus in a manner accompanied by spatial cognitive deficits. These neurological and cognitive impairments caused by MCAO were significantly attenuated by pre- and post-ischemic treatments with DK and edaravone, suggesting that DK, like edaravone, has therapeutic potential for cerebral ischemia-induced brain damage. DK and edaravone suppressed MCAO-induced changes in biomarkers for apoptosis (TUNEL-positive cell number and cleaved caspase-3 protein expression) and oxidative stress (glutathione and malondialdehyde contents) in the brain. Interestingly, DK, but not edaravone, mitigated an increase in blood–brain permeability and down-regulation of vascular endothelial growth factor protein expression caused by MCAO. Although the exact chemical constituents implicated in the effects of DK remain to be clarified, the present results indicate that DK exerts neuroprotective and therapeutic activity against transient focal cerebral ischemia-induced injury probably by suppressing oxidative stress, apoptotic process, and mechanisms impairing blood–brain barrier integrity in the brain.

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Acknowledgements

This research was in part financially supported by Ministry of Industry and Trade of the socialist republic of Vietnam under Grant number CTHD.DT.082/19-20.

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Authors and Affiliations

  1. Department of Pharmacology and Biochemistry, National Institute of Medicinal Materials, Hanoi, 10000, Vietnam

    Loan Thanh Thi Nguyen, Xoan Thi Le, Hang Nguyet Thi Pham & Phuong Thi Nguyen

  2. Department of Pharmacology, Hanoi Medical University, Hanoi, 10000, Vietnam

    Loan Thanh Thi Nguyen & Anh Van Thi Pham

  3. Department of Phytochemistry, National Institute of Medicinal Materials, Hanoi, 10000, Vietnam

    Tai Van Nguyen

  4. Faculty of Pharmacy, Duy Tan University, Danang, 550000, Vietnam

    Thu Bich Thi Nguyen

  5. Graduate School of Pharmaceutical Sciences, Daiichi University of Pharmacy, Fukuoka, 815-8511, Japan

    Kinzo Matsumoto

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  1. Loan Thanh Thi Nguyen
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Nguyen, L.T.T., Le, X.T., Pham, H.N.T. et al. Therapeutic effects of a standardized-flavonoid Diospyros kaki L.f. leaf extract on transient focal cerebral ischemia-induced brain injury in mice. J Nat Med 77, 544–560 (2023). https://doi.org/10.1007/s11418-023-01699-6

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