The Therapeutic Effects of SP-8356, a Verbenone Derivative, with Multimodal Cytoprotective Mechanisms in an Ischemic Stroke Rat Model

Song, Hwa Young; Jin, Sejong; Lee, Sekwang; Jalin, Angela Melinda Anthony; Roh, Kyung-Hye; Kim, Won-Ki

doi:10.3390/ijms252312769

Open AccessArticle

The Therapeutic Effects of SP-8356, a Verbenone Derivative, with Multimodal Cytoprotective Mechanisms in an Ischemic Stroke Rat Model

by

Hwa Young Song

^1,2,†,

Sejong Jin

^1,3,†

,

Sekwang Lee

^1,4

,

Angela Melinda Anthony Jalin

¹,

Kyung-Hye Roh

² and

Won-Ki Kim

^1,*

¹

Department of Neuroscience, Korea University College of Medicine, Seoul 02841, Republic of Korea

²

Central Research Institute, Shin Poong Pharmaceutical Company, Ltd., Ansan 15610, Republic of Korea

³

Department of Anesthesiology and Pain Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan 15355, Republic of Korea

⁴

Department of Physical Medicine and Rehabilitation, Korea University College of Medicine, Seoul 02841, Republic of Korea

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2024, 25(23), 12769; https://doi.org/10.3390/ijms252312769

Submission received: 14 October 2024 / Revised: 18 November 2024 / Accepted: 26 November 2024 / Published: 27 November 2024

(This article belongs to the Section Molecular Biology)

Download

Browse Figures

Versions Notes

Abstract

An ischemic cerebral stroke results from the interruption of blood flow to the brain, triggering rapid and complex cascades of excitotoxicity, oxidative stress, and inflammation. Current reperfusion therapies, including intravenous thrombolysis and mechanical thrombectomy, cause further brain injury due to reperfusion-induced cytotoxicity. To date, novel cytoprotective therapies that could address these challenges have yet to be developed, likely due to the limitations of targeting a single pathologic mechanism. To address these unmet clinical needs, we investigated a synthetic verbenone derivative, SP-8356, as a potential multi-target cytoprotective agent for acute ischemic strokes. In transient middle cerebral artery occlusion (MCAO) rats, SP-8356 significantly reduced brain infarct and edema volumes while improving acute neurological deficits in a dose-dependent manner. Furthermore, SP-8356 improved long-term outcomes, particularly by reducing mortality. These potent cytoprotective effects of SP-8356 were achieved by suppressing the excessive production of free radicals and pro-inflammatory cytokines, reducing the infiltration of inflammatory cells, and mitigating increases in blood–brain barrier permeability. Additional research is needed to determine whether co-administration of SP-8356 can extend the therapeutic time window of reperfusion therapies by mitigating ischemia/reperfusion injury.

Keywords: ischemic stroke; middle cerebral artery occlusion (MCAO); cytoprotective; SP-8356; verbenone; oxidative stress; inflammation; blood–brain barrier (BBB); brain edema

Share and Cite

MDPI and ACS Style

Song, H.Y.; Jin, S.; Lee, S.; Jalin, A.M.A.; Roh, K.-H.; Kim, W.-K. The Therapeutic Effects of SP-8356, a Verbenone Derivative, with Multimodal Cytoprotective Mechanisms in an Ischemic Stroke Rat Model. Int. J. Mol. Sci. 2024, 25, 12769. https://doi.org/10.3390/ijms252312769

AMA Style

Song HY, Jin S, Lee S, Jalin AMA, Roh K-H, Kim W-K. The Therapeutic Effects of SP-8356, a Verbenone Derivative, with Multimodal Cytoprotective Mechanisms in an Ischemic Stroke Rat Model. International Journal of Molecular Sciences. 2024; 25(23):12769. https://doi.org/10.3390/ijms252312769

Chicago/Turabian Style

Song, Hwa Young, Sejong Jin, Sekwang Lee, Angela Melinda Anthony Jalin, Kyung-Hye Roh, and Won-Ki Kim. 2024. "The Therapeutic Effects of SP-8356, a Verbenone Derivative, with Multimodal Cytoprotective Mechanisms in an Ischemic Stroke Rat Model" International Journal of Molecular Sciences 25, no. 23: 12769. https://doi.org/10.3390/ijms252312769

APA Style

Song, H. Y., Jin, S., Lee, S., Jalin, A. M. A., Roh, K.-H., & Kim, W.-K. (2024). The Therapeutic Effects of SP-8356, a Verbenone Derivative, with Multimodal Cytoprotective Mechanisms in an Ischemic Stroke Rat Model. International Journal of Molecular Sciences, 25(23), 12769. https://doi.org/10.3390/ijms252312769

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

The Therapeutic Effects of SP-8356, a Verbenone Derivative, with Multimodal Cytoprotective Mechanisms in an Ischemic Stroke Rat Model

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI