Esculetin facilitates post-stroke rehabilitation by inhibiting CKLF1-mediated neutrophil infiltration

 So your competent? doctor and hospital should get human testing going. But they won't!

Esculetin facilitates post-stroke rehabilitation by inhibiting CKLF1-mediated neutrophil infiltration

• Jia-qi He,
• Ruo-lan Yuan,
• Yu-tong Jiang,
• Ye Peng,
• Jun-rui Ye,
• Sha-sha Wang,
• Li-qing Li,
• Yuan Ruan,
• Pei-yi Li,
• Xu Yan,
• Wen-bin He,
• Gang Li,
• Shi-feng Chu,
• Zhao Zhang &
• Nai-hong Chen 

Acta Pharmacologica Sinica (2024)Cite this article

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Abstract

Esculetin (ESC) is a coumarin-derived phytochemical prevalent in traditional Chinese medicine that exhibits anti-acute ischemic stroke activities. Our previous studies demonstrate that CKLF1 is a potential anti-stroke target for coumarin-derived compound. In this study we investigated whether CKLF1 was involved in the neuroprotective effects of ESC against photothrombotic stroke in mice. The mice were treated with ESC (20, 40 or 80 mg·kg⁻¹·d⁻¹, i.g.) for two weeks. The therapeutic effect of ESC was assessed using MRI, neurological function evaluation, and a range of behavioral tests on D1, 3, 7 and 14 of ESC administration. We showed that oral administration of ESC dose-dependently reduced the cerebral infarction volume within one week after stroke, improved behavioral performance, and alleviated neuropathological damage within two weeks. Functional MRI revealed that ESC significantly enhanced the abnormal low-frequency fluctuation (ALFF) value of the motor cortex and promoted functional connectivity between the supplementary motor area (SMA) and multiple brain regions. We demonstrated that ESC significantly reduced the protein levels of CKLF1 and CCR5, as well as the CKLF1/CCR5 protein complex in the peri-infarcted area. We showed that ESC (0.1–10 μM) dose-dependently blocked CKLF1-induced chemotactic movement of neutrophils in the Transwell assay, reducing the interaction of CKLF1/CCR5 on the surface of neutrophils, thereby reducing neutrophil infiltration, and decreasing the expression of ICAM-1, VCAM-1 and MMP-9 in the peri-infarct tissue. Knockout of CKLF1 reduced brain infarction volume and motor dysfunction after stroke but also negated the anti-stroke efficacy and neutrophil infiltration of ESC. These results suggest that the efficacy of ESC in promoting post-stroke neural repair depends on its inhibition on CKLF1-mediated neutrophil infiltration, which offering novel perspectives for elucidating the therapeutic properties of coumarins.

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Citrus Fruits as a Treasure Trove of Active Natural Metabolites That Potentially Provide Benefits for Human Health

Only 4.5 years old.  Is that enough time for your doctor and stroke hospital to incompetently not create stroke diet protocols?  Up to you but I would have them all fired starting with the board of directors.   If your stroke medical 'professionals' can't see the word neuroprotection and immediately think of usefulness in stroke recovery then you have cesspools of incompetence.  But this is just my non-medical opinion.

Citrus Fruits as a Treasure Trove of Active Natural Metabolites That Potentially Provide Benefits for Human Health

. 2015 Dec 24;9:68.

doi: 10.1186/s13065-015-0145-9. eCollection 2015. 

Xinmiao Lv  ¹ , Siyu Zhao  ¹ , Zhangchi Ning  ¹ , Honglian Zeng  ¹ , Yisong Shu  ¹ , Ou Tao  ¹ , Cheng Xiao  ² , Cheng Lu  ³ , Yuanyan Liu  ¹

Affiliations

• PMID: 26705419
• PMCID: PMC4690266
• DOI: 10.1186/s13065-015-0145-9

Free PMC article

Abstract

Citrus fruits, which are cultivated worldwide, have been recognized as some of the most high-consumption fruits in terms of energy, nutrients and health supplements. What is more, a number of these fruits have been used as traditional medicinal herbs to cure diseases in several Asian countries. Numerous studies have focused on Citrus secondary metabolites as well as bioactivities and have been intended to develop new chemotherapeutic or complementary medicine in recent decades. Citrus-derived secondary metabolites, including flavonoids, alkaloids, limonoids, coumarins, carotenoids, phenolic acids and essential oils, are of vital importance to human health due to their active properties. These characteristics include anti-oxidative, anti-inflammatory, anti-cancer, as well as cardiovascular protective effects, neuroprotective effects, etc. This review summarizes the global distribution and taxonomy, numerous secondary metabolites and bioactivities of Citrus fruits to provide a reference for further study. Flavonoids as characteristic bioactive metabolites in Citrus fruits are mainly introduced.