Cryptotanshinone possesses therapeutic effects on ischaemic stroke through regulating STAT5 in a rat model

Abstract

Context

Cryptotanshinone (CT), a lipophilic compound extracted from roots of Salvia miltiorrhiza Bunge (Lamiaceae) (Danshen), has multiple properties in diseases, such as pulmonary fibrosis, lung cancer, and osteoarthritis. Our previous findings suggest that CT plays a protective role in cerebral stroke. However, the molecular mechanisms underlying CT protection in ischaemic stroke remain unclear.

Objective

This study examines the effect of CT on ischaemic stroke.

Materials and methods

We used the middle cerebral artery occlusion (MCAO) rat (Sprague-Dawley rats, 200 ± 20 g, n = 5) model with a sham operation group was treated as negative control. MCAO rats were treated with 15 mg/kg CT using intragastric administration. Moreover, TGF-β (5 ng/mL) was used to treat MCAO rats as a positive control group.

Results

The 50% inhibitory concentration (IC₅₀) of CT on CD4⁺ cell damage was 485.1 μg/mL, and median effective concentration (EC₅₀) was 485.1 μg/mL. CT attenuates the infarct region in the MCAO model. The percentage of CD4⁺CD25⁺FOXP3⁺ Treg cells in the peripheral blood of the MCAO group was increased with CT treatment. The protein level of FOXP3 and the phosphorylation of STAT5 were recovered in the CD4⁺CD25⁺ Treg cells of model group after treated with CT. Importantly, the effects of CT treatment were blocked by treatment with the inhibitor STAT5-IN-1 in CD4⁺ T cells of the MCAO model.

Discussion and conclusion

Our findings not only enhance the understanding of the mechanisms underlying CT treatment, but also indicate its potential value as a promising agent in the treatment of ischaemic stroke. Further study will be valuable to examine the effects of CT on patients with ischaemic stroke.

Keywords:

• Tregs
• FOXP3
• CD4 ⁺ CD25 ⁺ FOXP3⁺ Treg cells

Acknowledgements

The authors sincerely acknowledged the assistance given by Jinhua Central Hospital, Zhejiang Province; Mingyue Street No. 351, Jinhua City, Zhejiang 321000, P.R. China for present research.

Disclosure of statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was supported by the Public Welfare Project of Zhejiang Science and Technology Department [No. 2018C37094] and Social Development Key Projects of Jinhua Science and Technology Bureau [No. 2019-3-01].