Borneol-modified tanshinone IIA liposome improves cerebral ischemia reperfusion injury by suppressing NF-κB and ICAM-1 expression

Abstract

Objective

To investigate the metabolism and brain tissue distribution of borneol-modified tanshinone IIA liposome (BO-TA-Lip) and its effect on NF-κB and ICAM-1 in cerebral ischemia reperfusion rats, thereby exploring the ameliorative mechanism of BO-TA-Lip on ischemic encephalopathy.

Methods

Particle size, entrapment efficiency, drug loading were measured to evaluate the preparation comprehensively. Metabolism and brain tissue distributions in vivo were measured by HPLC, and the pharmacokinetic parameters were calculated. In addition, 24 SD rats were randomly divided into sham, model, STS (sodium tanshinone IIA sulfonate, 30 mg/kg) and BO-TA-Lip groups (44 mg/kg). The middle cerebral artery occlusion (MCAO) rats were constructed with thread embolism method. Neurological deficits were scored using Zea Longa scoring standard. TTC and HE staining were used for the cerebral infarction and histopathological examination, respectively. The protein expression was examined by immunohistochemistry and Western blot.

Results

The average particle size, encapsulation efficiency and drug loading of BO-TA-Lip were (135.33 ± 7.25) nm, (85.95 ± 3.20)% and (4.06 ± 0.31)%, respectively. Both in the pharmacokinetic analysis of plasma and brain tissue, in BO-TA-Lip group, the peak concentration and the area under the curve increased, and the clearance rate decreased. The neurological deficit scores and infarct area of the BO-TA-Lip group were significantly lower than that of the model and STS groups. Besides, BO-TA-Lip reduced the protein expression of NF-κB, ICAM-1, IL-1β, TNF-α and IL-6 in the brain tissue.

Conclusion

BO-TA-Lip had higher bioavailability and better absorption in brain tissue, and could improve cerebral ischemia reperfusion injury, which might be related to the inhibitory effect of BO-TA-Lip in expression of NF-κB and ICAM-1.

Keywords:

• Borneol-modified tanshinone IIA liposome (BO-TA-Lip)
• cerebral ischemia reperfusion
• NF-κB
• ICAM-1
• pharmacokinetic parameters

Disclosure statement

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

Data availability statement

The data used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by grants from the Natural Science Foundation of Zhejiang Province [LYY18H300001], Zhejiang Traditional Chinese Medicine Science and Technology Program [2015ZB079; 2021ZA111], and Zhejiang Medical and Health Science and Technology Plan Project [2021KY865].