Neuroprotective effect of berberine-loaded niosomes against brain injury in dyslipidemic rats: The interplay between oxidative stress, mitochondrial dysfunction and apoptotic signals.

UNLABELLED: Dyslipidemia is a major risk factor for the development of atherosclerosis, cardiovascular diseases, and brain injury. Berberine (BER), a type of isoquinoline alkaloid, has the potential to enhance mitochondrial performance owing to its remarkable antioxidant properties. This study aimed to explore how berberine-loaded niosomes (BER-NIO) would alleviate the adverse effects of brain injury in dyslipidemic rats. Hence, for this purpose, the genes of electron transport chain, mitochondrial dynamics, mitophagy, and apoptosis were assessed in brain tissue. Moreover, molecular docking analysis was done to predict this target pathway.

METHODS

Thirty-five male Sprague Dawley rats were separated into five groups: (I) Control (Ctl), (II) Poloxamer 407 (Plx), (III) Plx + BER-NIO, (IV) Plx + NC, and (V) Plx + BER-NIO + NC.

RESULTS

BER-NIO improved lipid profile, brain MDA, and brain total antioxidant capacity (TAC) compared to Plx group. Moreover, BER-NIO was able to notably restore the activity of mitochondrial respiratory chain complexes through upregulation of the mRNA expression levels of Ndufs1, Sdhc, Coq8a, Cox6a2 and Atp5f1a. It also enhanced the mitochondrial dynamics via modulation of the transcriptional level of DRP-1, MFN-1, and MFN-2. In addition, administration of BER-NIO to dyslipidemic rats regulated the mitophagy pathway through alteration of PINK-1/Prkn pathway within brain tissue. Furthermore, BER-NIO notably enhanced neurological function through reduction of brain pathological alterations, suppression of apoptosis and decrease of the biomarker for brain injury (GFAP). Interestingly, molecular docking analysis revealed a strong binding affinity between BER and MFN-2, PINK-1 and caspase-3.

CONCLUSION

The findings suggested that the BER-NIO is effective in the reduction of brain injury in dyslipidemic rats via modulation of brain oxidant/antioxidant status and mitochondrial functions.