Baicalin and its nanoliposome ameliorate diquat-induced liver injury by promoting PINK1/Parkin-dependent mitophagy

Abstract

Background

Diquat, a commonly employed bipyridyl herbicide, is recognized for its hepatotoxic effects attributed to the generation of reactive oxygen species. Baicalin (BAI), a flavonoid derivative, has garnered significant research interest for its hepatoprotective properties. Nevertheless, the clinical application of BAI is constrained by its limited water solubility and poor bioavailability. To address these challenges, BAI-nanoliposome (BAI-NL) has emerged as a novel drug delivery platform aimed at enhancing therapeutic outcomes.

Methods

We used diquat-induced liver injury mouse model and AML12 hepatocytes to test the protective effect of BAI and BAI-NL on liver inflammation, oxidative stress, and mitochondrial function. The parameters included histological, biochemical, and molecular biological analyses.

Results

In the diquat-induced model, both BAI and BAI-NL exhibited effectiveness on attenuating liver inflammation. Ex vivo analyses further indicated that BAI-NL was superior to BAI in preserving mitochondrial membrane potential, reducing oxidative stress, and modulating the phosphatase and tensin homolog-induced putative kinase 1 (PINK1)/Parkin RBR E3 ubiquitin-protein ligase (Parkin) signaling pathway. These findings enhanced mitophagy and facilitated the removal of damaged mitochondria.

Conclusions

BAI-NL exhibited superior hepatoprotective effects compared to free BAI, possibly by reducing inflammation, preserving mitochondrial homeostasis, and reinstating autophagic balance through modulation of the PINK1/Parkin signaling pathway. These outcomes indicate a groundbreaking method for addressing liver diseases and underscore the potential of nanoliposome technology in augmenting the efficacy of natural compounds.