Pectin-coated Malvidin-3-O-galactoside attenuates silica-induced pulmonary fibrosis by promoting mitochondrial autophagy and inhibiting cell apoptosis.

Abstract

Background: Blueberries are a rich source of anthocyanins, which have been established to have multiple beneficial properties. However, the structure of anthocyanin monomers is unstable and their bioavailability is low. To date, whereas functional studies on anthocyanins have focused mainly on the effects of their monomers on liver and kidney, few have examined the interventional effects on pulmonary fibrosis.

Purpose: In this study, we combined malvidin-3-O-galactoside (M3G)¹ derived from blueberries with pectin (PEC)² to form an anthocyanin-pectin complex (M3G-PEC),³ the anti-fibrotic effects of which were examined by administering to mice with modeled pulmonary fibrosis induced by silica particles (SP).⁴ METHODS: To evaluate the therapeutic effects and mechanisms of action of M3G-PEC with respect to the progression of pulmonary fibrosis, we measured autophagy- and apoptosis-related indices in C57BL/6 mice and mouse alveolar macrophage cell line (MH-S).⁵ RESULTS: The results of in vivo and in vitro studies revealed that M3G-PEC can alleviate the degree of pulmonary fibrosis, enhances the expression of Microtubule-associated protein light chain 3 (LC3),⁶ PTEN-inducible putative kinase 1 (PINK1),⁷ Parkin and B-cell lymphoma-2 (BCL-2),⁸ and causes the down-regulation of Caspase-3, P62, p-mammalian target of rapamyein (p-mTOR),⁹ phosphorylated protein kinase B (p-Akt)¹⁰ and Bax. And then, M3G-PEC contributes to maintaining a steady mitochondrial membrane potential and reduces the release of cytochrome c (Cyt-C)¹¹ in cells.

Conclusion: Collectively, these findings indicate that M3G-PEC can preserve the bioactivity of anthocyanins and effectively enhance their bioavailability. Moreover, by regulating the BECN-1/Akt/mTOR pathway, M3G-PEC can influence the progression of silica-induced pulmonary fibrosis.