Berberine-sonodynamic therapy induces autophagy and lipid unloading in macrophage

Abstract

Impaired autophagy in macrophages accompanies the progression of atherosclerosis and contributes to lipid loading in plaques and ineffective lipid degradation. Therefore, evoking autophagy and its associated cholesterol efflux may provide a therapeutic treatment for atherosclerosis. In the present study, berberine-mediated sonodynamic therapy (BBR-SDT) was used to induce autophagy and cholesterol efflux in THP-1 macrophages and derived foam cells. Following BBR-SDT, autophagy was increased in the macrophages, autophagy resistance in the foam cells was prevented, and cholesterol efflux was induced. The first two effects were blocked by the reactive oxygen species scavenger, N-acetyl cysteine. BBR-SDT also reduced the phosphorylation of Akt and mTOR, two key molecules in the PI3K/AKT/mTOR signaling pathway, which is responsible for inducing autophagy. Correspondingly, treatment with the autophagy inhibitor, 3-methyladenine, or the PI3K inhibitor, LY294002, abolished the autophagy-induced effects of BBR-SDT. Furthermore, induction of cholesterol efflux by BBR-SDT was reversed by an inhibition of autophagy by 3-methyladenine or by a small interfering RNA targeting Atg5. Taken together, these results demonstrate that BBR-SDT effectively promotes cholesterol efflux by increasing reactive oxygen species generation, and this subsequently induces autophagy via the PI3K/AKT/mTOR signaling pathway in both ‘normal' macrophages and lipid-loaded macrophages (foam cells). Thus, BBR-SDT may be a promising atheroprotective therapy to inhibit the progression of atherosclerosis and should be further studied.

The Glycoprotein and Nucleocapsid Protein of Hantaviruses Manipulate Autophagy Flux to Restrain Host Innate Immune Responses

“…Torin1, a potent inhibitor of mTORC1/2, is generally applied as an autophagy inducer (Min et al, 2018). Hydroxychloroquine sulfate (CQ), an acidification inhibitor that impedes lysosome-mediated degradation, can accumulate autophagosomes and suppress autophagic flux (Kou et al, 2017). Here, we discovered that in both Torin1-treated cells and HTNV-infected cells of the 6 hpi group, most LC3-positive autophagic vacuoles were red (Figure 2A), indicating that these stimuli trigger complete autophagy flux.…”

Berberine as a potential autophagy modulator

“…It has been demonstrated that at the early stage of pulmonary fibrosis, Brb is more beneficial and has more preventive effects, whereas at the late stage, the efficacy of Brb is lower and in both stages, Brb increases autophagy. Brb can be used as a potential therapy for atherosclerosis, as well (Kou et al, 2017). The Brbsonodynamic therapy elevates the production of reactive oxygen and, subsequently, inhibits the activation of the Nod-like receptor family pyrin domain containing 3 (NFRL3) inflammasome.…”

Targeting autophagy enhances heat stress-induced apoptosis via the ATP-AMPK-mTOR axis for hepatocellular carcinoma

“…The siRNA sequences were as follows: negative control (NC) siRNA: 5 0 -UUCUCCGAACGUGUCACGUTT-3 0 , 3 0 -ACGUGACACGU UCGGAGAATT-5 0 ; Beclin-1 siRNA 1: 5 0 -GGUCUAAGACGUC CAACAATT-3 0 , 3 0 -UUGUUGGACGUCUUAGACCTT-5 0 ; Beclin-1 siRNA 2: 5 0 -GGAGCCAUUUAUUGAAACUTT-3 0 , 3 0 -AGUUUCA AUAAAUGGCUCCTT-5 0 ; Beclin-1 siRNA 3: 5 0 -GCUGCCGUUA UACUGUUCUTT-3 0 , 3 0 -AGAACAGUAUAACGGCAGCTT-5 0 ; and Atg5 siRNA: 5 0 -GCUUCGAGAUGUGUGGUUUTT-3 0 , 3 0 -GCUUCG AGAUGUGUGGUUUTT-5 0 . Atg5 siRNA was chosen according to a previous study [19].…”