6-Bromoindirubin-3′-Oxime (6BIO) Suppresses the mTOR Pathway, Promotes Autophagy, and Exerts Anti-aging Effects in Rodent Liver

Abstract

Liver aging is associated with age-related histopathological and functional changes that significantly enhance the risk of numerous diseases or disorders developing in elderly populations. 6-Bromoindirubin-3′-oxime (6BIO), a potent inhibitor of glycogen synthase kinase-3 (GSK-3), has been implicated in various age-related diseases and processes, such as tumorigenesis, neurodegeneration, and diabetes. Recent studies have also revealed that 6BIO increases autophagy in yeast, mammalian cell lines, and dopaminergic neurons, which is one of the classical mechanisms strongly associated with liver aging. However, the impact or the mechanism of action of 6BIO in liver remains entirely unknown. Here, we find that 6BIO reduces oxidative stress, improves lipid metabolism, enhances autophagy, and significantly retards liver aging via modulating the GSK-3β pathway and mTOR pathway. Our findings suggest that 6BIO could be a potential agent to protect the liver in the field of anti-aging pharmacology.

6-Bromoindirubin-3′-oxime Promotes Osteogenic Differentiation of Periodontal Ligament Stem Cells and Facilitates Bone Regeneration in a Mouse Periodontitis Model

“…6-Bromoindirubin-3′-oxime (BIO) is a semisynthetic cell-permeable indirubin derivative that can be used in breast inflammation, diabetes, liver aging, neurodegenerative disorders, and other diseases and acts by reducing tumorigenesis, neurodegeneration, and oxidative stress and enhancing autophagy. − Indirubin and its derivatives are competitive adenosine-triphosphate (ATP) inhibitors of glycogen synthase kinase-3 (GSK-3) phosphorylation, thus activating the Wnt signaling pathway . Because the osteogenic differentiation of PDLSCs is a complex biological process that can be regulated by the Wnt pathway, we hypothesized that BIO may play a role in the regeneration of alveolar bone.…”

Drug Testing for Residual Progression of Diabetic Kidney Disease in Mice Beyond Therapy with Metformin, Ramipril, and Empagliflozin

“…Indeed, numerous studies have documented drug candidates with podocyte-protective effects in in vitro and in vivo models of podocyte injury, but rigorous testing of podocyte-directed therapies in a model mimicking closely the clinical scenario of residual progression of diabetic kidney disease beyond standard therapy is not yet available. Here, we focused on (2'Z,39E)-6-bromoindirubin-39-oxime (BIO), a compound modulating a number of the aforementioned molecular pathways, 20 to endorse podocyte viability and function in vitro, and podocyte de novo formation and terminal differentiation in vivo. [21][22][23] Altogether, we hypothesized that the particular renoprotective effects of BIO would attenuate CKD progression beyond metformin, ramipril, and empagliflozin (MRE) therapy in obese db/db mice with T2DM and progressive GFR decline.…”

Chemotherapeutic effects of Apigenin in breast cancer: Preclinical evidence and molecular mechanisms; enhanced bioavailability by nanoparticles

“…Numerous kinds of nanomaterials such as metallic–based nanomaterials, lipid-based and polymeric nanoparticles were developed in order to the highly effective delivery of AP [86] , [87] , [88] . The oral bioavailability of AP nanoparticles was about 5 fold upper compared to the naked AP, and this formulation shows no toxic outcome on the organs of mice [89] . Various studies have revealed that solid dispersion (SD) can be effectively applied in order to the improving the dissolution level of poorly water-soluble drugs [90] .…”