Translations:Berberine/11/en
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On the negative side, berberine has been found to impair muscle metabolism by two mechanisms. It impairs mitochondrial function stimulating the expression of atrogin-1 without affecting phosphorylation of forkhead transcription factors. The increase in atrogin-1 not only stimulates protein degradation but also suppresses protein synthesis, causing muscle atrophy.[1] It has also been found[2] to restore SOD1 activity inhibited by lipopolysaccharides.
- ↑ Wang et al.: Atrogin-1 affects muscle protein synthesis and degradation when energy metabolism is impaired by the antidiabetes drug berberine. Diabetes 2010;59:1879-89. PMID: 20522589. DOI. OBJECTIVE: Defects in insulin/IGF-1 signaling stimulate muscle protein loss by suppressing protein synthesis and increasing protein degradation. Since an herbal compound, berberine, lowers blood levels of glucose and lipids, we proposed that it would improve insulin/IGF-1 signaling, blocking muscle protein losses. RESEARCH DESIGN AND METHODS: We evaluated whether berberine ameliorates muscle atrophy in db/db mice, a model of type 2 diabetes, by measuring protein synthesis and degradation in muscles of normal and db/db mice treated with or without berberine. We also examined mechanisms for berberine-induced changes in muscle protein metabolism. RESULTS: Berberine administration decreased protein synthesis and increased degradation in muscles of normal and db/db mice. The protein catabolic mechanism depended on berberine-stimulated expression of the E3 ubiquitin ligase, atrogin-1. Atrogin-1 not only increased proteolysis but also reduced protein synthesis by mechanisms that were independent of decreased phosphorylation of Akt or forkhead transcription factors. Impaired protein synthesis was dependent on a reduction in eIF3-f, an essential regulator of protein synthesis. Berberine impaired energy metabolism, activating AMP-activated protein kinase and providing an alternative mechanism for the stimulation of atrogin-1 expression. When we increased mitochondrial biogenesis by expressing peroxisome proliferator-activated receptor gamma coactivator-1alpha, berberine-induced changes in muscle protein metabolism were prevented. CONCLUSIONS: Berberine impairs muscle metabolism by two novel mechanisms. It impairs mitochonidrial function stimulating the expression of atrogin-1 without affecting phosphorylation of forkhead transcription factors. The increase in atrogin-1 not only stimulated protein degradation but also suppressed protein synthesis, causing muscle atrophy.
- ↑ Sarna et al.: Berberine inhibits NADPH oxidase mediated superoxide anion production in macrophages. Can. J. Physiol. Pharmacol. 2010;88:369-78. PMID: 20393601. DOI. Oxidative stress and amplified redox signaling contribute to the pathogenesis of many human diseases including atherosclerosis. The superoxide-generating phagocytic NADPH oxidase is a key source of oxidative stress in the developing atheroma. The aim of the present study was to examine the effect of berberine, a plant-derived alkaloid, on NADPH oxidase-mediated superoxide anion production in macrophages. Lipopolysaccharide (LPS) treatment activated NADPH oxidase in THP-1 monocyte-derived macrophages and increased the intracellular level of superoxide anions. Preincubation of cells with berberine demonstrated a concentration-dependent (10-50 micromol/L) and time-dependent (6-24 h) inhibition of superoxide anion generation in LPS-stimulated macrophages. Cell viability tests confirmed that berberine, at concentrations sufficient for inhibiting NADPH oxidase-mediated superoxide anion generation in macrophages, did not affect cell viability. Real-time PCR analysis revealed that addition of berberine to the culture medium was able to reduce gp91phox mRNA expression in LPS-treated cells. Berberine also restored superoxide dismutase (SOD) activity, which was found to be inhibited by LPS treatment. In conclusion, results from the present study demonstrate that berberine can effectively reduce intracellular superoxide levels in LPS- stimulated macrophages. Such a restoration of cellular redox by berberine is mediated by its selective inhibition of gp91phox expression and enhancement of SOD activity. The therapeutic relevance of berberine in the prevention and management of atherosclerosis remains to be further investigated.
