Adenosine monophosphate-activated protein kinase modulation by berberine attenuates mitochondrial deficits and redox imbalance in experimental diabetic neuropathy

showing the therapeutic effects of Berberine (BRB) in experimental DN. BRB inhibits mitochondrial complex I partially and thereby cause increased AMP/ATP ratio, which stimulates AMPK activity (Thr 172 phosphorylation). Phosphorylated AMPK produces several beneficial therapeutic effects in DN either by transcriptional regulation or by direct phosphorylation of several cellular targets. Its activation can also exert changes in NAD pool to stimulate SIRT1 activity. SIRT1 activation is also observed to produce similar metabolic and mitochondrial effects as that of AMPK.(AMPK: AMP activated protein kinase, mTOR: mammalian target of rapamycin, Nrf2: Nuclear factor (erythroid-derived 2)-like 2, NF-κB: Nuclear factor kappa B, PGC-1α: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha).246