Oxidative stress plays a major role in acute and chronic liver injury. In hepatocytes, oxidative stress frequently triggers antioxidant response by activating nuclear erythroid 2‐related factor 2 (Nrf2), a transcription factor, which upregulates various cytoprotective genes. Thus, Nrf2 is considered a potential therapeutic target to halt liver injury. Several studies indicate that activation of Nrf2 signaling pathway ameliorates liver injury. The hepatoprotective potential of naturally occurring compounds has been investigated in various models of liver injuries. In this review, we comprehensively appraise various phytochemicals that have been assessed for their potential to halt acute and chronic liver injury by enhancing the activation of Nrf2 and have the potential for use in humans.

Nuclear factor-erythroid 2 related factor 2 (Nrf2)-mediated signaling plays a central role in maintaining cellular redox homeostasis of hepatic cells. Carbon monoxide releasing molecule-A1 (CORM-A1) has been reported to stimulate up-regulation and nuclear translocation of Nrf2 in hepatocytes. However, the role of CORM-A1 in improving lipid metabolism, antioxidant signaling and mitochondrial functions in nonalcoholic steatohepatitis (NASH) is unknown. In this study, we report that CORM-A1 prevents hepatic steatosis in high fat high fructose (HFHF) diet fed C57BL/6J mice, used as model of NASH. The beneficial effects of CORM-A1 in HFHF fed mice was associated with improved lipid homeostasis, Nrf2 activation, upregulation of antioxidant responsive (ARE) genes and increased ATP production. As, mitochondria are intracellular source of reactive oxygen species (ROS) and important sites of lipid metabolism, we further investigated the mechanisms of action of CORM-A1-mediated improvement in mitochondrial function in palmitic acid (PA) treated HepG2 cells. Cellular oxidative stress and cell viability were found to be improved in PA + CORM-A1 treated cells via Nrf2 translocation and activation of cytoprotective genes. Furthermore, in PA treated cells, CORM-A1 improved mitochondrial oxidative stress, membrane potential and rescued mitochondrial biogenesis thru upregulation of Drp1, TFAM, PGC-1α and NRF-1 genes. CORM-A1 treatment improved cellular status by lowering glycolytic respiration and maximizing OCR. Improvement in mitochondrial respiration and increment in ATP production in PA + CORM-A1 treated cells further corroborate our findings. In summary, our data demonstrate for the first time that CORM-A1 ameliorates tissue damage in steatotic liver via Nrf2 activation and improved mitochondrial function, thus, suggesting the anti-NASH potential of CORM-A1.

In order to study the less understood anti-tumor mechanism of pyrazolone based mixed ligand complexes, four Cu(II) mixed ligand complexes [Cu(L1)(Phen)NO₃] (1), [Cu(L2)(Bipy)NO₃] (2), [Cu(L2)(Phen)NO₃] (3) and [Cu(L2)(Bipy)NO₃] (4) [L1 = 3-methyl-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazole-4-carbaldehyde; L2 = 4-(1-naphthoyl)-3-methyl-1-(p-tolyl)-1H-pyrazol-5(4H)-one] have been synthesized and fully characterized. Single crystal X-ray diffraction analysis of three complexes indicated mononuclear structures exhibiting square pyramidal geometries. The inhibitory effects of the complexes on the cell population growth of the human lung carcinoma (A549) and human lung epithelial cell lines (L132) were determined by MTT assay, DAPI staining and DCFDA staining, which assessed mitochondrial dysfunction, nuclear condensation and intracellular oxidative stress, respectively. The expression levels of Bax (pro-apoptotic) and BCl2 (anti-apoptotic) genes were also studied in A549 cells wherein, both genes showed moderate downregulation after treatment with all the test complexes.

Cardioprotective potential of anthocyanin rich red cabbage extract (ARCE) was assessed in H₂O₂ treated rat neonatal cardiomyoblasts (H9c2 cells) and isoproterenol (ISO) induced rodent model of myocardial infarction. H₂O₂ treated H9c2 cells recorded cytotoxicity (48–50%) and apoptosis (57.3%), the same were reduced in presence of ARCE (7–10% & 12.3% respectively). Rats pretreated with ARCE for 30 days followed by ISO treatment recorded favourable heart: body weight ratio as compared to ISO treated group. Also, the mRNA levels of enzymatic antioxidants (sod and catalase) and apoptotic genes (bax and bcl-2) in ARCE+ISO treated group were similar to the control group suggesting that ARCE pretreatment prevents ISO induced depletion of enzymatic antioxidants and apoptosis. Histoarchitecture of ventricular tissue of ISO treated group was marked by infracted areas (10%) and derangement of myocardium whereas, ARCE+ISO treated group (4.5%) recorded results comparable to control (0%). ARCE+ISO treated group accounted for upregulation of caveolin-3 and SERCA2a expression as compared to the ISO treated group implying towards ARCE mediated reduction in membrane damage and calcium imbalance. Molecular docking scores and LigPlot analysis of cyanidin-3-glucoside (-8.7 Kcal/mol) and delphinidin-3-glucoside (-8.5 Kcal/mol) showed stable hydrophobic and electrostatic interactions with β₁ adrenergic receptor. Overall this study elucidates the mechanism of ARCE mediated prevention of experimentally induced myocardial damage.