Liver performs number of critical physiological functions in human system. Intoxication of liver leads to accumulation of free radicals that eventually cause damage, fibrosis, cirrhosis and cancer. Carbon tetrachloride (CCl4) belongs to hepatotoxin is converted to a highly reactive free radical by cytochrome P450 enzymes that causes liver damage. Plant extracts derived quercetin has substantial role in hepatoprotection. This study highlights the possible mechanism by which quercetin plays significant role in hepatoprotection. HPLC analysis revealed the abundance of quercetin in the fruit extracts of Gynocardia odorata and Diospyros malabarica, were isolated, purified and subjected to liver function analysis on Wistar rats. Post quercetin treatment improved liver function parameters in the hepatotoxic Wistar rats by augmenting bilirubin content, SGOT and SGPT activity. Gene expression profile of quercetin treated rats revealed down regulation of HGF, TIMP1 and MMP2 expressed during CCl4 induction. In silico molecular mechanism prediction suggested that quercetin has a high affinity for cell signaling pathway proteins BCL-2, JAK2 and Cytochrome P450 Cyp2E1, which all play a significant role in CCl4 induced hepatotoxicity. In silico molecular docking and molecular dynamics simulation have shown that quercetin has a plausible affinity for major signaling proteins in liver. MMGBSA studies have revealed high binding of quercetin (ΔG) -41.48±11.02, -43.53±6.55 and -39.89±5.78 kcal/mol, with BCL-2, JAK2 and Cyp2E1, respectively which led to better stability of the quercetin bound protein complexes. Therefore, quercetin can act as potent inhibitor against CCl4 induced hepatic injury by regulating BCL-2, JAK2 and Cyp2E1.
Cancer, bacteria, and immunity relationships are much-debated topics in the last decade. Microbiome′s importance for metabolic and immunologic modulation of the organism adaptation and responses has become progressively evident, and models to study these relationships, especially about carcinogenesis, have acquired primary importance. The availability of germ-free (GF) animals, i.e., animals born and maintained under completely sterile conditions avoiding the microbiome development offers a unique tool to investigate the role that bacteria can have in carcinogenesis and tumor development. The comparison between GF animals with the conventional (CV) counterpart with microbiome can help to evidence conditions and mechanisms directly involving bacterial activities in the modulation of carcinogenesis processes. Here, we review the literature about spontaneous cancer and cancer modeling in GF animals since the early studies, trying to offer a practical overview on the argument.
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