| In vitro: |
| Antimicrob Agents Chemother. 2013 Mar;57(3):1180-91. | | Lucidone suppresses hepatitis C virus replication by Nrf2-mediated heme oxygenase-1 induction.[Pubmed: 23254429] |
METHODS AND RESULTS:
Upon screening of plant-derived natural products against hepatitis C virus (HCV) in the replicon system, we demonstrate that Lucidone, a phytocompound, isolated from the fruits of Lindera erythrocarpa Makino, significantly suppressed HCV RNA levels with 50% effective concentrations of 15 ± 0.5 μM and 20 ± 1.1 μM in HCV replicon and JFH-1 infectious assays, respectively. There was no significant cytotoxicity observed at high concentrations, with a 50% cytotoxic concentration of 620 ± 5 μM. In addition, Lucidone significantly induced heme oxygenase-1 (HO-1) production and led to the increase of its product biliverdin for inducing antiviral interferon response and inhibiting HCV NS3/4A protease activity. Conversely, the anti-HCV activity of Lucidone was abrogated by blocking HO-1 activity or silencing gene expression of HO-1 or NF-E2-related factor 2 (Nrf2) in the presence of Lucidone, indicating that the anti-HCV action of Lucidone was due to the stimulation of Nrf-2-mediated HO-1 expression. Moreover, the combination of Lucidone and alpha interferon, the protease inhibitor telaprevir, the NS5A inhibitor BMS-790052, or the NS5B polymerase inhibitor PSI-7977, synergistically suppressed HCV RNA replication.
CONCLUSIONS:
These findings suggest that Lucidone could be a potential lead or supplement for the development of new anti-HCV agent in the future. | | Toxicol In Vitro. 2012 Aug;26(5):700-8. | | Hepatoprotective effect of lucidone against alcohol-induced oxidative stress in human hepatic HepG2 cells through the up-regulation of HO-1/Nrf-2 antioxidant genes.[Pubmed: 22484158 ] | Lucidone was previously reported to exhibit anti-inflammatory activity in vitro and in vivo.
METHODS AND RESULTS:
In the present study, we characterized the mechanisms underlying the hepatoprotective effect of Lucidone against alcohol-induced oxidative stress in vitro. Human hepatoma (HepG2) cells were pretreated with Lucidone (1-10μg/mL) and then hepatotoxicity was stimulated by the addition ethanol (100mM). With response to ethanol-challenge, increased amount of alanine aminotransferase (ALT) and aspirate aminotransferase (AST) release were observed, whereas Lucidone pretreatment significantly inhibited the leakage of AST and ALT in HepG2 cells without appreciable cytotoxic effects. We also found that Lucidone pretreatment significantly decreased ethanol-induced nitric oxide (NO), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), reactive oxygen species (ROS) and glutathione (GSH) depletion in HepG2 cells. Furthermore, Western blot and quantitative-PCR analyses showed that ethanol-exposure apparently down-regulated endogenous anti-oxidant hemoxygenase-1 (HO-1) expression, whereas pretreatment with Lucidone significantly up-regulates HO-1 expression followed by the transcriptional activation of NF-E2 related factor-2 (Nrf-2). Interestingly, the profound up-regulation of HO-1 and Nrf-2 were observed in only ethanol-challenged cells, which evidenced that Lucidone-induced induction of HO-/Nrf-2 were specific with oxidative stress.
CONCLUSIONS:
Thus, we concluded that Lucidone-mediated up-regulation of phase-II enzymes and HO-1 via Nrf-2 signaling pathway may provide a pivotal mechanism for its hepatoprotective action. |
|
| In vivo: |
| Int Immunopharmacol. 2010 Apr;10(4):385-92. | | Anti-inflammatory effect of lucidone in mice via inhibition of NF-kappaB/MAP kinase pathway.[Pubmed: 20079881] |
METHODS AND RESULTS:
Here, we investigated the anti-inflammatory activity of Lucidone, a phytocompound isolated from the fruits of Lindera erythrocarpa Makino, against lipopolysaccharide (LPS)-induced acute systemic inflammation in mice. Male ICR mice were injected intraperitoneally with LPS (5 microg/kg), and the effects of pretreatment with various concentrations of Lucidone (50-200 mg/kg) for 12h on the formation of nitric oxide (NO), prostaglandin-E(2) (PGE(2)) and tumor necrosis factor (TNF-alpha) were analyzed. Lucidone inhibited the production of NO, PGE(2) and TNF-alpha production in LPS-induced mice, and also induced mRNA and protein levels of inducible nitric oxide synthase (iNOS), and cyclooxigenase-2 (COX-2). The two common response elements of the iNOS and COX-2 genes are nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). NF-kappaB nuclear translocation and DNA binding were inhibited by Lucidone in the LPS-induced mice. Moreover, Lucidone decreased the expression and phosphorylation of c-Jun N-terminal kinase (JNK) protein thereby causing the subsequent inhibition of AP-1 activity. Finally, our results indicated that Lucidone was able to block mitogen-activated protein kinases activity and its downstream signaling activation of NF-kappaB and AP-1.
CONCLUSIONS:
We thus conclude that Lucidone exerts its anti-inflammatory effects in mice by inhibiting the expression of pro-inflammatory factors and their related signaling pathways. |
|
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