| Description: |
Alpha-Chaconine has anti-inflammatory effect, associated with the suppression of AP-1, and supports its possible therapeutic role for the treatment of sepsis. Alpha-Chaconine also has cytotoxic effects. |
| Targets: |
COX | AP-1 | IL Receptor | TNF-α | TGF-β/Smad | JNK | NADPH-oxidase |
| In vitro: |
| Food Chem. 2013 Nov 15;141(2):669-74. | | Synergistic cytotoxicity induced by α-solanine and α-chaconine.[Pubmed: 23790833] | α-Solanine and alpha-Chaconine are well-known potato toxins, but the mechanism of the synergistic cytotoxic effect of these alkaloids has been little clarified.
METHODS AND RESULTS:
This study confirmed their synergistic cytotoxic effects on C6 rat glioma cells by three different cell viability tests, namely WST-1 (water-soluble tetrazolium) assay sensitive to intracellular NADH concentration, menadione-catalysed chemiluminescent assay depending on both NAD(P)H concentration and NAD(P)H:quinone reductase activity, and LDH (lactate dehydrogenase) assay sensitive to the release of LDH from damaged cells. The maximum cytotoxic effect was observed at a ratio of 1:1 between α-solanine and alpha-Chaconine at micromolar concentrations.
CONCLUSIONS:
The cytotoxic effects of these alkaloids were observed immediately after incubation and were constant after 30min, suggesting that rapid damage of plasma membrane causes the lethal disorder of metabolism. |
|
| In vivo: |
| Chem Biol Interact . 2015 Jun 25;235:85-94. | | α-Chaconine isolated from a Solanum tuberosum L. cv Jayoung suppresses lipopolysaccharide-induced pro-inflammatory mediators via AP-1 inactivation in RAW 264.7 macrophages and protects mice from endotoxin shock[Pubmed: 25913072] | | Abstract
In this study, we investigated the molecular mechanisms underlying the anti-inflammatory effects of α-chaconine in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and in LPS-induced septic mice. α-Chaconine inhibited the expressions of cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) at the transcriptional level, and attenuated the transcriptional activity of activator protein-1 (AP-1) by reducing the translocation and phosphorylation of c-Jun. α-Chaconine also suppressed the phosphorylation of TGF-β-activated kinase-1 (TAK1), which lies upstream of mitogen-activated protein kinase kinase 7 (MKK7)/Jun N-terminal kinase (JNK) signaling. JNK knockdown using siRNA prevented the α-chaconine-mediated inhibition of pro-inflammatory mediators. In a sepsis model, pretreatment with α-chaconine reduced the LPS-induced lethality and the mRNA and production levels of pro-inflammatory mediators by inhibiting c-Jun activation. These results suggest that the anti-inflammatory effects of α-chaconine are associated with the suppression of AP-1, and support its possible therapeutic role for the treatment of sepsis.
Keywords: AP-1; Inflammatory mediators; MKK7; Sepsis; α-Chaconine. |
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