| Description: |
Damnacanthal possesses anti-cancer, immunomodulatory, antinociceptive and anti-inflammatory actions, it can treat or prevent hepatocellular carcinoma through its inhibitory effects on the HGF/c-Met axis. Damnacanthal inhibits mast cell activation induced by different stimuli and open a new window for the use of this compound as a mast cell stabilizer. Damnacanthal can inhibit the NF-κB/receptor-interacting protein-2/caspase-1 signal pathway by inhibiting p56lck tyrosine kinase. |
| Targets: |
Syk | Akt | IL Receptor | TNF-α | Caspase | NF-kB | p53 | p21 | p38MAPK | Bcl-2/Bax | Histamine Receptor |
| In vitro: |
| Mol Immunol. 2015 May;65(1):86-93. | | Damnacanthal inhibits IgE receptor-mediated activation of mast cells.[Pubmed: 25656801] | Damnacanthal, an anthraquinone obtained from the noni fruit (Morinda citrifolia L.), has been described to possess anti-cancer and anti-inflammatory properties. Since mast cells are key players in various inflammatory conditions as well as in cancer, we considered the possibility that the biological actions of Damnacanthal, at least partly, could be due to effects on mast cells. Many of the biological activities of mast cells are mediated by IgE receptor cross-linking, which results in degranulation with release of preformed granule mediators, as well as de novo synthesis and release of additional compounds.
METHODS AND RESULTS:
Here we show that Damnacanthal has profound inhibitory activity on mast cell activation through this pathway. The release of the granule compounds beta-hexosaminidase and tryptase release was completely abrogated by Damnacanthal at doses that were non-toxic to mast cells. In addition, Damnacanthal inhibited activation-dependent pro-inflammatory gene induction, as well as cytokine/chemokine release in response to mast cell stimulation. The mechanism underlying Damnacanthal inhibition was linked to impaired phosphorylation of Syk and Akt. Furthermore, Damnacanthal inhibited mast cell activation in response to calcium ionophore A23187.
CONCLUSIONS:
Altogether, the data presented here demonstrate that Damnacanthal inhibits mast cell activation induced by different stimuli and open a new window for the use of this compound as a mast cell stabilizer. | | Sci Rep. 2015 Jan 26;5:8021. | | Damnacanthal, a noni anthraquinone, inhibits c-Met and is a potent antitumor compound against Hep G2 human hepatocellular carcinoma cells.Damnacanthal, a noni anthraquinone, inhibits c-Met and is a potent antitumor compound against Hep G2 human hepatocell[Pubmed: 25620570] | Damnacanthal, an anthraquinone present in noni plants, targets several tyrosine kinases and has antitumoral effects. This study aims at getting additional insight on the potential of Damnacanthal as a natural antitumor compound.
METHODS AND RESULTS:
The direct effect of Damnacanthal on c-Met was tested by in vitro activity assays. Additionally, Western blots of c-Met phosphorylation in human hepatocellular carcinoma Hep G2 cells were performed. The antitumor effects of Damnacanthal were tested by using cell growth, soft agar clonogenic, migration and invasion assays. Their mechanisms were studied by Western blot, and cell cycle, apoptosis and zymographic assays. Results show that Damnacanthal targets c-Met both in vitro and in cell culture. On the other hand, Damnacanthal also decreases the phosphorylation levels of Akt and targets matrix metalloproteinase-2 secretion in Hep G2 cells. These molecular effects are accompanied by inhibition of the growth and clonogenic potential of Hep G2 hepatocellular carcinoma cells, as well as induction of Hep G2 apoptosis.
CONCLUSIONS:
Since c-Met has been identified as a new potential therapeutical target for personalized treatment of hepatocellular carcinoma, Damnacanthal and noni extract supplements containing it could be potentially interesting for the treatment and/or chemoprevention of hepatocellular carcinoma through its inhibitory effects on the HGF/c-Met axis. | | Pharm Biol. 2010 Apr;48(4):446-52. | | Immunomodulatory effects of damnacanthal isolated from roots of Morinda elliptica.[Pubmed: 20645725] | Morinda elliptica Ridley (Rubiaceae) has been used traditionally as a medicine to treat various diseases in Malaysia and southeast Asia.
In the present study we investigated the immunomodulatory effects of Damnacanthal isolated from the roots of Morinda elliptica.
METHODS AND RESULTS:
The immunomodulatory effect of this compound was evaluated by using the lymphocyte proliferation assay with mouse thymocytes and human peripheral blood mononuclear cells (PBMC). In addition, the effect of the compound on PBMC cell cycle progression was studied by using flow cytometry. The production of human interleukin-2 and human inteleukin-12 cytokines was also assessed using the enzyme linked immunosorbent assay (ELISA) technique. The lymphocyte proliferation assay showed that Damnacanthal was able to activate mouse thymocytes and PBMC at a low concentration (0.468 microg/mL). Moreover, the production of human interleukin-2 and human interleukin-12 cytokines in the culture supernatant from Damnacanthal activated lymphocytes was markedly up-regulated at 24 h and sustained until 72 h with a slight decrease with time. A positive correlation was found between the level of these two cytokines and the MTT-based proliferation assay.
CONCLUSIONS:
Based on the above results, Damnacanthal can act as an immunomodulatory agent which may be very useful for maintaining a healthy immune system. |
|
| In vivo: |
| Immunopharmacol Immunotoxicol. 2014 Oct;36(5):355-63. | | Damnacanthal inhibits the NF-κB/RIP-2/caspase-1 signal pathway by inhibiting p56lck tyrosine kinase.[Pubmed: 25139491] | Damnacanthal is a major constituent of Morinda citrifolia L. (noni) and exhibits anti-cancer and anti-inflammatory activities. However, the effects of Damnacanthal on allergic diseases have not been determined.
METHODS AND RESULTS:
In this study, we investigated the effect of Damnacanthal on mast cell-mediated allergic inflammatory responses. Damnacanthal significantly and dose-dependently inhibited compound 48/80-induced systemic anaphylactic shock, histamine release and intracellular calcium levels. In particular, IgE-mediated passive cutaneous anaphylaxis was significantly inhibited by the oral administration of Damnacanthal. In addition, we report for the first time that p56lck tyrosine kinase was expressed in phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-stimulated mast cells. Furthermore, Damnacanthal inhibited the up-regulation of p56lck tyrosine kinase activity by PMACI and repressed PMACI-induced histidine decarboxylase expression and activity. Damnacanthal also inhibited PMACI-induced interleukin (IL)-1β, IL-6 and tumor necrosis factor-α expressions by suppressing nuclear factor-kappa B (NF-κB) activation and suppressed the activation of caspase-1 and the expression of receptor interacting protein-2.
CONCLUSIONS:
This study shows Damnacanthal inhibits the NF-κB/receptor-interacting protein-2/caspase-1 signal pathway by inhibiting p56lck tyrosine kinase and suggests that Damnacanthal has potential for the treatment of mast cell-mediated allergic disorders. | | Biol Pharm Bull. 2011;34(1):103-7. | | The antinociceptive and anti-inflammatory action of the CHCl3-soluble phase and its main active component, damnacanthal, isolated from the root of Morinda citrifolia.[Pubmed: 21212526] | Morinda citrifolia (Rubiaceae, Noni) is a traditional medicine with various pharmacological activities.
METHODS AND RESULTS:
We investigated if the MeOH-, CHCl(3)- and BuOH-soluble phase and its main active component, Damnacanthal, isolated from the Noni root, have antinociceptive and anti-inflammatory actions in mice. The CHCl(3)-soluble phase (3 g/kg, per os (p.o.)) significantly reduced pain-related behavior observed in the formalin test. These effects were not suppressed by pretreatment with naloxone (1 mg/kg, intraperitoneally (i.p.)), an opioid receptor antagonist. The CHCl(3)-soluble phase (3 g/kg, p.o.) significantly reduced histamine-induced paw edema. The MeOH- and BuOH-soluble phase had no effect in either test. Furthermore, Damnacanthal (10-100 mg/kg, p.o.) exerted an antinociceptive effect on chemical nociceptive stimuli, and decreased histamine-induced paw edema. Damnacanthal was weakly bound to the histamine H(1) receptor.
CONCLUSIONS:
These data suggest that the CHCl(3)-soluble phase of the Noni root has antinociceptive and anti-inflammatory effects. Furthermore, these effects of Damnacanthal isolated from the Noni root is mediated in part by the histamine H(1) receptor. |
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