| Description: |
Parthenolide exhibits anti-cancer, anti-inflammatory, immunomodulatory, anti-Leishmania, and antimigraine effects,
it inhibits nociception and neurogenic vasodilatation in the trigeminovascular system by targeting the TRPA1 channel.Parthenolide is also an inhibitor of the nuclear factor-kappaB pathway, can ameliorate cardiovascular derangement and outcome in endotoxic shock in rodents.
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| In vitro: |
| BMB Rep. 2014 Aug;47(8):451-6. | | Parthenolide inhibits osteoclast differentiation and bone resorbing activity by down-regulation of NFATc1 induction and c-Fos stability, during RANKL-mediated osteoclastogenesis.[Pubmed: 24314143] | Parthenolide, a natural product derived from Feverfew, prevents septic shock and inflammation. We aimed to identify the effects of Parthenolide on the RANKL (receptor activator of NF-κB ligand)-induced differentiation and bone resorbing activity of osteoclasts.
METHODS AND RESULTS:
In this study, Parthenolide dose-dependently inhibited RANKL-mediated osteoclast differentiation in BMMs, without any evidence of cytotoxicity and the phosphorylation of p38, ERK, and IκB, as well as IκB degradation by RANKL treatment. Parthenolide suppressed the expression of NFATc1, OSCAR, TRAP, DC-STAMP, and cathepsin K in RANKL-treated BMMs. Furthermore, Parthenolide down-regulated the stability of c-Fos protein, but could not suppress the expression of c-Fos. Overexpression of NFATc1 and c-Fos in BMMs reversed the inhibitory effect of Parthenolide on RANKL-mediated osteoclast differentiation. Parthenolide also inhibited the bone resorbing activity of mature osteoclasts.
CONCLUSIONS:
Parthenolide inhibits the differentiation and bone-resolving activity of osteoclast by RANKL, suggesting its potential therapeutic value for bone destructive disorders associated with osteoclast-mediated bone resorption. | | Antimicrob Agents Chemother. 2005 Jan;49(1):176-82. | | Antileishmanial activity of parthenolide, a sesquiterpene lactone isolated from Tanacetum parthenium.[Pubmed: 15616293] | The in vitro activity of parthenolide against Leishmania amazonensis was investigated. Parthenolide is a sesquiterpene lactone purified from the hydroalcoholic extract of aerial parts of Tanacetum parthenium.
METHODS AND RESULTS:
This isolated compound was identified through spectral analyses by UV, infrared, (1)H and (13)C nuclear magnetic resonance imaging, DEPT (distortionless enhancement by polarization transfer), COSY (correlated spectroscopy), HMQC (heteronuclear multiple-quantum coherence), and electron spray ionization-mass spectrometry. Parthenolide showed significant activity against the promastigote form of L. amazonensis, with 50% inhibition of cell growth at a concentration of 0.37 microg/ml. For the intracellular amastigote form, parthenolide reduced by 50% the survival index of parasites in macrophages when it was used at 0.81 microg/ml. The purified compound showed no cytotoxic effects against J774G8 macrophages in culture and did not cause lysis in sheep blood when it was used at higher concentrations that inhibited promastigote forms. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis with gelatin as the substrate showed that the enzymatic activity of the enzyme cysteine protease increased following treatment of the promastigotes with the isolated compound. This finding was correlated with marked morphological changes induced by parthenolide, such as the appearance of structures similar to large lysosomes and intense exocytic activity in the region of the flagellar pocket, as seen by electron microscopy.
CONCLUSIONS:
These results provide new perspectives on the development of novel drugs with leishmanicidal activities obtained from natural products. | | Pharm Biol. 2015 Jan;53(1):104-9. | | Effect of parthenolide on growth and apoptosis regulatory genes of human cancer cell lines.[Pubmed: 25289524] | Parthenolide (a sesquiterpene lactone), a bioactive compound of Tanacetum parthenium (L.) Schultz Bip. (Asteraceae) herb, has been reported for antioxidant and anticancer activities. The present study evaluated the effect of Parthenolide on growth and apoptosis-regulatory genes of human cervical cancer (SiHa) and breast cancer (MCF-7) cell lines.
METHODS AND RESULTS:
The cytotoxic activity of Parthenolide (3.5-21 µM) was examined by MTT and LDH assays at 24 and 48 h time intervals. Apoptotic activity was evaluated by expression analysis of multiple apoptosis-regulatory genes (i.e., p53, Bcl-2, Bax, caspase-3, -6, and -9) by reverse transcriptase-PCR and DNA fragmentation assay. Parthenolide inhibited the growth of SiHa and MCF-7 cell lines in a concentration-dependent manner at 24 and 48 h time intervals (p < 0.001). The IC50 value of Parthenolide against SiHa and MCF-7 cells were 8.42 ± 0.76 and 9.54 ± 0.82 μM, respectively. Parthenolide-treated cells showed up-regulation of p53, Bax, caspase-3, -6, and -3 genes and down-regulation of Bcl-2 gene (p ≤ 0.008). At IC50, the p53 gene was up-regulated by 9.67- and 3.15-fold in SiHa and MCF-7 cells, respectively. The Bax to Bcl-2 ratio was 3.4 and 2.3 for SiHa and MCF-7 cells, respectively. Also, the fragmented genomic DNA in Parthenolide-treated cells showed the signs of apoptosis.
CONCLUSIONS:
Our study endorsed the biological activity of Parthenolide and demonstrated the Parthenolide-induced growth inhibition and apoptosis in SiHa and MCF-7 cells by modulating the expression of apoptosis-regulatory genes. |
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| In vivo: |
| Mol Pharmacol. 2002 May;61(5):953-63. | | Parthenolide, an inhibitor of the nuclear factor-kappaB pathway, ameliorates cardiovascular derangement and outcome in endotoxic shock in rodents.[Pubmed: 11961112] |
METHODS AND RESULTS:
Three groups of rats received Parthenolide (0.25, 0.5, or 1 mg/kg) 15 min before endotoxin; another group received Parthenolide (1 mg/kg) 3 h after endotoxin. In vehicle-treated rats, administration of endotoxin caused severe hypotension, which was associated with a marked hyporeactivity to norepinephrine in ex vivo thoracic aortas. Immunohistochemistry showed positive staining for nitrotyrosine, poly(ADP-ribose) synthetase (PARS) and apoptosis, whereas Northern blot analysis showed increased mRNA expression of inducible nitric-oxide synthase (iNOS) in thoracic aortas. Elevated levels of plasma nitrate/nitrite were also found. Elevated lung levels of myeloperoxidase activity were indicative of infiltration of neutrophils. These inflammatory events were preceded by cytosolic degradation of inhibitor kappaBalpha (IkappaBalpha) and activation of nuclear NF-kappaB in the lung. In vivo pretreatment and post-treatment with Parthenolide improved the hemodynamic profile and reduced plasma nitrate/nitrite and lung neutrophil infiltration in a dose-dependent fashion. Vascular hyporeactivity of ex vivo aortas was ameliorated. Treatment with Parthenolide also abolished nitrotyrosine formation, PARS expression, and apoptosis and reduced iNOS mRNA content in thoracic aortas. DNA binding of NF-kappaB was inhibited by Parthenolide in the lung, whereas degradation of IkappaBalpha was unchanged. In a separate set of experiments, pretreatment or post-treatment with Parthenolide significantly improved survival in mice challenged with endotoxin.
CONCLUSIONS:
We conclude that Parthenolide exerts beneficial effects during endotoxic shock through inhibition of NF-kappaB. |
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