| Description: |
Dehydroleucodine has antidiarrheal, anti-inflammatory, anti-microbial, embryotoxicity, gastric cytoprotective, anti-cancer activities. Dehydroleucodine has an important inhibitory effect in cellular pathways regulating adipocyte differentiation by modulating the PPARγ expression, which is known to play a pivotal role during adipogenesis. Dehydroleucodine may be attributed to interference with multiple targets on the level of transcription factors, such as NF-kappaB, and cytokines. Dehydroleucodine induces a TP73-dependent transcriptional regulation of multiple cell death target genes in human glioblastoma cells.
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| In vitro: |
| Cancer Lett. 2016 Mar 1;372(1):10-23. | | Dehydroleucodine inhibits tumor growth in a preclinical melanoma model by inducing cell cycle arrest, senescence and apoptosis.[Pubmed: 26718258 ] | Malignant melanoma represents the fastest growing public health risk of all cancer types worldwide. Several strategies and anti-cancer drugs have been used in an effort to improve treatments, but the development of resistance to anti-neoplastic drugs remains the major cause of chemotherapy failure in melanomas. Previously, we showed that the sesquiterpene lactone, dehydroleucodine (DhL), promotes the accumulation of DNA damage markers, such as H2AX and 53BP1, in human tumor cells. Also DhL was shown to trigger either cell senescence or apoptosis in a concentration-dependent manner in HeLa and MCF7 cells.
METHODS AND RESULTS:
Here, we evaluated the effects of DhL on B16F0 mouse melanoma cells in vitro and in a pre-clinical melanoma model. DhL inhibited the proliferation of B16F0 cells by inducing senescence or apoptosis in a concentration-dependent manner. Also, DhL reduced the expression of the cell cycle proteins cyclin D1 and B1 and the inhibitor of apoptosis protein, survivin. In melanomas generated by subcutaneous injection of B16F0 cells into C57/BL6 mice, the treatment with 20 mg DhL /Kg/day in preventive, simultaneous and therapeutic protocols reduced tumor volumes by 70%, 60% and 50%, respectively. DhL treatments reduced the number of proliferating, while increasing the number of senescent and apoptotic tumor cells.
To estimate the long-term effects of DhL, a mathematical model was applied to fit experimental data.
CONCLUSIONS:
Extrapolation beyond experimental time points revealed that DhL administration following preventive and therapeutic protocols is predicted to be more effective than simultaneous treatments with DhL in restricting tumor growth.
| | J Ethnopharmacol. 2011 Sep 2;137(2):1055-9. | | Sesquiterpene lactones from Gynoxys verrucosa and their anti-MRSA activity.[Pubmed: 21782013] | Because of its virulence and antibiotic resistance, Staphylococcus aureus is a more formidable pathogen now than at any time since the pre-antibiotic era. In an effort to identify and develop novel antimicrobial agents with activity against this pathogen, we have examined Gynoxys verrucosa Wedd (Asteraceae), an herb used in traditional medicine in southern Ecuador for the treatment and healing of wounds.
METHODS AND RESULTS:
The sesquiterpene lactones leucodine (1) and dehydroleucodine (2) were extracted and purified from the aerial parts of Gynoxys verrucosa, and their structure was elucidated by spectroscopic methods and single-crystal X-ray analysis. The in vitro anti-microbial activity of Gynoxys verrucosa extracts and its purified constituents was determined against six clinical isolates including Staphylococcus aureus and Staphylococcus epidermidis strains with different drug-resistance profiles, using the microtiter broth method.
Compound 1 has very low activity, while compound 2 has moderate activity with MIC(50)s between 49 and 195 μg/mL. The extract of Gynoxys verrucosa has weak activity with MIC(50)s between 908 and 3290 μg/mL.
CONCLUSIONS:
We are reporting the full assignment of the (1)H NMR and (13)C NMR of both compounds, and the crystal structure of compound 2, for the first time. Moreover, the fact that compound 2 has antimicrobial activity and compound 1 does not, demonstrates that the exocyclic conjugated methylene in the lactone ring is essential for the antimicrobial activity of these sesquiterpene lactones. However, the weak activity observed for the plant extracts, does not explain the use of Gynoxys verrucosa in traditional medicine for the treatment of wounds and skin infections. |
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| In vivo: |
| Food Chem Toxicol. 2012 Mar;50(3-4):672-4. | | Lethal effect of dehydroleucodine (DhL) on amphibian Bufo arenarum embryos.[Pubmed: 22240414 ] |
METHODS AND RESULTS:
The dehydroleucodine is a sesquiterpene lactone isolated from Artemisia douglasiana Besser which is used in popular medicine. Toxicity tests using embryos of amphibian have been widely used in order to predict toxic effects of different compounds. However, to our knowledge, there are not studies focussed on the toxic effects of dehydroleucodine on Bufo arenarum, which is an anuran widely distributed in South America. The effect of dehydroleucodine on the survival of embryos was evaluated in an acute test during the early life stage of B. arenarum embryos. Lethality and the degree of adverse effects were dehydroleucodine dose-dependent.
CONCLUSIONS:
Overall, amphibian early life stages appeared to be more susceptible to the embryotoxicity associated with exposure to dehydroleucodine, especially at concentration greater that 3mM. This increased susceptibility may result from the relatively high rate of cellular differentiation and morphogenesis that occurs at this early stage of development.
| | J Ethnopharmacol. 2003 Oct;88(2-3):195-8. | | Anti-inflammatory activity and effect on gastric acid secretion of dehydroleucodine isolated from Artemisia douglasiana.[Pubmed: 12963142] |
METHODS AND RESULTS:
The effect of Dehydroleucodine (DhL) on gastric acid secretion in rats was investigated at a dose of 40 mg/kg, while its anti-inflammatory effect was investigated in two experimental models: arthritis induced by Freund's adjuvant carrageenan- and cotton pellet-induced granuloma. DhL did not inhibit gastric acid secretion, suggesting that its anti-ulcerogenic effect can be attributed to its action on the mucosa defense factors. On the other hand, DhL inhibited both chronic and acute adjuvant carrageenan-induced inflammation phases, being most effective in the chronic phase. In the granuloma test, DhL also inhibited inflammation.
CONCLUSIONS:
It is suggested that the anti-inflammatory activity of DhL may be attributed to interference with multiple targets on the level of transcription factors, such as NF-kappaB, and cytokines. |
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