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the effect of a very low dose of LA (0.1 mg/kg) was potentiated by the same dose of pentoxifylline (PTX), a known TNF-alpha inhibitor. L

rich in triterpenes

Carrageenan-induced mice paw edema

LA (10, 25 and 50 mg/kg, i.p.) reduced both phases of the formalin test, and the results were significant at the two higher doses. However, the effects were mainly on the 2nd phase with 61% inhibition, whereas the 1st phase was inhibited by 41% at the LA dose of 50 mg/kg, i.p. The naloxone pretreatment completely reversed the LA effect, in the 1st and 2nd phases, indicating the participation of the opioid system in LA antinociceptive and anti-inflammatory actions.

On the other hand, while no significant enzyme release was observed with LA at the concentrations of 1, 10 and 25 μg/mL, a small but significant LDH release (around 2 times) was detected with the higher LA concentration (50 μg/mL), probably related to the presence of 0.2% Tween 80.

The results show that LA at the concentrations of 50, 100 and 200 μg/mL presents no radical scavenging capacity. On the contrary, vitamin E used as the reference drug significantly decreased the absorbance value, as related to controls

In the carrageenan-treated groups pretreated with LA (50 mg/kg, i.p.) or indomethacin (10 mg/kg, i.p.), there were significant reductions of iNOS expressing cells.

Lupeol is found in several other species and its antinociceptive and anti-inflammatory activities have been already demonstrated [24–28]. It is accepted that the anti-inflammatory property of lupeol often accompany its immune modulatory and anti-tumor action

lupeol acetate presents an anti-inflammatory activity by regulating TNF-alpha and IL-2 specific mRNA, besides upregulating the synthesis of IL-10 mRNA [31].

In the present work, we showed that lupeol acetate (LA, 93.2% purity) isolated from the H. drasticus latex presented a potent anti-inflammatory action, in several models of inflammation in mice

These authors concluded that lupeol possessed an anti-inflammatory activity which is probably related to its ability to prevent the production of pro-inflammatory mediators, such as TNF-α and IL-1β.

which might represent a novel non-toxic alternative to conventional cancer therapy available today.

These results clearly indicate that dandelion root extract can inhibit the ability of colorectal cancer cells to migrate and invade, and therefore metastasize to secondary locations.

morphological differences in tissue slices between the control untreated and the DRE treated group

aken together, these results established that systemic oral intake of the DRE was safe and its anti-cancer efficacy should be further investigated.

, but the DRE treatment efficiently suppressed the growth of both p53 WT and p53 mutant tumors in-vivo (Figure 4B – 4C)

with no difference between the control and DRE treated samples of NCM460

We observed a decrease in the viability of cells treated with α-amyrin, with 10 μM as the most effective concentration.

The results showed a progressive destabilization of the mitochondrial membrane following the DRE treatment, which was observed as early as 30 minutes post treatment (Figure ​6C). Pro-caspase-8 (green) was localized in the mitochondria (red) in control untreated cells; however, following the DRE treatment, activated caspase-8 was released from the mitochondria into cytoplasmic space, as indicated by the dispersed green fluorescence (Figure ​6C

suggesting that in HT-29 colorectal cancer cells the DRE-induced cell death was caspase-8 independent.

Others suggest that following activation, caspases re-localize to the mitochondria, where they interact with other pro-apoptotic proteins during the progression of apoptosis [15]. A third option, put forward by Qin and colleagues, suggests that inactive caspases are kept in the mitochondria, but following apoptotic stimuli and activation, they are released from the mitochondria into the cytoplasmic peri-nuclear space [

However, these results indicate that DRE and its anti-cancer components must be absorbed and circulated, in order to reach the site of the tumor (in order to inhibit tumor growth).

, we confirmed the vulnerability of cancer cell mitochondria by showing that the DRE treatment led to a decrease in the mitochondrial membrane potential and increase in ROS levels in the isolated mitochondria.

caspase-8 specific inhibitor, IETD-fmk, did not change the DRE response in these cells. This was in contrast to our previous study in leukemia and pancreatic cancer cells

he pro-apoptotic genes including Caspase-1, Interferon gamma and the TNF ligands and receptors, were up-regulated in HT-29 cells, prior to the apoptosis induction, while the same genes were down-regulated in NCM460 cells.

Previous findings show that taraxasterol has anti-inflammatory and chemopreventive activit

suggesting its importance in the anti-cancer activity of dandelion root extract, especially on the expression levels of COX-2. Additionally, we show that 10 μM lupeol is not very effective on its own

With DRE having proven its efficacy in successfully killing this aggressive, chemoresistant form of skin cancer, DRE toxicity on normal cells had to be evaluated

DRE was found to reduce cell viability in a dose-dependent fashion, over time, in A375 melanoma cells as was measured by WST-1 assay. Based on metabolic activity of A375s, it was confirmed that treatment at 2.5 mg/mL DRE resulted in ~50% reduction in cell viability against control within 24 hours (Figure 1(a))

Higher doses were then used and a response was observed at a concentration of 10 mg/mL (

Typical apoptotic morphology was observed in G361 cells treated with DRE starting at 5 mg/mL concentrations for 72 hours

) is more than a worthy chemopreventative, it is fast-acting, nontoxic, and therefore specific in its targeting of human melanoma cancer cells, making it a valuable chemotherapeutic. We have investigated the induction of apoptosis in human malignant melanoma cells and observed its long-term effects in human melanoma cancer.

We are yet to determine the effect of each of the individual components (such as the family of triterpene alcohols and phenolic acids—found in the roots—and cinnamic acids, flavinoids and coumarins—that are found in the leaves

Given that DRE has traditionally been used naturopathically for a variety of ailments, we assume that it would be relatively nontoxic to healthy cells. Our results show that the Normal Human Fibroblasts (NHFs) (which were treated at a low population doubling where NHFs have the best proliferation rate) and Peripheral Blood Mononuclear Cells remained unaffected and healthy after a 96-hour and 48- hour exposure to DRE, respectively (Figures 2(a)–2(d)).

Lupeol,

taraxasterol

More importantly, an increase in ROS production indicates prooxidant behaviour of DRE on cancer cell mitochondria, which is contrary to the antioxidant convictions of traditional medicine and previous studies on Taraxacum extracts citing reductions in NO, ROS, RNS, and COX-2 [10, 11] in mouse macrophages.

There are two main points that must be stated here: firstly, that noncancerous cells are unaffected by DRE treatment, and secondly, melanoma cells retain the signals to commit suicide long after DRE has been removed from the system

By 48 hours, human melanoma A375 cells uncharacteristically showed susceptibility to apoptosis induction by DRE

We believe that this nontoxic extract can undergo precipitous translation from bench top to bedside, with dandelion products that are already commercially available in the form of tea and supplements.