Biological Activities of Xanthatin from <i>Xanthium strumarium</i> Leaves

Nibret, Endalkachew; Youns, Mаhmoud; Krauth‐Siegel, R. Luise

doi:10.1002/ptr.3651

Cited by 66 publications

(45 citation statements)

References 44 publications

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“…Interestingly, other types of PCD were also reported when STLs were used against different pathogens. The STL xanthatin, which had good activity against Trypanosoma brucei brucei (IC 50 of 2.6 g/ml), triggered apoptosis in treated trypanosomes (38). Leishmania mexicana treated with 3 different STLs (helenalin, mexicanin, and dehydroleucodine) presented fragmented DNA, a hallmark of apoptosis-like death (14).…”

Section: Discussionmentioning

confidence: 99%

Activities of Psilostachyin A and Cynaropicrin against Trypanosoma cruzi In Vitro and In Vivo

Silva

Batista

Araújo

et al. 2013

Antimicrob Agents Chemother

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In vitro and in vivo activities against Trypanosoma cruzi were evaluated for two sesquiterpene lactones: psilostachyin A and cynaropicrin. Cynaropicrin had previously been shown to potently inhibit African trypanosomes in vivo, and psilostachyin A had been reported to show in vivo effects against T. cruzi, albeit in another test design. In vitro data showed that cynaropicrin was more effective than psilostachyin A. Ultrastructural alterations induced by cynaropicrin included shedding events, detachment of large portions of the plasma membrane, and vesicular bodies and large vacuoles containing membranous structures, suggestive of parasite autophagy. Acute toxicity studies showed that one of two mice died at a cynaropicrin dose of 400 mg/kg of body weight given intraperitoneally (i.p.). Although no major plasma biochemical alterations could be detected, histopathology demonstrated that the liver was the most affected organ in cynaropicrin-treated animals. Although cynaropicrin was as effective as benznidazole against trypomastigotes in vitro, the treatment (once or twice a day) of T. cruzi-infected mice (up to 50 mg/kg/day cynaropicrin) did not suppress parasitemia or protect against mortality induced by the Y and Colombiana strains. Psilostachyin A (0.5 to 50 mg/kg/day given once a day) was not effective in the acute model of T. cruzi infection (Y strain), reaching 100% animal mortality. Our data demonstrate that although it is very promising against African trypanosomes, cynaropicrin does not show efficacy compared to benznidazole in acute mouse models of T. cruzi infection.A merican trypanosomiasis, also known as Chagas disease (CD), is a neglected disease caused by the intracellular protozoan Trypanosoma cruzi. Despite a large reduction of new acute cases in recent years due to vectorial transmission control policies, other routes of infection, including vertical transmission (mother to fetus) and ingestion of contaminated food and drinks (1), are still a concern. T. cruzi is restricted to Latin America, where about 10 million people are infected and 25 to 90 million are at risk of acquiring the infection (2). According to the Pan American Health Organization (PAHO) and the World Health Organization (WHO), CD causes between 10,000 and 14,000 deaths per year (3). Currently, only two drugs, benznidazole (Bz) and nifurtimox, are available for chagasic patients (4). However, the poor tolerance to and limited efficacy of these drugs, especially in the later stage of the chronic phase, make the search for novel compounds and therapeutic strategies ever more important as a means to offer alternative therapies to patients refractory to both these nitro derivatives (5).Natural products are an excellent source of active compounds. In fact, despite them comprising Ͻ1 percent of known chemical compounds (DNP 2013 [http://dnp.chemnetbase.com/tour/]; Reaxys 2013 [https://www.reaxys.com/documentation/about _query.htm]), they have supplied or inspired more than half of all new drugs introduced to the market in the last 3 dec...

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Section: Discussionmentioning

confidence: 99%

Activities of Psilostachyin A and Cynaropicrin against Trypanosoma cruzi In Vitro and In Vivo

Silva

Batista

Araújo

et al. 2013

Antimicrob Agents Chemother

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“…Xanthatin (Figure 1), first isolated from cockleburs (Xanthium spp.) and characterized for its antimicrobial, anti-inflammatory, pro-apoptotic and trypanocidal properties [102,103], has been recovered from cultures of a strain of Paecilomyces sp. from Panax ginseng [104].…”

Section: Other Terpenoidsmentioning

confidence: 99%

Plant Bioactive Metabolites and Drugs Produced by Endophytic Fungi of Spermatophyta

2015

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Abstract:It is known that plant-based ethnomedicine represented the foundation of modern pharmacology and that many pharmaceuticals are derived from compounds occurring in plant extracts. This track still stimulates a worldwide investigational activity aimed at identifying novel bioactive products of plant origin. However, the discovery that endophytic fungi are able to produce many plant-derived drugs has disclosed new horizons for their availability and production on a large scale by the pharmaceutical industry. In fact, following the path traced by the blockbuster drug taxol, an increasing number of valuable compounds originally characterized as secondary metabolites of plant species belonging to the Spermatophyta have been reported as fermentation products of endophytic fungal strains. Aspects concerning sources and bioactive properties of these compounds are reviewed in this paper.

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“…Here, we focused on the biological effects of (-)-xanthatin on human breast cancer (MDA-MB-231 cells); however, experimental evidence that (-)-xanthatin has broad anti-proliferative effects coupled with cell death for different kinds of cancer cells is accumulating, such as human gastric carcinoma (MKN-45 cells) (Zhang et al, 2012a), human non-small-cell lung cancer (A549 cells) (Zhang et al, 2012b), and human leukemia (HL-60 cells) (Nibret et al, 2011). Taken together with these findings, it is suggested that (-)-xanthatin may be an intriguing chemical entity for inclusion with the other sesquiterpene lactones in future cancer clinical trials (Ghantous et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

(–)-Xanthatin induces the prolonged expression of c-Fos through an <i>N</i>-acetyl-L-cysteine (NAC)-sensitive mechanism in human breast cancer MDA-MB-231 cells

et al. 2013

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-We reported that (-)-xanthatin, a xanthanolide sesquiterpene lactone present in the Cocklebur plant, exhibited potent anti-proliferative effects on human breast cancer cells, in which GADD45γ, a novel tumor suppressor gene, was induced. Mechanistically, topoisomerase IIα (Topo IIα) inhibition by (-)-xanthatin was shown to be the upstream trigger that stimulated the expression of GADD45γ mRNA and concomitantly produced reactive oxygen species (ROS) to maintain this expression. Since the anticancer drug etoposide, a selective Topo IIα inhibitor, has also been shown to induce intracellular ROS, (-)-xanthatin may exert its anti-proliferative effects on cancer cells in a similar manner to those of etoposide. In the present study, to generalize its applicability to cancer therapy, we further investigated the biological activities of (-)-xanthatin by comparing its activities to those of the established anti-cancer drug etoposide. After the exposure of breast cancer cells to (-)-xanthatin or etoposide, a prolonged and marked up-regulation in the expression of c-fos, a proapoptotic molecule, was detected together with GADD45γ; and the expression of these molecules was stabilized by ROS and abrogated by the pretreatment with N-acetyl-L-cysteine (NAC), a potent ROS scavenger. (-)-Xanthatin in particular exhibited stronger antiproliferative potential than that of etoposide, which underlies the marked induction of c-fos/GADD45γ and ROS production.

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Biological Activities of Xanthatin from Xanthium strumarium Leaves

Cited by 66 publications

References 44 publications

Activities of Psilostachyin A and Cynaropicrin against Trypanosoma cruzi In Vitro and In Vivo

Activities of Psilostachyin A and Cynaropicrin against Trypanosoma cruzi In Vitro and In Vivo

Plant Bioactive Metabolites and Drugs Produced by Endophytic Fungi of Spermatophyta

(–)-Xanthatin induces the prolonged expression of c-Fos through an <i>N</i>-acetyl-L-cysteine (NAC)-sensitive mechanism in human breast cancer MDA-MB-231 cells

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