Toxic phytochemicals and their potential risks for human cancer.

Consuming plants for their presumed health benefits has occurred since early civilizations. Phytochemicals are found in various plants that are frequently included in the human diet and are generally thought to be safe for consumption because they are produced naturally. However, this is not always the case and in fact many natural compounds found in several commonly consumed plants are potential carcinogens or tumor promoters and should be avoided.

Insight into HIV of IFN-induced myxovirus resistance 2 (MX2) expressed by traditional Chinese medicine.

Recently, an important topic of the acquired immunodeficiency syndrome (AIDS) had been published in 2013. In this report, the expression of the IFN-induced myxovirus resistance 2 (MX2) had been defined the function to kill the human immunodeficiency virus (HIV). The screening from the Traditional Chinese Medicine (TCM) database by simulating molecular docking and molecular dynamics could select candidate compounds, which may express MX2 against HIV. Saussureamine C, Crotalaburnine, and Precatorine are selected based on the highest docking score and other TCM compounds. The data from molecular dynamics are helpful in the analysis and detection of protein-ligand interactions. According to the docking poses, hydrophobic interactions, and hydrogen bond with structure variations, this research could assess the interaction between protein and ligand interaction. In addition to the detection of TCM compound efficacy, we suggest that Saussureamine C is better than the others in protein-ligand interaction and the structural variation to express MX2.

Plants containing pyrrolizidine alkaloids used in the traditional Indian medicine--including ayurveda.

Pyrrolizidine alkaloids (PAs) show a hazardous potential for humans and animals. They can possess mutagenic, teratogenic, cancerogenic and fetotoxic properties. One pathway of a human intoxication can be the use of medicinal plants which contain toxic PAs. The Traditional Indian medicine--in particular Ayurveda--is a popular and well-known healing system. Within this system several PA-containing plants are used which, on account of their PA level, represent a severe health risk. In general, it is not recommended to use plants containing those toxic compounds.

Preventive activity of pyrrolizidine alkaloids from Seneciobrasiliensis (Asteraceae) on gastric and duodenal induced ulcer on mice and rats.

The alkaloid extract of Senecio brasiliensis inflorescences contain a mixture of the pyrrolizidine alkaloids (PA) senecionine, integerrimine, retrorsine, usaramine and seneciphylline. We evaluated this PA mixture on preventive antiulcerogenic effects on standard rodent models of induced gastric and duodenal ulcers. In the HCl/ethanol, indomethacin-bethanechol and hypothermic-restraint-induced gastric ulcer, the lesion was significantly inhibited by PA (p.o.) (p < 0.001). In the pylorus-ligature, PA (i.d.), significantly increased the gastric juice content and the pH values and decreased the acid output. In the cysteamine induced duodenal ulcers, PA (p.o.) showed significant inhibition (p < 0.001) of the duodenal lesions when compared to the respective control. The levels of the somatostatin hormone in the blood samples of animals pre-treated with the PA (12.5 mg/kg) and the free mucus and prostaglandin synthesis also increased (p < 0.001) after administration of PA extract (p.o.). The results suggested that the PA extract from Senecio brasiliensis inflorescences presents a significant anti-ulcer effect in the selected ulcer models. The mechanism involved with the action of the PA extract is the cytoprotection. Additional studies are in progress to determine other possible mechanisms involved with effect of the PA as anti-ulcer agents.

Modulation of gastrin and epidermal growth factor by pyrrolizidine alkaloids obtained from Senecio brasiliensis in acute and chronic induced gastric ulcers.

We investigated the antiulcerogenic activity of pyrrolizidine alkaloids (PAs) integerrimine, retrorsine, senecionine, usaramine and seneciplhylline, an alkaloidal extract obtained from Senecio brasiliensis. The PA extract demonstrated significantly activity in both, acute and chronic gastric ulcers on rats. The effects of PA extract were dose dependent. The mechanisms implicated on this activity were evaluated by determination of gastrin plasma levels in rats subjected to the acute treatment with PA extract and by expression of mRNA of Epidermal Growth Factor (EGF) after chronic treatment with this extract. The results showed that the PA extract increased both the levels of gastrin and the expression of EGF on these animals. Moreover, the histological examinations showed a reduction of exfoliation of superficial cells, hemorrhages and blood cell infiltration. We concluded that the PAs showed an important and qualitative antiulcerogenic activity mediated by increase in gastrin secretion and mRNA expression of EGF.

Hepatotoxic pyrrolizidine alkaloids in the Mexican medicinal plant Packera candidissima (Asteraceae: Senecioneae).

A study of the hepatotoxic pyrrolizidine alkaloids (PAs) contained in Packera candidissima (Greene) Weber & Löve (Senecio candidissimus Greene), a Mexican medicinal plant used for the treatment of kidney ailments and noted for its antiseptic properties, is reported. Analysis by TLC and GC-MS have shown the presence in high levels of both PAs and their N-oxides in the root (0.76% dry weight) and the aerial parts (0.36% dry weight) of the plant material. GC-MS analysis showed the presence of senecionine, integerrimine, retrorsine, and usaramine in the aerial parts. The root was found to contain senkirkine as the major component. These results indicate that users of this herb are at high risk of poisoning, especially members of certain cultural groups in Northern Mexico and the Hispanic population in the southwestern United States. In addition, two sesquiterpenes, neoadenostylone and epineoadenostylone were identified from the neutral extracts of this plant material. The 6 alpha-angeloyloxy-9-oxo-delta 10(1)-furanoeremophilane is reported for the first time as a natural product.

Phase I study of indicine N-oxide in patients with advanced cancer.

Indicine N-oxide is a pyrrolizidine alkaloid isolated from Heliotropium indicum, one of the widely used herbs in Ayurvedic medicine. Thirty-seven patients with solid tumors received the drug: 15 men and 22 women (mean age, 53 years). All had had prior chemotherapy, and 25 had had prior radiotherapy. Eighty-four percent had a performance status of 0-3 (Cancer and Leukemia Group B criteria). The drug was given as a short infusion over 15 minutes and repeated with a median interval of 4 weeks. Doses were escalated from 1 to 9 g/m2. A total of 55 courses were evaluable. Dose-limiting toxic effects were leukopenia and thrombocytopenia, and the toxicity was cumulative with repeated doses. Other toxic effects included nausea and vomiting, anemia, and hepatic dysfunction. The hematologic toxicity tended to be more pronounced in patients with hepatic dysfunction, poor marrow reserve, and heavy prior chemotherapy and radiotherapy. There were no complete or partial responses. One patient with skin melanoma and another with ovarian carcinoma had improvement lasting 2 months. The maximally tolerated dose is 9 g/m2 in our population. A recommended dose for therapeutic study is 7 g/m2. High-risk patients should be started at a dose of 5 g/m2. The treatment may be repeated at 4-week intervals with close monitoring of wbc and platelet counts. Dose reductions may be necessary for repeated courses.

Indicine-N-oxide: a new antitumor agent.

Indicine-N-oxide, a pyrrolizidine derivative, was selected for development because of activity in the murine P388 leukemia model. Route and schedule dependency have been demonstrated. It is believed that the antitumor activity of the drug is mediated via antimitotic effects and chromosomal damage. However, the active metabolic species responsible for these antitumor properties is not yet known. The major toxic effect was myelosuppression. Phase I clinical trials have arrived at recommended doses for further study. Colon carcinoma has been found to be possibly responsive, and several tumor types were reported stable during phase I testing. In a single phase II study in refractory leukemia, there were three responses, including one complete response, among seven patients. Phase II studies in all panel tumors are indicated, especially colon carcinoma and leukemias.