Cryosurgery and podophyllum in combination for condylomata.
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Combined Modality Therapy↗
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Instant methods to spot-check poisonous podophyllum root in herb samples of clematis root.
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Drug Contamination↗
Reduction in the number of infective Trichinella spiralis larvae in mice by use of homeopathic drugs.
BACKGROUND: Trichinellosis caused by the gastrointestinal nematode Trichinella spiralis occurs in humans, domestic animals and wild animals. It is difficult to control the muscle phase of the parasite. Homeopathic drugs such as Cina and Santoninum have anthelmintic properties. We have observed that in material doses, the homeopathic drug Podophyllum also has nematotoxic properties. We have also observed that homeopathic potency can influence the water permeability of cells. OBJECTIVE: The purpose of this study was to investigate whether potentized homeopathic drugs such as Cina 30, Santoninum 30 and Podophyllum mother tincture can affect the muscle phase of the parasite T. spiralis in mice. Another objective was to see whether trichinellosis and its treatment with the 3 named homeopathic drugs could alter the water content in the muscle tissue of mice. MATERIALS AND METHODS: Cina 30 and Santoninum 30 were prepared from the mother tincture of the flowering tops of Artemisia nilagirica and its active principle santonin, in each case by successive dilution (1:100) with 90% ethanol and sonication in 30 steps following the single glass method (K30). Ethanol 30 was prepared by successive dilution of 90% ethanol with 90% ethanol (1:100) followed by sonication in 30 steps. In each step, the dilution was sonicated at 20 KHz for 30 s. We have observed before that sonication is a more uniform, measurable and effective process of mechanical agitation of a liquid than manual succussion. Experimentally infected mice were orally treated with an aqueous Podophyllum suspension at 60 mg/kg/day. Each potentized drug was diluted 1:20 with distilled water and administered orally at 0.05 ml/mouse/day. Each mouse was inoculated with T. spiralis larvae at a dose of 200 larvae/mouse by esophageal intubation. Treatment was started on day 7 post-infection and continued for 120 days. After completion of treatment, the mice were sacrificed and the larvae were extracted from muscles by HCl-pepsin digestion. The water content of the muscles was measured by determining the difference between fresh weight and dry weight of the tissue. RESULTS: Podophyllum Theta, Cina 30 and Santoninum 30 reduced the larval population in the studied mice by 68.14%, 84.10% and 81.20%, respectively, as compared to the untreated control group. Ethanol 30 achieved no significant reduction in the larval population compared to the untreated control group. The water content of the muscle tissue in the untreated control group and the Podophyllum-treated groups was significantly higher than in the Ethanol 30-, Cina 30- and Santoninum 30-treated groups. CONCLUSIONS: (1) Podophyllum Theta, Cina 30 and Santoninum 30 were effective in the muscle phase of T. spiralis infection and significantly reduced the larval population in the treated mice. The potencies were more effective than the mother tincture, an effect which was not due to the medium ethanol. (2) The potencies significantly reduced the water content of the muscle tissue which might have affected the larvae. The effect of Podophyllum Theta might be due to the direct toxic effect of the drug on the larvae.
Animals↗
Experimental podophyllotoxin (bajiaolian) poisoning: I. Effects on the nervous system.
Bajiaolian, one of the species in the Mayapple family (Podophyllum pelatum), has been widely used as a traditional Chinese herbal medicine for the remedies of snake bites, general weakness, poisons, condyloma accuminata, lymphadenopathy, and certain tumors in China. In Western medicine, Podophyllum was first used medically as a laxative in the early 19th century. Since 1940, the resin of podophyllum has also been used topically for various skin lesions, such as warts and condyloma. Human poisonings have been reported. An animal model was established to investigate the neurotoxic effects of Bajiaolian. Podophyllotoxin, the major active ingredient in Podophyllum, was injected (ip) to young adult male rats at doses of 0, 5, 10, or 15 mg.kg-1 b.w.. The animals were sacrificed 72 h after injection. Neuronal changes were readily observable in animals treated with 10 or 15 mg.kg-1 of the toxin. Edematous changes of the anterior horn motoneurons were observed in the spinal cord. No neuronal necrosis was found. The type of neuronal swelling is believed to be only a transient change and would probably subside with time if no further assaults occur. More serious and perhaps longer term of changes were found in the dorsal ganglion neurons and the nerve fibers (axons) in the central and peripheral nervous system. Severe depletion of the Nissl substance (RNA/polyribosomes) was observed in the dorsal root ganglion neurons. Alterations in these sensory neurons would give rise to and correlate with the sensory disturbances experienced by the patients. Bodian staining also revealed a dose-related increase in the coarseness (thickness) of the nerve fibers (axons) in the cerebellum, cerebral cortex, brainstem, and spinal cord. This is the first scientific study showing the neurotoxicity of Bajiaolian, a commonly used Chinese herbal medicine. Toxicities on other organ systems by this drug certainly exist. Caution should be exercised in the dispensing and usage of this medicine.
Animals↗
[Controlling effects of plant extracts and pesticides on Myzus persicae and Lipaphis erysimi populations].
This paper studied the controlling effects of Xanthium sibiricum and Syngonium podophyllum ethanol extracts, mobile oil emulsion and 0.3% azadirachtin EC on Myzus persicae and Lipaphis erysimi populations both in laboratory and in field. The results showed that in laboratory, X. sibiricum extract was the key deterrent to Myzus persicae, while sprayed it with S. podophyllum extract and with petroleum spray oil or 0.3 % azadirachtin EC, the deterrent effect could be improved. As for pterigota Lipaphis erysimi, the extracts of the two plants were the main deterrents, and their interference effect was non-linear. In field, S. podophyllum extract had a stronger deterrent effect when sprayed independently. L. erysimi population could be successfully controlled by the mixtures of plant extracts and insecticides, with an efficiency of 95.7%. The best treatment against M. persicae population was X. sibiricum extract, with an efficiency of 87%, while S. podophyllum extract mixed with 0.3% azadirachtin EC, and X. sibiricum extract mixed with 0.3% azadirachtin EC had an efficiency of >80%.
Animals↗
No effect of a homeopathic preparation on neonatal calf diarrhoea in a randomised double-blind, placebo-controlled clinical trial.
A double-blind, placebo-controlled clinical trial of a homeopathic treatment of neonatal calf diarrhoea was performed using 44 calves in 12 dairy herds. Calves with spontaneously derived diarrhoea were treated with either the homeopathic remedy Podophyllum (D30) (n = 24) or a placebo (n = 20). No clinically or statistically significant difference between the 2 groups was demonstrated. Calves treated with Podophyllum had an average of 3.1 days of diarrhoea compared with 2.9 days for the placebo group. Depression, inappetence and fever were presented equally in the 2 groups. These results support the widely held opinion that scientific proof for the efficacy of veterinary homeopathy is lacking. In the European Union this implies a considerable risk for animal welfare, since in some countries priority is given to homeopathic treatments in organic farming.
Animals↗
Radioprotective effect of podophyllotoxin in Saccharomyces cerevisiae.
Recent reports showed that whole extract of Podophyllum hexandrum was radioprotective in mice. Podophyllotoxin is one of the major constituents of the whole extract of Podophyllum. In this study we report on the radioprotective action of podophyllotoxin in Saccharomyces cerevisiae yeast. Proliferating yeast cells pretreated with podophyllotoxin (2.5-5.0 microg/mL) for > or =3 hours showed a higher surviving fraction after (60)Co-gamma-irradiation (200-600 Gy) than did the irradiated cells not pretreated with podophyllotoxin. The maximum increase (2.0 times) in surviving fraction was observed in cells treated with 2.5 microg/mL podophyllotoxin, 5 hours before (60)Co-gamma-irradiation (400 Gy). Podophyllotoxin was not mutagenic or recombinogenic at radioprotective doses (2.5 microg/mL). A post-irradiation decrease in revertants and gene convertants was observed in cells treated with podophyllotoxin (2.5 microg/mL podophyllotoxin, -5 hours, 400 Gy). This study indicates that podophyllotoxin is radioprotective in yeast, and its radioprotective effects in higher eukaryotes would be worth investigating.
Dose-Response Relationship, Radiation↗
Condylomata acuminata in the pediatric population.
The incidence of condylomata acuminata infection has shown a steady increase for adults and children in recent years. With the discovery that the viral agents of this disease are potentially neoplastic, a disorder that was once considered a nuisance is now taking on new-found importance and concern. Furthermore, the knowledge that these lesions are often sexually transmitted and the ever-increasing concern over child abuse have combined to make the recognition and treatment of this disease in the pediatric population of even greater significance. Depending on location, podophyllum resin (podophyllin) is the initial therapy of choice. Available studies indicate a cure rate ranging from 22% to 98% depending on location of the warts, frequency of treatment, patient compliance, and freshness of the podophyllum resin preparation. Cure rates of 91% to 97% have been reported with cryotherapy and laser photocoagulation. Eradication of the viral agent and long-term follow-up are important.
Adolescent↗
Condyloma. A new epidemic.
Condyloma acuminatum of the anus is an increasingly frequent disease that may require a combination of therapies. Large bulky lesions can be reduced with topical freezing, cautery, or the scapel. Topical chemotherapy with podophyllum resin can be supplemented with cancer chemotherapeutic agents. Many of these drugs probably act, at least in part, by stimulating a strong local cellular immune reaction. Dinitrochlorobenzene was used to eradicate lesions that had been resistant to treatment with podophyllum resin. 5-Flourouracil was used as a control. All 23 patients studied were initially skin tested with both agents and randomized to either treatment group. All but one of the dinitrochlorobenzene-treated patients had excellent regressions. Immunotherapeutic agents, such as dinitrochlorobenzene, warrant further study as adjuvant therapeutic agents for this disease.
Antineoplastic Agents↗
Etoposide: a semisynthetic epipodophyllotoxin. Chemistry, pharmacology, pharmacokinetics, adverse effects and use as an antineoplastic agent.
Etoposide (VP 16) is a semi-synthetic derivative of 4'- demethylepipodophyllotoxin , a naturally occurring compound synthesized by the North American May apple (Podophyllum peltatum ) and the Indian species Podophyllum emodi Wallich . Although podophyllotoxins are classical spindle poisons causing inhibition of mitosis by blocking mitrotubular assembly, etoposide inhibits cell cycle progression at a premitotic phase (late S and G2), probably via inhibition of DNA synthesis. There appears to be a selective antileukemic dose response relationship when compared to normal hematopoietic elements. Etoposide is effective when administered orally at about twice the recommended parenteral dosage. Schedule dependency in both animal models and clinical trials has been observed; multiple dosing over three to five consecutive days is superior to weekly single dose administration. Etoposide's dose-limiting toxicity is myelosuppression (leukopenia), which is quite predictable; alopecia and Gl toxicity (nausea, vomiting, stomatitis) occur in about 20-30% of patients given recommended dosages. Etoposide appears to be one of the most active drugs for small cell lung cancer, testicular carcinoma (the Food and Drug Administration approved indication), ANLL and malignant lymphoma. Etoposide also has demonstrated activity in refractory pediatric neoplasms, hepatocellular, esophageal, gastric and prostatic carcinoma, ovarian cancer, chronic and acute leukemias and non-small cell lung cancer, although additional single and combination drug studies are needed to substantiate these data. Its contribution in front-line combination chemotherapeutic regimens for these cancers will be better defined in the forthcoming years. Etoposide appears to have minimal activity in breast cancer and, based on current data, it is inactive against malignant melanoma, colorectal adenocarcinoma and cancer of the head and neck, although the dosage and schedules used in many of the Phase II studies may have been suboptimal.
Antineoplastic Combined Chemotherapy Protocols↗
The production of cytotoxic lignans by plant cell cultures.
Cytotoxic lignans derived from podophyllotoxin are currently used in cancer chemotherapy. Podophyllotoxin for semi-synthetic derivatization is isolated from the rhizomes of Podophyllum plants growing wild, some of which are counted as endangered species. An alternative source for podophyllotoxin or related lignans may in future be cell cultures derived from different plant species, such as Podophyllum spp or Linum spp. These cell cultures were shown to accumulate considerable amounts of podophyllotoxin or 5-methoxypodophyllotoxin. Optimization of the cell cultivation regime might lead to a renewable source of cytotoxic lignans for medicinal uses. This Mini-Review summarizes the attempts to establish plant cell cultures for the production of podophyllotoxin and related lignans and their optimization towards high levels of these target compounds. It also summarizes the results of studies on the biosynthesis of podophyllotoxin and 5-methoxypodophyllotoxin.
Cell Culture Techniques↗
Podophyllotoxin.
Podophyllin, an ethanolic extract of Podophyllum peltatum L. or P. emodi Wall (syn. P. hexandnum Royle), is a good source of the aryltetralin-type lignan, podophyllotoxin. The latter compound, as well as its congeners and derivatives exhibit pronounced biological activity mainly as strong antiviral agents and as antineoplastic drugs. The podophyllotoxin derivatives etoposide, etopophos (etoposide phosphate), and teniposide are thus successfully utilized in the treatment of a variety of malignant conditions. Continued research on the Podophyllum lignans is currently focused on structure optimization to generate derivatives with superior pharmacological profiles and broader therapeutic scope, and the development of alternative and renewable sources of podophyllotoxin.
Podophyllotoxin↗
Screening of anti-bacterial activity of medicinal plants from Belize (Central America).
Twenty-one extracts from seven herbal drugs, Aristolochia trilobata (Aristolochiaceae) leaves and bark, Bursera simaruba (Burseraceae) bark, Guazuma ulmifolia (Sterculiaceae) bark, Hamelia patens (Rubiaceae) leaves and Syngonium podophyllum (Araceae) leaves and bark, used in traditional medicine of Belize (Central America) as deep and superficial wound healers, were evaluated for their anti-bacterial properties. Activity was tested against standard strains of Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923 and Enterococcus faecalis ATCC 29212. Almost all the extracts were able to inhibit the growth of one or more of the bacterial strains, except that of Enterococcus faecalis. For the first time an anti-microbial activity is reported for Aristolochia trilobata as well as for Syngonium podophyllum. The hexane extracts of Aristolochia trilobata leaves and bark were the most active extracts against Staphylococcus aureus (MIC=0.31 and 0.625mg/ml, respectively).
Anti-Bacterial Agents↗
Podophyllotoxin intoxication: toxic effect of Bajiaolian in herbal therapeutics.
Bajiaolian (Dysosma pleianthum), one species in the Mayapple family, has been widely used as a general remedy and for the treatment of snake bite, weakness, condyloma accuminata, lymphadenopathy and tumours in China for thousands of years. However, the textbooks of traditional Chinese medicine mention little about the toxicity of Bajiaolian. Within 1 year, the authors saw five people who manifested nausea, vomiting, diarrhoea, abdominal pain, thrombocytopenia, leucopenia, abnormal liver function tests, sensory ataxia, altered consciousness and persistant peripheral tingling or numbness after drinking infusions made with Bajiaolian. The herb was recommended by either traditional Chinese medical doctors or herbal pharmacies for postpartum recovery and treatment of a neck mass, hepatoma, lumbago and dysmenorrhoea. Podophyllotoxin is one of the main ingredients of the Bajiaolian root. The clinical manifestations observed in our patients were consistent with podophyllum intoxication. Podophyllotoxin intoxication usually results from the accidental ingestion or topical application of podophyllum resin. However, these cases of Bajiaolian intoxication were iatrogenic and results from 'therapeutic doses' of Bajiaolian cited in the textbooks of traditional Chinese medicine.
Adult↗
[Radio-chemotherapy of cervix carcinoma. I. Clinical part].
A prospective study was performed for a new model concerning the potentiation of radiation with Podophyllum (Proresid) and the radioprotection with Acethylhomocystein-thiolactone (Reducdyn) in cases of the squamous cell carcinoma of the uterine cervix. The study was carried out on the basis of alternated data of birth. The total number of the randomization was 256, consisting of 173 stages II und 83 stages III. All patients were irradiated with 6000 mgeh Ra and 4500 R 60Co. In addition to the irradiation one group of 128 patients received an infusion of 1g Podophyllum/day after irradiation. Another group of 46 patients was treated prior to irradiation with 1g Acethyl-homocystein-thiolactone (AHCT) and with Podophyllum after exposure. The total dosage was between 30 and 50g Pod. and 30 and 50g AHCT. It could be shown that the survival rate after three years was increased up to 15%. An earlier study revealed a five-year-survival rate of 23%.
Female↗
Topical treatment of penile condylomata acuminata with podophyllin, podophyllotoxin and colchicine. A comparative study.
The effect of alcoholic solutions with 20% podophyllin from Podophyllum peltatum and Podophyllum emodi, 8% podophyllotoxin, and 8% colchicine, when applied to penile condylomata acuminata in 227 men, were statistically alike. Of the patients initially judged to be cured after 1-2 applications, 13% showed recurrence, thus bringing down the permanent cure frequency to only 43%. Local side effects were absent after only half the series of colchicine applications, whereas as much as about 3/4 of the treatment course with podophyllin and pure podophyllotoxin could be completed without provoking discomfort. Warts in the urinary meatus healed significantly less well than warts on the other genital mucous membranes. Eighty-nine per cent of patients who had previously been cured of concylomata became wart-free after 1-2 treatments, as opposed to only 40% of those who had never had this wart type previously. The use of the commercially available colchicine offers an opportunity to establish a standardized therapy; following application of an 8% solution, rinsing off should be performed after 6-8 hours.
Administration, Topical↗
Podophyllotoxins: current status and recent developments.
Podophyllotoxin is a natural product isolated from Podophyllum peltatum and Podophyllum emodi and has long been known to possess medicinal properties. Etoposide (VP-16), a podophyllotoxin derivative, is currently in clinical use in the treatment of many cancers, particularly small cell lung carcinoma and testicular cancer. This compound arrests cell growth by inhibiting DNA topo-isomerase II, which causes double strand breaks in DNA. VP-16 does not inhibit tubulin polymerization, however, its parent compound, podophyllotoxin, which has no inhibitory activity against DNA topoisomerase II, is a potent inhibitor of microtubule assembly. In addition to these two mechanisms of action, an unknown third mechanism of action has also been proposed for some of the recent modifications of podophyllotoxins. Owing to its severe toxic side effects a number of modifications have been done on podophyllotoxin structure. Some of the congeners exhibited potent antitumor actiivity, of which etoposide and teniposide are in clinical use, NK 611 is in phase II clinical trials and many compounds are in the same line. Recent developments on podophyllotoxins have led structure-activity correlations which have assisted in the design and synthesis of new podophyllotoxin derivatives of potential antitumor activity. Modification of the A-ring gave compounds having significant activity but less than that of etoposide, whereas modification of the B-ring resulted in the loss of activity. One of the modifications in the D-ring produced GP-11 which is almost equipotent with etoposide. E-ring oxygenation did not affect the DNA cleavage which led to the postulation of the third mechanism of action. It has also been observed that free rotation of E-ring is necessary for the antitumor activity. The C4-substituted aglycones have a significant place in these recent developments. Epipodophyllotoxin conjugates with DNA cleaving agents such as distamycin increased the number of sites of cleavage. The substitution of a glycosidic moiety with arylamines produced enhanced activity. Modification in the sugar ring resulted in the development of the agent, NK 611 which is in clinical trial at present. This article review, the progress of podophyllotoxins from its early applications in folk medicine to the most recent modifications and the mechanism(s) of action, pharmacology and the structure-activity relationships.
Animals↗
Mandrake toxicity. A case of mistaken identity.
A 31-year-old man ingested an unknown amount of mandrake plant purchased at a local health food store and came to the emergency department with severe nausea and vomiting. He was hospitalized overnight but recovered uneventfully without obvious adverse systemic effects. This plant was almost certainly Podophyllum peltatum based on chromatographic identification of podophyllotoxin in a sample. However, the patient had mistakenly believed he was taking the anticholinergic and hallucinatory plant Mandragora officinarum, which is also known as mandrake. Other users of herbal substances and authors of the medical literature have also confused these 2 versions of mandrake. Given the growing popularity of alternative therapies, physicians should understand the distinction between these substances and should be aware of the medical effects of other commonly used herbal remedies.
Adult↗