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At least 19 recordsLinked to original sources

Iron chelation and related properties of Podophyllum hexandrum, a possible role in radioprotection.

Aqueous extract of Podophyllum species has been reported to render significant protection against radiation induced mortality, cytogenetic damage and cell death. In view of this, present study was undertaken to investigate its antioxidant properties. Chelation, oxidation and reduction of Fe2+ and Fe3+ were measured using chelating agents 2-2' bipiridyl and potassium thiocyanate respectively. Podophyllum extract, in a dose dependent manner, chelated Fe2+ more efficiently than Fe3+ and also modulated Fe2+/Fe3+ ratio. Homogenate of mouse liver was used to measure TBARS for estimating lipid peroxidation. Podophyllum extract also inhibited lipid peroxidation in a dose dependent manner and maximum inhibition (92%) was achieved at 1000 micrograms/ml concentration. These results demonstrates that Podophyllum exhibits antioxidant properties as seen through chelation and modulation of redox state of iron ions and these may primarily contribute towards its radioprotective manifestation.

Animals↗

Podophyllum toxicity: case report and literature review.

A case is reported of apparent podophyllum toxicity. The patient was a 17-year-old female Indian who had received some 3 to 8 cc of a 20 percent mixture of podophyllum resin in compound tincture of benzoin (approximately equal to 0.4 gm of podophylotoxin) as an application to her vulvar condylomata. She returned to the hospital 20 hours after application in a comatose state. On examination she demonstrated severe toxicity including bone marrow, liver, and central nervous system. She required a charcoal hemoperfusion at the University of Colorado, and six months after the event has several neurologic and physiologic sequelae. Podophyllum is a potentially severely toxic drug. Great care must be taken when treating patients with this drug. A large mass of condylomata or the status of pregnancy should be relative contraindications to the use of podophyllum.

Adolescent↗

Identification and characterization of Podophyllum emodi by API-LC/MS/MS.

An API-LC/MS/MS method was developed for the identification of the medicinal herb Podophyllum emodi based on the profile of its aryltetrahydronapthalene and related lignan marker compounds. This was done by matching the structural information from the tandem mass spectrometric data with those lignan marker compounds already reported for the herb. The method could be employed in the absence of reference standards for the markers and was particularly useful in view of the scarcity of supply of these chemical standards. It has been used successfully to differentiate Podophyllum emodi from two commonly used medicinal herbs of a different genus but having similar appearance, Radix clematidis and Radix gentiana, as well as a closely related herb, Podophyllum peltatum.

Biomarkers↗

Influence of Podophyllum hexandrum on endogenous antioxidant defence system in mice: possible role in radioprotection.

Podophyllum hexandrum, a Himalayan herb with known radioprotective and anti-tumour properties, was investigated for its mechanism of action. Glutathione S-transferase (GST), catalase, superoxide dismutase (SOD) activities and lipid peroxidation (LPx) were determined in the liver, jejunum and ileum at various time intervals, with and without the aqueous extract of P. hexandrum rhizome (200 mg/kg b.w. i.p.) in unirradiated and whole body irradiated (10 Gy,-2 h) male Swiss albino mice. Pre-irradiation treatment with P. hexandrum enhanced liver GST (P<0.01) and SOD (P<0.05) at 12 h post irradiation, the intestinal SOD (P<0.00005) at 84 h post irradiation was significantly elevated. However, no significant change was manifested in the catalase activity in the liver, at any of the post irradiation intervals (0, 12 and 84 h). The antioxidant defence with Podophyllum sp. treatment in mice can explain to some extent its protective action manifested in terms of survival against whole body lethal irradiation. However, some other possible mechanisms that may strengthen radioprotective action of the Podophyllum sp. extract need to be investigated further.

Animals↗

Retrospective findings of the clinical benefits of podophyllum resin 25% sol on hairy leukoplakia. Clinical results in nine patients.

Hairy leukoplakia was first described as an oral marker of human immunodeficiency virus infection in 1984. The clinical significance of this lesion in an otherwise healthy, high-risk symptom-free person is that it can be an early manifestation of human immunodeficiency virus infection. Because of its benign nature and the lack of clinical evidence that treatment of the lesion improves the prognosis of human immunodeficiency virus-infected patients, systemic therapy with antiviral drugs does not seem warranted at this time. Topical retinoids (Retin-A sol) and systemic antivirals such as acyclovir have been previously tried; however, lesions tend to recur a few days after treatment is discontinued. Nine patients with oral hairy leukoplakia seen at the Oral Medicine Clinic, University of California San Francisco were offered treatment with podophyllum resin 25% sol. All patients had a complete remission of their condition within 1 week (5 patients) or after the second application a week later (4 patients). Side effects were transient and reversible. These remissions of oral hairy leukoplakia lasted from 2 to 28 weeks, which suggests that podophyllum may be a relatively safe and cost-effective treatment of this otherwise symptom-free lesion.

Adult↗

Separation and determination of podophyllum lignans by micellar electrokinetic chromatography.

A micellar electrokinetic chromatography method was established for the quantitative analysis of seven podophyllum lignans in Podophyllum emodi Wall. var. chinesis sprague. The optimum buffer system was 10 mM NaH2PO4-5 mM borate-100 mM sodium dodecylsulfate-30% isopropanol (pH 7.20). Voltage was 18 kV and detection at 214 nm. The second derivative chromatogram was used to determine a low-content component and those not fully separated from adjacent ones. The RSD values of migration times and peak areas were <2.2 and <5.5%, respectively. The effects of several CE parameters on the resolutions were studied systematically.

Chromatography, Micellar Electrokinetic Capillary↗

Enhanced production of podophyllotoxin by Podophyllum hexandrum using in situ cell retention bioreactor.

The rhizomes of the rare plant Podophyllum hexandrum contain podophyllotoxin, which is a precursor of the anticancer drugs etoposide and teniposide. Batch cultivation of Podophyllum hexandrum was conducted using optimized medium in a 3 L bioreactor, which resulted in biomass and podophyllotoxin concentrations of 21.4 g/L and 13.8 mg/L in 24 and 26 days, respectively. The batch kinetics was used to identify the mathematical model. The model was extrapolated to identify the nutrient feeding rate (150 mL/d) and substrate concentration (105 g/L) in the incoming feed for nonlimiting and noninhibitory glucose concentration in the cell retention bioreactor. An improvement in cell growth to 53 g/L and intracellular podophyllotoxin accumulation of 48.8 mg/L was achieved in 60 days, when the bioreactor was operated in continuous cell retention cultivation mode.

Bioreactors↗

Effects of Podophyllum hexandrum on radiation induced delay of postnatal appearance of reflexes and physiological markers in rats irradiated in utero.

Effect of 2.0 Gy gamma-dose delivered to rats in utero on 17th day of gestation was studied to monitor the radiation induced retardation of neurophysiological development in postnatal young ones. Rhizome of Podophyllum hexandrum which has been well documented for mitigating radiation injuries in adult mice was attempted for modifying radiation damage. Rats were observed from postnatal day 1 to 25 for the age of the appearance of physiological markers (pinna detachment, inscisor's eruption, eye opening) and acquisition of reflexes (surface righting, visual placing, reflex suspension, negative geotaxis). In irradiated groups there was a significant weight reduction in mother rats and offsprings throughout the experimental period. There was radiation-induced delay in the appearance of pinna detachment but not in eye opening and inscisor's eruption. Appearance of the reflexes were also delayed due to irradiation. Preirradiation administration of the extract of Podophyllum hexandrum (i.p., 200 mg/kg/b.w.) mitigated radiation induced postnatal physiological alterations. These studies have implications in protection against damage (in utero) due to planned radiation exposure.

Animals↗

Treatment of HIV-related hairy leukoplakia with podophyllum resin 25% solution.

Ten HIV-infected patients who had bilateral hairy leukoplakia on the tongue were treated with topical podophyllum resin 25% solution. Only one side of the bilateral lesion was treated and the other side served as the control and was not treated. The lesions on both the treatment and control sides were evaluated at day 2, 7, and 30 by an investigator who had not been involved in the initial treatment and had no knowledge of which side had been treated. Therefore the treatment side is compared with the control side in a single-subject design, single-blind control setting. The lesions were judged by the degree of resolution and assigned a number of 0 to 4 with 4 indicating the highest degree of resolution and 0 indicating no resolution or worsening of the condition. The results were analyzed by Student's t test. Significant resolution of hairy leukoplakia was noted on the treatment side compared with the control side at the 2-, 7-, and 30-day levels; the 2-day results were the most significant. Furthermore, the patients reported minimal side effects, which included burning sensation, bad or altered taste, and pain, that were of mild intensity and short duration. The side effects were reported to occur immediately after the topical application. Patient tolerance and acceptance were found to be very favorable. No systemic side effect was reported. We conclude that single topical application of podophyllum resin 25% solution is efficacious in producing significant short-term resolution of HIV-related oral hairy leukoplakia. We also conclude that it is a safe topical regimen with minimal side effects.

Administration, Topical↗

Laryngeal papilloma: results of treatment with the CO2 laser and podophyllum.

From 1976 to 1982, 109 patients with recurrent laryngeal papillomas were treated with a total of 548 CO2 laser excisions followed by podophyllum painting. There was high incidence of multiple sites of involvement, especially the tracheobronchial tree (18.3%) and palate (8.3%). Four patients had pulmonary parenchymal involvement. Patients were treated at 2-month intervals until they entered remission. Thereafter, microdirect laryngoscopies were advised at longer intervals. Remission was achieved in 41%; it occurred at all ages although it was most common during adolescence and rarest in the very young and very old. Many patients obtained remission with the CO2 laser after multiple prior cup forceps removals had not achieved remission. Only two tracheotomies (1.8%) were required and no deaths occurred. When compared with mechanical methods of papilloma removal, CO2 laser excision with podophyllum painting represents a clear advance in terms of preservation of laryngeal physiology and avoidance of life-threatening complications.

Adolescent↗

Podophyllum: suspected teratogenicity from topical application.

A case demonstrating suspected teratogenic effects of topical podophylium is presented. Podophyllum resin was applied five times for a duration of 4 hr from the 23rd to the 29th week of pregnancy. At birth a simian crease on the left hand and a preauricular skin tag were noted. It is suggested that podophyllum be avoided during pregnancy. Alternative treatment for warts of the vaginal, perineal, or anal area are presented.

Abnormalities, Drug-Induced↗

Podophyllum toxicity: a report of a fatal case and a review of the literature.

A 59-yr-old male ingested 10 g of podophyllum in a fatal suicide attempt. Previously unreported nuclear and cytoplasmic changes were observed in circulating leukocytes. Symptoms did not occur until 10 h after ingestion with loss of reflexes, coma, and a marked lactic acidosis. Despite hemoperfusion, the patient expired 39 h after ingestion. The literature on podophyllum toxicity is reviewed.

Adolescent↗

Studies in sugar chemistry. VII. Glucuronides of podophyllum derivatives.

The antitumor activities of several glucuronide methyl esters of podophyllum derivatives were tested in vitro against two human tumor cell lines and their drug resistant sublines. The most active compound studied was methyl (4'-carbobenzoxy-4'-demethyl-epipodophyllotoxin-D-glucopyranoside)uronat e 19. Compound 19 was as potent in a colon carcinoma model and was twice as potent in a lung carcinoma model as etoposide 6. In vivo, however, in a mouse leukemia P388 model, it had only marginal activity, with a maximum T/C% value of 125 at 37 mg/kg (iv).

Animals↗

Podophyllum hexandrum prevents radiation-induced neuronal damage in postnatal rats exposed in utero.

Podophyllum hexandrum has been shown to mitigate radiation injuries and especially the haemopoietic syndrome in adult mice. To monitor the radiation-induced changes in the nervous system, the neurons of postnatal young mice and their modification by P. hexandrum, were studied histologically for differences in the apical and basal dendritic branching and intersections in the CA1 neurons of the hippocampal region of rats which were delivered a 2 Gy gamma dose while in utero (day 17 of gestation). Irradiation significantly reduced the dendritic branching and intersections but pre-irradiation administration of the extract of P. hexandrum (i.p. 200 mg/kg/b.w., 2 h) reduced the damage in postnatal young mice. These studies indicate that P. hexandrum provides protection to neurons against radiation-induced damage and the mechanism of neuronal damage and its repair need to be investigated further.

Animals↗

Dense bodies and Langerhans granules after application of podophyllum resin.

The application of an alcoholic solution of podophyllum resin at concentrations above 10% for seven hours on guinea-pig udders increases the number of dense intracytoplasmic bodies in the Langerhans cells localized in the epidermis. A close relationship can be established between these inclusions and the typical Langerhans granules in view of the numerous intermediate forms with features of one or the other. Serial sections of these structures confirm the irregularity not only of the lysosome-like bodies but also of the Langerhans granules, which may be fusiform or oblong or even present two vesicular dilatations, one at each end of the rod.

Cell Membrane↗

Effect of major nutrients on podophyllotoxin production in Podophyllum hexandrum suspension cultures.

The effect of major medium ingredients (sugar, nitrogen source and phosphate) in Podophyllum hexandrum suspension cultures was investigated in order to increase the production of podophyllotoxin, the raw material in the synthesis of anticancer drugs. Amongst B5, Eriksson, MS, Nitsch, Street and White's medium, MS medium resulted in high growth and podophyllotoxin accumulation. The optimum level of nitrogen was found to be 60 mM, with a combination of ammonium salts and nitrate in the ratio of 1:2. The highest level of podophyllotoxin was obtained at 60 g glucose/l and at 1.25 mM phosphate after 30 days. Statistical design was adopted to determine the optimum levels of the parameters for cell growth and podophyllotoxin production.

Antineoplastic Agents, Phytogenic↗

Dirigent-mediated podophyllotoxin biosynthesis in Linum flavum and Podophyllum peltatum.

Given the importance of the antitumor/antiviral lignans, podophyllotoxin and 5-methoxypodophyllotoxin, as biotechnological targets, their biosynthetic pathways were investigated in Podophyllum peltatum and Linum flavum. Entry into their pathways was established to occur via dirigent mediated coupling of E-coniferyl alcohol to afford (+)-pinoresinol; the encoding gene was cloned and the recombinant protein subsequently obtained. Radiolabeled substrate studies using partially purified enzyme preparations next revealed (+)-pinoresinol was enantiospecifically converted sequentially into (+)-lariciresinol and (-)-secoisolariciresinol via the action of an NADPH-dependent bifunctional pinoresinol/lariciresinol reductase. The resulting (-)-secoisolariciresinol was enantiospecifically dehydrogenated into (-)-matairesinol, as evidenced through the conversion of both radio- and stable isotopically labeled secoisolariciresinol into matairesinol, this being catalyzed by the NAD-dependent secoisolariciresinol dehydrogenase. (-)-Matairesinol was further hydroxylated to afford 7'-hydroxymatairesinol, this being efficiently metabolized into 5-methoxypodophyllotoxin. Thus much of the overall biosynthetic pathway to podophyllotoxin has been established, that is, from the dirigent mediated coupling of E-coniferyl alcohol to the subsequent conversions leading to 7'-hydroxymatairesinol.

Amino Acid Sequence↗

Protection against radiation induced damage to spermatogenesis by Podophyllum hexandrum.

Aqueous extract of rhizome of Podophyllum hexandrum (RP-1) has been found to render protection against lethal whole body irradiation (10 Gy), damage to haemopoietic and gastrointestinal tissue etc. in mice. In order to assess its suitability from clinical point of view its effects were investigated on male germinal tissue in mice. Swiss albino strain 'A' male mice (10-12 weeks) were exposed to varied radiation doses (0.5, 2.0, 5.0 and 10 Gy) with and without 200 mg/kg b.w. of RP-1 and sacrificed at different time periods (10, 35 and 70 days) to collect the tissue. Administration of RP-1, 2 h before irradiation rendered a significant increase in the testis weight, repopulating tubules, resting primary spermatocytes, stem cell survival index, sperm counts and reduction in abnormalities of sperm morphology, at all the time periods studied here. RP-1 treatment alone did not generate any adverse effects. These results reveal that RP-1, if put to clinical application, will not be harmful to the testicular system.

Animals↗