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At least 19 recordsLinked to original sources

PubMed2000

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↗

PubMed1979

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↗

PubMed2000

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↗

PubMed2001

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↗

PubMed2005

Radioprotective and antioxidant properties of low-altitude Podophyllum hexandrum (LAPH).

The development of nontoxic yet effective radioprotectors is needed because of the increasing risk of human exposure to ionizing radiation. We have reported that high-altitude Podophyllum hexandrum (HAPH) confers a radioprotective effect in in vitro and in vivo models. The present study reports on the antioxidant and radioprotective properties of low-altitude Podophyllum hexandrum (LAPH), from which the toxic compound podophyllotoxin has been partially removed during the extraction process. Using HPLC,we estimated the relative content of two marker compounds, podophyllotoxin and podophyllotoxin glycoside, in low-altitude Podophyllum extract (LAPE) and found them to be 23.3% and 9.50%, respectively. The ferrous ion chelation potential of LAPE was estimated using the 2,2 bipyridyl assay, and the activity was found to be increased concomitantly with the increase in its concentration, with a maximal inhibition at 25 microg/mL (42.20%) as compared to quercetin (34.9%). The electron donation potential of LAPE was also evaluated, because the antioxidant activities of natural products are known to bear a direct correlation with their ability to donate electrons. The concentration required to attain unit absorbance values at 700 nm were 0.230541+/-0.09 and 0.041+/-0.06 for butylated hydroxyl toluene and LAPE, respectively, indicating a higher antioxidant activity of LAPE. The free radical scavenging ability of LAPE was also assessed and exhibited a dose-dependant increase (1-100 microg/mL), comparable to that of quercetin at 25 microg/mL. The role of LAPE in protecting DNA was evaluated, and it was found that LAPE (30 microg/mL) rendered its maximum radioprotection against the 250 Gy-induced damage in the plasmid (pBR322) relaxation assay. LAPE significantly inhibited radiation-induced, iron/ascorbate- and combined stress (iron/ascorbate and radiation)-induced formation of TBARS (p<0.05). We conclude that LAPH, with its easy accessibility, ease of cultivation, multifarious radioprotective properties, and role as a renewable source of bioactive constituents, along with its low associated toxicity (due to partial removal of podophyllotoxin), enhances its possible use for human clinical applications.

Altitude↗

PubMed1992

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↗

PubMed2001

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↗

PubMedDate not supplied

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↗

PubMed2006

Secoisolariciresinol dehydrogenase: mode of catalysis and stereospecificity of hydride transfer in Podophyllum peltatum.

Secoisolariciresinol dehydrogenase (SDH) catalyzes the NAD+ dependent enantiospecific conversion of secoisolariciresinol into matairesinol. In Podophyllum species, (-)-matairesinol is metabolized into the antiviral compound, podophyllotoxin, which can be semi-synthetically converted into the anticancer agents, etoposide, teniposide and Etopophos. Matairesinol is also a precursor of the cancer-preventative "mammalian" lignan, enterolactone, formed in the gut following ingestion of, for example, various high fiber dietary foods, as well as being an intermediate to numerous defense compounds in vascular plants. This study investigated the mode of enantiospecific Podophyllum SDH catalysis, the order of binding, and the stereospecificity of hydride abstraction/transfer from secoisolariciresinol to NAD+. SDH contains a highly conserved catalytic triad (Ser153, Tyr167 and Lys171), whose activity was abolished with site-directed mutagenesis of Tyr167Ala and Lys171Ala, whereas mutagenesis of Ser153Ala only resulted in a much reduced catalytic activity. Isothermal titration calorimetry measurements indicated that NAD+ binds first followed by the substrate, (-)-secoisolariciresinol. Additionally, for hydride transfer, the incoming hydride abstracted from the substrate takes up the pro-S position in the NADH formed. Taken together, a catalytic mechanism for the overall enantiospecific conversion of (-)-secoisolariciresinol into (-)-matairesinol is proposed.

Alcohol Oxidoreductases↗

PubMed2005

Crystal structures of apo-form and binary/ternary complexes of Podophyllum secoisolariciresinol dehydrogenase, an enzyme involved in formation of health-protecting and plant defense lignans.

(-)-Matairesinol is a central biosynthetic intermediate to numerous 8-8'-lignans, including the antiviral agent podophyllotoxin in Podophyllum species and its semi-synthetic anticancer derivatives teniposide, etoposide, and Etopophos. It is formed by action of an enantiospecific secoisolariciresinol dehydrogenase, an NAD(H)-dependent oxidoreductase that catalyzes the conversion of (-)-secoisolariciresinol. Matairesinol is also a plant-derived precursor of the cancer-preventative "mammalian" lignan or "phytoestrogen" enterolactone, formed in the gut following ingestion of high fiber dietary foodstuffs, for example. Additionally, secoisolariciresinol dehydrogenase is involved in pathways to important plant defense molecules, such as plicatic acid in the western red cedar (Thuja plicata) heartwood. To understand the molecular and enantiospecific basis of Podophyllum secoisolariciresinol dehydrogenase, crystal structures of the apo-form and binary/ternary complexes were determined at 1.6, 2.8, and 2.0 angstrom resolution, respectively. The enzyme is a homotetramer, consisting of an alpha/beta single domain monomer containing seven parallel beta-strands flanked by eight alpha-helices on both sides. Its overall monomeric structure is similar to that of NAD(H)-dependent short-chain dehydrogenases/reductases, with a conserved Asp47 forming a hydrogen bond with both hydroxyl groups of the adenine ribose of NAD(H), and thus specificity toward NAD(H) instead of NADP(H). The highly conserved catalytic triad (Ser153, Tyr167, and Lys171) is adjacent to both NAD(+) and substrate molecules, where Tyr167 functions as a general base. Following analysis of high resolution structures of the apo-form and two complex forms, the molecular basis for both the enantio-specificity and the reaction mechanism of secoisolariciresinol dehydrogenase is discussed and compared with that of pinoresinol-lariciresinol reductase.

Alcohol Oxidoreductases↗

PubMed2002

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↗

PubMedDate not supplied

Characterization of two epimers, 4alpha and 4beta, of a novel podophyllotoxin-4-O-(D)-6-acetylglucopyranoside from Podophyllum hexandrum by LC-ESI-MS-MS.

High-performance liquid chromatography (HPLC) with diode array detection interfaced to electrospray ionization (ESI) mass spectrometry (MS) is applied to identify the two epimers of a novel and minor constituent, podophyllotoxin-4-O-(D)-6-acetylglucopyraniside from high-altitude Podophyllum hexandrum for the first time. This is done by matching the structural information from the tandem MS data with the reported lignan markers. The results show that LC-MS-MS is the method of choice for fast detection and detailed chemical analysis of mixtures in the crude extracts of Podophyllum. The method can be employed in the absence of reference standards for the markers and is particularly useful in view of the scarcity of these rare chemical standards.

Chromatography, Liquid↗

PubMed1995

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↗

PubMed2006

Podophyllum hexandrum Offers Radioprotection by Modulating Free Radical Flux: Role of Aryl-Tetralin Lignans.

We have evaluated the effect of variation in aryl-tetralin lignans on the radioprotective properties of Podophyllum hexandrum. Two fractionated fractions of P. hexandrum [methanolic (S1) and chloroform fractions (S2)], with varying aryl-tetralin lignan content were utilized for the present study. The peroxyl ion scavenging potentials of S1 and S2 were found to be comparable [i.e. 45.88% (S1) and 41% (S2)] after a 48 h interval in a time-dependent study, whereas in a 2 h study, S2 exhibited significant (P < 0.05) antioxidant activity in different metal ion + flux states. In the aqueous phase, S2 exhibited non-site-specific reactive oxygen species scavenging activity, i.e. 73.12% inhibition at 500 mug ml(-1). S1 exhibited 58.40 +/- 0.8% inhibition (at 0.025 mug ml(-1)) of the formation of reactive nitrite radicals, comparable to S2 (52.45 +/- 0.825%), and also showed 45.01% site-specific activity (1000 mug ml(-1)), along with significant (P < 0.05) electron donation potential (50-2000 mug ml(-1)) compared to S2. Such activities of S1 could be attributed to the significantly (P < 0.05) higher levels of podophyllotoxin beta-d-glucopyranoside (16.5 times) and demethyl podophyllotoxin glucoside (2.9 times) compared with S2. Together, these findings clearly prove that aryl-tetralin lignan content influences the radiation protective potential of the Podophyllum fractions to a great extent.

Journal Article↗

PubMedDate not supplied

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↗

PubMed1980

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↗

PubMed1982

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↗

PubMed2004

[Repellent effect of volatile oil from whitefly (Syngonium podophyllum) on aphids and its chemical constituents].

The interference effect of volatile oil from whitefly (Syngonium podophyllum) on aptera aphid, guard aphid (Aphis gossypii), mustard aphid (Lipaphis erysimi) and red peach aphid (Myzus persicae) was studied by using four arms olfraetometes. The results showed that the volatile oil had distinct repelling effect. The staying periods of test aphids in test areas were obviously shorter than in control areas, and the selecting frequencies were less than the control, too. The volatile oil did not show repelling effect on red peach aphid at the test concentrations. The components of the volatile oil from S. podophyllum were analysed by GC-MS. 43 constituents were identified.

Animals↗