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Aedes aegypti L. (Diptera: Culicidae) is a mosquito species that has adapted to urban environments and is the main vector of dengue viruses. Because of the increasing incidence of dengue, a more environmentally acceptable insecticide needs to be found. Natural products have been and continue to be an important source of leading compounds that can be modified in order to develop new drugs. The lignan family of natural products includes compounds with a diverse spectrum of biological activity. Podophyllotoxin and its related lignans represent an exciting class of natural products that can be targeted at different types of biological activity and are therefore worth exploring further. This study had the aim of evaluating the larvicidal activity of an ethanolic extract from the rhizomes and roots of Podophyllum hexandrum (PM-3) and its isolated lignans, podophyllotoxone (1) and desoxypodophyllotoxin (2), on the larvae of the mosquito vector Ae. aegypti. The PM-3 extract and the compounds (1) and (2) were dissolved in a mixture of acetone and dimethylsulfoxide at final concentrations of 1, 10, 30, 50, 100, and 200 μg/ml. After dilution, the solutions were applied (μg/ml) to the larvae-rearing medium. Overall, the ethanolic extract from the rhizomes and roots of P. hexandrum and the compounds (1) and (2) showed larvicidal activity against the larvae of Ae. aegypti According to the results from this study, it can be concluded that podophyllotoxone (1) and desoxypodophyllotoxin (2) exhibited significant toxicity toward Ae. aegypti larvae., (© The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The composition of lignans extracted fromPodophyllum hexandrumrhizomes was studied by sequential extraction with supercritical CO2,ethyl acetate modified CO2and methanol modified CO2. The results were compared with the extracts obtained by Accelerated Solvent Extraction (ASE) and soxhlet's methods. The lignan contents comprised of Podophyllotoxin, deoxypodophyllotoxin, 4′-demethylpodophyllotoxin, Picropodophyllotoxin, Isopicropodophyllotoxin, Podophllotoxin-β-D-glucopyranoside, and 4′-demethylpodophyllotoxin β-D-glucopyranoside in the extracts ofPodophyllum hexandrumrhizomes obtained by different methods was studied. There was a variation in the concentration of lignan in the extracts obtained by different methods of extraction. Podophyllotoxin formed the major component (36.55%) of the extract obtained by SFE and picropodophyllotoxin, isopicropodophyllotoxin, deoxypodophyllotoxin, and 4′-demethylpodophyllotoxin were present in 6.82, 1.51, 1.46, and 0.85%, respectively, whereas 4′-demethylpodophyllotoxin β-D-glucopyranoside was 1.89% in the extract obtained by ASE, which is higher than SFE extracts. Soxhlet's derived extract contains better concentration of isopicropodophyllotoxin (24.49%) than SFE. A simple, isocratic, and reliable analytical HPLC-UV (DAD) method was developed for simultaneous identification and quantification of different seven lignans in the extracts of different extraction techniques. [ABSTRACT FROM AUTHOR]

Podophyllotoxin, an aryltetralin lignan, is the source of important anticancer drugs etoposide, teniposide, and etopophos. Roots/rhizome of Podophyllum hexandrum form one of the most important sources of podophyllotoxin. In order to understand genes involved in podophyllotoxin biosynthesis, two suppression subtractive hybridization libraries were synthesized, one each from root/rhizome and leaves using high and low podophyllotoxin-producing plants of P. hexandrum. Sequencing of clones identified a total of 1,141 Expressed Sequence Tags (ESTs) resulting in 354 unique ESTs. Several unique ESTs showed sequence similarity to the genes involved in metabolism, stress/defense responses, and signalling pathways. A few ESTs also showed high sequence similarity with genes which were shown to be involved in podophyllotoxin biosynthesis in other plant species such as pinoresinol/lariciresinol reductase. A full length coding sequence of pinoresinol/lariciresinol reductase (PLR) has been cloned from P. hexandrum which was found to encode protein with 311 amino acids and show sequence similarity with PLR from Forsythia intermedia and Linum spp. Spatial and stress-inducible expression pattern of PhPLR and other known genes of podophyllotoxin biosynthesis, secoisolariciresinol dehydrogenase ( PhSDH), and dirigent protein oxidase ( PhDPO) have been studied. All the three genes showed wounding and methyl jasmonate-inducible expression pattern. The present work would form a basis for further studies to understand genomics of podophyllotoxin biosynthesis in P. hexandrum. [ABSTRACT FROM AUTHOR]

Podophyllotoxin, an aryltetralin lignan, is the source of important anticancer drugs etoposide, teniposide, and etopophos. Roots/rhizome of Podophyllum hexandrum form one of the most important sources of podophyllotoxin. In order to understand genes involved in podophyllotoxin biosynthesis, two suppression subtractive hybridization libraries were synthesized, one each from root/rhizome and leaves using high and low podophyllotoxin-producing plants of P. hexandrum. Sequencing of clones identified a total of 1,141 Expressed Sequence Tags (ESTs) resulting in 354 unique ESTs. Several unique ESTs showed sequence similarity to the genes involved in metabolism, stress/defense responses, and signalling pathways. A few ESTs also showed high sequence similarity with genes which were shown to be involved in podophyllotoxin biosynthesis in other plant species such as pinoresinol/lariciresinol reductase. A full length coding sequence of pinoresinol/lariciresinol reductase (PLR) has been cloned from P. hexandrum which was found to encode protein with 311 amino acids and show sequence similarity with PLR from Forsythia intermedia and Linum spp. Spatial and stress-inducible expression pattern of PhPLR and other known genes of podophyllotoxin biosynthesis, secoisolariciresinol dehydrogenase ( PhSDH), and dirigent protein oxidase ( PhDPO) have been studied. All the three genes showed wounding and methyl jasmonate-inducible expression pattern. The present work would form a basis for further studies to understand genomics of podophyllotoxin biosynthesis in P. hexandrum. [ABSTRACT FROM AUTHOR]

A new quantitative method using thin-layer chromatography silica gel 60F254 plates as the stationary phase and the mobile phase consisting of toluene-ethyl acetate-acetic acid (15.0:7.5:0.5, v/v) was employed for simultaneous determination of lignans and flavonoid in Podophyllum hexandrum. Densitometric determination of the constituents was performed at 254 nm in reflectance/absorbance mode. The method was validated for precision, accuracy, specificity, robustness, and recovery. The linear regression analysis data for the calibration plots showed a good linear relationship (r2 = 0.9903-0.9976) in the calibration range of 1-8 µg per band for 4'-Odemethylpodophyllotoxin (1), podophyllotoxin (2), and podophyllotoxone (4), and 2-10 µg per band for kaempferol (3) and deoxypodophyllotoxin (5) with respect to peak area. Limits of detection and quantitation were in the range of 250-617 ng per band and 856-1974 ng per band. The average recovery for 4'-O-demethylpodophyllotoxin, podophyllotoxin, kaempferol, podophyllotoxone, and deoxypodophyllotoxin was 96.38 ± 1.92 to 101.84 ± 1.05%, indicating the excellent reproducibility. Podophyllotoxin was found in highest content (9.92 µg mg-1) and podophyllotoxone in the lowest content (0.94 µg mg-1). The proposed method is rapid, simple, precise, specific, sensitive, accurate, and robust. [ABSTRACT FROM AUTHOR]

Abstract: The current study has concentrated on assessment of the radioprotective potential of REC-2001, a semi-purified fraction of rhizomes of Podophyllum hexandrum, in Swiss albino Strain ‘A’ mice exposed to 10Gy whole-body gamma radiation. Animals were treated with 10 and 15mg/kgbwt (i.p.) of REC-2001 1h prior to exposure to a lethal dose of γ-radiation (10Gy) and observed upto 30 days. For analysis of maximum tolerable dose (MTD), LD50 and acute toxic dose, different concentrations of the extract were administered to animals and their mortality and morbidity status was observed upto 72h and one week, respectively. Dose reduction factor (DRF) was determined by exposing REC-2001 pre-treated mice to supra-lethal doses of γ-radiation. Endogenous spleen colony forming units (CFU), DNA strand breaks in thymocytes (alkaline halo assay) and lipid degradation was studied to understand the mechanism of radioprotection . A single dose of REC-2001 (10 and 15mg/kgbwt i.p.) exhibited >90% survival in the pre-treated irradiated group versus no survival in radiation control group. Single doses of upto 75mg/kgbwt (i.p.) did not cause any mortality (MTD) in mice. REC-2001, a dose of 90mg/kgbwt, resulted in 50% mortality (LD50), while the LD100 was 115mg/kgbwt REC-2001 exhibited a DRF of 1.62. CFU counts in the REC-2001 treated group were found significantly high (5.33/spleen) as compared to controls. Exposure of thymocytes to 10Gy radiation resulted in increased halo diameter (45±3μm) in comparison to untreated controls (8±1μm). REC-2001 administration (500μg/ml) decreased the halo diameter to 15±2μm. Radiation-induced lipid degradation was also inhibited by REC-2001. The present study has revealed that REC-2001 is a promising radioprotective fraction that can be effectively used against lethal doses of γ-radiation after further investigations in higher animal models. [Copyright &y& Elsevier]

Abstract: The aryl tetralin lignans are synthesized by Podophyllum sps. and are in great demand worldwide due to their use in synthesis of topoisomerase inhibitors. However, the sustained production of these aryl tetralin lignans requires large-scale harvesting from the natural environments, which has resulted in the plant-endangered status. In view of the difficulties in their total chemical synthesis, cultivation and failure of metabolic engineering approaches, there is a need to search for alternative sources of production of aryl tetralin lignans. We unequivocally established the methodology for isolation, identification, and characterization of a novel fungal endophyte (Trametes hirsuta) that produces aryl tetralin lignans consistently as shown by HPLC, LC–MS, LC/MS–MS and 1H NMR. The lignans produced by the microorganism are biologically active, and exhibit potent antioxidant, anticancer and radioprotective properties. This strategy promises to improve the production of these therapeutically important compounds at lower costs. [Copyright &y& Elsevier]