Podophyllum Hexandrum Research Articles

Medicinal importance of Papra (Podophyllum hexandrum Royle) in Unani System of Medicine.

Podophyllum hexandrum Royle [=Sinopodophyllum hexandrum (Royle) T.S. Ying] is an important, endemic medicinal plant species of Himalaya. It is used in Unani System of Medicine under the name of 'Papra'. The drug was not mentioned in previous literatures, but the first time it introduced in Unani Medicine by a great scholar Hakim Najmul Ghani. He has mentioned its uses and benefits in his classical book Khazainul Advia. In Unani Medicine the plant species has been used to treat various ailments like constipation, fever, jaundice, liver disorders, syphilis, diseases of lymph glands etc. In Kashmir Himalaya it is used to treat various diseases by local medicinemen, but now it is listed in rare drugs. Various pharmacological studies have been done such as antioxidant, antimicrobial, anti-inflammatory, antifungal, radio-protective etc., recently it has also been reported that podophyllotoxin or podophyllin can be used to treat some forms of cancers also.

Effect of UV-B radiation on growth, flavonoid and podophyllotoxin accumulation, and related gene expression in Sinopodophyllum hexandrum.

Sinopodophyllum hexandrum is an alpine medicinal plant that produces the anticancer compound podophyllotoxin (PPT). Although a positive relationship between PPT content and altitude has been proved and low temperature enhances plant growth and PPT accumulation has also been revealed, the role of UV radiation in regulating growth and PPT accumulation is still unclear In this study, morphophysiological traits, metabolites content and related genes expression were investigated by exposing S. hexandrum seedlings to treatment with UV-B radiation. The results showed that the contents of soluble sugars and flavonoids, and the expression levels of genes involved in glycometabolism (XET and β-1,3-glucanase) and flavonoid biosynthesis (PAL,C4H,4CL,CHS1 and DTX41) were enhanced in response to UV-B compared to CK. Moreover, genes involved in stress tolerance (MYB, WRKY,APX3 and EX2) were also upregulated in response to UV-B radiation. Although the whole plant biomass exhibited slightly increased values that depended largely on root development, the contents of chlorophyll and PPT and the expression levels of genes involved in photosynthesis (matK, ndhF,rbcL and ycf5) and PPT biosynthesis (C3H,CCoAMT,CCR,CAD, DPO, PLR,SDH, CPY719A23,OMT3,CYP71CU1,OMT1and 2-ODD) were significantly decreased in response to UV-B compared to CK. It can be concluded that UV-B radiation promotes soluble sugars and flavonoids accumulation, but inhibits PPT biosynthesis in S. hexandrum.

Effect of seed priming on seed vigour in Podophyllum hexandrum Royle: An important medicinal herb of temperate Himalayan region

The present investigation was conducted with an objective to study the effect of seed priming on seed vigour in Podophyllum hexandrum Royle. The seeds of Podophyllum hexandrum were subjected to seventeen priming treatments and stored thereafter, for 0, 1and 2 months. Radicle length was found maximum (4.02 cm) in T8 i.e. GA3 100 ppm for 48 hours as compared to the control. Plumule length was maximum i.e. 4.11 cm which was found in T8 i.e. GA3 100 ppm for 48 hours as compared to the control. Untreated (control) seeds showed 19.88 mg seedling dry weight. Whereas it was maximum i.e. 32.58 mg found in T8 i.e. GA3 100 ppm for 48 hours as compared to the control, which was followed by T9 i.e. GA3 100 ppm for 72 hours. Untreated (control) seeds showed seedling vigour index I (SV-I) as 169.0, whereas it was maximum (340.79) found in T3 i.e. hydropriming for 48 hours as compared to the control and closely followed by T16 i.e. brassinolide 1.0 ppm 48 hours. Untreated (control) seeds registered 6.68 seedling vigour index II (SV-II). Maximum seedling vigour index II (13.97) was found in T16 i.e. brassinolide 1.0 ppm for 48 hours as compared to the control and followed by T3 i.e. hydropriming for 48 hours. Henceforth, it is concluded that above seed treatments can pave the way for improving vigour of P. hexandrum which otherwise shows late, low, and asynchronized germination.

Effect of seed priming on germination characteristics of seeds of Podophyllum hexandrum Royle: An endangered medicinal plant of western Himalaya

The present investigation was conducted to induce early, high and synchronized seed germination through priming in Podophyllum hexandrum Royle. The seeds of Podophyllum hexandrum were subjected to seventeen priming treatments and stored thereafter, for 0, 1and 2 months. The minimum number of days taken for onset of germination (19.67 days) was observed in seeds primed with GA3 100 ppm for 48 hours followed by 2 months storage as compared to the control (26.33 days). Maximum germination percentage (68.38%) was observed with hydroprimng for 72 hrs + 2 months storage, which was closely followed by brassinolide 1.0 ppm for 48 hours + 2 months storage (60.89%), brassinolide 0.5 ppm for 72 hours + 2 months storage (60.78%), brassinolide 1.0 ppm for 48 hours + 2 months storage (56.67%), brassinolide 0.5 ppm for 72 hours + 2 months storage (52.22%), hydropriming for 24 hours + 2 months storage (47.56%), KNO3 1% for 48 hours + 2 months storage (43.07%), GA3 100 ppm for 48 hours + 2 months storage (40.41%) and KNO3 1% for 72 hours + 1 month storage (40%) respectively as compared to the control i.e. 32.48, 32.29 and 35.89% for 0, 1 and 2 months storage respectively. Henceforth, it is concluded that the above seed treatments can pave the way for improving germination of P. hexandrum which otherwise shows late, low, and asynchronized germination.

Studies of extraction efficiency and comparison of different extraction methods for determination of Podophyllotoxin in the rootstock of Podophyllum hexandrum Royle

Studies of extraction efficiency and comparison of different extraction methods for determination of Podophyllotoxin in the rootstock of Podophyllum hexandrum Royle

Traditional therapeutic uses of some important medicinal and aromatic plants of the tribal area of Lahaul valley of Himachal Pradesh, India

Lahaul valley of Himachal Pradesh is inhabited by the tribal communities who believe in Amchi system of medicine which is being practiced in this region from a long time. The Amchi system of medicine is similar to the Ayurvedic medicine as this system involves the use of plants as the main source of drug or treatment strategy. Considering the importance of this system of medicine, an extensive field work was conducted in 8 different villages of Lahaul valley to explore the information on usage of ethnomedicinal plants by tribal communities and traditional healers. Questionnaire based interviews of 150 informants were conducted. The data generated were analysed using quantitative tools, i.e., use-value (UV), factor informant consensus (F ic ) and fidelity level (Fl). Information related to 64 plants was collected which possess effectiveness against 35 ailment categories. The maximum number of medicinal plants were recorded from the family Compositae followed by Lamiaceae, Apiaceae and Rosaceae. On the basis of use value, the most important medicinal plants were Arnebia euchroma , Artemisia maritima , Asparagus filicinus , Picrorhiza kurrooa , Podophyllum hexandrum , Taraxacum officinale and Thymus linearis. On the basis of factor informant consensus, important ailment categories of this region were related to respiratory and gastrointestinal disorders. This research involves the documentation of medicinal and aromatic plants used by tribal communities and traditional healers of the Lahaul valley. However, further phytochemical and pharmacological research is required for scientific validation of this information so as to determine the efficacy and safety of these ethnomedicinal plants for curing various ailments.

Ecological characterization of Morel (Morchella spp.) habitats: A multivariate comparison from three forest types of district Swat, Pakistan

Morchella spp. are wild edible mushrooms growing ephemerally under particular environmental conditions in temperate regions of the world. The present study was aimed to outline some principal eco-edaphic characteristics influencing distribution of these mushrooms from three different forest types of Swat, Pakistan. A randomized circular plots were laid down along the transect line in 14 stands in study areas. Environmental variables were recorded and soil characteristics were determined, analyzed and compared. Five species were collected from N to NW slope at elevation range of 1100-2695m asl. Mean relative humidity of 58.7%, range of air temperature 13 °C-27 °C and soil temperature 6-26 °C were recorded at morel growing sites. A higher canopy cover (average 57%) favours sporocarp formation in morels. Soil analysis showed that morel preferably appeared in sandy loam to loamy textured soil at slightly acidic to neutral pH (mean=6.4) and with consistently higher organic matter (1.5%) and salt activities (mean = 38.8 μS) in the soil. IVI calculation showed that Pinus wallichiana A. B. Jackson, Juglans regia L., Abies pindrow Royle, Cedrus deodara (Roxb. ex D. Don) G. Don were dominant trees and Viburnum grandiflorum Wall. ex DC, Hedra nepalensis K. Koch, Hert and Sarcococca saligna (D. Don) Muell. Arg. were shrub species associated with morels. Whilst Fragaria nubicola (Hook.f.) Lindl., Viola canescens Wall ex Roxb. and Podophyllum hexandrum Roylae were the predominant herbs in morel habitat. This study will help to understand the natural habitat and to provide a base line information for the future conservation and management planning in the area.

<p><strong>Role of polyamines on <em>in vitro </em>regeneration and podophyllotoxin production in <em>Podophyllum hexandrum</em> Royle</strong></p>

Podophyllum hexandrum is a popular medicinal plant endemic to Himalayas. In the present investigation, we report an efficient mass propagation protocol and Podophyllotoxin (PTOX) production in in vitro-derived plants of P. hexandrum, cultured on MS medium containing various plant growth regulators and polyamines. A combination of BA (1.5 mg/L), IAA (0.2 mg/L) and spermidine (20 mg/L) produced the highest number of multiple shoots per explant (23 shoots) after 6 weeks of culture; the regenerated shoots were elongated on the same medium. The elongated-shoots were rooted on root induction medium (half strength MS medium) supplemented with IBA (1.5 mg/L) and putrescine (15 mg/L). The rooted plantlets were successfully hardened and acclimatized with a survival rate of 68% in the greenhouse. The highest content of PTOX (4.23 mg/g DW) was recorded in in vitro derived roots followed by leaves when compared to field-grown parent plants. The present system offers the possibility to use in vitro culture techniques for mass propagation and PTOX production for commercial utilization.

Assembly of Plant Enzymes in E. coli for the Production of the Valuable (-)-Podophyllotoxin Precursor (-)-Pluviatolide.

Lignans are plant secondary metabolites with a wide range of reported health-promoting bioactivities. Traditional routes toward these natural products involve, among others, the extraction from plant sources and chemical synthesis. However, the availability of the sources and the complex chemical structures of lignans often limit the feasibility of these approaches. In this work, we introduce a newly assembled biosynthetic route in E. coli for the efficient conversion of the common higher-lignan precursor (+)-pinoresinol to the noncommercially available (-)-pluviatolide via three intermediates. (-)-Pluviatolide is considered a crossroad compound in lignan biosynthesis, because the methylenedioxy bridge in its structure, resulting from the oxidation of (-)-matairesinol, channels the biosynthetic pathway toward the microtubule depolymerizer (-)-podophyllotoxin. This oxidation reaction is catalyzed with high regio- and enantioselectivity by a cytochrome P450 monooxygenase from Sinopodophyllum hexandrum (CYP719A23), which was expressed and optimized regarding redox partners in E. coli. Pinoresinol-lariciresinol reductase from Forsythia intermedia (FiPLR), secoisolariciresinol dehydrogenase from Podophyllum pleianthum (PpSDH), and CYP719A23 were coexpressed together with a suitable NADPH-dependent reductase to ensure P450 activity, allowing for four sequential biotransformations without intermediate isolation. By using an E. coli strain coexpressing the enzymes originating from four plants, (+)-pinoresinol was efficiently converted, allowing the isolation of enantiopure (-)-pluviatolide at a concentration of 137 mg/L (ee ≥99% with 76% isolated yield).

Phenological change modelling for selected Himalayan medicinal herbs using herbarium records: A case study

Regarding the effects of warming on phenology, essentially that climate warming is advancing vegetation phenology around the globe, and case studies of specific species/regions work to gauge this impact. Thus, we attempted to demonstrate phenological patterns of selected 4 alpine/sub-alpine and 4 temperate medicinal herbs based on higher medicinal value of Indian Himalayan Region (IHR) using total 654 herbarium records and applied Generalized Additive Model (GAM) as non-normal and non-linear application. The GAM demonstrated an advancement in the flowering time for alpine/sub-alpine species (Arnebia benthamii, Meconopsis aculeata, Podophyllum hexandrum) and temperate species (Delphinium denudatum and Dioscorea deltoidea), while delayed flowering for Swertia cordata (p < 0.001). Combining the herbarium records, the model significantly projected advancement in flowering time (21–25 days) over the last 100 years only for alpine/sub-alpine species (p < 0.0001). However, the relationship between flowering time and warming winter temperature was predicted advancement in flowering time for alpine/sub-alpine species (6–10 days per 1 °C) and temperate species (8–11 days per 1 °C). The results reveal that long-term herbarium records may be considered as a useful tool for predicting the possible impact of climate change on plant phenology in the IHR using GAM approach.

Four New Prenylated Flavonoids from the Fruits of Sinopodophyllum hexandrum

Four new prenylated flavonoids, sinoflavonoids NF–NI (1–4), were isolated from the fruits of Sinopodophyllum hexandrum by different chromatographic methods such as silica gel, Sephadex LH-20, ODS, and preparative high-performance liquid chromatography (HPLC). Their structures were elucidated on the basis of extensive spectroscopic data (UV, IR, HR-ESI-MS, 1H NMR, 13C NMR, HSQC, HMBC).

Present Status Of Medicinal and Aromatic Plants of Jammu, Kashmir and Ladakh region of Himalayas

The conservation and cultivation of medicinal and aromatic plants (MAP) are getting more importance. MAPs in India are being collected/cultivated in diverse climatic conditions starting from seacoast to high Himalayas in varied soil conditions. Among them temperate, alpine and cold arid regions of country have vital importance for MAPS. The Northern region Himalayas viz. Jammu, Kashmir and Ladakh which represents temperate, alpine and cold arid region zone finds first place in medicinal and aromatic plants conservation/cultivation. It has more than 300 MAP and out of them around 16 very important and prioritized medicinal plants viz., Aconitum heterophyllum, Artemesia absinthium, Picrorhiza kurroa, Swertia chirayita, Saussurea costus, Withania somnifera, Acorus calamus, Atropa acuminata, Berberis aristata, Cathranthus roseus, Dioscorea deltoidea, Taxus wallichiana. Podophyllum hexandrum, Hippophae rhamnoides, Dactylorhiza hatagirea and Arnebia benthamii and aromatic plants viz. Levandula officinalis, Rosmarinus officinalis, Organium vulgare . Thymus serpyllum are exclusive aromatic crops of temperate region with potential to be commercialized. Most of these plants are extracted from wild and have very high demand.

A highly sensitive and selective molecularly imprinted electrochemical sensor modified with TiO2-reduced graphene oxide nanocomposite for determination of podophyllotoxin in real samples

To obtain an electrochemical sensor with high sensitivity and good selectivity for determination of podophyllotoxin (PPT), a kind of graphene composite ([email protected]2) with multi-layer structure and excellent conductivity was prepared by hydrothermal treatment of reduced graphene oxide (rGO) and TiO2 nanoparticles. The composite was characterized by transmission electron microscope (TEM), scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), and a sensor using [email protected]2 as a signal amplification element was fabricated by in-situ polymerization of PPT imprinted membrane (PPT-MIM) on the [email protected]2 modified glassy carbon electrode (PPT-MIM/[email protected]2/GCE). The structure and electrochemical performance of PPT-MIM/[email protected]2/GCE as well as the mechanism with superior conductivity of [email protected]2 exceeding the ones of the mixture of TiO2 and rGO (TiO2-rGO) or the pure TiO2 and rGO were explained with different technologies. Under the optimal conditions, the present sensor showed a linear response for the determination of PPT by differential pulse voltammetry (DPV) in the range of 1.0 × 10−9 − 1.0 × 10−7 mol L−1 (R2 = 0.9980) and 1.0 × 10−7 − 3.0 × 10−4 mol L−1 (R2 = 0.9991) with the limit of quantification is 1.0 × 10−9 mol L−1 and the limit of detection of 3.0 × 10−10 mol L−1. The sensor not only possesses high sensitivity and good selectivity, but also exhibits excellent repeatability and stability. It has been used to detect PPT in real samples (including Podophyllum hexandrum, human urine and human whole blood) with satisfied recoveries of 92.0%–102.3%.

Picropodophyllotoxin, an Epimer of Podophyllotoxin, Causes Apoptosis of Human Esophageal Squamous Cell Carcinoma Cells Through ROS-Mediated JNK/P38 MAPK Pathways.

Esophageal squamous cell carcinoma (ESCC), a major histologic type of esophageal cancer, is one of the frequent causes of cancer-related death worldwide. Picropodophyllotoxin (PPT) is the main component of Podophyllum hexandrum root with antitumor activity via apoptosis-mediated mechanisms in several cancer cells. However, the underlying mechanism of the PPT effects in apoptosis induction in cancer remains ambiguous. Hence, in this study, we evaluate the anti-cancer effects of PPT in apoptotic signaling pathway-related mechanisms in ESCC cells. First, to verify the effect of PPT on ESCC cell viability, we employed an MTT assay. PPT inhibited the viability of ESCC cells in time- and dose-dependent manners. PPT induced G2/M phase cell cycle arrest and annexin V-stained cell apoptosis through the activation of the c-Jun N-terminal kinase (JNK)/p38 pathways. Furthermore, the treatment of KYSE 30 and KYSE 450 ESCC cells with PPT induced apoptosis involving the regulation of endoplasmic reticulum stress- and apoptosis-related proteins by reactive oxygen species (ROS) generation, the loss of mitochondrial membrane potential, and multi-caspase activation. In conclusion, our results indicate that the apoptotic effect of PPT on ESCC cells has the potential to become a new anti-cancer drug by increasing ROS levels and inducing the JNK/p38 signaling pathways.

Non-food renewable and bioactive forest products for pest management: Valuation of agricultural properties of podophyllotoxin analogs derived from Podophyllum hexandrum as botanical pesticides

Due to appearance of pests resistance and negative effects on ecological environment, it is high desirable to explore candidate pesticides from non-food bioactive products. Here a series of succinic acid derivatives of podophyllotoxin derived from the renewable Sinopodophyllum hexandrum, were semisynthesized for pest management. The spatial configurations of three derivatives were determined by X-ray crystallography. Compounds IIIc and IIId (> 2-fold of podophyllotoxin) exhibited the most pronounced insecticidal activity. Compounds 5, IIIa and IIIb displayed > 11-fold promising acaricidal activity of podophyllotoxin. Especially compound IIIb showed the pronounced insecticidal and acaricidal activities. It will pave the way for further structural modifications and application of podophyllotoxins as potentially renewable botanical pesticidal agents in crop protection.

Podophyllotoxin profiles combined with SRAP molecular markers in Juniperus rigida: A promising alternative source of podophyllotoxin

Podophyllotoxin (PPT) exhibits the various bioactive activities in the traditional treatment of many diseases. As the important ethnomedicine resources of China, PPT produced by Juniperus rigida could become a promising alternative sources of Podophyllum hexandrum, which is endangered by overcollection. However, it is unclear whether the genetic diversity of J. rigida is associated with its PPT contents for the different regions. To search the characteristic of J. rigida with high PPT contents and genetic diversities, the superior genotypes of J. rigida were researched by combing PPT profiles with SRAP molecular markers. The results showed that the higher contents of PPT of J. rigida were found in YJ (Shaanxi, 189.18 mg/g) and XDC (Hebei, 184.81 mg/g) and the lower in JHX (Jilin, 71.90 mg/g), CBS (Jilin, 94.92 mg/g) and LYM (Liaoning, 71.11 mg/g). The higher genetic diversity was found in two varieties of J. rigida (i.e., CBS (Jilin) and LYM (Liaoning)). To explore the relationship between the PPT profiles and genetic diversity, J. rigida from ten regions were divided into the same two groups distinguished by PPT contents and SRAP molecular marker, which were PPT contents in the Loess Plateau of China higher than that in the northeast of China. Specially, the contents of PPT exhibited an extremely significant positive correlation with geographic distance/genetic distance. These findings would not only provide a scientific basis for the selecting powerful source of high PPT genotypes of J. rigida in breeding research, but also made J. rigida a promising alternative source of PPT for the pharmaceutical industry.

Temperature-regulated anatomical and gene-expression changes in Sinopodophyllum hexandrum seedlings

Sinopodophyllum hexandrum is a high-altitude perennial medicinal plant that produces the economically-valued anticancer metabolite, podophyllotoxin (PPT). While gene profiling under elevated altitude and low temperature conditions have identified transcriptions associated with increased PPT accumulation, changes in cell structure, with adaptive low-temperature conditions have yet to be identified. In this study, anatomical features including leaf micro- and ultra-structure were investigated by monitoring traits when S. hexandrum seedlings were grown under a cooler temperature (15 °C). Differences in leaf micro- and ultra-structure parameters including stomatal density and shape, chloroplast density as well as the abundance of starch grain, osmiophilic granule and thylakoid grana were observed with the lower temperature. Greater chlorophyll content and higher tissue amounts (e.g. leaf area, number of petioles and root size) were also observed at the cooler temperature. These anatomical and morphological changes were associated with elevated PPT levels on a dry weight and per plant basis, as well increased whole plant fresh and dry weights. To link anatomical and morphological changes with elevated PPT levels, mRNA transcripts encoding for photosynthesis, glyco-metabolism, stress response and PPT biosynthesis select genes were monitored and found to be differentially regulated at 15 versus 22 °C. These cool-temperature anatomical/morphological changes are consistent with S. hexandrum’s capacity to biosynthesize and accumulate elevated PPT in cooler environments.

Genetic diversity and structure of Sinopodophyllum hexandrum populations in the Tibetan region of Qinghai-Tibet plateau, China

Genetic diversity and structure of Sinopodophyllum hexandrum populations in the Tibetan region of Qinghai-Tibet plateau, China

Anti-obesity efficacy of the selected high altitude Himalayan herbs: in vitro studies.

Obesity is a serious health problem for all age groups and it also promotes Type 2 diabetes, cardiovascular diseases, cancer and hypertension. Herbs are used for the weight reduction from ancient times, therefore, 12 herbs viz. Betula utilis, Bunium periscum, Angelica glauce, Saussurea lappa, Podophyllum hexandrum, Bergenia ciliate, Rumex acetosa, Aconitum heterophyllum, Centella asiatica, Andrographis paniculata, Dactylorhiza hatagirea and Bauhina variegate were selected as per literature. Rumex acetosa roots showed the highest extraction rate (39.5%), while C. asiatica leaf showed lowest extraction rate (1.25%) as compared to other herbs. As well, S. lappa leaf extract (396.52mg GAE/g), R. acetosa root extract (181.5mg QE/g), and B. ciliate leaf extract (79.19%) showed significantly higher Total Phenolic Content, Total Flavonoid Content and antioxidant activity, respectively. Furthermore, lipase and amylase inhibition activity and IC50 value of herb extract were higher in S. lappa root extract (75.75%, 75.41% and 62.47, 61.37, respectively). Bauhina variegate leaf extract showed a significantly higher glucose level, percentage of glucose movement (1.446mg/dL and 63.85%) and (0.938mg/dL and 76.55%). Based upon these experiments, 5 herbs were selected and different formulations were prepared and out of these, F3 herb formulation showed higher lipase and amylase inhibition activity (81.75% and 70.66%) and therefore, F3 herbal formulation was selected for treatment of obesity.

Spatial transcriptional dynamics of geographically separated genotypes revealed key regulators of podophyllotoxin biosynthesis in Podophyllum hexandrum

Podophyllum hexandrum is the major source of podophyllotoxin (PTOX), a highly bioactive lignan of great pharmacological importance with anti-cancerous activities. The industrial demand of PTOX relies on the highly endangered natural resources only. It is therefore, desirable to elucidate global molecular processes and identify key genes for enhancing PTOX biosynthesis by overexpressing the targeted candidates. Transcriptome of leaf, rhizome, and stalk was generated to analyse the spatial regulation of PTOX biosynthesis in genetically diverse genotypes. Overall, 198 million high-quality paired-end reads were assembled into 85,531 transcripts. In addition, 32,341 transcripts were assigned gene ontologies with 6570 hits in distinct pathways and 15,886 transcription factors representing 70 families. Interestingly, comparative expression analyses revealed that 12 of 31 genes of PTOX biosynthesis were upregulated in rhizome. However, shikimate and phenylalanine pathways that generate PTOX precursors were abundantly upregulated in leaves. Thus, a further insight on the inducers of these genes can be extended to enrich the aerial tissues for downstream pathway through genetic manipulations. Additionally, higher expression of transcription factors WRKY, MYB, bZIP, bHLH, and AP2, transporters ABCB and ABCC, UGTs, CYP450s, and jasmonate pathway in rhizome supported the secondary metabolism. The comprehensive genomic resource created during this study will provide deeper understanding of lignan biosynthesis and its regulation. This will further enable selection of the elite genotypes and potential genes that can be directed to enhance PTOX production and yield at an industrial scale.