Integrative analysis of the metabolome and transcriptome revealed the regulatory mechanisms of lignan synthesis in Polygonatum

doi:10.21203/rs.3.rs-4932279/v1

The genus Polygonatum is an essential resource for traditional Chinese medicine (TCM). To investigate the molecular mechanism of lignan biosynthesis in Polygonatum sibiritumRed and Polygonatum kingianum var. grandifolium, we performed transcriptomic and metabolomic analyses of these two plants. Seventeen lignans were detected a total of 17 lignans. Among them,Cycloolivil-6-O-glucoside,Matairesinol-4,4'-di-O-glucoside,5'-Methoxyisolariciresitnol-9'-O-glucoside,Syringaresinol,Syringaresinol-4'-O-glucoside,Isolariciresinol-9'-O-glucoside, dihydrodehydrodiconiferyl alcohol-4-O-glucoside, Pinoresinol and Eleutheroside E were reported in the genus Polygonatum for the first time. Transcriptome sequencing identified 75 genes related to the lignin biosynthesis pathway belonging to 12 classes of transcription factor families, among which genes from the SET, C2H2, and GARP-G2-like families were dominant in lignin biosynthesis. In addition, a family of transcription factors such as SET, GARP-G2-like, C2H2, Trihelix, SWI/SNF-BAF60b, PHD, FAR1, C3H, AP2/ERF-ERF, and BES1 were found to have essential roles in lignin biosynthesis by combined metabolome and transcriptome analyses. This study lays the foundation for an in-depth understanding of Polygonatum lignan biosynthesis and metabolic mechanisms. This has significant reference value for the future cloning of critical genes for lignans and the selection and breeding of Polygonatumgermplasm resources with high lignan content.

Biological sciences/Biochemistry

Biological sciences/Plant sciences

Polygonatum

Lignans

Transcriptomics

Metabolomics

Transcription factor family

Polygonatum is a perennial herb belonging to the Liliaceae family [1]. Its primary use is the rhizome, which can tonify essence and antioxidants [2], and slow the aging process[3]. Previous studies have shown that Polygonatum is rich in polysaccharides, saponins, flavonoids, steroids, amino acids, and other micronutrients, which improve memory, lower blood sugar and blood lipids, and improve human immunity [4] .

Lignan are widely distributed in the xylem of plants and are formed by polymerization of dimeric phenylpropanoid derivatives. Kitts et al. found that lignan in flaxseeds have antioxidant properties and potential anticancer effects in mammals [5] .

Li-Xia Wang et al. found that some lignans have a particular effect on specific protein targets and have good anti-tumor ability and anti-virus activity, and so far have achieved suitable clinical applications [6]. Although lignan have been reported to possess various pharmacological activities, an in-depth understanding of their mechanisms of action still needs to be provided. Primary research has focused on lignin synthesis [7], structure and activity studies [8], functional activity research, and research on anticancer active substances [9] ; however, there are few reports on the mechanism of lignin synthesis. In existing studies, flaxseed [10] and schisandra [11] plants are not the only ones with high lignan content. Polygonatum is also rich in lignans [4]. Among the lignans reported in Polygonatum are Xanthophyllum neolignanoside A, benzofuran-type lignan,(+)-isolarchonin-9’-O-β-D-glucoside,trans-N-p-coumaroyltyramine, 3-(4-hydroxyphenyl)-N-[2-(4-hydroxyphenyl)-2-methoxyethyl]acrylamide, and 3-(4-hydroxy-3-methoxy (4-hydroxy-3-methoxyphenyl)-N-[2-(4-hydroxyphenyl)-2-methoxyethyl]acrylamide [12]. Therefore, it is of great theoretical and practical value to study the regulatory mechanism of lignin analog synthesis in Polygonatum to guide the breeding of Polygonatum germplasm with a higher lignin content.

Transcription factors are multifunctional proteins that play critical roles in sensing stress signals, responding to the expression of corresponding stress genes, and transducing stress signals [13]. The TF family (family of transcription factors) and TR family (family of transcriptional regulators) play crucial roles. TFs control cell growth, differentiation, and responses to environmental changes by directly or indirectly influencing the transcriptional activity of genes [14]. Members of the TR family regulate various biological processes, including carbon and nitrogen metabolism, by interacting with different small-molecule ligands [15]. Studies have shown that forsythia lignin synthesis is associated with the R2R3-MYB family of transcription factors [16] .

Studies on the biosynthesis of lignans in the rhizomes of different Polygonatum species have been reported. However, there is a need to be more understand the regulatory mechanisms and the family of transcription factors involved in the differential pathways, which significantly limits the ability of the pharmaceutical industry to extract specific lignans from Polygonatum on a large scale. In addition, genetic modification of Polygonatum rhizomes for selecting varieties with high lignin content has good prospects. In this study, we investigated the transcription and metabolic mechanisms during the biosynthesis of lignans in Polygonatum sibiritum Red and Polygonatum kingianum var. grandifolium as research materials. The main objectives of this study are as follows:

1.To determine the differences in lignans between the two

1.To determine the differences in lignans between the two Polygonatum

2.Screening differentially expressed genes and metabolites related to lignin biosynthesis and metabolism.

3.Correlation analyses were performed on the differentially expressed genes and the differentially expressed metabolites related to lignans.

These findings help further reveal the molecular and metabolic mechanisms of lignan biosynthesis and provide valuable information for the future selection and cultivation of fine varieties of high lignan content and related applications in the pharmaceutical industry.

2.1 Plant material

Experimental materials were selected from the rhizomes of Polygonatum sibiritum Red (SXHZ) and Polygonatum kingianum var. grandifolium (HBES). Polygonatum plants were cultivated at the experimental site at the School of Forestry and Horticulture, Hubei Minzu University. Three biological replicates of different Polygonatum rhizomes were collected from each group. Sampled rhizomes were chopped and mixed into sterile centrifuge tubes, snap-frozen in liquid nitrogen, and stored at -80°C until use.

2.2 Metabolite extraction and analysis

The analytical instruments used in this study included an ultra-performance liquid chromatography (UPLC) system and tandem mass spectrometry (MS/MS). The model of the chromatographic system was SHIMADZU Nexera X2, and the column was an Agilent SB-C18 with a particle size of 1.8 µm, an inner diameter of 2.1 mm, and a length of 100 mm. The mobile Phase A consisted of two phases: phase A consisted of ultrapure water with 0.1% formic acid and Phase B consisted of acetonitrile and 0.1% formic acid. The chromatographic conditions were set as follows: an initial B-phase ratio of 5%, followed by a linear increase to 95% over 9 min, held for 1 min, then reduced to 5% over the next 1.1 minutes, and held for 14 min to achieve equilibrium. The flow rate was set to 0.35 ml/min, the column temperature was maintained at 40°C, and the injection volume was four microlitres. The mass spectrometry conditions were as follows: the ion spray voltage was set at -4500 V in ESI mode and 5500 V in ESI + mode; the pressures of the ion source gas I (GSI), gas II (GSII), and curtain gas (CUR) were set at 50, 60, and 25 psi, respectively; the parameters of collision-induced ionization (CII) were optimized to be in high-efficiency mode, and the temperature of the ESI source was maintained at 550°C. The electrospray ionization source (ESI) temperature was maintained at 550°C. Metabolomic analyses were performed by Metware Biotechnology, Ltd. (Wuhan, China).

2.3 RNA extraction and sequencing analysis

Total RNA was extracted from Polygonatum rhizomes using a Plant RNA Kit (product no. R6827-02) obtained from Omega. cDNA libraries were constructed based on the extracted RNA. Based on Sequencing By Synthesis technology, Illumina's high-throughput sequencing platform sequenced the cDNA libraries and obtained high-quality raw data, which were filtered, checked for sequencing error rate, examined the distribution of GC content to obtain clean reads for subsequent analyses, and spliced the clean reads by Trinity as reference sequences for subsequent analyses. Trinity was used to splice the clean reads, and the spliced transcript sequences were used as reference sequences for subsequent analyses.

2.4 Gene expression and differential gene analysis

The basic annotation of genes included protein function, pathway, COG/KOG function, and GO annotations. To achieve detailed annotation of single genes, we used the BLASTx algorithm, set the E-value threshold to 1e-5, and performed sequence comparisons with NCBI's non-redundant protein database (Nr), Swiss-Prot, KEGG, and COG/KOG databases. Based on the comparison results, we were able to provide functional annotations for the proteins. Furthermore, we used the BLASTp program to compare the coding sequences of plant proteins of single genes with the Plant Transcription Factor Database (TFdb) to predict the possible transcription factor family members. Using DESeq2 software, we performed differential gene expression analyses under two biological conditions. We set the false discovery rate (FDR) to less than 0.05, and required a fold change of 2 or more as a criterion to identify differentially expressed genes.

2.5. Transcriptome and metabolome association analysis

To identify critical genes that are closely related to lignan analog synthesis, we performed an in-depth analysis of differentially expressed genes in HBES and SXHZ samples in combination with the differential accumulation of lignan analogs. By calculating the Pearson correlation coefficients between the differential metabolites and these differentially expressed genes, we were able to reveal potential links between them. In addition, we constructed co-expression networks using the Cytoscape software (version 3.9.1) to visualize gene interactions and regulatory relationships. This network analysis helps us understand the complexity of gene regulation during lignan synthesis.

3.1 Metabolomic analyses of rhizome-related constituents of Polygonatum sibiritum Red and Polygonatum kingianum var. grandifolium

We identified 20 lignans by qualitatively and quantitatively testing metabolites in the rhizomes of Polygonatum. Principal component analysis (PCA) showed significant differences in total metabolites between the HBES and SXHZ sample groups. In contrast, the differences between samples within the groups were minor (Fig. 1A). In this study, orthogonal partial least squares discriminant analysis (OPLS-DA) was used for model testing and differential metabolite screening (Fig. 1B). Therefore, the results of this study were reliable.

The metabolomic data showed that the nine lignans were differentially expressed metabolites (Fig. 2A). Analysis of the top 20 differentially expressed metabolites with the highest multiplicity of differences during rhizome development of Polygonatum revealed that two lignans ranked among the top 20 metabolites, Cycloolivil-6-O-glucoside and Matairesinol-4,4'-di-O-glucoside, respectively ( Fig. 2B).

To gain a deeper understanding of the variation of lignan-like metabolites in Rhizoma Polygonatum, we investigated the differentially expressed metabolites involved in lignan biosynthesis and metabolism and identified nine differential metabolites. Only one of these differential metabolites (pinoresinol) was enriched in three metabolic pathways (ko00998,ko01100, and ko01110), as shown in Table 1 and Fig. 3.

3.2. Analysis of lignin differential genes

This study continued to mine 2,613 enzyme genes related to lignin biosynthesis from annotated 92,858 Unigenes. In this study, the annotated pathways ko00998, ko01100, and ko01110 were used to screen 75 single genes that could be categorized as being related to the lignin biosynthesis pathway(Fig. 4). These genes were grouped into 12 categories, as detailed in Table 1.

Table 1

Major lignin synthase genes in SXHZ vs HBES
TF-Family	number	kegg
SET	21	K11422 K11426 K11420 K11430 K23700 K11433
GARP-G2-like	18	K00975 K00008 K00915
Trihelix	5	K00641 K01051
PHD	2	K00031 K11422
C3H	2	K13832 K00963
WRKY	1	K03847
SWI/SNF-BAF60b	2	K01062
MYB-related	5	K22845
FAR1	3	K14760
C2H2	13	K12309
BES1	1	K01177
AP2/ERF-ERF	2	K00411

3.3. Transcription + metabolism correlation analysis of the lignin biosynthetic pathway

In this study, we identified 75 differentially expressed genes related to lignin synthesis and screened nine differential metabolites from the transcriptome data. These differential genes and differential metabolites were mainly involved in the Biosynthesis of various secondary metabolites - part 2 (ko009998) pathway, the Metabolic pathways (ko01100) pathway, and the Biosynthesis of secondary metabolites (ko01110) pathway, and the results of the relevant analyses are shown below.(Fig. 5,Fig. 6,Fig. 7).

Lignans are critical secondary metabolites of plants and play an important role in insect resistance and stress growth. Meanwhile, lignans also have important pharmacological activities such as anti-tumor, anti-HIV, anti-inflammatory, hepatoprotective, and antioxidant activities [17]. The regulation of lignans involves a variety of enzymes and metabolic pathways, among which pinosyl alcohol plays a crucial role in lignan biosynthesis. In this study, we combined metabolomic and transcriptomic analyses to investigate the synthesis mechanism of lignans in Polygonatum, which deepened our understanding of its regulatory network, the accumulation of lignans during Polygonatum development, and the molecular mechanisms behind it and laid a valuable reference base for future related research work.

In the current study, it has been found that the TF family may affect lignin synthesis [18]. Tryptophan, phenylalanine, and tyrosine are three crucial aromatic amino acids that are used in plants not only for protein synthesis but also as metabolites in other biosynthetic pathways [19]. In the present study, these three substances were up-regulated in the lignin synthesis pathway. However, these amino acids are not directly involved in lignin biosynthesis per se, suggesting that they may indirectly affect lignin synthesis by regulating plant metabolic homeostasis.

Metabolomics data analysis showed that 17 lignans were detected from HBES and SXHZ rhizomes, of which nine were differential metabolites, with Cycloolivil-6-O-glucoside being unique to SXHZ and Eleutheroside E being unique to HBES. According to relevant studies, Cycloartol-6-O-glucoside is commonly associated with plant growth and development and defense mechanisms, and it may be involved in the regulation of plant responses to environmental stresses [20] ; this also indirectly suggests that the stress tolerance of Polygonatum sibiritum Red may be higher than that of Polygonatum kingianum var. grandifolium. Eleutheroside E reduces oxidative stress and NF-κB activation and reprogrammes the metabolic response to hypoxia-reperfusion injury, suggesting anti-inflammatory and cellular protection against oxidative stress damage [21]. It also significantly improves the inflammatory response induced by SBA [22] ., Our result provides a theoretical basis for the possibility of anti-inflammatory effects of Polygonatum. Compared with HBES, Cycloolivil-6-O-glucoside showed the highest multiplicative difference of 2,180.82-fold in SXHZ rhizomes, followed by Matairesinol-4,4'-di-O-glucoside at 43.94-fold.

he regulation of lignin is a complex process involving multiple enzymes and metabolic pathways. Pinoresinol plays a central role in this, while hormone signaling, aromatic amino acid metabolism, and cellular metabolic status may indirectly affect lignin synthesis [23]. In the present study, it was found that several lignan analogs in Polygonatum kingianum var. grandifolium, including Matairesinol-4,4'-di-O-glucoside,5'-Methoxyisolariciresinol-9'-O-glucoside, Syringaresinol, Syringaresinol-4'-O-glucoside, Isolariciresinol-9'-O-glucoside, and dihydrodehydrodiconiferyl alcohol-4-O-glucoside have all been implicated in the synthesis of pinosyl alcohol. Related studies suggest that matairesinol-4,4'-di-O-glucoside may have immunomodulatory [24], inhibition of protein kinase activity [25], anti-angiogenic [26], and other multiple biological activities. 5'-Methoxyisolariciresinol-9'-O-glucoside has significant biological activities, including anti-inflammatory and antioxidant effects, and in plants, it may protect against UV damage and participate in plant defense responses. Yringaresinol and Syringaresinol-4'-O-glucoside are known to have anti-inflammatory and anticancer activities. In plants, they may contribute to plant resilience and survival, especially in the face of adversity such as a pathogen attack [27]. Isolariciresinol-9'-O-glucoside and dihydrodehydrodiconiferyl alcohol-4-O-glucoside have anti-inflammatory and antioxidant properties, and in plants, it may help them resist environmental stresses such as temperature changes and drought conditions [28] .

By analyzing the data, this study found that lignans in the Polygonatum mainly function as pathogen resistance and antitoxicity. This study explored the regulatory mechanism of lignans synthesis in the Polygonatum, which not only filled the research gap in this field but also identified the effects of several critical gene families and enzyme genes on lignans synthesis, and these findings are of great significance as a guide for molecular breeding. In addition, these findings highlight the importance of lignin analogs in Polygonatum and provide theoretical support for the improvement of stress tolerance and pest resistance in Polygonatum.

Metabolic pathways (ko01100) pathway as well as Biosynthesis of secondary metabolites (ko01110), the gene families C2H2, GARP-G2-like, and SET were found to play essential roles in the regulation of lignan synthesis in the Polygonatum. The genes in these gene families have positive and negative effects on the synthesis of pinacol, affecting lignin synthesis. This finding also supports the idea in the current study that the regulation of lignin synthesis may be influenced by cancellol. Lariciresinol, Matairesinol, and Scoisolariciresinol were also found to be involved in the regulation of lignin synthesis.

When analyzing the metabolomic data of Polygonatum, we identified 17 lignans, nine of which differed significantly in their content. In particular, Cycloolivil-6-O-glucoside showed significant differences in the expression of the lignan biosynthetic pathway in the two Polygonatum. In addition, transcription factor families such as WRKY, Trihelix, SWI/SNF-BAF60b, SET, PHD, MYB-related, GARP-G2-like, FAR1, C3H, C2H2, BES1, and AP2/ERF-ERF were highly enriched in the transcriptome data, and these differences were significant. The differentially expressed genes in the lignin biosynthesis pathway were mainly from the GARP-G2-like and SET families, suggesting that the GARP-G2-like and SET family transcription factors may play critical roles in regulating the lignin synthesis pathway in Polygonatum. Meanwhile, changes in enzyme genes or substances of Pimaric alcohol, (+)-Larix pimaric alcohol reductase, (-)-Pimaric alcohol reductase, and (-)-Larix pimaric alcohol reductase may be one of the factors contributing to the differences in the lignin synthesis pathway in the two Polygonatum. These findings provide new insights into understanding the biosynthesis and accumulation of lignan compounds in the rhizomes of Polygonatum. Differential accumulation of different compounds may affect the medicinal value of different varieties of Polygonatum. Therefore, this study suggests further in-depth exploration of Polygonatum lignans' metabolism and regulatory mechanisms, aiming to guide the cultivation of new high-quality Polygonatum varieties with high lignans content. The synthesis of lignans in the Polygonatum is a complex process involving the co-regulation of multiple transcription factors and related enzymes. Through joint transcriptomic and metabolomic analyses, we can gain a deeper understanding of the molecular mechanism of this process, thus providing a theoretical basis for developing and improving the medicinal value of Polygonatum.

Author Contribution

Research Concept and Design: Qiang Xiao , Xiaolin Wan , Shi GuangdiField Data Collection and Laboratory Analysis: Wan Xiaolin, Shi GuangdiManuscript Writing: Shi GuangdiAll authors participated in the review of the manuscript.Corresponding Author: Xiao Qiang

Data Availability

The datasets generated and/or analyzed during the current study are available in the [Meiwei Cloud Platform] repository (the persistent network link is https://cloud.metware.cn/, Account: 1820231395, Password: XjPzk). All data generated or analyzed in this study are included in the published article [Enter the Meiwei Cloud Platform (the website is in Chinese), log in to the account, and then click on the project center project number MWXS-22-1110-b, MWXS-22-1110-b and MWXS-22-1110-c, the three compressed packages inside]. Other KEGG pathways are adopted from the official KEGG website: https://www.genome.jp/kegg/.

Yan, M., Dong, S., Gong, Q., Xu, Q. & Ge, Y. Comparative chloroplast genome analysis of four polygonatum species insights into dna barcoding, evolution, and phylogeny. Sci. Rep. -Uk. 13, 16495. https://doi.org/10.1038/s41598-023-43638-1 (2023).
Wan, K. et al. Transcriptomic analysis reveals the flavonoid biosynthesis pathway involved in rhizome development in polygonatum cyrtonema hua. Plants (Basel). 13. 1524. https://doi.org/10.3390/plants13111524 (2024).
Liu, X., Wan, Z., Shi, L. & Lu, X. Preparation and antiherpetic activities of chemically modified polysaccharides from polygonatum cyrtonema hua. Carbohyd Polym. 83, 737–742. https://doi.org/10.1016/j.carbpol.2010.08.044 (2011).
Yang, M., Chen, R., Zhou, X. & Chen, H. Research progress on pharmacological effects and mechanism of polygonatum sibiricum polysaccharides. Starch - Stärke. https://doi.org/10.1002/star.202300168 (2024).
Kitts, D. D., Yuan, Y. V., Wijewickreme, A. N. & Thompson, L. U. Antioxidant activity of the flaxseed lignan secoisolariciresinol diglycoside and its mammalian lignan metabolites enterodiol and enterolactone. Mol. Cell. Biochem. 202, 91–100. https://doi.org/10.1023/a:1007022329660 (1999).
Wang, L. et al. Review of lignans from 2019 to 2021: newly reported compounds, diverse activities, structure-activity relationships and clinical applications. Phytochemistry (Oxford). 202. 113326. https://doi.org/10.1016/j.phytochem.2022.113326 (2022).
Mori, N. Synthetic studies on optically active furofuran and diarylbutane lignans. Biosci. Biotechnol. Biochem. 82, 1–8. https://doi.org/10.1080/09168451.2017.1407235 (2018).
Marinov, T., Kokanova-Nedialkova, Z. & Nedialkov, P. T. Naturally occurring simple oxygenated benzophenones: structural diversity, distribution, and biological properties. Divers. (Basel). 15, 1030. https://doi.org/10.3390/d15101030 (2023).
Mukhija, M., Joshi, B. C., Bairy, P. S., Bhargava, A. & Sah, A. N. Lignans: a versatile source of anticancer drugs. Beni-Suef Univ. J. Basic. Appl. Sci. 11, 76. https://doi.org/10.1186/s43088-022-00256-6 (2022).
Zhu, D., Han, J., Liu, C., Zhang, J. & Qi, Y. Modeling of flaxseed protein, oil content, linoleic acid, and lignan content prediction based on hyperspectral imaging. Front. Plant. Sci. 15, 1344143. https://doi.org/10.3389/fpls.2024.1344143 (2024).
Piao, J. et al. Magnetic separation coupled with high-performance liquid chromatography–mass spectrometry for rapid separation and determination of lignans in schisandra chinensis. J. Sep. Sci. 41, 2056–2063. https://doi.org/10.1002/jssc.201701098 (2018).
Hui, Y. Z. J. K. A new benzofuran lignan from rhizomes of polygonatum sibiricum. Chin. Herb. Med. 51, 21–25. https://doi.org/10.7501/j.issn.0253-2670.2020.01.004 (2020).
Barnes, P. J. & Adcock, I. M. Transcription factors and asthma. Eur. Respir. J. 12, 221–234. https://doi.org/10.1183/09031936.98.12010221 (1998).
Azofeifa, J. et al. Abstract 1272: enhancer rna cell line database reveals new associations between tf activity and cancer subtype. Cancer Res. (Chicago Ill). 80, 1272. https://doi.org/10.1158/1538-7445.AM2020-1272 (2020).
Sun, W., Zhao, E. & Cui, H. Target enzymes in serine-glycine‐one‐carbon metabolic pathway for cancer therapy. Int. J. Cancer. 152, 2446–2463. https://doi.org/10.1002/ijc.34353 (2023).
S. P, C. D, Y. Z. Screening and identification of དྷ2དྷ3-myb transcription factor དྷelated to lignan synthesis in forsythia suspensa. J. Chin. Med. Mater. 44 1590–1596. (2021). https://doi.org/10.13863/j.issn1001-4454.2021.07.009
Yang, C., Zhi, X. & Xu, H. Advances on semisynthesis, total synthesis, and structure-activity relationships of honokiol and magnolol derivatives. Mini Rev. Med. Chem. 16, 404. https://doi.org/10.2174/1389557516666151120115558 (2016).
Zhang, Z. et al. Integrative analyses of targeted metabolome and transcriptome of isatidis radix autotetraploids highlighted key polyploidization-responsive regulators. BMC Genom. 22, 1–670. https://doi.org/10.1186/s12864-021-07980-w (2021).
Wu, J. et al. The cytosolic aminotransferase vas1 coordinates aromatic amino acid biosynthesis and metabolism. Sci. Adv. 10, k738. https://doi.org/10.1126/sciadv.adk0738 (2024).
Noctor, G. et al. Glutathione: a key modulator of plant defence and metabolism through multiple mechanisms. J. Exp. Bot. 75, 4549–4572. https://doi.org/10.1093/jxb/erae194 (2024).
Wang, S. & Yang, X. Eleutheroside e decreases oxidative stress and nf-κb activation and reprograms the metabolic response against hypoxia-reoxygenation injury in h9c2 cells. Int. Immunopharmacol. 84, 106513. https://doi.org/10.1016/j.intimp.2020.106513 (2020).
Zhao, B. et al. Mitigative effects of eleutheroside e against the mechanical barrier dysfunction induced by soybean agglutinin in ipec-j2 cell line. J. Anim. Physiol. N. 106, 664–670. https://doi.org/10.1111/jpn.13677 (2022).
Chen, Y. et al. Pinoresinol diglucoside (pdg) attenuates cardiac hypertrophy via akt/mtor/nf-κb signaling in pressure overload-induced rats. J. Ethnopharmacol. 272, 113920. https://doi.org/10.1016/j.jep.2021.113920 (2021).
Pierre, F. et al. Pre-clinical characterization of cx-4945, a potent and selective small molecule inhibitor of ck2 for the treatment of cancer. Mol. Cell. Biochem. 356, 37–43. https://doi.org/10.1007/s11010-011-0956-5 (2011).
Yokoyama, T. et al. Characterization of (–)-matairesinol as a potent inhibitor of casein kinase i in vitro. Biol. Pharm. Bull. 26, 371–374. https://doi.org/10.1248/bpb.26.371 (2003).
Lee, B., Kim, K. H., Jung, H. J. & Kwon, H. J. Matairesinol inhibits angiogenesis via suppression of mitochondrial reactive oxygen species. Biochem. Bioph Res. Co. 421, 76–80. https://doi.org/10.1016/j.bbrc.2012.03.114 (2012).
Wang, S. et al. Syringaresinol-4-o-β-d-glucoside alters lipid and glucose metabolism in hepg2 cells and c2c12 myotubes. Acta Pharm. Sinica B. 7, 453–460. https://doi.org/10.1016/j.apsb.2017.04.008 (2017).
Witvrouw, K. et al. M.W. Reassessing the claimed cytokinin-substituting activity of dehydrodiconiferyl alcohol glucoside. Proceedings of the National Academy of Sciences - PNAS 120 e2123301120. (2023). https://doi.org/10.1073/pnas.2123301120

No competing interests reported.

Integrative analysis of the metabolome and transcriptome revealed the regulatory mechanisms of lignan synthesis in Polygonatum

Status:

Version 1

Abstract

Figures

1. Introduction

1.To determine the differences in lignans between the two

2.Screening differentially expressed genes and metabolites related to lignin biosynthesis and metabolism.

2. Materials and methods

2.1 Plant material

2.2 Metabolite extraction and analysis

2.3 RNA extraction and sequencing analysis

2.4 Gene expression and differential gene analysis

2.5. Transcriptome and metabolome association analysis

3 Result

3.1 Metabolomic analyses of rhizome-related constituents of Polygonatum sibiritum Red and Polygonatum kingianum var. grandifolium

3.2. Analysis of lignin differential genes

3.3. Transcription + metabolism correlation analysis of the lignin biosynthetic pathway

4. Discussion

5. Conclusion

Declarations

Author Contribution

Data Availability

References

Additional Declarations

Status:

Version 1