Journal articles: 'Biosynthesis of ginsenosides'

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Jin, Shi Kun, and Shou Jing Zhao. "Progress in Understanding of the Key Enzyme Genes of Ginsenoside Biosynthesis in Panax ginseng." Advanced Materials Research 773 (September 2013): 374–79. http://dx.doi.org/10.4028/www.scientific.net/amr.773.374.

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Ginsenosides, the major bioactive ingredients of P. ginseng can improve the anti-disease abilities of human being, and generate significant social and economic benefits. However, along with gradually or rapidly or dramatically increasing demand of the ginsenosides, extensive studies have focused on regulating the ginsenoside biosynthetic pathway on a genetic level. In this article, ginsenoside biosynthesis of key enzyme genes are described, including squalene synthase (SS), squalene epoxidase (SE), oxidosqualene cyclase (OSC), dammarenediol synthase (DS), β-amyrin synthase (β-AS), lanosterol synthase (LAS), cycloartenol synthase (CAS) and P450. Additionally, this review critically analyzes and evaluates the background and theoretical basis of the previous researches, as well as the deficiencies of these researches.

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Zhang, Ru, Shiquan Tan, Bianling Zhang, Pengcheng Hu, and Ling Li. "Cerium-Promoted Ginsenosides Accumulation by Regulating Endogenous Methyl Jasmonate Biosynthesis in Hairy Roots of Panax ginseng." Molecules 26, no. 18 (September 16, 2021): 5623. http://dx.doi.org/10.3390/molecules26185623.

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Among rare earth elements, cerium has the unique ability of regulating the growth of plant cells and the biosynthesis of metabolites at different stages of plant development. The signal pathways of Ce3+-mediated ginsenosides biosynthesis in ginseng hairy roots were investigated. At a low concentration, Ce3+ improved the elongation and biomass of hairy roots. The Ce3+-induced accumulation of ginsenosides showed a high correlation with the reactive oxygen species (ROS), as well as the biosynthesis of endogenous methyl jasmonate (MeJA) and ginsenoside key enzyme genes (PgSS, PgSE and PgDDS). At a Ce3+ concentration of 20 mg L−1, the total ginsenoside content was 1.7-fold, and the total ginsenosides yield was 2.7-fold that of the control. Malondialdehyde (MDA) content and the ROS production rate were significantly higher than those of the control. The activity of superoxide dismutase (SOD) was significantly activated within the Ce3+ concentration range of 10 to 30 mg L−1. The activity of catalase (CAT) and peroxidase (POD) strengthened with the increasing concentration of Ce3+ in the range of 20–40 mg L−1. The Ce3+ exposure induced transient production of superoxide anion (O2•−) and hydrogen peroxide (H2O2). Together with the increase in the intracellular MeJA level and enzyme activity for lipoxygenase (LOX), there was an increase in the gene expression level of MeJA biosynthesis including PgLOX, PgAOS and PgJMT. Our results also revealed that Ce3+ did not directly influence PgSS, PgSE and PgDDS activity. We speculated that Ce3+-induced ROS production could enhance the accumulation of ginsenosides in ginseng hairy roots via the direct stimulation of enzyme genes for MeJA biosynthesis. This study demonstrates a potential approach for understanding and improving ginsenoside biosynthesis that is regulated by Ce3+-mediated signal transduction.

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Chu, Luan Luong, Nguyen Quang Huy, and Nguyen Huu Tung. "Microorganisms for Ginsenosides Biosynthesis: Recent Progress, Challenges, and Perspectives." Molecules 28, no. 3 (February 2, 2023): 1437. http://dx.doi.org/10.3390/molecules28031437.

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Ginsenosides are major bioactive compounds present in the Panax species. Ginsenosides exhibit various pharmaceutical properties, including anticancer, anti-inflammatory, antimetastatic, hypertension, and neurodegenerative disorder activities. Although several commercial products have been presented on the market, most of the current chemical processes have an unfriendly environment and a high cost of downstream processing. Compared to plant extraction, microbial production exhibits high efficiency, high selectivity, and saves time for the manufacturing of industrial products. To reach the full potential of the pharmaceutical resource of ginsenoside, a suitable microorganism has been developed as a novel approach. In this review, cell biological mechanisms in anticancer activities and the present state of research on the production of ginsenosides are summarized. Microbial hosts, including native endophytes and engineered microbes, have been used as novel and promising approaches. Furthermore, the present challenges and perspectives of using microbial hosts to produce ginsenosides have been discussed.

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Chen, Hong, Xiangzhu Li, Yongjun Zheng, Mingming Liu, and Kangyu Wang. "Effects of Different Culture Times Genes Expression on Ginsenoside Biosynthesis of the Ginseng Adventitious Roots in Panax ginseng." Horticulturae 9, no. 7 (July 1, 2023): 762. http://dx.doi.org/10.3390/horticulturae9070762.

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Panax ginseng is an ancient and very potent herb, which has a long history of medicinal use, and recent studies have shown that ginsenosides are the main active substances in its pharmacological effects. However, the saponin content of wild ginseng and cultivated ginseng can hardly meet the market supply, and the ginseng adventitious root suspension culture technology can produce ginsenosides in a targeted manner. The length of culture time is an important factor affecting the growth and development of plants and the accumulation of secondary metabolites. After transcriptome sequencing of ginseng adventitious root material at different culture times, the results showed that a total of 5784 differentially expressed genes were screened, which contained 239 transcription factors. KEGG analysis showed that these differentially expressed genes were mainly enriched in metabolic pathways and biosynthesis of secondary metabolites. A proposed temporal analysis of differentially expressed genes among the two groups distributed the differentially expressed genes under nine clusters, and the differentially expressed genes under different clusters had the same expression trends, indicating that these genes can be jointly involved in specific biological processes. Extraction of ginsenosides from ginseng adventitious roots using water-saturated n-butanol and detection of ginsenoside content by high-performance liquid chromatography revealed a significant increase in total saponins and protopanaxadiol ginsenosides (particularly significant for ginsenosides Rd and Rb1), an increase in bioaccumulation of some protopanaxatriol ginsenosides, and a decrease in some protopanaxatriol ginsenosides (S-Rh1, R-Rg3, and Rf) saponin content decreased. We also found seven genes involved in ginsenoside biosynthesis and that the changes in these genes’ expression may be related to the accumulation of ginsenosides.

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Lu, Jing. "Genome-Wide Comparative Profiles of Triterpenoid Biosynthesis Genes in Ginseng and Pseudo Ginseng Medicinal Plants." Life 13, no. 11 (November 19, 2023): 2227. http://dx.doi.org/10.3390/life13112227.

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Saponin-rich medicinal plants, particularly ginseng and Pseudo ginseng, are valuable in traditional medical practice due to the presence of different saponins. These plants benefit from natural saponins/triterpenoids drugs, such as Ginsenosides, Gypenosides, Platycodins, and Lancemasides. Ginsenosides are highly required for research and functional materials preparation in industrial practices, and some compounds, like Compound-K, have been taken to human trials for various therapeutic applications. To elucidate the genes/transcripts profiles responsible for secondary metabolites and ginsenoside biosynthesis in Ginseng and Pseudo ginseng plant genomes, a comparative analysis was conducted in this study. Nine plant genomes with a 99% BUSCO completeness score were used, resulting in 49 KEGG secondary metabolite pathways, 571 cytochromes genes with 42 families, and 3529 carbohydrate genes with 103 superfamilies. The comparative analysis revealed 24 genes/transcripts belonging to the CYP716 family, which is involved in the ginsenoside biosynthesis pathway. Additionally, it found that various ginsenosides demonstrated strong binding affinity with twelve targets, with ginsenoside Rg3, Rg2, Rh1, Rh5, F3, Rh9, Panaxadione, Protopanaxatriol, Floral ginsenoside C, and Floral ginsenoside E exhibiting the highest binding affinities with the tested enzymes. Since these groups of enzymes are not yet fully characterized for Pseudo ginseng plants in the interconversion of triterpenoids, this comparative bioinformatics analysis could aid experimentalists in selecting and conducting characterization with practical knowledge.

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Le, Kim-Cuong, Thanh-Tam Ho, Jong-Du Lee, Kee-Yoeup Paek, and So-Young Park. "Colchicine Mutagenesis from Long-term Cultured Adventitious Roots Increases Biomass and Ginsenoside Production in Wild Ginseng (Panax ginseng Mayer)." Agronomy 10, no. 6 (May 31, 2020): 785. http://dx.doi.org/10.3390/agronomy10060785.

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Panax ginseng Mayer is a perennial herb that has been used as a medicinal plant in Eastern Asia for thousands of years. The aim of this study was to enhance root biomass and ginsenoside content in cultured adventitious roots by colchicine mutagenesis. Adventitious P. ginseng roots were treated with colchicine at different concentrations (100, 200, and 300 mg·L−1) and for different durations (1, 2, and 3 days). Genetic variability of mutant lines was assessed using random amplification of polymorphic DNA (RAPD) analysis. Ginsenoside biosynthesis gene expression, ginsenoside content, enzyme activities, and performance in bioreactor culture were assessed in four mutant lines (100–1-2, 100–1-18, 300–1-16, and 300–2-8). The results showed that ginsenoside productivity was enhanced in all mutant lines, with mutant 100–1-18 exhibiting the most pronounced increase (4.8-fold higher than the control). Expression of some ginsenoside biosynthetic enzymes was elevated in mutant lines. Enzyme activities varied among lines, and lipid peroxidation activity correlated with root biomass. All four lines were suitable for bioreactor cultivation, with mutant 100–1-18 exhibiting the highest biomass after culture scale-up. The results indicated that colchicine mutagenesis of P. ginseng roots increased biomass and ginsenosides production. This technique, and the root lines produced in this study, may be used to increase industrial yields of P. ginseng biomass and ginsenosides.

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Jiang, Yang, Qi Zhang, Zixia Zeng, Yi Wang, Mingzhu Zhao, Kangyu Wang, and Meiping Zhang. "The AP2/ERF Transcription Factor PgERF120 Regulates Ginsenoside Biosynthesis in Ginseng." Biomolecules 14, no. 3 (March 13, 2024): 345. http://dx.doi.org/10.3390/biom14030345.

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Ginseng (Panax ginseng C.A. Meyer) is a perennial herb belonging to the family Araliaceae and has been used for thousands of years in East Asia as an essential traditional medicine with a wide range of pharmacological activities of its main active ingredient, ginsenosides. The AP2/ERF gene family, widely present in plants, is a class of transcription factors capable of responding to ethylene regulation that has an influential role in regulating the synthesis of major active ingredients in medicinal plants and in response to biotic and abiotic stresses, which have not been reported in Panax ginseng. In this study, the AP2/ERF gene was localized on the ginseng chromosome, and an AP2/ERF gene duplication event was also discovered in Panax ginseng. The expression of seven ERF genes and three key enzyme genes related to saponin synthesis was measured by fluorescence quantitative PCR using ethylene treatment of ginseng hairy roots, and it was observed that ethylene promoted the expression of genes related to the synthesis of ginsenosides, among which the PgERF120 gene was the most sensitive to ethylene. We analyzed the sequence features and expression patterns of the PgERF120 gene and found that the expression of the PgERF120 gene was specific in time and space. The PgERF120 gene was subsequently cloned, and plant overexpression and RNA interference vectors were constructed. Ginseng adventitious roots were transformed using the Agrobacterium tumefaciens-mediated method to obtain transgenic ginseng hairy roots, and the gene expression, ginsenoside content and malondialdehyde content in overexpression-positive hairy roots were also analyzed. This study preliminarily verified that the PgERF120 gene can be involved in the regulation of ginsenoside synthesis, which provides a theoretical basis for the study of functional genes in ginseng and a genetic resource for the subsequent use of synthetic biology methods to improve the yield of ginsenosides.

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Kochan, Ewa, Sylwia Caban, Grażyna Szymańska, Piotr Szymczyk, Anna Lipert, Paweł Kwiatkowski, and Monika Sienkiewicz. "Influence of methyl jasmonate on ginsenoside biosynthesis in suspension cultures of Panax quinquefolium L." Annales Universitatis Mariae Curie-Sklodowska, sectio C – Biologia 72, no. 1 (July 16, 2018): 27. http://dx.doi.org/10.17951/c.2017.72.1.27-35.

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<p>Panax quinquefolium L., belonging to the Araliaceae family, along with P. ginseng is one of the well-known species of ginseng. Multidirectional pharmacological action of this plant is attributed to triterpene saponins called ginsenosides. Pharmacopoeial raw material are roots obtained from the field crops which are time-consuming and require expensive agrotechnical procedures. Therefore, the new sources of ginseng biomass are sought such as in vitro suspension cultures. P. quinquefolium L. cell cultures, treated with the elicitation of methyl jasmonate (MJ) in concentration 50 and 250 μmol L-1, synthesize more ginsenosides than control cultures. The highest increase (2.2-fold) of all examined compounds was noted using 250 μmol L-1 MJ. In this condition, the predominantly quantitative metabolite was Rb1 ginsenoside belonging to protopanaxadiol derivatives.</p>

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Zhang, Tao, Mei Han, Limin Yang, Zhongming Han, Lin Cheng, Zhuo Sun, and Linlin Yang. "The Effects of Environmental Factors on Ginsenoside Biosynthetic Enzyme Gene Expression and Saponin Abundance." Molecules 24, no. 1 (December 20, 2018): 14. http://dx.doi.org/10.3390/molecules24010014.

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Panax ginseng C.A. Meyer is one of the most important medicinal plants in Northeast China, and ginsenosides are the main active ingredients found in medicinal ginseng. The biosynthesis of ginsenosides is regulated by environmental factors and the expression of key enzyme genes. Therefore, in this experiment, ginseng in the leaf opened stage, the green fruit stage, the red fruit stage, and the root growth stage was used as the test material, and nine individual ginsenosides and total saponins (the sum of the individual saponins) were detected by HPLC (High Performance Liquid Chromatography). There was a trend of synergistic increase and decrease, and saponin accumulation and transfer in different tissues. The expression of key enzyme genes in nine synthetic pathways was detected by real-time PCR, and the correlation between saponin content, gene expression, and ecological factors was analyzed. Correlation analysis showed that in root tissue, PAR (Photosynthetically Active Radiation) and soil water potential had a greater impact on ginsenoside accumulation, while in leaf tissue, temperature and relative humidity had a greater impact on ginsenoside accumulation. The results provide a theoretical basis for elucidating the relationship between ecological factors and genetic factors and their impact on the quality of medicinal materials. The results also have guiding significance for realizing the quality of medicinal materials.

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Zhou, Chen, Ting Gong, Jingjing Chen, Tianjiao Chen, Jinling Yang, and Ping Zhu. "Production of a Novel Protopanaxatriol-Type Ginsenoside by Yeast Cell Factories." Bioengineering 10, no. 4 (April 11, 2023): 463. http://dx.doi.org/10.3390/bioengineering10040463.

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Ginsenosides, the main active compounds in Panax species, are glycosides of protopanaxadiol (PPD) or protopanaxatriol (PPT). PPT-type ginsenosides have unique pharmacological activities on the central nervous system and cardiovascular system. As an unnatural ginsenoside, 3,12-Di-O-β-D-glucopyranosyl-dammar-24-ene-3β,6α,12β,20S-tetraol (3β,12β-Di-O-Glc-PPT) can be synthesized through enzymatic reactions but is limited by the expensive substrates and low catalytic efficiency. In the present study, we successfully produced 3β,12β-Di-O-Glc-PPT in Saccharomyces cerevisiae with a titer of 7.0 mg/L by expressing protopanaxatriol synthase (PPTS) from Panax ginseng and UGT109A1 from Bacillus subtilis in PPD-producing yeast. Then, we modified this engineered strain by replacing UGT109A1 with its mutant UGT109A1-K73A, overexpressing the cytochrome P450 reductase ATR2 from Arabidopsis thaliana and the key enzymes of UDP-glucose biosynthesis to increase the production of 3β,12β-Di-O-Glc-PPT, although these strategies did not show any positive effect on the yield of 3β,12β-Di-O-Glc-PPT. However, the unnatural ginsenoside 3β,12β-Di-O-Glc-PPT was produced in this study by constructing its biosynthetic pathway in yeast. To the best of our knowledge, this is the first report of producing 3β,12β-Di-O-Glc-PPT through yeast cell factories. Our work provides a viable route for the production of 3β,12β-Di-O-Glc-PPT, which lays a foundation for drug research and development.

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Kim, Yu-Jin, Dabing Zhang, and Deok-Chun Yang. "Biosynthesis and biotechnological production of ginsenosides." Biotechnology Advances 33, no. 6 (November 2015): 717–35. http://dx.doi.org/10.1016/j.biotechadv.2015.03.001.

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Zou, Xian, Yue Zhang, Xu Zeng, Tuo Liu, Gui Li, Yuxin Dai, Yuanzhu Xie, and Zhiyong Luo. "Molecular Cloning and Identification of NADPH Cytochrome P450 Reductase from Panax ginseng." Molecules 26, no. 21 (November 3, 2021): 6654. http://dx.doi.org/10.3390/molecules26216654.

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Ginseng (Panax ginseng C.A. Mey.) is a precious Chinese traditional medicine, for which ginsenosides are the most important medicinal ingredients. Cytochrome P450 enzymes (CYP450) and their primary redox molecular companion NADPH cytochrome P450 reductase (CPR) play a key role in ginsenoside biosynthesis pathway. However, systematic studies of CPR genes in ginseng have not been reported. Numerous studies on ginsenoside synthesis biology still use Arabidopsis CPR (AtCPR1) as a reductase. In this study, we isolated two CPR genes (PgCPR1, PgCPR2) from ginseng adventitious roots. Phylogenetic tree analysis showed that both PgCPR1 and PgCPR2 are grouped in classⅡ of dicotyledonous CPR. Enzyme experiments showed that recombinant proteins PgCPR1, PgCPR2 and AtCPR1 can reduce cytochrome c and ferricyanide with NADPH as the electron donor, and PgCPR1 had the highest enzymatic activities. Quantitative real-time PCR analysis showed that PgCPR1 and PgCPR2 transcripts were detected in all examined tissues of Panax ginseng and both showed higher expression in stem and main root. Expression levels of the PgCPR1 and PgCPR2s were both induced after a methyl jasmonate (MeJA) treatment and its pattern matched with ginsenoside accumulation. The present investigation suggested PgCPR1 and PgCPR2 are associated with the biosynthesis of ginsenoside. This report will assist in future CPR family studies and ultimately improving ginsenoside production through transgenic engineering and synthetic biology.

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Giang, Nguyen Van, Luu Han Ly, Pham Le Bich Hang, and Le Thi Thu Hien. "Isolation and characterization of a gene encoding farnesyl diphosphate synthase from \(\textit{Panax vietnamensis}\) Ha et Grushv." Academia Journal of Biology 43, no. 4 (December 30, 2021): 119–28. http://dx.doi.org/10.15625/2615-9023/16356.

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Panax vietnamensis Ha et Grushv. is a species of the genus Panax native to Central Vietnam, containing a family of triterpene saponins named ginsenosides. This group of biomolecules possesses valuable therapeutic properties against cancer, hepatitis, diabetes, inflammation as well as stress and anxiety. Farnesyl diphosphate synthase (FPS) is a key enzyme participating in the ginsenoside biosynthesis pathway. In this study, a FPS gene from P. vietnamensis (PvFPS) was isolated and characterized. The PvFPS cDNA contained an open reading frame of 1032 bp, encoding a polypeptide chain of 342 amino acid residues. Nucleotide sequence comparison showed that FPS was highly conserved among most species, with two Aspartate-rich motifs responsible for product chain length determination strongly sustained. PvFPS was closely related to those of the same genera and order and differed from those from other kingdoms. PvFPS expression was detected at a greater level in root tissues than in leaves in all ages. Our findings provided information concerning the properties of a crucial gene in the ginsenoside biosynthesis, thus enhancing our understanding of this important pathway.

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Panossian, Alexander, Sara Abdelfatah, and Thomas Efferth. "Network Pharmacology of Red Ginseng (Part I): Effects of Ginsenoside Rg5 at Physiological and Sub-Physiological Concentrations." Pharmaceuticals 14, no. 10 (September 29, 2021): 999. http://dx.doi.org/10.3390/ph14100999.

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Numerous in vitro studies on isolated cells have been conducted to uncover the molecular mechanisms of action of Panax ginseng Meyer root extracts and purified ginsenosides. However, the concentrations of ginsenosides and the extracts used in these studies were much higher than those detected in pharmacokinetic studies in humans and animals orally administered with ginseng preparations at therapeutic doses. Our study aimed to assess: (a) the effects of ginsenoside Rg5, the major “rare” ginsenoside of Red Ginseng, on gene expression in the murine neuronal cell line HT22 in a wide range of concentrations, from 10−4 to 10−18 M, and (b) the effects of differentially expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in HT22 cells after treatment with ginsenoside Rg5. Ginsenoside Rg5 exhibits soft-acting effects on gene expression of neuronal cells in a wide range of physiological concentrations and strong reversal impact at high (toxic) concentration: significant up- or downregulation of expression of about 300 genes at concentrations from 10−6 M to 10−18 M, and dramatically increased both the number of differentially expressed target genes (up to 1670) and the extent of their expression (fold changes compared to unexposed cells) at a toxic concentration of 10−4 M. Network pharmacology analyses of genes’ expression profiles using ingenuity pathway analysis (IPA) software showed that at low physiological concentrations, ginsenoside Rg5 has the potential to activate the biosynthesis of cholesterol and to exhibit predictable effects in senescence, neuroinflammation, apoptosis, and immune response, suggesting soft-acting, beneficial effects on organismal death, movement disorders, and cancer.

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Hu, Wei, Ning Liu, Yuhua Tian, and Lianxue Zhang. "Molecular Cloning, Expression, Purification, and Functional Characterization of Dammarenediol Synthase fromPanax ginseng." BioMed Research International 2013 (2013): 1–7. http://dx.doi.org/10.1155/2013/285740.

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The objective of this study is to clone and charecterize the expression of dammarenediol synthase gene and then to determine the relationship between the expression of dammarenediol synthase gene that is involved in the ginsenoside biosynthetic pathway and the ginsenoside content. A cDNA phage library was constructed from a five-year-old ginseng root. The cDNA library was screened for the dammarenediol synthase gene by using its specific primers. It was further cloned and expressed in pET-30a vector. The recombinant plasmid pET-30a-DS was expressed in RosettaE. coli. The recombinant DS protein was purified by affinity chromatography. The production of dammarenediol was detected by liquid chromatography-mass spectrometry (LC-MS). Results showed that dammarenediol synthase gene was cloned from the cDNA library and was expressed in RosettaE. coliand the SDS-PAGE analysis showed the presence of purified DS protein. LS-MS showed the activity of DS protein, as the protein content increases the dammarenediol increases. Our results indicate that the recombinant dammarenediol synthase protein could increase the production of dammarenediol and the expression of DS played a vital role in the biosynthesis of ginsenosides inP. ginseng.

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Liu, Chang, Kangyu Wang, Ziyi Yun, Wenbo Liu, Mingzhu Zhao, Yanfang Wang, Jian Hu, et al. "Functional Study of PgGRAS68-01 Gene Involved in the Regulation of Ginsenoside Biosynthesis in Panax ginseng." International Journal of Molecular Sciences 24, no. 4 (February 8, 2023): 3347. http://dx.doi.org/10.3390/ijms24043347.

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Ginseng (Panax ginseng C. A. Meyer) is a perennial herb from the genus Panax in the family Araliaceae. It is famous in China and abroad. The biosynthesis of ginsenosides is controlled by structural genes and regulated by transcription factors. GRAS transcription factors are widely found in plants. They can be used as tools to modify plant metabolic pathways by interacting with promoters or regulatory elements of target genes to regulate the expression of target genes, thereby activating the synergistic interaction of multiple genes in metabolic pathways and effectively improving the accumulation of secondary metabolites. However, there are no reports on the involvement of the GRAS gene family in ginsenoside biosynthesis. In this study, the GRAS gene family was located on chromosome 24 pairs in ginseng. Tandem replication and fragment replication also played a key role in the expansion of the GRAS gene family. The PgGRAS68-01 gene closely related to ginsenoside biosynthesis was screened out, and the sequence and expression pattern of the gene were analyzed. The results showed that the expression of PgGRAS68-01 gene was spatio-temporal specific. The full-length sequence of PgGRAS68-01 gene was cloned, and the overexpression vector pBI121-PgGRAS68-01 was constructed. The ginseng seedlings were transformed by Agrobacterium rhifaciens-mediated method. The saponin content in the single root of positive hair root was detected, and the inhibitory role of PgGRAS68-01 in ginsenoside synthesis is reported.

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Jiang, Yue, Sizhang Liu, Li Li, Kaiyou Zang, Yanfang Wang, Mingzhu Zhao, Kangyu Wang, et al. "Transcriptome and Phenotype Integrated Analysis Identifies Genes Controlling Ginsenoside Rb1 Biosynthesis and Reveals Their Interactions in the Process in Panax ginseng." International Journal of Molecular Sciences 23, no. 22 (November 13, 2022): 14016. http://dx.doi.org/10.3390/ijms232214016.

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Genes are the keys to deciphering the molecular mechanism underlying a biological trait and designing approaches desirable for plant genetic improvement. Ginseng is an important medicinal herb in which ginsenosides have been shown to be the major bioactive component; however, only a few genes involved in ginsenoside biosynthesis have been cloned through orthologue analysis. Here, we report the identification of 21 genes controlling Rb1 biosynthesis by stepwise ginseng transcriptome and Rb1 content integrated analysis. We first identified the candidate genes for Rb1 biosynthesis by integrated analysis of genes with the trait from four aspects, including gene transcript differential expression between highest- and lowest-Rb1 content cultivars, gene transcript expression–Rb1 content correlation, and biological impacts of gene mutations on Rb1 content, followed by the gene transcript co-expression network. Twenty-two candidate genes were identified, of which 21 were functionally validated for Rb1 biosynthesis by gene regulation, genetic transformation, and mutation analysis. These genes were strongly correlated in expression with the previously cloned genes encoding key enzymes for Rb1 biosynthesis. Based on the correlations, a pathway for Rb1 biosynthesis was deduced to indicate the roles of the genes in Rb1 biosynthesis. Moreover, the genes formed a strong co-expression network with the previously cloned Rb1 biosynthesis genes, and the variation in the network was associated with the variation in the Rb1 content. These results indicate that Rb1 biosynthesis is a process of correlative interactions among Rb1 biosynthesis genes. Therefore, this study provides new knowledge, 21 new genes, and 96 biomarkers for Rb1 biosynthesis useful for enhanced research and breeding in ginseng.

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Kong, Lingyao, Peng Chen, and Cheng Chang. "Drought Resistance and Ginsenosides Biosynthesis in Response to Abscisic Acid in Panax ginseng C. A. Meyer." International Journal of Molecular Sciences 24, no. 11 (May 24, 2023): 9194. http://dx.doi.org/10.3390/ijms24119194.

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Drought stress adversely affects the production of the perennial medicinal herb Panax ginseng C.A. Meyer. Phytohormone abscisic acid (ABA) regulates many processes in plant growth, development, and response to environments. However, whether drought resistance is regulated by ABA in Panax ginseng remains unknown. In this study, we characterized the response of drought resistance to ABA in Panax ginseng. The results showed that the growth retardation and root shrinking under drought conditions in Panax ginseng were attenuated by exogenous ABA application. Spraying ABA was shown to protect the photosynthesis system, enhance the root activity, improve the performance of the antioxidant protection system, and alleviate the excessive accumulation of soluble sugar in Panax ginseng under drought stress. In addition, ABA treatment leads to the enhanced accumulation of ginsenosides, the pharmaceutically active components, and causes the up-regulation of 3-hydroxy-3-methylglutaryl CoA reductase (PgHMGR) in Panax ginseng. Therefore, this study supports that drought resistance and ginsenosides biosynthesis in Panax ginseng were positively regulated by ABA, providing a new direction for mitigating drought stress and improving ginsenosides production in the precious medicinal herb.

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Zhang, Qiang, Xude Wang, Liyan Lv, Guangyue Su, and Yuqing Zhao. "Antineoplastic Activity, Structural Modification, Synthesis and Structure-activity Relationship of Dammarane-type Ginsenosides: An Overview." Current Organic Chemistry 23, no. 5 (July 1, 2019): 503–16. http://dx.doi.org/10.2174/1385272823666190401141138.

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Dammarane-type ginsenosides are a class of tetracyclic triterpenoids with the same dammarane skeleton. These compounds have a wide range of pharmaceutical applications for neoplasms, diabetes mellitus and other metabolic syndromes, hyperlipidemia, cardiovascular and cerebrovascular diseases, aging, neurodegenerative disease, bone disease, liver disease, kidney disease, gastrointestinal disease and other conditions. In order to develop new antineoplastic drugs, it is necessary to improve the bioactivity, solubility and bioavailability, and illuminate the mechanism of action of these compounds. A large number of ginsenosides and their derivatives have been separated from certain herbs or synthesized, and tested in various experiments, such as anti-proliferation, induction of apoptosis, cell cycle arrest and cancer-involved signaling pathways. In this review, we have summarized the progress in structural modification, shed light on the structure-activity relationship (SAR), and offered insights into biosynthesis-structural association. This review is expected to provide a preliminary guide for the modification and synthesis of ginsenosides.

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刘, 佳. "Advances in the Biosynthesis Research of Ginsenosides and Key Enzymes." Botanical Research 03, no. 03 (2014): 84–90. http://dx.doi.org/10.12677/br.2014.33013.

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Kochan, Ewa, Monika Sienkiewicz, Dagmara Szmajda-Krygier, Ewa Balcerczak, and Grażyna Szymańska. "Carvacrol as a Stimulant of the Expression of Key Genes of the Ginsenoside Biosynthesis Pathway and Its Effect on the Production of Ginseng Saponins in Panax quinquefolium Hairy Root Cultures." International Journal of Molecular Sciences 25, no. 2 (January 11, 2024): 909. http://dx.doi.org/10.3390/ijms25020909.

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The accumulation of ginsenosides (triterpenic saponins) was determined in Panax quinquefolium hairy root cultures subjected to an elicitation process using carvacrol at 5, 10, 25, 50, 100, 250, and 500 μM concentrations during 24 and 72 h exposure. This study was the first one in which carvacrol was applied as an elicitor. The content of eight ginsenosides, Rb1, Rb2, Rb3, Rc, Rd, Rg1, Rg2, and Re, was determined using HPLC analysis. Moreover, the quantitative RT-PCR method was applied to assess the relative expression level of farnesyl diphosphate synthase, squalene synthase, and dammarenediol synthase genes in the studied cultures. The addition of carvacrol (100 μM) was an effective approach to increase the production of ginsenosides. The highest content and productivity of all detected saponins were, respectively, 20.01 mg∙g−1 d.w. and 5.74 mg∙L−1∙day−1 after 72 h elicitation. The production profile of individual metabolites in P. quinquefolium cultures changed under the influence of carvacrol. The biosynthesis of most examined protopanaxadiol derivatives was reduced under carvacrol treatment. In contrast, the levels of ginsenosides belonging to the Rg group increased. The strongest effect of carvacrol was noticed for Re metabolites, achieving a 7.72-fold increase in comparison to the control. Saponin Rg2, not detected in untreated samples, was accumulated after carvacrol stimulation, reaching its maximum concentration after 72 h exposure to 10 μM elicitor.

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Trinh, Vu Thi, Luu Han Ly, Huynh Thi Thu Hue, and Le Thi Thu Hien. "Isolation, sequencing and expression of the gene encoding acetoacetyl-coa thiolase from Panax vietnamensis Ha et Grushv." Vietnam Journal of Biotechnology 19, no. 1 (July 18, 2021): 107–17. http://dx.doi.org/10.15625/1811-4989/16084.

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Panax vietnamensis Ha et Grushv., naturally distributed in Ngoc Linh Mountain, is an endemic Panax species of Vietnam. For centuries, P. vietnamensis has been used in traditional folk medicine to treat many serious diseases or enhance physical strength. Ginsenosides are responsible for most of the medicinal effects of the Panax species. Acetoacetyl-CoA thiolase (AACT) is considered as an important enzyme involved in the biosynthesis of ginsenoside. In this study, a full-length cDNA of the gene encoding AACT protein (GeneBank accession number MZ272018) was obtained from P. vietnamensis using reverse transcription PCR. The gene open reading frame (1224 bp) encodes 408 amino acids. This cDNA sequence is 99.08% similar to the cDNA sequence of Panax notoginseng (KJ804173.1). The functional analysis of its protein by InterPro showed that the structure of AACT monomer consists of three domains, including thiolase-like domain (17-285), N-terminal (18-276), and C-terminal (286-406). Although there were some differences in the nucleotide sequence of the AACT cDNA gene between P. vietnamensis and the reference species, all important domains and sites related to the thiolase activity were observed. Phylogenetic analysis using AACT cDNA gene sequence revealed a close relationship of P. vietnamensis with P. notoginseng and Trachyspemum ammi. The quantitative real-time PCR results indicated the expression of AACT gene of P. vietnamensis depended on types of tissue and plant developmental stages (1, 4, 6 and 11 years old). The gene was expressed at higher levels in roots than in leaves and the highest expression of AACT gene was detected in the 11-year-old roots. The results provided valuable information for further studies on the biosynthesis of ginsenoside in P. vietnamensis in particular and Panax species in general.

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Alcalde, Miguel Angel, Edgar Perez-Matas, Ainoa Escrich, Rosa M. Cusido, Javier Palazon, and Mercedes Bonfill. "Biotic Elicitors in Adventitious and Hairy Root Cultures: A Review from 2010 to 2022." Molecules 27, no. 16 (August 17, 2022): 5253. http://dx.doi.org/10.3390/molecules27165253.

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One of the aims of plant in vitro culture is to produce secondary plant metabolites using plant cells and organ cultures, such as cell suspensions, adventitious, and hairy roots (among others). In cases where the biosynthesis of a compound in the plant is restricted to a specific organ, unorganized systems, such as plant cell cultures, are sometimes unsuitable for biosynthesis. Then, its production is based on the establishment of organ cultures such as roots or aerial shoots. To increase the production in these biotechnological systems, elicitors have been used for years as a useful tool since they activate secondary biosynthetic pathways that control the flow of carbon to obtain different plant compounds. One important biotechnological system for the production of plant secondary metabolites or phytochemicals is root culture. Plant roots have a very active metabolism and can biosynthesize a large number of secondary compounds in an exclusive way. Some of these compounds, such as tropane alkaloids, ajmalicine, ginsenosides, etc., can also be biosynthesized in undifferentiated systems, such as cell cultures. In some cases, cell differentiation and organ formation is necessary to produce the bioactive compounds. This review analyses the biotic elicitors most frequently used in adventitious and hairy root cultures from 2010 to 2022, focusing on the plant species, the target secondary metabolite, the elicitor and its concentration, and the yield/productivity of the target compounds obtained. With this overview, it may be easier to work with elicitors in in vitro root cultures and help understand why some are more effective than others.

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Zhu, Lei, Jian Hu, Ruiqi Li, Chang Liu, Yang Jiang, Tao Liu, Mingming Liu, et al. "Transcriptome-Wide Integrated Analysis of the PgGT25-04 Gene in Controlling Ginsenoside Biosynthesis in Panax ginseng." Plants 12, no. 10 (May 15, 2023): 1980. http://dx.doi.org/10.3390/plants12101980.

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Panax ginseng is a valuable medicinal herb of the Araliaceae family with various pharmacological activities. The Trihelix transcription factors family is involved in growth and secondary metabolic processes in plants, but no studies have been reported on the involvement of Trihelix genes in secondary metabolic processes in ginseng. In this study, weighted co-expression network analysis, correlation analysis between PgGTs and ginsenosides and key enzyme genes, and interaction network analysis between PgGTs and key enzyme genes were used to screen out the PgGT25-04 gene, which was negatively correlated with ginsenoside synthesis. Using ABA treatment of ginseng hair roots, PgGT genes were found to respond to ABA signals. Analysis of the sequence characteristics and expression pattern of the PgGT25-04 gene in ginseng revealed that its expression is spatiotemporally specific. The interfering vector pBI121-PgGT25-04 containing the PgGT25-04 gene was constructed, and the ginseng adventitious roots were transformed using the Agrobacterium-mediated method to obtain the pBI121-PgGT25-04 positive hairy root monocot line. The saponin contents of positive ginseng hair roots were measured by HPLC, and the changes in PgGT25-04 and key enzyme genes in positive ginseng hair roots were detected via fluorescence quantitative RT-PCR. These results preliminarily identified the role of the PgGT25-04 gene in the secondary metabolism of ginseng in Jilin to provide a theoretical basis for the study of Trihelix transcription factors in Panax ginseng.

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Kim, Dongmin, Mihyang Kim, Gem Raña, and Jaehong Han. "Seasonal Variation and Possible Biosynthetic Pathway of Ginsenosides in Korean Ginseng Panax ginseng Meyer." Molecules 23, no. 7 (July 23, 2018): 1824. http://dx.doi.org/10.3390/molecules23071824.

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Whereas Korean ginseng, Panax ginseng Meyer, is harvested in the fall, the variation of ginsenoside content in field-grown ginseng across seasonal development has never been investigated in Korea. Thus, ultra-high performance liquid chromatography (UHPLC) analysis of nine major ginsenosides, including ginsenoside Rg1, Re, Rf, Rg2, Rb1, Rc, Rb2, Rd, and Ro, in the roots of five-year-old P. ginseng cultivated in Bongwha, Korea in 2017 was performed. The total ginsenoside content changed as many as three times throughout the year, ranging from 1.37 ± 0.02 (dry wt %) in January to 4.26 ± 0.03% in May. Total ginsenoside content in the harvest season was 2.49 ± 0.03%. Seasonal variations of panaxadiol-type ginsenosides (PPD) and panaxatriol-type ginsenosides (PPT) were found to be similar, but more PPD was always measured. However, the seasonal variation of oleanolic acid-type ginsenoside, Ro, was different from that of PPD and PPT, and the highest Ro content was observed in May. The ratio of PPD/PPT, as well as other representative ginsenosides, was compared throughout the year. Moreover, the percent composition of certain ginsenosides in both PPD and PPT types was found to be in a complementary relationship each other, which possibly reflected the biosynthetic pathway of the related ginsenosides. This finding would not only provide scientific support for the production and quality control of the value-added ginseng products, but also facilitate the elucidation of the ginsenoside biosynthetic pathway.

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Kochan, Ewa, Ewa Balcerczak, Piotr Szymczyk, Monika Sienkiewicz, Hanna Zielińska-Bliźniewska, and Grażyna Szymańska. "Abscisic Acid Regulates the 3-Hydroxy-3-methylglutaryl CoA Reductase Gene Promoter and Ginsenoside Production in Panax quinquefolium Hairy Root Cultures." International Journal of Molecular Sciences 20, no. 6 (March 15, 2019): 1310. http://dx.doi.org/10.3390/ijms20061310.

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Panax quinquefolium hairy root cultures synthesize triterpenoid saponins named ginsenosides, that have multidirectional pharmacological activity. The first rate-limiting enzyme in the process of their biosynthesis is 3-hydroxy-3-methylglutaryl CoA reductase (HMGR). In this study, a 741 bp fragment of the P. quinquefolium HMGR gene (PqHMGR), consisting of a proximal promoter, 5′UTR (5′ untranslated region) and 5′CDS (coding DNA sequence) was isolated. In silico analysis of an isolated fragment indicated a lack of tandem repeats, miRNA binding sites, and CpG/CpNpG elements. However, the proximal promoter contained potential cis-elements involved in the response to light, salicylic, and abscisic acid (ABA) that was represented by the motif ABRE (TACGTG). The functional significance of ABA on P. quinquefolium HMGR gene expression was evaluated, carrying out quantitative RT-PCR experiments at different ABA concentrations (0.1, 0.25, 0.5, and 1 mg·L−1). Additionally, the effect of abscisic acid and its time exposure on biomass and ginsenoside level in Panax quinquefolium hairy root was examined. The saponin content was determined using HPLC. The 28 day elicitation period with 1 mg·L−1 ABA was the most efficient for Rg2 and Re (17.38 and 1.83 times increase, respectively) accumulation; however, the protopanaxadiol derivative content decreased in these conditions.

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Jin, Shi Kun, and Shou Jing Zhao. "Recent Advances in Study of Ginsenoside Biosynthetic Pathway in Panax ginseng." Advanced Materials Research 773 (September 2013): 368–73. http://dx.doi.org/10.4028/www.scientific.net/amr.773.368.

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Ginsenosides, the major bioactive ingredients of P. ginseng can improve the anti-disease abilities of human being, and generate significant social and economic benefits. However, along with gradually or rapidly or dramatically increasing demand of the ginsenosides, extensive studies have focused on regulating the ginsenoside biosynthetic pathway on a genetic level. This review provides the latest research progress on biosynthetic pathway of ginsenosides, including the mevalonate (MVA) and the methylerythritol phosphate (MEP) pathway, which is newly discovered and located in P. ginseng. Moreover, it also indicated lanosterol synthase metabolic flux present in P. ginseng.

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Zhang, Jing-Jing, He Su, Lei Zhang, Bao-Sheng Liao, Shui-Ming Xiao, Lin-Lin Dong, Zhi-Gang Hu, et al. "Comprehensive Characterization for Ginsenosides Biosynthesis in Ginseng Root by Integration Analysis of Chemical and Transcriptome." Molecules 22, no. 6 (May 31, 2017): 889. http://dx.doi.org/10.3390/molecules22060889.

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Kim, Dongmin, and Jaehong Han. "Study on biosynthesis of ginsenosides in the leaf of Panax ginseng by seasonal flux analysis." Journal of Applied Biological Chemistry 62, no. 4 (December 31, 2019): 315–22. http://dx.doi.org/10.3839/jabc.2019.043.

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Li, Jinxin, Hongfa Li, Dahui Liu, Shujie Liu, Jianli Li, and Juan Wang. "Analysis of ginsenoside content, functional genes involved in ginsenosides biosynthesis, and activities of antioxidant enzymes in Panax quinquefolium L. adventitious roots by fungal elicitors." Research on Chemical Intermediates 43, no. 4 (October 17, 2016): 2415–32. http://dx.doi.org/10.1007/s11164-016-2770-x.

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WU, Wen-Ru, Chun-Song CHENG, Qi-Qing CHENG, Chi-Chou LAO, Hao CUI, Zi-Yu TANG, Yue OUYANG, Liang LIU, and Hua ZHOU. "Novel SNP markers on ginsenosides biosynthesis functional gene for authentication of ginseng herbs and commercial products." Chinese Journal of Natural Medicines 18, no. 10 (October 2020): 770–78. http://dx.doi.org/10.1016/s1875-5364(20)60017-6.

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Scossa, Federico, Maria Benina, Saleh Alseekh, Youjun Zhang, and Alisdair Fernie. "The Integration of Metabolomics and Next-Generation Sequencing Data to Elucidate the Pathways of Natural Product Metabolism in Medicinal Plants." Planta Medica 84, no. 12/13 (May 29, 2018): 855–73. http://dx.doi.org/10.1055/a-0630-1899.

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AbstractPlants have always been used as medicines since ancient times to treat diseases. The knowledge around the active components of herbal preparations has remained nevertheless fragmentary: the biosynthetic pathways of many secondary metabolites of pharmacological importance have been clarified only in a few species, while the chemodiversity present in many medicinal plants has remained largely unexplored. Despite the advancements of synthetic biology for production of medicinal compounds in heterologous hosts, the native plant species are often the most reliable and economic source for their production. It thus becomes fundamental to investigate the metabolic composition of medicinal plants to characterize their natural metabolic diversity and to define the biosynthetic routes in planta of important compounds to develop strategies to further increase their content. We present here a number of case studies for selected classes of secondary metabolites and we review their health benefits and the historical developments in their structural elucidation and characterization of biosynthetic genes. We cover the cases of benzoisoquinoline and monoterpenoid indole alkaloids, cannabinoids, caffeine, ginsenosides, withanolides, artemisinin, and taxol; we show how the “early” biochemical or the more recent integrative approaches–based on omics-analyses–have helped to elucidate their metabolic pathways and cellular compartmentation. We also summarize how the knowledge generated about their biosynthesis has been used to develop metabolic engineering strategies in heterologous and native hosts. We conclude that following the advent of novel, high-throughput and cost-effective analytical technologies, the secondary metabolism of medicinal plants can now be examined under the lens of systems biology.

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Zhang, Guang-Hui, Chun-Hua Ma, Jia-Jin Zhang, Jun-Wen Chen, Qing-Yan Tang, Mu-Han He, Xiang-Zeng Xu, Ni-Hao Jiang, and Sheng-Chao Yang. "Transcriptome analysis of Panax vietnamensis var. fuscidicus discovers putative ocotillol-type ginsenosides biosynthesis genes and genetic markers." BMC Genomics 16, no. 1 (2015): 159. http://dx.doi.org/10.1186/s12864-015-1332-8.

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Linsefors, Lotta, Lars Björk, and Klaus Mosbach. "Influence of Elicitors and Mevalonic Acid on the Biosynthesis of Ginsenosides in Tissue Cultures of Panax ginseng." Biochemie und Physiologie der Pflanzen 184, no. 5-6 (January 1989): 413–18. http://dx.doi.org/10.1016/s0015-3796(89)80039-3.

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Wang, Shi-hui, Wen-xia Liang, Jun Lu, Lu Yao, Juan Wang, and Wen-yuan Gao. "Penicillium sp. YJM-2013 induces ginsenosides biosynthesis in Panax ginseng adventitious roots by inducing plant resistance responses." Chinese Herbal Medicines 12, no. 3 (July 2020): 257–64. http://dx.doi.org/10.1016/j.chmed.2020.02.003.

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Kim, Su-Jin, Hyun-Ja Jeong, Byoung-Jae Yi, Tae-Hee Kang, Nyeon-Hyung An, Eun-Hyub Lee, Deok-Chun Yang, Hyung-Min Kim, Seung-Heon Hong, and Jae-Young Um. "Transgenic Panax ginseng Inhibits the Production of TNF-α, IL-6, and IL-8 as well as COX-2 Expression in Human Mast Cells." American Journal of Chinese Medicine 35, no. 02 (January 2007): 329–39. http://dx.doi.org/10.1142/s0192415x07004850.

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The most well-known medicinal plant, Panax ginseng (P. ginseng), contains various phytosterols and bioactive triterpene saponins (ginsenosides). Squalene synthase is a key regulatory enzyme for triterpene biosynthesis and overexpression of the squalene synthase confers the hyper-production of triterpene saponins to form transgenic ginseng. In this study, we have investigated whether and how transgenic P. ginseng modulates an inflammatory reaction in a stimulated human mast cell line, HMC-1. It was found that transgenic P. ginseng inhibited the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, and the expression of cyclooxygenase-2 in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 (PMACI)-stimulated HMC-1. Additionally, we have shown that transgenic P. ginseng suppressed the intracellular calcium level induced by PMACI. These results provide new insights into the pharmacological actions of transgenic P. ginseng as a potential molecule for use in therapy in mast cell-mediated inflammatory diseases.

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Wang, Shihui, Wenxia Liang, Lu Yao, Juan Wang, and Wenyuan Gao. "Effect of temperature on morphology, ginsenosides biosynthesis, functional genes, and transcriptional factors expression in Panax ginseng adventitious roots." Journal of Food Biochemistry 43, no. 4 (February 2019): e12794. http://dx.doi.org/10.1111/jfbc.12794.

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Yu, Lu, Yuan Chen, Jie Shi, Rufeng Wang, Yingbo Yang, Li Yang, Shujuan Zhao, and Zhengtao Wang. "Biosynthesis of rare 20(R)-protopanaxadiol/protopanaxatriol type ginsenosides through Escherichia coli engineered with uridine diphosphate glycosyltransferase genes." Journal of Ginseng Research 43, no. 1 (January 2019): 116–24. http://dx.doi.org/10.1016/j.jgr.2017.09.005.

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Tang, Qing-Yan, Geng Chen, Wan-Ling Song, Wei Fan, Kun-Hua Wei, Si-Mei He, Guang-Hui Zhang, et al. "Transcriptome analysis of Panax zingiberensis identifies genes encoding oleanolic acid glucuronosyltransferase involved in the biosynthesis of oleanane-type ginsenosides." Planta 249, no. 2 (September 15, 2018): 393–406. http://dx.doi.org/10.1007/s00425-018-2995-6.

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Ma, Rui, Rui Jiang, Xuenan Chen, Daqing Zhao, Tong Li, and Liwei Sun. "Proteomics analyses revealed the reduction of carbon- and nitrogen-metabolism and ginsenoside biosynthesis in the red-skin disorder of Panax ginseng." Functional Plant Biology 46, no. 12 (2019): 1123. http://dx.doi.org/10.1071/fp18269.

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Red-skin disorder (RSD), a non-infectious disorder in Panax ginseng, impairs the quality and yield of ginseng and impedes continuous cropping. Since the mechanism of this disorder is unknown, there are no effective prevention measures for RSD. The proteomic changes in RSD ginseng were analysed in this study by two-dimensional electrophoresis (2-DE) and isobaric tags for relative and absolute quantification (iTRAQ). The differential expression of 137 proteins (60 from 2-DE and 77 from iTRAQ) was identified in RSD ginseng as compared with healthy ginseng. Most changes are related to carbon- and nitrogen- metabolism, redox homeostasis, and stress resistance. We also found that the concentration of metal elements, such as iron (Fe), aluminium (Al), and manganese (Mn), was significantly increased in RSD ginseng. These increased metals would be chelated with phenols to form red spots on the ginseng epidermis. Moreover, RSD disturbed the carbon and nitrogen metabolism and affected the biosynthesis of nutrients (sugar, proteins, amino acids) and active components (ginsenosides), which reduced the survival rate and medicinal value of ginseng. These differences between RSD and healthy ginseng will contribute to the understanding of RSD mechanism.

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Wu, Qiong, Jingyuan Song, Yongqiao Sun, Fengmei Suo, Chenji Li, Hongmei Luo, Ying Liu, et al. "Transcript profiles ofPanax quinquefoliusfrom flower, leaf and root bring new insights into genes related to ginsenosides biosynthesis and transcriptional regulation." Physiologia Plantarum 138, no. 2 (February 2010): 134–49. http://dx.doi.org/10.1111/j.1399-3054.2009.01309.x.

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Lu, Jun, Lu Yao, Jin-Xin Li, Shu-Jie Liu, Yan-Ying Hu, Shi-Hui Wang, Wen-Xia Liang, et al. "Characterization of UDP-Glycosyltransferase Involved in Biosynthesis of Ginsenosides Rg1 and Rb1 and Identification of Critical Conserved Amino Acid Residues for Its Function." Journal of Agricultural and Food Chemistry 66, no. 36 (August 10, 2018): 9446–55. http://dx.doi.org/10.1021/acs.jafc.8b02544.

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Choi, Dong-Woog, JongDuk Jung, Young Im Ha, Hyun-Woo Park, Dong Su In, Hwa-Jee Chung, and Jang Ryol Liu. "Analysis of transcripts in methyl jasmonate-treated ginseng hairy roots to identify genes involved in the biosynthesis of ginsenosides and other secondary metabolites." Plant Cell Reports 23, no. 8 (November 5, 2004): 557–66. http://dx.doi.org/10.1007/s00299-004-0845-4.

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Zhang, He, Xin Hua, Dongran Zheng, Hao Wu, Chuanwang Li, Pan Rao, Mengliang Wen, et al. "De Novo Biosynthesis of Oleanane-Type Ginsenosides in Saccharomyces cerevisiae Using Two Types of Glycosyltransferases from Panax ginseng." Journal of Agricultural and Food Chemistry 70, no. 7 (February 11, 2022): 2231–40. http://dx.doi.org/10.1021/acs.jafc.1c07526.

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Li, Jinxin, Shujie Liu, Juan Wang, Jing Li, Dahui Liu, Jianli Li, and Wenyuan Gao. "Fungal elicitors enhance ginsenosides biosynthesis, expression of functional genes as well as signal molecules accumulation in adventitious roots of Panax ginseng C. A. Mey." Journal of Biotechnology 239 (December 2016): 106–14. http://dx.doi.org/10.1016/j.jbiotec.2016.10.011.

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Wang, Qiuguo, Siqi Yan, Xiaoran Zhou, Huiling Mei, Yu Xiang, Bin Fang, Leilei Zhang, Yu Hu, and Qiuguo Wang. "20(S)-Protopanaxatriol Promotes Fatty Acid-Induced ER Stress and Apoptosis in Multiple Myeloma By Down-Regulating SCD1 Expression." Blood 132, Supplement 1 (November 29, 2018): 3219. http://dx.doi.org/10.1182/blood-2018-99-118181.

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Abstract Multiple myeloma (MM), is a hematological malignancy characterized by the accumulation of clonal malignant plasma cells. Nowadays more and more studies concern that alert metabolism including glycolysis, glutaminolysis and lipid metabolism has potent in vivo anticancer activity in multiple myeloma. While glycolysis and glutaminolysis was well established, lipid metabolism of MM is poorly understood and there is a need for a new low-toxic therapy that selectively target MM. Lipid metabolism studies such as on the use of inhibitors of fatty acid synthesis and their effects on MM cell survival have been reported. Our study showed the increase of the expression of stearoyl CoA desaturase 1 (SCD1) and the elevated fatty acid biosynthesis in MM cells (Fig.1A, p<0.001). We found that SCD1 is overexpression in MM patients' samples and associated with clinical stage of myeloma (Fig 1B, p<0.05). Then we examined the level of lipid droplets(LDs) in MM cells, and the high level of LDs detected in MM cells demonstrated the lipid accumulation in MM (Fig.1C). Stable depletion of SCD1 inhibited fatty acid biosynthesis and decreased LDs levels and this reduction of LDs remained at low levels in MM cells (Fig.1D, E). These results suggest that MM cell growth party relies on SCD1-mediated fatty acid metabolism. The finding that 20(S)-protopanaxatriol(PPT) has significant effect on inhibiting the transcription of lipogenic genes have reported. Western blotting analysis shows that PPT decreased SCD1 protein levels in RPMI-8226, ARH-77 cell lines. In addition, PPT treatment decreased fatty acid biosynthesis and blocked lipid storage in lipid droplets(LDs) (Fig.1F). The proportion of saturated and monounsaturated was also decreased after treatment (Fig. 1G). Given that 20(S)-protopanaxatriol(PPT) has lipid-lowering effect in MM, we hypothesized that PPT exerts anti-myeloma effects by disrupting lipogenesis. In vitro experiments demonstrate the significant effect of PPT on decreasing proliferation and inducing apoptosis in multiple myeloma (Fig.1H). Supplementation with the SCD1 enzymatic product, oleic acid, rescued MM cells from PPT cell killing and SCD1 silencing, decreasing levels of SCD1 inhibition induced apoptosis and proliferation inhibition (Fig.1I). The results of Western Blot Analysis show a positive correlation between SCD1 inhibition and endoplasmic reticulum stress (ER stress) (Fig.1J). In addition, PPT can obviously induce ER stress after inhibiting SCD1, while ER-stress inhibitor TUDCA can significantly reverse the induced apoptosis of PPT treatment in MM cells (Fig.1K, p<0.05). These results suggest that excessive endoplasmic reticulum stress is the main cause of PPT induced apoptosis. In summary, our studies reveal that regulation of fatty acid metabolism in MM cells is an essential target. We show that the redeployed drug PPT killed MM cells by decreasing SCD1 protein levels and promoting fatty acid-induced ER stress. This study is relevant to the wider context of multiple myeloma therapeutics that developing therapeutics which can disrupt fatty acid biosynthesis. To our knowledge, this is the first study to describe the aglycone of ginsenosides 20(S)-protopanaxatriol with demonstrable anti-myeloma activity that target fatty acid biosynthesis Disclosures No relevant conflicts of interest to declare.

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Wu, Fulin, Sihan Lai, Hao Feng, Juntong Liu, Dongxing Fu, Caixia Wang, Cuizhu Wang, Jinping Liu, Zhuo Li, and Pingya Li. "Protective Effects of Protopanaxatriol Saponins on Ulcerative Colitis in Mouse Based on UPLC-Q/TOF-MS Serum and Colon Metabolomics." Molecules 27, no. 23 (November 30, 2022): 8346. http://dx.doi.org/10.3390/molecules27238346.

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Ulcerative colitis (UC) is a chronic, nonspecific inflammation of the bowel that mainly affects the mucosa and submucosa of the rectum and colon. Ginsenosides are the main active ingredients in ginseng and show many therapeutic effects in anti-inflammatory diseases, cancer, and nervous system regulation. Protopanaxatriol saponin (PTS) is an important part of saponins, and there is no research on its pharmacological effects on colitis. In this study, a model of ulcerative colitis in mice was induced by having mice freely drink 3.5% dextran sodium sulfate (DSS) solution, and UPLC-Q-TOF-MS-based metabolomics methods were applied to explore the therapeutic effect and protective mechanism of PTS for treating UC. The results showed that PTS could significantly prevent colon shortening and pathological damage and alleviate abnormal changes in UC mouse physiological and biochemical parameters. Moreover, PTS intervention regulated proinflammatory cytokines such as TNF-α, IL-6, and IL-1 in serum, and MPO and NO in colon. Interestingly, PTS could significantly inhibit UC mouse metabolic dysfunction by reversing abnormal changes in 29 metabolites and regulating eleven metabolic pathways. PTS has potential application in the treatment of UC and could alleviate UC in mice by affecting riboflavin metabolism, arachidonic acid metabolism, glycerophospholipid metabolism, retinol metabolism, and steroid hormone biosynthesis and by regulating pentose and glucuronate conversion, linoleic acid metabolism, phenylalanine metabolism, ether lipid metabolism, sphingolipid metabolism, and tyrosine metabolism, which points at a direction for further research and for the development of PTS as a novel natural agent.

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Di, Ping, Zhuo Sun, Lin Cheng, Mei Han, Li Yang, and Limin Yang. "LED Light Irradiations Differentially Affect the Physiological Characteristics, Ginsenoside Content, and Expressions of Ginsenoside Biosynthetic Pathway Genes in Panax ginseng." Agriculture 13, no. 4 (March 31, 2023): 807. http://dx.doi.org/10.3390/agriculture13040807.

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Light is essential for plants and plays a vital role in their growth and development. Light irradiation affects the physiological characteristics and synthesis of secondary metabolites in plants. As a semi-shade perennial plant, Panax ginseng C.A. Mey. is sensitive to changes in the light environment. Different light irradiations significantly affect the secondary metabolic processes of P. ginseng. However, few studies have investigated the changes in ginsenoside content in P. ginseng under different light irradiation conditions. In this study, 3-year-old P. ginseng was cultured under white (CK) light, blue (B) light, red (R) light, green (G) light, and natural light (NL) to explore the effects of light irradiation on the physiological characteristics and ginsenoside secondary metabolism of P. ginseng. The B and CK treatments significantly increased the photosynthetic level in P. ginseng leaves. The total saponin content under blue and red light treatments increased by 28.81% and 21.64%, respectively, compared with the CK treatment. Blue and red light improved the transcription levels of ginsenoside biosynthetic pathway genes. Blue light upregulated the expression of HMGR, SS, SE, DS, CYP716A52, and CYP716A47, and the expression of HMGR, SS, SE, DS, and CYP716A47 under red light treatment was significantly upregulated in P. ginseng roots. Principal component and correlation analyses revealed that the physiological and ecological processes of P. ginseng exhibited different responses to light irradiation. The total saponin content in the roots was positively correlated with the content of protopanaxatriol -type ginsenosides and water use efficiency in leaves. Our study indicates that light conditions can be improved by blue and red light or by blue and red film covering to facilitate the accumulation of saponin during the ecological cultivation of P. ginseng.

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Yu, Xiaochen, Jinghui Yu, Sizhang Liu, Mingming Liu, Kangyu Wang, Mingzhu Zhao, Yanfang Wang, et al. "Transcriptome-Wide Identification and Integrated Analysis of a UGT Gene Involved in Ginsenoside Ro Biosynthesis in Panax ginseng." Plants 13, no. 5 (February 23, 2024): 604. http://dx.doi.org/10.3390/plants13050604.

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Panax ginseng as a traditional medicinal plant with a long history of medicinal use. Ginsenoside Ro is the only oleanane-type ginsenoside in ginseng, and has various pharmacological activities, including anti-inflammatory, detoxification, and antithrombotic activities. UDP-dependent glycosyltransferase (UGT) plays a key role in the synthesis of ginsenoside, and the excavation of UGT genes involved in the biosynthesis of ginsenoside Ro has great significance in enriching ginsenoside genetic resources and further revealing the synthesis mechanism of ginsenoside. In this work, ginsenoside-Ro-synthesis-related genes were mined using the P. ginseng reference-free transcriptome database. Fourteen hub transcripts were identified by differential expression analysis and weighted gene co-expression network analysis. Phylogenetic and synteny block analyses of PgUGAT252645, a UGT transcript among the hub transcripts, showed that PgUGAT252645 belonged to the UGT73 subfamily and was relatively conserved in ginseng plants. Functional analysis showed that PgUGAT252645 encodes a glucuronosyltransferase that catalyzes the glucuronide modification of the C3 position of oleanolic acid using uridine diphosphate glucuronide as the substrate. Furthermore, the mutation at 622 bp of its open reading frame resulted in amino acid substitutions that may significantly affect the catalytic activity of the enzyme, and, as a consequence, affect the biosynthesis of ginsenoside Ro. Results of the in vitro enzyme activity assay of the heterologous expression product in E. coli of PgUGAT252645 verified the above analyses. The function of PgUGAT252645 was further verified by the result that its overexpression in ginseng adventitious roots significantly increased the content of ginsenoside Ro. The present work identified a new UGT gene involved in the biosynthesis of ginsenoside Ro, which not only enriches the functional genes in the ginsenoside synthesis pathway, but also provides the technical basis and theoretical basis for the in-depth excavation of ginsenoside-synthesis-related genes.

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Chu, Jianlin, Jiheng Yue, Song Qin, Yuqiang Li, Bin Wu, and Bingfang He. "Biocatalysis for Rare Ginsenoside Rh2 Production in High Level with Co-Immobilized UDP-Glycosyltransferase Bs-YjiC Mutant and Sucrose Synthase AtSuSy." Catalysts 11, no. 1 (January 18, 2021): 132. http://dx.doi.org/10.3390/catal11010132.

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Rare ginsenoside Rh2 exhibits diverse pharmacological effects. UDP-glycosyltransferase (UGT) catalyzed glycosylation of protopanaxadiol (PPD) has been of growing interest in recent years. UDP-glycosyltransferase Bs-YjiC coupling sucrose synthase in one-pot reaction was successfully applied to ginsenoside biosynthesis with UDP-glucose regeneration from sucrose and UDP, which formed a green and sustainable approach. In this study, the his-tagged UDP-glycosyltransferase Bs-YjiC mutant M315F and sucrose synthase AtSuSy were co-immobilized on heterofunctional supports. The affinity adsorption significantly improved the capacity of specific binding of the two recombinant enzymes, and the dual enzyme covalently cross-linked by the acetaldehyde groups significantly promoted the binding stability of the immobilized bienzyme, allowing higher substrate concentration by easing substrate inhibition for the coupled reaction. The dual enzyme amount used for ginsenoside Rh2 biosynthesis is Bs-YjiC-M315F: AtSuSy = 18 mU/mL: 25.2 mU/mL, a yield of 79.2% was achieved. The coimmobilized M315F/AtSuSy had good operational stability of repetitive usage for 10 cycles, and the yield of ginsenoside Rh2 was kept between 77.6% and 81.3%. The high titer of the ginsenoside Rh2 cumulatively reached up to 16.6 mM (10.3 g/L) using fed-batch technology, and the final yield was 83.2%. This study has established a green and sustainable approach for the production of ginsenoside Rh2 in a high level of titer, which provides promising candidates for natural drug research and development.

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Journal articles on the topic 'Biosynthesis of ginsenosides'

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