Bupleurum chinense DC. a medicinal plant valued for saikosaponins (SSs) with antipyretic and hepatoprotective properties, faces constrained SS biosynthesis mediated by abscisic acid (ABA) during growth. Basic helix-loop-helix (bHLH) transcription factors (TFs) are hypothesized to participate in ABA signaling cascades, but their mechanistic role in SS regulation remains undefined. In this study, 20 differentially expressed BcbHLH genes were identified by transcriptomic profiling of ABA-induced hairy roots, with four MYC-family candidates (BcbHLH1-BcbHLH4) demonstrating ABA-responsive regulatory potential. ABA exposure (100 or 200 μmol/L, 24-72 h) induced dose-dependent SS reduction, while correlation analyses revealed coordinated expression between BcbHLH1-BcHMGR (r = 0.62) and BcbHLH4-BcBAS (r = 0.78), pinpointing these TFs as critical nodes in SS pathway modulation. Tissue-specific profiling showed predominant BcbHLH expression in stems and young leaves, with nuclear localization confirming their transcriptional regulatory organelles. BcbHLH3/4 exhibited transcriptional activation activity in the MYC_N domain, while molecular docking predicted 11th Arginine in the HLH domain as essential for G-box DNA binding. Collectively, our findings suggest that BcbHLH1-BcbHLH4 may serve as potential switches for fine-tuning ABA responsiveness in SS biosynthesis. Strategic manipulation of BcbHLH activity through genetic engineering approaches such as CRISPR-based editing or overexpression could alleviate ABA-mediated biosynthetic repression. Furthermore, precision engineering of the critical functional domain in BcbHLH could enhance promoter-binding activity to target genes and improve SS biosynthesis efficiency. These findings provide a reference framework for harnessing transcriptional regulators to optimize SS production in Bupleurum chinense DC.

Ginsenosides, the primary bioactive components in ginseng, offer various health benefits, including anti-inflammatory, anti-osteoporosis, and neuroprotective effects. For consistent product quality and better understanding of these effects, accurate quantification of ginsenosides is essential. Although liquid chromatography-mass spectrometry (LC/MS) can identify up to 200 ginsenosides, it is costly, complex, and requires specialized personnel. In contrast, liquid chromatography coupled with ultraviolet (UV) or evaporative light scattering detectors (ELSD) is more accessible but typically limited to quantifying no more than 24 ginsenosides. In this study, we developed an LC/UV-ELSD platform that enables the simultaneous quantification of 41 ginsenosides in a single run-38 quantified by UV and 3 by ELSD. The platform demonstrated excellent reproducibility (RSD: 0.341-2.653 %) and sensitivity, with detection limits as low as 0.073 µg/mL for UV and 5-10 µg/mL for ELSD. Application to ginseng samples showed total ginsenoside concentrations of 39.54 ± 10.72 mg/g in field-cultivated roots, 103.68 ± 14.41 mg/g in wild-simulated leaves, and 37.02 ± 5.52 mg/g in wild-simulated roots. Quantification results closely matched those from LC/MS analysis, with a difference of less than 10 %. Our LC/UV-ELSD platform offers a simple, cost-effective, and reliable solution for comprehensive ginsenoside analysis and is well suited for both research and industry use in quality control and functional evaluation of ginseng products.

Lipid mediators are a superfamily of bioactive molecules that are crucially involved in immune responses, regulating all stages of inflammation. Panax (P.) ginseng has pleiotropic pharmacological effects, including anti-cancer, anti-diabetic, and anti-inflammatory properties. Ginsenosides, unique triterpenoid glycosides from the plant's root, are proposed as active ingredients responsible for the immunomodulating potential of P.ginseng. Here, we comprehensively screened 23 ginsenosides for manipulating the lipid mediator network in various primary human innate immune cells. Several ginsenosides selectively inhibited 5-lipoxygenase (5-LOX)-mediated formation of pro-inflammatory leukotriene B4, but not of prostaglandins, in monocyte-derived macrophages and polymorphonuclear leukocytes by a unique irreversible mechanism. Structure-activity relationships revealed (i) higher anti-5-LOX activity of PPD-type ginsenosides, (ii) correlation with lipophilicity (R2 = 0.91), and (iii) eudysmic ratios favoring the 20S-epimers. Our findings highlight ginsenosides as immunomodulatory principles of P. ginseng and reveal abrogation of leukotriene formation rather than interference with prostaglandins as immediate anti-inflammatory mechanism.

Neopicrorhiza scrophulariiflora (Pennell) D.Y.Hong, an endangered perennial herb, is rich in triterpenes, iridoids, and phenolic compounds, which exhibit significant pharmacological effects. However, the molecular mechanisms of triterpenoid biosynthesis in N. scrophulariiflora remain unclear. Here, transcriptomic and metabolomic analyses were performed to investigate the triterpene content in different tissues and the expression patterns of key enzyme-encoding genes related to triterpenoid biosynthesis. We functionally characterized eight upstream oxidosqualene cyclases (OSCs) involved in triterpenoid biosynthesis, among which NsOSC2 is a bifunctional enzyme capable of catalyzing the conversion of 2,3-oxidosqualene to β-amyrin and α-amyrin. Additionally, an efficient regeneration system and a stable genetic transformation system were established for N. scrophulariiflora. These findings reveal key genes in triterpenoid biosynthesis, providing a theoretical foundation for the future production of key triterpenoids in N. scrophulariiflora through synthetic biology approaches.

Stropharia rugosoannulata is a widely distributed edible mushroom rich in nutrients and bioactive compounds with various pharmacological properties. This study explores the mechanism involved in color variation in S. rugosoannulata mushroom cap under different temperature conditions. Transcriptome analysis revealed the role of cytochrome P450 (CYP) gene family members and the flavonoid biosynthesis pathway in color development. The study found that under low-temperature conditions, the expression of key genes in the flavonoid synthesis pathway was upregulated in red varieties, potentially leading to an accumulation of flavonoids and a change in color. Color changes in yellow varieties were related to genes in the terpenoid synthesis pathway. Gene Set Enrichment Analysis (GSEA) highlighted the role of zeaxanthin epoxidase genes in carotenoid synthesis, affecting color formation and possessing photoprotective and antioxidant functions. Additionally, Weighted correlation network analysis, also known as weighted gene co-expression network analysis (WGCNA) analysis revealed the role of C2H2-type transcription factors in color regulation, which may directly or indirectly regulate the genes responsible for pigment synthesis, influencing mushroom color. These factors may directly or indirectly regulate the genes responsible for pigment synthesis, influencing the mushroom color. This research offers insights into the molecular mechanisms underlying color variation in S. rugosoannulata and establishes a foundation for developing varieties in different colors, which could enhance their market appeal and application value in the food industry.

Ginsenoside compound K (CK) exhibits valuable pharmacological activity and has potential applications in the development of antitumor and immunity-enhancing drugs. As a metabolite of ginsenosides in the gut, ginsenoside CK is generally considered a kind of non-natural ginsenoside that cannot be synthesized in Panax species. In this study, necessary genetic modules for ginsenoside CK biosynthesis were found in Panax species, more specifically, in Panax japonicas (P. japonicus) for the first time. Based on the new findings, RNA sequencing was conducted on P. japonicus cells, and two UDP-glycosyltransferases (UGTs), UGTPj3 and UGTPj20, involved in the biosynthesis of protopanaxadiol (PPD)-type ginsenosides were identified. UGTPj3 and UGTPj20 can convert propanaxanediol to ginsenosides Rh2 and CK, respectively. Further analyses showed that UGTPj20 exhibited a lower affinity for propanaxanediol, compared with UGTPj3. Therefore, propanaxanediol tended to be converted to ginsenoside Rh2 by UGTPj3, which led to the absence of ginsenoside CK in P. japonicus. Moreover, ginsenoside CK was successfully synthesized in P. japonicus cells with CYP716A53V2 and UGTPj3 RNA interference and UGTPj20 overexpression in this study. The titer of ginsenoside CK in the P. japonicus cell suspension culture reached 85 mg L-1. This study has achieved ginsenoside CK biosynthesis in Panax species for the first time by regulating the metabolic pathway without introducing any foreign genes. The findings of this study also show that the variety of saponins synthesized by Panax species may be far richer than expected.

The Araliaceae family has significant economic and medicinal value. However, the phylogenetic relationships and the expression patterns of key genes of the active triterpenoid substance within this family are still unclear. In this study, we employed comparative transcriptomics to analyze the transcriptomes of 19 species from 11 genera of Araliaceae, aiming to elucidate the evolutionary history of the family and the expression patterns of key genes in the ginsenoside biosynthesis pathway. Our results divide Araliaceae into two subfamilies: Aralioideae and Hydrocotyloideae. Aralioideae is further classified into three groups: the Aralia-Panax group, the Polyscias-Pseudopanax group, and the Asian Palmate group. PhyloNet analysis reveals that the common ancestor of Panax ginseng, Panax quinquefolius, and Panax japonicus was an allopolyploid, likely resulting from hybridization between Panax notoginseng and Panax pseudoginseng. Additionally, all Aralioideae species underwent the pg-β event, which may be critical for ginsenoside biosynthesis. We discovered that Panax species exhibit distinct expression patterns of key enzyme genes (β-AS, DDS, CYP450, UGTs) compared to other Araliaceae species. These enzyme genes show independent evolutionary lineages in gene trees, suggesting unique functional adaptations that enable Panax species to efficiently synthesize ginsenosides. This study provides a theoretical foundation for the conservation and utilization of Araliaceae germplasm resources.

Ginsenosides are a class of triterpenoids from the ginseng genus, with many medicinal properties. Traditionally, ginsenosides are extracted from ginseng plants to satisfy market demand; however, this approach requires substantial plant biomass and a lengthy six-year growth period before harvest. The advancement of synthetic biology allows the production of ginsenosides by engineered yeast. In this study, we combined our previously reported cultivation method with in situ extraction to enhance the production and exportation of intracellular ginsenosides by the engineered Saccharomyces cerevisiae. Remarkably, ginsenoside production reached as high as 3.4 g/L in a single shake flask, with almost 100% of ginsenosides in the organic phase. The "empty yeasts" were successfully reused 10 times in sequential cultivations. These findings are discussed in the context of cultivation intensification for natural product synthesis. Increasing the level of triterpenoid synthesis facilitates rapid development and supports the industrialization of this intriguing group of natural products.

Panax ginseng, renowned for its therapeutic properties, derives much of its medicinal value from ginsenosides, a group of bioactive triterpenoid saponins. The biosynthesis of ginsenosides is regulated by various mechanisms, including microRNAs (miRNAs), which play key roles in gene regulation. Recent studies have identified numerous miRNAs in P. ginseng and other plants, highlighting their potential to influence triterpenoid biosynthesis by targeting key genes in the pathway. This mini-review explores the current understanding of miRNA-mediated regulation in P. ginseng and discusses the potential for controlling ginsenoside production through miRNA manipulation. Although miRNA research in P. ginseng is still primitive, ongoing studies suggest its potential for promising applications in agriculture and medicine. Further functional studies on these miRNAs could provide valuable insights into optimizing ginsenoside biosynthesis and enhancing medicinal properties.

Ginsenosides, the principal active ingredients in ginseng, have anti-bacterial, anti-inflammatory, antioxidant, anticancer, osteogenic, cardioprotective, and neuroprotective properties. Oral diseases afflict about half of the world's population. Ginsenosides' multifunctional properties have led to substantial investigation into their potential to prevent and treat oral disorders. However, their low absorption and poor targeting limit their effectiveness.

This review summarizes the latest research progress on ginsenoside-based drug delivery systems and the potential of ginsenosides in preventing and treating oral diseases to provide a theoretical basis for clinical applications.

Using "ginsenoside", "drug delivery", "nanoparticles", "liposomes", "hydrogel", "oral disease", "toxicology", "pharmacology", "clinical translation" and combinations of these keywords in PubMed, Web of Science, and Science Direct. The search was conducted until December 2024.

The limitations of natural ginsenosides can be overcome by utilizing drug delivery systems to improve pharmacological activity, bioavailability and targeting. The multifunctional pharmacological activities of ginsenosides offer promising avenues for treating oral diseases. In addition, the susceptibility of the oral cavity to infection by pathogenic bacteria and the diluting effect of saliva pose significant challenges to treatment. The emergence of drug delivery marks a breakthrough in addressing these issues.

Ginsenoside-based drug delivery methods improve bioactivity, targeting, and reduce costs. This review emphasizes current advancements in ginsenosides within novel drug delivery systems, specifically on its potential in preventing and treating oral disorders. However, multiple well-designed clinical trials are needed to further evaluate the efficacy and safety of these drugs.

The current unavailability of efficient myocardial repair therapies constitutes a significant bottleneck in the clinical management of myocardial infarction (MI). Ginsenoside Rb1 (GRb1) has emerged as a compound with potential benefits in safeguarding myocardial cells and facilitating the regeneration of myocardial tissue. However, its efficacy in treating MI-related ischemic conditions is hampered by its low bioavailability and inadequate angiogenic properties. In this study, the therapeutic potential of GRb1 is enhanced by a mesoporous basic copper carbonate (BCC) microsphere due to its excellent drug delivery capability and steady angiogenic degradation products (copper ions, Cu2+). The cell experiments revealed that GRb1 and Cu2+ could generate synergistic impacts on anti-cardiomyocyte apoptosis and endothelial cell angiogenesis, while a mouse model of MI illustrated that GRb1 loaded BCC (BCC@GRb1) could significantly enhance cardiac function, diminish the area of infarction and myocardial hypertrophy, reduce cardiomyocyte apoptosis, and augment vascularization within myocardial tissue. This investigation is pioneering in demonstrating the beneficial outcomes of combining drugs with bioactive carriers in myocardial regeneration and introduces a novel, precisely engineered drug delivery system as a potential therapeutic strategy for ischemic heart disease.

Periodontitis is mainly caused by bacterial destruction of periodontal tissue in dental plaque. Commonly used antibiotic treatment has some shortcomings, such as incomplete sterilization, drug resistance, and local flora imbalance. Because of this, there is a need to identify safe and non-drug resistant health products with high antibacterial activity. Ginsenosides, the primary active component in ginseng, have been shown to be antibacterial. In this study, we investigated the inhibitory effects of ginsenosides on Porphyromonas gingivalis and Fusobacterium nucleatum, along with their structure-activity relationships and mechanisms of action. Our results show that total ginsenosides elicit a significant inhibitory effect on the growth of periodontal pathogens, with antibacterial effects from PPD-type saponins being greater than those from PPT-type saponins. Among different monomer saponins, Rd had the best antibacterial effect and inhibited the growth of periodontal pathogens at 250 μM. Mechanistic analyses indicated that total ginsenosides mainly function at inhibiting biofilm formation by reducing cell surface hydrophobicity and extracellular polysaccharide content. Our study provides the basis for development of new, plant-based treatment drugs against periodontal disease.

Pulmonary fibrosis (PF) is a slow and irreparable damage of the lung caused by the accumulation of scar tissue, which eventually results in organ dysfunction and fatality from gas exchange failure. One of the extensively studied inflammatory pathways in PF is the NF-κB signalling pathway, which is reportedly involved in epithelial-mesenchymal transition, myofibroblast differentiation, and other cellular processes. Additionally, studies have evidence that NF-κB signalling pathways can be employed as a potential target for developing therapeutic agents against PF. In the current scenario, FDA-approved drugs, nintedanib and pirfenidone, have been used for the treatment of PF with potential side effects. Recently, the usage of bioactive compounds has attracted attention in the treatment of PF. This review focuses on the involvement of the NF-κB signalling pathway in PF and the significance of phytocompounds in regulating the NF-κB pathway. Both the in vitro and in vivo studies reveal that NF-κB-targeted plant-based bioactive compounds significantly ameliorate the PF condition as well as improve the health condition. Databases such as Scopus, PubMed, and Web of Science were used to conduct literature surveys and compile data on all the bioactive compounds. In conclusion, the plant-derived bioactive compounds are potent enough to target the NF-κB with its biological properties, and this could be a highly effective therapeutic strategy for PF in the future.

Plant triterpenoids, a vast and diverse group of natural compounds derived from six isoprene units, exhibit an extensive array of structural diversity and remarkable biological activities. In this review, we update the recent research progress in the catalytic mechanisms underlying triterpene synthesis and summarize the current insights into the biosynthetic pathways and regulatory mechanisms of triterpenoids. We emphasize the biosynthesis of pharmacologically active triterpenoids and the role of triterpenoid synthesis in plant growth, development, defense mechanisms, and plant-microbe interactions. This insight review offers a comprehensive perspective on the applications and future avenues of triterpenoid research.

Wild-simulated ginseng (WSG, Panax ginseng C.A. Meyer) is one of the most valuable medicinal plants in the world. This study aimed to investigate the correlation between growth and ginsenoside content of WSG in two different cultivation environments: coniferous and mixed forests. The results showed that air temperature, soil moisture content, and solar radiation were higher in mixed forest than in coniferous forest. Regarding soil properties, electrical conductivity, organic matter, total nitrogen, exchangeable potassium, and magnesium were higher in mixed forest than in coniferous forest. However, exchangeable sodium was lower in mixed forest than in coniferous forest. The analysis of growth characteristics revealed that the number of leaflets was significantly higher in WSG cultivated in mixed forest than in WSG cultivated in coniferous forest, whereas rhizome length, root diameter, root weight, and dry weight were significantly higher in coniferous forest. In contrast, total ginsenoside content and the content of each ginsenoside were much higher in WSG cultivated in mixed forest than in WSG cultivated in coniferous forest. The growth of WSG showed significantly positive correlations with electrical conductivity, organic matter, total nitrogen, exchangeable cations (K+, Mg2+, Na+), and cation exchange capacity. The number of leaflets per stem showed significantly positive correlations with six ginsenosides, whereas petiole length showed significantly negative correlations with mRb1, mRc, and Rb1. In conclusion, growth characteristics of WSG were higher in coniferous forest, but ginsenoside contents were higher in mixed forest. These results might be helpful for establishing the most optimal growth model of WSG, which is affected by various environmental factors.

Colorectal cancer (CRC) poses a significant health burden worldwide and necessitates novel treatment approaches with fewer side effects than conventional chemotherapy. Many natural compounds have been tested as possible cancer treatments. Plants in the genus Panax have been widely studied due to their therapeutic potential for various diseases such as inflammatory disorders and cancers. Extracts from plants of genus Panax activate upstream signals, including those related to autophagy and the generation of reactive oxygen species, to induce intrinsic apoptosis in CRC cells. The root extract of Panax notoginseng (P. notoginseng) regulated the gut microbiota to enhance the T-cell-induced immune response against CRC. Protopanaxadiol (PPD)-type ginsenosides, especially Rh2, Rg3, Rb1, and Rb2, significantly reduced proliferation of CRC cells and tumor size in a xenograft mouse model, as well as targeting programmed death (PD)-1 to block the immune checkpoint of CRC cells. Moreover, modified nanocarriers with ginsenosides upregulated drug efficacy, showing that ginsenosides can also be utilized as drug carriers. An increasing body of studies has demonstrated the potential of the genus Panax in curing CRC. Ginsenosides are promising active compounds in the genus Panax, which can also support the activity of conventional cancer therapies.

Ginsenosides, the most active components in Panax ginseng, exhibit pharmacological and therapeutic properties but are limited by their low abundance. Jasmonates (JAs), a class of stress-induced phytohormones, are integral in modulating plant defense responses and the biosynthesis of secondary metabolites, including ginsenosides. Jasmonoyl-isoleucine (JA-Ile), the primary bioactive JA compound, is biosynthesized by JA-Ile synthase 1 (JAR1). In this study, we cloned the 1555 bp PgJAR1 gene from ginseng roots and analyzed its structure, enzyme activity, and expression pattern. The PgJAR1 protein encompasses all the hallmark elements characteristic of the GH3 family. It exhibits N/C-terminal domains analogous to ANL, three ATP/AMP-binding motifs, and distinct secondary structures: an N-terminal beta-barrel with beta-sheets and alpha-helices, and a C-terminal beta-sheet surrounded by alpha-helices, similarly to AtGH3.11/AtJAR1. The recombinant PgJAR1 enzyme expressed in Escherichia coli BL21 specifically catalyzed jasmonic acid (JA) to JA-Ile. PgJAR1 is predominantly expressed in leaves and is upregulated by MeJA treatment. Moderate transient overexpression of PgJAR1 promoted the biosynthesis of both JA-Ile and ginsenosides, highlighting the crucial role of PgJAR1 in JA-Ile biosynthesis and its positive impact on ginsenoside accumulation. Nevertheless, elevated JA-Ile levels can impede cellular growth, reducing ginsenoside production. Consequently, balancing JA-Ile biosynthesis through PgJAR1 expression is essential for optimizing ginseng cultivation and enhancing its medicinal properties. Modulating endogenous JA-Ile levels offers a strategy for increasing ginsenoside production in ginseng plants.

Global climate change threatens the production, growth, and sustainability of plants. Crop wild relatives (CWRs) offer a practical and sustainable solution to these climatic issues by boosting genetic diversity and crop resilience. Even though CWRs are wild relatives of domesticated plants, they are nevertheless mostly neglected. This review focuses on the possible application of CWRs, which are found in the United Arab Emirates (UAE) and are known for their abiotic stress tolerance and potential medicinal properties. In olden days, traditionally, CWRs has been used as medicine for various ailments as they are rich in phytochemical compounds. However, the medicinal potential of these wild plant species is decreasing at an alarming rate due to climate change stress factors. The medicinal potential of these native crop wild plant species must be investigated because they could be a useful asset in the healthcare sector. Research on pangenomics studies of certain CWRs is also highlighted in the review, which reveals genetic variability caused due to climate change stress factors and how these genetic variability changes affect the production of secondary metabolites that have potent medicinal value. This provides insights into developing personalized medicine, in which particular CWRs plant species can be chosen or modified to generate medicinal compounds. Despite their superior medicinal properties, many CWRs in the UAE are still not well understood. Finding the desired genes coding for the biosynthesis of specific phytochemicals or secondary metabolites may help us better understand how these substances are synthesized and how to increase their production for a range of treatments.

Patients with cancer undergoing cisplatin chemotherapy frequently experience cardiotoxic side effects that significantly affect their prognosis and survival rates. Our study found that Panax ginseng root extract exerted a significant protective effect against cisplatin-induced myocardial cell injury.

The present study aims to elucidate the underlying mechanisms by which the bioactive components of Panax ginseng mitigate cisplatin-induced cardiotoxicity (CIC).

In vitro, the candidate active components were screened by network pharmacological prediction and in neonatal rat ventricular myocytes (NRVMs), and their mechanisms of action were verified by transcriptome sequencing, western blotting, gene overexpression, immunoprecipitation, immunofluorescence, and cellular thermal shift assays. A C57BL/6 CIC mouse model was established to verify the protective effects of the candidate components and the in vivo mechanism of the candidate components.

Through network pharmacology prediction and cellular activity screening of ginseng root compounds, ginsenoside Rh2(S) (Rh2) was identified as a significant active component. Transcriptomic, in vitro, and in vivo experiments demonstrated that Rh2 can activate the Pak1/Limk1/cofilin phosphorylation pathway, thereby inactivating the actin-severing protein cofilin and protecting cardiomyocytes from cisplatin-induced actin depolymerization. Additionally, Rh2 suppressed the ROS/caspase-3/GSDME pathway to inhibit cisplatin-induced pyroptosis. Furthermore, co-immunoprecipitation and overexpression experiments confirmed that Rh2 activated the FGFR1/HRAS axis, thereby simultaneously regulating the two aforementioned pathways to combat CIC.

This study demonstrated for the first time that Rh2 is the main active component in Panax ginseng that maintains cytoskeletal homeostasis and inhibits pyroptosis by regulating the FGFR1/HRAS pathway to resist CIC. This study aimed to provide a theoretical basis for expanding the targets and pathways of CIC treatment, and for the development of related drugs.

Protein kinase dysregulation is a hallmark of many cancers, yet their tumorigenic mechanisms remain elusive despite 60 years of study. Since learning that their mechanism includes catalyzing phosphorylation of amino acids in protein substrates, researchers began devising their inhibition strategies. Initially, protein kinase inhibitors (PKIs) derived from natural products were employed despite high cytotoxicity risks. While synthetic PKIs proved less toxic, they face significant drug resistance challenges. This review examines the progress in understanding protein kinases' role in cancer, their classification and modes of action since their discovery. To illuminate the path towards less toxic yet highly effective kinase inhibitors, this study analyzes the synthesis and modification of all FDA-approved natural product derived kinase inhibitors (NPDKIs) as well as those that failed clinical trials. By providing insights into successful and unsuccessful approaches, this review also aims to advance medicinal chemistry strategies for developing more effective and safer PKIs, potentially improving cancer treatment outcomes.

PnNAC03 positively regulates saponin biosynthesis and lignin accumulation during secondary cell wall formation by directly binding to the promoters of key saponin and lignin biosynthetic genes. The NAC transcription factor family plays a crucial role in the regulation of secondary metabolites biosynthesis. Saponins are the major bioactive compounds for Panax notoginseng, which is a world-globally recognized medicinal plant and possesses multiple pharmacological activities. The secondary cell wall is essential for P.notoginseng growth and stress resistance. However, the role of NAC transcription factors in regulating both saponin biosynthesis and secondary cell wall formation remains largely unknown. In this study, we characterized an NAC transcription factor, PnNAC03, which is a nuclear-localized protein and functions as a transcriptional activator. Silencing of PnNAC03 with the RNAi method in P. notoginseng calli resulted in a significant reduction in the content of saponin and the expression of key saponin biosynthetic genes, including PnSS, PnSE, and PnDS. Additionally, PnNAC03 specifically bound to the promoters of these genes, thereby enhancing their expression. Overexpression of PnNAC03 in Arabidopsis thaliana led to the increase of secondary cell wall thickness and lignin content, as well as upregulation of the expression of AtPAL and AtC4H. RNAi-mediated silencing of PnNAC03 in P. notoginseng further confirmed its role in lignin biosynthesis, as lignin content and the expression levels of PnPAL and PnC4H were significantly reduced. Furthermore, PnNAC03 could directly bind to the promoters of PAL and C4H genes in both A. thaliana and P. notoginseng. Collectively, our results highlight the dual regulatory role of PnNAC03 in promoting both saponin biosynthesis and lignin accumulation, providing valuable insights for the molecular breeding of P. notoginseng.

UDP-glycosyltransferases (UGTs) contribute to catalyzing the glycosylation of numerous functional natural products and novel derivatives with improved bioactivities. UDP-glucose sterol glucosyltransferase (SGT) is normally involved in the synthesis of sterol glycosides in a variety of organisms. SGT was derived from Salinispora tropica CNB-440 and heterologously expressed in Escherichia coli BL21 (DE3). Novel 12-O-glucosylginsenoside Rh2 was identified using HPLC, high-resolution MS (HR-MS), and NMR analysis. The cell viability assay was performed on 12-O-glucosylginsenoside-treated AGS stomach cancer, HeLa cervical cancer, U87MG glioma, and B16F10 melanoma cell lines. Protein structure modeling, molecular docking, and dynamics simulations were performed using AutoDock 4.2 and GROMACS 2020.1 software. The SGT gene is comprised of 1284 nucleotides and codes for 427 amino acids. The 12-O-glucosylginsenoside Rh2 may be a potential anticancer agent due to its potent viability inhibition of cancer cells. Structural analysis showed critical perspectives into the intermolecular interactions, stability, and binding energetics of the enzyme-ligand complex, with outcomes complementing the experimental data, thereby deepening our understanding of the structural basis of SGT-mediated glycosylation and its functional implications. This report presents a novel ginsenoside, 12-O-glucosylginsenoside Rh2, utilizing reshuffled SGT derived from S. tropica, and provides a promising candidate for anticancer drug research and development.

American ginseng (Panax quinquefolius) is considered as a functional food and a medicinal plant, with its fruit containing valuable bioactive ingredients. However, limited knowledge is available regarding its antioxidant capacity, variation in bioactive components, and biosynthetic pathways at various growth stages. The present study examined the in vitro antioxidant capacity of the American ginseng fruit from Wendeng, Shandong at various growth stages, and conducted metabolomic as well as transcriptomic analyses to elucidate the accumulation patterns and biosynthesis of bioactive compounds. The results showed that antioxidant capacity, total flavonoid content (TFC), and total phenolic content (TPC) in fruits at early, middle, and late developmental stages were significantly higher than those in 4-year-old ginseng roots. Notably, fruits at the early developmental stage exhibited the highest antioxidant capacity, which initially declined and subsequently increased as the fruits continued to grow and develop. TFC and TPC were closely correlated with antioxidant capacity in fruits. Widely targeted metabolomics identified 1,094 metabolites with significant changes throughout fruit development, including 223 terpenoids, 164 phenolic acids, and 149 flavonoids. A total of 139 metabolites were closely associated with antioxidant activity in the American ginseng fruits. Furthermore, several genes, such as DFR, LDOX, F3H, CHI, DDS, CYP, UGT, BAHD, as well as MYB, bHLH, and NAC transcription factors (TFs) were identified to be potentially associated with the fruit flavonoids and ginsenosides biosynthesis and their corresponding regulatory networks. The findings provid valuable insights for enhancing the development and utilization of American ginseng fruits as functional foods as well as advancing their quality and breeding practices.

Ginsenosides R2 and F2 are key active components of Panax japonicus var. major which exhibit a wide range of pharmacological effects. However, few UDP-glycosyltransferases (UGTs) involved in Rh2 and F2 biosynthesis have been identified. In this study, 12 UGTs from Panax japonicus var. major were predicted and characterized. Among them, one UGT (PjvmUGT45) exhibited superior catalytic activities by catalyzing the C3 hydroxyl glycosylation of protopanaxadiol (PPD) and compound K to form Rh2 and F2, respectively. Especially, PjvmUGT45 showed certain substrate specificity and regional specificity at the C-3 sites of PPD-type ginsenosides. Site-directed mutagenesis showed that Gln334, His349, Ser354, and Asp373 were key residues for PjvmUGT45, and the K280A mutant highly improved its activity. Our results revealed the biosynthetic mechanism of ginsenosides in Panax japonicus var. major, providing a novel alternative UGT for ginsenoside Rh2 production by synthetic biological methods.

Saponins are responsible for the clinical effects of Panax notoginseng leaves, which are traditionally produced as the single herb resource of 'Qiye Shenan Pian' in Chinese patent medicine. In this study, the metabolic characteristics of PNLSs were explored in rat feces. PNLSs as well as their metabolites were analyzed by ultra-performance liquid chromatography tandem/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). Subsequently, seventy-five metabolites were tentatively identified in the control group mainly due to the deglycosylation and dehydration biopathways, but only twenty low yields were determined in the pseudo-germ-free (GF) group. Ginsenoside compound K was the predominant metabolite in the control group. The data presented that gut microbiota played a pivotal role in the metabolic kinetics of PNLSs.

Ginsenoside Rh2(S) is well-known for its therapeutic potential against diverse conditions, including some cancers, inflammation, and diabetes. The enzymatic activity of uridine diphosphate glycosyltransferase 51 (UGT51) from Saccharomyces cerevisiae plays a pivotal role in the glycosylation process between UDP-glucose (donor) and protopanaxadiol (acceptor), to form ginsenoside Rh2. However, the catalytic efficiency of the UGT51 has remained a challenging task. To this end, we employed site-directed mutagenesis on UGT51 to improve its catalytic efficiency for enhanced production of ginsenoside Rh2. The mutated structure, featuring four key mutations (E805A, S998A, R1031A, and L1032A), exhibited heightened stability, binding affinity, and active site accessibility for protopanaxadiol (PPD) compared to the wild type. Under in vitro conditions, three mutants (E805A, R1031A, and L1032A) demonstrated 10%, 58%, and 65% higher enzymatic activities compared to the wild strain. Notably, the double mutant R1031A/L1032A exhibited an 85% increase in activity. Employing a fed-batch technology with PPD as the substrate yielded a Rh2 production of 4.663 g/L. The molecular dynamics (MD) simulations were employed to investigate the movements and dynamic dynamics of UGT51 mutations and PPD complexes. The root mean square deviation (RMSD) analysis revealed substantial alterations in structural conformation, particularly in the R1031A/L1032A mutations, correlating with boosted catalytic efficiency. Furthermore, the root mean square fluctuation (RMSF) simulation study aligned with both the RMSD and the solvent-accessible surface area (SASA) analyses. The computationally guided site-directed mutagenesis approach holds promise for extending its application to the development of commercially significant enzymes.

This study investigates the protective effect of ginsenoside Rg1 against manganese (Mn)-induced hepatotoxicity, highlighting its role as a PPAR-γ activator and its impact on TLR4/MyD88/MAPK pathway. Manganese induces liver damage through mechanisms involving oxidative stress and inflammation. Rg1, a principal bioactive compound of ginseng, significantly alleviates Mn-induced liver injury. Rg1 markedly enhances the activities of SOD, GSH, and CAT, while reducing levels of MDA and ROS, indicating an improvement in antioxidant defense capacity. Furthermore, Rg1 decreases inflammatory markers iNOS, TNF-α, IL-6, IL-12 and NO levels, underscoring its strong anti-inflammatory effects. Importantly, as a PPAR-γ activator, Rg1 upregulates PPAR-γ expression, subsequently inhibiting TLR4/MyD88/MAPK pathway. Additionally, silencing of PPAR-γ diminishes the protective effects of Rg1, while overexpression of PPAR-γ enhances them. The findings conclude that Rg1 exerts significant hepatoprotective effects against manganese-induced damage by activating PPAR-γ and modulating TLR4/MyD88/MAPK pathway, positioning it as a promising candidate for the treatment of Mn-induced hepatotoxicity.

Rare dehydrated ginsenosides barely exist in natural ginseng plants. Herein, the confined microwave technique was utilized to transform the main ginsenosides of Panax notoginseng leaves (PNL) into dehydrated ginsenosides. The main microwave-treated products of dried PNL are dehydrated ginsenoside Rk1, Rg5, notoginsenoside SFt3, and SFt4. Comparatively, the main microwave-treated products of water preimmersed PNL are dehydrated ginsenoside Rk2, Rh3, notoginsenoside SFt3, and SFt4. The impacts of solvent, solid-liquid ratio, microwave temperature and duration on the yield of dehydrated ginsenosides were explored. Based on theoretical calculation, primary ginsenosides in water preimmersed PNL are more prone to deglycosylation at the C-20 site and dehydration elimination reactions at the side chain during microwave treatment. Moreover, reference compounds were used to verify ginsenoside transformation pathway, and the dehydrated ginsenosides were individually purified and identified. In short, this study elucidates novel approach for preparing rare Δ20(21)- and Δ20(22)-dehydrated protopanoxadiol ginsenosides.

Non-alcoholic fatty liver disease (NAFLD) is the major cause of chronic liver disease worldwide, with no universally recognized effective treatments currently available. In recent years, ginseng and its principal active components, such as ginsenosides, have shown potential protective effects in the treatment of these liver diseases. In NAFLD, studies have demonstrated that ginseng can improve hepatic lipid metabolism, reduce inflammatory responses, and inhibit oxidative stress and fibrosis, thereby attenuating the progression of NAFLD. Additionally, ginseng inhibits oxidative stress by scavenging free radicals and enhancing antioxidant enzyme activities, and it can impede fibrosis by interfering with the fibrotic signaling pathways. These combined effects contribute to attenuating the progression of NAFLD. These findings highlight the promise of ginseng as a potential therapeutic candidate for the treatment of NAFLD. However, despite the significant efficacy of ginseng in human NAFLD treatment, the number and quality of clinical studies remain limited, with a lack of large-scale, multicenter clinical trials to confirm these effects. Moreover, the pharmacokinetic properties of different ginsenosides, optimal therapeutic dosages, and the safety of long-term use require further investigation. This review summarizes the existing evidence on the mechanisms of action of ginseng and its active components in human NAFLD, assesses their potential as therapeutic options, and proposes future research directions to provide stronger scientific support for clinical application. Additionally, we performed a network pharmacology analysis of ginseng in relation to NAFLD to identify and investigate potential targets of ginseng in the treatment of NAFLD. This analysis aims to provide a theoretical foundation for the development of ginseng -based drugs for combating NAFLD.

Ginseng is considered as a beneficial herbal remedy and over recent years its efficacy and safety have been verified in clinical therapy. There are two typical species of ginseng including Asian and American ginseng. The varieties of both species have been applied for commercialized materials in different stages of processing from raw to processed products. Panax vietnamensis Ha et Grushv. (P. vietnamensis) belongs to Asian ginseng and has been utilized as effective herbal remedy. P. vietnamensis is believed to improve immune response, longevity and consequent health. There are more than 300 bioactive compounds have been isolated from P. vietnamensis and classified in various groups, such as ginsenosides, flavonoids, phenolics.... These biological activities consist of anti-tumor, anti-inflammatory, neu-roprotective and anti-stress, which are validated by in vitro and in vivo studies. In this review, we systematize the literatures about ethnopharmacology, major bioactive constituents, and toxicology of P. vietnamensis, which were certified by various studies. Furthermore, we also summarize the current method to micro-propagate and lists of extracting sources of bioactive compounds (root, leave, stem.) and the solvents deployed during extraction process. Therefore, this review would provide the firm-evidences and premise for the therapeutic potentials of P. vietnamensis in the future.

Glioblastoma is recognized as the most aggressive form of intracranial tumor, presenting significant challenges in treatment. Recent emphasis has been placed on the potential of traditional Chinese medicine (TCM) as an adjuvant treatment for cancer.

We employed a series of assays-including CCK8, EdU, Transwell, and neurosphere formation-to evaluate the impact of ginsenoside RK3 on the phenotype of GBM. The modulation of macrophage M2 polarization by ginsenoside RK3 was assessed through flow cytometry, immunohistochemistry, and Western blot analysis. Furthermore, we utilized sequencing analysis and network pharmacology to identify potential therapeutic targets.

Our findings reveal that ginsenoside RK3 not only inhibits the phenotype of glioblastoma cells but also suppresses tumor progression in vivo while attenuating macrophage M2 polarization within the tumor immune microenvironment. Notably, ginsenoside RK3 down-regulates PPARG expression in tumor cells, leading to decreased secretion of CCL2, which subsequently diminishes macrophage M2 polarization. Additionally, we demonstrated that combining ginsenoside RK3 with temozolomide significantly enhances the inhibition of glioblastoma's malignant characteristics and progression.

This study innovatively highlights the dual mechanism of ginsenoside RK3 in glioblastoma treatment: it impedes tumor progression by modulating the PPARG/CCL2 pathway and enhances the efficacy of temozolomide. Our research underscores the promising role of herbal medicine in the management of glioblastoma, paving the way for novel therapeutic strategies that integrate traditional approaches with conventional treatments.

Rare ginsenosides Rg3 and Rh2, which exhibit diverse pharmacological effects, are derivatives of protopanaxadiol (PPD). UDP-glycosyltransferases, such as the M315F variant of Bs-YjiC (Bs-YjiCm) from Bacillus subtilis and UGTPg29 from Panax ginseng, can efficiently convert PPD into Rh2 and Rh2 into Rg3, respectively. In the present study, the N178I mutation of Bs-YjiCm was introduced, resulting in an increase in Rh2 production. UDP-glycosyltransferase UGTPg29 was then engineered to improve its robustness through semi-rational design. The variant R91M/D184M/A287V/A342L, which indicated desirable stability and activity, was utilized in coupling with the N178I variant of Bs-YjiCm and sucrose synthase AtSuSy from Arabidopsis thaliana to set up a "one-pot" three-enzyme reaction for the biosynthesis of Rg3. The influential factors, including the ratio and concentration of UDP-glycosyltransferases, pH, and the concentrations of UDP, sucrose, and DMSO, were optimized. On this basis, a fed-batch strategy was adopted to achieve a Rg3 yield as high as 12.38 mM (9.72 g/L) with a final yield of 68.78% within 24 h. This work may provide promising UDP-glycosyltransferase candidates for ginsenoside biosynthesis.

Ginseng has multi-directional pharmacological properties. Some data suggest that ginseng can enhance physical endurance, which, in turn, leads to protection of the cardiovascular system. However, not all experiments are conclusive. For this reason, the main aim of this research was to perform a meta-analysis and review of studies published between the years 2013 and 2023 concerning the ginseng effect on physical performance in animal and human models. Medline, Pubmed, and ClinicalKey electronic databases were used to analyze data. The search strategy included the following criteria: ginseng and exercise; ginseng supplementation; and ginseng supplements. The results suggest that ginseng supplementation may have a positive effect on CK levels in animal studies. Similar observations were stated in relation to serum lactate and BUN. Furthermore, a human study showed a significant increase in exercise time to exhaustion and VO2 max after supplementation. The review of the literature and conducted meta-analysis identified that ginseng supplementation may have a positive effect on exercise endurance. Due to the fact that most of the current studies were based on animal models, further research on human models is needed to identify the most effective dosage or form of applied ginseng to be a supportive element in CVD management.

Panax notoginseng is an important Chinese medicinal plant. Saponins are the major bioactive secondary metabolites with a wide range of medicinal and commercial value in P. notoginseng, so it is crucial to develop environmentally friendly methods to increase their production. The symbiotic relationship between endophytic bacteria and host plants offers a sustainable approach to enhance secondary metabolite biosynthesis. In this study, it was reported that the co-cultivation of an endophytic bacterium Enterobacter cloacae PN7, isolated from P. notoginseng and its host plant could greatly promote saponin accumulation in the root of seedlings. After six days of PN7 treatment, the total saponin concentration reached 21.64 mg/g, representing a 2.01-fold increase over the control. Transcriptome sequencing revealed that PN7 induction upregulated key genes in the saponin biosynthetic pathway (including DXS, HMGR, PMK, DS, CYP450, and GTs), modulated 253 plant hormone signaling genes (such as those related to JA, ETH, and ABA), and affected 284 transcription factor genes and 47 ABC transporter genes. Co-expression network analysis identified DEGs related to plant hormone signaling, transcription factors, and ABC transporters in saponin biosynthesis and distribution. The results suggested that JA signaling, mediated by transcription factors, such as bHLH and MYBs, and its interaction with ETH, played crucial roles in saponin biosynthesis. Additionally, potential ABC transporter candidates involved in saponin transport were identified. This study highlights the role of endophytic bacteria in enhancing saponin production in P. notoginseng and opens avenues for further research on microbial-plant interactions in secondary metabolite production.

Depression, a widespread mental disorder, presents significant risks to both physical and mental health due to its high rates of recurrence and suicide. Currently, single-target antidepressants typically alleviate depressive symptoms or delay the progression of depression rather than cure it. Ginsenoside Rg1 is one of the main ginsenosides found in Panax ginseng roots. It improves depressive symptoms through various mechanisms, suggesting its potential as a treatment for depression.

We evaluated preclinical studies to comprehensively discuss the antidepressant mechanism of ginsenoside Rg1 and review its toxicity and medicinal value. Additionally, pharmacological network and molecular docking analyses were performed to further validate the antidepressant effects of ginsenoside Rg1.

The antidepressant mechanism of ginsenoside Rg1 may involve various pharmacological mechanisms and pathways, such as inhibiting neuroinflammation and over-activation of microglia, preserving nerve synapse structure, promoting neurogenesis, regulating monoamine neurotransmitter levels, inhibiting hyperfunction of the hypothalamic-pituitary-adrenal axis, and combatting antioxidative stress. Moreover, ginsenoside Rg1 preserves astrocyte gap junction function by regulating connexin43 protein biosynthesis and degradation, contributing to its antidepressant effect. Pharmacological network and molecular docking studies identified five targets (AKT1, STAT3, EGFR, PPARG, and HSP90AA1) as potential molecular regulatory sites of ginsenoside Rg1.

Ginsenoside Rg1 may exert its antidepressant effects via various pharmacological mechanisms. In addition, multicenter clinical case-control and molecular targeted studies are required to confirm both the clinical efficacy of ginsenoside Rg1 and its potential direct targets.

Rare ginsenosides (Rg3, Rh2, C-K, etc.) refer to a group of dammarane triterpenoids that exist in low natural abundance, mostly produced by deglycosylation or side chain modification via physicochemical processing or metabolic transformation in gut, and last but not least, exhibited potent biological activity comparing to the primary ginsenosides, which lead to a high concern in both the research and development of ginseng and ginsenoside-related nutraceutical and natural products. Nevertheless, a comprehensive review on these promising compounds is not available yet.

In this review, recent advances of Rare ginsenosides (RGs) were summarized dealing with the structurally diverse characteristics, traditional usage, drug discovery situation, clinical application, pharmacological effects and the underlying mechanisms, structure-activity relationship, toxicity, the stereochemistry properties, and production strategies.

A total of 144 RGs with diverse skeletons and bioactivities were isolated from Panax species. RGs acted as natural ligands on some specific receptors, such as bile acid receptors, steroid hormone receptors, and adenosine diphosphate (ADP) receptors. The RGs showed promising bioactivities including immunoregulatory and adaptogen-like effect, anti-aging effect, anti-tumor effect, as well as their effects on cardiovascular and cerebrovascular system, central nervous system, obesity and diabetes, and interaction with gut microbiota. Clinical trials indicated the potential of RGs, while high quality data remains inadequate, and no obvious side effects was found. The stereochemistry properties induced by deglycosylation at C (20) were also addressed including pharmacodynamics behaviors, together with the state-of-art analytical strategies for the identification of saponin stereoisomers. Finally, the batch preparation of targeted RGs by designated strategies including heating or acid/ alkaline-assisted processes, and enzymatic biotransformation and biosynthesis were discussed. Hopefully, the present review can provide more clues for the extensive understanding and future in-depth research and development of RGs, originated from the worldwide well recognized ginseng plants.

Panax species, particularly Panax ginseng, Panax quinquefolius, and Panax vietnamensis are renowned for their medicinal properties and economic value. Of these, the endemic P. vietnamensis species (native to Vietnam, Laos, and southern China) is currently receiving focused attention due to its special ginsenosides accumulation in comparison to the others. Recent advances in next-generation sequencing (NGS) technologies have accelerated the molecular genetic studies in this Panax species, providing deeper insights into the ginsenosides biosynthesis pathway as well as other aspects such as genetic diversity and molecular evolution. This work aims to systematically review all studies on the application of NGS in P. vietnamensis, particularly in whole-genome sequencing and transcriptome analysis. These key findings significantly contribute to identifying critical genes involved in ginsenosides biosynthesis, developing various DNA markers (such as SSR and SNP) for molecular genetic studies, and gaining insights into the species' molecular evolution. Based on these findings, future research can further expand to complete the full genomic database of this species and further investigate the underlying regulatory mechanisms of ginsenosides biosynthesis. These efforts will be crucial for enhancing the conservation, molecular breeding, and agricultural productivity of this valuable medicinal species.

Ginseng, a cornerstone of traditional herbal medicine in Asia, garnered significant attention for its therapeutic potential. Central to its pharmacological effects are ginsenosides, the primary active metabolites, many of which fall within the dammarane-type and share protopanaxadiol as a common precursor. Challenges in extracting protopanaxadiol and ginsenosides from ginseng arise due to their low concentrations in the roots. Emerging solutions involve leveraging microbial cell factories employing genetically engineered yeasts. Here, we optimized the fermentation conditions via the Design of Experiment, realizing 1.2 g/L protopanaxadiol in simple shake flask cultivations. Extrapolating the optimized setup to complex ginsenosides, like compound K, achieved 7.3-fold (0.22 g/L) titer improvements. Our adaptable fermentation conditions enable the production of high-value products, such as sustainable triterpenoids synthesis. Through synthetic biology, microbial engineering, and formulation studies, we pave the way for a scalable and sustainable production of bioactive compounds from ginseng.

Microfluidic-engineered hydrogel microspheres have emerged as a promising avenue for advancements in tissue engineering and regenerative medicine, particularly through the precise manipulation of fluids to achieve personalized composite biomaterials. In this study, we employed microfluidic technology to fabricate hydrogel microspheres (HMs) using Chinese herbal Bletilla striata polysaccharide (BSP) as the primary material. Concurrently, the natural active ingredient 20(S)-protopanaxadiol (PPD) was encapsulated within the HMs in the form of liposomes (PPD-Lipo), resulting in the formation of nanocomposite hydrogel microspheres (PPD-Lipo@HMs) intended for diabetic wound tissue repair. PPD-Lipo@HMs are characterized by the expansive specific surface area, adjustable mechanical properties, and exceptional biocompatibility. PPD-Lipo@HMs can stimulate the production of vascular endothelial factors, which in turn enhances the migration of endothelial cells, the creation of tubes, angiogenesis, and tissue repair. Moreover, the PPD-Lipo@HMs accumulation produces a microsphere scaffold that effectively covers damaged tissues, promoting the attachment, spread, and multiplication of fibroblast and endothelial cells. The polysaccharide material BSP within PPD-Lipo@HMs can modulate the immune microenvironment of the damaged tissue, reducing inflammation, encouraging re-epithelialization and granulation tissue formation, accelerating angiogenesis and collagen deposition, ultimately leading to tissue repair. The findings highlight the superior therapeutic efficacy of the microfluidic-engineered PPD-Lipo@HMs in addressing the complex challenges of diabetic wound tissue repair, thereby affirming the significant potential of microfluidic engineering technology in tissue repair applications.

Panax japonicus, a traditional medicinal plant from the Araliaceae family, produces bioactive triterpenes with health benefits. In Traditional Chinese Medicine, its roots have been used, but the chemical basis of its medicinal use is unclear, particularly regarding the metabolism and regulation of triterpene saponin biosynthesis. This study employed an integrative approach using Ultra Performance Liquid Chromatography (UPLC) and transcriptome analysis. Our UPLC analysis showed that ginsenoside Ro and chikusetsusaponin IVa were mainly detected in P. japonicus root. Subsequently, a comparative transcriptome analysis of four P. japonicus tissues (roots, leaves, flowers and fruits) was conducted using Illumina sequencing. As a result, 90,985 unigenes were functionally annotated from a total of 211,650 assembled non-redundant transcripts. Among these, 42,829 unigenes were annotated in NR database. Tissue-specific gene analysis revealed that roots had the highest number of specifically expressed unigenes (11,832). The majority of these unigenes were associated with metabolic processes. Additionally, tissue expression patterns analysis for three common transcription factor families indicated that WRKY family genes showed a significantly root-specific expression pattern, potentially playing a role in triterpene saponin biosynthesis. Notably, we investigated the expression profiles of genes related to the biosynthesis of triterpene saponins and found that four genes, ACCT, HMGS, HMGR and SS, encoding key enzymes in triterpene saponins biosynthesis pathway, were primarily expressed in the root. Overall, our study provides a set of P. japonicus tissue transcriptome data, which will aid in the discovery of triterpene saponin biosynthetic genes and offers valuable genetic information for this medical plant.