Search Results (94)

The genus Panax contains traditional herbs that have been widely used in traditional medicine. The active constituents, collectively known as ginsenosides, are well characterized in the most representative species, P. notoginseng. However, the major bioactive chemical constituents of P. stipuleanatus together with P. vietnamensis are relatively less studied. In this study, an untargeted metabolomic analysis was performed in P. notoginseng, P. stipuleanatus, and P. vietnamensis using root and leaf organs. Further metabolomic differences in P. stipuleanatus were compared with those of the two most prevalent species. The analysis results revealed tissue-specific qualitative and quantitative metabolic differences in each species. Several differentially accumulated metabolites were enriched in the biosynthesis of secondary metabolites, including the biosynthesis of ginsenosides I. The ginsenosides Rb1, Rf, Rg1, Rh1, Rh8, and notoginsenosides E, M, and N had a higher abundance level in the roots of both P. notoginseng and P. vietnamensis. In P. stipuleanatus, the accumulation of potentially important ginsenosides is mainly found in the leaf. In particular, the dammarane-type ginsenosides Rb3, Rb1, Mx, and F2 as well as the notoginsenosides A, Fe, Fa, Fd, L, and N were identified to have a higher accumulation in the leaf. The strong positive correlation network of different ginsenosides probably enhanced secondary metabolism in each species. The comparative analysis revealed a significant differential accumulation of metabolites in the leaves of both species. The various compounds of dammarane-type ginsenoside, such as Rb1, Rg1, Rg6, Rh8, Rh10, Rh14, and majoroside F2, had a significantly higher concentration level in the leaves of P. stipuleanatus. In addition, several notoginsenoside compounds such as A, R1, Fe, Fd, and Ft1 showed a higher abundance in the leaf. These results show that the abundance level of major ginsenosides is significant in P. stipuleanatus and provides an important platform to improve the ginsenoside quality of Panax species. Full article

Diabetes mellitus (DM) is a multifactorial metabolic disorder characterized by chronic hyperglycemia and systemic metabolic dysregulation. Although ginsenosides, the primary bioactive components of Panax ginseng Meyer, exhibit regulatory effects on glucose and lipid metabolism, their precise mechanisms and key targets in DM remain incompletely understood. Unlike previous studies focusing solely on crude extracts or individual ginsenosides, this study integrates network pharmacology, molecular docking, and molecular dynamics (MD) simulations to systematically elucidate the multi-target mechanisms of ginsenosides, with experimental validation using the ginsenoside derivative AD-1. Network pharmacology identified 134 potential targets, with protein–protein interaction (PPI) analysis revealing 25 core targets (such as NFKB1, HDAC1, ESR1, and EP300). Molecular docking and MD simulations showed that ginsenosides have stable binding conformations with these targets and exhibit excellent dynamic stability. Notably, in vivo experiments using AD-1 in streptozotocin-induced type 1 diabetic mice confirmed its therapeutic efficacy, significantly downregulating key diabetic markers (e.g., NFKB1 and HDAC1) in pancreatic tissues—a finding unreported in prior studies. This study not only revealed the multitarget pharmacological mechanism of ginsenosides but also highlighted the therapeutic potential of AD-1. These findings provide a foundation for further mechanistic studies and suggest new strategies for the application of novel ginsenoside derivatives in diabetes therapy. Full article

Objective: Study the mechanism of ginsenoside Rg₁ in ameliorating hyperuricemia (HUA) induced by high-purine diet. Methods: Rats were randomly divided into groups, and the HUA model was established by administering a high-purine diet containing potassium oxonate combined with yeast. After the experiment, blood was collected via cardiac puncture, and the organ indices of the rats were calculated. Serum biochemical markers including aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC), xanthine oxidase (XOD), creatinine (CREA), uric acid (UA), and blood urea nitrogen (BUN) were measured. Histopathological sections of the kidney and intestine were prepared. Western blot was used to assess the expression levels of intestinal occludin and zonula occludens-1 barrier proteins and key proteins in IL-17/NF-κB inflammatory pathways. After the experiment, fecal samples were collected from the rats. The gut microbiota of HUA-induced rats was analyzed via 16S rRNA sequencing, and the levels of short-chain fatty acids in the fecal samples were quantified using gas chromatography–mass spectrometry. Results: Ginsenoside Rg₁ significantly increased body weight and organ indexes as well as reduced serum levels of BUN, CREA, ALT, AST, XOD, and UA. Pathologic analysis showed that ginsenoside Rg₁ improved renal cell injury, glomerulosclerosis, and renal interstitial fibrosis while restoring intestinal barrier function. Ginsenoside Rg₁ down-regulated the expression of inflammatory proteins and up-regulated the levels of intestinal barrier proteins. The results of 16S rRNA sequencing showed that ginsenoside Rg₁ significantly increased the diversity index of gut microbiota and enhanced the number of beneficial bacteria in HUA rats. Short-chain fatty acids analysis demonstrated that ginsenoside Rg₁ markedly elevated the levels of acetate, propionate, butyrate, and valerate in HUA rats. Conclusions: Ginsenoside Rg₁ ameliorates and treats HUA by improving the composition of intestinal flora and inhibiting the IL-17/NF-κB signaling pathway to reduce inflammatory factors in the intestinal tract in HUA rats. Full article

American ginseng (Panax quinquefolius L.) is a rare and valuable plant utilized for medicinal and culinary purposes, with its geographic origin and cultivation significantly affecting its quality and efficacy. However, the metabolic differences between cultivated and wild American ginseng are not well understood. An accurate and reliable method for tracing the origin and evaluating the quality of American ginseng is therefore urgently required. This study introduces a UHPLC-Q/TOF-MS-based comparative metabolomics and machine learning strategy for the rapid identification of wild and cultivated American ginseng. Both principal component analysis and hierarchical cluster analysis revealed distinct metabolic phenotypes between wild and cultivated American ginseng. Furthermore, the integration of univariate and multivariate statistical analyses identified eight differential metabolites in the ESI⁺ mode and three in the ESI^- mode, including seven ginsenosides. A potential ginsenosides marker panel was used to construct five machine learning models to assist in diagnosing the metabolic phenotypes of American ginseng. The Random Forest model, based on the eight differential metabolites in the ESI⁺ mode, achieved a 100% classification rate in both test and validation sets for distinguishing between wild and cultivated American ginseng. This study highlights the feasibility and application of our artificial intelligence-driven comparative metabolomics strategy for cultivar identification and geographic tracing of American ginseng, offering new insights into the molecular basis of metabolic variation in cultivated American ginseng. Full article

Background: Heart failure (HF), the terminal stage of cardiovascular disease with high morbidity and mortality, remains poorly managed by current therapies. Ventricular remodeling in HF is fundamentally characterized by myocardial fibrosis. While ginsenoside Rb₁ has demonstrated anti-fibrotic effects in HF, the underlying mechanism remains unclear. Twist1, an upstream regulator of energy metabolism factors PGC-1α and PPARα, may attenuate fibrosis by preserving systemic energy homeostasis, suggesting its pivotal role in HF pathogenesis. This study explores ginsenoside Rb₁′s anti-HF mechanisms through the regulation of ginsenoside Rb₁ on these metabolic regulators. Methods: Sprague Dawley rats were subjected to a ligation of the left anterior descending coronary artery to induce an HF model, followed by ginsenoside Rb₁ treatment for 6 weeks. Therapeutic effects were evaluated through cardiac function assessment, myocardial histopathological staining (HE, Masson, immunofluorescence, immunohistochemistry), mitochondrial morphology observation (transmission electron microscopy), energy metabolism analysis (electron transport chain efficiency, mitochondrial membrane potential, ATP content), and protein expression profiling (Twist1, PGC-1α, PPARα, GLUT4, PPARγ). Additionally, H9c2 cells induced with endothelin-1 to model HF were employed as an in vitro model to further investigate ginsenoside Rb₁′s regulatory effects on the Twist1/PGC-1α/PPARα signaling pathway. Results: Ginsenoside Rb₁ can restore cardiac function in HF rats, improve mitochondrial function, alleviate energy metabolism disorders, and inhibit ventricular remodeling. By modulating the Twist1/PGC-1α/PPARα signaling pathway, ginsenoside Rb₁ suppressed the abnormal overexpression of Twist1 and maintained normal expression of downstream PGC-1α and PPARα. In vitro experiments further demonstrated that ginsenoside Rb₁ significantly inhibited Twist1 expression in H9c2 cardiomyocytes with HF while promoting PGC-1α and PPARα expression, thereby restoring myocardial energy metabolism and mitigating ventricular remodeling in HF. Conclusions: Ginsenoside Rb₁ can inhibit the upregulation of Twist1 and activate the expression of its downstream PGC-1α and PPARα expression, by modulating the Twist1/PGC-1α/PPARα signaling pathway, alleviating ventricular remodeling in HF patients and improving myocardial energy metabolism dysfunction. Twist1 may be a key target for the treatment of HF. This study not only elucidates the mechanism by which ginsenoside Rb₁ alleviates HF, but also provides new insights into the clinical treatment of HF. Full article

Atherosclerosis (AS) is emerging as a major global public health problem. Researchers are developing and implementing various anti-AS strategies. This study aimed to investigate gut microbiota and metabolite changes associated with elevated serum low-density lipoprotein cholesterol (LDL-c). Mice were divided into two equal groups: Group C (mice with gut microbiota from healthy subjects) and Group B (mice with gut microbiota from AS). At the end of the 8-week study, blood samples were collected for blood lipid analysis; rectal feces were collected for microbial 16S rRNA sequencing analysis and metabolomics analysis. Our results showed that the B group significantly increased serum lipid levels of LDL-c. However, no statistically significant differences were observed in the richness and diversity of the gut microbiota, but we observed an increase in the ratio of Firmicutes to Bacteroidetes and an increase in the abundance of Parabacteroides Goldstein. In addition, untargeted metabolomic analysis of fecal samples revealed 128 metabolites that were differentially expressed between groups C and B. Notably, group B was found to have significantly increased levels of metabolites involved in lipid metabolism pathways, such as estrogen glucuronide, ginsenoside f1, Pe (16:1e/14,15-epete), and prostaglandin E1. Those data highlight the importance of understanding AS from the gut microbiota perspective and establish a foundation for future research on AS. Full article

Conditions like diabetes mellitus (DM), cancer, infections, inflammation, cardiovascular diseases (CVDs), and gastrointestinal (GI) disorders continue to have a major global impact on mortality and morbidity. Medicinal plants have been used since ancient times in ethnomedicine (e.g., Ayurveda, Unani, Traditional Chinese Medicine, and European Traditional Medicine) for the treatment of a wide range of disorders. Plants are a rich source of diverse phytoconstituents with antidiabetic, anticancer, antimicrobial, antihypertensive, antioxidant, antihyperlipidemic, cardioprotective, immunomodulatory, and/or anti-inflammatory activities. This review focuses on the 35 plants most commonly reported for the treatment of these major disorders, with a particular emphasis on their traditional uses, phytoconstituent contents, pharmacological properties, and modes of action. Active phytomolecules with therapeutic potential include cucurbitane triterpenoids, diosgenin, and limonoids (azadiradione and gedunin), which exhibit antidiabetic properties, with cucurbitane triterpenoids specifically activating Glucose Transporter Type 4 (GLUT4) translocation. Capsaicin and curcumin demonstrate anticancer activity by deactivating NF-κB and arresting the cell cycle in the G2 phase. Antimicrobial activities have been observed for piperine, reserpine, berberine, dictamnine, chelerythrine, and allitridin, with the latter two triggering bacterial cell lysis. Quercetin, catechin, and genistein exhibit anti-inflammatory properties, with genistein specifically suppressing CD8+ cytotoxic T cell function. Ginsenoside Rg1 and ginsenoside Rg3 demonstrate potential for treating cardiovascular diseases, with ginsenoside Rg1 activating PPARα promoter, and the PI3K/Akt pathway. In contrast, ternatin, tannins, and quercitrin exhibit potential in gastrointestinal disorders, with quercitrin regulating arachidonic acid metabolism by suppressing cyclooxygenase (COX) and lipoxygenase activity. Further studies are warranted to fully investigate the clinical therapeutic benefits of these plants and their phytoconstituents, as well as to elucidate their underlying molecular mechanisms of action. Full article

Background: Alzheimer’s disease is a central nervous system degenerative disease closely related to age with a complex pathogenesis. As a natural medicinal plant, forest-grown ginseng (GSF) contains abundant ginsenosides and offers significant neuroprotective effects. Methods: In this study, we comprehensively investigated the effect of GSF on the cell viability of PC12 cells in an AD model alongside metabolic changes in the serum and brains of mice, combined with an efficacy evaluation of PC12 cells in vitro and UHPLC-MS-based metabolomics in vivo. The goal of this study is to clarify the potential mechanism of GSF in treating AD. Results: The PC12 cell results showed that GSF can promote the proliferation of PC12 cells, reduce the content of IL-8, increase the activity of SOD, and alleviate the inflammation and oxidative stress induced by Aβ25~35. The immunohistochemical results for the mouse brain tissue also showed that GSF could reduce the inflammatory response of mouse brain tissue by reducing the overexpression of IBa1. AD was alleviated by reducing Aβ protein deposition in the mouse brain tissue. An untargeted metabolomics analysis was performed using UHPLC-Q-Exactive MS and principal component analysis (PCA) to identify the differentially expressed metabolites in the serum and brain tissue of AD mice after treatment. Twenty and seventeen different metabolites were identified in the serum and brain tissue, respectively. The pathway enrichment analysis of differential metabolites showed that GSF could treat AD by up-regulating succinic acid semialdehyde, carbamoyl phosphate, Sphingosine 1-phosphate, L-cystathionine, 2-ketobutyric acid, Vanillylmandelic acid, and D-Ribose to regulate sphingomyelin metabolism, the synthesis and metabolism of neurotransmitters and precursors, and energy metabolism. Conclusions: GSF can reduce neuroinflammation and alleviate Alzheimer’s disease by regulating the metabolic disorders of amino acids, sphingolipids, unsaturated fatty acids, and arachidonic acid in mice serum and brain tissue metabolites. These results suggest a link between metabolite imbalance and AD, and reveal the basis for the mechanism of ginsenosides in AD treatment. Full article

MADS-box genes are essential for plant development and secondary metabolism. The majority of genes within a genome exist in a gene family, each with specific functions. Ginseng is an herb used in medicine for its potential health benefits. The MADS-Box gene family in Jilin ginseng has not been studied. This study investigated the evolution and structural and functional diversification of the PgMADS gene family using bioinformatics and analyzed gene expression through methyl jasmonate (MeJA) regulation. The results revealed that the evolution of the PgMADS gene family is diverged into ten clusters of a constructed phylogenetic tree, of which the SOC1 cluster is the most prevalent with a higher number of PgMADS genes. Despite their distinct evolutionary clusters, a significant number of members contains common conserved motifs. The PgMADS gene family was functionally differentiated into three primary functional categories, biological process, molecular function, and cellular component. Their expression is variable within a tissue, at a developmental stage, and in cultivars. Regardless of the diversity of the functions of PgMADS genes and evolution, their expression correlated and formed a co-expression gene network. Weighted gene co-expression network analyses identified hub genes that could be regulating ginsenoside biosynthesis. Interestingly, the family also is involved in MeJA regulation. These findings provide a valuable reference for future investigations on PgMADS genes. Full article

Ginsenoside Re was the major bioactive component found rich in Panax ginseng C. A. Meyer, which exerted excellent cardiovascular protection, anti-inflammatory, and anti-oxidation effects. The generation of unexpected degradation products (DPs) may influence the therapeutic effect of Re, or even bring toxic effects to patients. However, to date, only a few reports were available about the stability of Re. The present study aims to systematically investigate the degradation behaviors of Re under different stress conditions, including hydrolysis (acidic, basic, and neutral), oxidation, humidity, thermal, and photolytic (ultraviolet and visible light) conditions. A total of thirteen DPs were putatively identified, and among them, nine were discovered for the first time in our study. The results showed that Re was sensitive to exposure to acidic, basic, and oxidation conditions. It underwent a series of chemical degradation reactions, including deglycosylation, dehydration, addition, oxidation at the double bond, and isomerization under various stress conditions. Structural characterization of these DPs was carried out by UHPLC-DAD-CAD and LC-LTQ/Orbitrap. A plausible mechanism of their formation was proposed to support the structures of all DPs of Re. In silico toxicity prediction and metabolism behavior assessment were done by Derek Nexus and Meteor Nexus software. Re and DP-1 to DP-6 were predicted to possess potential skin irritation/corrosion toxicity. DP-11 and DP-12 bear the potential for carcinogenicity, mutagenicity, irritation, hepatotoxicity, and skin sensitization. The observation of these DPs updates our knowledge regarding the stability of Re, which provides valuable information for quality control and to choose suitable storage conditions. Full article

This study aimed to investigate the protective effects of ginsenoside Rg1 on high-altitude hypoxia-induced acute lung injury (ALI) and elucidated its molecular targets and related pathways, specifically its association with the fluid shear stress pathway. Using a combination of bioinformatics analysis and both in vivo and in vitro experiments, we assessed the role of ginsenoside Rg1 in mitigating physiological and biochemical disturbances induced by hypoxia. In the in vivo experiments, we measured arterial blood gas parameters, levels of inflammatory cells and cytokines, erythrocyte and platelet parameters, and conducted histological analysis in rats. The in vitro experiments utilized human pulmonary microvascular endothelial cells (HPMECs) and A549 cells to examine cell viability, intracellular reactive oxygen species (ROS) and Ca²⁺ levels, and mitochondrial function. The results of the in vivo experiments demonstrate that ginsenoside Rg1 significantly increased arterial blood oxygen partial pressure and saturation, elevated arterial blood glucose levels, and stabilized respiratory and metabolic functions in rats. It also reduced inflammatory cells and cytokines, such as tumor necrosis factor-α and interleukin-6, and improved erythrocyte and platelet abnormalities, supporting its protective role through the regulation of the fluid shear stress pathway. Histological and ultrastructural analyses revealed that Rg1 significantly protected lung tissue structure and organelles. In vitro experiments further confirmed that Rg1 improved cell viability in HPMEC and A549 cells under hypoxic conditions, decreased intracellular ROS and Ca²⁺ levels, and enhanced mitochondrial function. These findings collectively demonstrate that ginsenoside Rg1 exerts significant protective effects against high-altitude hypoxia-induced ALI by enhancing oxygen delivery and utilization, reducing inflammatory responses, and maintaining cellular metabolism and vascular function. Notably, the protective effects of Rg1 are closely associated with the regulation of the fluid shear stress pathway, suggesting its potential for treating high-altitude hypoxia-related diseases. Full article

Ginsenoside Ro, as one of the few oleanane-type ginsenosides, is well known for its unique molecular structure and biological activities. Currently, research on the biosynthesis of ginsenoside Ro is still in its early stages. Therefore, the establishment of a new ginsenoside Ro cell factory is of great significance for the in-depth development and utilization of genes related to ginsenoside Ro synthesis, as well as for the exploration of pathways to obtain ginsenoside Ro. In this study, we cloned endogenous constitutive promoters, terminators, and other genetic elements from S. cerevisiae BY4741. These elements were then sequentially assembled with the uridine diphosphate glucuronic acid transferase gene identified in our previously study (PgUGAT252645) and several other reported key enzyme genes, to construct DNA fragments used for integration into the genome of S. cerevisiae BY4741. By sequentially transferring these DNA fragments into chemically competent cells of engineering strains and conducting screening and target product detection, we successfully constructed an engineered S. cerevisiae strain (BY-Ro) for ginsenoside Ro biosynthesis using S. cerevisiae BY4741 as the host cell. Strain BY-Ro produced 253.32 μg/L of ginsenoside Ro under optimal fermentation conditions. According to subsequent measurements and calculations, this equates to 0.033 mg/g DCW, corresponding to approximately 31% of the ginsenoside Ro content found in plant samples. This study not only included a deeper investigation into the function of PgUGAT252645 but also provides a novel engineering platform for ginsenoside Ro biosynthesis. Full article

A prior report showed that soil previously planted with American ginseng (Panax quinquefolius) contained compound(s) which could reduce ginseng resistance to root infection by Ilyonectria mors-panacis, and this was not found in extracts from ginseng roots or soils not previously planted with ginseng. However, the origin of this ginseng-related factor in ginseng soils is unknown. An isolate of Pseudomonas plecoglossicida obtained from soil where P. quinquefolius had been harvested grew more in culture media when ginseng root extract was included, indicating the use of compounds in the extract as nutrients. Treatment with cell-free extracts from media containing ginseng root extracts where P. plecoglossicida had been cultured resulted in root lesions caused by I. mors-panacis being significantly larger than roots treated with fresh media containing root extract or with cell-free media inoculated with the same bacterial isolate without root extract. Levels of ginsenosides in the media decreased over time with incubation. Genome sequencing revealed that the bacterium had genes homologous to those reported for ginsenoside metabolism, which can release sugars for microbial growth. Thus, a ginseng soil bacterium, P. plecoglossicida, can create compound(s) suppressive to root rot resistance, similar to that found in soils previously planted with ginseng, indicating that the activity suppressing root rot resistance in soil previously planted with ginseng may be of microbial origin, utilizing compounds from ginseng roots. Full article

Ginseng (Panax ginseng C. A. Meyer) is an ancient and valuable Chinese herbal medicine, and ginsenoside, as the main active ingredient of ginseng, has received wide attention because of its various pharmacological active effects. Cytochrome P450 is the largest family of enzymes in plant metabolism and is involved in the biosynthesis of terpenoids, alkaloids, lipids, and other primary and secondary plant metabolites. It is significant to explore more PgCYP450 genes with unknown functions and reveal their roles in ginsenoside synthesis. In this study, based on the five PgCYP450 genes screened in the pre-laboratory, through the correlation analysis with the content of ginsenosides and the analysis of the interactions network of the key enzyme genes for ginsenoside synthesis, we screened out those highly correlated with ginsenosides, PgCYP309, as the target gene from among the five PgCYP450 genes. Methyl jasmonate-induced treatment of ginseng adventitious roots showed that the PgCYP309 gene responded to methyl jasmonate induction and was involved in the synthesis of ginsenosides. The PgCYP309 gene was cloned and the overexpression vector pBI121-PgCYP309 and the interference vector pART27-PgCYP309 were constructed. Transformation of ginseng adventitious roots by the Agrobacterium fermentum-mediated method and successful induction of transgenic ginseng hairy roots were achieved. The transformation rate of ginseng hairy roots with overexpression of the PgCYP309 gene was 22.7%, and the transformation rate of ginseng hairy roots with interference of the PgCYP309 gene was 40%. Analysis of ginseng saponin content and relative gene expression levels in positive ginseng hairy root asexual lines revealed a significant increase in PPD, PPT, and PPT-type monomeric saponins Re and Rg2. The relative expression levels of PgCYP309 and PgCYP716A53v2 genes were also significantly increased. PgCYP309 gene promotes the synthesis of ginsenosides, and it was preliminarily verified that PgCYP309 gene can promote the synthesis of dammarane-type ginsenosides. Full article

Ginsenosides, bioactive compounds from the genus Panax, have potential therapeutic effects on diverse ailments, including diabetes. Emerging evidence suggests their involvement in bone metabolism. The present review summarizes the current understanding of the effects of ginsenosides on osteoporosis, periodontal disease, and osteoarthritis. Their mechanisms of action include effects on osteoblasts, osteoclasts, periodontal ligament fibroblasts (PDLFs), and chondrocytes, which are pivotal in maintaining bone, periodontal tissue, and cartilage homeostasis. Ginsenosides may exert their beneficial effects by enhancing PDLF and osteoblast activity, suppressing osteoclast function, augmenting chondrocyte synthesis in the cartilage matrix, and mitigating connective tissue degradation. Moreover, they possess antioxidant, anti-inflammatory, antimicrobial, and anti-pyroptotic properties. Their efficacy in increasing bone density, ameliorating periodontitis, and alleviating osteoarthritis symptoms has been demonstrated in preclinical studies using animal models. In terms of their mechanism of action, ginsenosides modulate cellular differentiation, activity, and key signaling pathway molecules, such as mitogen-activated protein kinases (MAPKs), while also regulating various mediators. Furthermore, the symptomatic relief observed in animal models lends further credence to their therapeutic utility. However, to translate these preclinical findings into clinical practice, rigorous animal and clinical investigations are imperative to ascertain the safety, efficacy, and optimal dosing regimens in human subjects. Full article