Search Results (226)

In the present work, the blackening process of Panax quinquefolius L. (PQ) was systematically investigated at temperatures of 70–90 °C, relative humidities (RHs) of 70–85%, and treatment times of 0–14 days. Ginsenoside compositions and transformation pathways were analyzed by high-performance liquid chromatography (HPLC) and liquid chromatography coupled with ion trap time-of-flight tandem mass spectrometry (LC-IT-TOF-MS/MS). The results demonstrated that blackening treatment significantly increased total saponin content from 2.72% to 5.73% after being treated at 80 °C and 70% RH for 12 days, accompanied by the highest conversion efficiencies for newly generated ginsenosides Rk1 (8.89 mg/g) and Rg5 (17.69 mg/g). Furthermore, compared with untreated PQ saponins (PQS), the blackened PQ saponins treated under optimal conditions (BPQS) exhibited superior 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) cation (ABTS⁺) radical scavenging activities, with IC₅₀ values of 0.2999 mg/mL and 0.2640 mg/mL, respectively, as well as stronger reducing power. Meanwhile, BPQS exhibited higher cytotoxicity toward HepG2 cells and effectively inhibited cell survival and proliferation by promoting the expression of apoptosis-related proteins, including caspase 3 and caspase 9. Our findings indicate that BPQS may be a functional ingredient suitable for use in dietary supplements and disease chemoprevention. Full article

Multidrug resistance (MDR), frequently mediated by overexpression of the P-glycoprotein (P-gp) efflux transporter, remains a major challenge in the treatment of leukemia by limiting intracellular accumulation of chemotherapeutic agents such as daunorubicin (DNR). This study evaluates the applicability of a microfluidic-based single-cell biochip to investigate the reversal effects of microgram-level ginsenosides on daunorubicin uptake in multidrug-resistant leukemia cells. Pure ginsenosides are difficult to obtain in bulk and are typically available only in milligram quantities, which restricts their evaluation using conventional MDR assays such as flow cytometry that require large cell populations and substantial amounts of compounds. To address this limitation, a microfluidic single-cell biochip (SCB) requiring microgram quantities of ginsenosides (<100 µg) and fewer than ten cells was employed. Intracellular DNR accumulation was measured in the CEM/VLB1000 leukemia cell line following treatment with DNR alone or in combination with ginsenoside Rg3-R, ginsenoside Rg3-S, 20(S)-protopanaxatriol (PPT), and 20(S)-protopanaxadiol (PPD), in order to compare their relative efficacy in enhancing drug accumulation. Although Rg3-R and Rg3-S share highly similar chemical structures and are glycosylated derivatives of the PPD aglycone, Rg3-S exhibited greater potency in increasing intracellular daunorubicin accumulation than Rg3-R, and both were more effective than PPD. These findings underscore the importance of ginsenoside stereochemistry modulating P-gp-associated drug resistance and demonstrate the utility of the SCB platform for quantifying daunorubicin accumulation in multidrug-resistant leukemia cells at single-cell resolution. Full article

The roots of Panax ginseng are well known for their bioactive properties, while its berries have recently attracted attention for their pharmacological potential. This study investigated whether fermentation with Lactiplantibacillus plantarum enhances the antioxidant properties of ginseng roots and berries and their protective effects against oxidative stress in vitro. Fermentation significantly increased total polyphenol, flavonoid, and saponin contents and promoted the conversion of major ginsenosides (ginsenoside Rg1, ginsenoside Rb1, and ginsenoside Rb2), which are relatively less bioavailable, into minor ginsenosides (ginsenoside Rh1, ginsenoside Rg2, and ginsenoside Rg3) with enhanced biological activity and bioavailability. Fermented extracts exhibited higher radical-scavenging activities in 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays than non-fermented extracts. In tert-butyl hydroperoxide (t-BHP)-stimulated Chang liver cells, fermented extracts reduced intracellular reactive oxygen species (ROS) generation, inhibited lipid peroxidation, restored the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, and enhanced antioxidant enzyme activities, including superoxide dismutase (SOD) and catalase (CAT). These results demonstrate that L. plantarum-mediated fermentation effectively enhances the antioxidant and cytoprotective potential of ginseng roots and berries, supporting their application as functional food ingredients. Full article

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, necessitating the development of novel multi-targeted therapeutic agents. This study investigates the anticancer effects of Panax notoginseng extract (PNE) against CRC using an integrative approach of network pharmacology and experimental validation. Phytochemical profiling via LC–MS identified major ginsenosides, including Rb1, Rg1, and Rd. Network pharmacology analysis revealed potential targets such as Bcl-xL, STAT3/CDK1, and IL-2, which are associated with apoptosis, cell cycle regulation, and immune modulation, respectively. Experimental results demonstrated that PNE significantly inhibited the proliferation of HCT 116 and HT-29 CRC cells, induced G0/G1 phase arrest by modulating CDK4/6 and p21/p27, and promoted apoptosis by regulating BCL2 family proteins. Furthermore, PNE treatment suppressed tumor growth in a CT26-bearing syngeneic mouse model. These findings highlight that PNE exerts potent anticancer effects through multi-pathway modulation, suggesting its potential as a therapeutic candidate for CRC. Full article

Background/Objectives: Alzheimer’s disease (AD) has an irreversible disease course, making early intervention a key measure to delay disease progression. However, existing therapies are limited by weak brain-targeted delivery efficiency due to the blood–brain barrier (BBB) and low bioavailability of drugs, making it difficult to address the complexity of AD’s pathological mechanisms. Methods: Addressing these limiting factors, this research aims to develop an early AD intervention formulation with “high targeting, high bioavailability, and high biosafety.” Based on the principle of drug synergistic effects, this study employed the reverse solvent method and optimized the combination ratio of Ginsenoside Rg3 and Naringenin (Nar) to design and prepare a self-assembling nano-delivery system (Rg3-Nar-NPs, GNN). The study utilized intranasal administration to bypass the BBB through the direct pathway between the nasal mucosa and central nervous system. Results: This approach enabled targeted accumulation of the drug in brain lesion areas, significantly reducing Aβ deposition, oxidative stress, and inflammatory factor surges caused by early AD, thereby improving cognitive dysfunction in mice. Moreover, GNN demonstrated superior biosafety and bioavailability compared to the individual components. Through transcriptomic analysis, the study elucidated for the first time that GNN can activate the OXT/ERK/Fos pathway to break the malignant cycle of ROS–neuroinflammation, inhibiting the amplification effect of early AD pathological damage. Conclusions: This research provides new molecular targets and drug options for multi-target synergistic intervention of early AD, showing potential as a candidate strategy for precise early AD intervention and laying theoretical and experimental foundations for subsequent clinical translation. Full article

This study investigated how harvest timing within the growing season and lactic acid bacterial fermentation influence the phytochemical composition and biological activities of mountain-cultivated ginseng sprouts (MCGS). Various nutritional and bioactive constituents were examined, and in vitro assays were conducted before and after lactic acid bacterial fermentation. Although all samples were derived from 5-year-old plants grown under the same cultivation conditions, differences in harvest timing within the same season may be associated with progressive environmental variation rather than plant age. Nevertheless, harvest timing exerted a relatively limited effect on overall metabolite variation, whereas fermentation significantly enhanced functional properties across all harvest stages. Fermentation increased total phenolic content (4.27 → 7.21 mg/g), total flavonoid content (0.47 → 1.38 mg/g), and Maillard reaction products (2.02 → 2.84 OD_420nm), contributing to enhanced antioxidant capacity and increased inhibitory activities against pancreatic lipase and α-glucosidase. Notably, the levels of bioactive ginsenosides Rg3 and compound K increased markedly after fermentation (0.67 → 1.62 mg/g and 0.68 → 3.37 mg/g, respectively), despite a decrease in total ginsenoside content, indicating selective bioconversion during fermentation. Overall, these findings suggest that fermentation serves as the primary driver of functional enhancement in MCGS, while harvest timing within the growing season may play a secondary modulatory role. Full article

Panax ginseng is a traditional Chinese herbal medicine. Ginsenosides, the main bioactive components responsible for the medicinal value of ginseng, are regulated by transcription factors. Among these regulatory factors, basic leucine zipper (bZIP) transcription factors play crucial roles in plant development and secondary metabolism. To verify that members of the bZIP gene family are involved in regulating ginsenoside biosynthesis and explore their potential mechanisms of action, a correlation analysis was first conducted in this study between the expression levels of PgbZIP genes and ginsenoside content. Additionally, the effects of single-nucleotide polymorphisms (SNPs) and Insertions/Deletions (InDels) on ginsenoside content were analyzed in this study. Through these analyses, PgbZIP48-3, a gene highly associated with ginsenoside biosynthesis, was identified. Subsequently, we systematically analyzed PgbZIP48-3, including its gene structure, protein properties, and phylogenetic relationships. To further verify the function of PgbZIP48-3, an overexpression vector was constructed. Positive ginseng hairy roots were obtained via Agrobacterium-mediated transformation of explants, and the ginsenoside content in these positive hairy roots was determined. The results showed that in the PgbZIP48-3 overexpression positive lines, the contents of ginsenosides Re, Rb2, Rb3, Rc, and Rd were significantly higher than those in the control group, whereas the contents of ginsenosides Rg1, Rf, and Rb1 were lower than those in the control group. Finally, by investigating the SNP/InDel data of PgbZIP48-3 in 346 accessions of a natural P. ginseng population and constructing a predicted interaction map between PgbZIP48-3 and key enzyme genes involved in ginsenoside synthesis, this study preliminarily revealed the potential molecular mechanism by which PgbZIP48-3 regulates ginsenoside biosynthesis from two dimensions: gene mutation and gene expression correlation. Meanwhile, this study provides genetic resources for the breeding of ginseng cultivars with high ginsenoside content. Full article

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, with limited therapeutic options and poor clinical outcomes. Mounting evidence suggests that targeting cancer-specific metabolic and redox adaptations represents a promising therapeutic strategy. Peroxiredoxin 1 (PRDX1), a key antioxidant enzyme that is frequently overexpressed in HCC, enables tumor cells to neutralize excessive reactive oxygen species (ROS), thereby sustaining survival and conferring therapeutic resistance. In this study, using human hepatocellular carcinoma HepG2 cells as an in vitro model, we identify ginsenoside Rg5 (Rg5) as a previously unrecognized small-molecule inhibitor of PRDX1. Structural and functional analyses demonstrate that Rg5 directly binds to the Asn145 residue of PRDX1, effectively suppressing its peroxidase activity. Mechanistically, this inhibition disrupts ROS detoxification in HepG2 cells, leading to mitochondrial ROS accumulation, activation of the intrinsic apoptotic pathway, and consequent HepG2 cell death. Additionally, Rg5 not only suppresses HepG2 cell survival but also acts synergistically with doxorubicin, a first-line chemotherapeutic agent, to markedly enhance antitumor efficacy and potentially mitigate chemoresistance. Collectively, these findings suggest that PRDX1 inhibition may represent a broadly exploitable vulnerability in liver cancer and establish Rg5 as a promising candidate for developing targeted and combinatorial therapies against HCC. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) lacks targeted therapies and has a poor prognosis. Wild ginseng (Panax ginseng) is traditionally valued for its medicinal properties, but its scarcity limits therapeutic application. Adventitious root culture technology provides a sustainable source of wild ginseng-derived bioactive compounds. This study investigated the anticancer effects of wild ginseng adventitious root extract (WGAR) on MDA-MB-231 TNBC cells and elucidated the underlying molecular mechanisms. Methods: WGAR was prepared from cultured adventitious roots of 100-year-old wild ginseng, and its chemical composition was analyzed by LC-MS/MS. Anticancer effects were evaluated using MTT assay, acridine orange/propidium iodide (AO/PI) staining, Matrigel invasion assay, Western blot analysis, and proteome profiler array. Molecular docking was performed to predict interactions between WGAR constituents and target proteins poly (ADP-ribose) polymerase (PARP)-1 and β-catenin. Results: LC-MS/MS analysis tentatively identified 17 compounds, including ginsenosides (Rg3, Rh1, Rf) and terpenoids (ursolic acid). WGAR reduced cell viability with an IC50 of 79 μg/mL at 48 h, inducing 51.2% cell death. WGAR activated the intrinsic apoptotic pathway through sequential caspase-9 and caspase-3 activation, followed by PARP cleavage, and was associated with changes in epithelial–mesenchymal transition (EMT)-related markers (reduced N-cadherin, Slug, and β-catenin) alongside decreased inhibitory Ser9 phosphorylation of GSK-3β. Proteome array analysis revealed suppression of ECM remodeling proteins (tenascin C, u-PA) and inflammatory mediators (IL-6, CXCL8). Molecular docking predicted that selected WGAR constituents, particularly terpenoid-type compounds, may potentially interact with PARP-1 and β-catenin; however, these in silico findings are hypothesis-generating and require experimental validation. Conclusions: WGAR exerts multi-target anticancer effects on TNBC cells through apoptosis induction and EMT suppression associated with modulation of GSK-3β/β-catenin signaling, suggesting its potential as a source of therapeutic agents for TNBC. Full article

There are a vast number of monoclonal antibodies (MAbs) against biological components; however, the number for natural products is less than 50. MAbs against ginsenosides, i.e., dammarane triterpene glycosides contained in ginseng, were prepared to develop an Eastern blotting method that can estimate the number of bound sugars and pharmacological activity. Meanwhile, as a method for producing ginsenoside Rg3, which is used as an anti-cancer drug, an affinity column for ginsenoside Rb1 was prepared to isolate the raw material ginsenoside Rb1 in a single step, and a method for obtaining ginsenoside Rg3 through fermentation was proposed. A unique MAb capable of detecting all solasodine glycosides contained in Solanum plants was created to prepare an affinity column capable of isolating solasodine glycosides from S. khasianum fruit in a single step. The single-chain variable fragment gene was induced from the MAb against solasodine glycoside and introduced into the hairy root system of S. khasianum, thereby increasing the solasodine glycoside content more than twofold. As a result, we recognized that this method can be used to breed plants with higher concentrations of plant secondary metabolites like solasodine glycosides. The above results collectively demonstrate that solasodine glycoside can be isolated from S. khasianum in high yields and that this compound enables the production of steroids in high yields through a one-step chemical reaction. Full article

Type 2 diabetes mellitus (T2DM) is a global health challenge characterized by insulin resistance and pancreatic β-cell dysfunction. While human umbilical cord mesenchymal stem cells (HUCMSCs) show therapeutic potential, their efficacy can be limited by the harsh in vivo microenvironment. 20(R)-Rg3, a ginsenoside with anti-inflammatory and antioxidant properties, may enhance HUCMSCs’ function, but the combined effect and mechanism of this “cell-molecule” strategy remain unclear. This study aimed to investigate the therapeutic effects and underlying mechanisms of a combination therapy using 20(R)-Rg3 and HUCMSCs in a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM mouse model. Diabetic mice were treated with PBS, HUCMSCs alone, or HUCMSCs pre-treated with 20(R)-Rg3. Fasting blood glucose and body weight were monitored. Insulin resistance was assessed via oral glucose tolerance tests (OGTTs) and intraperitoneal insulin tolerance tests (IPITTs). Serum biochemical parameters (lipids, liver and kidney function, insulin, C-peptide) were analyzed. Histopathological examination (H&E, PAS) of the liver, kidney, and pancreas was performed, alongside immunofluorescence for islet hormones. Transcriptomic analysis (RNA-seq) was conducted on HUCMSCs with or without 20(R)-Rg3 pretreatment to elucidate potential signaling pathways. Results demonstrated that the combination significantly reduced hyperglycemia and improved insulin sensitivity more effectively than HUCMSCs alone. It also ameliorated dyslipidemia, enhanced liver and kidney function, promoted glycogen synthesis, and facilitated pancreatic islet “regeneration”. Transcriptomic analysis indicated that the synergistic effect is primarily mediated through activation of the PI3K/Akt signaling pathway. These findings suggest that 20(R)-Rg3 potentiates the therapeutic efficacy of HUCMSCs, providing a promising combinatorial strategy for T2DM treatment. Full article

This study aimed to establish a high-performance liquid chromatography coupled with photodiode array detection (HPLC–PDA) method for the simultaneous quantification of 12 ginsenosides in red ginseng sprout (RGS) extract produced from smart-farm-cultivated ginseng sprouts and to evaluate its antioxidant activity as part of a quality assessment framework. Twelve representative major and heat-transformed minor ginsenosides were selected to capture the characteristic protopanaxadiol and protopanaxatriol profiles of RGS. Hydroponically cultivated ginseng sprouts were subjected to nine cycles of steaming and drying, followed by pressurized extraction. The total ginsenoside content was 31.54 mg/g, with Re and Rd as the predominant ginsenosides. The extract exhibited a high total phenolic content (7.98 mg gallic acid equivalents per gram) and flavonoid content (4.65 mg rutin equivalents per gram). Antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH IC₅₀ = 7.88 mg/mL) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS IC₅₀ = 24.81 mg/mL) radical scavenging assays. Pearson’s correlation analysis revealed strong positive correlations between ginsenosides (Re, Rg2, Rd, and Rh1), phenolic/flavonoid content, and antioxidant activity (R > 0.84, p < 0.01). This study provides an HPLC–PDA platform that achieves baseline-resolved, simultaneous quantification of 12 ginsenosides in RGS and links this compositional profile to antioxidant markers, supporting the quality control of smart-farm-derived ginseng products. Full article

This study elucidates the hepatoprotective mechanisms of heat-processed Gynostemma pentaphyllum (Thunb.) Makino saponins (HGyp) against APAP-induced liver injury using serum pharmacochemistry, metabolomics, and network pharmacology. HGyp significantly mitigated liver damage in mice, as confirmed by biochemical and histopathological analyses. UPLC-MS identified 38 bioactive compounds, including 16 prototype saponins and 11 metabolites. Network pharmacology and molecular docking revealed damulin A/B, gypenosides (L/LI/LVI/XLVI), and ginsenosides (Rg3/Rd) as key components targeting GRB2, FGF2, MMP2, STAT3, CASP3, and HSP90A. Western blotting confirmed the HGyp-mediated downregulation of hepatic HSP90A and STAT3. Metabolomics identified four critical pathways, PPAR, ferroptosis, and the inflammatory mediator regulation of TRP channels involved in hepatoprotection. HGyp exerts multi-target effects via anti-inflammatory activity, apoptosis, and metabolism, providing a framework for Chinese medicine and ethnomedicine research. Full article

Background: Given the need to optimize Panax notoginseng cultivation, screen high-quality germplasm, and clarify its insufficiently elucidated genetic–phenotype–quality associations (e.g., saponin accumulation), this study was conducted. Methods: Agronomic traits were measured, saponin accumulation was determined via high-performance liquid chromatography (HPLC), and comprehensive performance was evaluated through integrated cluster analysis and fuzzy membership function assessment; additionally, single-nucleotide polymorphism (SNP)-based genetic diversity analysis was conducted to explore the genetic basis of trait variations. Results: Agronomic traits exhibited coefficients of variation (CVs) of 2.95–18.12%, with primary root length showing the highest variability. Phenotypic cluster analysis divided the materials into three groups. Group I (“Miaoxiang No.1”, “Dianqi No.1”, “Miaoxiang Kangqi No.1”) was characterized by tall plants, sturdy stems, heavy roots, and long/large leaves. Saponin determination results revealed significant differences in notoginsenoside R1, ginsenoside Rb1, ginsenoside Re, ginsenoside Rd, and total saponins among cultivars (order: “Zijing” > “Dianqi No.1” > original cultivar > “Miaoxiang Kangqi No.1” > “Miaoxiang No.1” > “Miaoxiang No.2”), with “Zijing” having the highest total saponin accumulation (18.13%); no significant difference was observed in ginsenoside Rg1 accumulation. The GATK initially identified 16,329,600 SNPs, and 115,930 high-quality SNPs were retained after Samtools filtration. SNP-based Neighbor-joining (NJ) clustering grouped the cultivars into three categories, with the original cultivar clustered alone as one category. Through comprehensive evaluation, three superior germplasm lines (“Miaoxiang Kangqi No.1”, “Miaoxiang No.1”, “Dianqi No.1”) were identified. A significant negative correlation (p < 0.05) was found between compound leaf petiole length and saponin accumulation. Conclusions: This integrated analytical strategy clarifies the links between genetics, phenotype, and quality, providing a scientific foundation for P. notoginseng germplasm screening and facilitating future molecular breeding efforts. Full article

Ginsenosides, the primary bioactive components of Panax ginseng, have demonstrated significant immunomodulatory potential. While major ginsenosides have been extensively studied, rare ginsenosides produced through deglycosylation, heating, and steaming show enhanced biological activities with improved bioavailability. This review aimed to comprehensively analyze the immunomodulatory mechanisms, structure-activity relationships (SARs), therapeutic applications, and clinical translation strategies of five emerging rare ginsenosides: F1, Rg5, Rk1, Rh1, and Rg2. We conducted a comprehensive literature review examining the production methods, immunological effects, molecular mechanisms, pharmacokinetics, safety profiles, and clinical applications of these five compounds. Analysis focused on chemical structures, immune cell modulation, signaling pathways, disease model efficacy, and bioavailability enhancement strategies. Ginsenoside F1 uniquely demonstrated immunostimulatory effects, enhancing natural killer (NK) cell cytotoxicity and macrophage phagocytosis through mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) activation. Conversely, Rg5, Rk1, Rh1, and Rg2 exhibited anti-inflammatory properties via distinct mechanisms: Rg5 through Toll-like receptor 4 (TLR4)/NF-κB inhibition, Rk1 via triple pathway modulation (NF-κB, p38 MAPK, signal transducer and activator of transcription (STAT)), Rh1 by selective p38 MAPK and STAT1 inhibition, and Rg2 through modulation of both central nervous system (neuroinflammation) and peripheral organ systems. Structure-activity analysis revealed that sugar moiety positions critically determine immunological outcomes. Crucially, advanced delivery systems including nanostructured lipid carriers, self-microemulsifying systems, and specialized liposomes have overcome the major translational barrier of poor bioavailability, achieving up to 2.6-fold improvements and enabling clinical development. Safety assessments demonstrated favorable tolerability profiles across preclinical and clinical studies. These five rare ginsenosides represent promising immunomodulatory agents with distinct therapeutic applications. F1’s unique immunostimulatory properties position it for cancer immunotherapy, while the complementary anti-inflammatory mechanisms of Rg5, Rk1, Rh1, and Rg2 offer opportunities for precision medicine in inflammatory diseases. Advanced formulation technologies and optimized production methods now enable their significant clinical translation potential, providing promising therapeutic options for immune-related disorders pending further development. Full article