Search Results (100)

Lung cancer remains a leading cause of cancer-related mortality worldwide, where conventional chemotherapy is often limited by severe side effects and drug resistance. Ginsenosides, the primary bioactive triterpenoid saponins isolated from the root of Panax ginseng C. A. Mey, have demonstrated potential in combating non-small-cell lung cancer (NSCLC). However, their efficacy under nutrient-deficient conditions remains unclear. This study aimed to investigate the effects of ginsenosides on the growth and death of lung cancer cells under low-nutrient conditions and to explore the underlying mechanisms. A549 cells were divided into two groups: one cultured in 10% serum and another under serum-free conditions, followed by treatment with ginsenosides CK, Rh2(S), and Rg3(S) for 24 h. Cell proliferation and apoptosis were evaluated using a CCK-8 assay, Calcein/PI fluorescence staining, Hoechst 33258 staining, and flow cytometry. Potential targets and signaling pathways of ginsenosides were predicted using network pharmacology and bioinformatics analyses. The mRNA expression of key genes was measured by qRT-PCR, and mitochondrial membrane potential was assessed using JC-1 staining. The results showed that ginsenosides induced dose-dependent apoptosis in serum-starved A549 cells. Bioinformatics analysis suggested the involvement of the PI3K/Akt/FoxO signaling pathway, which was supported by decreased Akt mRNA levels and increased FoxO mRNA expression. Furthermore, mRNA levels of Bim, Caspase-3, Caspase-8, and Caspase-9 were significantly upregulated, accompanied by a loss of mitochondrial membrane potential. These findings indicate that under serum deprivation, ginsenosides enhance apoptosis in A549 cells, likely through the regulation of the PI3K/Akt/FoxO pathway. Full article

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

Microbial fermentation technology has emerged as a pivotal approach for enhancing ginseng efficacy through the transformation of active ingredient molecular structures. This paper reviews the impact of microbial fermentation on the structure–activity relationship of ginseng bioactive compounds and advances in its application. Bibliometric analysis indicates that Panax species (Panax ginseng, Panax notoginseng) are primarily fermented using lactic acid bacteria and Aspergillus spp., with research predominantly focused on conversion efficiency to rare ginsenosides (Compound K, Rg3, and Rh2). Specifically, this review details the biotransformation pathways of these rare ginsenosides and the resultant bioactivity enhancements. Additionally, it summarizes the effects of other microorganisms, such as fungal fruiting bodies, on additional ginseng constituents like polysaccharides and polyphenols. Microbial fermentation has been successfully implemented in functional products, including ginseng vinegar, wine, and fermented milk. This review subsequently examines these applications, emphasizing fermentation’s potential to enhance product functionality. However, challenges remain in strain screening, process standardization, and analysis of multi-component synergistic mechanisms. In summary, this review synthesizes recent advancements in understanding the mechanisms of microbial fermentation on ginseng and its translational applications in functional foods and pharmaceuticals. Full article

Solid-state microbial fermentation (SSMF) has been established as an effective bioprocessing strategy to augment the nutritional value of plant-derived feed substrates while reducing anti-nutritional factors (ANFs). However, there have been limited studies on the effects of microbial solid-state fermentation on the nutritional value and potential functional components in cottonseed hulls. This study investigated the nutritional enhancement of cottonseed hulls through anaerobic solid-state fermentation mediated by Candida utilis CU-3, while exploring the functional potential of the fermented feed by analyzing fungal community dynamics and metabolite profiling. The laboratory-preserved free gossypol-degrading strain Candida utilis CU-3 was inoculated into unsterilized, crushed, and screened cottonseed hulls for solid-state fermentation at room temperature for 10 days. The results demonstrated that, compared to the control group, the experimental group achieved a 61.90% increase in free gossypol degradation rate, a 27.78% improvement in crude protein content, and a 5.07% reduction in crude fiber, while crude fat showed no significant difference. During the fermentation process, microbial diversity decreased, and Candida utilis CU-3 became the dominant species. Untargeted metabolomics data revealed that cottonseed hulls inoculated with Candida utilis CU-3 produced functional bioactive compounds during fermentation, including chrysin, myricetin (anti-inflammatory, antibacterial, and antioxidant activities), and ginsenoside Rh2 (anticancer, antibacterial, and neuroprotective properties). This study demonstrates that inoculating Candida utilis CU-3 into cottonseed hulls enhances their health-promoting potential through the biosynthesis of diverse functional metabolites, providing a theoretical foundation for improving the nutritional profile of cottonseed hull-fermented feed. Full article

Background/Objectives: Endoplasmic reticulum stress (ERS) contributes to hepatocyte inflammation, triggered by prolonged exposure to lipotoxicity, and promotes non-alcoholic fatty liver disease (NAFLD) progression by recruiting and activating hepatic macrophages, which accelerate fibrosis and exacerbate disease progression. Here, we aimed to evaluate the therapeutic potential of ginsenoside Rh2 (Rh2) in a cell model of NAFLD induced by the ERS inducer thapsigargin (THA). Methods: HepG2 cells were treated with THA to induce ERS and mimic NAFLD conditions. The effects of Rh2 on ERS, lipid accumulation, and apoptosis were assessed in HepG2 cells. Additionally, THP-1 cells were used to investigate macrophage activation upon exposure to conditioned medium (CM) from THA- and Rh2-treated HepG2 cells. Gene and protein expression of inflammatory and lipid synthesis markers were analyzed, as well as M1/M2 macrophage polarization markers. Results: Rh2 inhibited THA-induced apoptosis, ERS, and lipid accumulation in HepG2 cells. It also reduced the expression of lipid synthesis genes (SREBF1, FAS) and inflammatory markers (IL-6, IL-1β, TNF-α, MCP-1). CM from Rh2-treated HepG2 cells suppressed macrophage activation in THP-1 cells, decreased M1 polarization markers (CD80, CD86), and increased M2 markers (CD163, Arg1, MRC-1). Conclusions: These results suggest that Rh2 effectively suppresses inflammation and lipid storage in ERS-induced HepG2 cells while modulating the crosstalk between hepatocytes and macrophages. These findings underscore the potential of Rh2 as a promising therapeutic agent for the prevention and early intervention of NAFLD progression. Full article

Background/Objectives: Limitations of conventional treatments for esophageal cancer, which include poor solubility, drug resistance, and undesirable side effects, make it imperative to explore new therapeutic approaches to slow the progression of this disease. This study aims to assess the potential of terpene compounds as anti-cancer agents for esophageal squamous cell carcinoma (ESCC). Methods: This work was carried out following the PRISMA 2020 guidelines to ensure rigorous methodology. Results: A systematic analysis of 34 compounds revealed various mechanisms of action, such as induction of oxidative stress and modulation of apoptotic pathways. The results also show that several compounds, including (1Z,3R,4S,5E,7Z)-1-bromo-3,4,8-trichloro-7-(dichloromethyl)-3-methylocta-1,5,7-triene, dehydrocostus lactone, (3R,4S)-3,4,6,7-tetrachloro-3,7-dimethyl-octene-1-ene, acetyl-macrocalin B, jesridonin, longikaurin A, sphaerococcenol A, DS2, rabdocoestin B, ingenol C, ingenol-3,20-dibenzonate, JDA-202, xerophilusin B, betulinic acid, euphol, and (20S) ginsenoside Rh2, with IC₅₀s below 10 µM, show promising efficacy both in vitro and in vivo, sometimes surpassing certain conventional treatments. Conclusions: However, despite these encouraging prospects, limitations remain, notably a lack of in vivo data and clearly defined mechanisms of action for certain compounds. These challenges require further research to validate their safety and efficacy, facilitating their development as viable therapeutic options for ESCC. Full article

Soil, as the foundation for the survival of understory ginseng, directly impacts its growth and development. However, studies focusing on the role of soil in determining the quality of understory ginseng are limited. This study examines the relationship between quality and yield of 5-, 9-, and 17-year-old understory ginseng and their soil microbiota. The results indicate that with the increase in growth years, the overall biomass of understory ginseng generally shows an upward trend, while its quality slightly decreases at 9 years. Compared to the other two growth years, the soil from 9-year-old ginseng shows lower enzyme activity and pH and a higher abundance of pathogens. The 17 years soil has higher OM and AHN content, along with increased abundance of denitrifying and nitrogen-reducing bacteria. Correlation networks reveal that AK significantly influences ginsenoside content, while AP and AHN are more closely related to soil microorganisms. Compared with other types of ginsenosides, ginsenosides Rh2 and Rd are affected by a greater variety of soil microorganisms and chemical factors. As growth years increase, the changes in ginseng quality, soil nutrients, and soil microbiota do not follow a single linear trend; instead, there appears to be a bottleneck phase at certain intermediate stages. Full article

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. Full article

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. Full article

The effects of puffing on the ginsenoside composition as well as antioxidant and anti-inflammatory activities of ginseng berry were investigated to increase the utilization of ginseng berry. There was no significant difference in extraction yield between the control and puffed samples at all moisture contents and pressure conditions (p < 0.05). Major ginsenosides of ginseng berry (especially ginsenoside Re) were degraded through deglycosylation and dehydration by heat and pressure, and new minor ginsenosides (Rg3, F2, Rh2 and Rb2) were produced after puffing. Puffed ginseng berries showed higher total phenolic content (TPC), total flavonoid content (TFC) and Maillard reaction products (MRPs) than those of the control group, and these contents were increased as puffing pressure increased. In addition, higher antioxidant activities were observed in puffed ginseng berries compared to the controls, possibly due to the increase in TPC and MRPs. Antioxidant activity increased with increasing puffing pressure at all moisture contents. Nitric oxide (NO) production showed no significant inhibitory effect between control and puffed ginseng berries (p < 0.05). In the case of inflammatory cytokines, IL-6 had an inhibitory effect, but TNF-α had no inhibitory effect. Consequently, puffing showed a positive effect on the composition and the transformation of ginsenosides as well as the antioxidant activity of ginseng berries, suggesting that puffed ginseng berries can be used as a high value-added food material. Full article

γ-aminobutyric acid (GABA) and rare ginsenosides are good antioxidant and anti-fatigue active components that can be enriched via probiotic fermentation. In this study, ginseng and germinated brown rice were used as raw materials to produce six fermented purees using fermentation and non-fermentation technology. We tested the chemical composition of the purees and found that the content of GABA and rare ginsenoside (Rh₄, Rg₃, and CK) in the puree made of ginseng and germinated brown rice (FGB) increased significantly after fermentation. The antioxidant activity of the six purees was determined using cell-free experiments, and it was found that FGB had better ferric-ion-reducing antioxidant power (FRAP) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging rates, exhibiting better antioxidant effects. We then evaluated the antioxidant effect of FGB in HepG₂ cells induced by H₂O₂ and found that FGB can reduce the generation of reactive oxygen species (ROS) in HepG₂ cells and increase the membrane potential level, thereby improving oxidative damage in these cells. In vivo experiments also showed that FGB has good antioxidant and anti-fatigue activities, which can prolong the exhaustive swimming time of mice and reduce the accumulation of metabolites, and is accompanied by a corresponding increase in liver glycogen and muscle glycogen levels as well as superoxide dismutase and lactate dehydrogenase activities. Finally, we believe that the substances with good antioxidant and anti-fatigue activity found in FGB are derived from co-fermented enriched GABA and rare ginsenosides. Full article

Lipopolysaccharide (LPS) triggers a severe systemic inflammatory reaction in mammals, with the dimerization of TLR₄/MD-2 upon LPS stimulation serving as the pivotal mechanism in the transmission of inflammatory signals. Ginsenoside Rh₂ (G-Rh₂), one of the active constituents of red ginseng, exerts potent anti-inflammatory activity. However, whether G-Rh₂ can block the TLR₄ dimerization to exert anti-inflammatory effects remains unclear. Here, we first investigated the non-cytotoxic concentration of G-Rh₂ on RAW 264.7 cells, and detected the releases of pro-inflammatory cytokines in LPS-treated RAW 264.7 cells, and then uncovered the mechanisms involved in the anti-inflammatory activity of G-Rh₂ through flow cytometry, fluorescent membrane localization, Western blotting, co-immunoprecipitation (Co-IP), molecular docking and surface plasmon resonance (SPR) analysis in LPS-stimulated macrophages. Our results show that G-Rh₂ stimulation markedly inhibited the secretion of LPS-induced interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and nitric oxide (NO). Additionally, G-Rh₂ blocked the binding of LPS with the membrane of RAW 264.7 cells through direct interaction with TLR₄ and MD-2 proteins, leading to the disruption of the dimerization of TLR₄ and MD-2, followed by suppression of the TLR₄/NF-κB signaling pathway. Our results suggest that G-Rh₂ acts as a new inhibitor of TLR₄ dimerization and may serve as a promising therapeutic agent against inflammation. Full article

Black ginseng is the processed product of ginseng, and it has been found that the content and types of rare ginsenosides increased after processing. However, there is limited research on the ginsenoside differences between cultivated and forest ginseng before and after processing and among various plant parts. This study investigated the effects of processing on ginsenosides in different parts of cultivated and forest ginseng. After processing, the contents of Re, Rg1, S-Rg3, Rg5, R-Rh1, Rk1, Rk3, and F4 were significantly increased or decreased, the growth age of forest ginseng was not proportional to the content of ginsenosides, and the differences in ginsenoside content in ginseng from different cultivation methods were relatively small. Chemometric analysis identified processing biomarkers showing varying percentage changes in different parts. Network pharmacology predicted the EGFR/PI3K/Akt/mTOR pathway as a potential key pathway for the anti-cancer effect of black ginseng. Full article

Background: Recent studies have demonstrated that the migrasome, a newly functional extracellular vesicle, is potentially significant in the occurrence, progression, and diagnosis of cardiovascular diseases. Nonetheless, its diagnostic significance and biological mechanism in acute myocardial infarction (AMI) have yet to be fully explored. Methods: To remedy this gap, we employed an integrative machine learning (ML) framework composed of 113 ML combinations within five independent AMI cohorts to establish a predictive migrasome-related signature (MS). To further elucidate the biological mechanism underlying MS, we implemented single-cell RNA sequencing (scRNA-seq) of cardiac Cd45+ cells from AMI-induced mice. Ultimately, we conducted mendelian randomization (MR) and molecular docking to unveil the therapeutic effectiveness of MS. Results: MS demonstrated robust predictive performance and superior generalization, driven by the optimal combination of Stepglm and Lasso, on the expression of nine migrasome genes (BMP1, ITGB1, NDST1, TSPAN1, TSPAN18, TSPAN2, TSPAN4, TSPAN7, TSPAN9, and WNT8A). Notably, ITGB1 was found to be predominantly expressed in cardiac macrophages in AMI-induced mice, mechanically regulating macrophage transformation between anti-inflammatory and pro-inflammatory. Furthermore, we showed a positive causality between genetic predisposition towards ITGB1 expression and AMI risk, positioning it as a causative gene. Finally, we showed that ginsenoside Rh1, which interacts closely with ITGB1, could represent a novel therapeutic approach for repressing ITGB1. Conclusions: Our MS has implications in forecasting and curving AMI to inform future diagnostic and therapeutic strategies for AMI. Full article

Ginseng holds high medicinal and cosmetic value, with stem and leaf extracts garnering attention for their abundant bioactive ingredients. Meanwhile, fermentation can enhance the effectiveness of cosmetics. The aim of this study was to optimize ginseng fermentation to produce functional cosmetics. Ginseng stem and leaf extracts were fermented with five different strains of lactic acid bacteria. Using 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl radical (·OH), and superoxide anion (O₂^·−) scavenging activities as indicators, the fermentation process was optimized via response surface methodology. Finally, validation of the antioxidant activity of the optimized fermentation broth was performed using human skin cells (HaCaT and BJ cells). Based on the antioxidant potency composite comprehensive index, Lactiplantibacillus plantarum 1.140 was selected, and the optimized parameters were a fermentation time of 35.50 h, an inoculum size of 2.45%, and a temperature of 28.20 °C. Optimized fermentation boosted antioxidant activity: DPPH scavenging activity increased by 25.00%, ·OH by 94.00%, and O₂^·− by 73.00%. Only the rare ginsenoside Rg₅ showed a substantial rise in content among the 11 ginsenosides examined after fermentation. Furthermore, the flavonoid content and ·OH scavenging activity were significantly negatively correlated (r = −1.00, p < 0.05), while the Rh₁ content and O₂^·− scavenging activity were significantly positively correlated (r = 0.998, p < 0.05). Both the 0.06% (v/v) and 0.25% (v/v) concentrations of the optimized broth significantly promoted cell proliferation, and notable protective effects against oxidative damage were observed in HaCaT cells when the broth was at 0.06%. Collectively, we demonstrated that ginseng fermentation extract effectively eliminates free radicals, preventing and repairing cellular oxidative damage. This study has identified new options for the use of fermented ginseng in functional cosmetics. Full article