Search Results (710)

Cancer is currently one of the most significant health threats facing humanity in general. The clinical treatment of cancer is constrained by the current development of chemotherapy drug resistance, poor pharmacokinetics, off-target toxicity, and insufficient intratumoral accumulation. Although surgery combined with chemotherapy is now maturely used in clinical practice, the results are unsatisfactory, and the incidence and mortality of cancer continue to increase year by year with high side effects from treatment. Therefore, it is important to find more effective therapeutic targets against cancer. Alterations in the tumor microenvironment can lead to cellular gene mutations, which are an important cause of tumorigenesis, and therapeutic interventions targeting the tumor microenvironment have been one of the most interesting research areas in the oncology community in recent years. Ginseng is rich in antitumor-active ingredients and is used in the treatment of many cancer diseases. Ginsenoside is one of the main active components of ginseng. This paper reviews the antitumor mechanism of action of ginsenoside through regulating the tumor microenvironment, emphasizing the key role of ginsenoside in the tumor microenvironment and providing a new target and theoretical basis for ginsenoside in the treatment of cancer. Full article

For decades, the pharmacological identity of Panax ginseng has been primarily attributed to triterpenoid saponins known as ginsenosides. However, accumulating evidence indicates that ginseng also contains a structurally distinct lipid–protein complex, termed gintonin, enriched in lysophosphatidic acid (LPA) species. Unlike ginsenosides, which predominantly exert modulatory effects on membrane dynamics and intracellular kinase pathways, gintonin directly activates LPA G protein-coupled receptors (GPCRs), thereby inducing rapid phospholipase C (PLC) activation and intracellular Ca²⁺ mobilization. Biochemical analyses have identified major LPA species within the gintonin fraction, including C16:0, C18:0, and C18:1, stabilized within a proteinaceous matrix that may influence receptor engagement kinetics. Pharmacological studies demonstrate that gintonin preferentially activates LPA₁ and LPA₃ receptor subtypes, triggering downstream signaling cascades involving MAPK, PI3K/Akt, and Rho pathways. These receptor-mediated effects occur on a rapid temporal scale, distinguishing gintonin from the slower transcriptional and kinase-modulating actions of ginsenosides. In this review, we synthesize current evidence regarding the chemical architecture, receptor pharmacology, and signaling dynamics of gintonin and propose a dual signaling framework in which steroid-like saponins and lipid GPCR ligands represent complementary molecular axes within P. ginseng. Recognition of this layered signaling organization refines the molecular understanding of ginseng biology and highlights gintonin as a unique plant-derived GPCR ligand system. Full article

Lung cancer progression is regulated by multiple factors, including ferroptosis and gut microbiota-mediated butyrate metabolism. This study investigates the anti-tumor effects of ginsenoside Rh4 on lung cancer cells via ferroptosis mechanisms in vitro and in vivo. In vitro, ginsenoside Rh4 inhibited the proliferation of Lewis lung carcinoma (LLC) and A549 cells and triggered ferroptosis, effects that were suppressed by the ferroptosis inhibitor Ferrostatin-1 (Fer-1). In vivo, tumor-bearing mouse models were established and treated with 100 mg/kg ginsenoside Rh4 for 21 days. Tumor growth, ferroptosis markers, gut microbiota, and butyrate were analyzed, with in vitro validation of butyrate’s pathway effects. Ginsenoside Rh4 induced ferroptosis in LLC cells both in vitro and in vivo, inhibiting tumor growth. It promoted ferroptosis by disrupting iron homeostasis through elevated Fe²⁺ and transferrin receptor (TFRC), and impaired antioxidant defense via depletion of glutathione (GSH) and reduction in ferritin heavy chain 1 (FTH1), solute carrier family 40 member 1 (SLC40A1), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4). Additionally, ginsenoside Rh4 enhanced lipid peroxidation, indicated by increased lipid peroxides (LPO) and malondialdehyde (MDA). In vivo, it suppressed the KEAP1/NRF2/HO-1 pathway, reducing antioxidant enzyme activity. Gut microbiota modulation and butyrate production further amplified ferroptosis by activating transcription factor 3 (ATF3)-mediated GPX4 suppression. Ginsenoside Rh4 induces ferroptosis by inhibiting the KEAP1/NRF2/HO-1 pathway and remodeling the gut microbiota to increase butyrate levels, which synergistically enhance tumor cell ferroptosis sensitivity through ATF3 activation and suppression of GPX4. Full article

Background/Objectives: Adaptogens are plant-derived substances that enhance the body’s nonspecific resistance to physical, chemical, biological, and psychological stressors by normalizing physiological functions. This article discusses the molecular mechanisms of action of seven key plant adaptogens—Rhodiola rosea, Schisandra chinensis, Withania somnifera, Eleutherococcus senticosus, Panax ginseng, Ocimum tenuiflorum, and Bacopa monnieri—in the context of chronic stress and lifestyle-related diseases. Methods: A review of the scientific literature is performed, including preclinical in vitro and in vivo studies, randomized placebo-controlled clinical trials, and studies employing network pharmacology analyses, molecular docking, and genomic techniques such as gene expression profiling. The interactions of active constituents with signaling pathways, molecular targets, and synergistic mechanisms were analyzed based on publications from the years 2010–2025. Results: Adaptogens exhibit pleiotropic activity: they regulate the HPA axis (Hypothalamic–Pituitary–Adrenal axis); induce Hsp70/Hsp16 expression; modulate SAPK/JNK, FOXO, and NF-κB pathways; and demonstrate antioxidant and mitoprotective effects. Specific mechanisms include: salidroside from R. rosea activating PI3K/Akt; schizandrin B from S. chinensis stimulating Hsp70; withanolides from W. somnifera inhibiting PDE4D; ginsenosides from P. ginseng suppressing FKBP51; and bacosides from B. monnieri enhancing acetylcholine synthesis. Clinical studies confirm reductions in cortisol levels (14–30%), decreased fatigue, and improved cognitive function without adverse effects. Conclusions: Understanding the molecular mechanisms of adaptogens supports their application in integrative medicine for the treatment of stress-related disorders, depression, anxiety, and neurodegenerative diseases. Further clinical studies are needed to optimize dosages and standardize extracts. 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

Ginsenosides are the primary bioactive constituents of Panax ginseng, exhibiting multiple pharmacological activities, including neuroprotection, antitumor effects, anti-aging properties, and metabolic regulation. In this review, the molecular mechanisms of ginsenosides in treating neurodegenerative diseases, cancer, and metabolic disorders are summarized, and the current status of clinical translational research on ginsenosides in advanced gastric cancer, breast cancer, stroke, and diabetes is introduced, incorporating critical evidence regarding safety assessments and potential toxicity risks. In addition, recent advances in biotransformation and modern preparation technologies are reviewed. Innovative solutions, including nanodelivery systems, structural modifications, and AI-driven formulation design, are systematically discussed to address the current issues, such as low oral bioavailability and limited blood–brain barrier permeability. The future development of ginsenosides continues to face several critical challenges, including a scarcity of high-quality clinical evidence, an incomplete understanding of their mechanisms of action, a dearth of long-term safety data, and variations in quality between batches. 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

Ginseng (Panax ginseng C. A. Mey.), a traditional Chinese medicine, exhibits spleen-fortifying, anti-inflammatory, and anti-ulcerative colitis (UC) effects. Rice-fried ginseng (RFG), prepared by stir-frying with rice together, yields a marked enrichment of rare ginsenosides, which is hypothesized to enhance its anti-inflammatory and anti-UC effects. Therefore, in this study, the chemical compositions of RFG and sun-dried ginseng (SDG) were systematically compared using LC–MS combined with MS-DIAL, and their protective effects against UC were evaluated using lipopolysaccharide (LPS)-induced Caco-2 cells and a dextran sulfate sodium (DSS)-induced UC mouse model. Rice-frying markedly altered the chemical composition of ginseng, and a total of 64 major compounds were identified, of which 31 increased and 33 decreased after processing. These compositional changes were associated with enhanced anti-inflammatory and immunomodulatory effects of RFG. Consistently, RFG enhanced Caco-2 cell viability, decreased TNF-α, IL-1β, and IL-6, and increased ZO-1, occludin, claudin-1, and E-cadherin. In DSS-induced UC mice, RFG attenuated body weight loss, reduced DAI, increased colon length, and decreased the spleen index, accompanied by improved histopathology, reduced pro-inflammatory cytokine levels, and increased expression of tight-junction proteins (TJPs) in a dose-dependent manner. In addition, RFG ameliorated DSS-induced gut microbiota dysbiosis. Metabolomics and network pharmacology analyses highlighted disturbances in linoleic acid and arachidonic acid metabolism and emphasized the involvement of the PI3K–Akt and NF-κB signaling pathways. Western blotting demonstrated decreased phosphorylation of PI3K, Akt, IKKβ, and NF-κB after RFG intervention. Overall, compared with SDG, RFG showed stronger protective effects in vitro and in vivo, accompanied by improved inflammatory readouts, altered lipid-related metabolites and gut microbiota profiles, and reduced phosphorylation of PI3K, Akt, IKKβ, and NF-κB. 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

Background: Cultivation environments impose distinct abiotic and biotic stresses that act as primary drivers reshaping the metabolic profile and microbiome assembly of medicinal plants. This study investigates the impact of simulative habitat versus arched greenhouse cultivation on the synthesis of bioactive ginsenosides and the associated root microbiome structure in Panax ginseng. Methods: A combined metabolomics and microbiomics approach was applied to compare ginsenoside accumulation and rhizosphere microbial community composition under the two cultivation modes. Results: Ginseng from simulative habitat cultivation exhibited significantly higher ginsenoside content, particularly ginsenoside Re, compared to arched greenhouse cultivation, with this advantage being more pronounced in long-term cultivation. Microbiome profiling revealed that specific taxa, including Bradyrhizobium, were strongly enriched in simulative habitats and positively correlated with enhanced ginsenoside accumulation, suggesting a microbiome-mediated mechanism for metabolic plasticity. In contrast, arched greenhouse cultivation was associated with a more complex microbial structure characterized by increased negative interactions, which may compromise metabolic quality. Conclusions: These findings, utilizing multi-omics correlations, provide a theoretical basis for optimizing Panax ginseng quality through ecological cultivation strategies that leverage stress-responsive microbe–metabolite interactions. Full article

Cancer is one of the major lethal diseases in the world, and Western medicine treatments are often affected by side effects and drug resistance. Ginseng is a commonly used Chinese medicine in clinical practice, and Ginsenoside Rh1, an important active ingredient in ginseng, has received widespread attention in recent years for its remarkable anticancer potential. In this paper, we systematically described the inhibitory effects of Ginsenoside Rh1 and its molecular mechanism in hepatocellular carcinoma, gastric carcinoma, colon carcinoma, breast carcinoma, ovarian carcinoma, cervical carcinoma, lung carcinoma and glioma. Studies have shown that Rh1 can inhibit cancer cell proliferation, migration, and invasion, and induce apoptosis by regulating multiple signaling pathways. In addition, Rh1 can inhibit MMPs expression and regulate angiogenesis and the immune microenvironment to exert synergistic anticancer effects. Although the efficacy of Rh1 has been confirmed in vitro and animal studies, the clinical translation of Rh1 requires further exploration of its in vivo pharmacokinetics, long-term safety, and precise targets. In this paper, we systematically summarize the multiple anticancer mechanisms of Rh1 and look forward to the prospect of combining Rh1 with existing therapies to provide a theoretical basis for the development of novel anticancer drugs. Full article

Perennial ginseng (Panax ginseng) has long been valued for its medicinal properties. However, ginseng sprouts are gaining prominence as a versatile food source due to the high levels of bioactive compounds in their leaves and stems. To further enhance their functional value, this study investigated the effects of fermentation using lactic acid bacteria, specifically Lactobacillus and Enterococcus strains, on the antioxidant and anti-inflammatory potential of ginseng sprout extract (GSE). Chemical analyses revealed that fermentation significantly increased total phenolic content (TPC) and ginsenoside Rb₁ levels, which were associated with enhanced radical-scavenging activity and superoxide dismutase (SOD)-like activity. In lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, fermented GSE (FGSE) exhibited significantly greater anti-inflammatory effects than non-fermented GSE. This enhancement was evidenced by marked downregulation of pro-inflammatory mediators, including nitric oxide (NO) and prostaglandin E₂ (PGE₂), along with their corresponding enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Notably, the anti-inflammatory profile of FGSE was distinguished by its ability to suppress specific cytokines that were not significantly affected by GSE. Although both GSE and FGSE attenuated interleukin-1beta (IL-1β) and interleukin-6 (IL-6), only FGSE achieved statistically significant inhibition of tumor necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1). These findings indicate that fermentation is a critical process for surpassing the efficacy threshold of GSE against key inflammatory signals. Overall, the enrichment of bioactive metabolites during fermentation suggests that FGSE can serve as a potent functional ingredient for modulating inflammatory responses, with considerable potential for the development of advanced functional foods. 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