Beyond saponins: An integrated mass spectrometry strategy for profiling, spatial mapping, and rapid authentication of non-saponin constituents in Panax species.

Ginsenoside Rf, a rare protopanaxatriol-type ginsenoside derived from Panax ginseng, exhibits notable neuroprotective, anti-inflammatory, and antitumor properties. However, its low natural abundance has impeded large-scale production. Here, we reprogrammed the sugar donor specificity of PnUGT94Q39 from UDP-xylose to UDP-glucose, thereby enabling efficient ginsenoside Rf biosynthesis. A single-point mutation (I142T) within a flexible loop not only switched the sugar donor preference to UDP-glucose but also established efficient catalysis (kcat/Km, 1.18 μM-1·min-1) toward this donor. Coupling the I142T mutant with sucrose synthase GmSUS in Escherichia coli enabled the production of ginsenoside Rf (Rf) from ginsenoside Rh1 (Rh1) without exogenous UDP-glucose addition. Under optimized whole-cell biocatalysis conditions, a ginsenoside Rf titer of 1219.49 mg·L-1 was achieved, corresponding to a 97.26% conversion rate from Rh1 to Rf. Collectively, this work generated an efficient PnUGT94Q39-I142T mutant and established a sustainable, high-efficiency route for ginsenoside Rf production.

Ginsenoside Rg2 delays brain aging via inhibiting α-synuclein expression and promoting FoxO-Mediated neurogenesis in mice.

This study employed a multiplatform approach to compare in vivo exposure of saponins across six ginseng species, namely Panax ginseng (PG), red ginseng (RG), P. quinquefolius (PQ), P. notoginseng (PN), P. japonicus (PJ), and P. japonicus var. major (PJm). A strategy combining in-source fragmentation tracing with liquid chromatography/mass spectrometry was developed, facilitating characterization of 242 ginsenoside prototypes and metabolites. Tissue distribution patterns were visualized through desorption electrospray ionization mass spectrometry imaging (DESI-MSI), revealing significant accumulation of specific ginsenosides in the heart and kidney of rats. Pharmacokinetics of eight ginsenosides were analyzed by scheduled multiple reaction monitoring. PN had the highest exposure to ginsenosides Rb1 and Rd, while PQ showed high ginsenoside Rb1 but low ginsenoside Re levels. PJ and PJm had low exposure to oleanolic acid-type ginsenosides. This study elucidated the in vivo behavior of ginsenosides simultaneously across six ginseng species, providing insights for their quality control and functional application.

Ginseng polysaccharide (GPS), the principal bioactive component of Panax ginseng, has attracted considerable interest for its health-promoting properties, including immunomodulation, neuroprotection, antioxidative effects, and gut microbiota regulation. However, the intricate chemical structures, complex in vivo dynamics, and poorly defined structure-activity relationships limit its application in health products. This review summarizes recent progress in GPS research, covering extraction, isolation, purification, structural characterization, and bioactivities. Furthermore, it elucidates the in vivo fate of GPS, including gut microbiota-mediated degradation, intestinal uptake, and tracking techniques, as well as GPS-based delivery systems and structural modifications to enhance bioavailability. We also discuss its potential in functional food development and outline future perspectives, including structure-activity relationships, microbial metabolism networks, and delivery challenges. This review aims to provide a solid theoretical foundation for the further utilization of GPS as a promising natural macromolecule for health applications.

Panax ginseng contains bioactive compounds called ginsenosides, which have become the subject of many studies investigating their anticancer actions. Ginsenosides act by modulating epigenetic processes, as aberrant functioning of the epigenome through abnormal methylation of DNA, modification of histones or expression of miRNA represents an important mechanism regulating the initiation and progression of cancer. Specifically, ginsenosides act through pathological pathways to inhibit tumor development by acting on the key regulators of epigenetic processes, such as HDACs or DNMTs, to restore normal expression of genes in cancer cells. Ginsenosides such as Rg3, Rh2, and compound K inhibit the activity of HDACs, thereby increasing acetylation of histones and promoting re-expression of tumor suppressor genes via this mechanism. In addition, ginsenosides regulate the activities of DNMTs, promoting the demethylation of the hypermethylated promoter regions, thereby reactivating genes that would otherwise remain silenced. Ginsenosides also modulate cancer-associated miRNA profiles, influencing cellular signaling pathways involved in proliferation, apoptosis, metastasis, and angiogenesis. Thus, through the regulation of miRNA networks, ginsenosides inhibit oncogenic signaling pathways and re-establish cellular homeostasis. In summary, ginsenosides provide an epigenetically multi-targeted strategy for treating cancer and provide a means of inhibiting tumor formation with fewer side effects than traditional chemotherapy. Thus, ongoing studies (preclinical and clinical) are needed to understand the mechanisms by which ginsenosides provide their anticancer action and to further define their clinical utility in cancer treatment.

In the originally published article [1], a phrase was unclear, which may have affected readability. This has now been revised to improve clarity and ensure that the intended meaning is accurately conveyed. The corrections do not affect the results, interpretations, or conclusions of the article. The original article can be found online at: https://www.eurekaselect.com/article/138842 Details of the error and its correction are provided below: ORIGINAL: Abstract: Treatment of hepatic diseases presents a significant challenge due to their diverse nature. Ginsenosides, bioactive compounds derived from the root of Panax ginseng and widely used in traditional Chinese medicine, offer multifaceted protection to various organs in the body. Their versatile effects, including antioxidant, anti-inflammatory, anti-apoptotic and more, make them a promising approach for addressing hepatic disorders. This review explores the intricate molecular mechanisms and properties of ginsenosides in the prevention and treatment of liver ailments, from mild conditions to severe damage and liver fibrosis. Given the increasing prevalence of hepatic disorders, this article sheds light on the significant pharmaceutical potential of ginsenosides in the realm of hepatic disease management. CORRECTED: Abstract: Treatment of hepatic diseases presents a significant challenge due to their diverse nature. Ginsenosides, bioactive compounds derived from the root of Panax ginseng and widely used in traditional Chinese medicine, offer multifaceted protection to various organs in the body. Their versatile effects, including antioxidant, anti-inflammatory, anti-apoptotic and more, make them a promising approach for addressing hepatic disorders. This review explores the intricate molecular mechanisms and properties of ginsenosides in the prevention and treatment of liver diseases, from mild conditions to severe damage and liver fibrosis. Given the increasing prevalence of hepatic disorders, this article sheds light on the significant pharmaceutical potential of ginsenosides in the realm of hepatic disease management. ORIGINAL: Ginsenosides refer to a collection of bioactive substances discovered in the root of Panax ginseng, a medicinal plant that has been employed in traditional Chinese medicine for many centuries [8]. The medicinal properties of ginseng have been extensively documented in the fields of the central nervous, cardiovascular, endocrine, and immune systems. Furthermore, it exhibits anti-cancer, anti-stress, and antioxidant properties [9, 10]. Even the protective effects of ginseng against coronavirus disease 2019 (COVID-19) have been recently reported [11]. The positive impacts of ginseng can be credited to its diverse array of pharmacologically active constituents; however, the majority of its pharmacological benefits are linked to ginsenosides [12]. Studies have extensively explored the hepatoprotective properties of ginsenosides, ranging from mild to severe liver damage with various etiologies and liver fibrosis. In this review, we provide a summary of the present knowledge and recent advancements regarding the effects of ginsenosides in mitigating various liver ailments. CORRECTED: Ginsenosides refer to a collection of bioactive substances discovered in the root of Panax ginseng, a medicinal plant that has been employed in traditional Chinese medicine for many centuries [8]. The medicinal properties of ginseng have been extensively documented in the fields of the central nervous, cardiovascular, endocrine, and immune systems. Furthermore, it exhibits anti-cancer, anti-stress, and antioxidant properties [9, 10]. Even the protective effects of ginseng against coronavirus disease 2019 (COVID-19) have been recently reported [11]. The positive impacts of ginseng can be credited to its diverse array of pharmacologically active constituents; however, the majority of its pharmacological benefits are linked to ginsenosides [12]. Studies have extensively explored the hepatoprotective properties of ginsenosides, ranging from mild to severe liver damage with various etiologies and liver fibrosis. In this review, we provide a summary of the present knowledge and recent advancements regarding the effects of ginsenosides in mitigating various liver diseases. The publishers apologize for any inconvenience caused.

Ischemic stroke is a leading cause of death and disability, yet effective pharmacological interventions remain limited. Ginsenoside Rb1, a principal bioactive compound of Panax ginseng, has demonstrated neuroprotective activity, but its metabolic mechanisms remain incompletely defined. Here, we combined lipid metabolomics with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to investigate the spatially resolved metabolic effects of Rb1 in a rat model of cerebral ischemia/reperfusion injury. Rb1 treatment significantly reduced infarct volume and improved neurological outcomes. Metabolomic profiling revealed that Rb1 reversed ischemia-induced disturbances in the glycerophospholipid and amino acid metabolism, while MSI demonstrated recovery of phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine distributions in the ischemic cortex. These metabolic improvements were strongly correlated with reduced levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and oxidative stress marker malondialdehyde, along with increased superoxide dismutase activity. Rb1 also preserved blood-brain barrier integrity by enhancing the expression of tight-junction proteins ZO-1 and Occludin. Together, these findings indicate that Rb1 confers neuroprotection through metabolic reprogramming linked to anti-inflammatory and antioxidant actions, and they highlight the value of integrating metabolomics with MSI to elucidate spatially defined drug mechanisms in the brain.

The orexinergic crossroads: Bidirectional links between sleep-wake disturbances and the pathogenesis of Alzheimer's disease in the aging brain.

Arsenic-induced nephrotoxicity, characterized by inflammation and fibrosis, represents a critical yet inadequately addressed health concern. This study investigated the potential of ginsenoside Rg1, a bioactive component from Panax ginseng, to counteract arsenic-triggered renal impairment and explored the involved molecular pathways. Male C57BL/6J mice were exposed to arsenic via drinking water for 12 weeks, with a subset receiving concomitant Rg1 intervention. Assessments included renal function biomarkers, histopathological evaluation of inflammation and fibrosis, and analysis of epithelial-mesenchymal transition (EMT) markers. Our findings indicated that Rg1 treatment significantly ameliorated arsenic-induced renal dysfunction and pathological injury. This protection was mechanistically linked to the suppression of inflammatory responses, inhibition of fibrotic deposition and EMT process, and concomitant modulation of key pro-fibrotic signaling cascades (TGF-β1/Smad2/3, PI3K/AKT, MAPK, and AHR). In conclusion, our results demonstrated that the substantial therapeutic potential of ginsenoside Rg1 against arsenic-induced kidney injury, providing a novel pharmacological perspective for intervention.

Ginseng stem and leaf saponins attenuates pulmonary fibrosis by regulating TFAM-mtDNA homeostasis and suppressing ZBP1-mediated PANoptosis.

A review of plant-derived products regulating amyloid beta-degrading enzymes in Alzheimer's disease.

Valorization of Panax ginseng residues: Functional fiber development through cross-linking combined with ultrasonication.

Formula design is a common aim for the research and development of traditional Chinese medicine (TCM) and health-functional foods. TCM emphasizes pharmacological effects and efficacies, while health-functional foods are developed based on improvement of biomarkers and health functions. As demand rises for TCM-derived health foods, a new formula design method integrating both framework is urgently needed. We developed SYSTCM-FD, a formula design method for TCM-based health products targeting health functions by integrating pharmacological research and TCM clinical experience. We integrated data of health functions, biomarkers, pharmacological effects, efficacies, and TCMs using SYSTCM database and literature mining. An exponential distribution was used to calculate TCM scores, and top-ranking TCMs were combined into formulae. SYSTCM-FD covered 24 health functions, 173 biomarkers, 40 pharmacological effects, 18 efficacies, and 167 TCMs. Using immune enhancement as a validation case, nine candidate TCMs and 126 candidate formulae were generated. A lead formula containing Siraitia grosvenorii, Ligustrum lucidum, Panax ginseng leaves, and Rosa rugosa was selected and characterized by UPLC-MS/MS, identifying 64 components. In an immunosuppressed mouse model, this formula significantly improved spleen indices, increased peripheral immune cell counts, and alleviated spleen damage. SYSTCM-FD provides a theoretical and practical strategy for developing of TCM-based functional health foods.

Response of rhizosphere microecology and ginsenoside content to continuous cultivation of Panax ginseng

Ginsenoside Rb1 as a multi-target modulator in heart failure: Mechanistic insights into extracellular remodeling and transcriptional pathways from network pharmacology, molecular dynamics, and binding free energy analyses.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by aggregates of α-synuclein and the degeneration of dopaminergic neurons in the substantia nigra. Current pharmaceutical therapies mainly alleviate symptoms without halting disease progression. Evidence suggests that traditional plant-based interventions may serve as supplementary therapies by targeting oxidative stress, mitochondrial dysfunction, neuroinflammation, and apoptosis. This review explores the neuroprotective properties of ten medicinal plants commonly used in traditional medicine: Bacopa monnieri, Curcuma longa, Mimosa pudica, Zingiber officinale, Ocimum sanctum, Emblica officinalis, Camellia sinensis, Cannabis sativa, Panax ginseng, and Withania somnifera. A systematic and comprehensive search of PubMed, Scopus, and Web of Science identified relevant in vitro, in vivo, and clinical studies. This study highlights the mechanisms by which plant-derived chemicals influence cellular pathways associated with PD, emphasising their therapeutic potential despite limited clinical validation. Studies have shown that bioactive compounds such as curcumin, bacoside, Epigallocatechin-3-gallate (EGCG), cannabidiol, ginsenosides, and withanolides exhibit antioxidant, anti-inflammatory, anti-apoptotic, and neuroprotective effects in PD models. Nanotechnology offers promising strategy to enhance the efficacy of herbal compounds, addressing challenges of poor solubility, rapid metabolism, low bioavailability, and restricted blood-brain barrier penetration. Nano-delivery systems including liposomes, polymeric nanoparticles, nanoemulsions, and metal nanoparticles can improve stability, brain targeting, controlled release, and cellular uptake of these bioactives, thereby enhancing therapeutic efficiency while reducing systemic toxicity. Green-synthesized plant-based nanoparticles further provide synergistic neuroprotective benefits, positioning phyto-nanomedicine as a multi-target approach for PD therapy. However, extensive clinical studies are required to confirm safety and effectiveness.

Background/Objectives: Shenfu Decoction (SFD) is a traditional Chinese herbal formula composed of Panax ginseng and Aconitum carmichaelii that can revive and counteract shock. However, how SFD can mitigate hypothermia caused by seawater immersion is poorly understood. Methods: Three commonly used ratios of SFD (Panax ginseng:Aconitum carmichaelii = 1:1, 1:2, 2:1) were prepared, and their chemical properties were analyzed with UPLC-Q-TOF-MS. A rat model of hypothermia caused by seawater immersion at 15 °C was utilized. Survival analysis was used to evaluate the prophylactic effect of single intragastric administration of SFD with different ratios and doses on the survival time of rats, and to identify the optimal intervention conditions. Network pharmacology analysis based on the absorbed constituents of SFD was performed to preliminarily predict the underlying mechanisms, which were subsequently validated using RT-PCR, Western blotting, ELISA, and H&E staining. Results: SFD contained 54 compounds, including ginsenosides and aconitine alkaloids, whose relative concentrations varied across different ratios of SFD. Animal studies showed that pretreatment of SFD (1:1) administered at a dose of 1.35 g/kg was very effective in increasing rats’ survival time in hypothermia and slowed down core body temperature decline. Based on the 28 plasma-absorbed compounds of SFD, network pharmacology identified 503 targets, enriched in cAMP and MAPK signaling pathways. SFD (1:1, 1.35 g/kg) resulted in larger lipid droplets in brown adipose tissue (BAT) and enhanced the respiratory metabolic rate in seawater-immersion-induced hypothermia rats. Furthermore, its thermogenic effect is likely associated with the upregulation of uncoupling protein 1 (UCP1) via activating p38 MAPK/PGC1α/PPARγ and NE-(β3-AR)-cAMP-PKA pathways. Conclusions: The results of this study demonstrate that a single prophylactic administration of the traditional Chinese medicine formula SFD prior to cold seawater exposure significantly prolongs the survival time of rats. This effect is associated with the upregulation of UCP1 and the subsequent enhancement of thermogenesis in BAT. These findings highlight the great potential of SFD as a promising intervention for the management of hypothermia.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and neuronal death. Approved therapies, including acetylcholinesterase inhibitors and NMDA receptor antagonists, provide only symptomatic relief without halting progression. AD involves multifaceted pathologies: amyloid-β (Aβ) accumulation, tau hyperphosphorylation, oxidative stress, neuroinflammation, mitochondrial dysfunction, and apoptosis. Multi-target natural compounds like ginsenosides from Panax ginseng show promise in preclinical models by modulating these pathways. Key ginsenosides (Rg1, Rb1, Rc, Rd, Re, Rg3) inhibit Aβ production (via BACE1 suppression and α-secretase enhancement), promote Aβ clearance (via IDE/NEP upregulation), reduce tau phosphorylation (via GSK-3β/CDK5 modulation), and exert antioxidant, anti-inflammatory, and anti-apoptotic effects. Limited clinical evidence from small open-label trials of Korean Red Ginseng suggests cognitive improvements (e.g., in ADAS-cog and MMSE scores), with good tolerability. However, poor oral bioavailability and limited blood-brain barrier (BBB) penetration remain challenges, addressable via intranasal or nanoparticle delivery. While preclinical data are robust, clinical translation is limited by study heterogeneity and small samples. Ginsenosides warrant further investigation as adjunctive multi-target agents for AD.

Ginseng (Panax ginseng Meyer), one of the most widely known Chinese herbs, has been used in traditional medicine for centuries. Ginsenoside Rg5 (Rg5) can exert protective effects on the liver and activate the Nrf2 pathway. This study aims to investigate the mechanism of Rg5 alleviating acute liver injury (ALI), and the related mechanisms will be discussed. Invitro experiments, an ALI model was established using HepG2 cells. The DCFHDA, the JC-1, and the ferrous ion fluorescent probe detected the reactive oxygen species (ROS) level, the mitochondrial membrane potential change, and the iron ions level. The oxidative stress indexes were detected by biochemical analysis. Western blot was used to detect the m6A demethylation, Nrf2, and ferroptosis signaling pathways. For invivo experiments, C57BL/6J mice were administered ethanol by gavage to establish the ALI model. Invitro, we observed that m6A methylation and FTO downregulation were involved in the ferroptosis process. Rg5 treatment alleviated ferroptosis after ethanol exposure, which was reflected by the decrease of intracellular iron content and ferroptosis-related proteins. The FTO knockdown exhibited ferroptosis-related proteins and YTHDF2 increase. The regulatory effect of FTO on ferroptosis was inhibited when Nrf2 was inhibited or knocked down. Invivo, HE staining revealed liver injury in the model group, with elevated liver-to-body weight ratios and serum ALT and AST levels. The Rg5 treatment has improved these phenomena. FTO, Nrf2, and anti-ferroptosis proteins were downregulated in the ethanol group, while the ferroptosis marker ACSL4 was upregulated. This study demonstrates that Rg5 alleviates ethanol-induced ALI by inhibiting ferroptosis via the FTO/YTHDF2/Nrf2 axis. Our work not only establishes a link between FTO-mediated m6A demethylation and ferroptosis but also provides new mechanistic insights into the hepatoprotective action of ginsenosides.