Damage-induced muscle regeneration after exercise in humans: Modulatory effects of ginsenoside Rg1.

20(R)-ginsenosides are formed by Walden inversion during ginseng processing and usually exhibit almost identical MS/MS behaviors, yet display distinct pharmacological activities compared with 20(S)-configurational isomers. It is thereby crucial for isomer differentiation to facilitate quality control. To pursue a program enabling 20(R)- and 20(S)-ginsenosides discrimination in complicated matrices using MS/MS, red ginseng, the processed form of ginseng, was deployed as a representative. Five pairs of ginsenoside epimers were collected for method development. MS1 and MS2 spectra of every trimeric complex ion formed by complexation of ginsenoside, l-Phe, and Cu2+ were recorded using direct infusion (DI)-MS/MS, and the abundance ratio between the two dimeric fragment ions was termed R. Moreover, energy-resolved MS (ER-MS) was deployed to monitor fragmentation trajectories of precursor and concerned fragment ions and to determine the R feature at optimal collision energy, denoted Rmax. To validate the applicability for differentiating epimers in complicated matrices, e.g., red ginseng extract, post-column infusion (PCI) was introduced to configure PCI-LC-ER-MS. 20(R)- vs. 20(S)-Rg3 as representatives, [Cuᴵᴵ(l-Phe)2(20(R)-/20(S))-Rg3)-H]+ complex ions were observed and R values of the dimeric fragment ions such as [Cuᴵᴵ(l-Phe)(20(R)-/20(S))-Rg3)-H]+ and [Cuᴵᴵ(l-Phe)2-H]+, exhibited differences. Rmax features obtained by DI-ER-MS showed significant differences when comparing other 20(R)- and 20(S)-configurational isomers, leading to a reliable way for epimer discrimination. The reproducibility of recognition capability on PCI-LC-ER-MS platform was justified and applied to epimer differentiation in red ginseng extract. Successes were reached for the differentiation of two pairs of epimers, 20(R)- and 20(S)-Rg3, and 20(R)- and 20(S)-Rh1. In summary, the proposed strategy combined the complexation driven by [CuII(l-Phe)2-H]+ with PCI-LC-ER-MS enables the differentiation of 20(R)- and 20(S)-configurational ginsenoside isomers in complicated matrices.

Protopanaxadiol (PPD) is a bioactive ginsenoside with significant anti-inflammatory potential; however, its low natural abundance and dependence on inefficient intestinal microbial bioconversion hinder pharmaceutical development. To overcome these supply and bioavailability constraints, we developed a metabolically engineered rice variety, DJ-PPD, capable of directly biosynthesizing the aglycone PPD. This study investigated the anti-inflammatory and antioxidant mechanisms of DJ-PPD extract in lipopolysaccharide (LPS)-stimulated BV2 cells. DJ-PPD treatment significantly reduced nitric oxide (NO) production, pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and the expression of iNOS and COX-2. Its efficacy surpassed conventional ginseng extract and was comparable to synthetic PPD (S-PPD). Mechanistically, DJ-PPD inhibited NF-κB, MAPKs, and Akt phosphorylation while activating the NRF2/HO-1 antioxidant pathway. These findings demonstrate that DJ-PPD simultaneously inhibits pro-inflammatory cascades and reinforces intrinsic antioxidant defences. By effectively bypassing the need for gut microbiota metabolism, this genetically engineered rice represents a sustainable, bioavailable, and commercially viable multi-target therapeutic candidate for neuroinflammatory conditions.

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

Evaluation of analytical buffers as alternatives to phosphate-buffered saline in diffusion studies with plant extracts using LC-MS detection.

Background: Red ginseng (RG) exhibits enhanced bioactivity compared to white ginseng. Although the beneficial effects of RG have been well investigated in disease models, its impacts on the metabolome, gut microbiota, and immune response under normal physiological conditions remain poorly understood. Methods: Rats were randomized into three groups: control (normal diet), RL (low-dose RGE at 100 mg/kg body weight), and RH (high-dose RGE at 200 mg/kg body weight). After five weeks, metabolite profiles of the blood, liver, kidney, and large intestinal contents were analyzed and the gut microbiota was assessed. Splenocytes were isolated and treated with or without ethanol-precipitated carbohydrate fractions isolated from RGE or from intestinal contents, and IL-12 secretion was measured. Additionally, the correlations among biochemical characteristics, metabolites, gut microbiota, and immune markers were analyzed. Results: RGE intake decreased plasma triglycerides, liver function biomarkers, and epididymal adipose tissue weight. It also altered metabolite profiles for plasma, liver, kidney, and intestinal contents and increased the hepatic NAD+/NADH ratio. RGE intake reduced the populations of harmful bacteria, whereas it increased Lachnospiraceae. RGE intake enhanced IL-12 production in splenocytes. Furthermore, splenocytes treated with carbohydrates isolated from the small and large intestinal contents of RGE-fed rats secreted higher IL-12 levels than those of the control group. Conclusions: RGE modulated the gut microbiota, metabolism, and immune responses in healthy rats under normal physiological conditions, warranting further investigation into the underlying mechanisms.

Ginseng in exercise training and injury recovery: Composition, mechanism of action, dosage recommendations, and safety analysis.

BackgroundLung cancer remains a leading cause of cancer-related death, and current therapies are limited by toxicity and drug resistance. Natural product-derived ginsenosides, particularly those in black ginseng extract (BGE), show potent anticancer activity, yet their effects on lung cancer overall are not well understood. Accordingly, we evaluated the preventive and therapeutic potential of BGE on human lung cancer cell proliferation and the growth of solid tumors in mice.MethodsThe antitumor activity of BGE was evaluated by assessing its cytotoxic and apoptotic effects on human lung cancer cell Calu-3 and NCI-H1975 cells in vitro. For the in vivo experiment, Athymic NCr-nu/nu male mice bearing Calu-3 cell-derived lung tumor xenografts were orally administered BGE. Tumor volume and body weight were monitored throughout the treatment period. At the end of the study, tumors were excised and weighed, and liver and spleen tissues were collected and examined histologically using hematoxylin and eosin (H&E) staining to assess tissue morphology and confirm the absence of BGE-induced abnormalities.ResultsIn vitro, BGE showed significant apoptosis-associated cytotoxicity in Calu-3 cells at a concentration of 10 mg/mL (P=0.002) and in NCI-H1975 cells at a concentration of 0.5 mg/mL (P<0.001). Conversely, in vivo administration of BGE in Calu-3 xenograft mice did not alter body weight (P=0.37) or tumor volume but significantly reduced tumor weight (P=0.042) and size (P=0.008). No significant changes were observed in the weights or histopathological features of the liver (P=0.67) and spleen (P=0.41), indicating that BGE does not cause toxicity in major organs.ConclusionsBGE demonstrated strong antitumor effects against lung cancer cells under both in vitro and in vivo conditions, with no detectable toxicity in key organs. These findings highlight the potential of BGE as a safe and effective therapeutic or preventive agent for lung cancer.

Black ginseng, a functional food, is known for enhanced bioactivity, yet systems-level understanding of how its specific bioactive compounds modulate host physiology remains to be elucidated. This study employed an integrated multi-omics approach to map the systemic host responses by which processed black ginseng influences gut health. Through bioactivity-guided screening in a dextran sulfate sodium (DSS)-induced zebrafish model, nine-time steamed black ginseng extract (BG-9) exhibited optimal efficacy in inhibiting neutrophil infiltration and oxidative stress. Chemical profiling by HPLC revealed that rare ginsenosides Rk1, Rg3, and Rg5 were the predominant components in BG-9, collectively accounting for 56.87% of the total ginsenosides. Among them, Rk1 showed the most potent protective effects in vivo. Integrated transcriptomic and metabolomic analyses uncovered that Rk1 intervention significantly reversed DSS-induced metabolic disturbances, primarily by regulating glycine, serine, threonine, and cysteine-methionine metabolism pathways, alongside neuroactive ligand-receptor interactions. These findings provide a multi-omics map delineating that rare ginsenoside Rk1 serves as the primary bioactive constituent through which black ginseng induces systemic physiological changes that modulate gut homeostasis. This work bridges the gap between the consumption of black ginseng as a functional food and its health benefits, offering a systems biology perspective for its application in gut health promotion.

Alcohol-induced liver damage (AILD), characterized by oxidative stress and inflammation, is a major health concern. While black ginseng extract (BGE) exhibits diverse pharmacological activities, its protective effects against AILD and underlying molecular mechanisms remain unclear. This study evaluated the protective effects of BGE against AILD using in vivo, in vitro, and in silico models. In mice, daily oral administration of 25% ethanol (5 g/kg) for 2 weeks induced liver injury. BGE (100-500 mg/kg) significantly reduced serum alanine aminotransferase (AST) and aspartate aminotransferase (ALT)levels while increasing catalase (CAT) and superoxide dismutase (SOD) activities. In ethanol-treated HepG2 cells, BGE inhibited nitric oxide (NO) production and suppressed cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) expression while increasing heme oxygenase-1 (HO-1)expression. Ginsenoside Rh1, quantified at 4.7 mg/g via quadrupole linear ion trap tandem mass spectrometry coupled with UPLC (UPLC-Q-TRAP-MS/MS), was identified as a key bioactive compound. Network pharmacology and molecular docking analyses revealed key inflammatory signaling pathways and core hub genes associated with ginsenoside Rh1. Integrated analyses suggest that ginsenoside Rh1 contributes to the multi-target effects of BGE by modulating inflammatory signaling pathways. Collectively, BGE is a potential therapeutic candidate for the prevention and treatment of AILD, with ginsenoside Rh1 serving as a key bioactive constituent and quality control marker.

ABSTRACT Many plant and fungal extracts (PFEs) show anti‐fatigue properties through various pathways, but synergistic formulas and mechanisms are unclear. We screened six PFEs using a sodium sulfite (Na 2 SO 3 )‐induced exercise fatigue zebrafish model and developed a synergistic anti‐fatigue formula based on the combination index (CI) method. Red ginseng (RG), Lycium ruthenicum (LR) and Ganoderma lucidum (GL) extracts were selected as formulation materials based on their potential synergistic possibilities. The formula demonstrated a strong synergistic effect on recovery rate with a CI of 0.04 when RG, LR, and GL were mixed at concentrations of 3.6, 4.0, and 14 μg/mL, respectively. Ginsenosides Re, LR anthocyanins and GL polysaccharides are the main anti‐fatigue components. The contents of ATP and SOD were increased by 39.1% and 53.9%, while lactic acid and malondialdehyde (MDA) contents were decreased by 31.3% and 15.6%. Zebrafish swimming ability was restored by 97.6% relative to the control group, demonstrating a fatigue recovery effect comparable to that of Red Bull. The formula exerts anti‐fatigue effects by regulating muscle contraction, energy metabolism and oxidative stress at the relative rRNA expression. These findings highlight the promising potential of rationally designed PFEs combinations for functional food.

Ginseng has a longstanding reputation as an adaptogen, antistress agent and cognitive enhancer. We conducted a systematic review of randomised controlled studies into the cognitive effects of ginseng in non-clinical populations. The initial search captured 1802 records, of which fourteen articles fulfilled the inclusion criteria and were included in this review. The majority of the studies (N = 11) examined the effects of standardized extracts of Panax ginseng (Asian ginseng), with most (N = 8) using a standardised extract. The other three used a standardised extract of Panax quinquefolius (American ginseng). All but one study included acute assessment ranging from 1 h to 6 h post-administration. Four studies included a ‘chronic’ assessment ranging from 8 days to 12 weeks, three of which included ‘acute-on-chronic’ evaluations. Overall, the effects of P. ginseng tended to benefit accuracy of secondary memory (although there was evidence of a speed accuracy trade-off for specific doses), and to some degree attentional processes. P. quinquefolius had a more positive impact on attentional measures and working memory/executive functions. These effects are likely due to differences in ginsenoside profiles and other components via action on numerous systems, including neurotransmitter systems and glucocorticoid and estrogen receptors. Although there were some methodological consistencies across studies, different cognitive measures and extracts were utilised. Notably, the studies which did not specify the ginsenoside constituents of the extract used did not report cognitive benefits, emphasising the need for standardisation and characterisation.

Cancer-related fatigue (CRF) is one of the most prevalent and debilitating long-term symptoms among cancer survivors, particularly those with gastrointestinal malignancies. Previous studies on Panax ginseng supplementation have shown inconsistent findings, and evidence in gastrointestinal (GI) cancer survivors remains limited. This study evaluated the efficacy and safety of standardized Panax ginseng extract in reducing CRF. In this randomized, double-blind, placebo-controlled trial, 65 survivors (≥ 4months post-treatment) with moderate-to-severe CRF (Brief Fatigue Inventory [BFI] score > 4) were allocated to receive either Panax ginseng extract (250mg/day) or placebo for four weeks. Fatigue severity (BFI total score) was assessed at baseline and post-intervention. Data analysis was performed with SPSS 27 software, where statistical significance was considered at p < 0.05.Data were analyzed using ANCOVA, controlling for baseline scores. Effect size (Cohen's d) and 95% confidence intervals (CI) were calculated. At baseline, mean fatigue scores were similar between groups (Intervention: 5.36 ± 1.18; Placebo: 5.35 ± 1.23). After four weeks, the intervention group demonstrated significant reductions in fatigue (3.99 ± 0.86 vs. 5.37 ± 1.27, p < 0.001), with an adjusted mean difference of - 1.38 (95% CI: - 1.90, - 0.86; Cohen's d = - 1.26). Significant improvements were also observed in general activity, walking ability, mood, and enjoyment of life in the intervention group. No treatment-related adverse events were reported. Short-term Panax ginseng supplementation significantly reduced fatigue and improved multiple dimensions of daily functioning in GI cancer survivors, with excellent tolerability. These findings support Panax ginseng as a potential adjunctive intervention for CRF management within supportive care. Larger multicenter studies with extended follow-up are warranted.

Immunosenescence is characterized by an age-associated decline in immune function, particularly involving T-cell dysfunction, which increases susceptibility to infections and chronic diseases. This study investigated the anti-aging and immunomodulatory effects of American ginseng extract (G1899) using in vitro and in vivo models of aging. Cellular senescence was induced in HepG2 cells by D-galactose treatment, followed by exposure to G1899 (20 and 100 μg/mL). Senescence-associated markers were assessed to evaluate cellular aging. An aging mouse model was established in male C57BL/6 mice through intraperitoneal administration of D-galactose (500 mg/kg) and tert-butyl hydroperoxide (0.4 mmol/kg), and G1899 was orally administered at 400 mg/kg. Thymic immune cell subsets and aging-related protein expression were analyzed using flow cytometry and Western blotting. G1899 significantly reduced p21 expression and senescence-associated β-galactosidase activity in senescent HepG2 cells. In aging-induced mice, G1899 restored CD4+ and CD8+ T-cell populations, normalized naïve T-cell levels, and reduced anergic CD28-negative T cells. Furthermore, G1899 regulated the expression of key aging-related proteins, including FOXO1, Sirt1, p53, and CD38. These findings demonstrate that G1899 attenuates age-related immune alterations by restoring thymic T-cell homeostasis and regulating aging-associated molecular pathways.

Qi deficiency liver cancer (QDLC) accounts for a high proportion of liver cancer patients and is an important aspect of traditional Chinese medicine research on liver cancer. Panax ginseng (PG) known as the king of herbs, has significant advantages in QDLC due to its unique Qi-replenishing properties. However, its potential pharmacodynamic components and mechanisms on QDLC are not fully understood. This study aimed to elucidate the mechanism by which PG alleviates QDLC. A QDLC rat model was established using exhaustive swimming combined with diethylnitrosamine induction. UHPLC-Q-Orbitrap-MS was employed to analysis the components of PG both in vitro and in vivo using the QDLC rat model. Multi-omics analysis combining network pharmacology, metabolomics, and transcriptomics was used to identify potential pharmacodynamic components and investigate potential mechanism of action. The results were further validated using transmission electron microscopy, immunofluorescence, and Western blotting. Molecular docking was performed to explore interactions between major PG constituents and core pathway proteins. A total of 52 and 14PG components were identified in vitro and from the livers of QDLC rat models, respectively. Integrated multi-omics and in vivo validation results indicate that PG alleviates QDLC by regulating the HIF-1α/PPARα-mediated fatty acid oxidation (FAO) signaling axis and mitochondrial dysfunction in the liver, with Rk3 playing a critical role in this process. The alleviating effect of PG on QDLC may be attributed to the activation of the HIF-1α/PPARα-mediated FAO signaling axis, which improves mitochondrial dysfunction in the liver.

Effects of Korean Red ginseng on the regulation of inflammation, cell death, and fibrosis in a mouse model of rheumatoid arthritis featuring spike protein overexpression.

BackgroundDietary patterns are effective in obesity treatment. This has led to more investigations on its mechanisms in combating obesity.ObjectivesThis study investigated the effects of ginseng and green tea extracts (GTE) on selected markers of lipid metabolism and the expression of some related genes in adipocytes.MethodsAfter a one-month period of consuming a high fatty content diet, a total of 42 male Wistar rats were assigned to seven groups randomly. The rats were then subjected to an eight-week treatment where they were administered different dosages of GTE and ginseng extract (GE) through oral administration. Then, some serologic parameters pertaining to lipid metabolism were analyzed in the treated rats. Furthermore, alterations in the expression levels of select genes, bone morphogenetic protein 7 (BMP7), hormone-sensitive lipase (HSL), and leptin, implicated in lipid metabolism, were quantified within the adipose tissue of the rats utilizing the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) methodology. Ultimately, the chemical composition of the extracts was analyzed by high performance liquid chromatography (HPLC).ResultsThe findings indicated that the utilization of the extracts had a notable impact on the reduction of body weight. There was a noteworthy enhancement of high-density lipoprotein levels across all study groups, as indicated by a statistically significant increase at a confidence level of 95%. The efficacy of the administered extracts was observed in a significant upregulation in BMP7 and HSL gene expression. Conversely, there was a notable reduction in leptin expression, which reached statistical significance at a confidence level of 95%. HPLC results detected 9 ginsenosides in the GE, among which Rb1 (100 mAU) was present in the largest amount, and 9 alkaloids in the GTE, among which epicatechin (EC) (380 mAU) and caffeine (320 mAU) were present in the largest amount.ConclusionsThe present study holds the potential to offer novel insights regarding the mechanism through which GE and GTE exert their anti-obesity effects.

Chronic ultraviolet (UV) exposure disrupts dermal collagen homeostasis and accelerates skin aging. This study evaluated the protective effects of black ginseng extract (BGE) against UV-induced photoaging in human dermal fibroblasts. BGE restored collagen-related markers, including COL5A1 and COL7A1, improved fibroblast proliferative capacity, and reduced senescence-associated changes under UV stress. Data-independent acquisition (DIA) proteomics identified broad pathway modulation by BGE, involving extracellular matrix remodeling, chromatin organization, and stress-response processes. To validate genome maintenance-related signals highlighted by proteomics, qPCR showed that BGE increased telomere/replication-associated genes compared with the UV group, including POT1 (2.29-fold) and ORC1 (6.70-fold). In addition, comet assay imaging indicated reduced UV-associated DNA damage features following BGE treatment. Overall, these findings indicate that BGE mitigates UV-induced photoaging phenotypes in fibroblasts, with collagen-related recovery and multi-level protective responses, supporting its potential as a natural bioactive ingredient for anti-photoaging skincare applications.

Black ginseng extract alleviates particulate matter-induced airway inflammation by suppressing the ROS/NLRP3/caspase-1 pathway in macrophages.

Background: Natural compounds are increasingly recognized for their ability to support regenerative health and counteract age-related decline through modulation of stem cell activity and mitochondrial function. Objective: This clinical proof-of-concept study evaluated the acute effects of four functional ingredients – Ginseng extract (from Panax ginseng), Olive extract (from Olea europaea), Chaga mushroom extract (from Inonotus Obliquus), and potassium hydrogen glucarate – using methods to document rapid changes in stem cells numbers and mitochondrial resilience in healthy adults. Methods: Using a randomized, double-blind, placebo-controlled, cross-over design, four healthy participants were enrolled following IRB-approved informed consent and consumed each ingredient or placebo on five separate days at least one week apart. Each participant was scheduled at the same time of the morning for all visits to minimize circadian influences. Results from the visit where placebo was consumed allowed data collection on that person’s normal circadian changes at that time, so this could be accounted for in the data analysis. Blood samples were collected at baseline, 1, 2, and 3 hours post-consumption. Stem cell numbers were quantified by flow cytometry. Mitochondrial volume and membrane potential were assessed ex vivo under oxidative and inflammatory stress using reporter dyes and flow cytometry. Results: All ingredients induced rapid, ingredient-specific mobilization of distinct stem cell types, with Chaga extract and Olive extract demonstrated robust effects across multiple stem cell types. All functional ingredients increased circulating pluripotential stem cells at 1 hour by at least 10% above levels observed after placebo consumption. Chaga intake resulted in an average 36% increase in endothelial stem cells compared to placebo. All ingredients modulated stress-induced changes in mitochondrial volume and membrane potential, with Ginseng extract and Olive extract showing particularly pronounced effects on mitochondrial adaptability. Novelty of the Study: This proof-of-concept clinical study presents novel evidence of acute biological effects following consumption of functional food extracts, with measureable changes in stem cell surveillance and mitochondrial stress responses observed as early as 1 hour after a single dose compared to placebo. Conclusion: These preliminary findings demonstrate rapid bioactivity of the tested functional ingredients in modulating regenerative and stress-response pathways, supporting their potential as early-phase interventions for promoting cellular resilience. The results further support the use of assessing mitochondrial resilience ex vivo as part of clinical evaluation of acute effects of functional ingredients. Keywords: Cellular resilience; Chaga mushroom; flow cytometry; mitochondrial volume; mito-chondrial membrane potential, olive extract; oxidative stress; Panax ginseng; polyphenols; pluripotential; potassium glucarate; progenitor; stem cell mobilization; stress response.