Aqueous preparation of arginyl-fructosyl-glucose (a maltose-arginine AC) and determination of Amadori compounds (ACs) in red ginseng by ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS).

Amadori compounds (ACs) are key Maillard intermediates in various foods after thermal processing, and are also important non-saponin components in red ginseng. Currently, due to the difficulty in obtaining AC standards, the determination of multiple ACs is limited and far from optimal. In this study, an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated. A green synthetic method was developed for arginyl-fructosyl-glucose (AFG), the major AC in red ginseng with potential health benefits. The UPLC-MS/MS method was then applied in identification and quantification of ACs in red ginseng samples, which showed for the first time that 12 other ACs also exist in red ginseng in addition to AFG and arginyl-fructose (total 98.88 % of all ACs). Contents of AFG and arginyl-fructose in whole red ginseng were 36.23 and 10.80 mg/g dry weight, respectively. Raw ginseng can be steamed and then dried whole to obtain whole red ginseng, or sliced before drying to obtain sliced red ginseng. Slicing before drying was found to reduce ACs content. Results of the present study will help to reveal the biological functions of red ginseng and related products associated with ACs and promote the standardization of red ginseng manufacture.

Target Cell Extraction and Spectrum-Effect Relationship Coupled with BP Neural Network Classification for Screening Potential Bioactive Components in Ginseng Extract with a Protective Effect against Myocardial Damage.

Cardiovascular disease has become a common ailment that endangers human health, having garnered widespread attention due to its high prevalence, recurrence rate, and sudden death risk. Ginseng possesses functions such as invigorating vital energy, enhancing vein recovery, promoting body fluid and blood nourishment, calming the nerves, and improving cognitive function. It is widely utilized in the treatment of various heart conditions, including palpitations, chest pain, heart failure, and other ailments. Although numerous research reports have investigated the cardiovascular activity of single ginsenoside, there remains a lack of systematic research on the specific components group that predominantly contribute to cardiovascular efficacy in ginseng medicinal materials. In this research, the spectrum-effect relationship, target cell extraction, and BP neural network classification were used to establish a rapid screening system for potential active substances. The results show that red ginseng extract (RGE) can improve the decrease in cell viability and ATP content and inhibit the increase in ROS production and LDH release in OGD-induced H9c2 cells. A total of 70 ginsenosides were identified in RGE using HPLC-Q-TOF-MS/MS analysis. Chromatographic fingerprints were established for 12 batches of RGE by high-performance liquid chromatography (HPLC). A total of 36 common ingredients were found in 12 batches of RGE. The cell viability, ATP, ROS, and LDH of 12 batches RGE were tested to establish gray relationship analysis (GRA) and partial least squares discrimination analysis (PLS-DA). BP neural network classification and target cell extraction were used to narrow down the scope of Spectral efficiency analysis and screen the potential active components. According to the cell experiments, RGE can improve the cell viability and ATP content and reduce the oxidative damage. Then, seven active ingredients, namely, Ginsenoside Rg1, Rg2, Rg3, Rb1, Rd, Re, and Ro, were screened out, and their cardiovascular activity was confirmed in the OGD model. The seven ginsenosides were the main active substances of red ginseng in treating myocardial injury. This study offers a reference for quality control in red ginseng and preparations containing red ginseng for the management of cardiovascular diseases. It also provides ideas for screening active ingredients of the same type of multi-pharmacologically active traditional Chinese medicines.

Pharmacological effects of ginseng and ginsenosides on intestinal inflammation and the immune system.

Intestinal inflammatory imbalance and immune dysfunction may lead to a spectrum of intestinal diseases, such as inflammatory bowel disease (IBD) and gastrointestinal tumors. As the king of herbs, ginseng has exerted a wide range of pharmacological effects in various diseases. Especially, it has been shown that ginseng and ginsenosides have strong immunomodulatory and anti-inflammatory abilities in intestinal system. In this review, we summarized how ginseng and various extracts influence intestinal inflammation and immune function, including regulating the immune balance, modulating the expression of inflammatory mediators and cytokines, promoting intestinal mucosal wound healing, preventing colitis-associated colorectal cancer, recovering gut microbiota and metabolism imbalance, alleviating antibiotic-induced diarrhea, and relieving the symptoms of irritable bowel syndrome. In addition, the specific experimental methods and key control mechanisms are also briefly described.

Ginsenoside Rk1 improves endothelial function in diabetes through activating peroxisome proliferator-activated receptors.

Ginsenoside Rk1, one kind of ginsenoside, is a minor ginsenoside found in Panax ginseng and used as traditional Chinese medicine for centuries. It exhibits anti-tumor and anti-aggregation effects. However, little research has been done on its effect on endothelial function. This study investigated whether ginsenoside Rk1 improved endothelial dysfunction in diabetes and the underlying mechanisms in vivo and in vitro. Male C57BL/6 mice were fed with a 12 week high-fat diet (60% kcal % fat), whereas treatment groups were orally administered with ginsenoside Rk1 (10 and 20 mg per kg per day) in the last 4 weeks. Aortas isolated from C57BL/6 mice were induced by high glucose (HG; 30 mM) and co-treated with or without ginsenoside Rk1 (1 and 10 µM) for 48 h ex vivo. Moreover, primary rat aortic endothelial cells (RAECs) were cultured and stimulated by HG (44 mM) to mimic hyperglycemia, with or without the co-treatment of ginsenoside Rk1 (10 µM) for 48 h. Endothelium-dependent relaxations of mouse aortas were damaged with elevated oxidative stress and downregulation of three isoforms of peroxisome proliferator-activated receptors (PPARs), PPAR-α, PPAR-ß/δ, and PPAR-γ, as well as endothelial nitric oxide synthase (eNOS) phosphorylation due to HG or high-fat diet stimulation, which also existed in RAECs. However, after the treatment with ginsenoside Rk1, these impairments were all ameliorated significantly. Moreover, the vaso-protective and anti-oxidative effects of ginsenoside Rk1 were abolished by PPAR antagonists (GSK0660, GW9662 or GW6471). In conclusion, this study reveals that ginsenoside Rk1 ameliorates endothelial dysfunction and suppresses oxidative stress in diabetic vasculature through activating the PPAR/eNOS pathway.

5-EPIFAT trial protocol: a multi-center, randomized, placebo-controlled trial of the efficacy of pharmacotherapy for fatigue using methylphenidate, bupropion, ginseng, and amantadine in advanced cancer patients on active treatment.

BACKGROUND: Cancer-related fatigue (CRF) is still undertreated in most patients, as evidence for pharmacological treatments is limited and conflicting. Also, the efficacy of the pharmacological agents relative to each other is still unclear. Therefore, medications that may potentially contribute to improving CRF will be investigated in this head-to-head trial. Our main objective is to compare the efficacy of methylphenidate vs. bupropion vs. ginseng vs. amantadine vs. placebo in patients with advanced cancer. METHODS: The 5-EPIFAT study is a 5-arm, randomized, multi-blind, placebo-controlled, multicenter trial that will use a parallel-group design with an equal allocation ratio comparing the efficacy and safety of four medications (Methylphenidate vs. Bupropion vs. Ginseng vs. Amantadine) versus placebo for management of CRF. We will recruit 255 adult patients with advanced cancer who experience fatigue intensity ≥ 4 based on a 0-10 scale. The study period includes a 4-week intervention and a 4-week follow-up with repeated measurements over time. The primary outcome is the cancer-related fatigue level over time, which will be measured by the functional assessment of chronic illness therapy-fatigue (FACIT-F) scale. To evaluate safety, the secondary outcome is the symptomatic adverse events, which will be assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events in cancer clinical trials (PRO-CTCAE). Also, a subgroup analysis based on a decision tree-based machine learning algorithm will be employed for the clinical prediction of different agents in homogeneous subgroups. DISCUSSION: The findings of the 5-EPIFAT trial could be helpful to guide clinical decision-making, personalization treatment approach, design of future trials, as well as the development of CRF management guidelines. TRIAL REGISTRATION: IRCT.ir IRCT20150302021307N6. Registered on 13 May 2023.

Ginseng Berry Juice (GBJ) Regulates the Inflammation in Acute Ulcerative Mouse Models and the Major Bioactive Substances Are Ginsenosides Rb3, Rc, Rd, and Re.

Panax ginseng fruit is known to have various biological effects owing to its large amount of saponins such as ginsenosides. In the present study, ginseng berry juice was confirmed to be effective against acute inflammation. Ginseng berry juice was used for analysis of active constituents, antioxidant efficacy, and in vivo inflammation. A high-performance liquid chromatography method was used for analysis of ginsenosides. In an HCl/ethanol-induced acute gastric injury model, microscopic, immunofluorescent, and immunohistochemical techniques were used for analysis of inhibition of gastric injury and mechanism study. In a mouse model of acute gastritis induced with HCl/ethanol, ginseng berry juice (GBJ, 250 mg/kg) showed similar gastric injury inhibitory effects as cabbage water extract (CB, 500 mg/kg, P.O). GBJ dose-dependently modulated the pro-inflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), and Interleukin-13 (IL-13). GBJ inhibited the activation of Nuclear Factor kappa bB (NF-κB) and suppressed the expressions of cyclooxigenase-2 (COX-2) and prostaglandin 2 (PGE2). The anti-inflammatory effect of GBJ is attributed to ginsenosides which have anti-inflammatory effects. Productivity as an effective food source for acute gastritis was analyzed and showed that GBJ was superior to CB. In addition, as a functional food for suppressing acute ulcerative symptoms, it was thought that the efficacy of gastric protection products would be higher if GBJ were produced in the form of juice rather than through various extraction methods.

Metals/bisulfite system involved generation of 24-sulfonic-25-ene ginsenoside Rg1, a potential quality control marker for sulfur-fumigated ginseng.

Ginseng is a most popular health-promoting food with ginsenosides as its main bioactive ingredients. Illegal sulfur-fumigation causes ginsenosides convert to toxic sulfur-containing derivatives, and reduced the efficacy/safety of ginseng. 24-sulfo-25-ene ginsenoside Rg1 (25-ene SRg1), one of the sulfur-containing derivatives, is a potential quality control marker of fumigated ginseng, but with low accessibility owing to its unknown generation mechanism. In this study, metals/bisulfite system involved generation mechanism was investigated and verified. The generation of 25-ene SRg1 in sulfur-fumigated ginseng is that SO2, formed during sulfur-fumigation, reacted with water and ionized into HSO3-. On the one hand, under the metals/bisulfite system, HSO3- generates HSO5- and free radicals which converted ginsenoside Rg1 to 24,25-epoxide Rg1; on the other hand, as a nucleophilic group, HSO3- reacted with 24,25-epoxide Rg1 and further dehydrated to 25-ene SRg1. This study provided a technical support for the promotion of 25-ene SRg1 as the characteristic quality control marker of sulfur-fumigated ginseng.

Effect of Enoxaparin and Daikenchuto Coadministration on Hepatic Disorder Markers in Gynecological Cancer Patients after Abdominal Surgery.

Enoxaparin and daikenchuto are commonly administered to prevent venous thromboembolism and intestinal obstruction after gynecological malignancy surgery. However, the effects of their combined use on hepatic function are not well studied. This study aimed to clarify the effects of the coadministration of enoxaparin and daikenchuto on hepatic function. First, Japanese Adverse Drug Event Report (JADER) data were analyzed to identify signals of hepatic disorders. Second, a retrospective observational study of patients who underwent surgery for gynecological malignancies was conducted. This study defined hepatic disorders as an increase in aspartate aminotransferase (AST) or alanine aminotransaminase (ALT) levels above the reference values, using 1-h postoperative values as the baseline. The analysis of JADER data revealed an increased risk for hepatic disorders with the coadministration of enoxaparin and daikenchuto. An observational study also showed higher odds ratios (95% confidence intervals) for the occurrence of hepatic disorders in the coadministration group (4.27; 2.11-8.64) and enoxaparin alone group (2.48; 1.31-4.69) than in the daikenchuto alone group. The median increase in the ALT level was also higher in the coadministration group (34; 15-59) than in the enoxaparin alone (19; 6-38) and daikenchuto alone groups (8; 3-33). In conclusion, our study suggests that compared with the use of enoxaparin or daikenchuto alone, enoxaparin and daikenchuto coadministration increases the risk of hepatic disorders, with more significant increases in AST and ALT levels. Healthcare workers need to be aware of these potential side effects when combining these drugs after surgery for gynecological malignancies.

Ginsenoside Rg3, enriched in red ginseng extract, improves lipopolysaccharides-induced suppression of brown and beige adipose thermogenesis with mitochondrial activation.

Brown adipose tissue (BAT) which is a critical regulator of energy homeostasis, and its activity is inhibited by obesity and low-grade chronic inflammation. Ginsenoside Rg3, the primary constituent of Korean red ginseng (steamed Panax ginseng CA Meyer), has shown therapeutic potential in combating inflammatory and metabolic diseases. However, it remains unclear whether Rg3 can protect against the suppression of browning or activation of BAT induced by inflammation. In this study, we conducted a screening of ginsenoside composition in red ginseng extract (RGE) and explored the anti-adipogenic effects of both RGE and Rg3. We observed that RGE (exist 0.25 mg/mL of Rg3) exhibited significant lipid-lowering effects in adipocytes during adipogenesis. Moreover, treatment with Rg3 (60 µM) led to the inhibition of triglyceride accumulation, subsequently promoting enhanced fatty acid oxidation, as evidenced by the conversion of radiolabeled 3H-fatty acids into 3H-H2O with mitochondrial activation. Rg3 alleviated the attenuation of browning in lipopolysaccharide (LPS)-treated beige adipocytes and primary brown adipocytes by recovered by uncoupling protein 1 (UCP1) and the oxygen consumption rate compared to the LPS-treated group. These protective effects of Rg3 on inflammation-induced inhibition of beige and BAT-derived thermogenesis were confirmed in vivo by treating with CL316,243 (a beta-adrenergic receptor agonist) and LPS to induce browning and inflammation, respectively. Consistent with the in vitro data, treatment with Rg3 (2.5 mg/kg, 8 weeks) effectively reversed the LPS-induced inhibition of brown adipocyte features in C57BL/6 mice. Our findings confirm that Rg3-rich foods are potential browning agents that counteract chronic inflammation and metabolic complications.

Endophytic fungi of Panax sokpayensis produce bioactive ginsenoside Compound K in flask fermentation.

Endophytes of Panax have the potential to produce their host plant secondary metabolites, ginsenosides. Panax sokpayensis, an endemic traditional medicinal plant of the Sikkim Himalayas was explored for the isolation of endophytic fungi. In the present study, we have isolated 35 endophytic fungal cultures from the rhizome of P. sokpayensis and screened for ginsenosides production by HPLC by comparing the peak retention time with that of standard ginsenosides. The HPLC analysis revealed that out of 35 isolates, the mycelial extracts of four fungal endophytes (PSRF52, PSRF53, PSRF49 and PSRF58) exhibited peaks with a similar retention time of the standard ginsenoside, Compound K (CK). LC-ESI-MS/MS analysis led to the confirmation of ginsenoside CK production by the four fungal endophytes which showed a compound with m/z 639.6278, similar to that of standard ginsenoside CK with yield in potato dextrose broth flask fermentation ranging from 0.0019 to 0.0386 mg/g of mycelial mass in dry weight basis. The four prospective fungal endophyte isolates were identified as Thermothielavioides terrestris PSRF52, Aspergillus sp. PSRF49, Rutstroemiaceae sp. strain PSRF53, and Phaeosphaeriaceae sp. strain PSRF58 based on ITS sequencing. The present finding highlights the need for further study on growth optimization and other culture parameters to exploit the endophytes as an alternative source for ginsenoside CK production.

Potential mechanism of ginseng in the treatment of periodontitis based on network pharmacology and molecular docking.

OBJECTIVES: To explore the mechanism of ginseng in the treatment of periodontitis based on network pharmacology and molecular docking technology. METHODS: Potential targets of ginseng and periodontitis were obtained through various databases. The intersection targets of ginseng and periodontitis were obtained by using VENNY, the protein-protein interaction network relationship diagram was formed on the STRING platform, the core target diagram was formed by Cytoscape software, and the ginseng-active ingredient-target network diagram was constructed. The selected targets were screened for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The core targets of ginseng's active ingredients in treating periodontitis were analyzed by molecular docking technique. RESULTS: The 22 ginseng's active ingredients, 591 potential targets of ginseng's active ingredients, 2 249 periodontitis gene targets, and 145 ginseng-periodontitis intersection targets were analyzed. Ginseng had strong binding activity on core targets such as vascular endothelial growth factor A and epidermal growth factor receptor, as well as hypoxia induced-factor 1 (HIF-1) signaling pathway and phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway. CONCLUSIONS: Ginseng and its active components can regulate several signaling pathways such as HIF-1 and PI3K-Akt, thereby indicating that ginseng may play a role in treating periodontitis through multiple pathways.

Analysis Transcriptome and Phytohormone Changes Associated with the Allelopathic Effects of Ginseng Hairy Roots Induced by Different-Polarity Ginsenoside Components.

The allelopathic autotoxicity of ginsenosides is an important cause of continuous cropping obstacles in ginseng planting. There is no report on the potential molecular mechanism of the correlation between polarity of ginsenoside components and their allelopathic autotoxicity. This study applied a combination of metabolomics and transcriptomics analysis techniques, combined with apparent morphology, physiological indexes, and cell vitality detection of the ginseng hairy roots, through which the molecular mechanism of correlation between polarity and allelopathic autotoxicity of ginsenosides were comprehensively studied. The hairy roots of ginseng presented more severe cell apoptosis under the stress of low-polarity ginsenoside components (ZG70). ZG70 exerted allelopathic autotoxicity by regulating the key enzyme genes of cis-zeatin (cZ) synthesis pathway, indole-3-acetic acid (IAA) synthesis pathway, and jasmonates (JAs) signaling transduction pathway. The common pathway for high-polarity ginsenoside components (ZG50) and ZG70 to induce the development of allelopathic autotoxicity was through the expression of key enzymes in the gibberellin (GA) signal transduction pathway, thereby inhibiting the growth of ginseng hairy roots. cZ, indole-3-acetamid (IAM), gibberellin A1 (GA1), and jasmonoyl-L-isoleucine (JA-ILE) were the key response factors in this process. It could be concluded that the polarity of ginsenoside components were negatively correlated with their allelopathic autotoxicity.

Characterization of the structure, anti-inflammatory activity and molecular docking of a neutral polysaccharide separated from American ginseng berries.

AIM: American ginseng berries, grown in the aerial parts and harvested in August, are a potentially valuable material. The aim of the study was to analyze the specific polysaccharides in American ginseng berries, and to demonstrate the anti-inflammation effect through in vitro and in vivo experiments and molecular docking. METHODS: After deproteinization and dialysis, the extracted crude polysaccharide was separated and purified. The structure of the specific isolated polysaccharide was investigated by Fourier Transform infrared spectroscopy (FT-IR), GC-MS and nuclear magnetic resonance (NMR), and anti-inflammatory activity was evaluated using in vitro and in vivo models (Raw 264.7 cells and zebrafish). Molecular docking was used to analyze the binding capacity and interaction with cyclooxygenase-2 (COX-2). RESULTS: A novel neutral polysaccharide fraction (AGBP-A) was isolated from American ginseng berries. The structural analysis demonstrated that AGBP-A had a weight-average molecular weight (Mw) of 122,988 Da with a dispersity index (Mw/Mn) value of 1.59 and was composed of arabinose and galactose with a core structure containing →6)-Gal-(1→ residues as the backbone and a branching substitution at the C3 position. The side-chains comprised of α-L-Ara-(1→, α-L-Ara-(1→, →5)-α-L-Ara-(1→, ß-D-Gal-(1→. The results showed that it significantly decreased pro-inflammatory cytokines in the cell model. In a zebrafish model, AGBP-A reduced the massive recruitment of neutrophils to the caudal lateral line neuromast, suggesting the relief of inflammation. Molecular docking was used to analyze the combined capacity and interaction with COX-2. CONCLUSION: Our study indicated the potential efficacy of AGBP-A as a safe and valid natural anti-inflammatory component.

Experimental trials to assess the immune modulatory influence of thyme and ginseng oil on NDV-vaccinated broiler chickens.

Background: The use of traditional medicine against viral diseases in animal production has been practiced worldwide. Herbal extracts possess organic substances that would improve chicken body performance. Aim: The current study was designed to evaluate the effect of either thyme or ginseng oil in regard to their immune-modulatory, antiviral, and growth promoter properties. Methods: Two hundred and forty-one-day-old broiler chicks were allocated into eight equal groups as the following: group 1; nonvaccinated and nontreated and group 2; Newcastle disease virus (NDV) vaccinated and nontreated. Birds of groups 3 and 4 were treated with thyme oil (200 mg/l of drinking water for 12 hours/day) without or with NDV vaccination. Birds of groups 5 and 6 were treated with ginseng oil (200 mg/l of drinking water for 12 hours/day) without or with NDV vaccination. Birds of groups 7 and 8 were treated with a combination of ginseng oil (100 mg/l of drinking water) and thyme oil (100 mg/l of drinking water) for 12 hours/day. On the 35th day of life, birds in all the experimental groups were given 0.1 ml of a virulent genotype VIId NDV strain suspension containing 106.3 EID50/ml intramuscularly. Results: Administration of ginseng and thyme oils each alone or simultaneously to birds either vaccinated or nonvaccinated elicited a significant improvement in body performance parameters. Administration of thyme and ginseng each alone or concurrently to vaccinated birds (Gp 4, 6, and 8) induced a higher hemagglutination inhibition (HI) titer of 6, 7.3, and 6.3 log2 at 21 days of age, 6.7, 7.6, and 7 log2, at 28 days of age and 7, 8, and 6.8 log2 at 35 days of age, respectively. Challenge with vNDV genotype VII led to an increase in the NDV-specific HI-Ab titers 10 days post challenge in all the experimental groups. In addition, thyme, ginseng oils, or a combination of them improved the protection from mortality in vaccinated birds; by 100%, 100%, and 90%, respectively, compared with 80% protection from mortality in vaccinated-only birds post-NDV challenge. Moreover, NDV-vaccinated birds treated either with thyme; ginseng or their combination showed negative detection of the virus in both tracheal and cloacal swabs and nonvaccinated groups that received oils showed improvement in vNDV shedding in tracheal and cloacal swabs. Conclusion: It could be concluded that the administration of thyme and ginseng essential oils to broilers can improve productive performance parameters, stimulate humoral immunity against, and protect from vNDV infection.

Ginsenoside CK Alleviates DSS-Induced IBD in Mice by Regulating Tryptophan Metabolism and Activating Aryl Hydrocarbon Receptor via Gut Microbiota Modulation.

Dysbiosis of gut microbiota is believed to be associated with inflammatory bowel disease (IBD). Ginsenoside compound K (CK), the main metabolite of Panax ginseng ginsenoside, has proven effective as an anti-inflammatory agent in IBD. However, the mechanisms by which CK modulates gut microbiota to ameliorate IBD remain poorly understood. Herein, CK demonstrated the potential to suppress the release of proinflammatory cytokines by gut microbiota modulation. Notably, supplementation with CK promoted the restoration of a harmonious balance in gut microbiota, primarily by enhancing the populations of Lactobacillus and Akkermansia. Furthermore, CK considerably elevated the concentrations of tryptophan metabolites derived from Lactobacillus that could activate the aryl hydrocarbon receptor. Overall, the promising alleviative efficacy of CK primarily stemmed from the promotion of Lactobacillus growth and production of tryptophan metabolites, suggesting that CK should be regarded as a prospective prebiotic agent for IBD in the future.

20(S)-Protopanaxadiol Exerts Antidepressive Effects in Chronic Corticosterone-Induced Rodent Animal Models as an Activator of Brain-Type Creatine Kinase.

20(S)-Protopanaxadiol (PPD) is one of the bioactive ingredients in ginseng and possesses neuroprotective properties. Brain-type creatine kinase (CK-BB) is an enzyme involved in brain energy homeostasis via the phosphocreatine-creatine kinase system. We previously identified PPD as directly bound to CK-BB and activated its activity in vitro. In this study, we explored the antidepressive effects of PPD that target CK-BB. First, we conducted time course studies on brain CK-BB, behaviors, and hippocampal structural plasticity responses to corticosterone (CORT) administration. Five weeks of CORT injection reduced CK-BB activity and protein levels and induced depression-like behaviors and hippocampal structural plasticity impairment. Next, a CK inhibitor and an adeno-associated virus-targeting CKB were used to diminish CK-BB activity or its expression in the brain. The loss of CK-BB in the brain led to depressive behaviors and morphological damage to spines in the hippocampus. Then, a polyclonal antibody against PPD was used to determine the distribution of PPD in the brain tissues. PPD was detected in the hippocampus and cortex and observed in astrocytes, neurons, and vascular endotheliocytes. Finally, different PPD doses were used in the chronic CORT-induced depression model. Treatment with a high dose of PPD significantly increased the activity and expression of CK-BB after long-term CORT injection. In addition, PPD alleviated the damage to depressive-like behaviors and structural plasticity induced by repeated CORT injection. Overall, our study revealed the critical role of CK-BB in mediating structural plasticity in CORT-induced depression and identified CK-BB as a therapeutic target for PPD, allowing us to treat stress-related mood disorders.

[Identification and visual analysis of ginsenosides in multi-steamed roots of Panax quinquefolium based on UPLC-Q-TOF-MS/MS and MALDI-MSI].

This study aims to investigate the component variations and spatial distribution of ginsenosides in Panax quinquefolium roots during repeated steaming and drying. Ultra performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to identify the ginsenosides in the root extract. Matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) was employed to visualize the spatial distribution and spatiotemporal changes of prototype ginsenosides and metabolites in P. quinquefolium roots. The UPLC results showed that 90 ginsenosides were identified during the steaming process of the roots, and polar ginsenosides were converted into low polar or non-polar ginsenosides. The content of prototype ginsenosides decreased, while that of rare ginsenosides increased, which included 20(S/R)-ginsenoside Rg_3, 20(S/R)-ginsenoside Rh_2, and ginsenosides Rk_1, Rg_5, Rs_5, and Rs_4. MALDI-MSI results showed that ginsenosides were mainly distributed in the epidermis and phloem. As the steaming times increased, ginsenosides were transported to the xylem and medulla. This study provides fundamental information for revealing the changes of biological activity and pharmacological effect of P. quinquefolium roots that are caused by repeated steaming and drying and gives a reference for expanding the application scope of this herbal medicine.

Biosynthesis of palladium, platinum, and their bimetallic nanoparticles using rosemary and ginseng herbal plants: evaluation of anticancer activity.

In this research, palladium (II) and platinum (II), as well as their bimetallic nanoparticles were synthesized using medicinal plants in an eco-friendly manner. Rosemary and Ginseng extracts were chosen due to their promising anticancer potential. The synthesized nanoparticles underwent characterization through FT-IR spectroscopy, DLS, XRD, EDX, SEM, and TEM techniques. Once the expected structures were confirmed, the performance of these nanoparticles, which exhibited an optimal size, was evaluated as potential anticancer agents through in vitro method on colon cancer cell lines (Ls180, SW480). MTT assay studies showed that the synthesized nanoparticles induced cell death. Moreover, real-time PCR was employed to investigate autophagy markers and the effect of nanoparticles on the apoptosis process, demonstrating a significant effect of the synthesized compounds in this regard.

Beneficial Effects of Small-Molecule Oligopeptides Isolated from Panax Ginseng C. A. Meyer on Cellular Fates in Oxidative Stress-Induced Damaged Human Umbilical Vein Endothelial Cells and PC-12.

Cell fate instability is a crucial characteristic of aging and appears to contribute to various age-related pathologies. Exploring the connection between bioactive substances and cell fate stability may offer valuable insights into longevity. Therefore, the objective of this study was to investigate the potential beneficial effects of ginseng oligopeptides (GOPs) isolated from Panax ginseng C. A. Meyer at the cellular level. Disruption of homeostasis of human umbilical vein endothelial cells (HUVECs) and PC-12 was achieved by culturing them in the growth medium supplemented with 200 µM of H2O2, and 25, 50, and 100 µg/mL GOPs for 4 h. Then, they were cultured in a H2O2-free growth medium containing different concentration of GOPs. We found that GOP administration retards the oxidative stress-induced cell instability in HUVECs by increasing cell viability, inhibiting the cell cycle arrest, enhancing telomerase (TE) activity, suppressing oxidative stress and an inflammatory attack, and protecting mitochondrial function. Furthermore, we hypothesized that GOPs may promote mitochondrial biosynthesis by upregulating PGC-1α expression. Similarly, GOPs positively regulated cell stability in PC-12; notably, the protective effect of GOPs on PC-12 mainly occurred through the inhibition of autophagic cell death of neuronal cells, while the protective effect on mitochondria was weak. In conclusion, it is evident that GOPs demonstrate potential beneficial effects in maintaining cell fate stability, thereby potentially contributing to an enhanced health span and overall well-being.

Ginseng-derived nanoparticles alleviate alcohol-induced liver injury by activating the Nrf2/HO-1 signalling pathway and inhibiting the NF-κB signalling pathway in vitro and in vivo.

BACKGROUND: Previous studies have confirmed the antioxidant and anti-inflammatory effects of active ginseng components that protect against liver injury. However, ginseng-derived nanoparticles (GDNPs), low-immunogenicity nanovesicles derived from ginseng, have not been reported to be hepatoprotective. PURPOSE: In this study, we investigated whether GDNPs could attenuate alcohol-induced liver injury in LO2 cells and mice by modulating oxidative stress and inflammatory pathways, thereby advancing the theoretical basis for the development of novel pharmacological treatments. STUDY DESIGN: Alcohol was used to construct in vitro and in vivo models of alcoholic liver injury. To explore the mechanisms by which GDNPs exert their protective effects against alcoholic liver injury, we examined the expression of oxidative stress-related genes and analysed inflammatory responses in vitro and in vivo. The experimental findings were verified using network pharmacology. METHODS: The composition of the GDNPs was analysed using liquid chromatography-mass spectrometry. GDNPs were extracted and purified using differential ultracentrifugation and sucrose density gradient centrifugation. In vitro models of alcoholic liver injury were established using LO2 cells, whereas C57BL/6 J mice were used as in vivo models. Oxidative stress, inflammation, and liver injury indicators were measured using appropriate kits. Levels of proteins associated with oxidative stress and inflammation were measured via western blot, while nuclear factor erythroid2-related factor 2 (Nrf2) and NF-κB protein expression was tested using immunofluorescence, immunohistochemistry, and flow cytometry. The levels of relevant transcription factors were determined using qPCR. Experimental haematoxylin and eosin staining was used to characterise the liver histological appearance and damage in mice. Network pharmacological analysis of GDNP mRNA sequencing of GDNPs was used to predict drug targets and disease associations using TCMSP. RESULTS: GDNPs primarily included 77 compounds, including organic acids and their derivatives, amino acids and their derivatives, sugars, terpenoids, and flavonoids. GDNPs have features that allow them to be taken up by LO2 cells and promote their proliferation. In vitro data indicated that GDNPs reduced the levels of alcohol-induced reactive oxygen species by activating the Nrf2/HO-1 signalling pathway, whilst inhibiting the NF-κB pathway and thereby reducing NO, tumour necrosis factor-α, and interleukin-1ß levels to alleviate inflammation. An in vivo model showed that GDNPs improved the liver parameters and pathology in mice with alcoholic liver injury. GDNPs activate the Nrf2/HO-1/Keap1 signalling pathway in a p62-dependent manner to exert antioxidant effects. Furthermore, the TLR4/NF-κB signalling pathway was involved in the in vivo anti-inflammatory effect. Network pharmacology also confirmed that the effects of GDNPs on liver disease were associated with oxidative stress and inflammation-related targets and pathways. CONCLUSION: This study showed for the first time that GDNPs can alleviate alcohol-induced liver damage by activating the Nrf2/HO1 signalling pathway and blocking the NF-κB signalling pathway, thus lowering oxidative stress and inflammatory responses. Hereby, we present the Nrf2/HO1 and NF-κB signalling pathways as potential targets and GDNPs as a novel therapeutic approach for the management of alcohol-induced liver damage.