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.

Steamed Ginseng Berry Powder Ameliorates Skeletal Muscle Atrophy via Myogenic Effects.

Sarcopenia is an age-related loss of muscle mass and function for which there is no approved pharmacological treatment. We tested direct efficacy by evaluating grip strength improvement in a sarcopenia mouse model rather than drug screening, which inhibits specific molecular mechanisms. Various physiological functions of ginseng berries are beneficial to the human body. The present study aimed to evaluate the efficacy and safety of steamed ginseng berry powder (SGBP). SGBP administration increased myotube diameter and suppressed the mRNA expression of sarcopenia-inducing molecules. SGBP also reduced the levels of inflammatory transcription factors and cytokines that are known to induce sarcopenia. Oral administration of SGBP improved muscle mass and physical performance in a mouse model of sarcopenia. In summary, our data suggest that SGBP is a novel therapeutic candidate for the amelioration of muscle weakness, including sarcopenia.

A new ocotillol-type ginsenoside from American ginseng berry.

A new ocotillol-type ginsenoside, named pseudoginsenoside F12 (1), was isolated from American ginseng berry, whose structure was elucidated as 6-O-[α-L-2,3-epoxy-rhamnopyranosyl-(1-2)-ß-D-glucopyranosyl]-dammar-20S,24R-epoxy-3ß, 6α,12ß,25-tetraol. In addition, the known alkaloids ß-carboline-1-carboxylic acid (2) and anoectochine (3) were isolated for the first time from the Araliaceae family. The new compound 1 was evaluated for cytotoxicity against MDA-MB-231 breast cancer cell line.

Skin wound healing effects of (+)-syringaresinol from ginseng berry.

Background: Ginseng has been used as a traditional medicine and functional cosmetic ingredients for many years. Recent studies have focused on the potential biological effects of the ginseng berry and its ingredients. (+)-Syringaresinol (SYR) is enriched in ginseng berry and its beneficial effects on the skin have been recently reported. However, little is known about the its effects on the wound healing process of skin. Methods: Here, we evaluated the skin wound healing effect of (+)-SYR using the human fibroblast Hs68 cell and ex vivo pig and human skin tissue model. Scratch wound test and hydrogen peroxide (HPO) induce chemical wound model were employed. Results: (+)-SYR promoted the migration and proliferation of Hs68 cells without significant cytotoxicity at the tested concentrations. Especially, in ex vivo pig and human skin tissue, HPO-induced chemical wound was recovered almost completely by (+)-SYR. In line with the finding in Hs68, the protein expression levels of TGF-ß and PCNA, a proliferation marker were increased, demonstrating the beneficial effects of (+)-SYR on skin wound repair. Conclusion: Collectively, we demonstrated that (+)-SYR from ginseng berry, can enhance the wound healing effect by accelerating cell proliferation and skin regeneration, suggesting the potential utility of (+)-SYR for skin wound repair.

Improvement of Cognitive Function by Fermented Panax ginseng C.A. Meyer Berries Extracts in an AF64A-Induced Memory Deficit Model.

This study investigated the potential therapeutic properties of fermented ginseng berry extract (GBE) for Alzheimer's disease (AD). Fermented GBE was examined for its ginsenoside content and physiological properties, which have been suggested to have neuroprotective effects and improve cognitive function. The results showed that fermented GBE contains high levels of major active ginsenosides and exhibits antioxidant and acetylcholinesterase inhibitory activities. Post-fermented GBE demonstrated therapeutic potential in AF64A-induced damaged neural stem cells and an animal model of AD. These findings suggest that fermented GBE may hold promise as a candidate for developing new therapeutic interventions for memory deficits and cognitive disorders associated with AD and other neurodegenerative conditions. However, further studies are needed to evaluate the safety, tolerability, and efficacy of fermented GBE in human subjects and to determine its clinical applications. In conclusion, our study provides evidence that fermented GBE has potential as a natural product for the prevention and treatment of AD. The high levels of active ginsenosides and antioxidant and acetylcholinesterase inhibitory activities of fermented GBE suggest that it may be a promising therapeutic agent for improving cognitive function and reducing neurodegeneration.

Structural characteristics of mixed pectin from ginseng berry and its anti-obesity effects by regulating the intestinal flora.

Ginseng berry is the mature berry of ginseng and its polysaccharide has hypolipidaemic effect, but its mechanism remains unclear. A pectin (GBPA) with a molecular weight of 3.53 × 104 Da was isolated from ginseng berry, it was mainly composed of Rha (25.54 %), GalA (34.21 %), Gal (14.09 %) and Ara (16.25 %). Structural analysis showed that GBPA is a mixed pectin containing rhamnogalacturonan-I and homogalacturonan domains and has a triple helix structure. GBPA distinctly improved lipid disorders in obese rats, and changed intestinal flora with enrichments of Akkermansia, Bifidobacterium, Bacteroides and Prevotella, improved the levels of acetic acid, propionic acid, butyric acid and valeric acid. Serum metabolites which involved in the lipid regulation-related pathway, including cinnzeylanine, 10-Hydroxy-8-nor-2-fenchanone glucoside, armillaribin, 24-Propylcholestan-3-ol, were also greatly changed after GBPA treatment. GBPA activated AMP-activated protein kinase, phosphorylated acetyl-CoA carboxylase, and reduced the expression of lipid synthesis-related genes sterol regulatory element-binding protein-1c and fatty acid synthases. The regulatory effects of GBPA on lipid disorders in obese rats are related to the regulation of intestinal flora and activation of AMP-activated protein kinase pathway. Ginseng berry pectin could be considered in the future as a health food or medicine to prevent obesity.

Korean Ginseng Berry Polysaccharide Enhances Immunomodulation Activities of Peritoneal Macrophages in Mice with Cyclophosphamide-Induced Immunosuppression.

Korean ginseng (Panax ginseng C. A. Meyer), a member of the Araliaceae family, is known as a traditional medicinal plant to have a wide range of health properties. Polysaccharides constitute a major component of Korean ginseng, and its berries exhibit immune-modulating properties. The purpose of this study was to investigate the immune effects of crude polysaccharide (GBPC) extracted from Korean ginseng berry on peritoneal macrophages in mice with cyclophosphamide (CY)- induced immunosuppression. BALB/c mice were divided into eight groups: normal control, normal control + CY, levamisole + CY, ginseng + CY, and four concentrations of 50, 100, 250, and 500mg/kg BW/day of GBPC + CY. Mice were orally administered with samples for 10 days. Immunosuppression was established by treating mice with CY (80 mg/kg BW/day) through intraperitoneal injection on days 4 to 6. The immune function of peritoneal macrophages was then evaluated. Oral administration of 500mg/kg BW/day GBPC resulted in proliferation, NO production, and phagocytosis at 100%, 88%, and 91%, respectively, close to the levels of the normal group (100%) of peritoneal macrophages. In CY-treated mice, GBPC of 50-500 mg/kg BW/day also dose-dependently stimulated the proliferation, NO production, and phagocytosis at 56-100%, 47-88%, and 53-91%, respectively, with expression levels of immune-associated genes, such as iNOS, COX-2, IL-1ß, IL-6, and TNF-α, of about 0.32 to 2.87-fold, compared to those in the CY group. GBPC could be a potential immunomodulatory material to control peritoneal macrophages under an immunosuppressive condition.

Change of metformin concentrations in the liver as a pharmacological target site of metformin after long-term combined treatment with ginseng berry extract.

Metformin as an oral glucose-lowering drug is used to treat type 2 diabetic mellitus. Considering the relatively high incidence of cardiovascular complications and other metabolic diseases in diabetic mellitus patients, a combination of metformin plus herbal supplements is a preferrable way to improve the therapeutic outcomes of metformin. Ginseng berry, the fruit of Panax ginseng Meyer, has investigated as a candidate in metformin combination mainly due to its anti-hyperglycemic, anti-hyperlipidemic, anti-obesity, anti-hepatic steatosis and anti-inflammatory effects. Moreover, the pharmacokinetic interaction of metformin via OCTs and MATEs leads to changes in the efficacy and/or toxicity of metformin. Thus, we assessed how ginseng berry extract (GB) affects metformin pharmacokinetics in mice, specially focusing on the effect of the treatment period (i.e., 1-day and 28-day) of GB on metformin pharmacokinetics. In 1-day and 28-day co-treatment of metformin and GB, GB did not affect renal excretion as a main elimination route of metformin and GB therefore did not change the systemic exposure of metformin. Interestingly, 28-day co-treatment of GB increased metformin concentration in the livers (i.e., 37.3, 59.3% and 60.9% increases versus 1-day metformin, 1-day metformin plus GB and 28-day metformin groups, respectively). This was probably due to the increased metformin uptake via OCT1 and decreased metformin biliary excretion via MATE1 in the livers. These results suggest that co-treatment of GB for 28 days (i.e., long-term combined treatment of GB) enhanced metformin concentration in the liver as a pharmacological target tissue of metformin. However, GB showed a negligible impact on the systemic exposure of metformin in relation to its toxicity (i.e., renal and plasma concentrations of metformin).

Protective effects of Panax ginseng berry extract on blue light-induced retinal damage in ARPE-19 cells and mouse retina.

Background: Age-related macular degeneration (AMD) is a significant visual disease that induces impaired vision and irreversible blindness in the elderly. However, the effects of ginseng berry extract (GBE) on the retina have not been studied. Therefore, this study aimed to investigate the protective effects of GBE on blue light (BL)-induced retinal damage and elucidate its underlying mechanisms in human retinal pigment epithelial cells (ARPE-19 cells) and Balb/c retina. Methods: To investigate the effects and underlying mechanisms of GBE on retinal damage in vitro, we performed cell viability assay, pre-and post-treatment of sample, reactive oxygen species (ROS) assay, quantitative real-time PCR (qRT-PCR), and western immunoblotting using A2E-laden ARPE-19 cells with BL exposure. In addition, Balb/c mice were irradiated with BL to induce retinal degeneration and orally administrated with GBE (50, 100, 200 mg/kg). Using the harvested retina, we performed histological analysis (thickness of retinal layers), qRT-PCR, and western immunoblotting to elucidate the effects and mechanisms of GBE against retinal damage in vivo. Results: GBE significantly inhibited BL-induced cell damage in ARPE-19 cells by activating the SIRT1/PGC-1α pathway, regulating NF-kB translocation, caspase 3 activation, PARP cleavage, expressions of apoptosis-related factors (BAX/BCL-2, LC3-Ⅱ, and p62), and ROS production. Furthermore, GBE prevented BL-induced retinal degeneration by restoring the thickness of retinal layers and suppressed inflammation and apoptosis via regulation of NF-kB and SIRT1/PGC-1α pathway, cleavage of caspase 3 and PARP, and expressions of apoptosis-related factors in vivo. Conclusions: GBE could be a potential agent to prevent dry AMD and progression to wet AMD.

Korean Ginseng Berry Extract Enhances the Male Steroidogenesis Enzymes In Vitro and In Vivo.

PURPOSE: Testosterone hormonal replacement is the most commonly prescribed solution for men with reproductive issues; however, this treatment has various drawbacks. Hence, the identification of a natural product that promotes steroidogenesis is urgently needed. Ginseng is a popular traditional medicine. This study aimed to investigate steroidogenic effects of Korean ginseng berry extract (GBE; Panax ginseng C.A. Meyer) in vitro and in vivo. MATERIALS AND METHODS: In vitro model, mouse Leydig cells were treated with varying concentrations of GBE, and the levels of steroidogenesis-related genes and proteins and testosterone were measured using western blotting, qRT-PCR, and enzyme-linked immunosorbent assay (ELISA). Similarly, in an in vivo model using lipopolysaccharide-injected C57BL/6J mice, expression of steroidogenesis-related genes and proteins and testosterone levels were analyzed. Additionally, sleep deprivation was used to simulate common life stressors related to late-onset hypogonadism (LOH) and the natural effects of aging. Mice were fed sham or GBE before being subjected to paradoxical sleep deprivation. RESULTS: In vitro, GBE induced steroidogenic effects by increasing the levels of enzymes associated with steroidogenesis, steroidogenic acute regulatory protein (STAR), CYP11A1, and CYP17A1. In vivo, GBE significantly increased mRNA and protein levels of steroidogenic enzymes. Furthermore, the synthetic testosterone levels in mouse Leydig cell supernatants and blood sera were increased. In the sleep deprivation study, mice fed GBE showed increased testosterone production and survival under such stressful conditions. CONCLUSIONS: GBE increased mRNA and protein levels of steroidogenesis-related enzymes STAR, CYP11A1, and CYP17A1. These key enzymes induced the increased production of testosterone both in vivo and in vitro. Thus, GBE might be a promising therapeutic or additive nutritional agent for improving men's health by increasing steroidogenesis or improving LOH.

Syringaresinol derived from Panax ginseng berry attenuates oxidative stress-induced skin aging via autophagy.

Background: In aged skin, reactive oxygen species (ROS) induces degradation of the extracellular matrix (ECM), leading to visible aging signs. Collagens in the ECM are cleaved by matrix metalloproteinases (MMPs). Syringaresinol (SYR), isolated from Panax ginseng berry, has various physiological activities, including anti-inflammatory action. However, the anti-aging effects of SYR via antioxidant and autophagy regulation have not been elucidated. Methods: The preventive effect of SYR on skin aging was investigated in human HaCaT keratinocytes in the presence of H2O2, and the keratinocyte cells were treated with SYR (0-200 µg/mL). mRNA and protein levels of MMP-2 and -9 were determined by real-time PCR and Western blotting, respectively. Radical scavenging activity was researched by 2,2 diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. LC3B level was assessed by Western blotting and confocal microscopy. Results: SYR significantly reduced gene expression and protein levels of MMP-9 and -2 in both H2O2-treated and untreated HaCaT cells. SYR did not show cytotoxicity to HaCaT cells. SYR exhibited DPPH and ABTS radical scavenging activities with an EC50 value of 10.77 and 10.35 µg/mL, respectively. SYR elevated total levels of endogenous and exogenous LC3B in H2O2-stimulated HaCaT cells. 3-Methyladenine (3-MA), an autophagy inhibitor, counteracted the inhibitory effect of SYR on MMP-2 expression. Conclusion: SYR showed antioxidant activity and up-regulated autophagy activity in H2O2-stimulated HaCaT cells, lowering the expression of MMP-2 and MMP-9 associated with skin aging. Our results suggest that SYR has potential value as a cosmetic additive for prevention of skin aging.

The Untapped Potential of Ginsenosides and American Ginseng Berry in Promoting Mental Health via the Gut-Brain Axis.

Despite the popularity of the ginseng (Panax) root in health research and on the market, the ginseng berry's potential remains relatively unexplored. Implementing ginseng berry cultivations and designing berry-derived products could improve the accessibility to mental health-promoting nutraceuticals. Indeed, the berry could have a higher concentration of neuroprotective and antidepressant compounds than the root, which has already been the subject of research demonstrating its efficacy in the context of neuroprotection and mental health. In this review, data on the berry's application in supporting mental health via the gut-brain axis is compiled and discussed.

The Administration of Panax Ginseng Berry Extract Attenuates High-Fat-Diet-Induced Sarcopenic Obesity in C57BL/6 Mice.

Sarcopenia and obesity are serious health problems that are highly related to several metabolic diseases. Sarcopenic obesity, a combined state of sarcopenia and obesity, results in higher risks of metabolic diseases and even mortality than sarcopenia or obesity alone. Therefore, the development of therapeutic agents for sarcopenic obesity is crucial. C57BL/6 mice were fed with a high-fat diet (HFD) for 9 weeks. Then, mice were administered with Panax ginseng berry extract (GBE) for an additional 4 weeks, with continuous HFD intake. GBE significantly decreased the food efficiency ratio, serum lipid and insulin levels, adipose tissue weights, and adipocyte size. It significantly increased the grip strength, muscle masses, and myofiber cross-sectional area. It deactivated the protein kinase C (PKC) theta and zeta, resulting in activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, which is known to regulate muscle synthesis and degradation. Furthermore, it inhibited the production of inflammatory cytokines in the muscle tissue. GBE attenuated both obesity and sarcopenia. Thus, GBE is a potential agent to prevent or treat sarcopenic obesity.

Synergetic effect of soluble whey protein hydrolysate and Panax ginseng berry extract on muscle atrophy in hindlimb-immobilized C57BL/6 mice.

Background: Sarcopenia, defined as loss of muscle mass and strength with age, becomes a public health concern as the elderly population increases. This study aimed to determine whether the mixture of soluble whey protein hydrolysate (WPH) and Panax ginseng berry extract (GBE) has a synergetic effect on sarcopenia and, if so, to identify the relevant mechanisms and optimal mixing ratio. Methods: In the first experiment, C57BL/6 mice were hindlimb immobilized for one-week and then administered WPH 800 mg/kg, GBE 100 mg/kg, WPH 800 mg/kg+ GBE 100 mg/kg mixture, and Fructus Schisandrae extract (SFE) 200 mg/kg for two weeks. In the second experiment, experimental design was same, but mice were administered three different doses of WPH and GBE mixture (WPH 800 mg/kg+ GBE 100 mg/kg, WPH 800 mg/kg+ GBE 90 mg/kg, WPH 1000 mg/kg+ GBE 75 mg/kg). Results: In the first experiment, we confirmed the synergetic effect of WPH and GBE on muscle mass and identified that GBE was more effective on the protein synthesis side, and WPH tended to be slightly more effective for protein degradation. In the second experiment, among three different ratios, the WPH 800 mg/kg+ GBE 100 mg/kg was most effective for muscle mass and strength. The mixtures activated muscle protein synthesis via PI3K/Akt/mTORc1 pathway and inhibited muscle protein degradation via suppressing ubiquitin-proteasome system (UPS) and autophagy-lysosome system (ALS), and these effects were more GBE dose-dependent than WPH. Conclusion: The WPH and GBE mixture having a synergetic effect is a potential agent to prevent sarcopenia.

Evaluation and Screening of Hypoglycemic Activity of Total Ginsenosides GBE-5 Fraction From Panax Ginseng Berry Based on UHPLC-MS Metabolomics.

Objective: Ginseng berry (GB) was the mature fruit of medicinal and edible herb, Panax ginseng C.A. Meyer, with significant hypoglycemic effect. Ginsenoside was the main hypoglycemic active component of GB. Evaluating and screening the effective components of GB was of great significance to further develop its hypoglycemic effect. Methods: The polar fractions of ginseng berry extract (GBE) were separated by a solvent extraction, and identified by ultra-high performance liquid chromatography-high-resolution mass spectrometry (UHPLC-MS). The insulin resistance model of HepG2 cells was established, and the hypoglycemic active fraction in GBE polar fractions were screened in vitro. Rat model of type 2 diabetes mellitus (T2DM) was established to verify the hypoglycemic effect of the GBE active fraction. The metabolomic study based on UHPLC-MS was used to analyze the differential metabolites in the serum of T2DM rats after 30 days of intervention with hypoglycemic active GBE fraction. The kyoto encyclopedia of genes and genomes (KEGG) metabolic pathway enrichment analysis was used to study the main metabolic pathways involved in the regulation of hypoglycemic active parts of GBE. Results: It was found that GBE-5 fraction had better hypoglycemic activity than other GBE polar fractions in vitro cell hypoglycemic activity screening experiment. After 30 days of treatment, the fasting blood glucose value of T2DM rats decreased significantly by 34.75%, indicating that it had significant hypoglycemic effect. Eighteen differential metabolites enriched in KEGG metabolic pathway were screened and identified in the rat serum from T2DM vs. GBE-5 group, and the metabolic pathways mainly involved in regulation include arachidonic acid (AA) metabolism, linoleic acid (LA) metabolism, unsaturated fatty acid biosynthesis, and ferroptosis. Conclusions: The hypoglycemic effect of GBE-5 fraction was better than that of total ginsenoside of GB. The AA metabolism, LA metabolism, unsaturated fatty acid biosynthesis, and ferroptosis were the potential metabolic pathways for GBE-5 fraction to exert hypoglycemic regulation.

The Panax ginseng Berry Extract and Soluble Whey Protein Hydrolysate Mixture Ameliorates Sarcopenia-Related Muscular Deterioration in Aged Mice.

Sarcopenia is prevalent as the aging population grows. Therefore, the need for supplements for the elderly is increasing. This study aimed to investigate the efficacy and mechanism of a Panax ginseng berry extract (GBE) and soluble whey protein hydrolysate (WPH) mixture on a sarcopenia-related muscular deterioration in aged mice. Ten-month-old male C57BL/6J mice were administered three different doses of the GBE + WPH mixture for 8 weeks; 700 mg/kg, 900 mg/kg, and 1100 mg/kg. Grip strength, serum inflammatory cytokines level, and mass of muscle tissues were estimated. The deteriorating function of aging muscle was investigated via protein or gene expression. Grip strength and mass of three muscle tissues were increased significantly in a dose-dependent manner, and increased anti-inflammatory cytokine alleviated systemic inflammatory state. The mixture resolved the imbalance of muscle protein turnover through activation of the PI3K/Akt pathway and increased gene expression of the muscle regeneration-related factors, while decreasing myostatin, which interferes with muscle protein synthesis and regeneration. Furthermore, we confirmed that increased mitochondria number in muscle with the improvement of mitochondrial biogenesis. These physiological changes were similar to the effects of exercise.

Comprehensive phytochemicals analysis and anti-myocardial ischemia activity of total saponins of American ginseng berry.

American ginseng berry (AGB) is a new medicinal source. Total saponins of American ginseng berry (TSAGB) are the main active ingredients. The effects and active saponins of TSAGB on myocardial ischemia (MI) rats were evaluated for the first time. First, there were 69 saponins identified or tentatively characterized by Ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS/MS) combined with UNIFI platform, among which, about 28 saponins were first identified in AGB. Second, MI model was established by ligating left coronary artery. It has been demonstrated that TSAGB could prevent the ST-segment elevation, reduce myocardial infarct size and levels of aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), and elevate the superoxide dismutase (SOD) level. Finally, network pharmacology combined with molecular docking to screen out four active saponins (ginsenoside Re, Rb3 , Rg3 , and PF11 ) and five key targets (SOD1, LDHA, CKB, GOT2, and ROS1) closely related to MI. PRACTICAL APPLICATIONS: This study enriches the chemical composition of TSAGB, and provides a basis for clarifying the pharmacological substances for anti-myocardial ischemia. TSAGB might be a potential anti-myocardial ischemia agent. The effect might be related to alleviating oxidative stress.

Immune-Enhancing Effects of Crude Polysaccharides from Korean Ginseng Berries on Spleens of Mice with Cyclophosphamide-Induced Immunosuppression.

Panax ginseng C. A. Meyer is well known as traditional herbal medicine, and ginseng berries are known to exhibit potential immune-enhancing functions. However, little is known about the in vivo immunomodulatory activity of Korean ginseng berries. In this study, crude Korean ginseng berries polysaccharides (GBP) were isolated and their immunomodulatory activities were investigated using cyclophosphamide (CY)-induced immunosuppressive BALB/c mice. In CY-treated mice, oral administration of GBP (50-500 mg/kg BW) remarkably increased their spleen sizes and spleen indices and activated NK cell activities. GBP also resulted in the proliferation of splenic lymphocytes (coordinating with ConA: plant mitogen which is known to stimulate T-cell or LPS: endotoxin which binds receptor complex in B cells to promote the secretion of pro-inflammatory cytokines) in a dose-dependent manner. In addition, GBP significantly stimulated mRNA expression levels of immune-associated genes including interleukin-1ß (IL-1ß), IL-2, IL-4, IL-6, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), toll-like receptor 4 (TLR-4), and cyclooxygenase-2 (COX-2) in CY-treated mice. These results indicate that GBP is involved in immune effects against CY-induced immunosuppression. Thus, GBP could be developed as an immunomodulation agent for medicinal or functional food application.

Anti-Inflammatory and Anti-Oxidant Effects of Korean Ginseng Berry Extract in LPS-Activated RAW264.7 Macrophages.

Inflammatory macrophages stimulated by LPS disrupt homeostasis in the production of inflammatory cytokines and nitric oxide (NO). These are the causes of inflammation-related diseases and various cancers. The present study aimed to evaluate the protective effects of Korean ginseng berry extract (KGB) on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophage cells. NO and prostaglandin E2 (PGE[Formula: see text] production was elevated in response to LPS stimulation and was dose-dependently reduced by pretreatment with KGB. The expression levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA and protein were also reduced by KGB treatment. KGB treatment significantly suppressed the LPS-induced gene expression and production of cytokines, including interleukin (IL)-1[Formula: see text], IL-6, and tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]. Furthermore, KGB inhibited the translocation of nuclear expression of nuclear factor-kappa B (NF-[Formula: see text]B) by preventing inhibitory factor-kappa B (I[Formula: see text]B[Formula: see text] phosphorylation and suppressing the phosphorylation of extracellular signal-related kinase (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. Additionally, decreased reactive oxygen species (ROS) generation and increased glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities were observed following KGB treatment. Taken together, these results indicated that KGB possesses anti-inflammatory and anti-oxidant effects, mediated by the inhibition of the mitogen-activated protein kinases (MAPKs) signaling pathway in LPS-induced RAW264.7 macrophages. KGB may represent a potential therapeutic agent for inflammatory and oxidative stress-related diseases.

Serum metabolomic analysis of the anti-diabetic effect of Ginseng berry in type II diabetic rats based on ultra high-performance liquid chromatography-high resolution mass spectrometry.

Serum metabolomic method was used to investigated the anti-diabetic effects and mechanism of Ginseng berry (GB) on high-fat diet combined streptozotocin induced type II diabetes mellitus (T2DM) rats based on ultra high performance liquid chromatography coupled with quadrupole Exactive orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap/MS). Serum samples from control group, T2DM group, metformin treatment group, and GB ginsenoside treatment group rats were collected after intervention. The biochemical parameters of serum were firstly analyzed. Then metabolomic studies based on UHPLC-Q-Exactive Orbitrap/MS and multivariate statistical analysis were performed for the pattern recognition and characteristic metabolites identification. The differential metabolites were analyzed by KEGG metabolic pathway to study the potential mechanism. The treatment of GB ginsenoside significantly reduced the blood glucose level, increased the content of serum SOD, and reduced the content of malondialdehyde. Respectively 16, 9, and 24 differential metabolites were found and identified in T2DM compared to control group, metformin compared to T2DM group and GB compared to T2DM group. Metabolic pathways analysis indicated that GB ginsenoside regulated bile acid metabolism, arachidonic acid metabolism, glucuronization to play a role in the treatment of T2DM. This study verified the anti-diabetic and anti-oxidation effects of ginseng berry, elaborated that GB regulated the secretion of bile acids, activated GLP-1 pathway, increased the secretion of insulin, promoted the hydrolysis of fat and triglyceride, inhibited the activity of 5α - reductase, reduced weight and insulin resistance, so as to improved and treated T2DM, and laid the foundation for the further development and utilization.