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Rainfall, particularly in continental climates with a monsoonal tendency, impacts the microbial niches during the growth of mountain cultivated ginseng. With shifts in the microbial community, diseases in ginseng cultivated and protected under rain shelter conditions may ultimately be altered. Such cultivation may influence microflora dynamics through variations in meteorological parameters; however, this is not yet clear. The present study found that rain shelter cultivation affected the distribution of fungal communities within mountain cultivated ginseng. This led to an improved community structure in the ginseng rhizosphere, characterized by the proliferation of antagonistic fungi and a reduction in pathogenic fungi. A correlation analysis of meteorological factors found that soil temperature and humidity were the primary meteorological factors affecting mountain cultivated ginseng. It is evident that rain shelter cultivation regulated the microecological environment of the mountain cultivated ginseng's rhizosphere and resulted in positive outcomes. A disease investigation supported this finding. The incidence of ginseng root diseases, such as rust and root rot, was reduced by 5–6%. The incidence of ginseng leaf diseases, including gray mold and black spot, was reduced by 5–10%. This research provides evidence to address the dynamics of microbial ecology under rain shelter cultivation and its benefits for sustainable mountain cultivated ginseng management. [ABSTRACT FROM AUTHOR]

In this study, the nutrients, phytochemicals (including isoflavone and ginsenoside derivatives), and antioxidant activities of cheonggukjang with different ratios (0%, 2.5%, 5%, and 10%) of mountain-cultivated ginseng (MCG) were compared and analyzed using microorganisms isolated from traditional cheonggukjang. The IDCK 30 and IDCK 40 strains were confirmed as Bacillus licheniformis and Bacillus subtilis, respectively, based on morphological, biological, biochemical, and molecular genetic identification, as well as cell wall fatty acid composition. The contents of amino acids and fatty acids showed no significant difference in relation to the ratio of MCG. After fermentation, isoflavone glycoside (such as daidzin, glycitin, and genistin) contents decreased, while aglycone (daidzein, glycitein, and genistein) contents increased. However, total ginsenoside contents were higher according to the ratio of MCG. After fermentation, ginsenoside Rg2, F2, and protopanaxadiol contents of cheonggukjang decreased. Conversely, ginsenoside Rg3 (2.5%: 56.51 → 89.43 μg/g, 5.0%: 65.56 → 94.71 μg/g, and 10%: 96.05 → 166.90 μg/g) and compound K (2.5%: 28.54 → 69.43 μg/g, 5.0%: 41.63 → 150.72 μg/g, and 10%: 96.23 → 231.33 μg/g) increased. The total phenolic and total flavonoid contents were higher with increasing ratios of MCG and fermentation (fermented cheonggukjang with 10% MCG: 13.60 GAE and 1.87 RE mg/g). Additionally, radical scavenging activities and ferric reducing/antioxidant power were significantly increased in fermented cheonggukjang. This study demonstrates that the quality of cheonggukjang improved, and cheonggukjang with MCG as natural antioxidants may be useful in food and pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Steroid-resistant asthma (SRA), resisting glucocorticoids such as dexamethasone (DEX), is a bottleneck in the treatment of asthma. It is characterized by a predominantly neutrophilic inflammatory subtype and is prone to developing into severe refractory asthma and fatal asthma. Currently, there is a lack of universally effective treatments for SRA. Moreover, since cold stimulation does increase the risk of asthma development and exacerbate asthma symptoms, the treatment of cold-stimulated SRA (CSRA) will face greater challenges. To find effective new methods to ameliorate CSRA, this study established a CSRA mouse model of allergic airway inflammation mimicking human asthma for the first time and evaluated the alleviating effects of 80% ethanol extract of mountain-cultivated ginseng (MCG) based on multi-omics analysis. The results indicate that cold stimulation indeed exacerbated the SRA-related symptoms in mice; the DEX individual treatment did not show a satisfactory effect; while the combination treatment of DEX and MCG could dose-dependently significantly enhance the lung function; reduce neutrophil aggregation; decrease the levels of LPS, IFN-γ, IL-1β, CXCL8, and IL-17; increase the level of IL-10; alleviate the inflammatory infiltration; and decrease the mucus secretion and the expression of MUC5AC. Moreover, the combination of DEX and high-dose (200 mg/kg) MCG could significantly increase the levels of tight junction proteins (TJs), regulate the disordered intestinal flora, increase the content of short-chain fatty acids (SCFAs), and regulate the abnormal gene profile and metabolic profile. Multi-omics integrated analysis showed that 7 gut microbes, 34 genes, 6 metabolites, and the involved 15 metabolic/signaling pathways were closely related to the pharmacological effects of combination therapy. In conclusion, integrated multi-omics profiling highlighted the benefits of MCG for CSRA mice by modulating the interactions of microbiota, genes, and metabolites. MCG shows great potential as a functional food in the adjuvant treatment of CSRA. [ABSTRACT FROM AUTHOR]

The current research was the first to prove the existence of fluctuations in the metabolite constituents and antioxidant properties in different organs (leaves, stems, and roots) of the mountain-cultivated ginseng (MCG) plant during a two-month maturation period. Four metabolites, including fatty acids, amino acids, ginsenosides, and phenolic phytochemicals, exhibited considerable differences in organs and maturation times with the following order: leaves > stems > roots. The predominant metabolite contents were found in leaves, with fatty acid (1057.9 mg/100 g) on 31 May, amino acid (1989.2 mg/100 g) on 13 July, ginsenosides (88.7 mg/g) on 31 May, and phenolic phytochemical (638.3 μg/g) on 31 May. Interestingly, ginsenoside content in leaves were highest, with 84.8 → 88.7 → 82.2 → 78.3 mg/g. Specifically, ginsenosides Re, Rd, and F2 showed abundant content ranging from 19.1 to 16.9 mg/g, 8.5 to 14.8 mg/g, and 9.5 to 13.1 mg/g, respectively. Phenolic phytochemicals exhibited remarkable differences in organs compared to maturation periods, with the highest total phenolic content and total flavonoid content recorded at 9.48 GAE and 1.30 RE mg/g in leaves on 31 May. The antioxidant capacities on radical, FRAP, and DNA protection differed significantly, with leaves on 31 May exhibiting the highest values: 88.4% (DPPH), 89.5% (ABTS), 0.84 OD593 nm (FRAP) at 500 μg/mL, and 100% DNA protection at 50 μg/mL. Furthermore, principal cluster analysis revealed metabolite variability as follows: ginsenoside (83.3%) > amino acid (71.8%) > phenolic phytochemical (61.1%) > fatty acid (58.8%). A clustering heatmap highlighted significant changes in metabolite components under the maturation times for each organ. Our findings suggest that MCG leaves on 31 May may be a potential source for developing nutraceuticals, offering highly beneficial components and strong antioxidants. [ABSTRACT FROM AUTHOR]

In this study, the nutrients, phytochemicals (including isoflavone and ginsenoside derivatives), and antioxidant activities of cheonggukjang with different ratios (0%, 2.5%, 5%, and 10%) of mountain-cultivated ginseng (MCG) were compared and analyzed using microorganisms isolated from traditional cheonggukjang. The IDCK 30 and IDCK 40 strains were confirmed as Bacillus licheniformis and Bacillus subtilis, respectively, based on morphological, biological, biochemical, and molecular genetic identification, as well as cell wall fatty acid composition. The contents of amino acids and fatty acids showed no significant difference in relation to the ratio of MCG. After fermentation, isoflavone glycoside (such as daidzin, glycitin, and genistin) contents decreased, while aglycone (daidzein, glycitein, and genistein) contents increased. However, total ginsenoside contents were higher according to the ratio of MCG. After fermentation, ginsenoside Rg2, F2, and protopanaxadiol contents of cheonggukjang decreased. Conversely, ginsenoside Rg3 (2.5%: 56.51 → 89.43 μg/g, 5.0%: 65.56 → 94.71 μg/g, and 10%: 96.05 → 166.90 μg/g) and compound K (2.5%: 28.54 → 69.43 μg/g, 5.0%: 41.63 → 150.72 μg/g, and 10%: 96.23 → 231.33 μg/g) increased. The total phenolic and total flavonoid contents were higher with increasing ratios of MCG and fermentation (fermented cheonggukjang with 10% MCG: 13.60 GAE and 1.87 RE mg/g). Additionally, radical scavenging activities and ferric reducing/antioxidant power were significantly increased in fermented cheonggukjang. This study demonstrates that the quality of cheonggukjang improved, and cheonggukjang with MCG as natural antioxidants may be useful in food and pharmaceutical applications.

Mountain‐cultivated ginseng is typically harvested after 10 years, while ginseng aged over 15 years is considered wild ginseng. This study aims to differentiate mountain‐cultivated ginseng by age, as the fraudulent practice of selling low‐aged cultivated ginseng disguised as high‐aged one is damaging the market. In this study, LC‐MS analyzed 98 ginseng samples, and multivariate statistical analysis identified patterns between samples to select influential components. Machine learning models were developed to identify ginseng samples of different ages. The untargeted metabolomic analysis clearly divided samples aged 4‐20 years into three age groups. Twenty‐two potential age‐dependent biomarkers were discovered to differentiate the three sample groups. Three machine learning models were used to predict new samples, and the optimal model was selected. Some biomarkers could determine age phases according to the differentiation of mountain‐cultivated ginseng samples. These biomarkers were thoroughly analyzed for variation trends. The machine learning models established using the screened biomarkers successfully predicted the age group of new samples. [ABSTRACT FROM AUTHOR]

Plant-derived miRNAs exist in mammals in a cross-kingdom manner and many studies have focused on their role in regulating and treating diseases. Mountain-cultivated ginseng (Panax ginseng C.A. Mey.) is a valuable Chinese medicine with anti-cancer activity. However, the miRNAs with anti-cancer activity are less studied. In this study, 12 mountain-cultivated ginseng samples were collected from Liaoning Province, China, at 4, 15, 18, and 20 growth years, three biological replicates of each growth year were performed. Small RNA libraries were constructed and sequenced on the BGISEQ-500 platform. By sequencing analysis, 299 miRNAs were identified, including 48 known miRNAs and 251 potential novel miRNAs. A total of 4633 potential human genes were predicted as putative targets of miRNAs by using RNA hybrid, Miranda, and Target Scan software. Then 75 miRNAs were screened to target 277 cancer genes. Interestingly, pgi-miR6135a targeted SOS1 to inhibit cancer occurrence, and its expression level increased with the growth years. It is suggested that the expression of miRNA may affect the anti-cancer activity of mountain-cultivated ginseng in different growth years. However, the human targets of mountain-cultivated ginseng miRNAs need to be confirmed through further experimental validation. This study predicted the miRNA of mountain-cultivated ginseng with anti-cancer activity and provided insights for researches investigating the efficacy of traditional Chinese medicine from the perspective of cross-kingdom regulation of plant-derived miRNAs. [ABSTRACT FROM AUTHOR]

The current research was the first to prove the existence of fluctuations in the metabolite constituents and antioxidant properties in different organs (leaves, stems, and roots) of the mountain-cultivated ginseng (MCG) plant during a two-month maturation period. Four metabolites, including fatty acids, amino acids, ginsenosides, and phenolic phytochemicals, exhibited considerable differences in organs and maturation times with the following order: leaves > stems > roots. The predominant metabolite contents were found in leaves, with fatty acid (1057.9 mg/100 g) on 31 May, amino acid (1989.2 mg/100 g) on 13 July, ginsenosides (88.7 mg/g) on 31 May, and phenolic phytochemical (638.3 μg/g) on 31 May. Interestingly, ginsenoside content in leaves were highest, with 84.8 → 88.7 → 82.2 → 78.3 mg/g. Specifically, ginsenosides Re, Rd, and F2 showed abundant content ranging from 19.1 to 16.9 mg/g, 8.5 to 14.8 mg/g, and 9.5 to 13.1 mg/g, respectively. Phenolic phytochemicals exhibited remarkable differences in organs compared to maturation periods, with the highest total phenolic content and total flavonoid content recorded at 9.48 GAE and 1.30 RE mg/g in leaves on 31 May. The antioxidant capacities on radical, FRAP, and DNA protection differed significantly, with leaves on 31 May exhibiting the highest values: 88.4% (DPPH), 89.5% (ABTS), 0.84 OD593 nm (FRAP) at 500 μg/mL, and 100% DNA protection at 50 μg/mL. Furthermore, principal cluster analysis revealed metabolite variability as follows: ginsenoside (83.3%) > amino acid (71.8%) > phenolic phytochemical (61.1%) > fatty acid (58.8%). A clustering heatmap highlighted significant changes in metabolite components under the maturation times for each organ. Our findings suggest that MCG leaves on 31 May may be a potential source for developing nutraceuticals, offering highly beneficial components and strong antioxidants.

Mountain-cultivated Panax ginseng C.A.Mey. (MCG) with high market price and various properties was valuable special local product in Northeast of Asia. MCG has been historically used to mitigate heart failure (HF) for thousand years, HF is a clinical manifestation of deficiency of "heart-qi" in traditional Chinese medicine. However, there was little report focus on the activities of extracted residue of MCG. A novel glycopeptide (APMCG-1) was isolated from step ethanol precipitations of alkaline protease-assisted extract from MCG residue. The molecular weight and subunit structure of APMCG-1 were determined by FT-IR, HPLC and GPC technologies, as well as the H9c2 cells, T g (kdrl:EGFP) zebrafish were performed to evaluated the protective effect of APMCG-1. APMCG-1 was identified as a glycopeptide containing seven monosaccharides and seven amino acids via O-lined bonds. Further, in vitro , APMCG-1 significantly decreased reactive oxygen species production and lactate dehydrogenase contents in palmitic acid (PA)-induced H9c2 cells. APMCG-1 also attenuated endoplasmic reticulum stress and mitochondria-mediated apoptosis in H9c2 cells via the PI3K/AKT signaling pathway. More importantly, APMCG-1 reduced the blood glucose, lipid contents, the levels of heart injury, oxidative stress and inflammation of 5 days post fertilization T g (kdrl:EGFP) zebrafish with type 2 diabetic symptoms in vivo. APMCG-1 protects PA-induced H9c2 cells while reducing cardiac dysfunction in zebrafish with type 2 diabetic symptoms. The present study provides a new insight into the development of natural glycopeptides as heart-related drug therapies. [Display omitted] [ABSTRACT FROM AUTHOR]

It has been recognized that serotonergic blocker showed serious side effects, and that ginsenoside modulated serotonergic system with the safety. However, the effects of ginsenoside on serotonergic impairments remain to be clarified. Thus, we investigated ginsenoside Re (GRe), a major bioactive component in the mountain-cultivated ginseng on (±)-8-hydroxy-dipropylaminotetralin (8-OH-DPAT), a 5-HT1A receptor agonist. In the present study, we observed that the treatment with GRe resulted in significant inhibition of protein kinase C δ (PKCδ) phosphorylation induced by the 5-HT1A receptor agonist (±)-8-hydroxy-dipropylaminotetralin (8-OH-DPAT) in the hypothalamus of the wild-type (WT) mice. The inhibition of GRe was comparable with that of the PKCδ inhibitor rottlerin or the 5-HT1A receptor antagonist WAY100635 (WAY). 8-OH-DPAT-induced significant reduction in nuclear factor erythroid-2-related factor 2 (Nrf2)-related system (i.e., Nrf2 DNA binding activity, γ-glutamylcysteine ligase modifier (GCLm) and γ-glutamylcysteine ligase catalytic (GCLc) mRNA expression, and glutathione (GSH)/oxidized glutathione (GSSG) ratio) was significantly attenuated by GRe, rottlerin, or WAY in WT mice. However, PKCδ gene knockout significantly protected the Nrf2-dependent system from 8-OH-DPAT insult in mice. Increases in 5-hydroxytryptophan (5-HT) turnover rate, overall serotonergic behavioral score, and hypothermia induced by 8-OH-DPAT were significantly attenuated by GRe, rottlerin, or WAY in WT mice. Consistently, PKCδ gene knockout significantly attenuated these parameters in mice. However, GRe or WAY did not provide any additional positive effects on the serotonergic protective potential mediated by PKCδ gene knockout in mice. Therefore, our results suggest that PKCδ is an important mediator for GRe-mediated protective activity against serotonergic impairments/oxidative burden caused by the 5-HT1A receptor. [ABSTRACT FROM AUTHOR]

Although there are differences in the appearance of Mountain-Cultivated Ginseng (MCG) and Garden-Cultivated Ginseng (GCG), it is very difficult to distinguish them when the samples are processed to slices or powder. Moreover, there is significant price difference between them, which leads to the widespread adulteration or falsification in the market. Thus, the authentication of MCG and GCG is crucial for the effectiveness, safety, and quality stability of ginseng. In the present study, a headspace solid-phase microextraction gas chromatography mass spectrometry (HS-SPME-GC-MS) coupled with chemometrics approach was developed to characterize the volatile component profiles in MCG and GCG with 5-,10-,15-growth years, and subsequently to discover differentiating chemical markers. As a result, we characterized, for the first time, 46 volatile components from all the samples by using the NIST database and the Wiley library. The base peak intensity chromatograms were subjected to multivariate statistical analysis to comprehensively compare the chemical differences among the above samples. MCG5-,10-,15-years and GCG5-,10-,15-years samples were mainly divided into two groups by unsupervised principal component analysis (PCA), and 5 potential cultivation-dependent markers were discovered based on orthogonal partial least squares-discriminant analysis (OPLS-DA). Moreover, MCG5-,10-,15-years samples were divided into three blocks, and 12 potential growth-year-dependent markers enabled differentiation. Similarly, GCG5-,10-,15-years samples were also separated into three groups, and six potential growth-year-dependent markers were determined. The proposed approach could be applied to directly distinguish MCG and GCG with different growth years and to identify the differentiation chemo-markers, which is an important criterion for evaluating the effectiveness, safety, and quality stability of ginseng. [ABSTRACT FROM AUTHOR]

This study investigated changes in nutrients (fatty acids, amino acids, and minerals), ginsenosides, and volatile flavors, and antioxidant activities during food processing of mountain-cultivated ginseng (MCG) with the cocktail lactic acid bacteria. Fatty acid content increased, but the free amino acid content decreased, and minerals were practically unaffected during processing. Total phenolic and flavonoid contents and maillard reaction products increased markedly according to processing stage. The total ginsenosides levels increased from 31.25 mg/g (DMCG) to 32.36 mg/g (red MCG, RMCG) and then decreased (27.27 mg/g, at fermented RMCG) during processing. Particularly, the contents of F2 (0.31 → 1.02 → 2.27 mg/g), Rg3 (0.36 → 0.77 → 1.93 mg/g), and compound K (0.5 → 1.68 → 4.13 mg/g) of ginsenosides and β-panasinsene (17.28 → 22.69 → 31.61%), biocycloelemene (0.11 → 0.84 → 0.92%), δ-cadinene (0.39 → 0.5 → 0.94%), and alloaromadendrene (1.64 → 1.39 → 2.6%) of volatile flavor compounds increased during processing, along with to the antioxidant effects (such as DPPH, ABTS, and hydroxyl radical scavenging activities, and FRAP). This study may provide several choices for the use of ginseng in functional foods and functional cosmetics. [ABSTRACT FROM AUTHOR]

Mountain-cultivated ginseng (MCG) is a very important health functional material in Korea and the USA. In this study, the growth and saponin of MCG change according to the sowing method were investigated. Six methods of sowing according to the natural cultivation method that grows in the Sancheong mountain ginseng farm were investigated. Germination rate and budding rate were different according to the sowing method. The growth characteristics of the MCG were also different in the sowing method. Among the six sowing methods, the length of leaves was the widest in BFS. The width of the leaves was wide in DFS and DS. The weight of the shoot was the heaviest in BFS, and the DF was the lightest. Root diameter was highest in BFS and DFS covering both fallen leaves and soil. Total fresh weight was the highest at 4.03 g in BFS, followed by DFS. The S/R ratio of DF was lower than that of the other methods. This suggests that the S/R ratio is lowered because the growth of the ground part is worse. The treatment group with the highest crude saponin content was BF and the lowest treatment group was BS. Shoot and root growth tended to increase with growing period, saponin content increased slightly within 1–3 years, but decreased slightly after that. In particular, the ratio of PD/PT, which has a great influence on the efficacy of ginseng, was also different according to the sowing method. The seed sowing method identified in this study will greatly contribute to the improvement of the survival rate decrease over the cultivation period, and it will also contribute to the production of high-quality MCG.

Panax ginseng C. A. Mey (PGCAM) is a herbaceous perennial belonging to the Araliaceae family, mainly including Mountain-Cultivated Ginseng (MCG) and Garden Ginseng (GG) on the market. We aimed to establish a rapid, accurate and effective method to distinguish 15-year-old MCG and GG using ultra-performance liquid chromatography-quadrupole time-of-flight-tandem mass spectrometry (UPLC-QTOF-MS/MS), and also explored the pharmacological mechanisms of the main components using the Integrative Pharmacology-based Network Computational Research Platform of Traditional Chinese Medicine (TCMIP V2.0; http://www.tcmip.cn/). Altogether, 23 potential quality markers were characterized to distinguish 15-year-old MCG and GG, including ginsenosides Ra2, Rg1, and Ra1, and malonyl-ginsenoside Ra3, etc. The contents of 19 constituents (mainly protopanaxadiol-type) were higher in MCG compared with that in GG, and four constituents (mainly carbohydrate compounds) were higher in GG. The 105 putative targets corresponding to 23 potential quality markers were mainly involved in 30 pathways, which could be divided into 10 models, such as immune regulation, systems (metabolic, nervous, cardiovascular, reproductive), blood-pressure regulation, as well as antitumor, antiaging, antibacterial and anti-inflammatory effects. Furthermore, the potential quality markers of MCG and GG could inhibit the proliferation of breast cancer by regulating the mRNA expression of PSA, S6K, MDM2, and P53 genes by acting on AR, MTOR, PI3K and other targets. The Integrative Pharmacology Strategy may provide an efficient way to identify chemical constituents and explore the pharmacological actions of TCM formulations.

Abstract Background There exist differences in morphological traits and phytochemical compositions between field- and mountain-cultivated Panax ginseng (FCG and MCG), which might be attributed to variations of terpenoids metabolism adapting to different growth conditions. The present work aims to uncover these variations. Results Among 26,648 differentially expressed genes, 496 genes distributed in seven dominant terpenoids pathways were identified. Diterpenoids and triterpenoids biosynthesis genes were significantly higher-expressed in FCG root. Conversely, biosynthesis of carotenoids was significantly more active in MCG root. Additionally, terpenoids backbones, monoterpenoids, sesquiterpenoids, and terpenoid-quinones biosyntheses were neither obviously inclined. Our determination also revealed that there were more gibberellins and steroids accumulated in FCG root which might be responsible for its quick vegetative growth, and enriched abscisic acid and germacrenes as well as protopanaxatriol-type ginsenosides might be major causes of enhanced stress-resistance in MCG root. Conclusions The study firstly provided an overview of terpenoids metabolism in roots of FCG and MCG in elucidating the underlying mechanisms for their different morphological appearances and phytochemical compositions.

To study the inhibitory effects of Chaetomium globosum strain FS-01 against Alternaria panax, Sclerotinia schinseng, Botrytis cinerea, Rhizoctonia solani and Fusarium solani of ginseng pathogens, mycelia, fermentation broth and conidia suspension were tested in laboratory. The results showed that Chaetomium globosum FS-01 had certain inhibitory effects against five kinds of ginseng pathogens by confront culture. Among them, the highest inhibition rate to mycelia growth of Alternaria panax, reached 30.80%, followed by Rhizoctonia solani, Sclerotinia schinseng, Fusarium solani and Botrytis cinerea; On the PDA plate mixed with Chaetomium globosum FS-01 fermentation broth, the highest inhibition rate to mycelia growth of Botrytis cinerea, reached 82.09%, followed by Sclerotinia schinseng, Alternaria panax, Rhizoctonia solani and Fusarium solani; On the PDA plate mixed with Chaetomium globosum FS-01 conidia suspension, the highest inhibition rate to mycelia growth of Alternaria panax, reached 83.72%, followed by Botrytis cinerea, Rhizoctonia solani, Sclerotinia schinseng and Fusarium solani. Endophytic fungi FS-01 strain had a significant inhibitory effects, it could be utilized as a biological control resource inhibiting ginseng pathogens. [ABSTRACT FROM AUTHOR]

Garden-cultivated Ginseng (GG) and mountain-cultivated Ginseng (MG) both belong to Panax Ginseng C. A. Meyer. However, the effective substances which can be used to distinguish GG from MG remain obscure. Therefore, the purpose of this study was to screen for discriminating markers that can assist in the correct identification of GG and MG. HPLC Q-TOF/MS and various chemometrics methods were used to analyze the chemical profiles of 13 batches of Ginseng and to explore the characteristic constituents of both GG and MG. The hepatocyte-protecting effects of GG and MG were investigated through a paclitaxel-induced liver injury model. Through a combination of correlation analysis and bioinformatic techniques, markers for differentiation between GG and MG were ascertained. A total of 40 and 41 compounds were identified in GG and MG, respectively, and 15 characteristic ingredients contributed significantly to the discrimination of GG from MG. Correlation analysis and network pharmacology were applied and ginsenosides Rg1, Re, Rb1, Rc, Rb2, and Rg3 were found to be discriminating markers of GG and MG. Six markers for the identification of GG and MG were screened out by a step-wise mutually oriented “chemical profiling–pharmaceutical effect” correlation strategy, which is of great significance for future quality assessment of Ginseng products.

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Background: Mountain-cultivated ginseng (MCG) and cultivated ginseng (CG) both belong to Panax ginseng and have similar ingredients. However, their pharmacological activities are different due to their significantly different growth environments. Methods: An ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS)-based approach was developed to distinguish MCG and CG. Multivariate statistical methods, such as principal component analysis and supervised orthogonal partial-least-squares discrimination analysis were used to select the influential components. Results: Under optimized UPLC-QTOF-MS/MS conditions, 40 ginsenosides in both MCG and CG were unambiguously identified and tentatively assigned. The results showed that the characteristic components of CG and MCG included ginsenoside Ra3/isomer, gypenoside XVII, quinquenoside R1, ginsenoside Ra7, notoginsenoside Fe, ginsenoside Ra2, ginsenoside Rs6/Rs7, malonyl ginsenoside Rc, malonyl ginsenoside Rb1, malonyl ginsenoside Rb2, palmitoleic acid, and ethyl linoleate. The malony ginsenosides are abundant in CG, but higher levels of the minor ginsenosides were detected in MCG. Conclusion: This is the first time that the differences between CG and MCG have been observed systematically at the chemical level. Our results suggested that using the identified characteristic components as chemical markers to identify different ginseng products is effective and viable.

Physicochemical characteristics and anti-oxidant capacities of seeds from two farm-cultivated and one mountain-cultivated ginsengs (Panax ginseng Meyer) (MG) were determined. The seeds had 17.9-22.1% (dry basis) crude lipids, 11.5-15.2% crude proteins, and 1.4-1.7% ash. Oleic acid (77.9-78.5%) was the predominant fatty acid in the seed oils, followed by linoleic acid (16.6-17.4%). The highest Hunter b value, carotenoids, (β + γ)-tocotrienol, and δ-tocotrienol, and the lowest α-tocotrienol were observed in the seed oils from MG. Squalene was also the most abundant in the MG seed oils. β-Sitosterol was the major phytosterol in the seed oils with MG the highest. Defatted seed meal extracts from MG possessed the most total phenolics and flavonoids, and the highest DPPH and ABTS radical scavenging activities. These results suggest that MG seeds may be a novel source of functional foods. [ABSTRACT FROM AUTHOR]

Mountain-cultivated ginseng ( MCG) can be considered a mimic of wild ginseng, whose seeds are sowed artificially, cultivated in the natural environment, and returned to the wild state before being used clinically. Cultivated ginseng ( CG) and MCG are mainly used as the commercial material for clinical applications. However, MCG is much more expensive but effective than CG. The aim of this study is to explore the differences in the pharmacokinetics and brain concentration of Rg1, Re, Rb1, and Rd after oral administration of MCG, CG, and pure ginsenosides. An ultra-performance liquid chromatography-tandem mass spectrometry method was developed and validated to determine the concentration of the four ginsenosides in rat plasma and brain tissue. Compared with the pure group, the area under the curve ( AUC) of all the four ginsenosides for CG and MCG increased. The mean brain concentrations of the four ginsenosides were found to be 10- to 15-fold lower than the corresponding contents in the plasma, and the poor permeability of ginsenosides into blood-brain barrier was indicated by the low concentrations of the four ginsenosides. [ABSTRACT FROM AUTHOR]

The multi-drug resistance is an inherent weakness in the chemotherapeutics of non-small cell lung cancer occurring frequently all over the world. Clinically, ginseng and Chinese medicinal prescriptions including ginseng usually used as anti-tumor adjuncts due to its characteristic of qi-invigorating, which could improve the curative effect of chemotherapy drugs and reduce their toxic side effects. Triterpenoid saponins are the crucial active ingredients in Panax ginseng, and Ginsenoside Rb 1 is of the highest quantities. However, the research on the tumor drug-resistance reversal effect and mechanism of ginsenoside Rb 1 is still not clear. This study aimed to systematically estimate the reversal activity of Ginsenoside Rb 1 on cisplatin-insensitivity of A549/DDP cells and to reveal its prospective molecular mechanism. MTT assay were conducted to evaluate the reversal activity on cisplatin-insensitivity of A549/DDP cells of Ginsenoside Rb 1 in vitro , and the behavior was also studied by establishing a subcutaneous transplanted tumor model of A549/DDP in BALB/c-nu mice. In addition, P-gp ATPase activity assay, cisplatin accumulation assay, Annexin V-FITC apoptosis assay, real-time qPCR analysis and western blotting analysis were used to clarify the potential mechanism. Ginsenoside Rb 1 could effectively reverse the cisplatin-resistance of A549/DDP in vitro and vivo. And after the co-treatment of Ginsenoside Rb 1 plus cisplatin, the accumulation of cisplatin increased in A549/DDP cells, which was accompanied with the down-regulation of the mRNA and protein expression levels of ABCB1, SHH, PTCH1 and GLI2. Besides, the apoptosis-inducing ability of cisplatin improved by the relative regulation on the protein expression level of Bax and Bcl-2. Far more importantly, the changes of CYP3A4 mRNA and protein levels were not significant. Ginsenoside Rb 1 could increase the concentration of intracellular cisplatin and improve the insensitivity for cisplatin on A549/DDP cells. Even better, there was perhaps no unpredictable CYP3A4-mediated pharmacokinetic interactions after the combination of Ginsenoside Rb 1 plus cisplatin. Ginsenoside Rb 1 was a probable reversal agent for the cisplatin-insensitivity of A549/DDP cells, with a bifunction of inhibiting the efflux of two drug pumps (P-gp and PTCH1) by targeting ABCB1 and Hedgehog (Hh) pathway. In general, this research laid the groundwork for the development of a new reversal agent for the cisplatin-insensitivity of NSCLC. [Display omitted] [ABSTRACT FROM AUTHOR]

Aiming at further systematically comparing the similarities and differences of the chemical components in ginseng of different ages, especially comparing the younger or the older and mountain-cultivated ginseng (MCG), 4, 5, 6-year-old cultivated ginseng (CG) and 12, 20-year-old MCG were chosen as the analytical samples in the present study. The combination of UPLC-QTOF-MSE, UNIFI platform and multivariate statistical analysis were developed to profile CGs and MCGs. By the screening analysis based on UNIFI, 126 chemical components with various structural types were characterized or tentatively identified from all the CG and MCG samples for the first time. The results showed that all the CG and MCG samples had the similar chemical composition, but there were significant differences in the contents of markers. By the metabolomic analysis based on multivariate statistical analysis, it was shown that CG4–6 years, MCG12 years and MCG20 years samples were obviously divided into three different groups, and a total of 17 potential age-dependent markers enabling differentiation among the three groups of samples were discovered. For differentiation from other two kinds of samples, there were four robust makers such as α-linolenic acid, 9-octadecenoic acid, linoleic acid and panaxydol for CG4–6 years, five robust makers including ginsenoside Re1, -Re2, -Rs1, malonylginsenoside Rb2 and isomer of malonylginsenoside Rb1 for MCG20 years, and two robust makers, 24-hydroxyoleanolic acid and palmitoleic acid, for MCG12 years were discovered, respectively. The proposed approach could be applied to directly distinguish MCG root ages, which is an important criterion for evaluating the quality of MCG. The results will provide the data for the further study on the chemical constituents of MCG.

Background: The multi-drug resistance is an inherent weakness in the chemotherapeutics of non-small cell lung cancer occurring frequently all over the world. Clinically, ginseng and Chinese medicinal prescriptions including ginseng usually used as anti-tumor adjuncts due to its characteristic of qi-invigorating, which could improve the curative effect of chemotherapy drugs and reduce their toxic side effects. Triterpenoid saponins are the crucial active ingredients in Panax ginseng, and Ginsenoside Rb 1 is of the highest quantities. However, the research on the tumor drug-resistance reversal effect and mechanism of ginsenoside Rb 1 is still not clear., Purpose: This study aimed to systematically estimate the reversal activity of Ginsenoside Rb 1 on cisplatin-insensitivity of A549/DDP cells and to reveal its prospective molecular mechanism., Methods: MTT assay were conducted to evaluate the reversal activity on cisplatin-insensitivity of A549/DDP cells of Ginsenoside Rb 1 in vitro, and the behavior was also studied by establishing a subcutaneous transplanted tumor model of A549/DDP in BALB/c-nu mice. In addition, P-gp ATPase activity assay, cisplatin accumulation assay, Annexin V-FITC apoptosis assay, real-time qPCR analysis and western blotting analysis were used to clarify the potential mechanism., Results: Ginsenoside Rb 1 could effectively reverse the cisplatin-resistance of A549/DDP in vitro and vivo. And after the co-treatment of Ginsenoside Rb 1 plus cisplatin, the accumulation of cisplatin increased in A549/DDP cells, which was accompanied with the down-regulation of the mRNA and protein expression levels of ABCB1, SHH, PTCH1 and GLI2. Besides, the apoptosis-inducing ability of cisplatin improved by the relative regulation on the protein expression level of Bax and Bcl-2. Far more importantly, the changes of CYP3A4 mRNA and protein levels were not significant., Conclusion: Ginsenoside Rb 1 could increase the concentration of intracellular cisplatin and improve the insensitivity for cisplatin on A549/DDP cells. Even better, there was perhaps no unpredictable CYP3A4-mediated pharmacokinetic interactions after the combination of Ginsenoside Rb 1 plus cisplatin. Ginsenoside Rb 1 was a probable reversal agent for the cisplatin-insensitivity of A549/DDP cells, with a bifunction of inhibiting the efflux of two drug pumps (P-gp and PTCH1) by targeting ABCB1 and Hedgehog (Hh) pathway. In general, this research laid the groundwork for the development of a new reversal agent for the cisplatin-insensitivity of NSCLC., Competing Interests: Declaration of competing interest The authors declare no conflicts of interests., (Copyright © 2023. Published by Elsevier GmbH.)

• Mountain-cultivated ginseng was systematically analyzed. • Ginsenosides were in-depth characterized with α-chain and β-chain annotated. • Enhanced quantification of 213 ginsenosides was conducted. • Mountain-cultivated ginseng was differentiated from garden-cultivated ginseng. • 25-year-old mountain-cultivated ginseng was differentiated from 15/20-year-old one. Panax ginseng can be generally divided into mountain-cultivated ginseng (MCG) and garden-cultivated ginseng (GCG). The market price of MCG is significantly higher than that of GCG. However, the chemical compositions of MCG and the differences from GCG remained unclear. In this study, an integrated strategy combing an offline two-dimensional liquid chromatography separation, LTQ-orbitrap dual mode acquisition, and Q-trap full quantification/quasi-quantification was proposed to explore and compare the chemical compositions of MCG. Consequently, 559 ginsenosides were characterized, among which 437 ginsenosides were in-depth characterized with α-chain and β-chain annotated. Subsequently, enhanced quantification of 213 ginsenosides was conducted in 57 batches of MCG and GCG. Ginsenosides were found more abundant in MCG than GCG. In addition, 25-year-old MCG could be distinctly differentiated from 15/20-year-old MCG. This strategy facilitated the enhanced profiling and comparison of ginsenosides, improved the quality control tactics of MCG and provided a reference approach for other ginseng related products. [ABSTRACT FROM AUTHOR]

Demand is increasing for mountain-cultivated Panax ginseng (MCG) because its quality is considered superior to that of field-cultivated ginseng (FCG). However, MCG grows very slowly, and the factors that might affect this are unknown. In addition, little information is available about the physiological characteristics of its roots. Here, we investigated local soil environments and compared the histological and chemical properties of MCG and FCG roots. Average diameters, lengths, and fresh weights were much smaller in the former. Photosynthesis rates and root cambial activity also were reduced in the MCG tissues. Our analysis of soil from the mountain site revealed an extremely low phosphorus content, although those samples were richer in total nitrogen and organic matter than were the field soils. MCG roots also contained higher amounts of ginsenosides, and total accumulations increased with age. Moreover, ginsenoside Rh2, a red ginseng-specific compound, accumulated in the MCG roots but not in those from FCG plants. Interestingly, numerous calcium oxalate crystals were found in MCG roots, particularly in their rhizomes (i.e., short stems). Therefore, we can conclude from these results that low levels of the essential mineral phosphorus in mountain soils are a critical factor that retards the growth of mountain ginseng. Likewise, the high accumulation of calcium oxalate crystals in MCG roots might be an adaptation mechanism for survival in such a harsh local environment. [ABSTRACT FROM AUTHOR]

Garden-cultivated Ginseng (GG) and mountain-cultivated Ginseng (MG) both belong to Panax Ginseng C. A. Meyer. However, the effective substances which can be used to distinguish GG from MG remain obscure. Therefore, the purpose of this study was to screen for discriminating markers that can assist in the correct identification of GG and MG. HPLC Q-TOF/MS and various chemometrics methods were used to analyze the chemical profiles of 13 batches of Ginseng and to explore the characteristic constituents of both GG and MG. The hepatocyte-protecting effects of GG and MG were investigated through a paclitaxel-induced liver injury model. Through a combination of correlation analysis and bioinformatic techniques, markers for differentiation between GG and MG were ascertained. A total of 40 and 41 compounds were identified in GG and MG, respectively, and 15 characteristic ingredients contributed significantly to the discrimination of GG from MG. Correlation analysis and network pharmacology were applied and ginsenosides Rg1, Re, Rb1, Rc, Rb2, and Rg3 were found to be discriminating markers of GG and MG. Six markers for the identification of GG and MG were screened out by a step-wise mutually oriented "chemical profiling–pharmaceutical effect" correlation strategy, which is of great significance for future quality assessment of Ginseng products. [ABSTRACT FROM AUTHOR]

Panax ginseng C. A. Mey (PGCAM) is a herbaceous perennial belonging to the Araliaceae family, mainly including Mountain-Cultivated Ginseng (MCG) and Garden Ginseng (GG) on the market. We aimed to establish a rapid, accurate and effective method to distinguish 15-year-old MCG and GG using ultra-performance liquid chromatography-quadrupole time-of-flight-tandem mass spectrometry (UPLC-QTOF-MS/MS), and also explored the pharmacological mechanisms of the main components using the Integrative Pharmacology-based Network Computational Research Platform of Traditional Chinese Medicine (TCMIP V2.0; http://www.tcmip.cn/). Altogether, 23 potential quality markers were characterized to distinguish 15-year-old MCG and GG, including ginsenosides Ra2, Rg1, and Ra1, and malonyl-ginsenoside Ra3, etc. The contents of 19 constituents (mainly protopanaxadiol-type) were higher in MCG compared with that in GG, and four constituents (mainly carbohydrate compounds) were higher in GG. The 105 putative targets corresponding to 23 potential quality markers were mainly involved in 30 pathways, which could be divided into 10 models, such as immune regulation, systems (metabolic, nervous, cardiovascular, reproductive), blood-pressure regulation, as well as antitumor, antiaging, antibacterial and anti-inflammatory effects. Furthermore, the potential quality markers of MCG and GG could inhibit the proliferation of breast cancer by regulating the mRNA expression of PSA, S6K, MDM2, and P53 genes by acting on AR, MTOR, PI3K and other targets. The Integrative Pharmacology Strategy may provide an efficient way to identify chemical constituents and explore the pharmacological actions of TCM formulations. [ABSTRACT FROM AUTHOR]

Background: Ginseng ( Panax ginseng Meyer) is an invaluable medicinal plant containing various bioactive metabolites (e.g., ginsenosides). Owing to its long cultivation period, ginseng is vulnerable to various biotic constraints. Biological control using endophytes is an important alternative to chemical control., Methods: In this study, endophytic Trichoderma citrinoviride PG87, isolated from mountain-cultivated ginseng, was evaluated for biocontrol activity against six major ginseng pathogens. T. citrinoviride exhibited antagonistic activity with mycoparasitism against all ginseng pathogens, with high endo-1,4-β-D-glucanase activity., Results: T. citrinoviride inoculation significantly reduced the disease symptoms caused by Botrytis cinerea and Cylindrocarpon destructans  and induced ginsenoside biosynthesis in ginseng plants. T. citrinoviride was formulated as dustable powder and granules. The formulated agents also exhibited significant biocontrol activity and induced ginsenosides production in the controlled environment and mountain area., Conclusion: Our results revealed that T. citrinoviride has great potential as a biological control agent and elicitor of ginsenoside production.

Background: There exist differences in morphological traits and phytochemical compositions between field- and mountain-cultivated Panax ginseng (FCG and MCG), which might be attributed to variations of terpenoids metabolism adapting to different growth conditions. The present work aims to uncover these variations. Results: Among 26,648 differentially expressed genes, 496 genes distributed in seven dominant terpenoids pathways were identified. Diterpenoids and triterpenoids biosynthesis genes were significantly higher-expressed in FCG root. Conversely, biosynthesis of carotenoids was significantly more active in MCG root. Additionally, terpenoids backbones, monoterpenoids, sesquiterpenoids, and terpenoid-quinones biosyntheses were neither obviously inclined. Our determination also revealed that there were more gibberellins and steroids accumulated in FCG root which might be responsible for its quick vegetative growth, and enriched abscisic acid and germacrenes as well as protopanaxatriol-type ginsenosides might be major causes of enhanced stress-resistance in MCG root. Conclusions: The study firstly provided an overview of terpenoids metabolism in roots of FCG and MCG in elucidating the underlying mechanisms for their different morphological appearances and phytochemical compositions. [ABSTRACT FROM AUTHOR]

Aiming at further systematically comparing the similarities and differences of the chemical components in ginseng of different ages, especially comparing the younger or the older and mountain-cultivated ginseng (MCG), 4, 5, 6-year-old cultivated ginseng (CG) and 12, 20-year-old MCG were chosen as the analytical samples in the present study. The combination of UPLC-QTOF-MSE, UNIFI platform and multivariate statistical analysis were developed to profile CGs and MCGs. By the screening analysis based on UNIFI, 126 chemical components with various structural types were characterized or tentatively identified from all the CG and MCG samples for the first time. The results showed that all the CG and MCG samples had the similar chemical composition, but there were significant differences in the contents of markers. By the metabolomic analysis based on multivariate statistical analysis, it was shown that CG4–6 years, MCG12 years and MCG20 years samples were obviously divided into three different groups, and a total of 17 potential age-dependent markers enabling differentiation among the three groups of samples were discovered. For differentiation from other two kinds of samples, there were four robust makers such as α-linolenic acid, 9-octadecenoic acid, linoleic acid and panaxydol for CG4–6 years, five robust makers including ginsenoside Re1, -Re2, -Rs1, malonylginsenoside Rb2 and isomer of malonylginsenoside Rb1 for MCG20 years, and two robust makers, 24-hydroxyoleanolic acid and palmitoleic acid, for MCG12 years were discovered, respectively. The proposed approach could be applied to directly distinguish MCG root ages, which is an important criterion for evaluating the quality of MCG. The results will provide the data for the further study on the chemical constituents of MCG. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the effect of the vinegar, which is made of 4-year-old mountain-cultivated ginseng ripened into 4-year-matured persimmon vinegar, on the blood lipids level and inflammatory cytokines concentration in obese female adolescents., Methods: Subjects ingested the vinegar, so-called 'mountain-cultivated ginseng persimmon vinegar (MPV)', without meals every day for 6 weeks with activities control. Subjects were grouped into control (CON), persimmon vinegar (PV), and MPV with 10 people in each group. Blood lipids, triglyceride (TG), total-cholesterol (TC), and high density lipoprotein-cholesterol (HDL-C) were analyzed. Also, glutamic oxaloacetic transaminase (GOT) and glutamate pyruvate transaminase (GPT) were analyzed for the hepatotoxicity. Blood cytokines, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) were analyzed., Results: Subjects showed a high reduction in body weight and body fat. Their blood lipid level was effectively improved, and the secretion of inflammatory cytokine was suppressed as well, except for TNF-α. However, the change ratio of the cytokines was high in PV and MPV. Such results were similar to those from research subjects who took persimmon vinegar only (PV), but the effect of the vinegar (MPV) was more remarkable. Besides, this mixture was found to have no effect on the hepatotoxicity., Conclusion: The significance of this study is that all the experiments were conducted without controlling research subjects' daily lives, and it is suggested that the vinegar may be recommended as a kind of health supplement food to suppress obesity. Especially, since these two products are traditional foods of Korean people, which have been taken for ages, it is expected that the fusing of two foods may be better applied to ordinary people who are concerned about obesity.