Advances in Ginsenosides

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Natural and Bio-derived Molecules".

Deadline for manuscript submissions: closed (29 February 2020) | Viewed by 83342

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Department of Life Sciences, National University of Kaohsiung, Kaohsiung 811, Taiwan
Interests: bioactive compounds; chromatography techniques; medicinal plants; phytochemicals; plant biotechnology; plant growth regulators; plant secondary metabolites
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Dear Colleagues,

Ginsenosides, also known as ginseng saponins or triterpene saponins, are the foremost bioactive constituents of ginseng which belongs to the Panax genus. The genus name Panax means “all-curing” in Greek, and Panax ginseng Meyer has been used as a top-grade herb in traditional Chinese medicine or the king of tonic for over 2000 years in oriental countries. Ginseng preparation possesses a wide range of benefits on human health, including enhancing immune function, improving circulation and vascular function, prevention of neurological diseases, modulation of metabolism, and improving vitality and health. Ginsenosides are unique to ginseng species, and there are more than 100 ginsenosides that have been identified. Ginsenosides have a variety of biological activities, such as neuroprotection, antioxidation, anticancer, antistress, anti-inflammatory, antiaging, antifatigue, cytotoxicity, inhibiting cell apoptosis, inhibiting platelet aggregation. Recent studies on the therapeutic potential of ginsenosides reveal the molecular mechanisms on cardiovascular diseases, anti-inflammatory, modulation of the endocrine system, immune system diseases, and nervous system diseases. In brief, ginsenosides possess complicated bioactive effects and regulate multiple metabolic pathways, and therefore, their efficacy is interconnected and difficult to be clarified.

This Special Issue aims to integrate recent innovative approaches and attempt to make significant progress in biochemistry of ginsenosides by expanding knowledge on a wide range of topics, including biotechnology, biosynthetic machinery, pharmacognostical and pharmacological studies, the application of high-throughput technologies such as genomics, transcriptomics, proteomics, metabolomics, and bioinformatics and other related topics. I sincerely invite scientists to contribute both original research articles and reviews on this Special issue.

Dr. Jen-Tsung Chen
Guest Editor

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Keywords

  • bioactive compounds
  • biotechnology
  • biosynthetic machinery
  • ginseng
  • ginsenosides
  • high-throughput technologies
  • genomics
  • transcriptomics
  • pharmacognosy
  • pharmacology
  • proteomics
  • metabolomics
  • bioinformatics

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Published Papers (15 papers)

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Editorial

Jump to: Research, Review

3 pages, 175 KiB  
Editorial
Advances in Ginsenosides
by Jen-Tsung Chen
Biomolecules 2020, 10(5), 681; https://doi.org/10.3390/biom10050681 - 28 Apr 2020
Cited by 16 | Viewed by 3013
Abstract
Ginsenosides are unique to plants that belong to the Panax genus [...] Full article
(This article belongs to the Special Issue Advances in Ginsenosides)

Research

Jump to: Editorial, Review

15 pages, 3039 KiB  
Article
(20S)G-Rh2 Inhibits NF-κB Regulated Epithelial-Mesenchymal Transition by Targeting Annexin A2
by Yu-Shi Wang, He Li, Yang Li, Shiyin Zhang and Ying-Hua Jin
Biomolecules 2020, 10(4), 528; https://doi.org/10.3390/biom10040528 - 31 Mar 2020
Cited by 13 | Viewed by 3214
Abstract
(1) Background: Epithelial-mesenchymal transition (EMT) is an essential step for cancer metastasis; targeting EMT is an important path for cancer treatment and drug development. NF-κB, an important transcription factor, has been shown to be responsible for cancer metastasis by enhancing the EMT process. [...] Read more.
(1) Background: Epithelial-mesenchymal transition (EMT) is an essential step for cancer metastasis; targeting EMT is an important path for cancer treatment and drug development. NF-κB, an important transcription factor, has been shown to be responsible for cancer metastasis by enhancing the EMT process. Our previous studies showed that (20S)Ginsenoside Rh2 (G-Rh2) inhibits NF-κB activity by targeting Anxa2, but it is still not known whether this targeted inhibition of NF-κB can inhibit the EMT process. (2) Methods: In vivo (20S)G-Rh2-Anxa2 interaction was assessed by cellular thermal shift assay. Protein interaction was determined by immuno-precipitation analysis. NF-κB activity was determined by dual luciferase reporter assay. Gene expression was determined by RT-PCR and immuno-blot. EMT was evaluated by wound healing and Transwell assay and EMT regulating gene expression. (3) Results: Anxa2 interacted with the NF-κB p50 subunit, promoted NF-κB activation, then accelerated mesenchymal-like gene expression and enhanced cell motility; all these cellular processes were inhibited by (20S)G-Rh2. In contrast, these (20S)G-Rh2 effect were completely eliminated by overexpression of Anxa2-K301A, an (20S)G-Rh2-binding-deficient mutant of Anxa2. (4) Conclusion: (20S)G-Rh2 inhibited NF-κB activation and related EMT by targeting Anxa2 in MDA-MB-231 cells. Full article
(This article belongs to the Special Issue Advances in Ginsenosides)
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12 pages, 1573 KiB  
Article
Characterization of a Novel Ginsenoside MT1 Produced by an Enzymatic Transrhamnosylation of Protopanaxatriol-Type Ginsenosides Re
by Byeong-Min Jeon, Jong-In Baek, Min-Sung Kim, Sun-Chang Kim and Chang-hao Cui
Biomolecules 2020, 10(4), 525; https://doi.org/10.3390/biom10040525 - 31 Mar 2020
Cited by 4 | Viewed by 3124
Abstract
Background: Ginsenosides, triterpene saponins of Panax species, are considered the main active ingredients responsible for various pharmacological activities. Herein, a new protopanaxatriol-type ginsenoside called “ginsenoside MT1” is described; it was accidentally found among the enzymatic conversion products of ginsenoside Re. Method: We analyzed [...] Read more.
Background: Ginsenosides, triterpene saponins of Panax species, are considered the main active ingredients responsible for various pharmacological activities. Herein, a new protopanaxatriol-type ginsenoside called “ginsenoside MT1” is described; it was accidentally found among the enzymatic conversion products of ginsenoside Re. Method: We analyzed the conversion mechanism and found that recombinant β-glucosidase (MT619) transglycosylated the outer rhamnopyranoside of Re at the C-6 position to glucopyranoside at C-20. The production of MT1 by trans-rhamnosylation was optimized and pure MT1 was obtained through various chromatographic processes. Results: The structure of MT1 was elucidated based on spectral data: (20S)-3β,6α,12β,20-tetrahydroxydammarene-20-O-[α-L-rhamnopyranosyl(1→2)-β-D-glucopyranoside]. This dammarane-type triterpene saponin was confirmed as a novel compound. Conclusion: Based on the functions of ginsenosides with similar structures, we believe that this ginsenoside MT1 may have great potential in the development of nutraceutical, pharmaceutical or cosmeceutical products. Full article
(This article belongs to the Special Issue Advances in Ginsenosides)
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13 pages, 5875 KiB  
Article
Ginsenoside Compound K Induces Adult Hippocampal Proliferation and Survival of Newly Generated Cells in Young and Elderly Mice
by Jung-Mi Oh, Jae Hoon Jeong, Sun Young Park and Sungkun Chun
Biomolecules 2020, 10(3), 484; https://doi.org/10.3390/biom10030484 - 23 Mar 2020
Cited by 14 | Viewed by 3682
Abstract
Cognitive impairment can be associated with reduced adult hippocampal neurogenesis, and it may contribute to age-associated neurodegenerative diseases such as Alzheimer’s (AD). Compound K (CK) is produced from the protopanaxadiol (PPD)-type ginsenosides Rb1, Rb2, and Rc by intestinal microbial conversion. Although CK has [...] Read more.
Cognitive impairment can be associated with reduced adult hippocampal neurogenesis, and it may contribute to age-associated neurodegenerative diseases such as Alzheimer’s (AD). Compound K (CK) is produced from the protopanaxadiol (PPD)-type ginsenosides Rb1, Rb2, and Rc by intestinal microbial conversion. Although CK has been reported as an inducing effector for neuroprotection and improved cognition in hippocampus, its effect on adult neurogenesis has not been explored yet. Here, we investigated the effect of CK on hippocampal neurogenesis in both young (2 months) and elderly (24 months) mice. CK treatment increased the number of cells co-labeled with 5-ethynyl-2′-deoxyuridine (EdU) and proliferating cell nuclear antigen (PCNA); also, Ki67, specific markers for progenitor cells, was more expressed, thus enhancing the generation of new cells and progenitor cells in the dentate gyrus of both young and elderly mice. Moreover, CK treatment increased the number of cells co-labeled with EdU and NeuN, a specific marker for mature neuron in the dentate gyrus, suggesting that newly generated cells survived and differentiated into mature neurons at both ages. These findings demonstrate that CK increases adult hippocampal neurogenesis, which may be beneficial against neurodegenerative disorders such as AD. Full article
(This article belongs to the Special Issue Advances in Ginsenosides)
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15 pages, 4742 KiB  
Article
Comparison of Ginsenoside Components of Various Tissues of New Zealand Forest-Grown Asian Ginseng (Panax Ginseng) and American Ginseng (Panax Quinquefolium L.)
by Wei Chen, Prabhu Balan and David G Popovich
Biomolecules 2020, 10(3), 372; https://doi.org/10.3390/biom10030372 - 28 Feb 2020
Cited by 46 | Viewed by 6014
Abstract
Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolium L.) are the two most important ginseng species for their medicinal properties. Ginseng is not only popular to consume, but is also increasingly popular to cultivate. In the North Island of [...] Read more.
Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolium L.) are the two most important ginseng species for their medicinal properties. Ginseng is not only popular to consume, but is also increasingly popular to cultivate. In the North Island of New Zealand, Asian ginseng and American ginseng have been grown in Taupo and Rotorua for more than 15 years. There are no publications comparing the chemical constituents between New Zealand-grown Asian ginseng (NZPG) and New Zealand-grown American ginseng (NZPQ). In this study, fourteen ginsenoside reference standards and LC–MS2 technology were employed to analyze the ginsenoside components of various parts (fine root, rhizome, main root, stem, and leaf) from NZPG and NZPQ. Fifty and 43 ginsenosides were identified from various parts of NZPG and NZPQ, respectively, and 29 ginsenosides were found in both ginseng species. Ginsenoside concentrations in different parts of ginsengs were varied. Compared to other tissues, the fine roots contained the most abundant ginsenosides, not only in NZPG (142.49 ± 1.14 mg/g) but also in NZPQ (115.69 ± 3.51 mg/g). For the individual ginsenosides of both NZPG and NZPQ, concentration of Rb1 was highest in the underground parts (fine root, rhizome, and main root), and ginsenoside Re was highest in the aboveground parts (stem and leaf). Full article
(This article belongs to the Special Issue Advances in Ginsenosides)
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19 pages, 4665 KiB  
Article
Exploration and Characterization of Novel Glycoside Hydrolases from the Whole Genome of Lactobacillus ginsenosidimutans and Enriched Production of Minor Ginsenoside Rg3(S) by a Recombinant Enzymatic Process
by Muhammad Zubair Siddiqi, Sathiyaraj Srinivasan, Hye Yoon Park and Wan-Taek Im
Biomolecules 2020, 10(2), 288; https://doi.org/10.3390/biom10020288 - 12 Feb 2020
Cited by 23 | Viewed by 3648
Abstract
Background: Several studies have reported that ginsenoside Rg3(S) is effective in treating metastatic diseases, obesity, and various cancers, however, its presence in white ginseng cannot be estimated, and only a limited amount is present in red ginseng. Therefore, the use of [...] Read more.
Background: Several studies have reported that ginsenoside Rg3(S) is effective in treating metastatic diseases, obesity, and various cancers, however, its presence in white ginseng cannot be estimated, and only a limited amount is present in red ginseng. Therefore, the use of recombinant glycosidases from a Generally Recognized As Safe (GRAS) host strain is a promising approach to enhance production of Rg3(S), which may improve nutritional activity, human health, and quality of life. Method: Lactobacillus ginsenosidimutans EMML 3041T, which was isolated from Korean fermented pickle (kimchi), presents ginsenoside-converting abilities. The strain was used to enrich the production of Rg3(S) by fermenting protopanaxadiol (PPD)-mix-type major ginsenosides (Rb1, Rb2, Rc, and Rd) in four different types of food-grade media (1, MRS; 2, Basel Food-Grade medium; 3, Basel Food-Grade medium-I, and 4, Basel Food-Grade medium-II). Due to its tendency to produce Rg3(S), the presence of glycoside hydrolase in Lactobacillus ginsenosidimutans was proposed, the whole genome was sequenced, and the probable glycoside hydrolase gene for ginsenoside conversion was cloned. Results: The L. ginsenosidimutans EMML 3041T strain was whole genome sequenced to identify the target genes. After genome sequencing, 12 sets of glycoside hydrolases were identified, of which seven sets (α,β-glucosidase and α,β-galactosidase) were cloned in Escherichia coli BL21 (DE3) using the pGEX4T-1 vector system. Among the sets of clones, only one clone (BglL.gin-952) showed ginsenoside-transforming abilities. The recombinant BglL.gin-952 comprised 952 amino acid residues and belonged to glycoside hydrolase family 3. The enzyme exhibited optimal activity at 55 °C and a pH of 7.5 and showed a promising conversion ability of major ginsenoside Rb1→Rd→Rg3(S). The recombinant enzyme (GST-BglL.gin-952) was used to mass produce Rg3(S) from major ginsenoside Rb1. Scale-up of production using 50 g of Rb1 resulted in 30 g of Rg3(S) with 74.3% chromatography purity. Conclusion: Our preliminary data demonstrated that this enzyme would be beneficial in the preparation of pharmacologically active minor ginsenoside Rg3(S) in the functional food and pharmaceutical industries. Full article
(This article belongs to the Special Issue Advances in Ginsenosides)
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12 pages, 2039 KiB  
Article
A Critical Regulation of Th17 Cell Responses and Autoimmune Neuro-Inflammation by Ginsenoside Rg3
by Young-Jun Park, Minkyoung Cho, Garam Choi, Hyeongjin Na and Yeonseok Chung
Biomolecules 2020, 10(1), 122; https://doi.org/10.3390/biom10010122 - 10 Jan 2020
Cited by 27 | Viewed by 4735
Abstract
Among diverse helper T-cell subsets, Th17 cells appear to be pathogenic in diverse autoimmune diseases, and thus, targeting Th17 cells could be beneficial for the treatment of the diseases in humans. Ginsenoside Rg3 is one of the most potent components in Korean Red [...] Read more.
Among diverse helper T-cell subsets, Th17 cells appear to be pathogenic in diverse autoimmune diseases, and thus, targeting Th17 cells could be beneficial for the treatment of the diseases in humans. Ginsenoside Rg3 is one of the most potent components in Korean Red Ginseng (KRG; Panax ginseng Meyer) in ameliorating inflammatory responses. However, the role of Rg3 in Th17 cells and Th17-mediated autoimmunity is unclear. We found that Rg3 significantly inhibited the differentiation of Th17 cells from naïve precursors in a dendritic cell (DC)–T co-culture system. While Rg3 minimally affected the secretion of IL-6, TNFα, and IL-12p40 from DCs, it significantly hampered the expression of IL-17A and RORγt in T cells in a T-cell-intrinsic manner. Moreover, Rg3 alleviated the onset and severity of experimental autoimmune encephalomyelitis (EAE), induced by transferring myelin oligodendrocyte glycoprotein (MOG)-reactive T cells. Our findings demonstrate that Rg3 inhibited Th17 differentiation and Th17-mediated neuro-inflammation, suggesting Rg3 as a potential candidate for resolving Th17-related autoimmune diseases. Full article
(This article belongs to the Special Issue Advances in Ginsenosides)
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12 pages, 3152 KiB  
Article
Molecular Insight into Stereoselective ADME Characteristics of C20-24 Epimeric Epoxides of Protopanaxadiol by Docking Analysis
by Wenna Guo, Zhiyong Li, Meng Yuan, Geng Chen, Qiao Li, Hui Xu and Xin Yang
Biomolecules 2020, 10(1), 112; https://doi.org/10.3390/biom10010112 - 9 Jan 2020
Cited by 9 | Viewed by 3197
Abstract
Chirality is a common phenomenon, and it is meaningful to explore interactions between stereoselective bio-macromolecules and chiral small molecules with preclinical and clinical significance. Protopanaxadiol-type ginsenosides are main effective ingredients in ginseng and are prone to biotransformation into a pair of ocotillol C20-24 [...] Read more.
Chirality is a common phenomenon, and it is meaningful to explore interactions between stereoselective bio-macromolecules and chiral small molecules with preclinical and clinical significance. Protopanaxadiol-type ginsenosides are main effective ingredients in ginseng and are prone to biotransformation into a pair of ocotillol C20-24 epoxide epimers, namely, (20S,24S)-epoxy-dammarane-3,12,25-triol (24S-PDQ) and (20S,24R)-epoxy dammarane-3,12,25-triol (24R-PDQ) that display stereoselective fate in vivo. However, possible molecular mechanisms involved are still unclear. The present study aimed to investigate stereoselective ADME (absorption, distribution, metabolism and excretion) characteristics of PDQ epimers based on molecular docking analysis of their interaction with some vital proteins responsible for drug disposal. Homology modeling was performed to obtain 3D-structure of the human isoenzyme UGT1A8, while calculation of docking score and binding free energy and ligand–protein interaction pattern analysis were achieved by using the Schrödinger package. Stereoselective interaction was found for both UGT1A8 and CYP3A4, demonstrating that 24S-PDQ was more susceptible to glucuronidation, whereas 24R-PDQ was more prone to oxidation catalyzed by CYP3A4. However, both epimers displayed similarly strong interaction with P-gp, a protein with energy-dependent drug-pump function, suggesting an effect of the dammarane skeleton but not C-24 stereo-configuration. These findings provide an insight into stereo-selectivity of ginsenosides, as well as a support the rational development of ginseng products. Full article
(This article belongs to the Special Issue Advances in Ginsenosides)
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22 pages, 7374 KiB  
Article
HMGB1-triggered inflammation inhibition of notoginseng leaf triterpenes against cerebral ischemia and reperfusion injury via MAPK and NF-κB signaling pathways
by Weijie Xie, Ting Zhu, Xi Dong, Fengwei Nan, Xiangbao Meng, Ping Zhou, Guibo Sun and Xiaobo Sun
Biomolecules 2019, 9(10), 512; https://doi.org/10.3390/biom9100512 - 20 Sep 2019
Cited by 110 | Viewed by 6674
Abstract
Ischemic stroke is a clinically common cerebrovascular disease whose main risks include necrosis, apoptosis and cerebral infarction, all caused by cerebral ischemia and reperfusion (I/R) injury. This process has particular significance for the treatment of stroke patients. Notoginseng leaf triterpenes (PNGL), as a [...] Read more.
Ischemic stroke is a clinically common cerebrovascular disease whose main risks include necrosis, apoptosis and cerebral infarction, all caused by cerebral ischemia and reperfusion (I/R) injury. This process has particular significance for the treatment of stroke patients. Notoginseng leaf triterpenes (PNGL), as a valuable medicine, have been discovered to have neuroprotective effects. However, it was not confirmed that whether PNGL may possess neuroprotective effects against cerebral I/R injury. To explore the neuroprotective effects of PNGL and their underlying mechanisms, a middle cerebral artery occlusion/reperfusion (MCAO/R) model was established. In vivo results suggested that in MCAO/R model rats, PNGL pretreatment (73.0, 146, 292 mg/kg) remarkably decreased infarct volume, reduced brain water content, and improved neurological functions; moreover, PNGL (73.0, 146, 292 mg/kg) significantly alleviated blood-brain barrier (BBB) disruption and inhibited neuronal apoptosis and neuronal loss caused by cerebral I/R injury, while PNGL with a different concertation (146, 292 mg/kg) significantly reduced the concentrations of IL-6, TNF-α, IL-1 β, and HMGB1 in serums in a dose-dependent way, which indicated that inflammation inhibition could be involved in the neuroprotective effects of PNGL. The immunofluorescence and western blot analysis showed PNGL decreased HMGB1 expression, suppressed the HMGB1-triggered inflammation, and inhibited microglia activation (IBA1) in hippocampus and cortex, thus dose-dependently downregulating inflammatory cytokines including VCAM-1, MMP-9, MMP-2, and ICAM-1 concentrations in ischemic brains. Interestingly, PNGL administration (146 mg/kg) significantly downregulated the levels of p-P44/42, p-JNK1/2 and p-P38 MAPK, and also inhibited expressions of the total NF-κB and phosphorylated NF-κB in ischemic brains, which was the downstream pathway triggered by HMGB1. All of these results indicated that the protective effects of PNGL against cerebral I/R injury could be associated with inhibiting HMGB1-triggered inflammation, suppressing the activation of MAPKs and NF-κB, and thus improved cerebral I/R-induced neuropathological changes. This study may offer insight into discovering new active compounds for the treatment of ischemic stroke. Full article
(This article belongs to the Special Issue Advances in Ginsenosides)
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15 pages, 4526 KiB  
Article
Comparative Analysis of Panax ginseng Berries from Seven Cultivars Using UPLC-QTOF/MS and NMR-Based Metabolic Profiling
by Dahye Yoon, Bo-Ram Choi, Young-Chang Kim, Seon Min Oh, Hyoung-Geun Kim, Jang-Uk Kim, Nam-In Baek, Suhkmann Kim and Dae Young Lee
Biomolecules 2019, 9(9), 424; https://doi.org/10.3390/biom9090424 - 28 Aug 2019
Cited by 19 | Viewed by 4577
Abstract
The commercial use of Panax ginseng berries is increasing as P. ginseng berries are known to contain large amounts of ginsenosides, and many pharmacological activities have been reported for the various ginsenosides. For the proper use of P. ginseng berries, it is necessary [...] Read more.
The commercial use of Panax ginseng berries is increasing as P. ginseng berries are known to contain large amounts of ginsenosides, and many pharmacological activities have been reported for the various ginsenosides. For the proper use of P. ginseng berries, it is necessary to study efficient and accurate quality control and the profiling of the overall composition of each cultivar. Ginseng berry samples from seven cultivars (Eumseung, Chung-buk Province, Republic of Korea) were analyzed using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-QTOF/MS) for profiling of the ginsenosides, and high-resolution magic-angle-spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy for profiling of the primary metabolites. Comparing twenty-six ginsenoside profiles between the variant representatives and between the violet-stem variant, Kumpoong and Sunwon were classified. In the case of primary metabolites, the cultivars Kumpoong and Gopoong were classified. As a result of correlation analyses of the primary and secondary metabolites, in the Gopoong cultivar, the metabolism was found to lean toward energy metabolism rather than ginsenoside synthesis, and accumulation of osmolytes was low. The Gopoong cultivar had higher levels of most of the amino acids, such as arginine, phenylalanine, isoleucine, threonine, and valine, and it contained the highest level of choline and the lowest level of myo-inositol. Except for these, there were no significant differences of primary metabolites. In the Kumpoong cultivar, the protopanaxatriol (PPT)-type ginsenosides, ginsenoside Re and ginsenoside Rg2, were much lower than in the other cultivars, while the other PPT-type ginsenosides were inversely found in much higher amounts than in other cultivars. The Sunwon cultivar showed that variations of PPT-type ginsenosides were significantly different between samples. However, the median values of PPT-type ginsenosides of Sunwon showed similar levels to those of Kumpoong. The difference in primary metabolites used for metabolism for survival was found to be small in our results. Our data demonstrated the characteristics of each cultivar using profiling data of the primary and secondary metabolites, especially for Gopoong, Kumpoong, and Sunwon. These profiling data provided important information for further research and commercial use. Full article
(This article belongs to the Special Issue Advances in Ginsenosides)
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Review

Jump to: Editorial, Research

40 pages, 1941 KiB  
Review
Ginsenoside Compound K: Insights into Recent Studies on Pharmacokinetics and Health-Promoting Activities
by Anshul Sharma and Hae-Jeung Lee
Biomolecules 2020, 10(7), 1028; https://doi.org/10.3390/biom10071028 - 10 Jul 2020
Cited by 99 | Viewed by 9808
Abstract
Ginseng (Panax ginseng) is an herb popular for its medicinal and health properties. Compound K (CK) is a secondary ginsenoside biotransformed from major ginsenosides. Compound K is more bioavailable and soluble than its parent ginsenosides and hence of immense importance. The [...] Read more.
Ginseng (Panax ginseng) is an herb popular for its medicinal and health properties. Compound K (CK) is a secondary ginsenoside biotransformed from major ginsenosides. Compound K is more bioavailable and soluble than its parent ginsenosides and hence of immense importance. The review summarizes health-promoting in vitro and in vivo studies of CK between 2015 and 2020, including hepatoprotective, anti-inflammatory, anti-atherosclerosis, anti-diabetic, anti-cancer, neuroprotective, anti-aging/skin protective, and others. Clinical trial data are minimal and are primarily based on CK-rich fermented ginseng. Besides, numerous preclinical and clinical studies indicating the pharmacokinetic behavior of CK, its parent compound (Rb1), and processed ginseng extracts are also summarized. With the limited evidence available from animal and clinical studies, it can be stated that CK is safe and well-tolerated. However, lower water solubility, membrane permeability, and efflux significantly diminish the efficacy of CK and restrict its clinical application. We found that the use of nanocarriers and cyclodextrin for CK delivery could overcome these limitations as well as improve the health benefits associated with them. However, these derivatives have not been clinically evaluated, thus requiring a safety assessment for human therapy application. Future studies should be aimed at investigating clinical evidence of CK. Full article
(This article belongs to the Special Issue Advances in Ginsenosides)
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17 pages, 1398 KiB  
Review
Effects of Red and Fermented Ginseng and Ginsenosides on Allergic Disorders
by Myung Joo Han and Dong-Hyun Kim
Biomolecules 2020, 10(4), 634; https://doi.org/10.3390/biom10040634 - 20 Apr 2020
Cited by 35 | Viewed by 7480
Abstract
Both white ginseng (WG, dried root of Panax sp.) and red ginseng (RG, steamed and dried root of Panax sp.) are reported to exhibit a variety of pharmacological effects such as anticancer, antidiabetic, and neuroprotective activities. These ginsengs contain hydrophilic sugar-conjugated ginsenosides and [...] Read more.
Both white ginseng (WG, dried root of Panax sp.) and red ginseng (RG, steamed and dried root of Panax sp.) are reported to exhibit a variety of pharmacological effects such as anticancer, antidiabetic, and neuroprotective activities. These ginsengs contain hydrophilic sugar-conjugated ginsenosides and polysaccharides as the bioactive constituents. When taken orally, their hydrophilic constituents are metabolized into hydrophobic ginsenosides compound K, Rh1, and Rh2 that are absorbable into the blood. These metabolites exhibit the pharmacological effects more strongly than hydrophilic parental constituents. To enforce these metabolites, fermented WG and RG are developed. Moreover, natural products including ginseng are frequently used for the treatment of allergic disorders. Therefore, this review introduces the current knowledge related to the effectiveness of ginseng on allergic disorders including asthma, allergic rhinitis, atopic dermatitis, and pruritus. We discuss how ginseng, its constituents, and its metabolites regulate allergy-related immune responses. We also describe how ginseng controls allergic disorders. Full article
(This article belongs to the Special Issue Advances in Ginsenosides)
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18 pages, 3130 KiB  
Review
Biotechnological Interventions for Ginsenosides Production
by Saikat Gantait, Monisha Mitra and Jen-Tsung Chen
Biomolecules 2020, 10(4), 538; https://doi.org/10.3390/biom10040538 - 2 Apr 2020
Cited by 34 | Viewed by 6128
Abstract
Ginsenosides are secondary metabolites that belong to the triterpenoid or saponin group. These occupy a unique place in the pharmaceutical sector, associated with the manufacturing of medicines and dietary supplements. These valuable secondary metabolites are predominantly used for the treatment of nervous and [...] Read more.
Ginsenosides are secondary metabolites that belong to the triterpenoid or saponin group. These occupy a unique place in the pharmaceutical sector, associated with the manufacturing of medicines and dietary supplements. These valuable secondary metabolites are predominantly used for the treatment of nervous and cardiac ailments. The conventional approaches for ginsenoside extraction are time-consuming and not feasible, and thus it has paved the way for the development of various biotechnological approaches, which would ameliorate the production and extraction process. This review delineates the biotechnological tools, such as conventional tissue culture, cell suspension culture, protoplast culture, polyploidy, in vitro mutagenesis, hairy root culture, that have been largely implemented for the enhanced production of ginsenosides. The use of bioreactors to scale up ginsenoside yield is also presented. The main aim of this review is to address the unexplored aspects and limitations of these biotechnological tools, so that a platform for the utilization of novel approaches can be established to further increase the production of ginsenosides in the near future. Full article
(This article belongs to the Special Issue Advances in Ginsenosides)
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11 pages, 797 KiB  
Review
Pro-Resolving Effect of Ginsenosides as an Anti-Inflammatory Mechanism of Panax ginseng
by Dong-Soon Im
Biomolecules 2020, 10(3), 444; https://doi.org/10.3390/biom10030444 - 13 Mar 2020
Cited by 126 | Viewed by 9867
Abstract
Panax ginseng, also known as Korean ginseng, is a famous medicinal plant used for the treatment of many inflammatory diseases. Ginsenosides (ginseng saponins) are the main class of active constituents of ginseng. The anti-inflammatory effects of ginseng extracts were proven with purified [...] Read more.
Panax ginseng, also known as Korean ginseng, is a famous medicinal plant used for the treatment of many inflammatory diseases. Ginsenosides (ginseng saponins) are the main class of active constituents of ginseng. The anti-inflammatory effects of ginseng extracts were proven with purified ginsenosides, such as ginsenosides Rb1, Rg1, Rg3, and Rh2, as well as compound K. The negative regulation of pro-inflammatory cytokine expressions (TNF-α, IL-1β, and IL-6) and enzyme expressions (iNOS and COX-2) was found as the anti-inflammatory mechanism of ginsenosides in M1-polarized macrophages and microglia. Recently, another action mechanism emerged explaining the anti-inflammatory effect of ginseng. This is a pro-resolution of inflammation derived by M2-polarized macrophages. Direct and indirect evidence supports how several ginsenosides (ginsenoside Rg3, Rb1, and Rg1) induce the M2 polarization of macrophages and microglia, and how these M2-polarized cells contribute to the suppression of inflammation progression and promotion of inflammation resolution. In this review, the new action mechanism of ginseng anti-inflammation is summarized. Full article
(This article belongs to the Special Issue Advances in Ginsenosides)
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20 pages, 1466 KiB  
Review
Panax ginseng Pharmacopuncture: Current Status of the Research and Future Challenges
by In-Seon Lee, Ki Sung Kang and Song-Yi Kim
Biomolecules 2020, 10(1), 33; https://doi.org/10.3390/biom10010033 - 25 Dec 2019
Cited by 35 | Viewed by 6368
Abstract
Despite the increasing use of ginseng pharmacopuncture in clinical practice, evidence of its physiological effects, safety, and clinical outcomes is insufficient. The purpose of this review is to summarize previous studies and suggest future challenges for the clinical use of ginseng pharmacopuncture. We [...] Read more.
Despite the increasing use of ginseng pharmacopuncture in clinical practice, evidence of its physiological effects, safety, and clinical outcomes is insufficient. The purpose of this review is to summarize previous studies and suggest future challenges for the clinical use of ginseng pharmacopuncture. We systematically searched clinical and animal studies that applied ginseng pharmacopuncture and reviewed the manufacturing processes of ginseng pharmacopuncture solution, safety, physiological responses, and clinical effects. Intravenous or point injection of the ginseng pharmacopuncture solution made by distillation extraction has been commonly used in studies. Ginseng pharmacopuncture does not show any toxicity in animals and humans, while it influenced the heart rate variability, pulse wave velocity, and protein synthesis in human subjects. In 25 case reports, patients with cancer, amyotrophic lateral sclerosis, skin wrinkles, and allergic rhinitis showed significant improvement of clinical outcomes. We found that more evidence is necessary to conclude that ginseng pharmacopuncture is safe and effective. First, the pharmacopuncture manufacturing process should be standardized on the basis of the safety and efficacy tests. Moreover, studies on the quantitative quality of the components of the solution and on the clinical comparison of various injection methods are required to improve clinical outcomes in the future. Full article
(This article belongs to the Special Issue Advances in Ginsenosides)
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