Medicinal Plant Panax Ginseng Research Articles

The R2R3-MYB transcription factor PgTT2 from Panax ginseng interacts with the WD40-repeat protein PgTTG1 during the regulation of proanthocyanidin biosynthesis and the response to salt stress

Proanthocyanidins (PAs) are flavonoid compounds with important defensive roles in plants. The application of PAs in industries such as the pharmaceutical industry has led to increased interest in enhancing their biosynthesis. In Arabidopsis thaliana, PAs are biosynthesized under the regulation of an R2R3-MYB transcription factor TRANSPARENT TESTA 2 (TT2), which can interact with other proteins, including TRANSPARENT TESTA GLABRA 1 (TTG1), while also regulating a plant's response to abiotic stressors. However, the regulation of PA biosynthesis in the high-value medicinal plant Panax ginseng (ginseng) has not yet been studied. Understanding the mechanism of PAs biosynthesis regulation in ginseng may be helpful in increasing the plant's range of pharmacological applications. This study found that the overexpression of PgTT2 increased PA biosynthesis by an average of 67.3% in ginseng adventitious roots and 50.5% in arabidopsis seeds. Furthermore, transgenic arabidopsis plants overexpressing PgTT2 produced increased reactive oxygen species (ROS) scavenging ability by influencing abscisic acid synthesis and signaling. However, under high salinity stress, seed germination and growth rate of seedlings were decreased. An expression analysis of plants facing salt stress revealed increased transcripts of an ABA biosynthetic gene, NCED3, and ABA signaling genes ABI5 and ABI3. Moreover, the PgTT2 protein showed a direct interaction with PgTTG1 in yeast two-hybrid assays. This study therefore reveals novel information on the transcriptional regulation of PA production in ginseng and shows how PgTT2 influences the ABA response pathway to regulate responses to ROS and salt stress.

Red ginseng polysaccharide exhibits anticancer activity through GPX4 downregulation-induced ferroptosis

Context Red ginseng polysaccharide (RGP) is an active component of the widely used medicinal plant Panax ginseng C. A. Meyer (Araliaceae), which has displayed promising activities against cancer cells. However, the detailed molecular mechanism of RGP in ferroptosis is still unknown. Objective This study evaluates the effects of RGP in cancer cells. Materials and methods A549 and MDA-MB-231 cells were used. Cell proliferation was measured by CCK-8 assay after being treated with RGP at concentrations of 0, 50, 100, 200, 400, 800 and 1600 μg/mL at 0, 12, 24 and 48 h. Lipid reactive oxygen species (ROS) levels were assessed by C11-BODIPY assay. The control group was treated with PBS. Results RGP inhibited human A549 (IC50: 376.2 μg/mL) or MDA-MB-231(IC50: 311.3 μg/mL) proliferation and induced lactate dehydrogenase (LDH) release, promoted ferroptosis and suppressed the expression of GPX4. Moreover, the effects of RGP were enhanced by the ferroptosis inducer erastin, while abolished by ferroptosis inhibitor ferrostatin-1. Discussion and conclusions Our study is the first to demonstrate (1) the anticancer activity of RGP in human lung cancer and breast cancer. (2) RGP presented the anti-ferroptosis effects in lung and breast cancer cells via targeting GPX4.

Pathogenesis strategies and regulation of ginsenosides by two species of Ilyonectria in Panax ginseng: power of speciation

BackgroundThe valuable medicinal plant Panax ginseng has high pharmaceutical efficacy because it produces ginsenosides. However, its yields decline because of a root-rot disease caused by Ilyonectria mors-panacis. Because species within Ilyonectria showed variable aggressiveness by altering ginsenoside concentrations in inoculated plants, we investigated how such infections might regulate the biosynthesis of ginsenosides and their related signaling molecules. MethodsTwo-year-old ginseng seedlings were treated with I. mors-panacis and I. robusta. Roots from infected and pathogen-free plants were harvested at 4 and 16 days after inoculation. We then examined levels or/and expression of genes of ginsenosides, salicylic acid (SA), jasmonic acid (JA), and reactive oxygen species (ROS). We also checked the susceptibility of those pathogens to ROS. ResultsGinsenoside biosynthesis was significantly suppressed and increased in response to infection by I. mors-panacis and I. robusta, respectively. Regulation of JA was significantly higher in I. robusta–infected roots, while levels of SA and ROS were significantly higher in I. mors-panacis–infected roots. Catalase activity was significantly higher in I. robusta–infected roots followed in order by mock roots and those infected by I. mors-panacis. Moreover, I. mors-panacis was resistant to ROS compared with I. robusta. ConclusionInfection by the weakly aggressive I. robusta led to the upregulation of ginsenoside production and biosynthesis, probably because only a low level of ROS was induced. In contrast, the more aggressive I. mors-panacis suppressed ginsenoside biosynthesis, probably because of higher ROS levels and subsequent induction of programmed cell death pathways. Furthermore, I. mors-panacis may have increased its virulence by resisting the cytotoxicity of ROS.

Codon Usage Study on Chloroplast Genome in Medicinal Plant <i>Panax Ginseng</i>

Panax ginseng is usually used as a famous plant medicine in many countries. In order to study the codon usage in whole chloroplast genome in Panax ginseng, whole chloroplast genome sequence is analyzed via codonW software and some results such as relationships between the codon adaptation index, frequency of optimal codons, codon bias index, effective number of codons, especially the relative synonymous codon usage are all discussed. Furthermore, PR2-bias plot, histogram GC content, Codon Bias Index are also analyzed for exploring the sequence characteristics of chloroplast genome in Panax ginseng. These results showed that codon usage bias in the chloroplast genome from Panax ginseng is weak, and the relative results could lay a foundation for other further study on the medicinal plant Panax ginseng.

Ginsenoside Rg1 attenuates ultraviolet B-induced glucocortisides resistance in keratinocytes via Nrf2/HDAC2 signalling.

Oxidative stress, which occurs after ultraviolet (UV) radiation, usually results in Glucocorticoid (GC) resistance and the subsequent development of skin inflammation. One approach to protecting the skin against UV radiation is the use of antioxidants. The ginsenoside Rg1 is a novel natural antioxidant isolated from the medicinal plant Panax ginseng C.A. Mey. We demonstrated that UVB exposure exacerbated inflammation and reduced both the level of the glucocorticoid receptor (GR) and the efficacy of dexamethasone (Dex) in human keratinocytes (HaCaT cells). Pretreatment with Rg1 increased the expression of GR and restored Dex responsiveness to inflammation in UVB-irradiated HaCaT cells. Mechanistically, Rg1 rescued UVB-induced HDAC2 degradation. HDAC2 knockdown partially abolished the Rg1-induced up-regulation of GR and the enhancement of GC sensitivity. In addition, Rg1 reduced the production of reactive oxygen species (ROS), which preceded the up-regulation of HDAC2, and consequent sensitization of cells to Dex. Moreover, Rg1 treatment promoted the translocation and activation of Nrf2. Nrf2 knockdown partially abolished the Rg1-induced decrease of ROS production and increase of HDAC2. Rg1 also potentiated the anti-inflammatory effects of Dex in UVB-irradiated mouse skin. In conclusion, we demonstrated that Rg1 attenuated UVB-induced GC insensitivity. Notably, these effects were partially mediated by the Nrf2/HDAC2 pathway.

Pharmacological importance, characterization and applications of gold and silver nanoparticles synthesized by Panax ginseng fresh leaves

Previously, we showed the rapid and eco-friendly synthesis of gold and silver nanoparticles within 3 and 45 min by fresh leaves extract of herbal medicinal plant Panax ginseng. In addition, we characterized the nanoparticles in terms of shape, size, morphology and stability by FE-TEM, EDX, elemental mapping, SEAD, XRD and particles size analysis. In addition of this, we showed their antimicrobial, anti-coagulant, and biofilm inhibition activity of nanoparticles. Continuing our previous study, here we highlight the further characterization and biomedical applications of P. ginseng leaf-mediated gold and silver nanoparticles. We characterized the nanoparticles further in terms of active functional group and capping layer, surface charge, and temperature stability. Based on these factors, we explored the nanoparticles for antioxidant efficacy, biocompatibility in HaCaT cells, 3T3-L1 pre-adipocytes cells, for anticancer efficacy in A549 lung cancer and B16BL6 skin melenoma cancer cell lines and for anti-inflammation efficacy in RAW 264.7 cell lines. Based on our findings, we suggest that the P. ginseng-mediated gold nanoparticles have high antioxidant activity and highly biocompatibility in HaCaT cells, 3T3-L1 pre-adipocytes cells, RAW 264.7 cells lines and could be considered for future drug delivery carriers. The silver nanoparticles also showed high potent antioxidant efficacy, additionally it showed high anticancer effect in A549 lung cancer and B16BL6 skin melenoma cancer cell lines as compared to precursor salts. Moreover, both gold and silver nanoparticles have anti-inflammatory efficacies in RAW 264.7 cells. Thus, the study may provide useful insights of P. ginseng leaves extract-mediated biocompatible gold and silver nanoparticles and improving their applicability in designing nanoparticles carrier systems for drug delivery applications.

Ginsenoside Rg3 attenuates myocardial ischemia/reperfusion injury via Akt/endothelial nitric oxide synthase signaling and the B‑cell lymphoma/B‑cell lymphoma‑associated X protein pathway.

Previous studies have suggested that ginsenoside Rg3 (GSRg3) extract from the medicinal plant Panax ginseng, may increase nitric oxide production via increases in the phosphorylation and expression of endothelial nitric oxide synthase (eNOS). The present study used an invitro neonatal rat cardiomyocyte (NRC) model of anoxia‑reoxygenation injury and an invivo rat model of myocardial ischemia/reperfusion (MI/R) injury. Hemodynamic, histopathological and biochemical assessment of the myocardial injury was performed and the expression levels of lactate dehydrogenase (LDH), superoxide dismutase and creatine kinase (CK) were measured in serum from the animal model, which may reflect myocardial injury. NRC injury was determined using a Cell Counting kit‑8. The GSRg3 anti‑apoptotic effects were assessed using flow cytometry to investigate the number of early‑late apoptotic cells and western blot analysis was performed to analyze the protein expression levels of caspase‑3, caspase‑9, B‑cell lymphoma‑2 (Bcl‑2), phosphorylated (p‑)Akt and eNOS. The results suggested that pretreatment with GSRg3 (60mg/kg) significantly improved rat cardiac function, as demonstrated by increased left ventricular systolic pressure, heart rate and first derivative of left ventricular pressure. GSRg3 also reduced the size of the myocardial infarct and LDH/CK levels in the blood following MI/R. Invitro investigations revealed that GSRg3 (10mM) decreased NRC apoptosis through inhibiting the activation of caspase‑3 and caspase‑9, and increasing the expression levels of p‑Akt, eNOS and the ratio of Bcl‑2/Bcl‑2‑associated X protein (Bax). Overall, the present study revealed that GSRg3 mediated a cardioprotective effect against MI/R‑induced apoptosis via Akt/eNOS signaling and the Bcl‑2/Bax pathway.

Overexpression of PgSQS1 Increases Ginsenoside Production and Negatively Affects Ginseng Growth Rate in Panax ginseng

The medicinal plant Panax ginseng (P. ginseng) contains various phytosterols and bioactive triterpene saponins (ginsenosides). Squalene synthase catalyzes the first committed step in ginsenoside biosynthesis. Transgenic plants of P. ginseng were generated by introducing the squalene synthase gene derived from P. ginseng. Adventitious roots of the transgenic ginseng grew best in B5 medium, and 2 g of inoculum secured an optimal growth rate. Two phytohormones, indolebutyric acid and 1-naphtalene acetic acid, increased root growth and decreased ginsenoside production. Treatment with two selected elicitors, chitosan and jasmonic acid, and a precursor of the isoprenoid pathway, mevalonic acid, enhanced ginsenoside production and retarded ginseng growth rate.

Identification and characterization of class I chitinase in Panax ginseng C. A. Meyer

The role of plant chitinases in protecting plants against a variety of fungal pathogens is well established. In the present study, a cDNA clone containing a class I chitinase (Chi-1) gene, designated as PgChi-1, has been isolated from the oriental medicinal plant Panax ginseng. PgChi-1 is predicted to encode a protein of 34.9 kDa consisting of 323 amino acid residues. PgChi-1 was found to be expressed constitutively in all of the studied organs of ginseng plant. Under various abiotic stress treatments including Cu, H2O2, mannitol, SA, JA, and NaCl, the expression of PgChi-1 in plantlets and hairy roots increased significantly compared to the control. When different parts of root were analyzed, maximum level was observed in taproot. In addition, levels of PgChi-1 expression were compared between healthy root and fungal, bacterial, and nematode infected root. Significant increase of PgChi-1 was noticed in pathogen infected roots than healthy roots. This study revealed that PgChi-1 may protect the P. ginseng under both biotic and abiotic stress conditions.

Falcarinol is a covalent cannabinoid CB 1 receptor antagonist and induces pro-allergic effects in skin

The skin irritant polyyne falcarinol (panaxynol, carotatoxin) is found in carrots, parsley, celery, and in the medicinal plant Panax ginseng. In our ongoing search for new cannabinoid (CB) receptor ligands we have isolated falcarinol from the endemic Sardinian plant Seseli praecox. We show that falcarinol exhibits binding affinity to both human CB receptors but selectively alkylates the anandamide binding site in the CB 1 receptor ( K i = 594 nM), acting as covalent inverse agonist in CB 1 receptor-transfected CHO cells. Given the inherent instability of purified falcarinol we repeatedly isolated this compound for biological characterization and one new polyyne was characterized. In human HaCaT keratinocytes falcarinol increased the expression of the pro-allergic chemokines IL-8 and CCL2/MCP-1 in a CB 1 receptor-dependent manner. Moreover, falcarinol inhibited the effects of anandamide on TNF-alpha stimulated keratinocytes. In vivo, falcarinol strongly aggravated histamine-induced oedema reactions in skin prick tests. Both effects were also obtained with the CB 1 receptor inverse agonist rimonabant, thus indicating the potential role of the CB 1 receptor in skin immunopharmacology. Our data suggest anti-allergic effects of anandamide and that falcarinol-associated dermatitis is due to antagonism of the CB 1 receptor in keratinocytes, leading to increased chemokine expression and aggravation of histamine action.

Isolation of S-adenosyl-L-methionine synthetase gene from Panax ginseng C.A. meyer and analysis of its response to abiotic stresses.

A cDNA clone containing a S-adenosyl-L-methionine synthetase (SAMS) gene, named as PgSAM, was isolated from a commercial medicinal plant Panax ginseng. PgSAM is predicted to encode a precursor protein of 307 amino acid residues, and its sequence shares high homology with a number of other plant SAMS. PgSAM is expressed at different levels in various organs of ginseng. The expression of PgSAM in adventitious roots and hairy roots of P. ginseng were analyzed using reverse transcriptase (RT)-PCR and real-time PCR under various abiotic stresses. Salt, salicylic acid, abscisic acid and chilling stresses induced PgSAM significantly at different time points within 2-72 h post-treatment. This study revealed that PgSAM may help to protect the plants against various abiotic stresses.

Protective effects of Panax ginseng on muscle injury and inflammation after eccentric exercise

Eccentric muscle contraction causes fibre injury associated with disruption of the myofibrillar cytoskeleton. The medicinal plant Panax ginseng C.A. Meyer, known for its therapeutic properties, was studied to explore its protective effects after eccentric contraction. A crude extract and a standardised extract (G115) of different saponin compositions were tested as to their efficacy in reducing lipid peroxidation, inflammation and release of myocellular proteins after the realisation of an eccentric contraction protocol on a rat treadmill. Plasma creatine kinase (CK) levels were significantly reduced by approximately 25% after ingestion of both extracts of ginseng. Both extracts reduced lipid peroxidation by approximately 15% as measured by malondialdehyde levels. β-Glucuronidase concentrations and glucose-6-phosphate dehydrogenase (G6PDH) levels, which can be considered markers of inflammation, were also significantly reduced. The values of β-glucuronidase were increased from 35.9±1.5 to 128.4±8.1 in vastus and to 131.1±12.1 U g −1 in rectus, the protection due to ginseng administration being approximately 40% in both muscles. Both extracts appeared to be equally effective in reducing injuries and inflammation caused by eccentric muscle contractions.

The growth of cultured human fibroblasts treated with hydrocortisone and extracts of the medicinal plant Panax ginseng

The medicinal plant Panax ginseng is used extensively by the elderly in several countries. These is as yet no clear pharmacological evidence to justify a geriatric use for ginseng. Experiments are reported showing that extracts of the root of Panax ginseng have a dose dependent mitogenic action on cultured cells. They are also capable of delaying cellular necrosis. Cortisone produces similar effects when given to cells in cultured, and it cal also extend their lifespan. The comparative effects of cortisone and ginseng are discussed, particularly in the light of evidence that the active constituents of Panax ginseng are terpenoidal glycosides.