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Biomedicine & Pharmacotherapy =... Dec 2022Ginsenoside Rh2 (Rh2), the major bio-active ginsenoside that originated from the root of Panax ginseng, has become a "hot topic" for playing multifunctional roles in... (Review)
Review
Ginsenoside Rh2 (Rh2), the major bio-active ginsenoside that originated from the root of Panax ginseng, has become a "hot topic" for playing multifunctional roles in both tumor treatment and tumor microenvironment (TME) immunomodulation. Up to now, emerging experimental research about Rh2 in tumor therapy and immuno-regulation has been published, however, the specific reviews focused on its role in the TME were limited. Hence, in this article, we briefly summarized existing evidence supporting the anticancer effects and potential mechanisms of Rh2 according to the tumor type, including anti-proliferation, anti-invasion, and metastasis, induction of cell cycle arrest, anti-angiogenesis, promotion of reactive oxygen species and differentiation. Meanwhile, we shed light on the role of Rh2 in TME, with an emphasis on regulating tumor immunogenicity, immune cells, cytokines, and physicochemical properties of TME. Finally, the current research limitation and prospects of Rh2 were discussed.
Topics: Ginsenosides; Tumor Microenvironment; Panax; Neoplasms; Immunomodulation
PubMed: 36288668
DOI: 10.1016/j.biopha.2022.113912 -
Nutrients Jan 2024Meyer and Thunb. are well established in traditional medicine and are known for their therapeutic properties in managing a range of ailments such as diabetes, asthma,...
Meyer and Thunb. are well established in traditional medicine and are known for their therapeutic properties in managing a range of ailments such as diabetes, asthma, and cancer. Although and can alleviate pulmonary fibrosis (PF), the anti-fibrosis effect on PF by the combination of two herbal medicines remains unexplored. Therefore, this study explores this combined effect. In conditions that were not cytotoxic, MRC-5 cells underwent treatment using the formula combining and (ISE081), followed by stimulation with transforming growth factor (TGF)-β1, to explore the fibroblast-to-myofibroblast transition (FMT). After harvesting the cells, mRNA levels and protein expressions associated with inflammation and FMT-related markers were determined to evaluate the antiinflammation activities and antifibrosis effect of ISE081. Additionally, the anti-migratory effects of ISE081 were validated through a wound-healing assay. ISE081 remarkably reduced the mRNA levels of interleukin (IL)-6, IL-8, α-smooth muscle actin (SMA), and TGF-β1 in MRC-5 cells and suppressed the α-SMA and fibronectin expressions, respectively. Furthermore, ISE081 inhibited Smad2/3 phosphorylation and wound migration of MRC-5 cells. Under the same conditions, comparing those of ISE081, did not affect the expression of α-SMA, fibronectin, and Smad2/3 phosphorylation, whereas significantly inhibited them but with cytotoxicity. The results indicate that the synergistic application of and enhances the anti-fibrotic properties in pulmonary fibroblasts and concurrently diminishes toxicity. Therefore, ISE081 has the potential as a prevention and treatment herbal medicine for PF.
Topics: Humans; Inula; Fibronectins; Panax; Fibrosis; Pulmonary Fibrosis; Fibroblasts; Transforming Growth Factor beta1; RNA, Messenger
PubMed: 38276557
DOI: 10.3390/nu16020319 -
Molecules (Basel, Switzerland) Jul 2021Respiratory tract infections are underestimated, as they are mild and generally not incapacitating. In clinical medicine, however, these infections are considered a... (Review)
Review
Respiratory tract infections are underestimated, as they are mild and generally not incapacitating. In clinical medicine, however, these infections are considered a prevalent problem. By 2030, the third most comprehensive reason for death worldwide will be chronic obstructive pulmonary disease (COPD), according to the World Health Organization. The current arsenal of anti-inflammatory drugs shows little or no benefits against COPD. For thousands of years, herbal drugs have been used to cure numerous illnesses; they exhibit promising results and enhance physical performance. Ginseng is one such herbal medicine, known to alleviate pro-inflammatory chemokines and cytokines (IL-2, IL-4, IFN-γ, TNF-α, IL-5, IL-6, IL-8) formed by macrophages and epithelial cells. Furthermore, the mechanisms of action of ginsenoside are still not fully understood. Various clinical trials of ginseng have exhibited a reduction of repeated colds and the flu. In this review, ginseng's structural features, the pathogenicity of microbial infections, and the immunomodulatory, antiviral, and anti-bacterial effects of ginseng were discussed. The focus was on the latest animal studies and human clinical trials that corroborate ginseng's role as a therapy for treating respiratory tract infections. The article concluded with future directions and significant challenges. This review would be a valuable addition to the knowledge base for researchers in understanding the promising role of ginseng in treating respiratory tract infections. Further analysis needs to be re-focused on clinical trials to study ginseng's efficacy and safety in treating pathogenic infections and in determining ginseng-drug interactions.
Topics: Animals; Complementary Therapies; Ginsenosides; Humans; Panax; Phytotherapy; Respiratory Tract Infections
PubMed: 34279434
DOI: 10.3390/molecules26134095 -
International Journal of Molecular... May 2023In this study, we evaluated the ameliorative effect and molecular mechanism of red ginseng ( C.A. Meyer) extract (RGE) on D-galactose (D-gal)-induced premature ovarian...
In this study, we evaluated the ameliorative effect and molecular mechanism of red ginseng ( C.A. Meyer) extract (RGE) on D-galactose (D-gal)-induced premature ovarian failure (POF) using network pharmacology analysis. Ginsenosides are important active ingredients in ginseng, which also contains some sugar and amino acid derivatives. We aimed to determine the key proteins through which RGE regulates POF. In this work, we retrieved and screened for active ingredients in ginseng and the corresponding POF disease targets in multiple databases. A PPI network of genes was constructed in the STRING database and core targets were screened using topological analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted in R software. Finally, molecular docking was conducted to validate the results. Female ICR mice were used to establish a POF mouse model for in vivo experiments. Serum levels of relevant estrogens were determined using ELISA and expression levels of relevant proteins in ovarian tissues were detected using immunofluorescence and western blot analysis. Network pharmacology analysis predicted that PI3K, Akt, Bax, Bcl-2, p16, and other proteins were highly correlated with POF and RGE. The results clearly showed that RGE could increase estradiol (E2) and lower follicle-stimulating hormone (FSH) levels in D-gal-fed mice. RGE restored the expression levels of related proteins by reducing Nrf2-mediated oxidative stress, PI3K/Akt-mediated apoptosis, and senescence signaling pathways. Overall, RGE has the potential to prevent and treat POF and is likely to be a promising natural protector of the ovaries.
Topics: Humans; Mice; Female; Animals; Primary Ovarian Insufficiency; Galactose; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Molecular Docking Simulation; Network Pharmacology; Mice, Inbred ICR; Menopause, Premature; Panax
PubMed: 37175917
DOI: 10.3390/ijms24098210 -
Biomolecules Jul 2020Ginseng () is an herb popular for its medicinal and health properties. Compound K (CK) is a secondary ginsenoside biotransformed from major ginsenosides. Compound K is... (Review)
Review
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.
Topics: Animals; Anti-Inflammatory Agents; Clinical Trials as Topic; Ginsenosides; Health Promotion; Humans; Panax
PubMed: 32664389
DOI: 10.3390/biom10071028 -
Nutrients Dec 2022The physicochemical properties and multiple bioactive effects of ginseng oligopeptides (GOPs), plant-derived small molecule bioactive peptides, suggest a positive...
The physicochemical properties and multiple bioactive effects of ginseng oligopeptides (GOPs), plant-derived small molecule bioactive peptides, suggest a positive influence on health span and longevity. Given this, cellular senescence is the initiating factor and key mechanism of aging in the organism, and thus the current study sought to explore the effects of GOPs on HO-induced cellular senescence and its potential mechanisms. Senescence was induced in mouse embryonic fibroblasts NIH/3T3 by 4 h of exposure to 200 µM HO and confirmed using CCK-8 assay and Western blot analyses of p16 and p21 after 24 h of growth medium administration with or without GOPs supplementation (25, 50, and 100 µg/mL). We found that GOPs delayed oxidative stress-induced NIH/3T3 senescence by inhibiting the G1 phase arrest, increasing DNA synthesis in the S phase, decreasing the relative protein expression of p16 and p21, promoting cell viability, protecting DNA, and enhancing telomerase (TE) activity. Further investigation revealed that the increase in antioxidative capacity and anti-inflammation capacity might form the basis for the retarding of the senescence effects of GOPs. Furthermore, GOPs supplementation significantly improved mitochondrial function and mitochondrial biogenesis via the NAD/SIRT1/PGC-1𝛼 pathway. These findings indicate that GOPs may have a positive effect on health span and lifespan extension via combating cellular senescence, oxidative stress, and inflammation, as well as modulating longevity regulating pathway NAD/SIRT1/PGC-1𝛼.
Topics: Animals; Mice; Sirtuin 1; NAD; Hydrogen Peroxide; Cyclin-Dependent Kinase Inhibitor p16; Panax; Fibroblasts; Signal Transduction; Oxidative Stress; Cellular Senescence; Cyclin-Dependent Kinase Inhibitor p21; Oligopeptides
PubMed: 36558448
DOI: 10.3390/nu14245289 -
Cells May 2023Astrocytes play a key role in brain functioning by providing energy to neurons. Increased astrocytic mitochondrial functions by Korean red ginseng extract (KRGE) have...
Astrocytes play a key role in brain functioning by providing energy to neurons. Increased astrocytic mitochondrial functions by Korean red ginseng extract (KRGE) have been investigated in previous studies. KRGE administration induces hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in astrocytes in the adult mouse brain cortex. VEGF expression can be controlled by transcription factors, such as the HIF-1α and estrogen-related receptor α (ERRα). However, the expression of ERRα is unchanged by KRGE in astrocytes of the mouse brain cortex. Instead, sirtuin 3 (SIRT3) expression is induced by KRGE in astrocytes. SIRT3 is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase that resides in the mitochondria and maintains mitochondrial homeostasis. Mitochondrial maintenance requires oxygen, and active mitochondria enhance oxygen consumption, resulting in hypoxia. The effects of SIRT3 on HIF-1α-mediated mitochondria functions induced by KRGE are not well established. We aimed to investigate the relationship between SIRT3 and HIF-1α in KRGE-treated normoxic astrocyte cells. Without changing the expression of the ERRα, small interfering ribonucleic acid targeted for SIRT3 in astrocytes substantially lowers the amount of KRGE-induced HIF-1α proteins. Reduced proline hydroxylase 2 (PHD2) expression restores HIF-1α protein levels in SIRT3-depleted astrocytes in normoxic cells treated with KRGE. The translocation of outer mitochondrial membranes 22 (Tom22) and Tom20 is controlled by the SIRT3-HIF-1α axis, which is activated by KRGE. KRGE-induced Tom22 increased oxygen consumption and mitochondrial membrane potential, as well as HIF-1α stability through PHD2. Taken together, in normoxic astrocytes, KRGE-induced SIRT3 activated the Tom22-HIF-1α circuit by increasing oxygen consumption in an ERRα-independent manner.
Topics: Mice; Animals; Mitochondrial Membranes; Sirtuin 3; Astrocytes; Vascular Endothelial Growth Factor A; Panax; Hypoxia-Inducible Factor 1, alpha Subunit
PubMed: 37296633
DOI: 10.3390/cells12111512 -
Frontiers in Cellular and Infection... 2022Panax ginseng, as the king of Chinese herb, has significant therapeutic effects on obesity, type 2 diabetes mellitus, fatty liver disease, colitis, diarrhea, and many... (Review)
Review
Panax ginseng, as the king of Chinese herb, has significant therapeutic effects on obesity, type 2 diabetes mellitus, fatty liver disease, colitis, diarrhea, and many other diseases. This review systematically summarized recent findings, which show that ginseng plays its role by regulating gut microbiota diversity, and gut microbiota could also regulate the transformation of ginsenosides. We conclude the characteristics of ginseng in regulating gut microbiota, as the potential targets to prevent and treat metabolic diseases, colitis, neurological diseases, cancer, and other diseases. Ginseng treatment can increase some probiotics such as , , , , and reduce pathogenic bacteria such as , , against various diseases. Meanwhile, , , and were found to be the key bacteria for ginsenoside transformation . Overall, ginseng can regulate gut microbiome diversity, further affect the synthesis of secondary metabolites, as well as promote the transformation of ginsenosides for improving the absorptivity of ginsenosides. This review can provide better insight into the interaction of ginseng with gut microbiota in multiple disorders and ginsenoside transformation.
Topics: Bacteria; Bifidobacterium; Colitis; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Ginsenosides; Humans; Panax
PubMed: 35548468
DOI: 10.3389/fcimb.2022.853981 -
Biomedicine & Pharmacotherapy =... Nov 2022Panax notoginseng saponins (PNS), the main active ingredient of herbal medicine Panax notoginseng, has been generally applied for the therapy of cardiovascular and...
Panax notoginseng saponins alleviates inflammation induced by microglial activation and protects against ischemic brain injury via inhibiting HIF-1α/PKM2/STAT3 signaling.
Panax notoginseng saponins (PNS), the main active ingredient of herbal medicine Panax notoginseng, has been generally applied for the therapy of cardiovascular and cerebrovascular diseases, especially for stroke. It is believed that PNS has obvious anti-inflammatory effect, however, the roles of PNS on microglia after stroke have not been completely explored and the underlying mechanism of microglia-mediated inflammation remains to be clarified. In this study, cerebral ischemia injury was induced by photothrombotic (PT) stroke in mice. Two days after operation, PNS administration alleviated ischemic brain injury by increasing grip strength, relieving neurological deficits, improving local cerebral blood flow, and reducing pathological damage in the brain cortex and hippocampus. Moreover, microglial activation occurred in the acute stage after stroke and mediated inflammation, whereas PNS administration could inhibit microglial activation and inflammation. Meanwhile, we firstly demonstrated that PKM2 expression was upregulated in the nucleus of activated microglia after stroke, which could be inhibited after PNS administration. We hypothesized that suppression of nuclear PKM2 upregulation in microglia along with downregulation of HIF-1α/PKM2/STAT3 signaling could partially underlie the potential anti-inflammatory mechanism of PNS against ischemic brain injury. Our findings offer some new standpoints about PNS against microglia-mediated inflammation after stroke. Despite strengths, this study has limitation. PKM2 is not specifically expressed by microglia, but could be expressed by neurons, vascular endothelial cells, etc. Here we only explored the effect of PKM2 on activated microglia, and we would further investigate the impact of PKM2 expressed in other cells on stroke outcome in the future.
Topics: Animals; Mice; Panax notoginseng; Saponins; Microglia; Endothelial Cells; Inflammation; Stroke; Brain Injuries
PubMed: 36271540
DOI: 10.1016/j.biopha.2022.113479 -
Microbial Biotechnology Jul 2021Endophytes may participate in the conversion of metabolites within medicinal plants, influencing the efficacy of host. However, the distribution of endophytes within...
Endophytes may participate in the conversion of metabolites within medicinal plants, influencing the efficacy of host. However, the distribution of endophytes within medicinal plants P. notoginseng and how it contributes to the conversion of saponins are not well understood. Here, we determined the distribution of saponins and endophytes within P. notoginseng compartments and further confirm the saponin conversion by endophytes. We found metabolites showed compartment specificity within P. notoginseng. Potential saponin biomarkers, such as Rb1, Rg1, Re, Rc and Rd, were obtained. Endophytic diversity, composition and co-occurrence networks also showed compartment specificity, and bacterial alpha diversity values were highest in root compartment, consistently decreased in the stem and leaf compartments, whereas those of fungi showed the opposite trend. Potential bacterial biomarkers, such as Rhizobium, Bacillus, Pseudomonas, Enterobacter, Klebsiella, Pantoea and fungal biomarkers Phoma, Epicoccum, Xylariales, were also obtained. Endophytes related to saponin contents were found by Spearman correlation analysis, and further verification experiments showed that Enterobacter chengduensis could convert ginsenoside Rg1 to F1 at a rate of 13.24%; Trichoderma koningii could convert ginsenoside Rb1 to Rd at a rate of 40.00% and to Rg3 at a rate of 32.31%; Penicillium chermesinum could convert ginsenoside Rb1 to Rd at a rate of 74.24%.
Topics: Endophytes; Enterobacter; Ginsenosides; Hypocreales; Panax notoginseng; Penicillium
PubMed: 34081833
DOI: 10.1111/1751-7915.13842