Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 36
Filter
Add more filters










Publication year range
1.
Molecules ; 26(16)2021 Aug 10.
Article in English | MEDLINE | ID: mdl-34443430

ABSTRACT

Parkinson's disease (PD) is a currently incurable neurodegenerative disorder characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta and α-synuclein aggregation. Accumulated evidence indicates that the saponins, especially from ginseng, have neuroprotective effects against neurodegenerative disorders. Interestingly, saponin can also be found in marine organisms such as the sea cucumber, but little is known about its effect in neurodegenerative disease, including PD. In this study, we investigated the anti-Parkinson effects of frondoside A (FA) from Cucumaria frondosa and ginsenoside Rg3 (Rg3) from Panax notoginseng in C. elegans PD model. Both saponins were tested for toxicity and optimal concentration by food clearance assay and used to treat 6-OHDA-induced BZ555 and transgenic α-synuclein NL5901 strains in C. elegans. Treatment with FA and Rg3 significantly attenuated DAergic neurodegeneration induced by 6-OHDA in BZ555 strain, improved basal slowing rate, and prolonged lifespan in the 6-OHDA-induced wild-type strain with downregulation of the apoptosis mediators, egl-1 and ced-3, and upregulation of sod-3 and cat-2. Interestingly, only FA reduced α-synuclein aggregation, rescued lifespan in NL5901, and upregulated the protein degradation regulators, including ubh-4, hsf-1, hsp-16.1 and hsp-16.2. This study indicates that both FA and Rg3 possess beneficial effects in rescuing DAergic neurodegeneration in the 6-OHDA-induced C. elegans model through suppressing apoptosis mediators and stimulating antioxidant enzymes. In addition, FA could attenuate α-synuclein aggregation through the protein degradation process.


Subject(s)
Caenorhabditis elegans/physiology , Ginsenosides/pharmacology , Glycosides/pharmacology , Parkinson Disease/pathology , Triterpenes/pharmacology , Animals , Animals, Genetically Modified , Apoptosis/drug effects , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/metabolism , Disease Models, Animal , Dopaminergic Neurons/drug effects , Dopaminergic Neurons/pathology , Gene Expression Regulation/drug effects , Ginsenosides/chemistry , Ginsenosides/toxicity , Glycosides/chemistry , Glycosides/toxicity , Longevity/drug effects , Nerve Degeneration/complications , Nerve Degeneration/pathology , Oxidopamine , Parkinson Disease/complications , Proteolysis/drug effects , Triterpenes/chemistry , Triterpenes/toxicity , alpha-Synuclein/metabolism
2.
Food Chem Toxicol ; 155: 112403, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34246707

ABSTRACT

As a main metabolite of ginsenosides, compound K (CK) has a vast array of pharmacological effects. However, due to its low polarity and insoluble in water, its oral application has been greatly limited. In this work, the interaction between serum albumin and ginsenoside CK was elucidated by multi-spectroscopic studies. The result of ultraviolet/visible absorption spectroscopy showed that the conformation of serum albumin could be changed via binding with CK. The result of fluorescence spectroscopy suggested that CK could form complex with serum albumin. CK could quench the fluorescence and the fluorescence residues of serum albumin were located in or near the binding position. Molecular docking indicated that CK bound at Sudlow's site II of serum albumin and formed hydrogen-bonding interactions with three residues. Furthermore, the flexible side chain of CK was difficult to be stabilized at the binding site, resulting in its serious perturbation during dynamics simulation. This work also performed the cytotoxic study and the result showed that serum albumin enhanced the inhibitory effect of CK on the proliferation of both Caco-2 and HCT-116 cells. To sum up, this work revealed that serum albumin might be an appropriate carrier of hydrophobic compounds, with the advantage of improving their biocompatibility.


Subject(s)
Ginsenosides/metabolism , Ginsenosides/toxicity , Serum Albumin, Bovine/metabolism , Animals , Binding Sites , Cattle , Cell Line, Tumor , Ginsenosides/chemistry , Humans , Hydrogen Bonding , Molecular Docking Simulation , Molecular Dynamics Simulation , Protein Binding , Serum Albumin, Human/chemistry , Serum Albumin, Human/metabolism , Spectrometry, Fluorescence , Spectrophotometry, Ultraviolet
3.
Ecotoxicol Environ Saf ; 213: 112065, 2021 Apr 15.
Article in English | MEDLINE | ID: mdl-33636464

ABSTRACT

Listeria monocytogenes widely exists in the natural environment and does great harm, which can cause worldwide public safety problem. Infection with L. monocytogenes can cause rapid death of Kupffer cell (KCs) in liver tissue and liver damage. American ginseng saponins is a natural compound in plants, which has great potential in inhibiting L. monocytogenes infection. Therefore, American ginseng stem-leaf saponins (AGS) and American ginseng heat-transformed saponins (HTS) were used as raw materials to study their bacteriostatic experiments in vivo and in vitro. In this experiment, female Kunming mice were randomly divided into five groups: control group, negative group, AGS group, HTS group (10 mg/kg/day in an equal volume via gastric administration) and penicillin group, each group containing six mice. Profiles AGS and HTS components were evaluated by high-performance liquid chromatography (HPLC) analysis. The bacteriostatic effect of AGS and HTS on L. monocytogenes was evaluated by inhibition zone test, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The bacteriostatic effect of AGS and HTS pretreatment on mice infected with L. monocytogenes were studies by animal experimental. The results showed that the content of polar saponins in AGS was 0.81 ± 0.003 mg/mg, less polar saponins was 0.08 ± 0.02 mg/mg, the content of polar saponins in HTS was 0.10 ± 0.01 mg/mg, less polar saponins was 0.76 ± 0.02 mg/mg. The in vitro bacteriostatic diameter of HTS (16.6 ± 0.8 mm) is large than that of AGS (10.2 ± 1.2 mm). AGS and HTS pretreatment could reduce the colony numbers in the livers of mice infected with Listeria monocytogenes. The levels of alanine aminotransferase (ALT), IL-1ß, IL-6, TNF-α and IFN-γ in the livers of mice in the pretreatment group were significantly lower than those in the negative group. There were obvious leukoplakia, calcification and other liver damage on the liver surface in the negative control group, and obvious inflammatory cell infiltration in HE sections. AGS and HTS pretreatment can reduce liver injury caused by L. monocytogenes and protect the liver. Compared with AGS, HTS has higher content of less polar saponins and better bacteriostatic effect in vitro. The count of bacterial in liver tissue of HTS group was significantly lower, the survival rate was significantly higher than that of AGS group. Less polar saponins had better bacteriostatic effect. Collectively, less polar saponins pretreatment has a protective effect on mice infected with L. monocytogenes, to which alleviated liver damage, improved anti-inflammatory ability and immunity of the body, protected liver may contribute.


Subject(s)
Ginsenosides/toxicity , Listeria monocytogenes/drug effects , Animals , Female , Listeriosis/immunology , Listeriosis/metabolism , Listeriosis/microbiology , Listeriosis/veterinary , Liver/metabolism , Mice , Microbial Sensitivity Tests , Stomach , Tumor Necrosis Factor-alpha
4.
Int J Pharm ; 587: 119669, 2020 Sep 25.
Article in English | MEDLINE | ID: mdl-32702454

ABSTRACT

Organ-on-a-chip as a new technology distinguishes it from animal and cell models at least in three aspects: (1) it responds to drugs' efficacy or toxicity more really by mimicking the human body's fluid microenvironment; (2) it can be used for high throughput screening a large number of compounds; (3) it has physiological accuracy. It is well known that ginsenosides compound K (CK) as a carbohydrate drug has numerous biological activities and physiological functions. However, pharmacokinetic studies of carbohydrate-based CK haven't been performed on organ chips. Here, we established and evaluated the function of single-organ chips and multi-organ chips based on intestinal, vascular, liver, and kidney chips. Each single-organ-on-a-chip performed itself well. Based on organ-on-chips, absorption, metabolism and toxicity of CK were successfully investigated. The pharmacokinetic results of CK provided by chip were consistent with previous reports, demonstrating the reliability of the organ-on-a-chip platform and its potential for use in pharmacokinetic studies of carbohydrate-drugs. As far as we know, this study would be the first report on the pharmacological investigation of carbohydrate drugs on organ-on-a-chip, which provides a theoretical basis for carbohydrate-based drug discovery.


Subject(s)
Ginsenosides , Animals , Ginsenosides/toxicity , Humans , Kidney , Lab-On-A-Chip Devices , Reproducibility of Results
5.
J Ethnopharmacol ; 248: 112323, 2020 Feb 10.
Article in English | MEDLINE | ID: mdl-31639487

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Ginsenoside compound K (CK), a product produced by the intestinal bacteria-mediated breakdown of ginsenoside, exhibits a wide array of pharmacological activities against diverse targets. However, few of preclinical safety evaluation of CK is reported. AIMS OF THE STUDY: The present study therefore sought to assess the toxicity of oral CK in Beagle dogs over a 26-week period. MATERIAL AND METHODS: All dogs received 4, 12, or 36 mg/kg oral CK doses for 26 weeks with regular monitoring, followed by a 4-week recovery period. Animals were monitored through measurements of temperature, weight, food intake, blood chemistry and hematological findings, electrocardiogram (ECG) measurements, urinalysis, gross necropsy and organ weight and tissue histopathology. RESULTS: Animals in the 36 mg/kg group exhibited an apparent reduction in body weight over the study period, in addition to the presence of focal liver necrosis and increased plasma enzyme levels (alanine aminotransferase, ALT; alkaline phosphatase, ALP) consistent with hepatotoxicity, although there was some evidence suggesting this toxicity was reversible. Animals in the 4 and 12 mg/kg groups did not exhibit any apparent toxicity for any measured parameters. CONCLUSION: These results thus indicate that the no observed adverse effect level (NOAEL) in dogs is 12 mg/kg.


Subject(s)
Chemical and Drug Induced Liver Injury/etiology , Ginsenosides/toxicity , Liver/drug effects , Administration, Oral , Alanine Transaminase/blood , Alkaline Phosphatase/blood , Animals , Biomarkers/blood , Chemical and Drug Induced Liver Injury/blood , Chemical and Drug Induced Liver Injury/pathology , Dogs , Dose-Response Relationship, Drug , Female , Ginsenosides/administration & dosage , Liver/metabolism , Liver/pathology , Male , Necrosis , No-Observed-Adverse-Effect Level , Risk Assessment , Time Factors , Weight Loss/drug effects
6.
Regul Toxicol Pharmacol ; 110: 104522, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31726191

ABSTRACT

20(s)-ginsenoside Rg3 is a red ginseng-derived compound with the formula C42H72O13 that has been increasingly used by humans, leading to safety concerns regarding this use. In the current study, we conducted a 26-week study during which 20(S)-ginsenoside Rg3 (0, 7, 20, or 60 mg/kg) was continuously administered orally to Beagle dogs in order to explore its toxicity in these animals, with control dogs receiving a vehicle capsule. In total, 10 dogs received each dose of this compound (n = 5 male, n = 5 female per dose). Animals were continuously monitored for a 26-week administration period and a subsequent 4-week follow-up recovery period. At the end of study, we observed no evidence of 20(S)-ginsenoside Rg3 toxicity in clinical indications, body weight, food intake, ophthalmoscopy, electrocardiogram, urinalysis, hematology, serum biochemistry, gross and histopathology findings. However, the kidney relative weight of animals receiving 60 mg/kg of compound was significantly elevated relative to control animals (5.15 ±â€¯0.88‰ vs. 4.11 ±â€¯0.59‰. P < 0.05), and this effect was reversed after 4-week recovery period. Based on these results, the NOAEL value for orally administered 20(S)-ginsenoside Rg3 in dogs is 20 mg/kg.


Subject(s)
Antineoplastic Agents, Phytogenic/toxicity , Ginsenosides/toxicity , Administration, Oral , Animals , Dogs , Female , Kidney/drug effects , Kidney/pathology , Male , No-Observed-Adverse-Effect Level , Organ Size/drug effects , Toxicity Tests, Subchronic
7.
Food Chem Toxicol ; 131: 110578, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31201900

ABSTRACT

Ginsenoside compound K (CK) is a hydrolysate of ginsenosides in the soil bacteria. This study evaluated the toxicity of CK as acute and the 26-week repeated-dose. The results of acute toxicity show that CK administered orally to rats and mice did not cause mortality or toxicity at the maximum dosage of 8 g/kg and 10 g/kg, respectively. In the toxicity study for 26-week, rats were administered with CK at doses of 13, 40, or 120 mg/kg, and were observed for 26 weeks and recovery periods of four weeks. Under the conditions, asthenia, hypoactivity, loss of fur and body weight reduction were transiently noticed in males of 120 mg/kg group. Hepatotoxicity and nephrotoxicity also were evident including the elevation of liver and kidney relative weight, along with focal liver necrosis as well as the increase in plasma enzymes (ALT and ALP) in male rats receiving CK (120 mg/kg), but this toxicity might be reversible. For 13 and 40 mg/kg CK groups, there was no significant variation in food habits, clinical signs, urine analysis, body weight, biochemical and hematological values, organ coefficient and histopathology examination. The NOAEL for male and female rats were observed to be 40 and 120 mg/kg, respectively.


Subject(s)
Ginsenosides/toxicity , Administration, Oral , Animals , Body Weight/drug effects , Female , Ginsenosides/administration & dosage , Kidney/pathology , Liver/pathology , Male , Mice , No-Observed-Adverse-Effect Level , Organ Size/drug effects , Pilot Projects , Rats, Sprague-Dawley , Time Factors , Toxicity Tests, Acute
8.
Environ Toxicol ; 34(9): 1001-1012, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31112002

ABSTRACT

Ginsenoside Rb1 (GRb1), the major saponin component of ginseng root, has a wide range of therapeutic applications for various diseases. Previously, our group showed that GRb1 triggers ROS-mediated apoptotic cascades in mouse blastocysts, leading to decreased cell viability and impairment of pre- and postimplantation embryonic development, both in vitro and in vivo. In this study, we further found that GRb1 exerted dose-dependent effects on oocyte maturation and sequent development in vitro. Oocytes preincubated with 25 µg/mL GRB1 displayed significantly enhanced maturation and in vitro fertilization (IVF) rates, along with progression of subsequent embryonic development. In contrast, treatment with 50 and 100 µg/mL GRB1 led to impairment of mouse oocyte maturation, decreased IVF rates, and injurious effects on subsequent embryonic development. In vivo, intravenous injection of 1 mg/kg body weight GRb1 significantly promoted mouse oocyte maturation, IVF, and early-stage embryo development after fertilization while administration of 5 mg/kg body weight GRb1 led to a marked decrease in oocyte maturation and IVF rates concomitant with impairment of early embryonic development in our animal model. In terms of the mechanisms underlying the regulatory effects of GRb1 demonstrated increased intracellular reactive oxygen species (ROS) production and apoptosis in the 100 µg/mL GRb1 treatment group. However, we observed a significant decrease in total intracellular ROS content and inhibition of apoptosis events in the 25 µg/mL GRb1 treatment group, signifying that the intracellular ROS content serves as a key upstream regulator of GRb1 that influences its dose-dependent beneficial or deleterious effects on oocyte maturation and sequent embryonic development. For further clarification of the mechanisms underlying GRb1-triggered injurious effects, oocytes were pretreated with Ac-DEVD-CHO, a caspase-3-specific inhibitor, which effectively blocked injury to oocyte maturation, fertilization, and sequent development. In sum, study findings highlight the potential involvement of p53-, p21-, and caspase-3-dependent regulatory signaling cascades in GRb1-mediated apoptotic processes.


Subject(s)
Fetal Development/drug effects , Ginsenosides , Oocytes/drug effects , Oogenesis/drug effects , Animals , Apoptosis/drug effects , Blastocyst/drug effects , Blastocyst/metabolism , Dose-Response Relationship, Drug , Embryonic Development/drug effects , Female , Fertilization in Vitro , Ginsenosides/administration & dosage , Ginsenosides/pharmacology , Ginsenosides/toxicity , In Vitro Techniques , Mice , Mice, Inbred ICR , Oocytes/metabolism , Pregnancy , Reactive Oxygen Species/metabolism , Signal Transduction
9.
Photochem Photobiol ; 95(6): 1412-1423, 2019 11.
Article in English | MEDLINE | ID: mdl-31074886

ABSTRACT

Ginsenosides are compounds responsible for the primary pharmacological effects of American ginseng. Compound-Y (C-Y) is a minor ginsenoside and a metabolite of Panax ginseng. In this study, we investigated the protective effect of ginsenoside UVB-irradiated NHDFs and its potential for use as an antihyperpigmentation agent through ginsenoside C-Y as a functional food and cosmetic ingredient. Ginsenoside C-Y is a natural antioxidant isolated from the American ginseng PDD-ginsenoside. Our data showed that ginsenoside C-Y block UVB-exposed ROS, restrict MMP-1 production and promote procollagen type I synthesis. Interestingly, ginsenoside C-Y suppresses UVB-exposed VEGF, and TNF-α secretion, could be related with NFAT signal path. Ginsenoside C-Y has exhibited photoaging effects by increasing TGF-ß1 level, fortifying Nrf2 nuclear translocation and restricting AP-1 and MAPK phosphorylation. Assessment of the melanogenic response indicated that ginsenoside C-Y inhibited melanin secretion and tyrosinase activity and decreased melanin content in Melan-a and zebrafish embryos. These results suggest that ginsenoside C-Y can be used as a potential botanical agent to protect premature skin from UVB-induced photodamage and prevent skin hyperpigmentation.


Subject(s)
Ginsenosides/metabolism , Ginsenosides/pharmacology , Melanins/biosynthesis , Skin Aging/drug effects , Ultraviolet Rays/adverse effects , Animals , Antioxidants/chemistry , Antioxidants/metabolism , Antioxidants/pharmacology , Cell Line , Cell Survival/drug effects , Down-Regulation , Free Radical Scavengers , Gene Expression Regulation/drug effects , Ginsenosides/toxicity , Humans , Reactive Oxygen Species , Zebrafish
10.
Chem Biodivers ; 14(12)2017 Dec.
Article in English | MEDLINE | ID: mdl-28944607

ABSTRACT

Three new triterpenoid saponins, named ginsenoside-Rh23 (1), ginsenoside-Rh24 (2), and ginsenoside-Rh25 (3), were isolated from notoginseng medicinal fungal substance. Their structures were elucidated by a combination of 1D- and 2D-NMR, MS and chemical analysis. Compounds 1 - 3 exhibited moderate cytotoxic activity against MCF-7 and NCI-H460 cancer cell lines.


Subject(s)
Ginsenosides/chemistry , Panax/chemistry , Saponins/chemistry , Triterpenes/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Chromatography, Thin Layer , Ginsenosides/isolation & purification , Ginsenosides/toxicity , Humans , MCF-7 Cells , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Conformation , Panax/metabolism , Plant Roots/chemistry , Plant Roots/metabolism , Saponins/toxicity , Triterpenes/toxicity
11.
Food Chem Toxicol ; 107(Pt A): 362-372, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28698154

ABSTRACT

The use of Panax ginseng and Panax quinquefolius in traditional Chinese medicine dates back to about 5000 years ago thanks to its several beneficial and healing properties. Over the past few years, extensive preclinical and clinical evidence in the scientific literature worldwide has supported the beneficial effects of P. ginseng and P. quinquefolius in significant central nervous system, metabolic, infectious and neoplastic diseases. There has been growing research on ginseng because of its favorable pharmacokinetics, including the intestinal biotransformation which is responsible for the processing of ginsenosides - contained in the roots or extracts of ginseng - into metabolites with high pharmacological activity and how such principles act on numerous cell targets. The aim of this review is to provide a simple and extensive overview of the pharmacokinetics and pharmacodynamics of P. ginseng and P. quinquefolius, focusing on the clinical evidence which has shown particular effectiveness in specific diseases, such as dementia, diabetes mellitus, respiratory infections, and cancer. Furthermore, the review will also provide data on toxicological factors to support the favorable safety profile of these medicinal plants.


Subject(s)
Ginsenosides/toxicity , Panax/chemistry , Plant Extracts/toxicity , Animals , Ginsenosides/chemistry , Humans , Panax/classification , Panax/toxicity , Plant Extracts/chemistry , Plant Roots/chemistry , Plant Roots/toxicity
12.
Environ Toxicol ; 32(7): 1937-1951, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28371286

ABSTRACT

Ginsenoside Rg1, which is the most abundant compound found in Asian ginseng (Panax ginseng), has demonstrated various pharmacological actions, including neuroprotective, immune-stimulatory, and antidiabetic effects. Pregnant women, especially in the Asian community, consume ginseng as a nutritive supplement. Thus, the effects of ginsenoside-Rg1 on embryonic development need to be investigated, such as in a mouse model. As previous investigations have found that ginsenoside Rg1 appears to either trigger or prevent apoptosis in different cell lines, the effects of this agent on apoptosis remain to be clarified. In this study, we investigated whether ginsenoside Rg1 exerts a hazardous effect on mouse blastocysts and/or affects subsequent embryonic development in vitro and in vivo. Blastocysts treated with 25-100 µM ginsenoside Rg1 exhibited significant induction of apoptosis and a corresponding decrease in the inner cell mass (ICM) cell number. Importantly, the implantation rate was lower among ginsenoside Rg1-treated blastocysts compared to untreated controls. Moreover, embryo transfer assays revealed that blastocysts treated with 100 µM ginsenoside Rg1 exhibited increased resorption of postimplantation embryos and decreased weight among surviving fetuses. In vivo, intravenous injection of mice with ginsenoside Rg1 (2, 4, or 6 mg/kg body weight/day) for 4 days was associated with increased apoptosis of blastocyst-stage embryos and negatively impacted early embryonic development. Further experiments revealed that these effects may reflect the ability of ginsenoside Rg1 to trigger oxidative stress-mediated intrinsic apoptotic signaling. Our in vitro results indicate that ginsenoside Rg1 treatment increases intracellular oxidative stress, decreases mitochondrial membrane potential, increases the Bax/Bcl-2 ratio, and activates caspase-9 and caspase-3, but not caspase-8. Taken together, our study results strongly suggest that ginsenoside Rg1 induces apoptosis and impairs the early preimplantation and postimplantation development of mouse embryos, both in vitro and in vivo.


Subject(s)
Apoptosis/drug effects , Drugs, Chinese Herbal/toxicity , Embryonic Development/drug effects , Ginsenosides/toxicity , Animals , Blastocyst/cytology , Blastocyst/drug effects , Caspase 3/metabolism , Caspase 8/metabolism , Caspase 9/metabolism , Cell Count , Enzyme Activation , Female , Membrane Potential, Mitochondrial/drug effects , Mice, Inbred ICR , Oxidative Stress/drug effects , Pregnancy , Signal Transduction/drug effects
13.
Environ Toxicol ; 32(8): 1990-2003, 2017 Aug.
Article in English | MEDLINE | ID: mdl-27640876

ABSTRACT

Ginsenoside Rb1, the major saponin component of ginseng root, has a wide range of therapeutic application. Previous studies have established that ginsenoside Rb1 inhibits the cell cycle and induces apoptosis. However, its side-effects, particularly those on embryonic development, have not been well characterized to date. In the current study, we examined whether ginsenoside Rb1 exerts a cytotoxic effect on mouse embryos at the blastocyst stage, and affects subsequent embryonic development in vitro and in vivo. Blastocysts treated with 25-100 µg mL-1 ginsenoside Rb1 exhibited significantly increased apoptosis and a corresponding decrease in total cell number. Notably, the implantation success rate of blastocysts pretreated with ginsenoside Rb1 was lower than that of their control counterparts. Moreover, in vitro treatment with 25-100 µg mL-1 ginsenoside Rb1 was associated with increased resorption of post-implantation embryos and decreased fetal weight. In an in vivo model, intravenous injection with ginsenoside Rb1 (1, 3, 5 mg kg-1 body weight/day) for 4 days resulted in apoptosis of blastocyst stage embryos and early embryonic developmental injury. In addition, ginsenoside Rb1 appeared to induce injury in mouse blastocysts through oxidative stresses-triggered intrinsic apoptotic signaling processes to impair sequent embryonic development. The collective results strongly indicate that ginsenoside Rb1 induces apoptosis and retards early pre- and post-implantation development of mouse embryos, both in vitro and in vivo. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1990-2003, 2017.


Subject(s)
Apoptosis/drug effects , Embryonic Development/drug effects , Ginsenosides/toxicity , Oxidative Stress/drug effects , Animals , Blastocyst/drug effects , Embryo Implantation/drug effects , Female , Male , Mice, Inbred ICR , Pregnancy , Signal Transduction/drug effects
14.
Regul Toxicol Pharmacol ; 83: 5-12, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27840091

ABSTRACT

SHENMAI injection (SMI), derived from famous Shen Mai San, is a herbal injection widely used in China. Ginsenosides are the major components of SMI. To monitor the exposure level of SMI during long-term treatment, a 6-month toxicokinetic experiment was performed. Twenty-four beagle dogs were dived into four groups (n = 6 in each group): a control group (0.9% NaCl solution) and three SMI groups (2, 6 or 3 mg/kg). The dogs were i.v. infused with vehicle or SMI daily for 180 d. Blood samples for analysis were collected at specific time points as follows: pre-dose (0 h); at 10, 30, and 60 min during infusion; and at 10, 30, 60, 90, 120, 240, and 300 min post-administration. Concentrations of ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1 in the plasma were determined simultaneously by liquid chromatography-tandem mass spectrometry. Non-compartmental parameters were further calculated and analyzed. Significant differences were found between the kinetic behavior of 20(S)-protopanaxadiol-type (PPD-type) and 20(S)-protopanaxatriol-type (PPT-type) ginsenosides. Increasing in the exposure level of PPD-type ginsenosides was observed in dogs during the experiment. Therefore, PPD-type ginsenosides are closely related to the immunity modulation effect of SMI. Increased PPD-type ginsenoside exposure level may present potential toxicity and induce drug-drug interaction risks during SMI administration. As such, PPD-type ginsenoside accumulation must be carefully monitored in future SMI research.


Subject(s)
Drugs, Chinese Herbal/toxicity , Ginsenosides/toxicity , Sapogenins/toxicity , Toxicokinetics , Animals , Body Burden , Chromatography, High Pressure Liquid , Dogs , Drug Combinations , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/pharmacokinetics , Female , Ginsenosides/administration & dosage , Ginsenosides/blood , Ginsenosides/pharmacokinetics , Infusions, Intravenous , Male , Models, Biological , Reproducibility of Results , Sapogenins/administration & dosage , Sapogenins/blood , Sapogenins/pharmacokinetics , Tandem Mass Spectrometry , Time Factors
15.
Int J Mol Sci ; 16(12): 29345-56, 2015 Dec 09.
Article in English | MEDLINE | ID: mdl-26690140

ABSTRACT

Our previous study indicated that the combination of salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1), the main components of Salvia miltiorrhizae and Panax notoginseng, improves myocardium structure and ventricular function in rats with ischemia/reperfusion injury. The present study aimed to determine the safety of the combined SalB and Rg1 (SalB-Rg1) in mice. The safety of SalB-Rg1 was evaluated through acute toxicity and repeated-dose toxicity. In the acute toxicity study, the up and down procedure was carried out firstly, and then, the Bliss method was applied. In the toxicity study for seven-day repeated treatment of SalB-Rg1, forty Kunming mice were randomly divided into four groups. The intravenous median lethal dose (LD50) of the SalB-Rg1 combination was 1747 mg/kg using the Bliss method. For both the acute toxicity study and the seven-day repeated toxicity study, SalB-Rg1 did not induce significant abnormality on brain, heart, kidney, liver and lung structure at any dose based on H&E stain. There were no significant changes related to the SalB-Rg1 toxicity detected on biochemical parameters for two kinds of toxicity studies. The LD50 in mice was 1747 mg/kg, which was more than one hundred times higher than the effective dose. Both studies of acute toxicity and seven-day repeated dose toxicity indicated the safety of the SalB-Rg1 combination.


Subject(s)
Benzofurans/toxicity , Cardiovascular Agents/toxicity , Ginsenosides/toxicity , Animals , Drug Combinations , Drug Evaluation, Preclinical , Female , Lethal Dose 50 , Male , Mice
16.
Zhongguo Zhong Yao Za Zhi ; 40(8): 1433-8, 2015 Apr.
Article in Chinese | MEDLINE | ID: mdl-26281575

ABSTRACT

Ginsenosides are the abundant secondary metabolites in American ginseng (Panax quinquefolium), it could be released into soil through root exudation and decomposition during plant growth. This study determined ginsenoside contents in American ginseng cultivated soil by HPLC. Three ginsenosides, Rb1, Rb2 and Rd, were detected in the rhizosphere soil of 3-4 years old American ginseng cultivated in Huairou District, Beijing, and their contents were 0.80-3.19 mg x kg(-1). Correspondingly, the contents of the three ginsenosides in soil solution were 4-16 mg x L(-1) at field water-holding capacity of 20%. According to the field soil test data, we designed the concentration of ginsenosides for bioassays (0.2-125 mg x L(-1) in solution or 0.2-125 mg x kg(-1) in soil). The results showed that radicle lengths of American ginseng were reduced by 6%-23% in solution containing 0.2-125 mg x L(-1) ginsenoside extract, and a significant difference was observed at concentration of 125 mg x L(-1) (P < 0.05). The shoot lengths of American ginseng were not significantly inhibited by 0.2-125 mg x L(-1) ginsenosides extractions. After 20 days of growth in nutrient solution amended with 25 mg x L(-1) ginsenosides extraction, plant height of 3-year-old American ginseng seedling was decreased by 28% compared to the control, and the biomass of aerial parts was also reduced by 50% (P < 0.05). However, the growth of newly-grown fibrous root was not significantly inhibited. Comparatively, when American ginseng embryos were cultivated into sterile or non-sterile soil, neither radicle lengths nor shoot lengths were significantly affected by 0.2-125 mg x kg(-1) ginsenoside extracts. In conclusion, ginsenosides showed autotoxic effect on growth of American ginseng radicle and adult seedling, however, this effect was weakened in field soil.


Subject(s)
Ginsenosides/toxicity , Panax/growth & development , Chromatography, High Pressure Liquid , Culture Media/chemistry , Culture Media/metabolism , Ginsenosides/analysis , Ginsenosides/metabolism , Panax/chemistry , Panax/drug effects , Panax/metabolism , Plant Roots/chemistry , Plant Roots/drug effects , Plant Roots/growth & development , Plant Roots/metabolism , Soil/chemistry
17.
PLoS One ; 10(2): e0118555, 2015.
Article in English | MEDLINE | ID: mdl-25695831

ABSTRACT

BACKGROUND AND AIMS: Sanqi ginseng (Panax notoginseng) growth is often hampered by replant failure. In this study, we aimed to examine the role of autotoxicity in Sanqi replant failures and assess the role of ginsenosides in autotoxicity. METHODS: The autotoxicities were measured using seedling emergence bioassays and root cell vigor staining. The ginsenosides in the roots, soils, and root exudates were identified with HPLC-MS. RESULTS: The seedling emergence and survival rate decreased significantly with the continuous number of planting years from one to three years. The root exudates, root extracts, and extracts from consecutively cultivated soils also showed significant autotoxicity against seedling emergence and growth. Ginsenosides, including R1, Rg1, Re, Rb1, Rb3, Rg2, and Rd, were identified in the roots and consecutively cultivated soil. The ginsenosides, Rg1, Re, Rg2, and Rd, were identified in the root exudates. Furthermore, the ginsenosides, R1, Rg1, Re, Rg2, and Rd, caused autotoxicity against seedling emergence and growth and root cell vigor at a concentration of 1.0 µg/mL. CONCLUSION: Our results demonstrated that autotoxicity results in replant failure of Sanqi ginseng. While Sanqi ginseng consecutively cultivated, some ginsenosides can accumulate in rhizosphere soils through root exudates or root decomposition, which impedes seedling emergence and growth.


Subject(s)
Ginsenosides/toxicity , Panax notoginseng/physiology , Rhizosphere , Ginsenosides/analysis , Panax notoginseng/drug effects , Panax notoginseng/metabolism , Plant Roots/drug effects , Seedlings/drug effects , Soil/chemistry
18.
Mol Med Rep ; 10(4): 1779-85, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25051397

ABSTRACT

In previous experiments, ginsenoside Rh2 induced apoptosis and cell cycle arrest, which indicates a potential role for ginsenoside Rh2 in anticancer treatment. The effect of ginsenoside Rh2 on cancer is marked and ginsenoside Rh2 has been shown to inhibit pancreatic tumor migratory ability. In the present study, Transwell chambers were used in order to investigate whether ginsenoside Rh2 inhibits the migratory ability of HepG2 liver carcinoma cells. Furthermore, to analyze activator protein 1 (AP-1) transcription factor expression following Rh2 treatment, ten plasmids encoding Renilla luciferase coupled to the transcription factors were transiently transfected into the HepG2 cells and luciferase was detected by the Luciferase Reporter Assay system reagent. The results indicated that ginsenoside Rh2 inhibited HepG2 cell migratory ability. The expression levels of AP-1 transcription factors were increased in HepG2 cells following induction by phorbol 12-myristate 13-acetate, but ginsenoside Rh2 suppressed this induced AP­1 expression. AP-1 transcription factors recruit histone deacetylase (HDAC)4 and affect its transcription, thus, the expression levels of HDAC4 were also analyzed, and these were found to be increased in the Rh2 treatment group. Matrix metalloproteinase 3 (MMP3), a gene downstream of AP-1, was then investigated, and the treatment group expressed reduced levels of MMP3 gene and protein. Therefore, the inhibitory effect of ginsenoside Rh2 on the migratory ability of HepG2 may be presumed to occur by the recruitment of HDAC and the resulting inhibition of AP­1 transcription factors, in order to reduce the expression levels of MMP3 gene and protein.


Subject(s)
Cell Movement/drug effects , Ginsenosides/toxicity , Transcription Factor AP-1/metabolism , Down-Regulation/drug effects , Hep G2 Cells , Histone Deacetylases/genetics , Histone Deacetylases/metabolism , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Matrix Metalloproteinase 3/genetics , Matrix Metalloproteinase 3/metabolism , RNA, Messenger/metabolism , Repressor Proteins/genetics , Repressor Proteins/metabolism , Tetradecanoylphorbol Acetate/analogs & derivatives , Tetradecanoylphorbol Acetate/pharmacology , Transcription Factor AP-1/antagonists & inhibitors , Transcription Factor AP-1/genetics
19.
J Ethnopharmacol ; 154(2): 391-9, 2014 Jun 11.
Article in English | MEDLINE | ID: mdl-24747029

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: 'SHENMAI' injection (SMI) has been widely used in cardioprotection and modulation of the immune system because of its great efficacy. SMI primarily comprises the saponins from Panax ginseng and Ophiopogon japonicas. The profiles of saponins in SMI during long-term toxicokinetics remain unclear. MiR-146a possesses excellent sensitivity as a bio-marker in the innate immunity modification effect of SMI. AIM OF THE STUDY: Is to monitor the exposure level of SMI during a one-month toxicokinetic experiment, an analytical method involving ESI-LC-MS/MS technology was developed to determine 20 (S)-protopanaxadiol-type ginsenoside (Rb1, Rb2, Rc, Rd), 20 (S)-protopanaxatriol-type ginsenoside (Rg1, Re, Rf), oleanolic acid-type ginsenoside (Ro), and ophiopogonin D in rats. The levels of AST, CK, ALT, SOD, GSH-pX, MDA, miR-146a, and ECG were measured to explore the effects of SMI in cardiologic function and immune activity. RESULTS: Results show that the levels of AST, CK, and MDA decreased upon the administration of SMI. The level of miR-146a increased upon the administration of SMI dosage. During the administration of SMI, increasing exposure levels of 20 (S)-protopanaxadiol-type ginsenosides were also observed. CONCLUSION: The 20 (S)-protopanaxadiol-type ginsenosides were considered potential PK/TK markers because of their high exposure levels that continuously increased. Oxidative stress was slightly alleviated during the toxicokinetic study. Based on the level of miR-146a, negatively regulated innate immunity was observed. The regulation became more serious with increasing exposure levels of 20 (S)-protopanaxadiol-type ginsenosides. Negatively regulated innate immunity could be induced by long-term administration of SMI (>0.4g/kg).


Subject(s)
Drugs, Chinese Herbal/toxicity , Ginsenosides/toxicity , Immunity, Innate/drug effects , Saponins/toxicity , Spirostans/toxicity , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Biomarkers/blood , Creatine Kinase/blood , Dose-Response Relationship, Drug , Drug Combinations , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/pharmacokinetics , Ethnopharmacology , Female , Ginsenosides/administration & dosage , Ginsenosides/blood , Immunity, Innate/immunology , Male , Medicine, Chinese Traditional , MicroRNAs/blood , Rats, Sprague-Dawley , Saponins/administration & dosage , Saponins/blood , Spirostans/administration & dosage , Spirostans/blood , Time Factors , Toxicokinetics
20.
Eur J Med Chem ; 68: 444-53, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23994872

ABSTRACT

A novel class of ocotillol-type triterpenoid derivatives have been synthesized and evaluated for their in vitro antibacterial activity against several representative pathogenic bacterial strains. Compounds 20(S)-protopanaxadiol (PPD), 3, 5, 16 and 24 exhibited potent antibacterial activity against Gram-positive bacteria. Compounds 3 and 5 also displayed promising antibacterial activity against a community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA; strain USA300). Furthermore, compounds PPD, 3 and 16 combined with two commercially available antibiotics kanamycin and chloramphenicol showed strong synergistic inhibitory effects at their sub-MIC concentrations against S. aureus USA300 and Bacillus subtilis 168. Additionally, cytotoxic activity assay showed that the compounds tested did not affect cell viability of the human epithelial kidney (HEK-293) and human cervical (HeLa) cells at their MICs.


Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Ginsenosides/chemical synthesis , Ginsenosides/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/toxicity , Cell Survival/drug effects , Ginsenosides/chemistry , Ginsenosides/toxicity , HEK293 Cells , HeLa Cells , Humans , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship
SELECTION OF CITATIONS
SEARCH DETAIL
...