Jingang Hou

Highly selective microbial transformation of major ginsenoside Rb1 to gypenoside LXXV by Esteya vermicola CNU120806

This study examined the biotransformation pathway of ginsenoside Rb1 by the fungus Esteya vermicola CNU 120806.

Compound K is able to ameliorate the impaired cognitive function and hippocampal neurogenesis following chemotherapy treatment

Chemotherapy frequently results in neurocognitive deficits that include impaired learning and memory. Thus, it is important to prevent or ameliorate the persistence of cognitive impairment. Compound K was employed to examine the ameliorating effect on chronic treatment with cyclophosphamide. Eight week-old ICR mice were given 80 mg/kg cyclophosphamide, cyclophosphamide combined with compound K (2.5, 5 and 10 mg/kg) or saline injections once per week for 4 weeks. Passive avoidance test and Y maze were used to evaluate memory and learning ability. Immunohistochemical staining for progenitor cell and immature neurons was used to assess changes in neurogenesis. Compound K (10 mg/kg) is able to ameliorate the decrease of neurogenesis in the hippocampus caused by cyclophosphamide. These results suggest that compound K might be a potential strategy to ameliorate or repair the disrupted hippocampal neurogenesis induced by the side effect of chemotherapy agent.

Long-term administration of ginsenoside Rh1 enhances learning and memory by promoting cell survival in the mouse hippocampus

Ginsenosides, the secondary plant metabolites produced by Panax ginseng are responsible for the enhancing effects on learning observed following treatment with Panax ginseng. A number of studies have provided correlational evidence that cell proliferation and survival are closely associated with hippocampal-dependent learning tasks. In this study, to investigate the beneficial effects of ginsenoside Rh1 on hippocampal cells and learning, mice (6 months old) were administered ginsenoside Rh1 at a dose of 5 and 10 mg/kg/day for a period of 3 months. Saline-treated mice were used as controls. The enhancement of memory and learning in the mice was evaluated by hippocampal-dependent tasks (passive avoidance tests and Morris water maze tests) and the immunohistochemical marker of cell proliferation, bromodeoxyuridine (BrdU). In addition, the levels of brain-derived neurotrophic factor (BDNF) were measured following treatment. Based on our data, the Rh1-treated group (5 and 10 mg/kg) showed a significantly improved learning and memory ability in the passive avoidance tests compared with the control group; however, only treatment with 10 mg/kg ginsenoside Rh1 significantly promoted spatial learning ability in the Morris water maze test. Ginsenoside Rh1 significantly enhanced cell survival in the dentate gyrus of mice, although it did not enhance hippocampal cell proliferation. In addition, ginsenoside Rh1 upregulated the expression of BDNF. These findings address the potential therapeutic significance of ginsenoside Rh1 as a nutritional supplement in memory loss and neurodegenerative diseases.

Isolation, synthesis and structures of ginsenoside derivatives and their anti-tumor bioactivity.

Protopanaxatriol saponins obtained with AB-8 macroporous resin mainly consisted of ginsenosides Rg1 and Re. A novel mono-ester of ginsenoside-Rh1 (ginsenoside-ORh1) was synthesized through further enzymatic hydrolysis and octanoyl chloride modifications. A 53% yield was obtained by a facile synthetic method. The structures were identified on the basis of 1D-NMR and 2D-NMR, as well as ESI-TOF-MS mass spectroscopic analyses. The isolated and synthetic compounds were applied in an anti-tumor bioassay, in which ginsenoside ORh1 showed moderate effects on Murine H22 Hepatoma Cells.

Laboratory studies on the development of a conidial formulation of Esteya vermicola

Abstract The endoparasitic nematophagous fungus, Esteya vermicola, has potential as a biocontrol agent against pinewood nematode, Bursaphelenchus xylophilus. An E. vermicola conidial formulation was developed to improve conidial resistance to ultraviolet (UV), drought and heat stress. The effective concentration of each protective additive [UV protectant [fulvic acid (FA) and skim milk (SM)]; drought protectant (sorbitol) and heat protectant (calcium chloride)] was determined based on the germination rate of E. vermicola conidia after exposure to the different stressors. A combination of 0.2% FA and 4% SM, 5% sorbitol and 0.05% calcium chloride provided the most effective protection. In addition, the concentrations of spreader–sticker and antibiotic were also decided. The final formulation could be used to improve the resistance of E. vermicola conidia to multiple stressors and to increase nematode mortality compared with unformulated conidia.

Ginsenoside Rd as a potential neuroprotective agent prevents trimethyltin injury

Trimethyltin (TMT) is a potent neurotoxicant that affects various regions within the central nervous system, including the neocortex, cerebellum, and hippocampus. In the present study, ginsenoside Rd was investigated as a candidate neuroprotective agent in a primary hippocampal neuron culture and mouse models. TMT induced neurotoxicity in a seven-day primary hippocampal neuron culture in a dose-dependent manner (2.5-10 µM). However, pre-treatment with 20 µg/ml ginsenoside Rd for 24 h reversed the toxic action. ICR mice were administered a single injection of 2 mg/kg body weight TMT. Apparent tremor seizure and impaired passive avoidance tests demonstrated significant differences when compared with a saline treated control group. Nissl staining was performed to evaluate the neuronal loss in the hippocampus. In addition, immunostaining of glial fibrillary acidic protein characterized the features of astroglial activation. These results demonstrated that TMT markedly induced Cornu Ammonis 1 subregion neuronal loss and reactive astrocytes in the hippocampus, indicating disrupted hippocampal function. Notably, ginsenoside Rd attenuated the tremor seizures and cognitive decline in behavioral tests. Additionally, significantly reduced neuronal loss (P=0.018) and active astroglials (P=0.003) were observed in the ginsenoside Rd treated group. Ginsenoside Rd prevented TMT-induced cell apoptosis via regulation of B-cell lymphoma 2 (Bcl-2), bcl-2-like protein 4 and caspase-3. These results demonstrate that ginsenoside may be developed as a neuroprotective agent to prevent TMT-induced neurotoxicity.

Ginsenoside Rh2 Improves Learning and Memory in Mice

A wide range of plant foods and dietary supplements are able to modify the functioning of the central nervous system. In the present study, we observed that oral administration of ginsenoside Rh2 (10 mg/mL) for 3 weeks significantly improved spatial learning and memory. Spatial memory and learning was evaluated in mice by hippocampus-dependent tasks (Morris water maze test) and immunohistochemical marker of cell genesis bromodeoxyuridine. Ginsenoside Rh2 treatment (30 days) promoted cell survival and genesis. Further, ginsenoside Rh2 treatment in enriched condition had no significant effects on cell survival compared with standard condition exposure. These results revealed that ginsenoside Rh2-mediated spatial learning and memory improvement was associated with cell genesis and survival and may be parallel to the mechanism of environmental enrichment. Therefore, ginsenoside Rh2 may have efficacy as a dietary supplement for spatial learning and memory improvement.

Effects of mineral salts on the growth, sporulation and virulence of Esteya vermicola, an endoparasitic fungus of the pinewood nematode, Bursaphelenchus xylophilus

Esteya vermicola, an endoparasitic fungus of pinewood nematode, exhibits great potential as a biological agent against nematodes. In this study, various mineral supplements, such as chloride salts (KCl, CaCl2, MgCl2, FeCl2, and FeCl3) and calcium salts (CaCl2, CaCO3, and CaSO4) were evaluated for their ability to enhance the growth, sporulation and virulence of E. vermicola. Of the cations tested, CaCl2 provided the greatest enhancement of growth speed and sporulation. Of the anions tested, CaCO3 produced the highest proportion of lunate conidia, and CaCl2 produced the highest adhesive rate and mortality against the nematode, Bursaphelenchus xylophilus. The optimum concentration of CaCl2 for optimization of sporulation and virulence was 0.4–0.6%. In conclusion, CaCl2 is highly effective in enhancing growth, sporulation and virulence of Esteya vermicola.

Ginsenoside Rg3 Prevents Oxidative Stress-Induced Astrocytic Senescence and Ameliorates Senescence Paracrine Effects on Glioblastoma

Senescent astrocytes in aging brain express senescence-associated secretory phenotype (SASP) and link with increased brain aging and its related diseases. In order to determine whether ginsenosides ameliorate the astrocytic senescence in vitro, human astrocytic CRT cells and primary rat astrocytes were used in the present study. Ginsenosides Rg1, Re, Rb1 and Rg3 (5 μg/mL) could effectively prevent the astrocytic senescence induced by H2O2 exposure. However, these ginsenosides did not reverse the astrocytic senescence. Importantly, senescent astrocytes herein produce SASP. The expression of major components of SASP, IL-6 and IL-8, are greatly increased in senescent astrocytes. Ginsenoside Rg3 (10 μg/mL) effectively suppressed the expressions of IL-6 and IL-8, which is associated with regulations of NF-κB and p38MAPK activation. In addition, after incubation with Rg3, conditioned medium from senescent astrocytic CRT cells significantly decreased the ability to promote the proliferation of astrocytoma U373-MG, U87-MG and U251-MG cells compared with non-treated senescent samples. Similar patterns were confirmed in chemotherapy-induced glioblastoma senescent cells. The present study explored a potential candidate for amelioration of astrocytic senescence and SASP in brain aging, which provided a basis for developing strategies to reduce the dark side of senescence in normal or pathological aging process.

Ginsenoside F1 suppresses astrocytic senescence-associated secretory phenotype

Senescence is one of the hallmarks of aging and identified as a potential therapeutic target in the treatment of aging and aging-related diseases. Senescent cells accumulate with age in a variety of human tissues where they develop a complex senescence-associated secretory phenotype (SASP). SASP in brain could contribute to age-related inflammation and chronic neurodegenerative diseases. We confirmed that senescent astrocytes express a characteristic of SASP in vitro by human cytokine antibody array. Ginsenoside F1 suppresses the SASP from astrocytes induced by d-galactose via suppressing p38MAPK-dependent NF-κB activity. A specific inhibitor of p38MAPK, SB203580 significantly decreased the secretion of IL-6 and IL-8, the major components of SASPs. Additionally, treatment of senescent astrocytes with NF-κB inhibitor, BAY 11-7092, also suppressed the secretion of IL-6 and IL-8, suggesting NF-κB was required for SASP. Importantly, conditioned media from senescent astrocytes promoted the migration of glioblastoma cells, such as U373-MG, U251-MG and U87-MG assessed by scratch wound healing. This migration was significantly decreased by F1 treatment in senescent astrocytes. Interestingly, IL-8, the main mediator regulating glioblastoma cell invasion, was suppressed in both transcriptional and protein level. Herein, we propose ginsenoside F1 as a potential therapeutic strategy for reducing the deleterious contribution of senescent astrocytes in aged brain and related diseases.