Sorafenib is the only approved systemic, therapeutic agent for hepatocellular carcinoma (HCC). The use of Ginseng Extract (GE) in cancer patients is growing worldwide; however, drug interaction between sorafenib and GE has not been illuminated. Four different human cancer cell lines including HepG2 were used and immunocompetent mice were implanted subcutaneously with a mouse HCC cell line. Treatment with low dose GE stimulated cell growth, while a high dose inhibited growth. pERK (phosphorylation of extracellular signal-regulated kinase) was concomitantly increased and decreased respective of different doses of GE. Antitumoral effect of sorafenib decreased in non-proliferating phase cells but was sensitized after low dose GE (LDG) treatment. PD98059 (ERK phosphorylation inhibitor) efficiently blocked ERK phosphorylation, resulting in loss of sorafenib sensitization even after LDG treatment. In the HCC mouse model, LDG alone slightly increased tumor size while sorafenib alone significantly decreased it. However, a combination of LDG and sorafenib significantly decreased tumor size compared with sorafenib alone. Increase of pERK was observed in some normal mice organs and mild inflammatory change was observed in some of these organs, suggesting pERK activation by LDG may cause unexpected toxicity in normal cells. GE, dose-dependently, induced stimulation or inhibition in some human cancer cell lines. Combinational use of GE and sorafenib possibly potentiated an antitumoral response to sorafenib. pERK level has been provided as a potential predictive marker for sorafenib. Our result may suggest GE's dual effects in relation to pERK level in HCC cancer cell lines, and that certain doses of GE can sensitize sorafenib.
The survival or colonization of beneficial organsisms and suppression of root rot of ginseng (Panax ginseng) by two distinct bacteria, Pseudomonas cepacia, Bacillus cereus and three mycorrhiza in pot soil were investigated and compared with uninoculated root. In separate inoculation, colonization of roots by P. cepacia was maintained at 6.25 (log cfu/g root) during growth for 10 days under pot culture conditions comparing to $5.62{\sim}6.19$ by mixed treatment with other organisms. Colonizations of P. cepacia were gradually decreased from 6.25 (log cfu/g root) in 10 days growth to 3.01 (log cfu/g root) in 270 days incubation period. This reduction was also investgated in combination treatments by B. cereus or F. solani. The numbers of Fusarium spp. were colonized high number in rhizosphere soil from 3.33 to 3.67 (log cfu/g root) in control within $10{\sim}60$days after treatment of pathogen F. solani, but it's numbers were markedly decreased in 270 days cultivation of plant from 3.33 to 1.02 (log cfu/g root) after treatment. In treatment of beneficial strains of P. cepacia and B. cereus, P. cepacia significantly suppressed the development of root rot from 4.3 in control to 1.2 in treatment, whereas B. cereus alone had no effect on the rate of disease suppression. The disease index $(1.8{\sim}2.3)$ in combination of two bacteria was reduced in plants inoculated with both P. cepacia and B. cereus comparing to the index (4.3) of control. As an effect of inoculation with mycorrhiza on disease suppression, suppression of root rot by F. solani was reduced to $1.2{\sim}1.6$ in disease index in treatment of Glomus albidum and Acaulospora longular comparing to 4.3 of control. In the treatment of bacterial strain P. cepacia and mycorrhizal fungus Glomus albidum, the disease suppression was apparent to 1.2 and 1.2 comparing to 4.3 of control in disease index respectively.
Nitrate nitrogen was absorbed dominantly among the inorganic nitrogen nutrients by tobacco plant. Transport and reduction of $NO_3-N$ in plant tissue were the important metabolism for supplying synthetic N compounds to developing tissues during growth period. Under field and environment-controlled condition tobacco plants were grown and seperated to leaf tissues at stalk positions for investigation of nitrogen transport and assimilation ability during period of rapid vegative growth. The results of studies were summarized as follows: 1. $NO_3-N$ absorbed from roots was transported as inorganic nitrogen through the vascular tissue of leaf veins as resulting from the high $NO_3-N$ ratio of the nitrogen content in leaf veins, but these ratios in mesophyll tissue of the same leaf laminae decreased remarkably in disregard of higher accumulation of nitrogen being compared to midvien. 2. Mesophyll tissue of mature leaves appeared higher value of nitrate reductase activity (NRA) comparing with other tissues, stem, leaf vien, and meristmatic tissue at emergence point with young leaves. 3. Matured leaves at lower position being reducing nitrate nitrogen vigorously observed thick laminae and kept high amount of water in them. 4. Mature leaves of young plant reduced $NO_3-N$ vigorously for supply synthetic N compounds to meristmatic tissues at growing point by the reason of narrow and few leaves at young stage, but in advancing growth period NRA of mature leaves along upper position reached to lower value. This appearence attributed to distribution of organic-N compound demanding for growth to increasing numbers of wide leaves.
For the elucidation of saponin synthesis during ontogeny changes of ginsenosides and free sugars in seeds during stratification and seedlings in early growth stage were investigated with high performance liquid chrom-atography. Embryo plus endosperm at 40-day stratification showed 80% decrease of total saponin, disappear-ance of Rc, Rb$_2$ and Rb$_1$ and appearance of Rg$_3$ (probable) and 20-Glc-Rf (probable). Leaf ginsenoside F$_3$ was found not in fruit plup but seed and decreased during stratification. Both decomposition and synthesis of saponin seemed to occure during stratification. Ginsenosides in endosperm and embryo might be originated from fruit pulp by penetration. In seedling saponin appeared first in shoot and in root about one month later. Ginsenoside Rc, Rb$_2$, Rb$_1$ appeared in root at the last investigation (June 30) indicating normal saponin synthetic capacity of root. Saponin synthetic rate was twice in leaf than in root. Leaf ginsenoside F$_3$ was found in seedling root. Root saponin Rg$_3$ and 20-Glc-Rf were found in leaf and stem in seedling and decreased with growth suggesting that rate saponin is not such in certain growth stage. Total saponin content was negatively correlated with PT/PD in seeds and arial parts of seedling due to greater change of PD. than PT. Seed at 70days stratification showed high sucrose content. In seedling glucose was main sugar in stem all the while and sucrose in root at early stage while glucose, fructose and sucrose were found in leaf.
Panax ginseng C. A. MEYER is one of the most widely used herbal medicines in the Asian countries and has diverse functions including anti-diabetic action. The dysfunctions of mesangial cells in hyperglycemic conditions are implicated in the development of diabetic nephropathy. Insulin-like growth factors (IGFs) are also associated with the onset of diabetic nephropathy. Thus, we examined the effect of ginsenosides against high glucose-induced dysfunction of primary cultured rat mesangial cells. In the present study, high glucose increased IGF-I and IGF-II secretion in mesangial cells. Ginsenoside total saponin (GTS) prevented high glucose-induced increase of IGF-I and IGF-II secretion in mesangial cells. In addition, GTS prevented high glucose-induced increase of lipid peroxide formation and decrease of GSH contents. GTS also ameliorates high glucose-induced increase of arachidonic acid release and decrease of prostaglandin $E_2$. In conclusion, GTS prevented high glucose-induced dysfunction of mesangial cells via inhibition of oxidative stress and arachidonic acid pathways.
Ginsenoside Rg4 is a rare ginsenoside that is naturally found in ginseng, and exhibits a wide range of biological activities including antioxidant and anti-inflammatory properties in several cell types. The purpose of this study was to use an in vivo model of hair follicle (HF)-mimic based on a human dermal papilla (DP) spheroid system prepared by three-dimensional (3D) culture and to investigate the effect of Rg4 on the hair-inductive properties of DP cells. Treatment of the DP spheroids with Rg4 (20 to 50 ㎍/ml) significantly increased the viability and size of the DP spheres in a dose-dependent manner. Rg4 also increased the mRNA and protein expression of DP signature genes that are related to hair growth including ALP, BMP2, and VCAN in the DP spheres. Analysis of the signaling molecules and luciferase reporter assays further revealed that Rg4 induces the activation of phosphoinositide 3-kinase (PI3K)/AKT and the inhibitory phosphorylation of GSK3β, which activates the WNT/β-catenin signaling pathway. These results correlated with not only the increased nuclear translocation of β-catenin following the treatment of the DP spheres with Rg4 but also the significant elevation of mRNA expression of the downstream target genes of the WNT/β-catenin pathway including WNT5A, β-catenin, and LEF1. In conclusion, these results demonstrated that ginsenoside Rg4 promotes the hair-inductive properties of DP cells by activating the AKT/GSK3β/β-catenin signaling pathway in DP spheres, suggesting that Rg4 could be a potential natural therapy for hair growth.
Kim, Mi-Ki;Jung, Ji-Ho;Ahn, Jae-Sun;Yim, Jung-Hoon;An, Min-Seop;Park, Jin-Su;Lee, Hai-Ja;Park, Eun-Jung
The Journal of Pediatrics of Korean Medicine
/
v.23
no.3
/
pp.143-153
/
2009
Objectives The purpose of this study is to get the basic information from patients how much they understood about their medication and also to know whether patients are making reasonable drug choice between Health Functional Foods and Herbal medicine. Methods 500 questionnaires were handed out to the parents of students in two elementary schools located in OO, Junlabukdo province. 421 questionnaires were completed to be evaluated. Results Among 421 subjects, 53.0% were female, and 47.0% were male. The percentages of the subjects consuming Health Functional Foods and herbal medicine were67.7% and 67.8%, respectively. Among those people who consumed Health Functional Food, 44.1% were using nutritional supplements, red ginseng or ginseng products (26.9%), chlorella products (11.5%), and plum extract products (7.7%). As for the reason to consume Health Functional Foods were varied, but 'in order to be healthy, although currently displaying no illness.'(43.0%) were the most responses among the given choices. On the other hand, the reason for consuming herbal medicine was 'In order to grow taller'(26.1%), 'In order to cure weak physical state frequently displaying common illnesses',(25.9%), and 'In order to cure diseases.'(23.3%). For the questions about effectiveness after consumption,the 69.9% subjects said that it seemed to be effected, and that % was slightly higher than that of subjects with consuming Health Functional Foods(64.4%). For question concerning preferences between Health Functional Foods and herbal medicine, 57.5% chose herbal medicine, and this percentage was higher than that of Health Functional Foods(42.5%).As for the reasons of additional consumption of the Health Functional Foods, subject answered as 'Easy to consume.'(41,6%), which was the most common among the subjects consuming Health Functional Foods. On other hand, the subjects of herbal medicine answered as that herbal medicine is 'more effective'(45.7%), and 'more trustworthy in preventing side-effects.'(40.3%). After consumption of the herbal medication, only 3.9% of the subjects consuming either Health Functional Foods or herbal medicine had side-effects. The most common side-effects were 'dermal reaction' which is normally caused by Health Functional Foods and 'indigestion' problems caused by herbal consumption. Conclusions According to the 421 subjects those involved in study, the percentages of consuming Health Functional Foods(67.7%) and herbal medicine(67.8%) were similar. The most commonly consumed products were a type of Health Functional Foods which were the nutrition-supplying products. Ginseng or red ginseng products were the next commonly used products. Health Functional Foods were commonly consumed for preventing illness and maintaining health rather than any other purpose. In contrary, herbal medicines were more commonly consumed for purposes such as for growth or treating certain type of disease. As a result of consumption, more than half of both subject replied as 'satisfied'. As for the side effects, dermal reaction was the most common problem for those with consuming Health Functional Foods, while indigestion was the most common side effect from the subjects with consuming herbal medicine.
This experiment was conducted to study the effect of $CO_2$(0, 2, 500, 5, 000, 10, 000ppm) enrichment by enabling ventilation on micropropagation of multi-shoot and on the saponin contents in vitro in Korean ginseng (Panax ginseng C. A. Meyer). Embryo was cultured in Murashige and Skoog medium added 3mg/ l of Indolbutyric acid, Benzyladenin and Gibberellic acid $(GA_3)$, respectively. $CO_2$, enrichment had little effects on the number of adventitious buds and shoots originated from adventitious buds. The ratio of differentiated shoots to adventitious buds were about 50% in $CO_2$, enrichment treatment. The shoots originated from adventitious bud showed more rapid growth and had larger leaf area than the shoots originated from the leaf primordia did. The number of shoot primordia was the highest in 2, 500ppm of $CO_2$ enrichment treatment. On the contrary, 10,000ppm of $CO_2$, enrichment made smaller the number of shoot primordia and ratio of shoots to shoot primordia. The range of shoots differentiated was from shoot primordia were 15. 4 to 23. 9. The rate of dry weight of cultured shoots showed lowest (7. 5%) in control and highest (8. 59%) in 2, 500ppm of $CO_2$, enrichment. Rate of in vitro flower in control was 7.6% and that in 2500ppm of $CO_2$ was about twice (15.7-16.3%) as much as in control. Flower number per a embryo cultured was about 1.2-1.3. In the multi-shoots with callus enriched by 2, 500ppm of $CO_2$, the contents of crude saponin and ginsenosides in multi-shoots alone were higher than in multi-shoots with callus. The characteristics of ginsenosides in multi-shoots were especially the higher content of ginsenoside Rd, Re, and $Rg_1$.
Changes of light intensity under and above shading materials were measured at different relative light intensity(R.L.I. 5% of common straw shading, 15% of polyester shading and 20% of polyester shading at 12 o'clock on clear day) and lines(lst, 3rd and 5th lines) on clear and cloudy days in 5-year -old ginseng plant populations. Rates of photosynthesis and respiration, microclimate and root yield were also measured in field. Air temperature of R.L.I. 5% were lower 2$^{\circ}C$ compared with R.L.I. 15% and lower 3$^{\circ}C$ compared with R. L. I. 20% from 12 to 14 o'clock on clear day, but there were not difference among R. L. I. on cloudy day. Relative humidity of R. L. I. 5% were higher 5% compared compared with R.L.I. 20% from 10 to 14 o'clock on clear day, R. L. I. on cloudy day. Light intensity were below 5,000 lux at R.L.I. 5%, about 15,000 lux at R.L.I. 15% and about 20,000 lux at R.L.I. 20% from 10 to 15 o'clock on clear day. But light intensity were below 3, 000 lux at R. L. I. 5% about 10, 000 lux at R. L. I. 15% and about 15, 000 lux at R. L. I. 20% from 10 to 15 o'clock on cloudy. Photosynthetic rate of R.L.I. 15% and R.L.I. 20% were higher compared with R.L.I. 5% on clear and cloudy days. Tatal photosynthesis in a day were increased by R.L.I. 5%, 20%, 15% in turn on clear and cloudy days. R. L. I. 15% and 20% were not notable difference of photosynthetic rates among lines but R. L. I. with R. L. I. 15%, and higher 8% but there were not different among 5% was notable difference of one. Root fresh weight were increased by R.L.I. 5%, 20% and 15% in turn and R.L.I. 15% and 20% were not notable difference of root yield among lines but R. L. I. 5% was notable difference of one.
The present study was performed to find the effects of ginseng and its saponins. which is written in Chung Yao Ta Tsu Tien as anti-amnesia in its chief indication. on experimental amnesia in mice. In the step through test. ginsenoside $Rb_1\;(GRb_1)\;and\;GRg_1$ facilitated the registration of memory and antagonized the electroconvulsive shock (ECS)-induced inhibition of the retention of memory. Moreover. $GRg_1$ antagonized the EtOH-induced inhibition of the retrieval of memory. In the step down test. $GRb_1\;GRb_2\;and\;GRg_1$ antagonized the ECS-induced inhibition of the retention of memory. Moreover. $GRg_1$ antagonized the EtOH-induced inhibition of the retrieval of memory and facilitated the acquisition of short term memory. In the shuttle hox and lever press tests. they have no effects on acquisition and retrieval of memory. except $GRb_1\;GRb_1$ depressed the retrieval of conditioned avoidance response in the shuttle box test. After the end of four tests. the effects of these orally administered drugs on sedative. analgesic. antipyretic and anticonvulsant actions. and on spontaneous and exploratory movements were tested in doses of less than 500mg/kg. but they had none of these effects. Present study may indicate that $GRg_1$ had effects on the retrieval of memory and on the acquisition process of learning response. The recent research on the role of NGF for the survival. regeneration and regulation of brain in adult animals. indicated the importance of NGF on dementia and amnesia. During our research on the specificity of the neurite out growth induced by NGF. we found that the effect of NGF was potentiated by $GRb_1$ in organ cultures of chick embryonic dorsal root ganglia. Then. the effect of $GRb_1$ on neuronal cell survivalin cell culture system was studied. $GRb_1$ potentiated the NGF-mediated increase of neurofilaments in cell cultures of chick embryonic sensory and sympathetic neurons. NGF with $GRb_1$ also showed a tendency to increase the number of surviving neurons of rat embryonic cerebral cortex. NGF increased choline acetyl transferase activity in cell cultures of rat embryonic septum area neurons. but $GRb_1$ did not potentiate NGF activity in cell cultures of rat embryonic septum area neurons. Present study may indicate that $GRb_1$ plays an important role for the survival or regeneration of neurons in the brain.
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