• Journal of Ginseng Research
• /
• v.23 no.4
• /
• pp.235-238
• /
• 1999

ATP-sensitive $K^+$ channels $(K_{ATP})$ are expressed in vascular smooth muscle cells, skeletal muscle cells, pancreatic ${\beta}$ cells, neurons and epithelial cells. $K_{ATP}$ contributes to regulate membrane potential to control vascular tone, to protect myocardial ischemia, and to regulate insulin secretion in pancreatic ${\beta}$ cells. We previously demonstrated that ginseng saponins and ginsenoside $Rg_3$ activated maxi $Ca^{2+}-activated\;K^+$ channel, and this might cause vasodilation. Because $K_{ATP}$ plays an important roles to regulate the resting membrane potential in vascular smooth muscle cells, we investigated whether ginsenoside $Rg_3$ produces vasodilation by activating $K_{ATP}$ We showed in this study that $K_{ATP}$ is expressed in rabbit coronary artery smooth muscle cells. $K_{ATP}$ was inwardly rectifying and was inhibited by intemal application of ATP. Micromolar minoxidil activated, but glyburide inhibited the activity of $K_{ATP}$ Ginsenoside $Rg_3$ relieved inactivaiton of whole-cell $K_{ATP}$ current without affecting the peak amplitude of $K_{ATP}$ currents presumably due to more opening of the channels.

• Journal of Ginseng Research
• /
• v.29 no.4
• /
• pp.192-205
• /
• 2005

This study is for geochemical relationships between ginsengs and soils from three representative soil types from Keumsan, shale, phyllite and granite areas. For this study, ginsengs (2, 3 and 4 years), with the soils and their host rock, are collected and are analysed for the transitional elements. In the weathered soils, the shale area is high in the most of elements, but low in the granite area. High correlation relationships are shown in the shale area. In the field soils, the shale area is mainly high, but low in the granite area. Comparing with ages, most of elements are high in the 2 year soils, but low in the 4 year soils. Regardless of the localities, positive and negative correlations are dominant in the shale area. In the host rocks, high element contents are shown in the phyllite and shale areas. Positive and negative correlations are found in the shale and phyllite areas for large numbers of the element pairs. In the ginsengs, differences of the element contents with ages are not clear, but show high element contents in the 2 year ginsengs of the shale and phyllite areas, and low contents in the 4 year ginsengs of the granite area. Positive correlations are shown in the Cu-Zn pair in the shale and phyllite areas, and Co-Cu pair in the granite area. In the relative ratios(weathered soil/field soil), most of elements from the shale area are high, above I, suggesting high element contents in the weathered soils of the shale area relative to the granite and phyllite areas. In the relative ratios(weathered soil/host rock), most of elements are above 1, suggesting the high element contents in the weathered soils relative to the host rocks. Relative ratios (soil/ginseng) of the element contents are several to ten times. Regardless of the areas, big differences of the relative ratios are found in the Co and small differences are in the Cu and Zn, which suggest that differences between soils and ginsengs are big in the Co contents and small in the Cu and Zn contents. Regardless of the ages, differences among relative ratios are small in granite area relative to the shale area, which suggest more similar contents between ginsengs and soils in the granite areas.

• Journal of Ginseng Research
• /
• v.32 no.2
• /
• pp.107-113
• /
• 2008

In this study, we have investigated the effect of panaxatriol (PT) on phosphoinositides (PIS) breakdown and $Ca^{2+}$-elevation in thrombin-induced platelet aggregation. Thrombin (5U/ml), a potent platelet agonist which activates phospholipase $C_{\beta}$ via protease activated receptor (PAR), hydrolyzed PIS in platelet membrane. The phosphatidylinositol 4, 5-bisphosphate $(PIP_2)$ was hydrolyzed after 10 sec of the thrombin-stimulation, and both the phosphatidylinositol 4-monophosphate (PIP) and phosphatidylinositol (PI) were brokendown after 30 sec of the thrombin-stimulation. However, PT inhibited the thrombin-stimulated hydrolysis of $PIP_2$, PIP, and PI. On the other hand, thrombin increased the level of phosphatidic acid (PA) which is phosphorylated from diacylglycerol (DG) generated by PIS-hydrolysis. However, Pr inhibited the thrombin-increased PA level non-significantly. Thrombin increased cytosolic free $Ca^{2+}([Ca^{2+}])_i$) up to 72% as compared with control $(30.8{\pm}0.9 nM)$ in intact platelet. However, PT (100 ${\mu}g/ml$) inhibited the thrombin-elevated $[Ca^{2+}]_i$ to 100%. These results suggest that PT may have a beneficial effect on platelet aggregation-mediated thrombotic disease by inhibiting thrombin-induced platelet aggregation via suppression of the $[Ca^{2+}]_i$ level and PIS breakdown.

• Korean Journal of Medicinal Crop Science
• /
• v.18 no.5
• /
• pp.323-328
• /
• 2010

Root extract of Lythrum salicaria reported a hepato-protective effect on $CCl_4$-induced liver toxicity of rat was prepared into fractions such as n-hexane up layer (HA), n-hexane down layer (HB), diethyl ether (E), ethylacetate (EA), n-butanol (B) and water (W). Fractions prepared were tested their activities in vitro and in vivo condition. All of the fractions showed effective antioxidant asctivities on DPPH radical and $CuSO_4$-induced oxidation of human low density lipoprotein and E fraction showed the highest inhibitory effect (98.1% at $50\;{\mu}g/m{\ell}$) on linoleic acid autoxidation at $40^{\circ}C$, which was more effective than $\alpha$-tocopherol (82.4%). Five fractions (H = HA plus HB, E, EA, B, and W, 150 mg/kg/day) were fed into Sprague Dawley, male rats for 4 days, which were intoxicated with intra-peritoneal injection of carbon tetrachloride ($1\;m{\ell}/kg$ in corn oil) at the 4th day and were sacrificed in 24 hrs. Serum tumor necrosis factor-alpha (TNF-$\alpha$), a proinflammatory cytokine, elevated with $CCl_4$-intoxication in negative control group ($83\;pg/m{\ell}$) was significantly decreased in E fraction-supplemented group ($18\;pg/m{\ell}$). Cu, Zn-superoxide dismutase (SOD) activity increased in negative control group (0.12 U/mg protein) was decreased in E fraction (0.07 U/mg protein). From the results, it is suggested that ether fraction from root extract of L. salicaria would be a potent antioxidant candidate for ameliorating liver injury induced by chemical intoxicant.

• Journal of Ginseng Research
• /
• v.45 no.3
• /
• pp.401-407
• /
• 2021

Background: Gintonin is an exogenous ginseng-derived G-protein-coupled lysophosphatidic acid (LPA) receptor ligand. LPA induces in vitro morphological changes and migration through neuronal LPA1 receptor. Recently, we reported that systemic administration of gintonin increases blood-brain barrier (BBB) permeability via the paracellular pathway and its binding to brain neurons. However, little is known about the influences of gintonin on in vivo neuron morphology and migration in the brain. Materials and methods: We examined the effects of gintonin on in vitro migration and morphology using primary hippocampal neural precursor cells (hNPC) and in vivo effects of gintonin on adult brain neurons using real time microscopic analysis and immunohistochemical analysis to observe the morphological and locational changes induced by gintonin treatment. Results: We found that treating hNPCs with gintonin induced morphological changes with a cell rounding following cell aggregation and return to individual neurons with time relapses. However, the in vitro effects of gintonin on hNPCs were blocked by the LPA1/3 receptor antagonist, Ki16425, and Rho kinase inhibitor, Y27632. We also examined the in vivo effects of gintonin on the morphological changes and migration of neurons in adult mouse brains using anti-NeuN and -neurofilament H antibodies. We found that acute intravenous administration of gintonin induced morphological and migrational changes in brain neurons. Gintonin induced some migrations of neurons with shortened neurofilament H in the cortex. The in vivo effects of gintonin were also blocked by Ki16425. Conclusion: The present report raises the possibility that gintonin could enter the brain and exert its influences on the migration and morphology of adult mouse brain neurons and possibly explains the therapeutic effects of neurological diseases behind the gintonin administration.

• Journal of Ginseng Research
• /
• v.46 no.6
• /
• pp.738-749
• /
• 2022

Background: Ginseng possesses antitumor effects, and ginsenosides are considered to be one of its main active chemical components. Ginsenosides can further be hydrolyzed to generate secondary saponins, and 20(R)-panaxotriol is an important sapogenin of ginsenosides. We aimed to synthesize a new ginsengenin derivative from 20(R)-panaxotriol and investigate its antitumor activity in vivo and in vitro. Methods: Here, 20(R)-panaxotriol was selected as a precursor and was modified into its derivatives. The new products were characterized by ¹H-NMR, ¹³C-NMR and HR-MS and evaluated by molecular docking, MTT, luciferase reporter assay, western blotting, immunofluorescent staining, colony formation assay, EdU labeling and immunofluorescence, apoptosis assay, cells migration assay, transwell assay and in vivo antitumor activity assay. Results: The derivative with the best antitumor activity was identified as 6,12-dihydroxy-4,4,8,10,14-pentamethyl-17-(2,6,6-trimethyltetrahydro-2H-pyran-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl(tert-butoxycarbonyl)glycinate (A11). The focus of this research was on the antitumor activity of the derivatives. The efficacy of the derivative A11 (IC₅₀ < 0.3 µM) was more than 100 times higher than that of 20(R)- panaxotriol (IC₅₀ > 30 µM). In addition, A11 inhibited the protein expression and nuclear accumulation of the hypoxia-inducible factor HIF-1α in HeLa cells under hypoxic conditions in a dose-dependent manner. Moreover, A11 dose-dependently inhibited the proliferation, migration, and invasion of HeLa cells, while promoting their apoptosis. Notably, the inhibition by A11 was more significant than that by 20(R)-panaxotriol (p < 0.01) in vivo. Conclusion: To our knowledge, this is the first study to report the production of derivative A11 from 20(R)-panaxotriol and its superior antitumor activity compared to its precursor. Moreover, derivative A11 can be used to further study and develop novel antitumor drugs.

• Journal of Ginseng Research
• /
• v.45 no.6
• /
• pp.665-675
• /
• 2021

Background: Ginsenoside Rg1 (Rg1), an active ingredient in ginseng, may be a potential agent for the treatment of Alzheimer's disease (AD). However, the protective effect of Rg1 on neurodegeneration in AD and its mechanism of action are still incompletely understood. Methods: Wild type (WT) and APP/PS1 AD mice, from 6 to 9 months old, were used in the experiment. The open field test (OFT) and Morris water maze (MWM) were used to detect behavioral changes. Neuronal damage was assessed by hematoxylin and eosin (H&E) and Nissl staining. Immunofluorescence, western blotting, and quantitative real-time polymerase chain reaction (q-PCR) were used to examine postsynaptic density 95 (PSD95) expression, amyloid beta (Aβ) deposition, Tau and phosphorylated Tau (p-Tau) expression, reactive oxygen species (ROS) production, and NAPDH oxidase 2 (NOX2) expression. Results: Rg1 treatment for 12 weeks significantly ameliorated cognitive impairments and neuronal damage and decreased the p-Tau level, amyloid precursor protein (APP) expression, and Aβ generation in APP/PS1 mice. Meanwhile, Rg1 treatment significantly decreased the ROS level and NOX2 expression in the hippocampus and cortex of APP/PS1 mice. Conclusions: Rg1 alleviates cognitive impairments, neuronal damage, and reduce Aβ deposition by inhibiting NOX2 activation in APP/PS1 mice.

• Journal of Ginseng Research
• /
• v.47 no.1
• /
• pp.44-53
• /
• 2023

Background: The genus Panax in the Araliaceae family has been used as traditional medicinal plants worldwide and is known to biosynthesize ginsenosides and phytosterols. However, genetic variation between Panax species has influenced their biosynthetic pathways is not fully understood. Methods: Simultaneous analysis of transcriptomes and metabolomes obtained from adventitious roots of two tetraploid species (Panax ginseng and P. quinquefolius) and two diploid species (P. notoginseng and P. vietnamensis) revealed the diversity of their metabolites and related gene expression profiles. Results: The transcriptome analysis showed that 2,3-OXIDOSQUALENE CYCLASEs (OSCs) involved in phytosterol biosynthesis are upregulated in the diploid species, while the expression of OSCs contributing to ginsenoside biosynthesis is higher in the tetraploid species. In agreement with these results, the contents of dammarenediol-type ginsenosides were higher in the tetraploid species relative to the diploid species. Conclusion: These results suggest that a whole-genome duplication event has influenced the triterpene biosynthesis pathway in tetraploid Panax species during their evolution or ecological adaptation. This study provides a basis for further efforts to explore the genetic variation of the Panax genus.

• Korean Journal of Medicinal Crop Science
• /
• v.11 no.2
• /
• pp.102-108
• /
• 2003

This experiment was conducted to evaluate the diversity and purity of the Korean ginseng (Panax gjnseng) lines developed by the pure line selection using RAPD markers. Four primer (OPA 19, OPM 11, URP 3 and UBC 98) out of the 48 primer tested produced band which showed within-line polymorphisms at least in one line. Within-line polymorphisms were detected in six lines by OPA 19, in four lines by URP 03, in five lines by OPM 11, and in one line by UBC 98 respectively. Five plants obtained from the commercial cultivar 'Cheonpung' were differentiated using the primers OPA 19 and OPM 11. Five plants obtained from the 'Yeonpung were differentiated using the primer OPM 11. Detection of within-line RAPD polymorphisms might be attributed to the fact that cross pollination appear in P. gjnseng and a long period of three to four years required to reach the reproductive stage thereby delay the process to homozygosity.

• Journal of Ginseng Research
• /
• v.47 no.2
• /
• pp.199-209
• /
• 2023

Background: Due to the interrupted blood supply in cerebral ischemic stroke (CIS), ischemic and hypoxia results in neuronal depolarization, insufficient NAD+, excessive levels of ROS, mitochondrial damages, and energy metabolism disorders, which triggers the ischemic cascades. Currently, improvement of mitochondrial functions and energy metabolism is as a vital therapeutic target and clinical strategy. Hence, it is greatly crucial to look for neuroprotective natural agents with mitochondria protection actions and explore the mediated targets for treating CIS. In the previous study, notoginseng leaf triterpenes (PNGL) from Panax notoginseng stems and leaves was demonstrated to have neuroprotective effects against cerebral ischemia/reperfusion injury. However, the potential mechanisms have been not completely elaborate. Methods: The model of middle cerebral artery occlusion and reperfusion (MCAO/R) was adopted to verify the neuroprotective effects and potential pharmacology mechanisms of PNGL in vivo. Antioxidant markers were evaluated by kit detection. Mitochondrial function was evaluated by ATP content measurement, ATPase, NAD and NADH kits. And the transmission electron microscopy (TEM) and pathological staining (H&E and Nissl) were used to detect cerebral morphological changes and mitochondrial structural damages. Western blotting, ELISA and immunofluorescence assay were utilized to explore the mitochondrial protection effects and its related mechanisms in vivo. Results: In vivo, treatment with PNGL markedly reduced excessive oxidative stress, inhibited mitochondrial injury, alleviated energy metabolism dysfunction, decreased neuronal loss and apoptosis, and thus notedly raised neuronal survival under ischemia and hypoxia. Meanwhile, PNGL significantly increased the expression of nicotinamide phosphoribosyltransferase (NAMPT) in the ischemic regions, and regulated its related downstream SIRT1/2/3-MnSOD/PGC-1α pathways. Conclusion: The study finds that the mitochondrial protective effects of PNGL are associated with the NAMPT-SIRT1/2/3-MnSOD/PGC-1α signal pathways. PNGL, as a novel candidate drug, has great application prospects for preventing and treating ischemic stroke.