scholarly journals Red Ginseng Inhibits Tau Aggregation and Promotes Tau Dissociation In Vitro

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Soo Jung Shin ◽  
Yong Ho Park ◽  
Seong Gak Jeon ◽  
Sujin Kim ◽  
Yunkwon Nam ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Paired Helical Filaments ◽  
Red Ginseng ◽  
Tau Pathology ◽  
Korean Red Ginseng ◽  
Ginseng Extract ◽  
Microtubule Binding Domain ◽  
Mature Neurons ◽  
Tau Aggregation

Tau, a microtubule-associated protein expressed in mature neurons, interacts with tubulin to promote the assembly and stabilization of microtubules. However, abnormally hyperphosphorylated tau dissociates from microtubules and self-aggregates. Tau aggregates, including paired helical filaments and neurofibrillary tangles, promote neuronal dysfunction and death and are the defining neuropathological feature of tauopathies. Therefore, suppressing tau aggregation or stimulating the dissociation of tau aggregates has been proposed as an effective strategy for treating neurodegenerative diseases associated with tau pathology such as Alzheimer’s disease (AD) and frontotemporal dementia. Interestingly, ginsenosides extracted from Panax ginseng reduced the hippocampal and cortical expression of phosphorylated tau in a rat model of AD. However, no studies have been conducted into the effect of red ginseng (RG) and its components on tau pathology. Here, we evaluated the effect of Korean red ginseng extract (KRGE) and its components on the aggregation and disassociation of tau. Using the thioflavin T assay, we monitored the change in fluorescence produced by the aggregation or disassociation of tau K18, an aggregation-prone fragment of tau441 containing the microtubule-binding domain. Our analysis revealed that KRGE not only inhibited tau aggregation but also promoted the dissociation of tau aggregates. In addition, the KRGE fractions, such as saponin, nonsaponin, and nonsaponin fraction with rich polysaccharide, also inhibited tau aggregation and promoted the dissociation of tau aggregates. Our observations suggest that RG could be a potential therapeutic agent for the treatment of neurodegenerative diseases associated with tauopathy.

scholarly journals Alleviation of Ulcerative Colitis Potentially through th1/th2 Cytokine Balance by a Mixture of Rg3-enriched Korean Red Ginseng Extract and Persicaria tinctoria

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5230
Author(s):  
Evelyn Saba ◽  
Yuan Yee Lee ◽  
Man Hee Rhee ◽  
Sung-Dae Kim
Keyword(s):  
Ulcerative Colitis ◽  
Mitogen Activated Protein Kinase ◽  
Raw 264.7 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Red Ginseng ◽  
Korean Red Ginseng ◽  
Ginseng Extract ◽  
Anti Inflammatory

Ginseng is a vastly used herbal supplement in Southeast Asian countries. Red ginseng extract enriched with Rg3 (Rg3-RGE) is a formula that has been extensively studied owing to its various biological properties. Persicaria tinctoria (PT), belonging to the Polygonaceae family, has also been reported for its anti-inflammatory properties. Ulcerative colitis (UC) is inflammation of the large intestine, particularly in the colon. This disease is increasingly common and has high probability of relapse. We investigated, separately and in combination, the effects of Rg3-RGE and PT using murine exemplary of UC induced by DSS (Dextran Sulfate Sodium). For in vitro and in vivo experiments, nitric oxide assay, qRT-Polymerase Chain Reaction (PCR), Western blot, ulcerative colitis introduced by DSS, Enzyme Linked Immunosorbent Assay (ELISA), and flow cytometry analysis were performed. The results obtained demonstrate that treatment with Rg3-RGE + PT showed synergism to suppress inflammation (in vitro) in RAW 264.7 cells via mitogen-activated protein kinase and nuclear factor κB pathways. Moreover, in C57BL/6 mice, this mixture exhibits strong anti-inflammatory effects in restoring colon length, histopathological damage, pro-inflammatory mediators, and cytokines amount, and decreasing levels of NLRP3 inflammasome (in vivo). Our results recommend that this mixture can be used for the prevention of UC as a prophylactic/therapeutic supplement.

scholarly journals Toxic Tau Oligomers Modulated by Novel Curcumin Derivatives

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Filippa Lo Cascio ◽  
Nicha Puangmalai ◽  
Anna Ellsworth ◽  
Fabio Bucchieri ◽  
Andrea Pace ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Therapeutic Strategy ◽  
Tau Pathology ◽  
Human Neuroblastoma ◽  
Aggregation State ◽  
Tau Oligomers ◽  
Curcumin Derivatives ◽  
Tau Aggregation ◽  
Insight Into

AbstractThe pathological aggregation and accumulation of tau, a microtubule-associated protein, is a common feature amongst more than 18 different neurodegenerative diseases that are collectively known as tauopathies. Recently, it has been demonstrated that the soluble and hydrophobic tau oligomers are highly toxic in vitro due to their capacity towards seeding tau misfolding, thereby propagating the tau pathology seen across different neurodegenerative diseases. Modulating the aggregation state of tau oligomers through the use of small molecules could be a useful therapeutic strategy to target their toxicity, regardless of other factors involved in their formation. In this study, we screened and tested a small library of newly synthesized curcumin derivatives against preformed recombinant tau oligomers. Our results show that the curcumin derivatives affect and modulate the tau oligomer aggregation pathways, converting to a more aggregated non-toxic state as assessed in the human neuroblastoma SH-SY5Y cell line and primary cortical neuron cultures. These results provide insight into tau aggregation and may become a basis for the discovery of new therapeutic agents, as well as advance the diagnostic field for the detection of toxic tau oligomers.

scholarly journals Oral (−)-Epicatechin Inhibits Progressive Tau Pathology in rTg4510 Mice Independent of Direct Actions at GSK3β

2021 ◽  
Vol 15 ◽  
Author(s):  
Katriona L. Hole ◽  
Lydia E. Staniaszek ◽  
Gayathri Menon Balan ◽  
Jody M. Mason ◽  
Jon T. Brown ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Amyloid Β ◽  
Paired Helical Filaments ◽  
Tau Pathology ◽  
Direct Inhibition ◽  
Plaque Pathology ◽  
A Cell ◽  
Tau Aggregation ◽  
Molecular Weight Form

Aggregation of the microtubule-associated protein tau into paired helical filaments (PHFs) and neurofibrillary tangles is a defining characteristic of Alzheimer’s Disease. Various plant polyphenols disrupt tau aggregation in vitro but display poor bioavailability and low potency, challenging their therapeutic translation. We previously reported that oral administration of the flavonoid (−)-epicatechin (EC) reduced Amyloid-β (Aβ) plaque pathology in APP/PS1 transgenic mice. Here, we investigated whether EC impacts on tau pathology, independent of actions on Aβ, using rTg4510 mice expressing P301L mutant tau. 4 and 6.5 months old rTg4510 mice received EC (∼18 mg/day) or vehicle (ethanol) via drinking water for 21 days and the levels of total and phosphorylated tau were assessed. At 4 months, tau appeared as two bands of ∼55 kDa, phosphorylated at Ser262 and Ser396 and was unaffected by exposure to EC. At 6.5 months an additional higher molecular weight form of tau was detected at ∼64 kDa which was phosphorylated at Ser262, Ser396 and additionally at the AT8 sites, indicative of the presence of PHFs. EC consumption reduced the levels of the ∼64 kDa tau species and inhibited phosphorylation at Ser262 and AT8 phosphoepitopes. Regulation of the key tau kinase glycogen synthase kinase 3β (GSK3β) by phosphorylation at Ser9 was not altered by exposure to EC in mice or primary neurons. Furthermore, EC did not significantly inhibit GSK3β activity at physiologically-relevant concentrations in a cell free assay. Therefore, a 21-day intervention with EC inhibits or reverses the development of tau pathology in rTg4510 mice independently of direct inhibition of GSK3β.

scholarly journals Improved Hygroscopicity and Bioavailability of Solid Dispersion of Red Ginseng Extract with Silicon Dioxide

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1022
Author(s):  
Sojeong Jin ◽  
Chul Haeng Lee ◽  
Dong Yu Lim ◽  
Jaehyeok Lee ◽  
Soo-Jin Park ◽  
...  
Keyword(s):  
Silicon Dioxide ◽  
Intestinal Permeability ◽  
Solid Dispersion ◽  
Ussing Chamber ◽  
Red Ginseng ◽  
Scanning Calorimetry ◽  
Korean Red Ginseng ◽  
Ginseng Extract ◽  
Powder Formulation ◽  
Significant Difference

This study aims to develop a powder formulation for the Korean red ginseng extract (RGE) and to evaluate its in vitro and in vivo formulation characteristics. The solid dispersion of RGE was prepared with hydrophilic carriers using a freeze-drying method. After conducting the water sorption–desorption isothermogram (relative humidity between 30 and 70% RH), differential scanning calorimetry thermal behavior, dissolution test, and intestinal permeation study, a solid dispersion formulation of RGE and silicon dioxide (RGE-SiO2) was selected. RGE-SiO2 formulation increased intestinal permeability of ginsenoside Rb1 (GRb1), GRb2, GRc, and GRd by 1.6-fold in rat jejunal segments as measured by the Ussing chamber system. A 1.6- to 1.8-fold increase in plasma exposure of GRb1, GRb2, GRc, and GRd in rats was observed following oral administration of RGE-SiO2 (375 mg/kg as RGE). No significant difference was observed in the time to reach maximum concentration (Tmax) and half-life in comparison to those in RGE administered rats (375 mg/kg). In conclusion, formulating solid dispersion of RGE with amorphous SiO2, the powder formulation of RGE was successfully formulated with improved hygroscopicity, increased intestinal permeability, and enhanced oral bioavailability and is therefore suitable for processing solid formulations of RGE product.

scholarly journals Characterization of hyperglycemia due to sub-chronic administration of red ginseng extract via comparative global proteomic analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ann-Yae Na ◽  
Jung Jae Jo ◽  
Oh Kwang Kwon ◽  
Piljoung Cho ◽  
Yan Gao ◽  
...  
Keyword(s):  
Proteomic Analysis ◽  
Herbal Remedy ◽  
Chronic Administration ◽  
Serum Glucose ◽  
Control Group ◽  
Red Ginseng ◽  
Korean Red Ginseng ◽  
Ginseng Extract ◽  
Glucose Levels ◽  
Term Administration

AbstractGinseng (Panax ginseng Meyer) is commonly used as an herbal remedy worldwide. Few studies have explored the possible physiological changes in the liver although patients often self-medicate with ginseng preparations, which may lead to exceeding the recommended dose for long-term administration. Here, we analyzed changes in the hepatic proteins of mouse livers using quantitative proteomics after sub-chronic administration of Korean red ginseng (KRG) extract (control group and 0.5, 1.0, and 2.0 g/kg KRG) using tandem mass tag (TMT) 6‐plex technology. The 1.0 and 2.0 g/kg KRG groups exhibited signs of liver injury, including increased levels of aspartate transaminase (AST) and alanine aminotransferase (ALT) in the serum. Furthermore, serum glucose levels were significantly higher following KRG administration compared with the control group. Based on the upregulated proteins found in the proteomic analysis, we found that increased cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE) levels promoted greater hydrogen sulfide (H2S) synthesis in the liver. This investigation provides novel evidence that sub-chronic administration of KRG can elevate H2S production by increasing protein expression of CBS and CSE in the liver.

scholarly journals Pectin lyase-modified red ginseng extract exhibits potent anti-glycation effects in vitro and in vivo

2017 ◽  
Vol 21 (2) ◽  
pp. 56-62 ◽  
Author(s):  
Chan-Sik Kim ◽  
Kyuhyung Jo ◽  
Mi-Kyung Pyo ◽  
Jin Sook Kim ◽  
Junghyun Kim
Keyword(s):  
Pectin Lyase ◽  
Red Ginseng ◽  
Ginseng Extract
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