title: Ginsenoside Re Attenuates Neuroinflammation in a Symptomatic ALS Animal Model.
abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of upper and lower motor neurons, which cause paralysis and respiratory dysfunction. There is currently no permanently effective drug for patients with ALS. Ginsenoside Re (G-Re), one of the most active ingredients of ginseng, has pharmacological activities that affect a number of targets. To investigate the effects of G-Re on neuroinflammation, we used G-Re (2.5[Formula: see text][Formula: see text]g/g) at the Joksamni acupressure point (ST36) once every other day for one week. To evaluate G-Re function in symptomatic human-superoxide dismutase 1 (hSOD1[Formula: see text] transgenic mice, immunohistochemistry and Western blot analysis were performed with the spinal cord of symptomatic hSOD1(G93A) transgenic mice. Here, we report that G-Re exhibits potent neuroprotective effects against neuroinflammation in a murine model of ALS. G-Re treatment reduced the loss of motor neurons and active-microglia-related expression of Iba-1 in the spinal cord of symptomatic hSOD1(G93A) transgenic mice. In addition, compared with age-matched hSOD1(G93A) mice, G-Re-treated hSOD1(G93A) mice showed a significant reduction in expression of pro-inflammatory proteins such as CD14 and TNF-[Formula: see text] protein related to TLR4 signaling pathway. G-Re administration also led to a decrease in cell death-related phospho-p38 protein levels, and had an antioxidative effect by reducing HO1 expression. Together, our data suggest that G-Re could have potent anti-neuroinflammatory effects on ALS by inhibiting the TLR4 pathway.
authors.affiliation: 1 Department of Clinical Research, Korea Institute of Oriental Medicine, 483 Expo-ro Daejeon, Yuseong-gu 305-811, Republic of Korea.
authors.forename: Mudan
authors.initials: M
authors.lastname: Cai
authors.affiliation: 1 Department of Clinical Research, Korea Institute of Oriental Medicine, 483 Expo-ro Daejeon, Yuseong-gu 305-811, Republic of Korea.
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Yang
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D036145:Ginsenosides / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D009046:Motor Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use*; D005894:Panax / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D036145:Ginsenosides; D018836:Inflammation Mediators; D018950:Lipopolysaccharide Receptors; D008840:Microfilament Proteins; D018696:Neuroprotective Agents; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C049864:ginsenoside Re
keywords: Amyotrophic Lateral Sclerosis; Ginsenoside Re; Neuroinflammation; Toll-like Receptor 4 (TLR4)