title: Ginsenoside Rb1 Attenuates Acute Inflammatory Nociception by Inhibition of Neuronal ERK Phosphorylation by Regulation of the Nrf2 and NF-κB Pathways.
abstract: Ginsenoside-Rb1 (Rb1) has anti-inflammatory effects. However, the potential antinociceptive value of Rb1 for the treatment of acute inflammatory nociception is still unknown. In this study, we examined whether Rb1 has any antinociceptive effects on acute inflammatory nociception in Sprague Dawley rats given intrathecal (i.t.) introduction of Rb1 (2, 10, and 50 μg) 20 minutes before injection of formalin (5%, 50 μL) into the plantar surface of the hind paws. I.t. introduction of Rb1 significantly decreased nociceptive behavior during phase II (16-60 minutes), but not phase I (0-10 minutes), after formalin stimulation, corresponding to the reduced activation of c-Fos in the L4 to L5 spinal dorsal horn after formalin stimulation. Rb1 also reduced the phosphorylation of extracellular signal-regulated kinase in the neurons, but not the microglia and astrocytes. Microscopic examination of the microglia and astrocytes revealed no morphological changes due to formalin stimulation and i.t. introduction of Rb1. Interestingly, Rb1 activated the nuclear factor erythroid 2-related factor 2 pathway and inhibited nuclear factor kappa B pathways.
  
  
  CONCLUSIONS
  Our findings indicate that i.t. introduction of Rb1 might effectively inhibit formalin-induced acute inflammatory nociception by inhibition of neuronal extracellular signal-regulated kinase phosphorylation, which is thought to regulate the nuclear factor erythroid 2-related factor 2 nuclear factor kappa B pathways in the spinal dorsal horn, which suggests therapeutic potential for suppression of acute inflammatory pain.
authors.affiliation: Department of Convergence Medical Science, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea; Department of Cancer Preventive Material Development, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Minhee
authors.initials: M
authors.lastname: Jang
authors.affiliation: Department of Convergence Medical Science, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea; Brain Korea 21 Plus Program, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Convergence Medical Science, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea; Brain Korea 21 Plus Program, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Jong Hee
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Convergence Medical Science, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea; Brain Korea 21 Plus Program, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Eun-Jeong
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea.
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
authors.affiliation: Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea.
authors.forename: Hak-Jae
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Integrative Plant Science, Chung-Ang University, Anseong, Republic of Korea.
authors.forename: Sanghyun
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Medicinal Crop Research Institute, National Institute of Horticultural & Herbal Science, Rural Development Administration, Eumseong, Republic of Korea.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Medicinal Crop Research Institute, National Institute of Horticultural & Herbal Science, Rural Development Administration, Eumseong, Republic of Korea.
authors.forename: Young Ock
authors.initials: YO
authors.lastname: Kim
authors.affiliation: Department of Convergence Medical Science, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea; Brain Korea 21 Plus Program, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea; Institute of Oriental Medicine, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea. Electronic address: ihcho@khu.ac.kr.
authors.forename: Ik-Hyun
authors.initials: IH
authors.lastname: Cho
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005557:Formaldehyde; D036145:Ginsenosides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D059225:Nociception / Q000187:drug effects / Q000502:physiology; D059226:Nociceptive Pain / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D000700:Analgesics; D036145:Ginsenosides; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495637:Nfe2l2 protein, rat; D016760:Proto-Oncogene Proteins c-fos; D005557:Formaldehyde; C442759:ginsenoside Rb1; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Ginsenoside-Rb1; inflammatory nociception; intrathecal introduction; nuclear factor erythroid 2-related factor 2; nuclear factor-kappa B; phospho-ERK