Anti-inflammatory effect of jeongshintang through suppression of p38 activation in human astrocytoma, U373MG cells.

Jeongshintang (JST) is a Korean herbal prescription, which has been successfully used for cerebral diseases. However, the anti-inflammatory effect of JST on Alzheimer's disease (AD) is still not fully understood. In this study, we investigated the effects of JST in attenuating the inflammatory response induced by interleukin (IL)-1beta plus beta-amyloid [1-42] fragment (A beta) in the human astrocyte cell line, U373MG. The production of IL-6, IL-8, and prostaglandin (PG)E2 was significantly increased by IL-1beta plus A beta (1-42) in a time-dependent manner (P < 0.05). JST significantly inhibited the IL-1beta plus A beta (1-42)-induced IL-6, IL-8, and PGE2 production at 24 h (P < 0.05). Maximal inhibition rate of IL-6, IL-8, and PGE2 production by JST was about 54.40%, 56.01%, and 44.06% respectively. JST (0.01-1 mg/ml) also attenuated the expression of cyclooxygenase (COX)-2 and activation of p38 MAPK induced by IL-1beta and A beta (1-42). These results demonstrated that JST has an anti-inflammatory effect, which might explain its beneficial effect in the treatment of various neurodegenerative diseases such as AD.

[1]  M. Greenberg,et al.  β-Amyloid Induces Neuronal Apoptosis Via a Mechanism that Involves the c-Jun N-Terminal Kinase Pathway and the Induction of Fas Ligand , 2001, The Journal of Neuroscience.

[2]  M. Hirouchi [Current status and perspectives on the development of therapeutic agents for Alzheimer's disease]. , 2004, Nihon yakurigaku zasshi. Folia pharmacologica Japonica.

[3]  R. Strieter,et al.  Production and function of monocyte chemoattractant protein-1 and other β-chemokines in murine glial cells , 1995, Journal of Neuroimmunology.

[4]  Brian J Cummings,et al.  Early association of reactive astrocytes with senile plaques in Alzheimer's disease , 1995, Experimental Neurology.

[5]  G. Forloni,et al.  β-AMYLOID FRAGMENT POTENTIATES IL-6 AND TNF-α SECRETION BY LPS IN ASTROCYTES BUT NOT IN MICROGLIA , 1997 .

[6]  P. Worley,et al.  Cyclooxygenases and the central nervous system. , 1997, Prostaglandins.

[7]  U. Schreiter-Gasser,et al.  Interleukin‐6 and α‐2‐macroglobulin indicate an acute‐phase state in Alzheimer's disease cortices , 1991, FEBS letters.

[8]  Byung-Soo Koo,et al.  Inhibitory effects of the fragrance inhalation of essential oil from Acorus gramineus on central nervous system. , 2003, Biological & pharmaceutical bulletin.

[9]  T. Arendt,et al.  Neuronal COX-2 expression and phosphorylation of pRb precede p38 MAPK activation and neurofibrillary changes in AD temporal cortex , 2004, Neurobiology of Disease.

[10]  Mushfiquddin Khan,et al.  Inflammatory mediator and beta-amyloid (25-35)-induced ceramide generation and iNOS expression are inhibited by vitamin E. , 2004, Free radical biology & medicine.

[11]  Lina Zhang,et al.  Antitumor activities of heteropolysaccharides of Poria cocos mycelia from different strains and culture media. , 2003, Carbohydrate research.

[12]  L. V. Van Eldik,et al.  β-Amyloid Stimulation of Inducible Nitric-oxide Synthase in Astrocytes Is Interleukin-1β- and Tumor Necrosis Factor-α (TNFα)-dependent, and Involves a TNFα Receptor-associated Factor- and NFκB-inducing Kinase-dependent Signaling Mechanism* , 2000, The Journal of Biological Chemistry.

[13]  Cheorl-Ho Kim,et al.  Inhibition of tumor necrosis factor-alpha-induced apoptosis by Asparagus cochinchinensis in Hep G2 cells. , 2000, Journal of ethnopharmacology.

[14]  M. Hüll,et al.  Prostaglandin E2 Induces Interleukin‐6 Synthesis in Human Astrocytoma Cells , 1997, Journal of neurochemistry.

[15]  J. Bauer,et al.  Interleukin-6 is present in early stages of plaque formation and is restricted to the brains of Alzheimer's disease patients , 2004, Acta Neuropathologica.

[16]  K. Suzuki,et al.  Arachidonate metabolites affect the secretion of an N-terminal fragment of Alzheimer's disease amyloid precursor protein. , 1995, Biochemical and biophysical research communications.

[17]  R. Ransohoff,et al.  Astrocyte expression of mRNA encoding cytokines IP‐10 and JE/MCP‐1 in experimental autoimmune encephalomyelitis , 1993, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[18]  D. Butterfield Amyloid beta-peptide [1-42]-associated free radical-induced oxidative stress and neurodegeneration in Alzheimer's disease brain: mechanisms and consequences. , 2003, Current medicinal chemistry.

[19]  S. Goodman,et al.  Nonsteroidal Anti-Inflammatory Drugs for the Prevention of Alzheimer’s Disease: A Systematic Review , 2004, Neuroepidemiology.

[20]  Georg W. Kreutzberg,et al.  Neuroglial activation repertoire in the injured brain: graded response, molecular mechanisms and cues to physiological function , 1999, Brain Research Reviews.

[21]  M. Ferencik,et al.  Alzheimer's disease, inflammation and non-steroidal anti-inflammatory drugs. , 2001, Bratislavske lekarske listy.

[22]  L. Eiden,et al.  Upregulation of COX-2 and CGRP Expression in Resident Cells of the Borna Disease Virus-Infected Brain Is Dependent upon Inflammation , 1999, Neurobiology of Disease.

[23]  T. Hemnani,et al.  Alzheimer’s disease pathogenesis and therapeutic interventions , 2004, Journal of Clinical Neuroscience.

[24]  D. Teplow,et al.  Cyclooxygenase-2 promotes amyloid plaque deposition in a mouse model of Alzheimer's disease neuropathology. , 2002, Gene expression.

[25]  A. Manning,et al.  New targets for anti-inflammatory drugs. , 1999, Current opinion in chemical biology.

[26]  P. Baeuerle,et al.  Transcription factor NF-κB is activated in primary neurons by amyloid β peptides and in neurons surrounding early plaques from patients with Alzheimer disease , 1997 .

[27]  R. Rydel,et al.  Amyloid beta peptide potentiates cytokine secretion by interleukin-1 beta-activated human astrocytoma cells. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[28]  M. Ceska,et al.  β-Amyloid(25–35) induces the production of interleukin-8 from human monocytes , 1995, Journal of Neuroimmunology.

[29]  S. Sung,et al.  A new neuroprotective pinusolide derivative from the leaves of Biota orientalis. , 2002, Chemical & pharmaceutical bulletin.

[30]  L. Iversen,et al.  The toxicity in vitro of beta-amyloid protein. , 1995, The Biochemical journal.

[31]  S Shimohama,et al.  Activation of MKK6, an upstream activator of p38, in Alzheimer's disease , 2001, Journal of neurochemistry.

[32]  W. Markesbery,et al.  p38 Kinase Is Activated in the Alzheimer's Disease Brain , 1999, Journal of neurochemistry.

[33]  D. Gruol,et al.  Physiological and pathological roles of interleukin-6 in the central nervous system , 1997, Molecular Neurobiology.

[34]  M. Karin,et al.  Mammalian MAP kinase signalling cascades , 2001, Nature.