ESP-102, a standardized combined extract of Angelica gigas, Saururus chinensis and Schizandra chinensis, significantly improved scopolamine-induced memory impairment in mice.

We assessed the effects of oral treatments of ESP-102, a standardized combined extract of Angelica gigas, Saururus chinensis and Schizandra chinensis, on learning and memory deficit. The cognition-enhancing effect of ESP-102 was investigated in scopolamine-induced (1 mg/kg body weight, s.c.) amnesic mice with both passive avoidance and Morris water maze performance tests. Acute oral treatment (single administration prior to scopolamine treatment) of mice with ESP-102 (doses in the range of 10 to 100 mg/kg body weight) significantly reduced scopolamine-induced memory deficits in the passive avoidance performance test. Another noteworthy result included the fact that prolonged oral daily treatments of mice with much lower amounts of ESP-102 (1 and 10 mg/kg body weight) for ten days reversed scopolamine-induced memory deficits. In the Morris water maze performance test, both acute and prolonged oral treatments with ESP-102 (single administration of 100 mg/kg body weight or prolonged daily administration of 1 and 10 mg/kg body weight for ten days, respectively, significantly ameliorated scopolamine-induced memory deficits as indicated by the formation of long-term and/or short-term spatial memory. In addition, we investigated the effects of ESP-102 on neurotoxicity induced by amyloid-beta peptide (Abeta25-35) or glutamate in primary cultured cortical neurons of rats. Pretreatment of cultures with ESP-102 (0.001, 0.01 and 0.1 mug/ml) significantly protected neurons from neurotoxicity induced by either glutamate or Abeta25-35. These results suggest that ESP-102 may have some protective characteristics against neuronal cell death and cognitive impairments often observed in Alzheimer's disease, stroke, ischemic injury and other neurodegenerative diseases.

[1]  Ki Yong Lee,et al.  Decursin from Angelica gigas mitigates amnesia induced by scopolamine in mice , 2003, Neurobiology of Learning and Memory.

[2]  S. Otani,et al.  Effect of Gomisin A (TJN-101) on liver regeneration. , 1992, Planta medica.

[3]  N. Nishiyama,et al.  Beneficial effects of S-113m, a novel herbal prescription, on learning impairment model in mice. , 1995, Biological & pharmaceutical bulletin.

[4]  S. Kang,et al.  Anti-tumor activities of decursinol angelate and decursin fromAngelica gigas , 2003, Archives of pharmacal research.

[5]  H. Suh,et al.  Antinociceptive profiles of crude extract from roots of Angelica gigas NAKAI in various pain models. , 2003, Biological & pharmaceutical bulletin.

[6]  S. Sung,et al.  Hepatoprotective flavonol glycosides of Saururus chinensis herbs , 1997 .

[7]  G. Benzi,et al.  Is there a rationale for the use of acetylcholinesterase inhibitors in the therapy of Alzheimer's disease? , 1998, European journal of pharmacology.

[8]  Y. Jang,et al.  Protopine from Corydalis ternata has anticholinesterase and antiamnesic activities. , 1999, Planta Medica.

[9]  P. Doraiswamy Non-cholinergic strategies for treating and preventing Alzheimer's disease. , 2002, CNS drugs.

[10]  J. Coyle,et al.  Alzheimer disease: Evidence for selective loss of cholinergic neurons in the nucleus basalis , 1981, Annals of neurology.

[11]  J. Ha,et al.  Inhibition of methanol extract from the aerial parts of Saururus chinensis on lipopolysaccharide-induced nitric oxide and prostagladin E2 production from murine macrophage RAW 264.7 cells. , 2003, Biological & pharmaceutical bulletin.

[12]  D. Collerton,et al.  Cholinergic function and intellectual decline in Alzheimer's disease , 1986, Neuroscience.

[13]  S. Ferris Evaluation of memantine for the treatment of Alzheimer’s disease , 2003, Expert opinion on pharmacotherapy.

[14]  C. Behl,et al.  Hydrogen peroxide mediates amyloid β protein toxicity , 1994, Cell.

[15]  R. Bartus,et al.  The cholinergic hypothesis of geriatric memory dysfunction. , 1982, Science.

[16]  J. G. Kim,et al.  Low-density lipoprotein-antioxidant constituents of Saururus chinensis. , 2001, Journal of natural products.

[17]  S. Kim,et al.  Dibenzocyclooctadiene lignans from Schisandra chinensis protect primary cultures of rat cortical cells from glutamate‐induced toxicity , 2004, Journal of neuroscience research.

[18]  G. Wilcock,et al.  The cholinergic hypothesis of Alzheimer’s disease: a review of progress , 1999, Journal of neurology, neurosurgery, and psychiatry.

[19]  S. Sung,et al.  Coumarins isolated from Angelica gigas inhibit acetylcholinesterase: structure-activity relationships. , 2001, Journal of natural products.

[20]  P. Doraiswamy Alzheimer's disease and the glutamate NMDA receptor. , 2003, Psychopharmacology bulletin.

[21]  B. Shukitt-Hale,et al.  Blueberry Supplementation Enhances Signaling and Prevents Behavioral Deficits in an Alzheimer Disease Model , 2003, Nutritional neuroscience.

[22]  Y. Jang,et al.  E‐p‐Methoxycinnamic acid protects cultured neuronal cells against neurotoxicity induced by glutamate , 2002, British journal of pharmacology.

[23]  Chi-Rei Wu,et al.  Effects of Fructus schizandrae on cycloheximide‐induced amnesia in rats , 1999, Phytotherapy research : PTR.

[24]  M. Kopelman,et al.  Cholinergic 'blockade' as a model for cholinergic depletion. A comparison of the memory deficits with those of Alzheimer-type dementia and the alcoholic Korsakoff syndrome. , 1988, Brain : a journal of neurology.

[25]  S. Kim,et al.  Aristolactam BII of Saururus chinensis attenuates glutamate-induced neurotoxicity in rat cortical cultures probably by inhibiting nitric oxide production. , 2004, Planta medica.

[26]  N. Greig,et al.  Current drug targets for Alzheimer's disease treatment , 2002 .

[27]  Medicinal chemistry approaches for the treatment and prevention of Alzheimer's disease , 2003, Medicinal research reviews.

[28]  K. Courtney,et al.  A new and rapid colorimetric determination of acetylcholinesterase activity. , 1961, Biochemical pharmacology.

[29]  B. Winblad,et al.  The glutamatergic system and neurodegeneration in dementia: preventive strategies in Alzheimer's disease , 1999, International journal of geriatric psychiatry.

[30]  Sanghyun Lee,et al.  Platelet anti-aggregatory effects of coumarins from the roots ofAngelica genuflexa andA. gigas , 2003, Archives of pharmacal research.

[31]  M. Tohkin,et al.  Mechanism of antihepatotoxic activity of wuweizisu C and gomisin A. , 1985, Planta medica.

[32]  R. Morris Developments of a water-maze procedure for studying spatial learning in the rat , 1984, Journal of Neuroscience Methods.

[33]  Ki Yong Lee,et al.  Anti-amnestic activity of E-p-methoxycinnamic acid from Scrophularia buergeriana. , 2003, Brain research. Cognitive brain research.

[34]  Ki Yong Lee,et al.  New acetylcholinesterase-inhibitory pregnane glycosides of Cynanchum atratum roots , 2003 .

[35]  Jun-Sub Jung,et al.  Protection against β-amyloid peptide-induced memory impairment with long-term administration of extract of Angelica gigas or decursinol in mice , 2004, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[36]  D. Mak,et al.  In Vivo Antioxidant Action of a Lignan-Enriched Extract of Schisandra Fruit and an Anthraquinone-Containing Extract of Polygonum Root in Comparison with Schisandrin B and Emodin , 2002, Planta medica.

[37]  Young-Soo Hong,et al.  Lignans from Saururus chinensis inhibiting the transcription factor NF-κB , 2003 .

[38]  N. Nishiyama,et al.  An herbal prescription, S-113m, consisting of biota, ginseng and schizandra, improves learning performance in senescence accelerated mouse. , 1996, Biological & pharmaceutical bulletin.

[39]  S. Kang,et al.  Antibacterial coumarins fromAngelica gigas roots , 2003, Archives of pharmacal research.

[40]  T. Mosmann Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[41]  S. Sung,et al.  Hepatoprotective diastereomeric lignans from Saururus chinensis herbs. , 2000, Journal of natural products.