Chronic Administration of Cardanol (Ginkgol) Extracted from Ginkgo biloba Leaves and Cashew Nutshell Liquid Improves Working Memory-Related Learning in Rats

Abstract

Cardanol (ginkgol) extracted from Ginkgo biloba leaves and cashew nutshell liquid enhances the growth of NSC-34 immortalized motor neuron-like cells and, when chronically administered to young rats, improves working memory-related learning ability as assessed by eight-arm radial maze tasks. These findings suggest that cardanol is one of the components in Ginkgo biloba leaves that improves cognitive learning ability.Key words Ginkgo biloba; Anacardium occidentale; cardanol; motor neuron-like cell; working memoryrelated learning ability Ginkgo biloba L., although grown mainly in China and Japan, is currently well-known in various European countries. The plant is believed to be one of the oldest living species trees and the only living member of the family Ginkgoaceae. It is called a living fossil because its fossils, as much as two hundred million years old, are found throughout the world. In the 19th century it was shown to be a dioecious plant that propagates by a unique and ancient mechanism.2) In Europe the extract of its leaves, referred to as EGb 761, is commonly used to alleviate symptoms of dementia.Various chemical components have been isolated from the plant, including flavonoids, 3) terpenoids (ginkgolides, bilobalides) 4,5) and organic acids (anacardic acid, cardanol). 6,7)Several biomedical studies on its activity have been carried out, [8][9][10][11] however, its pharmacologic effects appear to be due more to the synergistic action of multiple components than to a single compound.12) Studies on its therapeutic effect have also yielded conflicting results. [12][13][14][15] Therefore, in the current study, we sought a particular component in the extract that alone has activity related to the treatment of dementia.Diterpenoid ginkgolides have recently received a great deal of attention because of their unique structures and specific ability to antagonize the effect of a platelet activating factor (PAF). We examined the effect of cardanol and related organic acids (Fig. 1) in the current study because of their ability to cross the blood-brain barrier.11) On the other hand, the organic acids, anacardic acid and cardanol (gingkol acid and ginkgol; assigned the name derived more from cashew nuts Anacardium occidental L., Anacardiaceae, than from Ginkgo biloba L. in this study) and related compounds have not been discussed from the viewpoint of active ingredients because of their unfavorable side effects, such as allergenic properties.We first examined the neurotrophic effect of cardanol (isolated from Ginkgo leaves and the crude organic acids extracted from cashew nutshell) on NSC-34 murine immortalized motor neuron-like cells established by fusing mouse neuroblastoma N18TG2 with mouse neuron-enriched embryonic spinal cord cells. 16) According to favorable results obtained from in vitro studies, large amounts of cardanol and cardanol acetate were prepared from commercially available cashew nutshell liquid for in vivo studies. The effect of cardanol acetate was investigated by administering it to young rats ...

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“…generates an inflammatory process characterized by leukocyte aggregation and fluid extravasation; with participation of cytokines, nitric oxide, leukotrienes, and PGE2 [44]. Our data suggest that 2-AP reduces carrageenan-induced leukocyte migration as well as eugenol and estragole, both phenylpropanoids which have been shown to reduce chemotactic-stimulated cell migration [12, 48].…”

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Neural Cell Activation by Phenolic Compounds from the Siberian Larch (Larix sibirica)

“…These results show that especially (+)-dihydroquercetin ( 1 ) and (−)-secoisolariciresinol ( 2 ) enhance neurite outgrowth more actively than the previously described cardanol and curcuminoids, which are only active in the micromolar range and achieved maximal stimulation of neurite outgrowth by 2-fold. For instance, Tobinaga et al showed that cardanol (ginkgol) extracted from Ginkgo biloba leaves enhanced the growth of NSC-34 immortalized motoneuron-like cells (1.4-fold) and improved working memory-related learning in rats when administered chronically. Moreover, certain curcuminoids were shown to promote neurite outgrowth in PC12 cells at micromolar concentrations, and the total neurite length was increased by 1.4- to 2.2-fold…”

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