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      Pharmacological Actions of Multi-Target-Directed Evodiamine

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          Abstract

          Evodiamine, a naturally occurring indole alkaloid, is one of the main bioactive ingredients of Evodiae fructus. With respect to the pharmacological actions of evodiamine, more attention has been paid to beneficial effects in insults involving cancer, obesity, nociception, inflammation, cardiovascular diseases, Alzheimer's disease, infectious diseases and themoregulative effects. evodiamine has evolved a superior ability to bind various proteins, so we also argue that it is good starting point for multi-target drugs. This review is primarily addressed to the description of the recent advances in the biological activity studies of evodiamine, with a focus on pharmacological mechanism. The present review also includes the pharmacokinetics and the detailed exploration of target-binding properties of evodiamine in an attempt to provide a direction for further multi-target drug design.

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          Most cited references131

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          The vanilloid receptor: a molecular gateway to the pain pathway.

          The detection of painful stimuli occurs primarily at the peripheral terminals of specialized sensory neurons called nociceptors. These small-diameter neurons transduce signals of a chemical, mechanical, or thermal nature into action potentials and transmit this information to the central nervous system, ultimately eliciting a perception of pain or discomfort. Little is known about the proteins that detect noxious stimuli, especially those of a physical nature. Here we review recent advances in the molecular characterization of the capsaicin (vanilloid) receptor, an excitatory ion channel expressed by nociceptors, which contributes to the detection and integration of pain-producing chemical and thermal stimuli. The analysis of vanilloid receptor gene knockout mice confirms the involvement of this channel in pain sensation, as well as in hypersensitivity to noxious stimuli following tissue injury. At the same time, these studies demonstrate the existence of redundant mechanisms for the sensation of heat-evoked pain.
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            Nitric oxide as a secretory product of mammalian cells.

            C. Nathan (1992)
            Evolution has resorted to nitric oxide (NO), a tiny, reactive radical gas, to mediate both servoregulatory and cytotoxic functions. This article reviews how different forms of nitric oxide synthase help confer specificity and diversity on the effects of this remarkable signaling molecule.
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              Resveratrol promotes clearance of Alzheimer's disease amyloid-beta peptides.

              Several epidemiological studies indicate that moderate consumption of wine is associated with a lower incidence of Alzheimer's disease. Wine is enriched in antioxidant compounds with potential neuroprotective activities. However, the exact molecular mechanisms involved in the beneficial effects of wine intake on the neurodegenerative process in Alzheimer's disease brain remain to be clearly defined. Here we show that resveratrol (trans-3,4',5-trihydroxystilbene), a naturally occurring polyphenol mainly found in grapes and red wine, markedly lowers the levels of secreted and intracellular amyloid-beta (Abeta) peptides produced from different cell lines. Resveratrol does not inhibit Abeta production, because it has no effect on the Abeta-producing enzymes beta- and gamma-secretases, but promotes instead intracellular degradation of Abeta via a mechanism that involves the proteasome. Indeed, the resveratrol-induced decrease of Abeta could be prevented by several selective proteasome inhibitors and by siRNA-directed silencing of the proteasome subunit beta5. These findings demonstrate a proteasome-dependent anti-amyloidogenic activity of resveratrol and suggest that this natural compound has a therapeutic potential in Alzheimer's disease.
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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                31 January 2013
                February 2013
                : 18
                : 2
                : 1826-1843
                Affiliations
                [1 ]State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, the Third Military Medical University, Chongqing 400042, China; E-Mail: huiyu2008@ 123456hotmail.com
                [2 ]The Second Affiliated Hospital, Baotou Medical College, Baotou 014030, China
                [3 ]State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China; E-Mails: jinhw@ 123456bjmu.edu.cn
                [4 ]The First Affiliated Hospital, Baotou Medical College, Baotou 014010, China; E-Mail: gongwz73@ 123456sina.com
                Author notes
                [* ]Authors to whom correspondence should be addressed; E-Mails: wang.zhanli@ 123456hotmail.com (Z.W.); huaping_liang@ 123456yahoo.com.cn (H.L.); Tel.: +86-0472-217-8195 (Z.W.); Fax: +86-0472-212-9235 (Z.W.); Tel.: +86-023-6875-7411 (H.L.); Fax: +86-023-6875-7404 (H.L.).
                Article
                molecules-18-01826
                10.3390/molecules18021826
                6270287
                23434865
                ac22b608-cbd8-40a3-b469-1d7d85a313f5
                © 2013 by the authors;

                licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 14 December 2012
                : 28 January 2013
                : 29 January 2013
                Categories
                Review

                evodiamine,bioactivity,mechanism,receptor binding
                evodiamine, bioactivity, mechanism, receptor binding

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