Echinacoside, an Inestimable Natural Product in Treatment of Neurological and Other Disorders

molecules Review Echinacoside, an Inestimable Natural Product in Treatment of Neurological and other Disorders Jingjing Liu 1,†, Lingling Yang 1,†, Yanhong Dong 1, Bo Zhang 1 and Xueqin Ma 1,2,* ID 1 Department of Pharmaceutical Analysis, School of Pharmacy, Ningxia Medical University, 1160 Shenli Street, Yinchuan 750004, China; [email protected] (J.L.); [email protected] (L.Y.); [email protected] (Y.D.); [email protected] (B.Z.) 2 Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, 1160 Shenli Street, Yinchuan 750004, China * Correspondence: [email protected]; Tel.: +86-951-6880693 † These authors contributed equally to this work. Academic Editors: Nancy D. Turner and Isabel C. F. R. Ferreira Received: 1 May 2018; Accepted: 15 May 2018; Published: 18 May 2018 Abstract: Echinacoside (ECH), a natural phenylethanoid glycoside, was first isolated from Echinacea angustifolia DC. (Compositae) sixty years ago. It was found to possess numerous pharmacologically beneficial activities for human health, especially the neuroprotective and cardiovascular effects. Although ECH showed promising potential for treatment of Parkinson’s and Alzheimer’s diseases, some important issues arose. These included the identification of active metabolites as having poor bioavailability in prototype form, the definite molecular signal pathways or targets of ECH with the above effects, and limited reliable clinical trials. Thus, it remains unresolved as to whether scientific research can reasonably make use of this natural compound. A systematic summary and knowledge of future prospects are necessary to facilitate further studies for this natural product. The present review generalizes and analyzes the current knowledge on ECH, including its broad distribution, different preparation technologies, poor pharmacokinetics and kinds of therapeutic uses, and the future perspectives of its potential application. Keywords: echinacoside; preparation; pharmacokinetics; Parkinson’s disease; Alzheimer’s disease 1. Introduction—Treasure from the Garden: The Discovery and Distribution of ECH Phenylethanoid glycosides (PhGs) are naturally occurring water-soluble compounds that are widely distributed in the plant kingdom, and most of which are isolated from garden plants and medicinal herbs. Structurally, these compounds are characterized by cinnamic acid and hydroxyl phenyl ethyl moieties that are attached to a β-glucopyranose (apiose, galactose, rhamnose, xylose, etc.) via a glycosidic bond. In recent years, interest has been growing in using PhGs [1] as their potential in the prevention and treatment of various human diseases and disorders. Echinacoside (ECH, Figure1), a natural PhG, was first isolated from Echinacea angustifolia DC. (Compositae), a garden plant sixty years ago, [2] and subsequently prepared from the species of Cistanches [3] as well as the aerial part of landscape herb, Penstemon crandallii A. Nels. (Scrophulariaceae) [4], whole plants of Pedicularis striata Pall. [5] and now successively found in 40 plant species [6–12] belonging to 18 genus and 10 families (Figure2). To date, the species of genus Cistanches (Orobanchaceae) and Echinacea (Asteraceae) were the main natural plant sources for the preparation of ECH. Molecules 2018, 23, 1213; doi:10.3390/molecules23051213 www.mdpi.com/journal/molecules Molecules 2018, 23, x FOR PEER REVIEW 2 of 22 Molecules 2018, 23, 1213 2 of 23 Molecules 2018, 23, x FOR PEER REVIEW 2 of 22 Figure 1. Chemical structure of Echinacoside (ECH) (Glu-Glu-Rha). ECH was found in both underground and aboveground parts of medicinal herbs but with widely varying levels of content (Figure 2), including different stages of plant growth [8,13], different parts of the same plant [14], and vice versa, the same parts of different plants [15,16]. Until now, the highest content of ECH was found in haustorium phloem of Cistanches tubulosa which was reached almost 15.5% [17], thusFigure could 1. Chemical be a good structure resource of EchinacosideEchina for thecoside isolation (ECH) of (Glu-Glu-Rha). pure ECH. ECH was found in both underground and aboveground parts of medicinal herbs but with widely varying levels of content (Figure 2), including different stages of plant growth [8,13], different parts of the same plant [14], and vice versa, the same parts of different plants [15,16]. Until now, the highest content of ECH was found in haustorium phloem of Cistanches tubulosa which was reached almost 15.5% [17], thus could be a good resource for the isolation of pure ECH. Figure 2. The broad distribution and discovery of ECH in the plant kingdom. Figure 2. The broad distribution and discovery of ECH in the plant kingdom. ECH was found in both underground and aboveground parts of medicinal herbs but with widely varying levels of content (Figure2), including different stages of plant growth [ 8,13], different parts of the same plant [14], and vice versa, the same parts of different plants [15,16]. Until now, the highest Figure 2. The broad distribution and discovery of ECH in the plant kingdom. Molecules 2018, 23, 1213 3 of 23 content of ECH was found in haustorium phloem of Cistanches tubulosa which was reached almost 15.5%Molecules [17 2018], thus, 23, x couldFOR PEER be aREVIEW good resource for the isolation of pure ECH. 3 of 22 2. Preparation of ECH As PhG compounds exhibited significant significant activities in the prevention and treatment of various human diseases and disorders, it was important important to develop develop sustainable sustainable methods methods to produce produce sufficient sufficient quantities ofof ECH ECH for for pharmaceutical pharmaceutical applications. applications. Firstly Firstly and alsoand usually, also usually, like other like natural other bioactive natural bioactivecompounds, compounds, high purity high of ECH purity was of obtained ECH was from obtained medicinal from plants medi by usingcinal classicplants isolationby using methods classic isolationand semi-preparative methods and liquid semi-preparative chromatography liquid (LC) ch [18romatography] or high-speed (LC) counter-current [18] or high-speed chromatography counter- currentmethods chromatography [14] as Figure3 shown, methods and [14] the as yieldFigure of 3 ECH shown, was and usually the yield between of ECH 0.2%~0.4%. was usually An efficientbetween 0.2%~0.4%.ultrasound-assisted An efficient aqueous ultrasound-assisted two-phase extraction aqueous processtwo-phase for extraction preparation process of ECH for frompreparationCistanche of ECHdeserticola fromenhanced Cistanche thedeserticola content enhanced of ECH in the the content extracts of (27.56 ECH mg/g)in the extracts which was (27.56 2.46-fold mg/g) higherwhich thanwas 2.46-foldthe amounts higher obtained than the in ultrasound-assistedamounts obtained in extraction ultrasound-assisted [19]. Interestingly, extraction it was [19]. found Interestingly, the content it wasof ECH found in medicinal the content herbs of wasECH significantly in medicinal influenced herbs was by significantly the factors of influenced preparation by processing the factors [20 of], preparationincluding the processing slice thickness, [20], including drying temperature, the slice th andickness, the time drying for inactivationtemperature, of and the enzymethe time [21for]. Therefore,inactivation it of was the worth enzyme noting [21].that Therefore, ECH was it wa demonstrateds worth noting to bethat highly ECH susceptiblewas demonstrated to “enzymic” to be highlydegradation susceptible and oxidation to “enzymic” in hydroalcoholic degradation and solutions oxidation during in hydroalcoholic the extraction process,solutions and during ECH the in extractionbiosamples process, was susceptible and ECH toindegradation biosamples was at a highersusceptible temperature to degradation during at the a wholehigher process,temperature thus duringthe operation the whole must process, be carried thus outthe carefullyoperation atmust a lower be carried temperature. out carefully Secondly, at a lower besides temperature. the above Secondly,classic isolation besides method, the above plant cell/tissueclassic isolation culture, method called, “green plant cellcell/tissue factories”, cultur hase, become called increasingly“green cell factories”,attractive ashas a become cost-effective increasingly alternative attractive to classical as a cost-effective approaches alternative for the sustainable to classical mass approaches production for theof plant-derived sustainable moleculesmass production [22]. Several of publishedplant-deri dataved demonstratedmolecules [22]. an increasedSeveral accumulationpublished data of demonstratedECH in both plant an increased tissue culture accumulation [23] and cellof ECH suspension in both cultureplant tissue [24] ofcultureCistanche [23] deserticolaand cell suspension, and some culturerevulsant [24] including of Cistanche tyrosine, deserticola phenylalanine,, and cladosporiumsome revulsant fulvum, including methyl tyrosine, jasmonate phenylalanine, and salicylic cladosporiumacid were found fulvum, couldpromote methyl thejasmonate accumulation and ofsalicylic ECH [ 25acid–27 ].were Thirdly, found as an could inestimable promote natural the productaccumulation which of possesses ECH [25–27]. a broad Thirdly, spectrum as an of in beneficialestimable activities,natural product the chemical which possesses synthesis a of broad ECH spectrumis needed of to beneficial satisfy its activities, comprehensive the chemical application. synthesis

Load more