Next Article in Journal
Effect of Marination Time on the Antioxidant Properties of Peptides Extracted from Organic Dry-Fermented Beef
Next Article in Special Issue
Therapeutic Potential of α- and β-Pinene: A Miracle Gift of Nature
Previous Article in Journal
Reliable Generation of Native-Like Decoys Limits Predictive Ability in Fragment-Based Protein Structure Prediction
Previous Article in Special Issue
Effects on the Caco-2 Cells of a Hypoglycemic Protein from Lupin Seeds in a Solution and Adsorbed on Polystyrene Nanoparticles to Mimic a Complex Food Matrix
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:

Fructans as Immunomodulatory and Antiviral Agents: The Case of Echinacea

Laboratory of Molecular Plant Biology, KU Leuven, 3001 Leuven, Belgium
Institute for Plant Biotechnology, Department of Genetics, Faculty of AgriSciences, Stellenbosch University, Matieland 7602, South Africa
Author to whom correspondence should be addressed.
Equally contributing senior authors.
Biomolecules 2019, 9(10), 615;
Submission received: 19 September 2019 / Revised: 11 October 2019 / Accepted: 14 October 2019 / Published: 16 October 2019


Throughout history, medicinal purposes of plants have been studied, documented, and acknowledged as an integral part of human healthcare systems. The development of modern medicine still relies largely on this historical knowledge of the use and preparation of plants and their extracts. Further research into the human microbiome highlights the interaction between immunomodulatory responses and plant-derived, prebiotic compounds. One such group of compounds includes the inulin-type fructans (ITFs), which may also act as signaling molecules and antioxidants. These multifunctional compounds occur in a small proportion of plants, many of which have recognized medicinal properties. Echinacea is a well-known medicinal plant and products derived from it are sold globally for its cold- and flu-preventative and general health-promoting properties. Despite the well-documented phytochemical profile of Echinacea plants and products, little research has looked into the possible role of ITFs in these products. This review aims to highlight the occurrence of ITFs in Echinacea derived formulations and the potential role they play in immunomodulation.

1. Herbal Medicines Comprise the Second Largest Therapeutic Market Globally

The use of herbal medicine is an ancient practice that relies on the use of a broad range of plant and plant-derived products (botanical materials) for medicinal purposes. These herbal products are prepared and used in various forms, including capsules (dry powder), tinctures (ethanol extracts), infusions (extractions usually based on water or oil, such as tea), macerations (soaking of plant material), and decoctions (boiling of plant material). The largest proportion (80%) of communities in developing countries (particularly Asia and Africa) relies on herbal medicine and associated herbal preparations as primary healthcare. Compared to other therapeutics used in modern medicine (MM), herbal medicines are perceived as being more affordable, accessible, and acceptable to the communities using it [1,2]. The use of herbal products as an alternative and complementary to MM created a global market recognized by the World Health Organization (WHO) as the second-largest therapeutics market worldwide [3,4]. The uncertainties (pertaining to efficacy and safety) arising around the use of MM therapeutics is one of the driving factors to search for alternative or complementary medicines in the form of natural resources. In this regard, the use of herbal medicines for immunomodulation could, therefore, provide an effective and safe complement to MM [5,6,7]. Consequently, research efforts largely focus on identifying and investigating specific groups of plant-related compounds (such as flavonoids, polysaccharides, lactones, alkaloids, diterpenoids, and glycosides) and their potential implication in immunomodulation [8,9,10]. Typically, in crude extracts, these compounds occur together in a mixture. Understanding the relative contribution of each compound to the overall immunomodulatory effect is usually a challenging task.
Immunomodulators could act (stimulate or suppress) on both the innate- and adaptive immune systems to (i) exert positive effects on the host defense mechanisms, (ii) have an anti-proliferative effect on tumor cells and, (iii) enhance the host’s ability to tolerate damages caused by toxic compounds (such as chemotherapeutics). Echinacea preparations are among the most popular herbal products with immunomodulatory properties [11,12]. While immunomodulatory aspects of an array of different biomolecules (e.g., phenolic compounds, alkamides, arabinogalactan proteins) occurring in Echinacea preparations have been highlighted before [13,14,15,16,17], here we review knowledge on Echinacea derived inulin-type fructans (ITFs) and highlight their presence in commercially available Echinacea products. The potential contribution of ITFs to immunomodulatory effects in the human body is discussed.

2. Echinacea Plant Extracts Exert Immunomodulatory Properties

Echinacea is a plant genus within the family Asteraceae (previously termed the Compositae) and is comprised of 11 taxa of herbaceous and flowering plants [18,19]. Echinacea preparations (which are mainly based on three commercially important species; Echinacea purpurea, Echinacea angustifolia, and Echinacea pallida) are commonly used for preventing and alleviating the symptoms of bacterial and viral infections [11,12,18]. Furthermore, some Echinacea preparations are known to exert antioxidant and anti-inflammatory activity espousing to its potential immunomodulatory activities [12,19,20].
Both in vitro and in vivo studies demonstrated that different extracts from Echinacea, either from roots, above-ground parts, or a mixture of both, could stimulate and signal immune responses [21]. Both aqueous extracts and alcoholic extracts are used. Differences between the species, the soil in which the plants are cultivated, the parts of the plant used, and the extraction procedures can result in substantial differences in chemical composition and biological activity [21]. Immunological studies have used aqueous or alcoholic extracts, as well as purified polysaccharides. Their effects on monocytes, macrophages, natural killer (NK) cells, T cells, and dendritic cells (DC) have been thoroughly studied [20,21,22]. A number of these immune-related cells are equipped with Pattern Recognition Receptors (PRRs), which are specialized in recognizing Microbe Associated Molecular Patterns (MAMPs) and Damage Associated Molecular Patterns (DAMPs). Collectively, these factors regulate the homeostasis of the immune system to maintain a state of health in the host. Further research concluded that several purified compounds from Echinacea (e.g., glycoproteins, soluble polysaccharides, caffeic acid derivatives, phenolic compounds and alkamides) could induce transcriptional changes that activate immunomodulation pathways [12,19,23,24,25,26,27,28,29]. While the immunomodulatory properties for the polyphenol and alkylamide fractions present in Echinacea are well-described, relatively little information is available about the polysaccharide fraction. In general, immunomodulatory and prebiotic polysaccharides have been implicated in the overall health and well-being of humans by (i) enhancing physiological parameters (e.g., blood pressure, hematological parameters), (ii) increasing tolerance against pathogens and, (iii) modulating immune responses [30,31]. Of interest in this review is a group of fructose-based oligo- and polysaccharides collectively termed fructans.

3. General Function of Fructans in the Human Body

Fructans are water-soluble, sucrose-derived compounds that occur in about 15% of flowering plants [32], including the economically important Poaceae and Asteraceae (including Echinacea) families. Based on structural differences, three types of fructans can be distinguished: inulin (β2→1 linkage), levan (β2→6 linkage), and graminan (β2→1 and β2→6 linkages). The chain-length of plant fructans (defined by the degree of polymerization: DP) is variable, with a few species (e.g., Viguiera discolor; Echinops ritro) standing out, producing higher DPs by specific fructosyltransferases [33]. Short-chain fructooligosaccharides with a DP < 10 are often referred to as FOS, whereas long-chain polymers with DP > 10 are usually called inulin or ITFs [34], well-known prebiotics contributing to overall health and well-being. Short-chain FOS are primarily metabolized in the proximal colon, while long-chain ITFs are fermented by bacteria in the distal colon, where many chronic diseases originate [35,36,37,38,39]. The beneficial immunomodulatory effects of fructans in the human gastrointestinal tract, and by extension to all other eukaryotic organisms, including animals and plants, are often attributed to their capacity to (i) stimulate the growth and proliferation of beneficial intestinal bacteria (prebiotics), (ii) act as signaling molecules and (iii) act as reactive oxygen species (ROS) scavengers [35,38,39,40,41,42]. These effects are, to a large extent, dependent on fructan DP [35,43].
The immunomodulatory function of ITFs was shown to be dependent on Toll-Like Receptors (TLRs), in particular, TLR2 and to a lesser extent, TLR4, 5, 7, 8 [35]. Fructans may be mimicking MAMPs. After binding to TLRs and used at lower doses, they may slightly trigger signaling pathways dependent on the nuclear factor NF-κB, resembling a ‘priming’ or ‘vaccination’ like effect [38]. However, an additional signaling pathway dependent on the peptidoglycan recognition protein 3 (PGlyRP3) has also been proposed [44]. This recognition protein, which responds to bacterial cell wall peptidoglycan, forms part of a larger group of highly conserved host defense proteins in mammals and insects. It has been demonstrated that FOS enhances the activity of peroxisome proliferator-activated receptors (PPAR), a group of nuclear receptor proteins that function as transcription factors to modulate the expression of several genes involved in lipid and carbohydrate metabolism, as well as cell proliferation, differentiation, and death [45,46]. The activation of peroxisome proliferator-activated receptor gamma (PPARγ) was shown to be induced by PGlyRP3, resulting in a decreased production of proinflammatory cytokines and inhibition of NF-κB-dependent signaling [44]. Further insights into the mechanism and modulation of these pathways would provide valuable information on the extent to which fructans contribute to immunomodulation.

3.1. Fructans as Immunomodulatory and Antiviral Compounds

Respiratory infections, such as the common cold and the seasonal flu, are often infectious diseases caused by different viruses [47]. Although vaccination is considered as an effective method to prevent infectious diseases, vaccination of healthy adults would only reduce the incidence of acute respiratory infections by 16% [5]. Apart from directly affecting an individual’s quality of life, the common cold and flu indirectly affects a society’s economy due to work absenteeism [26]. In turn, this is a driving factor for discovering alternative herbal medicines for the treatment of viral infections. In this regard, maintaining healthy homeostasis of the immune defense system (often by stimulating NK cell activity and salivary immunoglobulin A production) could play an important role in preventing viral infections. In this context, Echinacea extracts show profound antiviral activity against several viruses (including human and avian influenza viruses, H3N2-type IV, H1N1-type IV, herpes simplex, and rhinoviruses), and reversed virus-induced pro-inflammatory responses [48,49,50]. It is necessary to better understand what role ITFs and other fructans may play in immunomodulation, when administered as part of a collective plant extract, given the knowledge that a variety of other herbal medicines (such as the Indian Ayurveda and Japanese Chikuyo–Sekko–To) with well-established immunomodulatory effects have been identified to contain fructans as key compounds [51,52].
Fructans have been demonstrated to exert immunomodulatory and antiviral effects directly. An ITF (CSH1-1, Mw = 4.0 × 103) isolated from traditional Japanese herbal medicine (Chikuyo–Sekko–To) was shown to be effective against herpes simplex virus type 2 (HSV-2) in a murine model [51]. The antiviral properties were attributed to the ability of the fructan to enhance the production of nitric oxide (NO; a viral replication inhibitor) and other immunostimulatory factors (e.g., interleukine-1 beta (IL)-1β, IL-6, IL-10, interferon gamma (IFN)-γ, and tumor necrosis factor alpha (TNF)-α) on RAW264.7 cells. Similarly, ITFs from chicory (Cichorium intybus) are known to increase NO production in INF-γ-primed RAW 264.7 cells in an NF-κB-dependent manner [53]. A fructan isolated from Welsh onion (Allium fistulosum L.) demonstrated an inhibitory effect on influenza A virus replication in mice [54]. Intriguingly, fructans from burdock (Arctium lappa L.) strongly stimulate NO synthesis and defense signaling in plants [55], suggesting that the overall underlying mechanisms and pathways may be similar in all multicellular organisms. Both high and low DP fructans from aged and fresh garlic (Allium sativum) have the capacity to activate macrophages and subsequently phagocytosis, again in combination with a release of NO [56,57]. Garlic is also an important component of the traditional Ayurveda Rasayana drugs, together with the Inula racemosa and Bombax ceiba. The immunomodulating properties of these three plants were attributed to their high fructan content [58,59,60]. Fructans were also shown to be important immunomodulatory compounds in extracts of onion (Allium cepa), yacon (Smallanthus sonchifolius), Curcuma (Curcuma kwangsiensis), blue agave (Agave tequilana), and mugwort (Artemisia vulgaris) [61,62,63,64,65].

3.2. Fructans as Antioxidative and Anti-inflammatory Compounds

Fructans and other plant-derived sugars are known to exert antioxidant properties by directly and indirectly affecting ROS balances and countering the damage caused by oxidative stress [41,66,67,68]. Oxidative stress is further known to trigger inflammation (an innate immune response) and, although an important response in the human body, it has been linked to severe autoimmune disorders. Echinacea and several other plants encompassed in herbal medicine (e.g., ginger, turmeric, and cannabis) have been shown to alleviate the effects of inflammation. It is interesting to note that these plants display enhanced antioxidant capacity, which could, in turn, be used to manage inflammation-related disorders induced by oxidative stress [69].
Fructan-related antioxidant capacity (and ability to act as ROS scavengers) has also been demonstrated in humans in both in vitro and in vivo studies, suggesting that the consumption of foods rich in fructans could exert beneficial immunomodulatory properties by acting as antioxidants [68,70,71]. The ability of ITFs to bind to TLR2 suggests a potential role in anti-inflammatory pathways through the activation of regulatory T-cells (Tregs) [38,72]. In line with this reasoning, inulin was shown to create an immunosuppressive environment in human peripheral blood mononuclear cells (PBMC) by promoting the expression of forkhead box P3 (FOXP3; a Treg biomarker) and the secretion of the anti-inflammatory cytokine IL-10 [73]. TLR2 signaling is also known to decrease intestinal permeability, a condition directly linked to inflammatory intestinal diseases such as celiac disease, inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS) [74,75]. Interestingly, it was demonstrated that ITFs, independently of their action on microbiota, have the ability to enhance the expression of fucosyltransferase 2 (FUT2), an enzyme responsible for the fucosylation of gut epithelial cells and considered to play a major role in immunomodulation [76]. ITFs may also have anti-inflammatory effects through the inhibition of NF-κB, which has been proposed by Zenhom et al. [44].
It is well-known that ITFs indirectly influence AMP-activated protein kinase (AMPK) signaling through modulation of the microbiota, for instance, by stimulating the growth of Lactobacilli and Bifidobacteria, producing short-chain fatty acids (SCFAs) that activate AMPK [77]. It is also possible that ITFs exert a more direct effect on AMPK, as previously proposed [40]. Metformin, a popular antidiabetic drug, is known to activate AMPK and to inhibit NF-κB activation [78]. Surprisingly, ITFs and metformin have very similar physical outcomes [79]. PPARγ, modulated by ITFs, is also known to influence AMPK signaling [80]. These properties of ITFs make them good candidates for the treatment of current inflammatory diseases such as diabetes, obesity and IBD [81,82]. The immunomodulatory and anti-inflammatory properties of Echinacea preparations are well-known and have been ascribed to the myriad of compounds that display antioxidant activity [83]. Both Echinacea angustifolia and Echinacea purpurea were shown to improve symptoms of colitis in rats by decreasing the number of inflammatory mediators (IL-1β and TNF-α) [84]. Echinacea preparations were also reported to reduce inflammatory conditions caused by insulin resistance and induced by pathogens, respectively [79,85,86,87,88,89].

4. ITFs and Polyphenols in Echinacea Preparations May Exert Synergistic Effects

Chicoric acid is a well-known antioxidant [68], and one of the major phenolic constitutes in Echinacea preparations, but its absorption from the gastrointestinal tract into the human body is not clear. Nevertheless, similar to what has been proposed for fructans, immunomodulatory, and anti-inflammatory effects, linked to AMPK signaling and downregulation of NF-κB, have also been suggested [90,91]. Moreover, Phuwamongkolwiwat et al. [92] suggested that FOS stimulated the uptake of phenolic compounds, an example of putative synergism between the two classes of biomolecules. Such synergistic effects between ITFs and polyphenols, although depending on entirely different mechanisms, were also suggested in chicory plant vacuoles [68,93,94]. Conversely, ITFs have been shown to reduce the bioavailability of phenolic compounds and subsequently, the total antioxidant function in vitro, suggesting that the interaction between phenolic compounds and ITFs is complex, particularly in the human system, and remain to be fully elucidated [95]. The speculation that phenolics, ITFs, other types of polysaccharides, and other compounds (e.g., alkamides through PPARγ signaling) may act together in a synergistic way is consistent with the widely accepted hypothesis that Echinacea preparations have such powerful immunomodulatory properties because of their complex composition [96].

5. Possible Significance of ITFs in Commercial Echinacea Preparations

Echinacea preparations are among the best-selling herbal medicines in the Western world for the treatment and possible prevention of upper respiratory infections, including the common cold and seasonal flu [11,12,26]. The mechanisms of action of such Echinacea preparations have usually been explained by a combination of antiviral, immunomodulating, anti-inflammatory, and antioxidant activities [12,25]. Echinacea preparations were reported to stimulate increases in both the number of white and red blood cells [97]. In line with the possible anticancer activities of Echinacea preparations [98], it has been demonstrated that Echinacea extracts are potent activators of NK cell cytotoxicity. Echinacea extracts increase the frequency of NK cell target conjugates and speed up their lytic activities [99]. It has been speculated that the action of Echinacea preparations is based on differential multi-level modulation of the responses of different types of leukocytes and T cells, regulating the production of chemokines and cytokines such as IL1-β, IL-6, IL-8, IL-10, IL-12, IFN-γ, and TNF-α [100,101,102,103]. Additionally, the modulation of DC activity, important for Treg induction, has been reported [20,22,104]. The polysaccharide fraction of Echinacea was shown to inhibit inflammatory responses by inhibiting the expression of the NF-κB p65 protein [105]. Furthermore, Echinaforce® has been shown to prevent virus-induced bacterial adhesion by suppressing the expression of NF-κB [106]. There is a striking similarity between the above-discussed immunomodulatory properties of fructans and those of the Echinacea preparations.
Further research is necessary to decipher whether, and to what extent, ITFs contribute to the observed immunomodulatory effects of Echinacea preparations. The connection between the Echinacea polysaccharides and their immunomodulating properties has been suggested multiple times [23,24,107,108,109,110]. However, within the polysaccharide fraction, most research focused on the immune-stimulatory activity of cell-wall-derived arabinogalactans. Macrophage activation by the polysaccharide arabinogalactan isolated from plant cell cultures of Echinacea purpurea was already reported decades ago [111], but unfortunately, the inulin fraction in these polysaccharide preparations was completely neglected.
The occurrence of ITFs in Echinacea [112] prompted us to investigate whether fructans were present in an array of commercial Echinacea preparations. A range of low and high DP ITFs was found [113]. The average DP of the fructans present in the different preparations seem to be dependent on the method of extraction, with a higher occurrence of high DP fructans in dry extracts compared to ethanol extracts. The parts of the plant used were, however, not indicative of the relative fructan composition as both low and high DP fructans were found in preparations based on either above-ground or root material. The occurrence of fructans in Echinacea preparations was already reported by Giger et al. (1989), who found that the fructan content differed between Echinacea angustifolia and Echinacea purpurea, depending on the harvesting period [114]. They also found a tenfold lower fructan content in preparations based on the above-ground material compared to preparations based on root material. More recent studies also highlighted the presence of fructans in Echinacea preparations and found that the amount of ethanol used for extraction determines the fructan content of the extract [16,115]. As higher DP fructans are not soluble in ethanol, higher ethanol concentrations prevent the extraction of higher DP fructans while favoring a lower average DP.
We further demonstrated the total antioxidant capacity (TAC) and consequent DNA protection ability of the commercial products and the polysaccharide fractions, derived thereof, respectively. Not surprisingly, the products displayed significant TAC, as well as the ability to protect human DNA in vitro. Interestingly, we found that the polysaccharide fraction in two out the five products displayed significant differential TAC profiles, although not displaying clear DNA protection ability. In contrast, the polysaccharide fractions of the remaining three products displayed protective DNA abilities. We speculate that the occurrence of high DP fructans within polysaccharide fractions of these products could play some role in the efficacy thereof. Since ITFs only represent a small part of these preparations, it seems unlikely that prebiotic effects on their own would explain the observed immunomodulatory and health-promoting effects. More likely, ITFs present in Echinacea preparations stimulate the activity of immune cells directly by activating signaling pathways in vivo, as described [116,117,118]. Furthermore, it is important to note that the amount of ITFs required for prebiotic effects (8 to 12 g a day) is much higher than the recommended daily intake of a commercially available Echinacea preparation [8,119,120,121]. Taken together, the emerging evidence of the immunomodulating properties of ITFs in the literature and the present confirmation that commercial Echinacea products contain these fructans, strongly suggests that they could be among the contributors for the overall effect of these products.

6. Final Remarks

Numerous herb- and medicinal plant extracts have been successfully employed as immunomodulatory substances for maintaining human health. The resources of these extracts have historically been part of cultural traditions (such as Indian Ayurveda and Traditional Chinese Medicine) and have been carefully developed through anecdotal or pragmatic experience. Currently, a holistic approach based on a combination of modern therapeutics and herbal medicines is targeted for disease prevention. Various plant extracts are known to contain an array of active compounds with the ability to activate or regulate the immune system through direct or indirect mechanisms (such as signaling, stimulation, and modulation of macrophages, lymphocytes, and cytokine production). Immunomodulatory compounds from plant extracts include (i) flavonoids, (ii) glycosides, (iii) polysaccharides, (iv) terpenoids, (v) essential oils, and (vi) alkaloids. Many efforts have been undertaken to demonstrate the multidimensional effects of these compounds on overall health and well-being by influencing the immune system. The polysaccharide fraction, with emphasis on ITFs, of plant extracts used in herbal medicine has been largely overlooked in recent years. We speculate that these fractions may play an important role in the modulation of the immune system, either independently or synergistically. Further research efforts are required to identify and determine the functionality of these polysaccharides, especially ITFs, among various herbal medicines.

Author Contributions

All authors contributed equally to the preparation of the manuscript.


W.V.d.E. is supported by grants from the FWO Vlaanderen.

Conflicts of Interest

The authors declare no conflicts of interest.


  1. Licciardi, P.V.; Underwood, J.R. Plant-derived medicines: A novel class of immunological adjuvants. Int. Immunopharmacol. 2011, 11, 390–398. [Google Scholar] [CrossRef] [PubMed]
  2. Sato, A. Revealing the popularity of traditional medicine in light of multiple recourses and outcome measurements from a user’s perspective in Ghana. Health Policy Plan. 2012, 27, 625–637. [Google Scholar] [CrossRef] [PubMed]
  3. Ernst, E.; Pittler, M.H. Herbal medicine. Med. Clin. N. Am. 2002, 86, 149–161. [Google Scholar] [CrossRef]
  4. Schneiderman, L.J. The (alternative) medicalization of life. J. Law Med. Ethics 2003, 31, 191–197. [Google Scholar] [CrossRef] [PubMed]
  5. Demicheli, V.; Jefferson, T.; Ferroni, E.; Rivetti, A.; Di Pietrantonj, C. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst. Rev. 2003, 2, CD001269. [Google Scholar]
  6. Burch, J.; Corbett, M.; Stock, C.; Nicholson, K.; Elliot, A.J.; Duffy, S.; Westwood, M.; Palmer, S.; Stewart, L. Prescription of anti-influenza drugs for healthy adults: A systematic review and meta-analysis. Lancet Infect. Dis. 2009, 9, 537–545. [Google Scholar] [CrossRef]
  7. Nahas, R.; Balla, A. Complementary and alternative medicine for prevention and treatment of the common cold. Can. Fam. Phys. 2011, 57, 31–36. [Google Scholar]
  8. Jantan, I.; Ahmad, W.; Bukhari, S.N.A. Plant-derived immunomodulators: An insight on their preclinical evaluation and clinical trials. Front. Plant Sci. 2015, 6, 655. [Google Scholar] [CrossRef]
  9. Nair, A.; Chattopadhyay, D.; Saha, B. Plant-derived immunomodulators. In New Look to Phytomedicine, 1st ed.; Ahmad Khan, M.S., Ahmad, I., Chattopadhyay, D., Eds.; Academic Press: Cambridge, MA, USA, 2019; pp. 435–499. [Google Scholar]
  10. Sultan, M.T.; Buttxs, M.S.; Qayyum, M.M.; Suleria, H.A. Immunity: Plants as Effective Mediators. Crit. Rev. Food Sci. Nutr. 2014, 54, 1298–1308. [Google Scholar] [CrossRef]
  11. Barrett, B. Medicinal properties of Echinacea: A critical review. Phytomedicine 2003, 10, 66–86. [Google Scholar] [CrossRef]
  12. Sharma, M.; Arnason, J.T.; Burt, A.; Hudson, J.B. Echinacea extracts modulate the pattern of chemokine and cytokine secretion in rhinovirus-infected and uninfected epithelial cells. Phytother. Res. 2006, 20, 147–152. [Google Scholar] [CrossRef] [PubMed]
  13. Blaschek, W.; Döll, M.; Franz, G. Echinacea-Polysaccharide. Z. Phytother. 1998, 19, 255–262. [Google Scholar]
  14. Bruni, R.; Brighenti, V.; Caesar, L.K.; Bertelli, D.; Cech, N.B.; Pellati, F. Analytical methods for the study of bioactive compounds from medicinally used Echinacea species. J. Pharm. Biomed. Anal. 2018, 160, 443–477. [Google Scholar] [CrossRef] [PubMed]
  15. Classen, B. Arabinogalaktan-Proteine (AGPs) aus dem kurzzeiterhitzten presssaft von Echinacea purpurea. Z. Phytother. 2018, 39, 152–158. [Google Scholar] [CrossRef]
  16. Classen, B.; Pferschy-Wenzig, E.; Geske, T.; Ardjomand-Wölkart, K.; Bauer, R. Analytische charakterisierung und vergleich medizinisch genutzter Echinacea-haltiger zubereitungen. Z. Phytother. 2019, 40, 148–157. [Google Scholar] [CrossRef]
  17. Pugh, N.D.; Jackson, C.R.; Pasco, D.S. Total bacterial load within Echinacea purpurea, determined using a new PCR-based quantification method, is correlated with LPS levels and in vitro macrophage activity. Planta Med. 2013, 79, 9–14. [Google Scholar] [PubMed]
  18. Kim, D.H.; Heber, D.; Still, D.W. Genetic diversity of Echinacea species based upon amplified fragment length polymorphism markers. Genome 2004, 47, 102–111. [Google Scholar] [CrossRef]
  19. Sharifi-Rad, M.; Mnayer, D.; Morais-Braga, M.F.B.; Carneiro, J.N.P.; Bezerra, C.F.; Coutinho, H.D.M.; Salehi, B.; Martorell, M.; del Mar Contreras, M.; Soltani-Nejad, A.; et al. Echinacea plants as antioxidant and antibacterial agents: From traditional medicine to biotechnological applications. Phyther. Res. 2018, 32, 1653–1663. [Google Scholar] [CrossRef]
  20. El-Ashmawy, N.E.; El-Zamarany, E.A.; Salem, M.L.; El-Bahrawy, H.A.; Al-Ashmawy, G.M. In vitro and in vivo studies of the immunomodulatory effect of Echinacea purpurea on dendritic cells. J. Genet. Eng. Biotechnol. 2015, 13, 185–192. [Google Scholar] [CrossRef]
  21. Goldrosen, M.H.; Straus, S.E. Complementary and alternative medicine: Assessing the evidence for immunological benefits. Nat. Rev. Immunol. 2004, 4, 912–921. [Google Scholar] [CrossRef]
  22. Wang, C.Y.; Chiao, M.T.; Yen, P.J.; Huang, W.C.; Hou, C.C.; Chien, S.C.; Yeh, K.C.; Yang, W.C.; Shyur, L.F.; Yang, N.S. Modulatory effects of Echinacea purpurea extracts on human dendritic cells: A cell- and gene-based study. Genomics 2006, 88, 801–808. [Google Scholar] [CrossRef] [PubMed]
  23. Dalby-Brown, L.; Barsett, H.; Landbo, A.K.R.; Meyer, A.S.; Molgaard, P. Synergistic antioxidative effects of alkamides, caffeic acid derivatives, and polysaccharide fractions from Echinacea purpurea on in vitro oxidation of human low-density lipoproteins. J. Agric. Food Chem. 2005, 53, 9413–9423. [Google Scholar] [CrossRef] [PubMed]
  24. Pillai, S.; Pillai, C.; Mitscher, L.A.; Cooper, R. Use of quantitative flow cytometry to measure ex vivo immunostimulant activity of Echinacea: The case for polysaccharides. J. Altern. Complement. Med. 2007, 13, 625–634. [Google Scholar] [CrossRef] [PubMed]
  25. Ramasahayam, S.; Baraka, H.N.; Abdel Bar, F.M.; Abuasal, B.S.; Widrlechner, M.P.; El Sayed, K.A.; Meyer, S.A. Effects of chemically characterized fractions from aerial parts of Echinacea purpurea and E. angustifolia on myelopoiesis in rats. Planta Med. 2011, 77, 1883–1889. [Google Scholar] [CrossRef]
  26. Rondanelli, M.; Miccono, A.; Lamburghini, S.; Avanzato, I.; Riva, A.; Allegrini, P.; Faliva, M.A.; Peroni, G.; Nichetti, M.; Perna, S. Self-care for common colds: The pivotal role of vitamin D, vitamin C, zinc, and Echinacea in three main immune interactive clusters (physical barriers, innate and adaptive immunity) involved during an episode of common colds-practical advice on dosages and on the time to take these nutrients/botanicals in order to prevent or treat common colds. Evidence-based complementary and alternative medicine. Evid. Based Complement. Altern. Med. 2018, 2018, 5813095. [Google Scholar]
  27. Kour, K.; Bani, S. Augmentation of immune response by chicoric acid through the modulation of CD28/CTLA-4 and Th1 pathway in chronically stressed mice. Neuropharmacology 2011, 60, 852–860. [Google Scholar] [CrossRef]
  28. Park, C.M.; Jin, K.; Lee, Y.; Song, Y.S. Luteolin and chicoric acid synergistically inhibited inflammatory responses via inactivation of PI3K-Akt pathway and impairment of NF-κB translocation in LPS stimulated RAW 264.7 cells. Eur. J. Pharmacol. 2011, 660, 454–459. [Google Scholar] [CrossRef]
  29. Raduner, S.; Majewska, A.; Chen, J.Z.; Xie, X.Q.; Hamon, J.; Faller, B.; Altmann, K.H.; Gertsch, J. Alkylamides from Echinacea are a new class of cannabinomimetics-Cannabinoid type 2 receptor-dependent and -independent immunomodulatory effects. J. Biol. Chem. 2006, 281, 14192–14206. [Google Scholar] [CrossRef]
  30. Vos, A.P.; van Esch, B.C.; Stahl, B.; M’Rabet, L.; Folkerts, G.; Nijkamp, F.P.; Garssen, J. Dietary supplementation with specific oligosaccharide mixtures decreases parameters of allergic asthma in mice. Int. Immunopharmacol. 2007, 7, 1582–1587. [Google Scholar] [CrossRef]
  31. Delgado, G.T.C.; Tamashiro, W.; Pastore, G.M. Immunomodulatory effects of fructans. Food Res. Int. 2010, 43, 1231–1236. [Google Scholar] [CrossRef]
  32. Hendry, G.A.F. Evolutionary origins and natural functions of fructans – a climatological, biogeographic and mechanistic appraisal. New Phytol. 1993, 123, 3–14. [Google Scholar] [CrossRef]
  33. De Sadeleer, E.; Struyf, T.; Vergauwen, R.; Le Roy, K.; Van den Ende, W. 1-FFT amino acids involved in high DP inulin accumulation in Viguiera discolor. Front. Plant Sci. 2015, 6, 616. [Google Scholar] [CrossRef] [PubMed]
  34. Van den Ende, W. Multifunctional fructans and raffinose family oligosaccharides. Front. Plant Sci. 2013, 4, 247. [Google Scholar] [PubMed] [Green Version]
  35. Vogt, L.; Ramasamy, U.; Meyer, D.; Pullens, G.; Venema, K.; Faas, M.M.; Schols, H.A.; de Vos, P. Immune modulation by different types of beta 2->1-fructans is toll-like receptor dependent. PLoS ONE 2013, 8, e68367. [Google Scholar] [CrossRef]
  36. Allsopp, P.; Possemiers, S.; Campbell, D.; Oyarzábal, I.S.; Gill, C.; Rowland, I. An exploratory study into the putative prebiotic activity of fructans isolated from Agave angustifolia and the associated anticancer activity. Anaerobe 2013, 22, 38–44. [Google Scholar] [CrossRef]
  37. Terpend, K.; Possemiers, S.; Daguet, D.; Marzorati, M. Arabinogalactan and fructo-oligosaccharides have a different fermentation profile in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®). Environ. Microbiol. Rep. 2013, 5, 595–603. [Google Scholar] [CrossRef]
  38. Peshev, D.; Van den Ende, W. Fructans: Prebiotics and immunomodulators. J. Funct. Foods 2014, 8, 348–357. [Google Scholar] [CrossRef]
  39. Guarner, F. Inulin and oligofructose: Impact on intestinal diseases and disorders. Br. J. Nutr. 2005, 93, S61–S65. [Google Scholar] [CrossRef]
  40. Roberfroid, M. Prebiotics: The concept revisited. J. Nutr. 2007, 137, 830S–837S. [Google Scholar] [CrossRef]
  41. Matros, A.; Peshev, D.; Peukert, M.; Mock, H.P.; Van den Ende, W. Sugars as hydroxyl radical scavengers: Proof-of-concept by studying the fate of sucralose in Arabidopsis. Plant J. 2015, 82, 822–839. [Google Scholar] [CrossRef]
  42. Van den Ende, W.; Peshev, D.; De Gara, L. Disease prevention by natural antioxidants and prebiotics acting as ROS scavengers in the gastrointestinal tract. Trends Food Sci. Technol. 2011, 22, 689–697. [Google Scholar] [CrossRef]
  43. Ito, H.; Takemura, N.; Sonoyama, K.; Kawagishi, H.; Topping, D.; Conlon, M.; Morita, T. Degree of Polymerization of Inulin-Type Fructans Differentially Affects Number of Lactic Acid Bacteria, Intestinal Immune Functions, and Immunoglobulin A Secretion in the Rat Cecum. J. Agric. Food Chem. 2011, 59, 5771–5778. [Google Scholar] [CrossRef] [PubMed]
  44. Zenhom, M.; Hyder, A.; de Vrese, M.; Heller, K.J.; Roeder, T.; Schrezenmeir, J. Prebiotic oligosaccharides reduce proinflammatory cytokines in iIntestinal caco-2 cells via activation of PPARγ and peptidoglycan recognition Protein 3. J. Nutr. 2011, 141, 971–977. [Google Scholar] [CrossRef] [PubMed]
  45. Di Giacomo, E.; Benedetti, E.; Cristiano, L.; Antonosante, A.; d’Angelo, M.; Fidoamore, A.; Barone, D.; Moreno, S.; Ippoliti, R.; Cerù, M.P.; et al. Roles of PPAR transcription factors in the energetic metabolic switch occurring during adult neurogenesis. Cell Cycle 2017, 16, 59–72. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  46. Dabrowski, A.N.; Conrad, C.; Behrendt, U.; Shrivastav, A.; Baal, N.; Wienhold, S.M.; Hackstein, H.; N’Guessan, P.D.; Aly, S.; Reppe, K.; et al. Peptidoglycan recognition protein 2 regulates neutrophil recruitment into the lungs after Streptococcus pneumoniae infection. Front. Microbiol. 2019, 10, 199. [Google Scholar] [CrossRef]
  47. Roxas, M.; Jurenka, J. Colds and influenza: A review of diagnosis and conventional, botanical, and nutritional considerations. Altern. Med. Rev. 2007, 12, 25–48. [Google Scholar]
  48. Pleschka, S.; Stein, M.; Schoop, R.; Hudson, J.B. Anti-viral properties and mode of action of standardized Echinacea purpurea extract against highly pathogenic avian Influenza virus (H5N1, H7N7) and swine-origin H1N1 (S-OIV). Virol. J. 2009, 6, 197. [Google Scholar] [CrossRef]
  49. Senchina, D.S.; Martin, A.E.; Buss, J.E.; Kohut, M.L. Effects of Echinacea extracts on macrophage antiviral activities. Phyther. Res. 2010, 24, 810–816. [Google Scholar]
  50. Vimalanathan, S.; Schoop, R.; Hudson, J. High-potency anti-influenza therapy by a combination of Echinacea purpurea fresh herb and root tinctures. J. Appl. Pharm. Sci. 2013, 3, 1–5. [Google Scholar]
  51. Lee, J.B.; Fukai, T.; Hayashi, K.; Hayashi, T. Characterization of fructan from Chikuyo-Sekko-To, a Kampo prescription, and its antiherpetic activity in vitro and in vivo. Carbohydr. Polym. 2011, 85, 408–412. [Google Scholar] [CrossRef]
  52. Thakur, M.; Weng, A.; Fuchs, H.; Sharma, V.; Bhargava, C.S.; Chauhan, N.S.; Dixit, V.K.; Bhargava, S. Rasayana properties of Ayurvedic herbs: Are polysaccharides a major contributor. Carbohydr. Polym. 2012, 87, 3–15. [Google Scholar] [CrossRef]
  53. Koo, H.N.; Hong, S.H.; Seo, H.G.; Yoo, T.S.; Lee, K.N.; Kim, N.S.; Kim, C.H.; Kim, H.M. Inulin stimulates NO synthesis via activation of PKC-alpha and protein tyrosine kinase, resulting in the activation of NF-kappa B by IFN-gamma-primed RAW 264.7 cells. J. Nutr. Biochem. 2003, 14, 598–605. [Google Scholar] [CrossRef] [PubMed]
  54. Hayashi, K.; Umetsu, R.; Chijimatsu, T.; Hayashi, T.; Miyake, S.; Lee, J.B. Anti-influenza A virus effects of fructan from Welsh onion (Allium fistulosum L.). Food Chem. 2012, 134, 2164–2168. [Google Scholar]
  55. Guo, Y.; Guo, M.; Zhao, W.; Chen, K.; Zhang, P. Burdock fructooligosaccharide induces stomatal closure in Pisum sativum. Carbohydr. Polym. 2013, 97, 731–735. [Google Scholar] [CrossRef] [PubMed]
  56. Chandrashekar, P.M.; Prashanth, K.V.H.; Venkatesh, Y.P. Isolation, structural elucidation and immunomodulatory activity of fructans from aged garlic extract. Phytochemistry 2011, 72, 255–264. [Google Scholar] [CrossRef] [PubMed]
  57. Chandrashekara, P.M.; Venkatesh, Y.P. Immunostimulatory properties of fructans derived from raw garlic (Allium sativum L.). Bioact. Carbohydrates Diet. Fibre 2016, 8, 65–70. [Google Scholar] [CrossRef]
  58. Balasubramani, S.P.; Venkatasubramanian, P.; Kukkupuni, S.K.; Patwardhan, B. Plant-based Rasayana drugs from Ayurveda. Chin. J. Integr. Med. 2011, 17, 88–94. [Google Scholar] [CrossRef]
  59. Mishra, A.; Thakur, M.; Alok, S. Evaluation of immunomodulatory activity of polysacchride fraction of Inula racemosa, Bombax ceiba and Allium sativum. Int. J. Pharm. Sci. Res. 2016, 7, 3749–3755. [Google Scholar]
  60. Li, S.P.; Yu, Q.T.; Deng, Y.; Yan, Y.X.; Zhao, J.; Ge, Y.Z.; Wang, Y.; Wu, D.T.; Li, M. Comparison of immunomodulatory effects of fresh garlic and black garlic polysaccharides on RAW 264.7 macrophages. J. Food Sci. 2017, 82, 765–771. [Google Scholar] [CrossRef]
  61. Dong, C.X.; Zhang, L.J.; Xu, R.; Zhang, G.; Zhou, Y.B.; Han, X.Q.; Zhang, Y.; Sun, Y.X. Structural characterization and immunostimulating activity of a levan-type fructan from Curcuma kwangsiensis. Int. J. Biol. Macromol. 2015, 77, 99–104. [Google Scholar] [CrossRef]
  62. Kumar, V.P.; Prashanth, K.V.H.; Venkatesh, Y.P. Structural analyses and immunomodulatory properties of fructo-oligosaccharides from onion (Allium cepa). Carbohydr. Polym. 2015, 117, 115–122. [Google Scholar] [CrossRef]
  63. Corrêa-Ferreira, M.L.; Verdan, M.H.; dos Reis Lívero, F.A.; Galuppo, L.F.; Telles, J.E.Q.; Alves Stefanello, M.É.; Acco, A.; de Oliveira Petkowicz, C.L. Inulin-type fructan and infusion of Artemisia vulgaris protect the liver against carbon tetrachloride-induced liver injury. Phytomedicine 2017, 24, 68–76. [Google Scholar]
  64. Gutiérrez Nava, Z.J.; Jiménez-Aparicio, A.R.; Herrera-Ruiz, M.L.; Jiménez-Ferrer, E. Immunomodulatory effect of Agave tequilana evaluated on an autoimmunity like-SLE model induced in Balb/c mice with pristane. Molecules 2017, 22, 848. [Google Scholar]
  65. Paredes, L.L.R.; Smiderle, F.R.; Santana-Filho, A.P.; Kimura, A.; Iacomini, M.; Sassaki, G.L. Yacon fructans (Smallanthus sonchifolius) extraction, characterization and activation of macrophages to phagocyte yeast cells. Int. J. Biol. Macromol. 2018, 108, 1074–1081. [Google Scholar] [CrossRef]
  66. Stoyanova, S.; Geuns, J.; Hideg, E.; Van den Ende, W. The food additives inulin and stevioside counteract oxidative stress. Int. J. Food Sci. Nutr. 2011, 62, 207–214. [Google Scholar] [CrossRef]
  67. Keunen, E.; Peshev, D.; Vangronsveld, J.; Van den Ende, W.; Cuypers, A. Plant sugars are crucial players in the oxidative challenge during abiotic stress: Extending the traditional concept. Plant Cell Environ. 2013, 36, 1242–1255. [Google Scholar] [CrossRef]
  68. Peshev, D.; Vergauwen, R.; Moglia, A.; Hideg, E.; Van den Ende, W. Towards understanding vacuolar antioxidant mechanisms: A role for fructans? J. Exp. Bot. 2013, 64, 1025–1038. [Google Scholar] [CrossRef]
  69. Geronikaki, A.; Gavalas, A. Antioxidants and inflammatory disease: Synthetic and natural antioxidants with anti-inflammatory activity. Comb. Chem. High Throughput Screen. 2006, 9, 425–442. [Google Scholar] [CrossRef]
  70. Shang, H.M.; Zhou, H.Z.; Yang, J.Y.; Li, R.; Song, H.; Wu, H.X. In vitro and in vivo antioxidant activities of inulin. PLoS ONE 2018, 13, e0192273. [Google Scholar] [CrossRef]
  71. Petkova, N.T.; Ivanov, I.G.; Raeva, M.; Topuzova, M.G.; Todorova, M.M.; Denev, P.P. Fructans and antioxidants in leaves of culinary herbs from asteraceae and amaryllidaceae families. Food Res. 2019, 3, 407–415. [Google Scholar] [CrossRef]
  72. Zhang, Z.; Xiang, Y.; Mao, X.; Wang, K.; Hu, C.; Jia, Y.; Li, Q.; Tang, B.; Tong, Y.; Han, D. TLR2/TLR4 activation induces Tregs and suppresses intestinal inflammation caused by Fusobacterium nucleatum in vivo. PLoS ONE 2017, 12, e0186179. [Google Scholar]
  73. Amarante, M.K.; Ariza, C.B.; de Oliveira, C.E.C.; Gualtieri, K.A.; Oda, J.M.M.; Watanabe, M.A.E. Inulin induces IL-10 secretion and increased FOXP3 gene expression in human peripheral blood mononuclear cells. Braz. Arch. Biol. Technol. 2018, 61, e1816059. [Google Scholar] [CrossRef]
  74. Cario, E.; Gerken, G.; Podolsky, D.K. Toll-Like Receptor 2 controls mucosal inflammation by regulating epithelial barrier function. Gastroenterology 2007, 132, 1359–1374. [Google Scholar] [CrossRef]
  75. Suzuki, T. Regulation of intestinal epithelial permeability by tight junctions. Cell. Mol. Life Sci. 2013, 70, 631–659. [Google Scholar] [CrossRef]
  76. Fransen, F.; Sahasrabudhe, N.M.; Elderman, M.; Bosveld, M.; El Aidy, S.; Hugenholtz, F.; Borghuis, T.; Kousemaker, B.; Winkel, S.; van der Gaast-de Jongh, C.; et al. β2→1-fructans modulate the immune system in vivo in a microbiota-dependent and -independent fashion. Front. Immunol. 2017, 8, 154. [Google Scholar] [CrossRef]
  77. Peng, L.; Li, Z.; Green, R.S.; Holzman, I.R.; Lin, J. Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J. Nutr. 2009, 139, 1619–1625. [Google Scholar] [CrossRef]
  78. Kim, H.G.; Han, E.H.; Hwang, Y.P.; Choi, J.H.; Kwon, K.I.; Kim, B.H.; Kim, S.K.; Song, G.Y.; Jeong, H.G.; Hien, T.T.; et al. Metformin inhibits P-glycoprotein expression via the NF-κB pathway and CRE transcriptional activity through AMPK activation. Br. J. Pharmacol. 2011, 162, 1096–1108. [Google Scholar] [CrossRef]
  79. Xue, J.; Li, X.; Liu, P.; Li, K.; Sha, L.; Yang, X.; Zhu, L.; Wang, Z.; Dong, Y.; Zhang, L.; et al. Inulin and metformin ameliorate polycystic ovary syndrome via anti-inflammation and modulating gut microbiota in mice. Endocr. J. 2019. [Google Scholar] [CrossRef]
  80. Lee, W.H.; Kim, S.G. AMPK-Dependent Metabolic Regulation by PPAR Agonists. PPAR Res. 2010, 2010, 549101. [Google Scholar] [CrossRef]
  81. Tak, P.P.; Firestein, G.S. NF-κB: A key role in inflammatory diseases. J. Clin. Investig. 2001, 107, 7–11. [Google Scholar] [CrossRef]
  82. Peng, X.W.; Zhou, H.H.; Dai, J.; Zhang, L. Advances on the anti-inflammatory and protective effect of AMPK activators. Sheng Li Xue Bao 2019, 71, 319–326. [Google Scholar]
  83. Manayi, A.; Saeidnia, S.; Vazirian, M. Echinacea purpurea: Pharmacology, phytochemistry and analysis methods. Pharmacogn. Rev. 2015, 9, 63. [Google Scholar]
  84. Dogan, Z.; Ergul, B.; Sarikaya, M.; Filik, L.; Gonultaş, M.A.; Hucumenoglu, S.; Can, M. The protective effect of Echinacea spp. (Echinacea angustifolia and Echinacea purpurea) in a rat colitis model induced by acetic acid. Pak. J. Pharm. Sci. 2014, 27, 1827–1835. [Google Scholar]
  85. Sharma, M.; Schoop, R.; Hudson, J.B. Echinacea as an antiinflammatory agent: The influence of physiologically relevant parameters. Phyther. Res. 2009, 23, 863–867. [Google Scholar] [CrossRef]
  86. Sharma, S.M.; Anderson, M.; Schoop, S.R.; Hudson, J.B. Bactericidal and anti-inflammatory properties of a standardized Echinacea extract (Echinaforce®): Dual actions against respiratory bacteria. Phytomedicine 2010, 17, 563–568. [Google Scholar] [CrossRef]
  87. Gargari, B.P.; Dehghan, P.; Aliasgharzadeh, A.; Jafar-Abadi, M.A. Effects of high performance inulin supplementation on glycemic control and antioxidant status in women with type 2 diabetes. Diabetes Metab. J. 2013, 37, 140–148. [Google Scholar] [CrossRef]
  88. Mao, C.F.; Zhang, X.R.; Johnson, A.; He, J.L. Modulation of diabetes mellitus-induced male rat reproductive dysfunction with micro-nanoencapsulated Echinacea purpurea ethanol extract. Biomed. Res. Int. 2018, 2018, 4237354. [Google Scholar] [CrossRef]
  89. Chambers, E.S.; Byrne, C.S.; Morrison, D.J.; Murphy, K.G.; Preston, T.; Tedford, C.; Garcia-Perez, I.; Fountana, S.; Serrano-Contreras, J.I.; Holmes, E.; et al. Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: A randomised cross-over trial. Gut 2019, 68, 1430–1438. [Google Scholar]
  90. Schlernitzauer, A.; Oiry, C.; Hamad, R.; Galas, S.; Cortade, F.; Chabi, B.; Casas, F.; Pessemesse, L.; Fouret, G.; Feillet-Coudray, C.; et al. Chicoric acid is an anti-oxidant molecule stimulating AMP kinase pathway in L6 myotubes and extends lifespan in Caenorhabditis elegans. PLoS ONE 2013, 8, e78788. [Google Scholar]
  91. Zhu, D.; Zhang, N.; Zhou, X.; Zhang, M.; Liu, Z.; Liu, X. Cichoric acid regulates the hepatic glucose homeostasis via AMPK pathway and activates the antioxidant response in high glucose-induced hepatocyte injury. RSC Adv. 2017, 7, 1363–1375. [Google Scholar] [CrossRef] [Green Version]
  92. Phuwamongkolwiwat, P.; Suzuki, T.; Hira, T.; Hara, H. Fructooligosaccharide augments benefits of quercetin-3-O-b-glucoside on insulin sensitivity and plasma total cholesterol with promotion of flavonoid absorption in sucrose-fed rats. Eur. J. Nutr. 2013, 53, 457–468. [Google Scholar] [CrossRef]
  93. Dimitrova, M.P.; Petkova, N.T.; Denev, P.P.; Aleksieva, I.N. Carbohydrate composition and antioxidant activity of certain morus species. Int. J. Pharmacogn. Phytochem. Res. 2015, 7, 621–627. [Google Scholar]
  94. Petkova, N.; Vrancheva, R.; Mihaylova, D.; Ivanov, I.; Pavlov, A.; Denev, P. Antioxidant activity and fructan content in root extracts from elecampane (Inula helenium L.). J. Biosci. Biotechnol. 2015, 4, 101–107. [Google Scholar]
  95. Tomas, M.; Beekwilder, J.; Hall, R.D.; Diez Simon, C.; Sagdic, O.; Capanoglu, E. Effect of dietary fiber (inulin) addition on phenolics and in vitro bioaccessibility of tomato sauce. Food Res. Int. 2018, 106, 129–135. [Google Scholar] [CrossRef]
  96. Spelman, K.; Cech, N.B.; Iiams-Hauser, K.; Wenner, C.A.; Taylor, E.W.; Smirnoff, N. Role for PPARγ in IL-2 inhibition in T cells by Echinacea-derived undeca-2E-ene-8,10-diynoic acid isobutylamide. Int. Immunopharmacol. 2009, 9, 1260–1264. [Google Scholar] [CrossRef]
  97. Modaresi, M. Effect of Echinacea purpurea hydro alcoholic extract on the blood parameters in mice. Asian J. Chem. 2013, 25, 1373–1375. [Google Scholar]
  98. Miller, S.C. Can herbs be useful in cancer therapy? A review of studies on the influence of Echinacea on cells of the immune system and on tumor amelioration. Biomed. Res. India 2012, 23, 9–16. [Google Scholar]
  99. Gan, X.H.; Zhang, L.; Heber, D.; Bonavida, B. Mechanism of activation of human peripheral blood NK cells at the single cell level by Echinacea water soluble extracts: Recruitment of lymphocyte-target conjugates and killer cells and activation of programming for lysis. Int. Immunopharmacol. 2003, 3, 811–824. [Google Scholar] [CrossRef]
  100. Ritchie, M.R.; Gertsch, J.; Klein, P.; Schoop, R. Effects of Echinaforce (R) treatment on ex vivo-stimulated blood cells. Phytomedicine 2011, 18, 826–831. [Google Scholar] [CrossRef]
  101. Uluisik, D.; Keskin, E. Effects of Ginseng and Echinacea on cytokine mRNA expression in rats. Sci. World J. 2012, 2012, 6. [Google Scholar] [CrossRef]
  102. Fonseca, F.N.; Papanicolaou, G.; Lin, H.; Kennelly, E.; Cassileth, B.R.; Cunningham-Rundles, S. Echinacea Purpurea, L. modulates human t-cell cytokine response. Planta Medica 2012, 78, 1090. [Google Scholar] [CrossRef]
  103. Yu, D.Q.; Yuan, Y.; Jiang, L.; Tai, Y.L.; Yang, X.M.; Hu, F.; Xie, Z.W. Anti-inflammatory effects of essential oil in Echinacea purpurea L. Pak. J. Pharm. Sci. 2013, 26, 403–408. [Google Scholar]
  104. Benson, J.M.; Pokorny, A.J.; Rhule, A.; Wenner, C.A.; Kandhi, V.; Cech, N.B.; Shepherd, D.M. Echinacea purpurea extracts modulate murine dendritic cell fate and function. Food Chem. Toxicol. 2010, 48, 1170–1177. [Google Scholar] [CrossRef]
  105. Jiang, Q.D.; Nie, F.R.; Zhou, X.G.; Liu, T.Y.; Zhang, L.H.; Xiao, Z. The effect of EPS to LPS injure RAW264.7 cell NF-κB and MAPK signaling pathway. Genet. Mol. Res. 2017, 16. [Google Scholar] [CrossRef]
  106. Vimalanathan, S.; Schoop, R.; Suter, A.; Hudson, J. Prevention of influenza virus induced bacterial superinfection by standardized Echinacea purpurea, via regulation of surface receptor expression in human bronchial epithelial cells. Virus Res. 2017, 233, 51–59. [Google Scholar] [CrossRef]
  107. Stimpel, M.; Proksch, A.; Wagner, H.; Lohmann Matthes, M.L. Macrophage activation and induction of macrophage cytotoxicity by purified polysaccharide fractions from the plant Echinacea purpurea. Infect. Immun. 1984, 46, 845–849. [Google Scholar]
  108. Wagner, H.; Stuppner, H.; Schafer, W.; Zenk, M. Immunologically active polysaccharides of Echinacea purpurea cell cultures. Phytochemistry 1988, 27, 119–126. [Google Scholar] [CrossRef]
  109. Roesler, J.; Steinmuller, C.; Kindrelen, A.; Emmendorfer, A.; Wagner, H.; Lohmann Matthes, M.L. Application of purified polysaccharides from cell cultures of the plant Echinacea purpurea to mice mediates protection against systemic infections with Listeria monocytogenes and Candida albicans. Int. J. Immunopharmacol. 1991, 13, 27–37. [Google Scholar] [CrossRef]
  110. Melchart, D.; Clemm, C.; Weber, B.; Draczynski, T.; Worku, F.; Linde, K.; Weidenhammer, W.; Wagner, H.; Saller, R. Polysaccharides isolated from Echinacea purpurea herba cell cultures to counteract undesired effects of chemotherapy-a pilot study. Phytother. Res. 2002, 16, 138–142. [Google Scholar] [CrossRef]
  111. Luettig, B.; Steinmuller, C.; Wagner, H.; Steinmüller, C.; Gifford, G.E.; Lohmann Matthes, M.L. Macrophage activation by the polysaccharide arabinogalactan isolated from plant cell cultures of Echinacea purpurea. J. Nat. Canc. Inst. 1989, 81, 669–675. [Google Scholar] [CrossRef]
  112. Wack, M.; Blaschek, W. Determination of the structure and degree of polymerisation of fructans from Echinacea purpurea roots. Carbohydr. Res. 2006, 341, 1147–1153. [Google Scholar] [CrossRef]
  113. Dobrange, E.; Xonti, A.; Peshev, D.; Van den Ende, W.; Loedolff, B. Fructans and their potential role as paradoxical antioxidants in Echinacea products. F1000Research 2019, 8, 1650, (poster). [Google Scholar]
  114. Giger, E.; Keller, F.; Baumann, T.W. Fructans in Echinacea and in its phytotherapeutic preparations. Planta Med. 1989, 55, 638–639. [Google Scholar] [CrossRef]
  115. Babaeva, E.Y.; Zvereva, V.I.; Semkina, O.A. Inulin-like fructosan content in the below-ground organs of Echinacea purpurea and its processing products. Pharm. Chem. J. 2018, 52, 623–626. [Google Scholar] [CrossRef]
  116. Hershberg, R.M.; Mayer, L.F. Antigen processing and presentation by intestinal epithelial cells-polarity and complexity. Immunol. Today 2000, 21, 123–128. [Google Scholar] [CrossRef]
  117. Cario, E.; Brown, D.; McKee, M.; Lynch-Devaney, K.; Gerken, G.; Podolsky, D.K. Commensal-associated molecular patterns induce selective toll-like receptor-trafficking from apical membrane to cytoplasmic compartments in polarized intestinal epithelium. Am. J. Pathol. 2002, 160, 165–173. [Google Scholar] [CrossRef]
  118. Forchielli, M.L.; Walker, W.A. The role of gut-associated lymphoid tissues and mucosal defence. Br. J. Nutr. 2006, 93, S41–S48. [Google Scholar] [CrossRef]
  119. Cummings, J.H.; Christie, S.; Cole, T.J. A study of fructo- oligosaccharides in the prevention of travellers’ diarrhoea. Aliment. Pharmacol. Ther. 2001, 15, 1139–1145. [Google Scholar] [CrossRef]
  120. Lewis, S.; Burmeister, S.; Brazier, J. Effect of the prebiotic oligofructose on relapse of Clostridium difficile-associated diarrhea: A randomized, controlled study. Clin. Gastroenterol. Hepatol. 2005, 3, 442–448. [Google Scholar] [CrossRef]
  121. Welters, C.F.M.; Heineman, E.; Thunnissen, F.; van den Bogaard, A.; Soeters, P.B.; Baeten, C. Effect of dietary inulin supplementation on inflammation of pouch mucosa in patients with an heal pouch-anal anastomosis. Dis. Colon Rectum 2002, 45, 621–627. [Google Scholar] [CrossRef]

Share and Cite

MDPI and ACS Style

Dobrange, E.; Peshev, D.; Loedolff, B.; Van den Ende, W. Fructans as Immunomodulatory and Antiviral Agents: The Case of Echinacea. Biomolecules 2019, 9, 615.

AMA Style

Dobrange E, Peshev D, Loedolff B, Van den Ende W. Fructans as Immunomodulatory and Antiviral Agents: The Case of Echinacea. Biomolecules. 2019; 9(10):615.

Chicago/Turabian Style

Dobrange, Erin, Darin Peshev, Bianke Loedolff, and Wim Van den Ende. 2019. "Fructans as Immunomodulatory and Antiviral Agents: The Case of Echinacea" Biomolecules 9, no. 10: 615.

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop