|Year : 2016 | Volume
| Issue : 2 | Page : 55-62
Modulation of dendritic cell immune functions by plant components
Alia M Aldahlawi
Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University, Jeddah, ; Immunology Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
|Date of Web Publication||6-Feb-2018|
Alia M Aldahlawi
Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University, Jeddah; Immunology Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah
Source of Support: None, Conflict of Interest: None
Dendritic cells (DCs) are the key linkage between innate and adoptive immune response. DCs are classified as specialized antigen-presenting cells that initiate T-cell immune responses during infection and hypersensitivity, and maintain immune tolerance to self-antigens. Initiating T-cell immune responses may be beneficial in infectious diseases or cancer management, while, immunosuppressant or tolerogenic responses could be useful in controlling autoimmunity, allergy or inflammatory diseases. Several types of plant-derived components show promising properties in influencing DC functions. Various types of these components have been proven useful in clinical application and immune-based therapy. Therefore, focusing on the benefits of plant-based medicine regulating DC functions may be useful, low-cost, and accessible strategies for human health. This review illustrates recent studies, investigating the role of plant components in manipulating DC phenotype and function towards immunostimulating or immunosuppressing effects either in vitro or in vivo.
Dendritic cells, Herbal medicine, Immunostimulation, Immunosuppression, Plant extract
|How to cite this article:|
Aldahlawi AM. Modulation of dendritic cell immune functions by plant components. J Microsc Ultrastruct 2016;4:55-62
|How to cite this URL:|
Aldahlawi AM. Modulation of dendritic cell immune functions by plant components. J Microsc Ultrastruct [serial online] 2016 [cited 2019 Mar 20];4:55-62. Available from: http://www.jmau.org/text.asp?2016/4/2/55/224851
| 1. Introduction|| |
Dendritic cells (DCs) are professional antigen-presenting cells that provide a link between the innate and the adaptive immune responses. DCs stimulate adaptive immune response by activating T lymphocytes, inducing an effector response or tolerance depending on the DC differentiation level. In addition, DCs play a crucial role in immunosuppression and maintain tolerance against self-antigens. Therefore, DCs have become a key target for research activities focused on manipulating DCs to obtain novel biological modifiers that can be used for the treatment or management of different infectious and immune-related diseases. Herbal plants offer a wide range of medicinal components that have proved beneficial in treating different diseases worldwide.
Several plant-derived components may have immunostimulatory, immunosuppressive, and/or anti-inflammatory activities depending on the plant type and extraction method. Most of these therapeutic plants may be effective in modulating DC activities and considered as an alternative tool for treatment. Therefore, I present the findings of recent studies investigating the role of plant components in manipulating DC functions either in vitro or in vivo.
| 2. Modulation of DC activities|| |
DCs are a heterogeneous population of immune cells, comprising different subsets that can be distinguished by their phenotypic and functional properties. Functional properties include the ability to upregulate specific maturation markers and the capacity to stimulate naïve T cells. The maturation status of DCs may be responsible for either induction of immunity or tolerance. The process of DC maturation is highly regulated and results in conversion of immature DCs in the periphery into fully competent antigen-presenting cells. During conversion, DCs undergo a number of phenotypical and morphological changes (e.g., formation of dendrites; [Figure 1]). In addition, there are reallocation of major histocompatibility complex (MHC) molecules from intracellular endocytic compartments to the DC surface; downregulation of antigen internalization; an increase in the surface expression of co-stimulatory molecules; cytoskeletal reorganization; secretion of chemokines, cytokines, and proteases; and surface expression of adhesion molecules and chemokine receptors ,. This process can be induced by a variety of infectious agents, cytokines, and natural products. Several researchers have studied the impact of various natural product extracts during the recent years.
|Figure 1: (A) Morphology of immature DCs generated from peripheral blood monocytes cultured in RPMI-1640 medium supplemented with granulocyte-macrophage colony-stimulating factor and interleukin-4 for 7 days. (B) Immature DCs stimulated with 1 μg/mL lipopolysaccharide for 24 hours showed long cytoplasmic veils typical for mature DCs. Cells were photographed using a digital camera assembled on a bright field inverted microscope. Original magnification was 40×. (Unpublished data, Immunology Unit, King Fahad Medical Research Center, KAU, Jeddah, Saudi Arabia.). DC = dendritic cell.|
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2.1. Plant components modulating DC differentiation and maturation
Different types of plants and plant components were shown to induce DC differentiation either in vitro or in vivo including pinecone extract , the traditional Japanese herbal plants kampo and Hochu-ekki-to (HOT) , and the water soluble extract of fern Polypodium leucotomos named Anapsos . Anapsos especially was found to enhance production of interleukin (IL)-1α, IL-1β, and tumor necrosis factor α proposing a stimulation of monocytes and DCs in vitro. In addition, Astragalus mongholicus polysaccharide isolated from one of the Chinese herbs was found to enhance the co-expression of CD-11c and MHC class II molecules on murine bone marrow (BM)-derived DC (BMDC) surfaces, reduce fluorescein isothiocyanate-dextran uptake, and produce a higher level of IL-12 than untreated DCs, suggesting that it modulates DC maturation .
Moreover, some plant components were reported to induce both the differentiation and maturation of DCs in vitro, such as lupane acetate of cortex periplocae , the aqueous and organic fractions from Petiveria alliacea , acidic polysaccharide isolated from ginseng (Panax ginseng Meyer) , and Lycium bararum polysaccharide (LBP) extracts . One interesting study on LBP demonstrated its ability to induce phenotypic and functional maturation of DCs . The therapeutic effects of LBPs were related to their ability to induce DC maturation through Toll-like receptor (TLR)2- and/or TLR4-mediated nuclear factor(NF)-κB signaling pathways . Likewise, Achyranthes bidentata, a traditional Chinese medicine also provides phenotypic and functional maturation of murine DCs, suggesting that it may be used to boost immune responses . Similarly, the polysaccharide obtained from a Chinese medicinal herb, Zhu Ling [the sclerotium of Polyporus umbellatus (Per) Fr], was found to induce the activation and maturation of murine BMDCs through TLR4 .
Some plant extracts were found to interfere with DC differentiation and maturation, as shown by the exposure of monocytes to areca nut extracts. These extracts did not effect the expression of HLA-DR and CD11c, but markedly decreased the proportion of CD40-positive cells, expression of CD86, and IL-12 production. Curcumin was found to induce an immunosuppressant effect on DCs and prevent response to lipopolysaccharide (LPS) by blocking of maturation markers, cytokines, chemokine expression, and endocytosis . Moreover, fisetin, a flavonoid commonly present in fruits and vegetables, in addition to TongXinLuo, Semen cuscutae, and Acanthopanax koreanum, a traditional Chinese medicine, impair functional maturation of DCs ,,,. Acetylcorynoline component derived from Cory dalis bungeana herbs was also reported to work as a potent immunosuppressive agent through its ability to alter of DC maturation and function .
2.2. Activities of stimulated DCs
2.2.1. Activation of T cells
The ability of matured DCs to activate T-cell responses was studied by various research groups that found that some plant components lead to the stimulation and upregulation of several chemokine and cytokine genes . A mixture extracted from the butanol fraction of a stem and leaf extract of Echinacea purpurea had a significant influence on mouse BMDC phenotype and maturation. These effects coincide with induction of metabolism, cytoskeleton-, or NF-κB signaling-related proteins. Flow cytometric analysis showed that the polysaccharide-rich root extract increased the expression of MHC class II, CD86, and CD54 surface markers, whereas the alkylamide-rich leaf extract inhibited the expression of these molecules. Moreover, the leaf but not root extract inhibited the antigen-specific activation of naive CD4+ T cells ,. The effect of Plantago asiatica L. (ES-PL) seeds, a traditional Chinese medicine, was found to increase levels of MHC class II molecules and major co-stimulatory molecules on DCs, suggesting it may enhance antigen presenting abilities to primed T lymphocytes indicating functional maturation of DCs . BRC-301 (a polyherbal extract), BRC-304 (a mixture of vitamins, minerals, antioxidant enzymes, botanical extracts, and carotenoids), and BRC-306 [a trademarked blend of Uncaria tomentosa (cat’s claw) and Phytolens] were found to affect the innate responsiveness of murine DCs and enhance their ability to stimulate T-cell-mediated immunity .
2.2.2. Activation of B cells
Fermented Noni Exudate, a traditional medicine, activates DCs to stimulate B-cell differentiation and immunoglobulin class switching .
2.2.3. Induction of cytokine secretion
An in vitro study of okra (Abelmoschus esculentus L.) extract on DCs derived from rat bone marrow hematopoietic cells (BMHCs) showed that A. esculentus L. polysaccharides displays DC stimulatory effects demonstrated by upregulation of the MHC class II and CD80/86 expression, reduced endocytosis activity, and increased levels of T helper (Th)1 cytokines IL-12 and interferon (IFN)-γ . Further study on a Chinese tonifying herb, named Cordyceps sinensis showed activation of DCs toward a Th1-type immunity, whereas in a potential inflammatory reaction, it reduced the over-reactivity of stimulated Th1 immunity and shifted activation toward a Th2 response .
A variety of the Japanese soybean, Glycine max cv. Kurosengoku (Kurosengoku) extracts trigger the production of IL-12 from DCs mediated by TLR4 and TLR2 and sequentially induced IFN-γ production . Triterpene esters, uncarinic acid C (1) and uncarinic acid D (2) obtained from the hooks of Uncaria rhynchophylla were found to activate cytokine production of human DCs towards Th1 . Also, purified galactomannan from Caesalpinia spinosa induced phenotypic maturation in monocyte-derived DCs (MDDCs) revealed by increased expression of maturation markers, reduced antigen uptake, and increased protein and mRNA levels of proinflammatory cytokines .
2.3. Activities of immunosuppressant DCs
It was found that modulating DCs by natural plant products that inhibit DC maturation might alter immune-mediated inflammatory reactions in vivo and induce immunoregulatory responses, suggesting that it can be used as a valuable strategy to prevent inflammation associated with inflammatory diseases.
2.3.1. Inhibition of T-cell activation
Several lines of evidence support the immunosuppressive properties of resveratrol, a natural polyphenol present in grapes and grape products such as wine, which inhibited expression of co-stimulatory molecules (CD80 and CD86), suppressed the capacity of BMDCs to produce intracellular IL-12 p40/p70 and IL-12 p70, increased antigen capturing and endocytosis, and reduced stimulation of naive allogeneic T-cell proliferation. These data indicated therapeutic use of resveratrol for chronic immune and/or inflammatory diseases .
Recently, Gold Lotion, a formulated product prepared from the peels of six citrus fruits, displayed immunomodulatory effect on LPS-stimulated mouse BMDC maturation and function by significantly decreasing production of proinflammatory cytokines and chemokines, inhibiting expression of maturation markers, increasing phagocytic ability, and reducing the propensity to stimulate autologous CD4+ and CD8+ T-cell proliferation . Ziziphora tenuior L. (Kakuti in Persian) a traditional medicine for treatment of gastrointestinal disorders was found to stimulate CD40 expression on DCs and cytokine production at low concentrations; however, it can prevent T-cell stimulation of DCs at high concentrations . Likewise, extract of Chrysanthemum coronarium L. induces DC maturation and production of IL-12 . Triptolide isolated from Chinese herbal medicine demonstrated T-cell suppression and inhibition of DC maturation . The hydroethanolic extraction of turmeric was also found to reduce the activation of human DCs in response to inflammatory cytokines, and to inhibit DC ability to stimulate the mixed lymphocyte reaction . Similarly, ethanolic root extract of Cichorium intybus, a traditional medicine, was found to inhibit T-cell proliferation, while low concentrations can modulate cytokine secretion toward a Th1 pattern as shown by increased production of IFN-γ .
2.3.2. Modulation of cytokine secretion
Arctium lappa fruit extract was found to inhibit IL-6 and TNF-α concentration generated by DCs . A recent study documented the effect of Saucerneol D, a lignan constituent of Saururus chinensis plant, on BMDCs, which decreased expression of maturation proteins (MHC I/II, CD40, CD80, and CD86), inflammatory mediators (NO, IL-12, IL-1|3, and TNF-α), and inhibition of allogenic T-cell activation . Birch bark extracts from Betula pubescens ethanolic extract lower DC production of IL-6, IL-10, and IL-12p40 and expression of CD83, CD86, chemokine CC receptor 7, and Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN) in contrast to control DCs . Likewise, aqueous extract from Achillea millefolium reduces the ability of DCs to induce a Th17 response . Luteolin, a flavonoid found in various herbal extracts, was found to block LPS-induced NF-κB signaling and proinflammatory gene expression in intestinal epithelial cells and DCs . Panax notoginseng extract, a traditional Chinese herbal medicine, was also found to inhibit TLR-activated DCs, leading to inhibition of the production of inflammatory cytokines and innate immune responsiveness . Additionally, the effects of apple polyphenol extract and procyanidin induced downregulation of HLA-DR (MHC class II), suggesting immunomodulatory properties . Furthermore, several active compounds isolated from leaves and stems of plant such as Desmodium caudatum, Astragalus membranaceus, Cassia alata, Eleusine indica, Carica papaya, Eremomastax speciosa, and Polyscias fulva showed inhibitory effects on LPS-induced inflammatory cytokines from DCs, suggesting their anti-inflammatory potential ,.
2.3.3. Induction of regulatory DCs
Treatment with cinnamon extract inhibited maturation of DCs and stimulated regulatory DCs, and expressed high levels of immunoregulatory cytokines IL-10 . Ethyl acetate extract from Urtica dentate showed anti-allograft rejection by enhancing regulatory T-cell differentiation, inhibition of Th1 cytokines and increased Th2 cytokines, suggesting it is beneficial in autoimmune disease treatment .
2.4. Clinical applications of DCs
2.4.1. Cancer treatment
DCs display a key role during the initiation of specific immune responses required for anticancer immunity. DC functions are often altered in cancer patients; therefore, immunomodulation of DC function is suggested as a key event in cancer prevention and treatment. Consequently, several studies have been performed to investigate the role of plant products or extracts on the behavior of DCs toward cancer cells .
18.104.22.168. Human trial studies. Li etal  showed that injecting Shenqi Fuzheng Chinese herbal medication during chemotherapy of breast cancer patients induced DC activation. Likewise, combined treatment of Chinese herbal medicine, Lingdankang Composite and DC-cytokine-induced killer cells, was effective in clearing molecular biological remission in leukemia patients . Tolerogenic DCs, which may be involved in induction of regulatory T cells was found to be reduced by Neem leaf glycoprotein in cervical cancer stage IIIB (CaCx-IIIB) patients . Chinese herb Ganoderma lucidum showed immunomodulatory effects mediated by DCs . Further studies also indicated that Astragulus membranes induced DC maturation in vitro and enhanced antigen presentation in children with acute leukemia. In addition, DCs exposed to Amomi Semen extract exhibited activated phenotypes, secreted IL-12p70, and inhibited the growth of tumor cells . Recently, effective stimulation of intercellular adhesion molecule 1 expression in primary DCs was also achieved by the glycolipid mixture containing β-glucosylceramides purified from Juzen-taiho-to herb that used in East Asia for cancer patients .
22.214.171.124. In vitro studies. Fermented mistletoe extract significantly enhanced maturation of immature DCs, as showed by upregulation of CD83, CD80 and CD86, as well as HLA class I and II molecules on these cells . Likewise, different molecular weight fractions of pine cones (termed poly-phenylpropanoid polysaccharide complex) extract were introduced to murine BMDCs and human monocyte U937 cells, resulting in enhanced maturation of murine DCs and inhibiting growth of human cancer cell lines, indicating the efficacy of this extract in cancer treatment . Mucuna (Mucuna pruviens var. utilis) biologically active component was found to induce DC differentiation and maturation as well as apoptosis in human cancer cell lines . Similarly, heat-stable extract from azuki bean (Vigna angula) encouraged differentiation of immature DCs and suppressed the growth of human leukemia U937 cells, through induction of apoptosis . Ocimum basilicum polysaccharide extract (basil polysaccharide) and curcumin regulated invasion of ovarian cancer cells and human monocyte-derived DCs by markedly downregulating osteopontin, CD44 and matrix metalloproteinase-9 expression .
In vivo studies. Numerous studies were performed on animal models to emphasize the effect of different plant products on DCs toward tumor suppression. Astragulus injection modulated action of DCs and resulted in inhibition of tumor metastasis in mice with metastatic lung cancer . Another study using H22-bearing mice indicated a significant decrease in DCs in the tumor microenvironment, while treatment with LBP increased the number of DCs associated with enhanced anti-tumor function of the immune system . Furthermore, an alcoholic extract of Tinospora cordifolia boosts the differentiation of tumor-associated macrophages to DCs in response to granulocyte-macrophage colony-stimulating factor, IL-4, and TNF, and led to enhanced tumor cytotoxicity and production of tumoricidal soluble molecules and increased survival of tumor-bearing mice . The extract of Larix leptolepis, one of the most common woods in Hokkaido, Japan, strongly activated type 1 immunity and significantly inhibited the growth of tumor in a mouse model . Green plant DNA is a natural source of CpG DNA, and may provide the ability to activate DCs and inhibit tumor growth in tumor-bearing mice by stimulating secretion of IL-12, and enhances expression of MHC and co-stimulatory molecules by BMDCs . Moreover, grape seed proanthocyanidins might lower UV-induced immunosuppression throughout DNA-repair-dependent functional activation of DCs in mice . Polysaccharide fractions obtained from the root of Astragalus membranaceus and Codonopsis pilosulae and Ficus carica polysaccharides displayed enhanced efficiency of DC-based cancer vaccine ,. In a mouse model, CM-Glucan (carboxymethylated Beta-(1, 3) (1, 6) glucan); trade name Immunomax®; injections significantly prolonged total survival and cured 31% of mice, which wasassociated with activation of DCs via TLR-4 and stimulation of natural killer cells .
2.4.2. Treatment of infectious diseases
Many plant materials enhance the ability of the immune system to fight infection. Although microbial agents have different effects in stimulating the immune system, the availability of plant or herbal extracts that enhance the immune response against infectious agents has increased dramatically. This may be crucial to introduce and provide an alternative and inexpensive medication.
126.96.36.199. Viral infections. Ginseng extract (CVT-E002) reduces symptoms of viral infection in clinical trials mediated by DC modulation and increased T-cell activation . Moreover, Astragalus polysaccharides enhance the immune response and have been used as an adjuvant for hepatitis B virus DNA vaccine by stimulating DC maturation and reducing the amount of the regulatory T cells . Additionally, the traditional Chinese medicines Bushen Jiedu Recipe and Jianpi Jiedu Recipe, were demonstrated to stimulate the recovery of DC function in patients with chronic hepatitis B virus infection . A combination of herbal extracts comprising Tanacetum vulgare (tansy), Rosa canina and Urtica dioica (nettle) in addition to selenium, flavonoids, and carotenes known as Setarud, was found to inhibit maturation of myeloid DCs and significantly increase CD4 count, and therefore, used for the treatment of HIV infection . Three Guatemalan plant extracts from Justicia reptans, Neurolaena lobata, and Pouteria viridis were found to inhibit HIV replication, by preventing transmission of virus from DCs to lymphocytes . Total extract of Korean Red Ginseng and its constituents were found to affect influenza A virus infection by induction of TNF-α/inducible nitric oxide synthase-producing DCs in mouse lungs . Additionally, treatment of human respiratory epithelial cells (16HBE) infected by influenza virus H1N1 with Patchouli alcohol extract induces antiviral effects by inhibition of cytokines released by immune cells including DCs in vitro .
188.8.131.52. Bacterial infections. Dietary rice bran was found to increase myeloid DCs in the lamina propria and mesenteric lymph nodes, suggesting promising influence on the modulation of mucosal immunity for protection against enteric infections .Astragalus root and elderberry fruit extracts induced IFN-β production, slightly reduced the prionflammatory response to Escherichia More Details coli, and improved endocytosis in immature DCs. Therefore, both extracts may be beneficial in microbial activity .
184.108.40.206. Parasitic infections. In leishmaniasis, the interactions between the parasites and DCs are complex and involve conflicting processes leading to control or progress of the infection. Alkaloid extract of Evanta or the purified alkaloid 2-phenilquinoline decreased DC secretion of IL-12p40 and levels of IFN-γ and IL-10 secreted by T cells co-cultured with these DCs, which may contribute to the regulatory effects toward inflammation . P. ginseng was also found to affect cutaneous leishmaniasis caused by Leishmania mexicana in vitro by induction of Th1 cytokine IL-12 by DCs .
2.4.3. Treatment of allergy
Allergy affects many people and is a major cause of hospitalization for anaphylactic reactions worldwide. DCs play an important role in the establishment of allergy leading to Th2-mediated responses. Plant and herbal extracts may play an essential role in modulating DC function and activation of T-cell responses. In a murine model of asthma, Shikonin exhibits dose-dependent inhibition of BMDC maturation in vitro and inhibits allergic inflammation and airway hyper-responsiveness . It is reported that treatment of children with asthma with traditional Chinese medicine Wuhu Decoction suppresses several DC markers. This suggests an effective medication for children with asthma that may be related to its ability to regulate the co-stimulatory molecules of DCs . Protein-free oat plantlet extract displays anti-inflammatory and immunoregulatory activities in vitro, which are demonstrated by their effect on the phenotype and function of DCs differentiated from monocytes. This extract decreased DC expression of MHC class II molecules and significantly weakened their stimulatory activity on autologous T cells. Protein-free extract may be useful to avoid developing sensitization to dietary proteins in atopic patients .
2.4.4. Treatment of inflammatory and autoimmune diseases
Several lines of research have demonstrated the ability of some plant/herb products or extracts to suppress DC response, maturation and cytokine secretions either in vitro or in vivo. Water extract of Malian medicinal plant Biophytum petersianum Klotzsch (Oxalidaceae) was found to induce activation of DCs, while there was slight response on T cells, B cells, and natural killer cells, suggesting the valuable use of the plant in the treatment of several types of immune diseases . Additionally, water extract of Zataria multiflora and Thymus vulgaris (thyme) plants showed immunomodulatory effects on allogenic T-cell proliferation and activated DCs . An active compound extracted from peony root has been used to treat rheumatoid arthritis by suppressing DC maturation, activation and differentiation of Th1 cells . Similarly, MCS-18, a natural product obtained from Helleborus purpurascens, has been shown to inhibit the expression of important murine BMDC-specific molecules and lead to impaired T-cell stimulation and reduced B-cell proliferation and immunoglobulin production, which may suggest its use in inflammatory and autoimmune disorders . Also, the extract of the stinging nettle leaf IDS 30 (Hox alpha) was shown to prevent DC maturation and cytokine secretion, whereas it increased endocytosis of DCs to dextran, without stimulating T cells, suggesting it as a possible treatment in rheumatoid arthritis . Similarly, Cymbopogon citratus (lemongrass), either dried leaves or its fractions, significantly inhibited the LPS-induced NO production and inducible NO synthase expression by DCs, suggesting its beneficial role in the treatment of inflammatory diseases . The effect of 18-β-glycyrrhetinic acid, the main bioactive component of licorice root extracts showed anti-inflammatory effects mediated by DC on Propionibacterium acnes-induced acute inflammatory liver injury . Treatment of experimental colitis rats in vivo with Qingchang Huashi Recipe showed significant suppression effects of DC infiltration and activation . Also, total glucosides of peony extracted from the roots of Paeonia lactiflora inhibit DC maturation and function, which reduces immune-mediated inflammation in vivo . Additionally, Wedelia chinensis, a medicinal herb commonly used in Asia, showed anti-colitis effects in mice by suppressing Th1, Th17, and DC responses in colon tissues . Moreover, stem bark of Kalopanax pictus (Araliaceae) extract are beneficial in the treatment of various inflammatory diseases through their ability to suppress DC inflammatory cytokines such as IL-12 p40 and IL-6 . Finally, Panax quinquefolium saponins (American ginseng), Dan-hong (extracted from Radix Salviae miltiorrhizae and Flos Carthami tinctorii), were found to suppress atherosclerotic effects mediated by DC maturation inhibition ,.
| 3. Conclusion|| |
The immune response can be either stimulated or suppressed in favor of human health. DCs are crucial cells of the immune system that are adapted to perform these mechanisms. Plants and plant products and their purified components have become an area of research interest. Further studies are required to explore the benefit of these products to be used as tools for immunomodulation required for disease prevention and therapy with minimal side effects at lowest cost.
Conflict of interest
I wish to confirm that there are no known conflicts of interest associated with this publication.
| References|| |
Steinman RM, Idoyaga J. features of the dendritic cell lineage. Immunol Rev 2010;234:5-17.
Collin M, McGovern N, Haniffa M. Human dendritic cell subsets. Immunology 2013;140:22-30.
Bradley WG, Widen RH, Weiser AM, Powers JJ, Fountain LB, Punjwani P, et al. The novel differentiation of human blood mononuclear cells into CD1a-negative dendritic cells is stimulated in the absence of exogenous cytokines by an extract prepared from pinecones. Int Immunopharmacol 2003;3:209-23.
Nabeshima S, Murata M, Hamada M, Chong Y, Yamaji K, Hayashi J. Maturation of monocyte-derived dendritic cells by Hochu-ekkito, a traditional Japanese herbal medicine. Int Immunopharmacol 2004;4:37-45.
Bernd A, Ramirez-Bosca A, Huber H, Diaz Alperi J, Thaci D, Sewell A, et al. In vitro
studies on the immunomodulating effects of polypodium leucotomos extract on human leukocyte fractions. Arzneimittelforschung 1995;45:901-4.
Shao P, Zhao LH, Zhi C, Pan JP. Regulation on maturation and function of dendritic cells by Astragalus mongholicus
polysaccharides. Int Immunopharmacol 2006;6:1161-6.
Zhang J, Shan BE, Zhang C, Zhao RN, Li QL, Liu JH, et al. The effect on the differentiation and maturation of dendritic cells by lupane acetate of cortex periplocae. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2006;22:26-8, 32.
Santander SP, Hernandez JF, Barreto CC, Masayuki A, Moins-Teisserenc H, Fiorentino S. Immunomodulatory effects of aqueous and organic fractions from Petiveria alliacea
on human dendritic cells. Am J Chin Med 2012;40:833-44.
Wang Z, Meng J, Xia Y, Meng Y, Du L, Zhang Z, et al. Maturation of murine bone marrow dendritic cells induced by acidic Ginseng polysaccharides. Int J Biol Macromol 2013;53:93–100.
Zhu J, Zhao LH, Chen Z. Stimulation by Lycium bararum
polysaccharides of the maturation of dendritic cells in murine bone marrow. Zhejiang Da Xue Xue Bao Yi Xue Ban 2006;35:648-52.
Chen Z, Lu J, Srinivasan N, Tan BK, Chan SH. Polysaccharide-protein complex from Lycium barbarum
L. is a novel stimulus of dendritic cell immunogenicity. J Immunol 2009;182:3503–9.
Zhu J, Zhang Y, Shen Y, Zhou H, Yu X. Lycium barbarum
polysaccharides induce Toll-like receptor 2-and 4-mediated phenotypic and functional maturation of murine dendritic cells via activation of NF-kappaB. Mol Med Rep 2013;8:1216–20.
Zou Y, Meng J, Chen W, Liu J, Li X, Li W, et al. Modulation of phenotypic and functional maturation of murine dendritic cells (DCs) by purified Achyranthes bidentata
polysaccharide (ABP). Int Immunopharmacol 2011;11:1103–8.
Li X, Xu W, Chen J. Polysaccharide purified from Polyporus umbellatus
(Per) Fr induces the activation and maturation of murine bone-derived dendritic cells via toll-like receptor 4. Cell Immunol 2010;265:50–6.
Shirley SA, Montpetit AJ, Lockey RF, Mohapatra SS. Curcumin prevents human dendritic cell response to immune stimulants. Biochem Biophys Res Commun 2008;374:431–6.
Nhiem NX, Kiem PV, Minh CV, Tai BH, Quang TH, Soung KS, et al. Anti-inflammatory activity on LPS-stimulated dendritic cells of lupanetype triterpenoids from the leaves of Acanthopanax koreanum
. Arch Pharm Res 2011;34:1593–8.
Lin MK, Yu YL, Chen KC, Chang WT, Lee MS, Yang MJ, et al. Kaempferol from Semen cuscutae
attenuates the immune function of dendritic cells. Immunobiology 2011;216:1103–9.
Su W, Sun A, Xu D, Zhang H, Yang L, Yuan L, et al. Tongxinluo inhibits oxidized low-density lipoprotein-induced maturation of human dendritic cells via activating peroxisome proliferator-activated receptor gamma pathway. J Cardiovasc Pharmacol 2010;56: 177–83.
Liu SH, Lin CH, Hung SK, Chou JH, Chi CW, Fu SL. Fisetin inhibits lipopolysaccharide-induced macrophage activation and dendritic cell maturation. J Agric Food Chem 2010;58:10831–9.
Fu RH, Wang YC, Liu SP, Chu CL, Tsai RT, Ho YC, et al. Acetylcorynoline impairs the maturation of mouse bone marrow-derived dendritic cells via suppression of IkappaB kinase and mitogen-activated protein kinase activities. PLoS ONE 2013;8:e58398.
Shainheit MG, Smith PM, Bazzone LE, Wang AC, Rutitzky LI, Stadecker MJ. Dendritic cell IL-23 and IL-1 production in response to schistosome eggs induces Th17 cells in a mouse strain prone to severe immunopathology. J Immunol 2008;181:8559–67.
Benson JM, Pokorny AJ, Rhule A, Wenner CA, Kandhi V, Cech NB, et al. Echinacea purpurea
extracts modulate murine dendritic cell fate and function. Food Chem Toxicol 2010;48:1170-7.
Yin SY, Wang WH, Wang BX, Aravindaram K, Hwang PI, Wu HM, et al. Stimulatory effect of Echinacea purpurea
extract on the trafficking activity of mouse dendritic cells: revealed by genomic and proteomic analyses. BMC Genomics 2010;11:612.
Huang DF, Tang YF, Nie SP, Wan Y, Xie MY, Xie XM. Effect of phenylethanoid glycosides and polysaccharides from the seed of Plantago asiatica
L. on the maturation of murine bone marrow-derived dendritic cells. Eur J Pharmacol 2009;620:105–11.
Miller AK, Benson JM, Muanza DN, Smith JR, Shepherd DM. Anti-inflammatory effects of natural product formulations on murine dendritic cells. J Diet Suppl 2011;8:19–33.
Zhang X, Li J, Wong DK, Wagner TE, Wei Y. Fermented Noni Exudate-treated dendritic cells directly stimulate B lymphocyte proliferation and differentiation. Oncol Rep 2009;21:1147–52.
Sheu SC, Lai MH. Composition analysis and immuno-modulatory effect of okra (Abelmoschus esculentus
L.) extract. Food Chem 2012;134:1906–11.
Li CY, Chiang CS Tsai ML, Hseu RS, Shu WY, Chuang CY, et al. Two-sided effect of Cordyceps sinensis
on dendritic cells in different physiological stages. J Leukoc Biol 2009;85:987–95.
Tanaka S, Koizumi S, Makiuchi N, Aoyagi Y, Quivy E, Mitamura R, et al. The extract of Japanese soybean, Kurosengoku activates the production of IL-12 and IFN-gamma by DC or NK1.1(+) cells in a TLR4-and TLR2-dependent manner. Cell Immunol 2011;266:135–42.
Umeyama A, Yahisa Y, Okada M, Okayama E, Uda A, Shoji N, et al. Triterpene esters from Uncaria rhynchophylla
drive potent IL-12-dependent Th1 polarization. J Nat Med 2010;64:506–9.
Santander SP, Aoki M, Hernandez JF, Pombo M, Moins-Teisserenc H, Mooney N, et al. Galactomannan from Caesalpinia spinosa
induces phenotypic and functional maturation of human dendritic cells. Int Immunopharmacol 2011;11:652–60.
Kim GY, Cho H, Ahn SC, Oh YH, Lee CM, Park YM. Resveratrol inhibits phenotypic and functional maturation of murine bone marrow-derived dendritic cells. Int Immunopharmacol 2004;4:245-53.
Li S, Lin YC, Ho CT, Lin PY, Suzawa M, Wang HC, et al. Formulated extract from multiple citrus peels impairs dendritic cell functions and attenuates allergic contact hypersensitivity. Int Immunopharmacol 2014;20:12-23.
Azadmehr A, Latifi R, Mosalla S, Hajiaghaee R, Shahnazi M. Immunomodulatory effects of Ziziphora tenuior
L. extract on the dendritic cells. Daru 2014;22:63.
Tanaka S, Koizumi S, Masuko K, Makiuchi N, Aoyagi Y, Quivy E, et al. Toll-like receptor-dependent IL-12 production by dendritic cells is required for activation of natural killer cell-mediated Type-1 immunity induced by Chrysanthemum coronarium
L. Int Immunopharmacol 2011;11:226-32.
Chen X, Murakami T, Oppenheim JJ, Howard OM. Triptolide, a constituent of immunosuppressive Chinese herbal medicine, is a potent suppressor of dendritic-cell maturation and trafficking. Blood 2005;106:2409-16.
Krasovsky J, Chang DH, Deng G, Yeung S, Lee M, Leung PC, et al. Inhibition of human dendritic cell activation by hydroethanolic but not lipophilic extracts of turmeric (Curcuma longa)
. Planta Med 2009;75:312-5.
Karimi MH, Ebrahimnezhad S, Namayandeh M, Amirghofran Z. The effects of Cichorium intybus
extract on the maturation and activity of dendritic cells. Daru 2014;22:28.
Knott A, Reuschlein K, Mielke H, Wensorra U, Mummert C, Koop U, et al. Natural Arctium lappa
fruit extract improves the clinical signs of aging skin. J Cosmet Dermatol 2008;7:281-9.
Ryu HS, Lee HK, Kim JS, Kim YG, Pyo M, Yun J, et al. Saucerneol D inhibits dendritic cell activation by inducing heme oxygenase-1, but not by directly inhibiting toll-like receptor 4 signaling. J Ethnopharmacol 2015;166:92-101.
Freysdottir J, Sigurpalsson MB, Omarsdottir S, Olafsdottir ES, Vikingsson A, Hardardottir I. Ethanol extract from birch bark (Betula pubescens)
suppresses human dendritic cell mediated Th1 responses and directs it towards a Th17 regulatory response in vitro
. Immunol Lett 2011;136:90-6.
Jonsdottir G, Omarsdottir S, Vikingsson A, Hardardottir I, Freysdottir J. Aqueous extracts from Menyanthes trifoliate
and Achillea millefolium
affect maturation of human dendritic cells and their activation of allogeneic CD4+ T cells in vitro. J
Kim JS, Jobin C. The flavonoid luteolin prevents lipopolysaccharide-induced NF-kappaB signalling and gene expression by blocking IkappaB kinase activity in intestinal epithelial cells and bone-marrow derived dendritic cells. Immunology 2005;115:375-87.
Rhule A, Rase B, Smith JR, Shepherd DM. Toll-like receptor ligand-induced activation of murine DC2.4 cells is attenuated by Panax notoginseng
. J Ethnopharmacol 2008;116:179-86.
Katayama S, Kukita T, Ishikawa E, Nakashima S, Masuda S, Kanda T, et al. Apple polyphenols suppress antigen presentation of ovalbumin by THP-1-derived dendritic cells. Food Chem 2013;138:757-61.
Sagnia B, Fedeli D, Casetti R, Montesano C, Falcioni G, Colizzi V. Antioxidant and anti-inflammatory activities of extracts from Cassia alata, Eleusine indica, Eremomasta speciosa, Carica papaya
and Polyscias fulva
medicinal plants collecte in Cameroon. PLoS ONE 2014;9:e103999.
Li W, Sun YN, Yan XT, Yang SY, Kim S, Lee YM, et al. Flavonoids from Astragalus membranaceus
and their inhibitory effects on LPS-stimulated pro-inflammatory cytokine production in bone marrow-derived dendritic cells. Arch Pharm Res 2014;37:186-92.
Kwon HK, Hwang JS, Lee CG, So JS, Sahoo A, Im CR, et al. Cinnamon extract suppresses experimental colitis through modulation of antigen-presenting cells. World J Gastroenterol 2011;17:976-86.
Xiang M, Hou WR, Xie SN, Zhang WD, Wang X. Immunosuppressive effects of an ethyl acetate extract from Urtica dentata
Hand on skin allograft rejection. J Ethnopharmacol 2009;126:57-63.
Okamoto M, Oh EG, Oshikawa T, Furuichi S, Tano T, Ahmed SU, et al. Toll-like receptor 4 mediates the antitumor host response induced by a 55-kilodalton protein isolated from Aeginetia indica
L., a parasitic plant. Clin Diagn Lab Immunol 2004;11:483-95.
Li HS, Yang B, Su XC. Effect of shenqi fuzheng injection on repairing the immune function in patients with breast cancer. Zhongguo Zhong Xi Yi Jie He Za Zhi 2009;29:537-9.
Liu QC, Wu WH, Li GR. Effect of lingdankang composite combined dendritic cell-cytokine induced killer cells in treating leukemia. Zhongguo Zhong Xi Yi Jie He Za Zhi 2009;29:347-50.
Roy S, Barik S, Banerjee S, Bhuniya A, Pal S, Basu P, et al. Neem leaf glycoprotein overcomes indoleamine 2,3 dioxygenase mediated tolerance in dendritic cells by attenuating hyperactive regulatory T cells in cervical cancer stage IIIB patients. Hum Immunol 2013;74:1015-23.
Chan WK, Lam DT, Law HK, Wong WT, Koo MW, Lau AS, et al. Ganoderma lucidum
mycelium and spore extracts as natural adjuvants for immunotherapy. J Altern Complement Med 2005;11:1047-57.
Fukui H, Mitsui S, Harima N, Nose M, Tsujimura K, Mizukami H, et al. Novel functions of herbal medicines in dendritic cells: role of Amomi Semen in tumor immunity. Microbiol Immunol 2007;51: 1121-33.
Takaoka A, Iacovidou M, Hasson TH, Montenegro D, Li X, Tsuji M, et al. Biomarker-guided screening of Juzen-taiho-to, anoriental herbal formulation for immunostimulation. Planta Med 2014;80:283-9.
Stein GM, Bussing A, Schietzel M. Stimulation of the maturation of dendritic cells in vitro
by a fermented mistletoe extract. Anticancer Res 2002;22:4215-9.
An WW, Kanazawa Y, Ozawa M, Nakaya K, Saito T, Tanaka A, et al. Dendritic cell differentiation and tumor cell apoptosis induced by components of a poly-phenylpropanoid polysaccharide complex. Anticancer Res 2010;30:613-22.
Kurokawa K, Ishii R, An WW, Kanazawa Y, Ozawa M, Ichiyanagi T, et al. A heat-stable extract from Mucuna
stimulates the differentiation of bone marrow cells into dendritic cells and induces apoptosis in cancer cells. Nutr Cancer 2011;63:100-8.
Nakaya K, Nabata Y, Ichiyanagi T, An WW. Stimulation of dendritic cell maturation and induction of apoptosis in leukemia cells by a heat-stable extract from azuki bean (Vigna angularis)
, a promising immunopotentiating food and dietary supplement for cancer prevention. Asian Pac J Cancer Prev 2012;13:607-11.
Lv J, Shao Q, Wang H, Shi H, Wang T, Gao W, et al. Effects and mechanisms of curcumin and basil polysaccharide on the invasion of SKOV3 cells and dendritic cells. Mol Med Rep 2013;8:1580-6.
Jing XN, Qiu B, Wang JF, Wu YG, Wu JB, Chen DD. In vitro
antitumor effect of human dendritic cells vaccine induced by Astragalus
polysacharin: an experimental study. Zhongguo Zhong Xi Yi Jie He Za Zhi 2014;34:1103-7.
He YL, Ying Y, Xu YL, Su JF, Luo H, Wang HF. Effects of Lycium barbarum
polysaccharide on tumor microenvironment T-lymphocyte subsets and dendritic cells in H22-bearing mice. Zhong Xi Yi Jie He Xue Bao 2005;3:374-7.
Singh N, Singh SM, Shrivastava P. Effect of Tinospora cordifolia
on the antitumor activity of tumor-associated macrophages-derived dendritic cells. Immunopharmacol Immunotoxicol 2005;27:1-14.
Koizumi S, Masuko K, Wakita D, Tanaka S, Mitamura R, Kato Y, et al. Extracts of Larix leptolepis
effectively augments the generation of tumor antigen-specific cytotoxic T lymphocytes via activation of dendritic cells in TLR-2 and TLR-4-dependent manner. Cell Immunol 2012;276:153-61.
Wang Y, Wang W, Li N, Yu Y, Cao X. Activation of antigen-presenting cells by immunostimulatory plant DNA: a natural resource for potential adjuvant. Vaccine 2002;20:2764-71.
Vaid M, Singh T, Prasad R, Elmets CA, Xu H, Katiyar SK. Bioactive grape proanthocyanidins enhance immune reactivity in UV-irradiated skin through functional activation of dendritic cells in mice. Cancer Prev Res (Phila) 2013;6:242-52.
Chang WT, Lai TH, Chyan YJ, Yin SY, Chen YH, Wei WC, et al. Specific medicinal plant polysaccharides effectively enhance the potency of a DC-based vaccine against mous mammary tumor metastasis. PLoS ONE 2015;10:e0122374.
Tian J, Zhang Y, Yang X, Rui K, Tang X, Ma J, et al. Ficus carica polysaccharides promote the maturation and function of dendritic cells. Int J Mol Sci 2014;15:12469-79.
Ghochikyan A, Pichugin A, Bagaev A, Davtyan A, Hovakimyan A, Tukhvatulin A, et al. Targeting TLR-4 with a novel pharmaceutical grade plant derived agonist, Immunomax(R), as a therapeutic strategy for metastatic breast cancer. J Transl Med 2014;12:322.
Ilarraza R, Wu Y, Davoine F, Ebeling C, Adamko DJ. Human dendritic cells promote an antiviral immune response when stimulated by CVT-E002. J Pharm Pharmacol 2011;63:670-8.
Du X, Zhao B, Li J, Cao X, Diao M, Feng H, et al. Astragalus
polysaccharides enhance immune responses of HBV DNA vaccination via promoting the dendritic cell maturation and suppressing Treg frequency in mice. Int Immunopharmacol 2012;14:463-70.
Ou S, Sun KW, Peng JP, Qi SL, Wen J, Hu L. Effects of Bushen Jiedu Recipe and Jianpi Jiedu Recipe containing plasma on dendritic cells of chronic hepatitis B virus infection patients under different immune states. Zhongguo Zhong Xi Yi Jie He Za Zhi 2013;33:208-13.
Paydary K, Emamzadeh-Fard S, Khorram Khorshid HR, Kamali K, SeyedAlinaghiS, Mohraz M. Safety and efficacy of Setarud (IMODTM) among people living with HIV/AIDS: a review. Recent Pat Antiinfect Drug Discov 2012;7:66-72.
Bedoya LM, Alvarez A, Bermejo M, Gonzalez N, Beltran M, Sanchez-Palomino S, et al. Guatemalan plants extracts as virucides against HIV-1 infection. Phytomedicine 2008;15:520-4.
Yin SY, Kim HJ, Kim HJ. A comparative study of the effects of whole red ginseng extract and polysaccharide and saponin fractionson influenza A (H1N1) virus infection. Biol Pharm Bull 2013;36: 1002-7.
Seo JK, Wu J, Lii Y, Li Y, Jin H. Contribution of small RN pathway components in plant immunity. Mol Plant Microbe Interact 2013;26:617-25.
Henderson AJ, Kumar A, Barnett B, Dow SW, Ryan EP. Consumption of rice bran increases mucosal immunoglobulin A concentrations and numbers of intestinal Lactobacillus
spp. J Med Food 2012;15: 469-75.
Frokiaer H, Henningsen L, Metzdorff SB, Weiss G, Roller M, Flanagan J, et al. Astragalus
root and elderberry fruit extracts enhance the IFN-beta stimulatory effects of Lactobacillus acidophilus
in murine-derived dendritic cells. PLoS ONE 2012;7:e47878.
Calla-Magarinos J, Fernandez C, Troye-Blomberg M, Freysdottir J. Alkaloids from Galipea longiflora
Krause modify the maturation of human dendritic cells and their ability to stimulate allogeneic CD4+ T cells. Int Immunopharmacol 2013;16:79-84.
Lezama-Davila CM, Pan L, Isaac-Marquez AP, Terrazas C, Oghumu S, Isaac-Marquez R, et al. Pentalinon andrieuxii root extract is effective in the topical treatment of cutaneous leishmaniasis caused by Leishmania mexicana
. Phytother Res 2014;28:909-16.
Lee CC, Wang CN, Lai YT, Kang JJ, Liao JW, Chiang BL, et al. Shikonin inhibits maturation of bone marrow-derived dendritic cells and suppresses allergic airway inflammation in a murine model of asthma. Br J Pharmacol 2010;161:1496-511.
Huang T, Wang MQ, Luo YH. Effect of wuhu decoction on surface co-stimulation molecule expression of peripheral dendritic cells in infants with asthma. Zhongguo Zhong Xi Yi Jie He Za Zhi 2009;29:889-91.
Mandeau A, Aries MF, Boe JF, Brenk M, Crebassa-Trigueros V, Vaissiere C, et al. Rhealba(R) oat plantlet extract: evidence of proteinfree content and assessment of regulatory activity on immune inflammatory mediators. Planta Med 2011;77:900-6.
Inngjerdingen M, Inngjerdingen KT, Patel TR, Allen S, Chen X, Rolstad B, et al. Pectic polysaccharides from Biophytumpetersianum
Klotzsch, and their activation of macrophages and dendritic cells. Glycobiology 2008;18:1074-84.
Amirghofran Z, Ahmadi H, Karimi MH. Immunomodulatory activity of the water extract of Thymus vulgaris, Thymus daenensis
, and Zataria multiflora
on dendritic cells and T cells responses. J Immunoassay Immunochem 2012;33:388-402.
Lin J, Xiao L, Ouyang G, Shen Y, Huo R, Zhou Z, et al. Total glucosides of paeony inhibits Th1/Th17 cells via decreasing dendritic cells activation in rheumatoid arthritis. Cell Immunol 2012;280:156-63.
Littmann L, Rossner S, Kerek F, Steinkasserer A, Zinser E. Modulation of murine bone marrow-derived dendritic cells and B-cells by MCS-18 a natural product isolated from Helleborus purpurascens
. Immunobiology 2008;213:871-8.
Broer J, Behnke B. Immunosuppressant effect of IDS 30, a stinging nettle leaf extract, on myeloid dendritic cells in vitro
. J Rheumatol 2002;29:659-66.
Figueirinha A, Cruz MT, Francisco V, Lopes MC, Batista MT. Antiinflammatory activity of Cymbopogon citratus
leaf infusion in lipopolysaccharide-stimulated dendritic cells: contribution of the polyphenols. J Med Food 2010;13:681-90.
Xiao Y, Xu J, Mao C, Jin M, Wu Q, Zou J, et al. 18 Beta-glycyrrhetinic acid ameliorates acute Propionibacterium acnes
-induced liver injury through inhibition of macrophage inflammatory protein-1alpha. J Biol Chem 2010;285:1128-37.
Zhai JH, Shen H, Ni FF. Effects of qingchang huashi recipe on the dendritic cells of the colonic mucosa and the mesenteric lymph nodes in experimental colitis rats. Zhongguo Zhong Xi Yi Jie He Za Zhi 2012;32:1366-9.
Zhou Z, Lin J, Huo R, Huang W, Zhang J, Wang L, et al. Total glucosides of paeony attenuated functional maturation of dendritic cells via blocking TLR4/5 signaling in vivo
. Int Immunopharmacol 2012;14:275-82.
Huang YT, Wen CC, Chen YH, Huang WC, Huang LT, Lin WC, et al. Dietary uptake of Wedelia chinensis
extract attenuates dextran sulfate sodium-induced colitis in mice. PLoS ONE 2013;8:e64152.
Quang TH, Ngan NT, Van Minh C, Van Kiem P, Nhiem NX, Tai BH, et al. Inhibitory effects of oleanane-type triterpenes and saponins from the stem bark of Kalopanax pictus
on LPS-stimulated pro-inflammatory cytokine production in bone marrow-derived dendritic cells. Arch Pharm Res 2013;36:327-34.
Liu H, Wang S, Sun A, Huang D, Wang W, Zhang C, et al. Danhong inhibits oxidized low-density lipoprotein-induced immune maturation of dentritic cells via a peroxisome proliferator activated receptor gamma-mediated pathway. J Pharmacol Sci 2012;119:1-9.
Liu H, Shi D, Wang W, Zhang C, Fu M, Ge J. Panax quinquefolium
saponins inhibited immune maturation of human monocyte-derived dendritic cells via blocking nuclear factor-kappaB pathway. J Ethnopharmacol 2012;141:982-8.