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Frontiers in Biology

Front Biol    2013, Vol. 8 Issue (1) : 78-100
Multidisciplinary perspectives on mechanisms of activity of popular immune-enhancing herbal supplements used by athletes
David S. SENCHINA1(), Justus E. HALLAM2, David J. CHENEY3
1. Department of Biology, Drake University, Des Moines, IA 50311, USA; 2. Department of Kinesiology, Iowa State University, Ames, IA 50011, USA; 3. Mayo Clinic, Rochester, MN 55905, USA
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This paper examines cellular and molecular mechanisms that may underpin the purported effects of five herbal supplements in the context of athlete immune function. Ginseng and echinacea are used frequently by athletes, whereas astragalus and elderberry are used infrequently and pequi is just emerging as a possible supplement. In vivo studies of these products on athlete immune function have yielded heterogeneous results, likely due to experimental design differences. Ginseng, echinacea, elderberry, and pequi are considered asterids sensu lato. Ginseng appears to exert strongest effects on components of adaptive immunity, in particular maintaining Th1/Th2 balance of CD4+ T cells and their downstream effects, via its ginsenosides, flavonoids, and polysaccharides. Echinacea alkamides, caffeic acid derivatives, and polysacchardies may target both innate and adaptive immunity, though perhaps the former more consistently. Elderberry harbors anthocyanins and lectins which may modulate innate immunity. Data on pequi is limited but suggests that carotenoids, phenols, and fatty acids may alter circulating leukocyte populations. More phylogenetically distant, astragalus is a rosid sensu lato and may influence the innate immune system through flavonoids, polysaccharides, and saponins. Supplements generally demonstrate no effects on physiologic parameters such as lactate, oxygen dynamics, or athletic performance. Bioavailability studies indicate that purported bioactive molecules of these supplements may reach circulation in low but therapeutically-relevant quantities. Difficulties in cross-comparisons due to study design differences, coupled with an overall dearth of research on the topic, currently hamper any formal conclusions regarding the efficacy of these supplements as immunoregulators for athletes.

Keywords athlete      dietary supplement      exercise      herb      immunity      mechanism     
Corresponding Author(s): SENCHINA David S.,   
Issue Date: 01 February 2013
 Cite this article:   
David S. SENCHINA,Justus E. HALLAM,David J. CHENEY. Multidisciplinary perspectives on mechanisms of activity of popular immune-enhancing herbal supplements used by athletes[J]. Front Biol, 2013, 8(1): 78-100.
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Justus E. HALLAM
Common nameScientific nameFamily (Order)HabitEndemic Region
Astragalus, locoweed, or milk vetchAstragalus spp. L.Fabaceae (Fabales)Herbaceous perennial, rarely shrubNorthern Hemisphere
Echinacea or coneflowerEchinacea spp. MoenchAsteraceae (Asterales)Herbaceous perennialNorth America
ElderberrySambucus spp. L.Adoxaceae* (Dipsicales)Shrub or treeGlobal
GinsengPanax spp. L.Araliaceae (Apiales)Herbaceous perennialEastern Asia (most species) and North America
Pequi or souariCaryocar brasilense Cambess.Caryocaraceae (Ericales?)TreeSouth America
Tab.1  Botanical characteristics of herbs in this review
Fig.1  Plants discussed and their most commonly-utilized organs. (A) Ginseng ( spp.; pictured is ). The root is most commonly used. (B) Echinacea ( spp.; pictured is ). Although the underground parts of spp. contain the highest concentrations of purported bioactive molecules, many contemporary commercial operations harvest aboveground parts and allow belowground parts to regenerate to yield multiple harvests. (C) Astragalus ( spp.; pictured is ). Dried roots are most commonly used. (D) Elderberry ( spp.; pictures is ). Most supplements are produced from berry clusters. (E) Pequi (). The nut is used in supplement production.
Fig.2  Selected bioactive molecules from the specimens in Figure 1. (A) Ginsenoside Rc from ginseng. (B) Alkamides and caffeic acid derivatives (such as caftaric acid) from echinacea. (C) Astragaloside IV from astragalus. (D) Quercetin from elderberry. (E) Zeaxanthin from pequi.
ReferencesPopulation*Treatment?Exercise?Immune Outcome§
Engels et al., 2003TR ♂PG 8 wkThree 30 s Wingate testsNo differences in salivary IgA between GT and C
Gaffney et al., 2001TR ♂PG 8 wkNormal in-season trainingNo differences in circulating leukocyte populations between GT and C
Hsu, 2010TR ♂PQ 4 wk60 min treadmill run at 60% VO2max, 10% downhill gradePlasma IL-4 ↑ post-exercise in GT compared to C; no differences in TNF, IL-1β, IL-10
Jung et al., 2011TR ♂RG 7 dTwo 45 min treadmill runsPlasma IL-6 ↓ at 2 h post-exercise in GT compared to C; plasma CK ↓ 72 h post-exercise in GT compared to C
Park et al., 2008TR ♂RG 7 dTwo 45 min treadmill runsPlasma IL-6 ↓ at 2 h post-exercise in GT compared to C
Biondo et al., 2008UT ♂PQ 35 d36 min on cycle ergometer (various % VT based on VO2max)Blood CD8+ T-cells ↑ and in vitro PHA-stimulated PBMC proliferation ↑ in GT compared to C; no differences in other cell subsets, proliferation, or neutrophil oxidative burst
Biondo et al., 2010UT ♀PQ 4 wk36 min on cycle ergometer (various % VT based on VO2max)Blood CD4+CD45RO+, CD4+CD28+, and CD28+ T-cells ↓ post-exercise in GT compared to C; in vitro neutrophil oxidative burst ↑ in GT compared to C; no differences in other cell subsets, proliferation, or NK cell activity
Lau et al., 2011UT ♂PP 3 d30 min treadmill run at 60% VO2maxNo differences in plasma IL-6 between GT and C
Tab.2  Summary of exercise-associated studies of ginseng supplements and immune function in humans
Fig.3  Representative model of current mechanisms research on ginseng supplements with a focus on ginsenoside interactions with rodent splenocyte and blood models. (Bottom): Endurance athletes including runners, cyclists, or triathletes are the populations that consume ginseng most often. (Top) CD4 T-cell-mediated immune responses can be categorized as either Th1 (top left panel) or Th2 (top right panel; see text). Ginsenosides appear to augment both Th1 and Th2 in a balanced way (represented by the see-saw).
Fig.4  Representative model of current mechanisms research on echinacea supplements with a focus on the rodent macrophage. (Right): Echinacea supplements are typically consumed by aerobically-trained athletes such as swimmers. (Left): Summary of selected current research on the effects of echinacea on rodent macrophage inflammation-associated pathways (see text). Positive signs (+) indicate upregulation, negative signs (-) indicate downregulation, and “NE” stands for “no effect.”
ReferenceSpecies*OrganExtractionConstituent (Solvent)?Stimulant?MΦ Type§
Cech et al., 2010PURRootEthanolALK (ethanol)H1N1RAW 264.7
Chen et al., 2005ANG, PAL, PURRootEthanol, methanol, chloroform, hexaneALK (methanol)LPSRAW 264.7
Goel et al., 2002aPURAerialEthanol-waterALK, CAD, POLY (ethanol-water)LPSALV
Goel et al., 2002bPURAerialEthanol-waterALK, CAD, POLY (ethanol-water)LPSALV
LaLone et al., 2007ANG, PAL, PURRootEthanol, chloroform, hexaneALK (ethanol, DMSO)NoneRAW 264.7
LaLone et al., 2009ANG, PAL, PUR, TENRootEthanol, waterALK, KET (ethanol, water)LPSRAW 264.7
Rininger et al., 2000UnknownAerial, RootUnknownUnknownNoneRAW 264.7
Senchina et al., 2010ANG, PAL, PUR, TENRootEthanol, ethanol-waterEthanol, ethanol-waterHSVRAW 264.7
Stevenson et al., 2005ANG, PURRootEthanol-waterALK, CAD (ethanol-water)LPSRAW 264.7
Sullivan et al., 2008PURAerial, rootUnknownPOLY (C-RPMI)NonePER
Zhai et al., 2007ANG, PAL, PURRootEthanol, chloroform, hexaneALK, CAD (ethanol, water)LPS, Salmonella entericaPER,RAW 264.7
Zhai et al., 2009ANG, PAL, PURRootEthanol, chloroform, hexaneALK, CAD (ethanol, water)LPSRAW 264.7
Tab.3  Experimental variables for the data presented in Figure 4
CompoundHigh DoseMiddle DoseLow Dose
Vehicle control765.8±21.9N/AN/A
Caftaric acid790.0±29.1771.8±19.8728.3±6.1
Chlorogenic acid695.8±20.8742.6±30.2798.6±36.2
Cichoric acid746.4±23.2748.8±44.9789.2±47.1
Tab.4  Demonstration of how individual caffeic acid derivatives may have different effects on immune cell proliferation
CytokineSolvent ControlE. angustifoliaE. pallidaE. paradoxaE. purpureaE. tennesseensis
Tab.5  Demonstration of how different species grown and processed under identical conditions can exert different effects on cytokine production by human peripheral blood mononuclear cells
Fig.5  Representative model of current mechanisms research on supplements with a focus on the rodent macrophage. (Right) Astragalus supplements are consumed by a wide range of athletes for general immune-enhancing effects. (Left) Summary of selected current research on the effects of astragalus on rodent macrophage inflammation-associated pathways. Positive signs (+) indicate upregulation, negative signs (-) indicate downregulation, and “NE” stands for “no effect.”
ReferencesOrganExtractionConstituent (Solvent)*Stimulant?mRNA or ProteinMΦ Type?
(Chao et al., 2009)Root?EthanolUnknown (ethyl acetate, hexane, water)LPS/IFN-γProteinPER
(Cho and Leung, 2007)RootEthanol, waterUnknown (ethanol, water)NoneProteinPER
(Clement-Kruzel et al., 2008)RootAlcohol, waterUnknown (alcohol, water)LPSProteinJ774A.1
(Lee and Jeon, 2005)RootWater, salinePOLY (ethanol)NoneBothPER, RAW 264.7
(Lee et al., 2005)RootWaterUnknown (water)MTXBothRAW 264.7
(Ryu et al., 2008)RootWaterUnknown (PBS)LPS, ZYMBothRAW 264.7
(Shao et al., 2004)RootWater, saline, ethanolPOLY (water)NoneBothPER
(Wang et al., 1989)RootUnknownPOLY (saline)NoneProteinPER
(Xu et al., 2007)UnknownUnknownPOLY, SAP (unknown)GCMProteinPER
(Yin et al., 2010b)UnknownUnknownPOLY (unknown)LPSBothPER
(Yoshida et al., 1997)UnknownWaterUnknown (water)THIO then LPSProteinPER
(Zhang et al., 2011)RootEthanolFLAV (ethanol, methanol)LPSProteinRAW 264.7
(Zhao et al., 2011)RootEthanol, waterPOLY (water)LPSProteinRAW 264.7
Tab.6  Experimental variables for the data presented in Figure 5
Fig.6  Representative model of current mechanisms research on elderberry supplements. (Center) No studies of elderberry supplements on athlete immune function exist, but given its immunostimulatory, antioxidant, and antiviral properties, elderberry supplements may be of benefits to athlete groups like football players. (Top, Left): Interactions between elderberry supplement components and influenza virus. (Top, Right) Effects of elderberry on macrophage and basophil activities.
Fig.7  Representative model of current mechanisms research in pequi supplements. (Left) To date, all studies on pequi supplements have been performed in runners. (Right) Cut-away view of a blood vessel showing possible effects of pequi supplement ingestion on leukocyte subsets from one study (). Arrows indicate direction of cell counts from pre- to post-treatment and “NE” stands for “no effect.”
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