Table 2.
Plant derived immunomodulatory agents.
| Chemical class | Plant source | Mechanism | Reference |
|---|---|---|---|
| Alkaloids | |||
| Berberine | Coptis chinensis Franch | Down-regulate T-helper cells cytokines [Th1 (TNF-α, IL-2), and Th2 (IL-4)] production. | Lin and Lin (2011) |
| Chelerythrine | Chelidonium majus L. | Inhibit PGE2 release by regulating cyclooxygenase-2 activity | Niu et al. (2011) |
| Gelselegine | Gelsemium elegans | Inhibited T lymphocyte proliferation. | Xu et al. (2012) |
| Pseudocoptisine | Corydalis turtschaninovii Besser | Suppressing the phosphorylation of ERK and p38 to inhibit NF-κB activation, which resulted in reduction of pro-inflammatory mediators level (iNOS, COX-2, TNF-α, and IL-6). | Yun et al. (2009) |
| Leonurine | Leonurus japonicas Houtt | Downregulate TNF-α, IL-6, iNOS, and COX-2 and upregulate IL-10 by inhibiting the expression of toll like receptors and the activation of NF-κB. Inhibit the ICAM-1, VCAM-1 activity. | Liu et al. (2012), Song et al. (2015) |
| Piperine | Piper longum Linn | Reduce level of pro inflammatory cytokines IL-1β, IL-6, and TNF-α. Down regulate expression of COX-2, NOS-2, and NF-κB. Inhibit eicosanoide generation by inhibiting phospholipase A2 and TXA2 synthase activity. |
Vaibhav et al. (2012), Son et al. (2014) |
| Sinomenine | Sinomenium acutum (Thunb.) Rehd.etWils | Inhibit the production and release of inflammatory cytokine. Inhibit expression of VCAM-1. |
Chen et al. (2011), Oh et al. (2012) |
| Koumine | Gelsemium elegans | Inhibit T lymphocyte proliferation. | Xu et al. (2012) |
| Lycorine | Lycoris radiate | Inhibit iNOS and COX-2 activity. | Kang et al. (2012) |
| Sophocarpine | Sophora alopecuroides L. | Inhibit production of NO and pro inflammatory cytokines TNF-α and IL-6. Inhibit expression of iNOS and COX-2. | Zhang et al. (2008), Gao et al. (2012) |
| Rhynchophylline | Uncaria rhynchophylla (Miq.) Jack | Inhibit phosphorylation of mitogen-activated protein kinases. Inhibit production of pro inflammatory cytokines, NO, PGE2, monocyte chemoattractant protein MCP-1, TNF-α, IL-1β. |
Song et al. (2012) |
| Tetrandrine | Stephania tetrandra | Wu et al. (2011) | |
| Matrine | Sophora flavescens Ait | Reduced production of reactive oxygen species inflammatory mediators. Inhibit myeloperoxidase and maleic dialdehyde activity. |
Zhang et al. (2011) |
| Essential oils | |||
| Z-ligustilide | Angelica sinensis (Oliv.) Diels | Inhibit iNOS and COX-2 induction by regulating the NF-kB and MAPK signal pathways. | Chung et al. (2012) |
| Tetramethylpyra-zine | Ligusticum chuanxiong Hort | Inhibit pro inflammatory cytokines and reactive oxygen species production. Inhibit macrophages chemotaxis, neutrophile infiltration, and nitric oxide synthase activity. Block the phosphorylation of p38 mitogen-activated protein kinase. |
Liu et al. (2010), Hu et al. (2013) |
| Flavonoids | |||
| Chalcone | |||
| Butein | Semecarpus anacardium, Dalbergia odorifera, Toxicodendron vernicifluum | Suppress NO production by attenuating iNOS expression. Inhibit translocation of NF-κB. |
Wang et al. (2014) |
| Xanthohumol | Humulus lupulus | Inhibit NO production which is induced by LPS and INF-γ. | Zhao et al. (2003) |
| Dihydroxanthohumol | Humulus lupulus | Inhibit NO production which is induced by LPS and INF-γ. | Zhao et al. (2003) |
| Mallotophilippens C, D, E | Mallotus, Philippinensis | Inhibit mRNA gene expression of iNOS, COX-2, IL-6, and IL-1β. Inactivate NF-κB. |
Daikonya et al. (2004) |
| Licochalcone E | Glycyrrhiza inflata | Inhibit secretion of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α by inhibiting the activity of NF-κB and activator protein (AP-1). | Lee et al. (2013a) |
| Flavones | |||
| Luteolin |
Lonicera Japonica |
Decreased secretion of inflammatory mediators (INF-γ, IL-6) reduced COX-2, ICAM-1 expression. Block heat shock protein 90 activity. |
Chen et al. (2007, 2014), Ziyan et al. (2007) |
| Apigenin | Cynodon dactylon, Salvia officinalis L., Portulaca oleracea, Mentha longifolia | Downregulate expression of cytokines (IL-1α, TNF-α, IL-8). Decreased response of Th1 and Th17 cells. Downregulate the expression of COX-2 and iNOS. Decreased expression of ICAM and VCAM leading to decreased neutrophile Chemotaxis. |
Nicholas et al. (2007), Kang et al. (2009) |
| Chrysin | Picea crassifolia | Inhibited production of pro-inflammatory cytokine (TNFα, IL-1β, and IL-6). By modulation of intracellular calcium reduce histamine release from mast cells. |
Hougee et al. (2005), Shin et al. (2009), Bae et al. (2011) |
| Nobiletin | Citrus nobilis Lour, Citrus aurantium L. | Inhibit pro-inflammatory mediators, COX-2 and iNOS expression by blocking NF-κB and MAPK signaling pathway. | Kang et al. (2011) |
| Baicalein | Scutellaria altissima L. | Inhibit mRNA expression of iNOS, COX-2, and TNF-α. Inhibit production of NO and inflammatory cytokine (IL-1β, PGE2, and TNF-α) by regulating NF-κB and ER-dependent pathway. Inhibit adhesion and migration of leukocytes by inhibiting cell adhesion molecules expression. |
Chandrashekar et al. (2012), Fan et al. (2013), Lee et al. (2015) |
| Oroxylin A | Scutellariae baicalensis Georgi | Inhibit NO production and iNOS and COX-2 proteins expression of via inhibiting nuclear factor-κB pathway. Enhance antioxidant response element-luciferase reporter activity by increasing the expression of nuclear factor erythroid 2-related factor 2 proteins. |
Chen et al. (2000), Li et al. (2007), Ye et al. (2014) |
| Wogonin | Scutellaria baicalensis Georgi | Inhibit adhesion and migration of leukocytes by inhibiting cell adhesion molecules expression. Reduces allergic airway inflammation by inducing eosinophil apoptosis through activation of caspase-3. |
Guo et al. (2007), Lee et al. (2015), Lucas et al. (2015) |
| Flavonols | |||
| Quercetin | Dysosma veitchii Hemsl. et Wils | Decreased expression of pro-inflammatory cytokines, NF-κB, and iNOS. Reduce expression of VCAM-1 and E-selectin. |
Shaik et al. (2006), Kleemann et al. (2011), Choi et al. (2012) |
| Kaempferol | Found in various fruits and vegetables e.g., tea, tomato, cruciferous vegetables, apple, etc. |
Reduce iNOS and COX-2 activity through suppression of the signaling of STAT-1, NF-kappa B, and AP-1. Decrease the gene expression of ICAM-1, VCAM-1, and monocyte chemotactic protein-1 (MCP-1). | Hamalainen et al. (2007), Kong et al. (2013) |
| Rutin | Ruta graveolens | Inhibit leukocyte migration. Suppress production of TNF-α and IL-6. Inhibit activation of NF-κB and extracellular regulated kinases. |
Yoo et al. (2014) |
| Flavanols | |||
| Epigallocatechin-3-gallate | Camellia sinensis L. | Inhibit reactive oxygen species generation, MAPKs phosphorylation, adhesion molecules expression signal transducers and activators of transcription 3 (STAT-3) and activating transcription factor 2 translocation through induction of heme oxygenase-1 and suppressors of cytokine signaling -3 expression. | Lee et al. (2013b) |
| Isoflavones | |||
| Daidzein | Pueraria mirifica, Pueraria lobata, Glycine max | Decreases TNF-α, IL-1β, MCP-1, NO, and iNOS expression at mRNA level. | Hamalainen et al. (2007) |
| Genistein | Glycine max | Inhibited expression of iNOS and COX-2. Decreased IL-1β and TNF-α production via activation of PPARs. |
Valles et al. (2010) |
| Puerarin | Pueraria lobata (wild) Ohwi | Decrease cytokines level. Inhibit NF-κB and activation of signal transducers and activators of transcription 3 (STAT3). |
Liu et al. (2013) |
| Phloroglucinols | |||
| Myrtucommulone | Myrtus communis L. | Inhibit the PGE2 production by inhibiting the mPGES-1 activity without significantly inhibiting the COX enzymes activity. | Koeberle et al. (2009) |
| Arzanol | Helichrysum italicum | Reduce eicosanoids generation by inhibiting lipooxygenase and cyclooxygenase activity in arachidonic acid metabolism pathway. | Rossi et al. (2009), Bauer et al. (2011) |
| Quinones | |||
| Thymoquinone | Nigella sativa L. | Inhibited LPS-induced fibroblast proliferation and H2O2-induced 4-hydroxynonenal generation. Inhibit IL-1β, TNF-α, MMP-13, COX-2, and PGE2 while blocking phosphorylation of MAPK p38, ERK1/2, and NF-kBp65. |
Vaillancourt et al. (2011) |
| Shikonin | Lithospermum erythrorhyzon Sieb. etZucc. | Inhibit NF-κB activity, inhibit Th1 cytokines expression and induce Th2 cytokines. | Andújar et al. (2010) |
| Emodin-8-O-β-D glucoside | Polygonum amplexicaule D. Don var. sinense Forb. | Stimulate proliferation and differentiation of osteoblasts. Inhibit PGE2 production by increased alkaline phosphatase expression in MC3T3-E1. |
Xiang et al. (2011) |
| Other | |||
| Apocynin | Apocynum cannabinum L. (Canadian hemp), Picrorhiza kurroa Royle ex Benth. | Inhibit NADPH oxidase activity. Suppress pro-inflammatory cytokines and CD4+ and CD8+T cells production. |
Stefanska and Pawliczak (2008), Kim et al. (2012) |
| Stilbenes | |||
| Resveratrol | Fallopia japonica, grape, nuts | Decrease MPO activity and mPGES-1 to basal levels. Inhibit iNOS and COX-2 expression. Reduce the pro-inflammatory cytokines IL-8, TNFα, IFN-γ, and IL-1α. Increase the anti-inflammatory cytokine IL-10 level. |
Youn et al. (2009), Vang et al. (2011) |
| Piceatannol | Fallopia japonica, grape, nuts | Decrease iNOS expression. Inhibit transcription factors activation such as NF-kB, ERK, and STAT3. |
Youn et al. (2009), Vang et al. (2011) |
| Terpenoid | |||
| 14-deoxyandrographolide | Andrographis paniculata | Enhanced proliferation of lymphocytes. Enhanced IL-2 induction in lymphocytes. |
Kumar et al. (2004) |
| 14-deoxy-11,12-didehydroandrographolide | Andrographis paniculata | Enhanced proliferation of lymphocytes. Enhanced IL-2 induction in lymphocytes. |
Kumar et al. (2004) |
| Ginsan | Panax ginseng | Enhances the production of cytokines and reactive oxygen species by macrophages. Stimulates the phagocytic activity of macrophages. |
Shen et al. (2002), Song et al. (2002) |
| Oleanolic acid | Luffa cylindrica, Phytolacca americana | Reduce level of IL-1α, IL-6, and TNF-α, as well as their effect on complement pathway though the inhibition of C3 convertase. Inhibits adenosine deaminase activity. |
Brinker et al. (2007) |
| Echinocystic acid | Luffa cylindrica | Enhance phagocytic index of macrophages in humoral and cell-mediated immune responses. | Khajuria et al. (2007) |
| Triptolide | Tripterygium wilfordii | Inhibits lymphocyte activation and pro-inflammatory cytokines gene expression (IL-2, iNOS, TNF-α, COX-2, and IFN-γ). It also inhibits activation of transcription factors such as NF-kB, NFAT, and STAT3. |
Brinker et al. (2007) |
| Demethylzelasteral | Tripterygium wilfordii | Inhibits proliferation of vascular endothelial cells. | Ramgolam et al. (2000) |
| Celastrol | Tripterygium wilfordii | Inhibit expression of pro-inflammatory cytokines, adhesion molecules, proteasome activity, and topoisomerase II. | Kannaiyan et al. (2011) |
| Asiaticoside | Centella asiatica | Decrease NO production. | Hartog et al. (2009) |
| Madecassoside | Centella asiatica | Reduce spleen cells proliferation. Inhibition of pro-inflammatory mediators such as TNF-α and IL-6. Inhibit production of PGE2, and COX-2. |
Li et al. (2009) |
| 11-keto-β-boswellic acid | Boswellia carteri | Decrease pro-inflammatory cytokines such as IL-1, IL-2, IL-4, IL-6, and IFN-γ through inhibition of NF-kB activation. | Ammon (2006) |