Herbal Medicine Interventions for Immunity

The immune system is significantly complex in its physiology and functionality. Maintaining homeostasis involves an intricate interaction between the innate and adaptive immune systems and the cells, receptors, molecules and chemical substances that comprise these systems.[1-3]

This complexity also extends to the impact of many factors on immune function, including diet and nutritional status, lifestyle, age, medications, stress, microbiome composition, and physiological and genetic variability.[4-8]

Echinacea purpurea (echinacea)

E. purpurea is commonly used for the amelioration of upper respiratory tract infections (URTI), cold and flu symptoms and overall immune system support, and is perhaps the herb most commonly associated with improvement of immunity.[9]

It has been used in traditional medicine for many health concerns including wound healing, throat and yeast infections and coughs,[10,11] and overall the clinical evidence indicates it is beneficial for the treatment of cold, flu and URTI symptoms as well as urinary tract infections via immune stimulation and modulation.[9-11] The primary active constituents isolated from the aerial parts and roots includes the caffeic acid derivative cichoric acid (2,3-odicaffeoyl-tartaric acid), alkamides, volatile oils, polysaccharides and melanins, and these constituents are responsible for the herb’s impact on immunity.[9-13]

E. purpurea influences both innate and adaptive immune activity via a number of mechanisms including promoting white blood cell (leukocyte, monocyte, lymphocyte) production, activation and mobility, stimulating phagocytic activity, and cytokine synthesis in granulocytes and macrophages (tumour necrosis factor alpha [TNF-alpha], interleukins 1, 6, 8 and 10, interferon),[9-11] as well as modulating regulatory T-cells number and function,[14,15] and dendritic cell differentiation and expression.[16,17]

Other mechanisms include inhibiting viral receptor binding capacity and pro-inflammatory compounds (COX-1, COX-II, NF-kB).[10,18]

Andrographis paniculata (andrographis)

The aerial parts of A. paniculata have been used extensively in traditional Ayurvedic and Chinese medicine systems for a range of conditions including URTI symptoms, sinusitis, bronchitis and tonsillitis, pneumonia, whooping cough and urinary tract infections.[19,20,22]

The active constituent that is considered to be the most biologically significant for its immune modulatory and anti-inflammatory activity is the diterpene lactone andrographolide.[19-22] Human clinical evidence demonstrates that A. paniculata is beneficial for the alleviation of URTI symptom severity and frequency.[20,23,24]

Animal and in vitro data has found that there are many underlying mechanisms that contribute to these therapeutic effects.

These include stimulation of innate immunity via macrophage phagocytosis and lymphocyte production and activity,[20-22] and adaptive immunity by induction of antibody synthesis and activity.[19,22] Other mechanisms include reduction of pro-inflammatory mediators (TNF-alpha, inteferon, IL-1, IL-6),[19,25,26] inhibition of gram-positive and gram-negative bacterial growth,[27-29] viral replication[22] and pro-inflammatory cytokines.[30]

Astragalus membranaceous (astragalus)

The root of A. membranaceous is an important therapeutic herb in the traditional Chinese medicine system for many health issues including immune support, the treatment of viral infections, debility and wound healing.[31,32]

The primary active constituents are considered to be the triterpene saponins (astrogalosides), flavonoids and polysaccharides,[11,31,33] and clinical data supports the traditional use of the herb for modulation of the immune system due to the effects of these constituents.[11,31,32]

The specific mechanisms contributing to the therapeutic effects of A. membranaceous include increasing monocyte, neutrophil and lymphocyte levels, stimulating macrophage maturation and T-cell activity[11,31,35,36] and antibody production[11,34] as well as modulating the synthesis of inflammatory mediators (NO, IL-2, IL-4, IL-10, IL-12, NF-kB).[31,34,37-39]

Inula helenium (elecampane)

I. helenium root has a long history of use in Mongolian traditional medicine for immune related conditions, as well as in the west for respiratory health.[40,41]

The biologically active constituents that have been isolated include coumarins, flavonoids, polysaccharides, fatty acids and saponins.[40]

The polysaccharides have been observed to induce a Th1 immune response, macrophage production of NO[42] and stimulation of the complement system activity.[40]

Other mechanisms of action include inhibition of Staphylococcus aureus infection[43] and anti-inflammatory activity through p38 MAPK-dependent HO-1 signalling pathway induction.[44]

Olea europaea (olive leaf)

Olive leaf has been used in traditional and folk medicine for fevers and diseases such as malaria.[45,46]

The main active constituents of O. europaea, the secoiridoids like oleuropein, as well as flavonoids and phenolic compounds,[45,46] contribute to the immune associated antimicrobial, antibacterial, antiviral and anti-inflammatory effects of the herb.[45]

The mechanisms of these constituents observed in preliminary data include stimulation of macrophage activation, inhibition of a wide range of bacterial and microbial pathogens (Escherichia coli, S. aureus, Salmonella typhyimurium and Bacillus subtilis, Campylobacter jejuni)[45,47,48] and preventing viral host cell entry.[45] Anti-inflammatory mechanisms include inhibition of the classical complement system pathway and pro-inflammatory cytokine synthesis (NO, IL-17).[45,49]

Sambucus nigra (elder)

Both the fruit and flowers from S. nigra have been documented in traditional western medicine for use against the cold and as a diaphoretic in catarrhal complaints.[50]

Several types of anthocyanins have been identified as the primary active constituents of S. nigra, with smaller quantities of carbohydrates, vitamins and minerals.[50]

Clinical trials have observed improvements in cold and flu symptom severity and duration with use of the herb.[50,51]

The specific effects of S. nigra on the immune system includes inhibiting H1N1 viral replication, propagation and host cell entry,[50,52,53] stimulation of macrophage activity, increased production of pro-inflammatory cytokines (TNF-alpha, IL-1, IL-6, IL-8, IFN-gamma)[50,54] and antimicrobial activity against gram-positive and gram-negative bacteria.[52]

Thymus vulgaris (thyme)

Different types of preparations of T. vulgaris have been used in traditional medicine for conditions such as laryngitis, bronchitis, pertussis, tonsillitis and coughs related to colds.[9,11]

The German Commission E Monographs approves the use of T. vulgaris for the symptoms of bronchitis, whooping cough and upper respiratory catarrh.[9]

The phenols thymol and carvacrol, flavonoids, caffeic acid, rosmarinic acid, polysaccharides and triterpenes are the main constituents of the herb.[11,55]

Animal and in vitro data has demonstrated that the mechanism of T. vulgaris and its constituents involves inhibition of PPAR-gamma-dependent COX-2 expression, NF-kB transcription and subsequent cytokine gene expression and secretion,[55-57] and inhibition of gram-positive and gram-negative bacteria growth and colonisation (Candida albicans, S. aureus, E. coli, Enterococcus).[55,58]

Conclusion

The physiological effects of Echinacea purpurea, Andrographis paniculata, Astragalus membranaceous, Inula helenium, Olea europaea, Sambucus nigra and Thymus vulgaris on innate and adaptive immunity are diverse. The variability of these mechanisms highlights the importance of utilising a combination of herbs therapeutically to support the complex immune system for clinically relevant outcomes.

References

1. Yatim KM, Lakkis FG. A brief journey through the immune system. Clin J Am Soc Nephrol 2015;10(7):1274-1281. [Full text]
    
2. Vasquez MI, Catalan-Dibene J, Zlotnik A. B cells responses and cytokine production are regulated by their immune microenvironment. Cytokine 2015;74(2):318-326. [Full text]
    
3. Dunn GP, Okada H. Principles of immunology and its nuances in the central nervous system. Neuro Oncol 2015;17 Suppl 7:vii3-vii8. [Full text]
    
4. Casas R, Sacanella E, Estruch R. The immune protective effect of the Mediterranean Diet against chronic low-grade inflammatory diseases. Endocr Metab Immune Disord Drug Targets 2016;14(4):245-254. [Full text]
    
5. Brod S, Rattazzi L, Piras G, D’Acquisto F. ‘As above, so below’ examining the interplay between emotion and the immune system. Immunology 2014;143(3):311-318. [Full text]
    
6. Salleh MR. Life event, stress and illness. Malays J Med Sci 2008;15(4):9-18. [Full text]
    
7. Peterson C, Round JL. Defining dysbiosis and its influence on host immunity and disease. Cell Microbiol 2014;16(7):1024-1033. [Full text]
    
8. DeWitt JC, Germolec DR, Luebke RW, et al. Associating changes in the immune system with clinical diseases for interpretation in risk assessment. Curr Protoc Toxicol 2016;67:18.1.1-18.1.22. [Full text]
    
9. Blumenthal M, Goldberg A, Brinkcmann J, et al (Ed). Herbal Medicine. Expanded Commission E Monographs. American Botanical Council, Aust Texas 2000. 
    
10. European Medicines Agency. Committee on Herbal Medicinal Products. Assessment Report on Echinacea purpurea (L.) Moench., herba recens. 24 Nov 2014. [Full text]
     
11. World Health Organisation. WHO monographs on selected medicinal plants (Vol 1) 1999. Viewed 14 June 2017, http://apps.who.int/medicinedocs/en/d/Js2200e/
     
12. Goel V, Lovlin R, Chang C, et al. A proprietary extract from the Echinacea plant (Echinacea purpurea) enhances systemic immune response during a common cold. Phytother Res 2005;19(8):689-694. [Abstract]
     
13. Hall H, Fahlman MM, Engels HJ. Echinacea purpurea and mucosal immunity. Int J Sports Med 2007;28(9):792-797. [Abstract]
     
14. Kim HR, Oh SK, Lim W, et al. Immune enhancing effects of Echinacea purpurea root extract by reducing regulatory T cell number and function. Nat Prod Commun 2014;9(4):511-514. [Abstract]
     
15. Fonseca FN, Papanicolaou G, Lin H, et al. Echinacea purpurea (L.) Moench modulates human T-cell cytokine response. Int Immunopharmacol 2014;19(1):94-102. [Full text]
     
16. Yin SY, Wang WH, Wang BX, et al. Stimulatory effect of Echinacea purpurea extract on the trafficking activity of mouse dendritic cells: revealed by genomic and proteomic analysis. BMC Genomics 2010;11:612. [Full text]
     
17. Wang CY, Chiao MT, Yen PJ, et al. Modulatory effects of Echinacea purpurea extracts on human dendritic cells: a cell- and gene-based study. Genomics 2006;88(6):801-808. [Full text]
     
18. Pugh ND, Jackson CR, Pasco DS. 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(1):9-14. [Full text]
     
19. European Medicines Agency. Committee on Herbal Medicinal Products. Assessment Report on Andrographis paniculata Nees, folium 2014. Viewed 14 June 2017, http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_HMPC_asses...
     
20. World Health Organisation. WHO monographs on selected medicinal plants (Vol 2) 2004. Viewed 14 June 2017, http://apps.who.int/medicinedocs/en/d/Js4927e/
     
21. Jayakumar T, Hsieh CY, Lee JJ, et al. Experimental and clinical pharmacology of Andrographis paniculata and its major bioactive constituent andrographolide. Evid Based Complement Alt Med 2013;2013:846740. [Full text]
     
22. Hossain MD, Urbi Z, Sule A, et al. Andrographis paniculata (Burm. F.) Wall. ex Nees: a review of ethnobotany, phytochemistry and pharmacology. Scientific World J 2014;2014:274905. [Full text]
     
23. Saxena RC, Singh R, Kumar P, et al. A randomised double blind placebo controlled clinical evaluation of extract of Andrographis paniculata (KalmCold) in patients with uncomplicated upper respiratory tract infection. Phytomedicine 2010;17(3):178-185. [Abstract]
     
24. Wagner L, Cramer H, Klose P, et al. Herbal medicine for cough: a systematic review and meta-analysis. Forsch Komplementmed 2015;22(6):359-368. [Full text]
     
25. Low M, Khoo CS, Munch G, et al. An in vitro study of anti-inflammatory activity of standardised Andrographis paniculata extracts and pure andrographolide. BMC Complement Altern Med 2015;15:18. [Full text]
     
26. Cai W, Chen S, Li Y, et al. 14-Deoxy-11,12-didehydroandrographolide attenuates excessive inflammatory responses and protects mice lethally challenged with highly pathogenic A(H5N1) influenza viruses. Antiviral Res 2016;133:95-105. [Abstract]
     
27. Mishra US, Mishra A, Kumari R, et al. Antibacterial activity of ethanol extract of Andrographis paniculata. Indian J Pharm Sci 2009;71(14):436-438. [Full text]
     
28. Panda SK, Mohanta YK, Padhi L, et al. Large scale screening of ethnomedicinal plants for identification of potential antibacterial compounds. Molecules 2016;21(3):293. [Full text]
     
29. Banerjee M, Parai D, Chattopadhyay S, et al. Andrographolide: antibacterial activity against common bacteria of human health convern and possible mechanism of action. Folia Microbiol (Praha) 2017;62(3):237-244. [Abstract] 
     
30. Sheeja K, Kuttan G. Andrographis paniculata downregulates pro-inflammatory cytokine production and augments cell mediated immune response in metastatic tumor-bearing mice. Asian Pac J Cancer Prev 2010;11(3):723-729. [Full text]
     
31. Denzler KL, Waters R, Jacobs BL, et al. Regulation of inflammatory gene expression in PBMCs by immunostimulatory botanicals. PLoS One 2010;5(9):e12561. [Full text]
     
32. Liu M, Li P, Zeng X, et al. Identification and pharmacokinetics of multiple potential bioactive constituents after oral administration of Radix Astragali on cyclophosphamide-induced immunosuppression of Balb/c mice. Int J Mol Sci 2015;16:5047-5071. [Full text]
     
33. Li X, Qu L, Dong Y, et al. A review of recent research progress on the Astragalus genus. Molecules 2014;19:18850-18880. [Full text]
     
34. Yang B, Xiao B, Sun T. Antitumour and immunomodulatory activity of Astragalus membranaceus polysaccharides in H22 tumour bearing mice. Int J Biol Macromol 2013 62:287-290. [Abstract]
     
35. Qin Q, Niu J, Wang Z, et al. Astragalus membranaceus extract activates immune response in macrophages via heparanase. Molecules 2012;17(6):7232-7240. [Full text]
     
36. Lv X, Chen D, Yang L, Zhu N, Li J, Zhao J et al. Comparative studies on the immunoregulatory effects of three polysaccharides using high content imaging system. Int J Biol Macromol 2016;86:28-42. [Abstract]
     
37. Du X, Chen X, Zhao B, et al. Astragalus polysaccharides enhance the humoral and cellular immune responses of hepatitis B surface antigen vaccination through inhibiting the expression of transforming growth factor beta and the frequency of regulatory T cells. FEMS Immunol Med Microbiol 2011;63(2):228-235. [Full text]
     
38. Lai PK, Chan JY, Wu SB, et al. Anti-inflammatory activities of an active fraction isolated from the root of Astragalus membranaceus in RAW 264.7 macrophages. Phytother Res 2014;28(3):395-404. [Abstract]
     
39. Zhang WJ, Frei B. Astragaloside IV inhibits Nf-kB activation and inflammatory gene expression in LPS-treated mice. Mediators Inflamm 2015;2015:274314. [Full text]
     
40. Batbayar N, Banzragch D, Inngjerdingen KT, et al. Polysaccharides from Mongolian plants and their effect on the complement system: I. Polysaccharides from plants of the Asteraceae family. Asian J Trad Med 2008;3(1):33-41. [Full text]
     
41. Mazzio EA, Bauer D, Mendonca P, et al. Natural product HTP screening for attenuation of cytokine-induced neutrophil chemo attractants (CINCs) and NO2- in LPS/IFN-gamma activated glioma cells. J Neuroimmunol 2017;302:10-19. [Full text]
     
42. Danilets MG, Bel’skii IuP, Gur’ev AM, et al. [Effect of plant polysaccharides on TH1-dependent immune response: screening investigation]. Eksp Klin Farmakol 2010;73(6):19-22. [Abstract]
     
43. O’Shea S, Lucey B, Cotter L. In vitro activity of Inula helenium against clinical Staphylococcus aureus strains including MRSA. Br J Biomed Sci 2009;66(40):186-189. [Abstract]
     
44. Park EJ, Kim YM, Park SW, et al. Induction of HO-1 through p38 MAPK/Nrf2 signaling pathway by ethanol extract of Inula helenium L. reduces inflammation in LPS-activated RAW 264.7 cells and CLP-induced septic mice. Food Chem Toxicol 2013;55:386-395. [Abstract]
     
45. European Medicines Agency. Committee on Herbal Medicinal Products. Assessment Report on Olea europaea L., folium 2011. Viewed 14 June 2017, http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_HMPC_asses...
     
46. Ghanbari R, Anwar F, Alkharfy KM, et al. Valuable nutrients and functional bioactives in different parts of olive (Olea europaea L.)—A review. Int J Mol Sci 2012;13(3):3291-3340. [Full text]
     
47. Sudjana AN, D'Orazio C, Ryan V, et al. Antimicrobial activity of commercial Olea europaea (Olive) leaf extract. Int J Antimicrob Agents 2009;33(5):461-463. [Abstract]
     
48. Markin D, Duek L, Berdicevsky I. In vitro antimicrobial activity of olive leaves. Mycoses 2003;46(3-4):132-136. [Abstract]
     
49. Park JH, Jung JH, Yang JY, et al. Olive leaf down-regulates the oxidative stress and immune dysregulation in streptozotocin-induced diabetic mice. Nutr Res 2013;33(11):942-951. [Abstract]
     
50. European Medicines Agency. Committee on Herbal Medicinal Products. Assessment report on Sambucus nigra L. fructus 2013. Viewed 14 June 2017, http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_HMPC_asses...
     
51. Tiralongo E, Wee SS, Lea RA. Elderberry supplementation reduces cold duration and symptoms in air-travellers: a randomized, double-blind, placebo-controlled clinical trial. Nutrients 2016;8:182. [Full text]
     
52. Krawitz C, Mraheil MA, Stein M, et al. Inhibitory activity of a standardised elderberry liquid extract against clinically-relevant human respiratory bacterial pathogens and influenza A and B viruses. BMC Complement Altern Med 2011;11:16. [Full text]
     
53. Kinoshita E, Hayashi K, Katayama H, et al. Anti-influenza virus effects of elderberry juice and its fractions. Biosci Biotechnol Biochem 2012;76(9):1633-1638. [Full text]
     
54. Badescu M, Badulescu O, Badescu L. et al. Effects of Sambucus nigra and Aronia melanocarpa extracts on immune system disorders within diabetes mellitus. Pharm Biol 2015;53(4):533-539. [Abstract]
     
55. European Medicines Agency. Committee on Herbal Medicinal Products. Assessment report on Thymus vulgaris L. vulgaris zygis L., herba 2013. Viewed 14 June 2017, http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_HMPC_asses...
     
56. Hotta M, Nakata R, Katsukawa M, et al. Carvacrol, a component of thyme oil, activates PPAR-alpha and gamma and suppresses COX-2 exprssion. J Lipid Res 2010;51(1):132-139. [Full text]
     
57. Oliviero M, Romilde I, Beatrice MM, et al. Evaluations of thyme extract effects in human normal bronchial and tracheal epithelial cells lines and in human lung cancer cell line. Chem Biol Interact 2016;256:125-133. [Abstract]
     
58. Sienkiewicz M, Kysakowska M, Denys P, et al. The antimicrobial activity of thyme essential oil against multidrug resistant clinical bacterial strains. Microb Drug Resist 2012;18(2):137-148. [Abstract]

---

DISCLAIMER: 

The information provided on FX Medicine is for educational and informational purposes only. The information provided on this site is not, nor is it intended to be, a substitute for professional advice or care. Please seek the advice of a qualified health care professional in the event something you have read here raises questions or concerns regarding your health.