Review
Plant-derived medicines: A novel class of immunological adjuvants

https://doi.org/10.1016/j.intimp.2010.10.014Get rights and content

Abstract

Plant-derived medicines have a long history of use for the prevention and treatment of human disease. Today, many pharmaceuticals currently approved by the Food and Drug Administration (FDA) have origins to plant sources. A major role for plant-derived compounds based on the reported immunomodulatory effects has emerged in recent times and has led to the rigorous scientific examination to determine efficacy and safety. The discovery of novel plant compounds with immune system modulating activities has become an increasingly important area of research, particularly in the search for new-generation vaccine adjuvants. This review discusses the important role of plant-derived medicines as immunomodulators and provides evidence in support of the continued investigation of this new class of drugs for the maintenance of human health. The identification and characterization of plant compounds that augment new or existing vaccines, and in particular mucosally administered vaccines, will be of significant interest to vaccinologists and immunologists.

Introduction

The use of plant-derived medicines in the treatment and prevention of disease has been documented over five millennia. Plants were extensively utilised by ancient civilisations of Mesopotamia, Egypt, Greece, India and China for inflammation, cancer and for the maintenance of health [1], [2], [3]. In particular, popular plant-derived medicines such as Ginseng, Echinacea and garlic have persisted over time and remarkably, continue to be used today for indications similar to those described historically [4], [5]. In the early nineteenth century, the advent of modern medicine saw a rapid decline in botanical medicinal use. Vaccination, the discovery of antibiotics and improvements in medical technology all contributed to this demise. Today, plant-derived medicines are classified as complementary and alternative medicines (CAM) and are regulated by the Therapeutic Goods Administration (TGA) in Australia and by the Dietary Health and Supplement Education Act (DHSEA) under the Federal Drug Administration (FDA) in the USA [6], [7], [8].

It has been estimated by the World Health Organisation (WHO) that up to 80% of the world's population, mostly in developing countries, rely on plant medicines for primary health care [9], [10], [11], [12]. Countries such as Ethiopia, India and Rwanda have reported that 90%, 70% and 70% of the population, respectively, use plant-derived medicines routinely for health [13]. In Western countries, botanical medicinal consumption is on the increase owing to a variety of reasons including an inability of Western medicine to effectively treat certain diseases (e.g. AIDS, malaria, and cancer), a preference for natural alternatives, perceived efficacy and safety of natural products and a willingness to self-medicate [14], [15], [16]. The magnitude of botanical medicinal acceptance in Western society is realised by global market evaluations of at least US $15 billion per year with the WHO recently estimating the market at close to US $60 billion or 20% of the total drug market [17], [18]. In Australia, AU $1 billion is spent annually on CAM therapies comprising AU $200 million on plant-derived medicines [8].

Plant-derived medicines have contributed significantly to Western healthcare. Almost 30% of all FDA-approved pharmaceuticals currently available have a botanical origin [12], [19]. Drugs such as Digoxin, Taxol, Morphine, Salbutamol, Vincristine and Vinblastine are examples of common ‘Western’ prescription medicines based on plant compounds (Table 1; [20], [21]). Moreover, the pain-relieving properties of aspirin, a medicinal compound isolated from the bark of the willow tree and one of the most widely used over-the-counter medications today, was first described by Hippocrates [22]. Although plant medicines are used increasingly in Western society, there is still reluctance by the medical establishment to accept that these may have potential benefits to human health. Only the rigorous scientific investigation of plant-derived medicines will validate or refute any perceived or actual biological properties. Consumer use of plant medicines for health has reached unparalleled levels in Western society and has prompted the necessity for such investigations.

A major research interest has focussed on the immunomodulatory properties of plant-derived medicines. This review will discuss the evidence for plant-derived medicines to modulate immune responses particularly antigen-specific, adaptive immunity.

Section snippets

Immunomodulation by plant-derived medicines

The immune system is a complex defence network that protects the host from disease. Generation of an effective immune response typically involves the critical steps of antigen presentation, activation of T- and/or B-lymphocytes and the resultant secretion of immune effector molecules such as antibodies and cytokines. Indeed, the principles of vaccination rely on the ability to modulate these immune parameters to confer life-long protection from disease. Vaccines induce protective immune

The use of plant-derived medicines in healthcare

The historical record dictates that plants have been integrally associated with the practice of medicine. Over the past twenty years, the widespread use of these natural alternatives has provided the impetus for rigorous scientific investigation to validate the perceived benefits. Many plant-derived medicines are said to provide a ‘tonic’ effect that assists the body in the maintenance of health. From this, it may be reasonable to presume some immune basis for this effect, since improved

Conclusion

Evidence from the scientific literature supports the use of plant-derived medicines to stimulate immune function. Characterisation of these preparations in terms of biological activity and bioactive components will promote the utility of such preparations in the future. While the potential for use of plant-derived medicines should not be underestimated, the cellular and molecular mechanisms of action need to be clearly defined. One major limitation appears to be the lack of congruence in

References (116)

  • M. Takei et al.

    Dendritic cells maturation promoted by M1 and M4, end products of steroidal ginseng saponins metabolized in digestive tracts, drive a potent Th1 polarization

    Biochem Pharmacol

    (2004)
  • A. Rhule et al.

    Toll-like receptor ligand-induced activation of murine DC2.4 cells is attenuated by Panax notoginseng

    J Ethnopharmacol

    (2008)
  • C.Y. Wang et al.

    Modulatory effects of Echinacea purpurea extracts on human dendritic cells: a cell- and gene-based study

    Genomics

    (2006)
  • J.M. Benson et al.

    Echinacea purpurea extracts modulate murine dendritic cell fate and function

    Food Chem Toxicol

    (2010)
  • P.H. Makela

    Vaccines, coming of age after 200 years

    FEMS Microbiol Rev

    (2000)
  • L. Krakowski et al.

    The effect of nonspecific immunostimulation of pregnant mares with 1, 3/1, 6 glucan and levamisole on the immunoglobulins levels in colostrum, selected indices of nonspecific cellular and humoral immunity in foals in neonatal and postnatal period

    Vet Immunol Immunopathol

    (1999)
  • U. Tiwari et al.

    Immunomodulatory effects of aqueous extract of Tridax procumbens in experimental animals

    J Ethnopharmacol

    (2004)
  • B. Morein et al.

    Immunomodulation by iscoms, immune stimulating complexes

    Methods

    (1999)
  • L. Yang et al.

    Compound Chinese herbal medicinal ingredients can enhance immune response and efficacy of RHD vaccine in rabbit

    Vaccine

    (2008)
  • G. Ragupathi et al.

    Evaluation of widely consumed botanicals as immunological adjuvants

    Vaccine

    (2008)
  • A. Estrada et al.

    Isolation and evaluation of immunological adjuvant activities of saponins from Polygala senega L

    Comp Immunol Microbiol Infect Dis

    (2000)
  • T. Nagai et al.

    Onjisaponins, from the root of Polygala tenuifolia Willdenow, as effective adjuvants for nasal influenza and diphtheria–pertussis–tetanus vaccines

    Vaccine

    (2001)
  • H.X. Sun

    Haemolytic activities and adjuvant effect of Bupleurum chinense saponins on the immune responses to ovalbumin in mice

    Vaccine

    (2006)
  • H.X. Sun et al.

    Immunological adjuvant effect of Glycyrrhiza uralensis saponins on the immune responses to ovalbumin in mice

    Vaccine

    (2006)
  • Y. Sun et al.

    Haemolytic activities and adjuvant effect of Anemone raddeana saponins (ARS) on the immune responses to ovalbumin in mice

    Int Immunopharmacol

    (2008)
  • N. Makare et al.

    Immunomodulatory activity of alcoholic extract of Mangifera indica L. in mice

    J Ethnopharmacol

    (2001)
  • T. Nagai et al.

    In vivo anti-influenza virus activity of kampo (Japanese herbal) medicine “Sho-seiryu-to” and its mode of action

    Int J Immunopharmacol

    (1994)
  • T. Nagai et al.

    Pinellic acid from the tuber of Pinellia ternata Breitenbach as an effective oral adjuvant for nasal influenza vaccine

    Int Immunopharmacol

    (2002)
  • F.S. Quan et al.

    Ginseng and Salviae herbs play a role as immune activators and modulate immune responses during influenza virus infection

    Vaccine

    (2007)
  • A. Estrada et al.

    Adjuvant action of Chenopodium quinoa saponins on the induction of antibody responses to intragastric and intranasal administered antigens in mice

    Comp Immunol Microbiol Infect Dis

    (1998)
  • C. Bodinet et al.

    Effect of an orally applied herbal immunomodulator on cytokine induction and antibody response in normal and immunosuppressed mice

    Phytomedicine

    (2002)
  • C.A. Akdis et al.

    Mechanisms and treatment of allergic disease in the big picture of regulatory T cells

    J Allergy Clin Immunol

    (2009)
  • M. Kato et al.

    Characterization of the immunoregulatory action of saikosaponin-d

    Cell Immunol

    (1994)
  • Y. Ikeda et al.

    Possible involvement of suppression of Th2 differentiation in the anti-allergic effect of Sho-seiryu-to in mice

    Jpn J Pharmacol

    (2002)
  • E. Ko et al.

    Traditional Korean medicine (SCRT) modulate Th1/Th2 specific cytokine production in mice CD4+ T cell

    J Ethnopharmacol

    (2004)
  • T. Nagai et al.

    Anti-allergic activity of a Kampo (Japanese herbal) medicine “Sho-seiryu-to (Xiao-Qing-Long-Tang)” on airway inflammation in a mouse model

    Int Immunopharmacol

    (2004)
  • E. Zvetkova et al.

    Aqueous extracts of Crinum latifolium (L.) and Camellia sinensis show immunomodulatory properties in human peripheral blood mononuclear cells

    Int Immunopharmacol

    (2001)
  • Z. Amirghofran et al.

    Evaluation of the immunomodulatory effects of five herbal plants

    J Ethnopharmacol

    (2000)
  • E.H. Kim et al.

    Soamsan, a traditional Korean medicine, enhances antigen-specific immune responses in low-responder mice via the combined activity of glycoproteins and endotoxins

    Int Immunopharmacol

    (2002)
  • J.C. Lee et al.

    Selective priming of Th1-mediated antigen-specific immune responses following oral administration of mixed prescriptions of traditional Korean medicines

    Clin Chim Acta

    (2003)
  • A. Matthias et al.

    Echinacea alkylamides modulate induced immune responses in T-cells

    Fitoterapia

    (2008)
  • P. Morazzoni et al.

    In vitro and in vivo immune stimulating effects of a new standardized Echinacea angustifolia root extract (Polinacea)

    Fitoterapia

    (2005)
  • Z. Xiao et al.

    Beta-glucan enhancement of T cell IFNgamma response in swine

    Vet Immunol Immunopathol

    (2004)
  • A. Panossian et al.

    Effect of andrographolide and Kan Jang–fixed combination of extract SHA-10 and extract SHE-3–on proliferation of human lymphocytes, production of cytokines and immune activation markers in the whole blood cells culture

    Phytomedicine

    (2002)
  • T. Ganguly et al.

    Immunomodulatory effect of Tylophora indica on Con A induced lymphoproliferation

    Phytomedicine

    (2001)
  • D.J. Newman et al.

    The influence of natural products upon drug discovery

    Nat Prod Rep

    (2000)
  • N. Wiseman

    Traditional Chinese medicine: a brief outline

    J Chem Inf Comput Sci

    (2002)
  • C. Berlin

    Herbal medicine

    Clin Pediatr (Phila)

    (2001)
  • H.B. Matthews et al.

    Medicinal herbs in the United States: research needs

    Environ Health Perspect

    (1999)
  • P. Talalay

    The importance of using scientific principles in the development of medicinal agents from plants

    Acad Med

    (2001)
  • Cited by (86)

    • Immunogenetic disorders: Treatment with phytomedicines

      2022, Immunogenetics: a Molecular and Clinical Overview: Clinical Applications of Immunogenetics, Volume II
    • Panax quinquefolius (North American ginseng) cell suspension culture as a source of bioactive polysaccharides: Immunostimulatory activity and characterization of a neutral polysaccharide AGC1

      2019, International Journal of Biological Macromolecules
      Citation Excerpt :

      The recognition and binding of complex carbohydrate structures by Toll-like receptors (TLR-4) or by the carbohydrate-recognition domain (CRD) of lectins activate innate immune cells such as macrophages, triggering several coordinated processes including increased phagocytic activity, chemokinesis and chemotaxis [6,7]. Therefore, these complex carbohydrates have the potential to be used as exogenous immunomodulators or adjuvants for existing immunotherapy and vaccine purposes [8]. The development of therapies to enhance the immune response has been proposed as an efficient and effective long-term healthcare strategy [1].

    View all citing articles on Scopus
    View full text