clinical applications for immune system support

Clinical Applications for Immune System Support

2

Hypericum perforatum

Immune System Support

While being vigilant and practicing good daily habits such as healthy

eating, adequate sleep, exercise and personal hygiene are key to the

defence against bacterial and viral infections, herbal medicine has shown

to be effective in supporting various aspects of the immune system to

enhance the body’s defences.

This book provides a detailed list of infections that may commonly present in

clinical practice, alongside evidence-based herbs and their active constituents

responsible for supporting the immune system.

Additionally, there is a dedicated section on how a `cytokine storm’ can be

triggered during severe infections. Furthermore, clinically researched herbs

are discussed which may support innate immune functions.

How to use this book

The book is designed to provide naturopaths and herbalists

with foundational support related to commonly seen

bacterial and viral infections.

It includes herbs that can form a base in the

development of herbal formulations and

treatment plans.

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Contents

Antibacterial Support ..............................................................................................................................................................................................4

Herbal Antibacterial Support: Gram-negative ............................................................................................................................. 5

Herbal Antibacterial Support: Gram-positive ................................................................................................................................ 6

References ............................................................................................................................................................................................................................................... 7

Antiviral Support ............................................................................................................................................................................................................8

Herbal Antiviral Support ................................................................................................................................................................................................... 9

Cytokine Storm .............................................................................................................................................................................................................10

References ...........................................................................................................................................................................................................................................10

General Guide for Immune System Health as a Preventative Measure ...............................12

Innate Immune System ................................................................................................................................................................................................12

First-line Defence Protection ................................................................................................................................................................................12

Second-line Defence Protection .....................................................................................................................................................................12

Herbal Support..............................................................................................................................................................................................................................14

Conclusion ............................................................................................................................................................................................................................................15

References ...........................................................................................................................................................................................................................................15

MediHerb® Clinical Applications for Immune System Support 3

Antibacterial Support

Bacteria are classified under 2 categories, determined under microscopic evaluation by their shape and the colour they turn under a staining method.1

Gram-positive bacteria stain blue under microscopic evaluation due to the thick peptidoglycan cell wall. Gram-positive bacteria comprise of cocci, bacilli, or branching filaments.1

Gram-negative bacteria do not stain under microscopic evaluation due to the thinner outer membrane, which serves as a highly resistant permeable barrier. Gram-negative bacteria have an ‘enveloped’ outer cell wall containing an outer membrane which house lipopolysaccharides (endotoxins); partially cross-linked peptidoglycan cell wall; and the inner membrane. Gram-negative bacteria are the most likely bacteria to develop antibiotic resistance.2

4

Cinnamomum verum


Bacteria Herb (common name)

Active Constituent (primary active responsible for the mechanism of action)

Mechanism of Action

Escherichia coli Thyme Oil

Oregano Oil

Thymol, linalyl acetate, menthol Inhibits growth of bacteria; damages membrane integrity of bacteria; interferes with negative charge of cell3

Nigella Thymoquinone Reduced sepsis-related mortality by over 80% in a mouse study; reduced TNF-α and IL-24

Phellodendron and Golden Seal

Berberine Exhibited antibacterial activity on E. coli5

Helicobacter pylori Garlic Allicin, alliin Direct antibacterial action6

Pomegranate Gallic acid, ellagic acid, punicalin, tannins

Demonstrated strong inhibition of bacteria in vitro7

Propolis Phenolic compounds, essential oils Strong inhibitory effect; inhibited urease8

Pseudomonas aeruginosa

Oregano oil Thymol and carvacrol Antimicrobial; increased permeability of cells; dissipated pH gradients; leakage of inorganic ions9

Clove oil Oregano oil Peppermint oil

Eugenol (Clove oil), Carvone and carveol, (Peppermint oil), and thymol (Oregano oil)

Anti-adherence, anti-biofilm effect; interferes with formation of mature biofilms10

Myrrh Sesquiterpenes, monoterpenoids Inhibition of bacteria in vitro11, 12

Klebsiella spp. Pomegranate Gallic acid, ellagic acid, punicalin, tannins

Inhibition of bacteria13

Propolis Polyphenols, flavonoids Inhibited bacterial growth and multiplication of bacteria; antioxidant with radical scavenging activity14

Cinnamon Cinnamaldehyde, transcinnamaldehyde

Inhibits bacteria due to interference with electron transfer and reaction with nitrogen components15

Shigella spp. Oregano Oil

Thyme Oil

Carvacrol, thymol Inhibition of bacteria in washing at 0.5%, undetectable levels detected at 1% solution16


Antibacterial action inhibitory effect in vitro17

Cinnamon oil Cinnamaldehyde Inhibitory effects and direct killing of bacteria completely18

Methicillin-resistant Staphylococcus aureus (MRSA)

Oregano oil Carvacrol and thymol Demonstrated topical antimicrobial effects19

Phellodendron Berberine Antimicrobial action; inhibit the MRSA adhesion and intracellular invasion20, 21


Inhibits bacteria; damages cell walls of resistant bacteria7

Green Tea Polyphenols, EGCG, tannins Inhibits bacteria; prevents attachment of bacteria to host cell membrane (anti-adhesive agent); EGCG may interact with outer membrane22

Herbal Antibacterial Support: Gram-negative


Bacteria Herb (common name)


Mechanism of Action

Enterococcus spp. Myrrh Sesquiterpenes, monoterpenes Ethanolic extracts found to have high antimicrobial action in vitro23


Antimicrobial action; tannins inhibit mitochondrial mechanisms of bacteria; destabilise cytoplasmic membrane; deprive substrates required for growth of bacteria24

Staphylococcus aureus Phellodendron, Golden Seal

Berberine Antimicrobial action; efflux pump inhibitor25

Oregano Oil

Thyme Oil

Thymol, linalyl acetate, menthol Inhibits growth of bacteria; damages membrane integrity of bacteria; interferes with negative charge of cell3, 9

Nigella Thymoquinone Inhibits biofilms; antimicrobial; increased oxidative activity in bacterial cell26, 27

Myrrh Sesquiterpenes Ethanolic extract of myrrh found to have high antibacterial effect in vitro28

Streptococcus spp. Pomegranate Gallic acid, ellagic acid, punicalin, tannins

Inhibitory effect demonstrated in vitro17

Oregano oil Thymol, carvacrol Reduced resistant bacteria to antibiotic therapy – combination antimicrobial effect29

Phellodendron, Golden Seal

Berberine Anti-adherence effect of bacteria onto host cells; immobilised fibronectin30

Clostridium difficile Nigella Thymoquinone Antibacterial activity noted in vitro31

Myrrh Oleoresins, sesquiterpenes, monoterpenoids

Antibacterial activity noted in vitro32

Nigella sativa

Herbal Antibacterial Support: Gram-positive


References

1: Sizar O, Unakal CG. Gram Positive Bacteria. StatPearls [Internet]: StatPearls Publishing; 2019.2: Exner M, Bhattacharya S, Christiansen B, Gebel J, Goroncy-Bermes P, Hartemann P, et al. Antibiotic resistance: What is so special about multidrug-resistant Gram-negative bacteria? GMS hygiene and infection control. 2017;12.3: Trombetta D, Castelli F, Sarpietro MG, Venuti V, Cristani M, Daniele C, et al. Mechanisms of antibacterial action of three monoterpenes. Antimicrobial agents and chemotherapy. 2005;49(6):2474-8.4: Alkharfy KM, Al-Daghri NM, Al-Attas OS, Alokail MS. The protective effect of thymoquinone against sepsis syndrome morbidity and mortality in mice. International immunopharmacology. 2011;11(2):250-4.5: Kong W-J, Xing X-Y, Xiao X-H, Zhao Y-L, Wei J-H, Wang J-B, et al. Effect of berberine on Escherichia coli, Bacillus subtilis, and their mixtures as determined by isothermal microcalorimetry. Applied microbiology and biotechnology. 2012;96(2):503-10.6: Zardast M, Namakin K, Kaho JE, Hashemi SS. Assessment of antibacterial effect of garlic in patients infected with Helicobacter pylori using urease breath test. Avicenna journal of phytomedicine. 2016;6(5):495.7: Howell AB, D’Souza DH. The pomegranate: effects on bacteria and viruses that influence human health. Evidence-Based Complementary and Alternative Medicine. 2013;2013.8: Baltas N, Karaoglu SA, Tarakci C, Kolayli S. Effect of propolis in gastric disorders: inhibition studies on the growth of Helicobacter pylori and production of its urease. Journal of enzyme inhibition and medicinal chemistry. 2016;31(sup2):46-50.9: Lambert R, Skandamis PN, Coote PJ, Nychas GJ. A study of the minimum inhibitory concentration and mode of action of oregano essential oil, thymol and carvacrol. Journal of applied microbiology. 2001;91(3):453-62.10: El Abed S, Houari A, Latrache H, Remmal A, Koraichi SI. In vitro activity of four common essential oil components against biofilm-producing Pseudomonas aeruginosa. Research Journal of Microbiology. 2011;6(4):394.11: Omer S, Adam S, Mohammed O. Antimicrobial activity of Commiphora myrrha against some bacteria and Candida albicans isolated from gazelles at King Khalid Wildlife Research Centre. Research Journal of Medicinal Plant. 2011;5(1):65-71.12: Biggs I, Sirdaarta J, White A, Cock IE. GC-MS Analysis of Commiphora molmol Oleo-Resin Extracts which Inhibit the growth of Bacterial Triggers of Selected Autoimmune Diseases. Pharmacognosy Journal. 2016;8(3).13: Malviya S, Jha A, Hettiarachchy N. Antioxidant and antibacterial potential of pomegranate peel extracts. Journal of food science and technology. 2014;51(12):4132-7.14: Kubiliene L, Laugaliene V, Pavilonis A, Maruska A, Majiene D, Barcauskaite K, et al. Alternative preparation of propolis extracts: comparison of their composition and biological activities. BMC complementary and alternative medicine. 2015;15(1):156.15: Al-Qurashi FMS, Kadhum ZIA. Antibacterial Effect of some Herbal plants against Pathogenic Bacteria Isolated from Patients with Urinary Tract Infections (UTI). AL-yarmouk Journall. 2019;11(1):36-47.16: Bagamboula C, Uyttendaele M, Debevere J. Inhibitory effect of thyme and basil essential oils, carvacrol, thymol, estragol, linalool and p-cymene towards Shigella sonnei and S. flexneri. Food microbiology. 2004;21(1):33-42.

17: Hassan SM, Hamad AK, Farhan A. The effect of pomegranate extracts on bacteria. Journal of Raparin University-Vol. 2018;5(15):5.18: Saha SR, Bari M, Inatsu Y, Kawampto S, Hoque MM. Antibacterial Activity of Cinnamaldehyde and Carvacrol against Foodborne Pathogens and Spoilage Bacteria. Bangladesh Journal of Microbiology. 2017;34(2):91-6.19: Nostro A, Blanco AR, Cannatelli MA, Enea V, Flamini G, Morelli I, et al. Susceptibility of methicillin-resistant staphylococci to oregano essential oil, carvacrol and thymol. FEMS microbiology letters. 2004;230(2):191-5.20: Yu H-H, Kim K-J, Cha J-D, Kim H-K, Lee Y-E, Choi N-Y, et al. Antimicrobial activity of berberine alone and in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus. Journal of medicinal food. 2005;8(4):454-61.21: Tillhon M, Ortiz LMG, Lombardi P, Scovassi AI. Berberine: new perspectives for old remedies. Biochemical pharmacology. 2012;84(10):1260-7.22: Radji M, Agustama RA, Elya B, Tjampakasari CR. Antimicrobial activity of green tea extract against isolates of methicillin–resistant Staphylococcus aureus and multi–drug resistant Pseudomonas aeruginosa. Asian Pacific journal of tropical biomedicine. 2013;3(8):663-7.23: Chandrasekharnath N, Mahlakshmi Y, Jayalakshmi L, Venkanna B, Uma A. Screening and isolation of bioactive factors from Commiphora myrrha and evaluation of their antimicrobial activity. IJERA. 2013;3(2):1291-4.24: Jain PA, Tejaswi S, Parinitha M, Shetty S, Ambikathanaya U. Comparative Evaluation of Antibacterial Activity of Punica granatum, Acacia nilotica and Emblica officinalis against Enterococcus faecalis and Their Smear Layer Removal Ability When Used as Endodontic Irrigants: an In-Vitro Study. International Journal of Research and Review. 2019;6(8):184-94.25: Patil T, Patil S, Patil S, Patil A. Antimicrobial Profile of Antidiabetic Drug: Berberine. Int J Pharmacogn Phytochem Res. 2015;7:45-50.26: Chaieb K, Kouidhi B, Jrah H, Mahdouani K, Bakhrouf A. Antibacterial activity of Thymoquinone, an active principle of Nigella sativa and its potency to prevent bacterial biofilm formation. BMC complementary and alternative medicine. 2011;11(1):29.27: Goel S, Mishra P. Thymoquinone inhibits biofilm formation and has selective antibacterial activity due to ROS generation. Applied microbiology and biotechnology. 2018;102(4):1955-67.28: Goyal P, Chauhan A, Kaushik P. Assessment of Commiphora wightii (Arn.) Bhandari (Guggul) as potential source for antibacterial agent. Journal of Medicine and Medical Sciences. 2010;1(3):71-5.29: Palaniappan K, Holley RA. Use of natural antimicrobials to increase antibiotic susceptibility of drug resistant bacteria. International journal of food microbiology. 2010;140(2-3):164-8.30: Sun D, Courtney HS, Beachey EH. Berberine sulfate blocks adherence of Streptococcus pyogenes to epithelial cells, fibronectin, and hexadecane. Antimicrobial agents and chemotherapy. 1988;32(9):1370-4.31: Randhawa MA, Alenazy AK, Alrowaili MG, Basha J. An active principle of Nigella sativa L., thymoquinone, showing significant antimicrobial activity against anaerobic bacteria. Journal of intercultural ethnopharmacology. 2017;6(1):97.32: Aljarallah KM. Inhibition of Clostridium difficile by natural herbal extracts. Journal of Taibah University Medical Sciences. 2016;11(5):427-31.


Antiviral Support

A virus is a particle (known as a virion) that requires a host cell to replicate. All viruses have a capsid which holds either RNA or DNA, depending on the type of virus, it will contain 4 - 200 proteins for encoding.1 Once inside of a cell, it will commandeer the cellular machinery to replicate the genetic material of the virus. Some viruses will also contain an outer lipid bilayer known as an envelope.2 Viral entry into a cell can be via receptor mediated fusion and endocytosis.

Enveloped viruses will release a capsid into the cytosol through fusing directly with the plasma membrane of a cell.

Non-enveloped viruses enter by disrupting the plasma membrane or forming pores. Utilising intracellular trafficking pathways is another way in which some viruses will invade a cell.3

When selecting an antiviral herb, it is important to assess whether the target virus is enveloped or non-enveloped. In cases where the virus has not been identified, then herbs which target both may be advantageous.

Phellodendron amurense

Non-enveloped Virus

Papillomaviruses9

Rhinoviruses10

Adenoviruses10

Enveloped Virus

Influenza viruses4

Corona viruses5

Herpes viruses (eg. HSV 1 and 2, EBV, Varicella)6

Paramyxovirus (eg. Measles, Mumps)7

Dengue viruses8


Virus Herb (common name)


Mechanism of Action

Influenza A and B11,12 Elderberry Cyanidin 3-glucoside13 Prevention of virus entry into the host cell and transmission to other host cells. In addition to this, it has been shown to upregulate TNF-α, IL-6 and IL-8. Its antiviral activity has been observed to be most efficacious in the prodromal stage13

Influenza A14 Licorice Glycyrrhizin, glycyrrhetinic acid14 Inhibition of viral uptake into the cells, reduced viral latency and T-cell mediated induction of interferon-gamma14HSV14

Varicella zoster14

Arboviruses14

SARS14

EBV14

HSV15 Propolis Caffeic acids, flavonoids, benzoic acid esters15

Disruption of virus envelope, inhibition of transmission to cells and propagation15

Influenza A16

Influenza B16

Polio16

HIV16

Influenza A14 St. John’s Wort Hypericin, pseudohypericin17 Viral inhibition is dependent on the envelope and several mechanisms have been observed. These include: inhibition of budding virions, prevention of viral uncoating and prevention of replication through inhibition of protein kinase activity17

HSV14

Parainfluenza virus14

Cytomegalovirus14

Verruca vulgaris (common warts)18

Thuja Thuja polysaccharides, essential oil including thujone18

Stimulation of cytokine production including TNF-α, IL-1 and IL-6, increased antibody production and macrophage activation18

Influenza A18

HIV18

HSV19

Herbal Antiviral Support


References

1: Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J. Viruses: Structure, function, and uses. InMolecular Cell Biology. 4th edition 2000. WH Freeman.2: Cohen FS. How viruses invade cells. Biophysical journal. 2016 Mar 8;110(5):1028-32.3: Thorley JA, McKeating JA, Rappoport JZ. Mechanisms of viral entry: sneaking in the front door. Protoplasma. 2010 Aug 1;244(1-4):15-24.4: Bouvier NM, Palese P. The biology of influenza viruses. Vaccine. 2008 Sep 12;26:D49-53.5: Fehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. In Coronaviruses 2015 (pp. 1-23). Humana Press, New York, NY.6: Davison AJ. Evolution of the herpesviruses. Veterinary microbiology. 2002 Apr 22;86(1-2):69-88.7: Harrison MS, Sakaguchi T, Schmitt AP. Paramyxovirus assembly and budding: building particles that transmit infections. The international journal of biochemistry & cell biology. 2010 Sep 1;42(9):1416-29.8: Khetarpal N, Khanna I. Dengue fever: causes, complications, and vaccine strategies. Journal of immunology research. 2016;2016.9: Buck CB, Thompson CD, Pang YY, Lowy DR, Schiller JT. Maturation of papillomavirus capsids. Journal of virology. 2005 Mar 1;79(5):2839-46.10: Suomalainen M, Greber UF. Uncoating of non-enveloped viruses. Current opinion in virology. 2013 Feb 1;3(1):27-33.11: Roschek Jr B, Fink RC, McMichael MD, Li D, Alberte RS. Elderberry flavonoids bind to and prevent H1N1 infection in vitro. Phytochemistry. 2009 Jul 1;70(10):1255-61.12: Zakay-Rones Z, Thom E, Wollan T, Wadstein J. Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections. Journal of International Medical Research. 2004 Apr;32(2):132-40.13: Torabian G, Valtchev P, Adil Q, Dehghani F. Anti-influenza activity of elderberry (Sambucus nigra). Journal of functional foods. 2019 Mar 1;54:353-60.

14: Bone K, Mills S. Principles and Practice of Phytotherapy: Modern Herbal Medicine. 2nd Edition ed. Sydney: Elsevier Ltd; 2013.15: Schnitzler P, Neuner A, Nolkemper S, Zundel C, Nowack H, Sensch KH, Reichling J. Antiviral activity and mode of action of propolis extracts and selected compounds. Phytotherapy Research. 2010 Jan;24(S1):S20-8.16: Pobiega K, Gniewosz M, Kraśniewska K. Antimicrobial and antiviral properties of different types of propolis. Zesz. Probl. Postępów Nauk Rol. 2017;589:69-79.17: Birt DF, Widrlechner MP, Hammer KD, Hillwig ML, Wei J, Kraus GA, Murphy PA, McCoy JA, Wurtele ES, Neighbors JD, Wiemer DF. Hypericum in infection: Identification of anti-viral and anti-inflammatory constituents. Pharmaceutical biology. 2009 Aug 1;47(8):774-82.18: Naser B, Bodinet C, Tegtmeier M, Lindequist U. Thuja occidentalis (Arbor vitae): a review of its pharmaceutical, pharmacological and clinical properties. Evidence-based complementary and alternative medicine. 2005;2(1):69-78.19: Bone K. A Clinical Guide to Blending Liquid Herbs: Herbal Formulations for the Individual Patient. St. Louis: Churchill Livingstone; 2003.20: Liu Q, Zhou YH, Yang ZQ. The cytokine storm of severe influenza and development of immunomodulatory therapy. Cellular & molecular immunology. 2016 Jan;13(1):3-10.21: Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG. Into the eye of the cytokine storm. Microbiol. Mol. Biol. Rev. 2012 Mar 1;76(1):16-32.22: Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet. 2020 Mar 16.23: D’Elia RV, Harrison K, Oyston PC, Lukaszewski RA, Clark GC. Targeting the “cytokine storm” for therapeutic benefit. Clin. Vaccine Immunol. 2013 Mar 1;20(3):319-27.

Cytokine Storm

In a mild infection, the body has mechanisms to handle disruption which allow it to return to homeostasis quickly. However, in severe infections, what is known as a “cytokine storm” has been observed by Liu et al.20. Some viruses which have been associated with a cytokine storm include: H1N1 and H5N1 influenza viruses, cytomegalovirus (CMV), severe acute respiratory syndrome coronavirus (SARS-CoV), Esptein-Barr virus (EBV) associated haemophagocytic lymphohistiocytosis21 and SARS-CoV-2 (COVID-19).22

When infected cells undergo necrosis or apoptosis, inflammation is triggered. Chemokines activate leukocytes and mediate their migration to the site of inflammation or infection20. Pro-inflammatory cytokines are recruited to initiate the healing process. Cytokines such as IL-1β and TNF-α trigger permeability and vasodilation to allow for immune cells to move to the site.23 IL-β and IL-6 activate the complement system and opsonization.23

This process of inflammation is highly regulated by cytokines which exert anti-inflammatory activity including transforming growth factor β-1 and IL-10. This regulation leads to the resolution of inflammation and homeostasis is restored.23

Some pathogens can disrupt this process and severe inflammation can lead to unregulated and higher release of cytokines including TNFs, ILs, interferons and chemokines. This leads to immunopathologic injury, capillary damage and organ dysfunction.20

*Note that cytokine release is a healthy and normal response to immune challenge. It is the unregulated overproduction of cytokines which may cause complications.


Granulocyte

Red blood cell

Cytokines

Chemoskines

Legend

Lymphocyte

Monocyte

Macrophage

Dendntic Cell

Blood vessel

Influenza virus

Alveolus

Cyto

kine

sto

rmFigure 1: Representation of a cytokine storm in a severe infection20


General Guide for Immune System Health as a Preventative Measure

While Western herbal medicine offers an array of options for the management of various bacterial and viral challenges, it is important to support innate/non-specific immune functions to enhance body defences and help prevent the incidence of bacterial and viral infections.

Innate Immune System

First-line defence:

• • Epithelial barriers (skin and mucous membranes).

Second-line defence:

• • Macrophages, polymorphonuclear leucocytes, natural killer (NK) cells, neutrophils, dendritic cells, complement, cytokines, and acute phase proteins.1

First-line Defence Protection

One of the best defences against bacterial and viral infections is to be vigilant with personal hygiene practices. Guidelines include:

Clean your hands regularly with soap and water or an alcohol-based hand sanitiser.

Cover your nose and mouth with a tissue or bent elbow when coughing or sneezing.

Avoid touching your face, nose and mouth.

Avoid contact with anyone who is unwell – try to stay 1.5 m away from anyone coughing or sneezing.

If unwell, seek immediate guidance from a medical professional.

Second-line Defence Protection

Herbal medicine has been shown to have a beneficial effect in supporting various aspects of the innate/non-specific immune system to enhance body defences; through increases in macrophages, polymorphonuclear leucocytes, natural killer (NK) cells, neutrophils, and dendritic cells, herbal medicine can assist in preventing bacterial and viral infections.1


Echinacea purpurea

“

Professor Kerry Bone

“

Cytokines are in effect the language of the immune system and play a critical communicative role in initiating and sustaining both the innate and adaptive immune responses to an invading pathogen.


Herbal Support

Echinacea

It is known that Native Americans used Echinacea for centuries as a treatment for respiratory tract infections and inflammatory conditions (common cold, cough, bronchitis, etc.).2 Alkylamides, a key active constituent found in Echinacea has been shown to mimic the endocannabinoid anandamide (inhibits LPS-induced TNF-α) and reduces fatty acid amino hydrolase (FAAH) enzyme activity, which breaks down anandamide.3 In addition to this, Echinacea has shown to strongly bind to cannabinoid type 2 (CB2) receptors to modulate immune function and TNF‐α production.4, 5

Echinacea exhibits immune modulation by inducing heat shock protein 70 (HSP70) expression in humans in response to stressors which contributes to increased CD4, CD8 and NK cells.6 Furthermore, Echinacea has been found to enhance innate immunity through activation of neutrophils and macrophages.7

In a meta-analysis consisting of six clinical studies with a total of 2,458 participants, Echinacea was found to be associated with reduced risk of recurrent respiratory infections. Additionally, in individuals with higher susceptibility, stress or a state of immunological weakness, Echinacea halved the risk of recurrent respiratory infections.8

A clinical trial evaluated in the aforementioned meta-analysis found Echinacea was beneficial in reducing the total number of cold episodes, total episode days, and pain-killer medicated episodes. Echinacea was also found to inhibit virally confirmed colds and prevent enveloped virus infections.9

Astragalus

Astragalus has been used for hundreds of years in Traditional Chinese Medicine (TCM) for deficiency of ‘qi’, general debility, chronic illness, lack of strength, and to increase overall vitality.10

Astragalus has been found to have a significant dose dependent stimulation of white blood cell (WBC) counts in leukopaenia patients;11 restore T-cell function and NK cells; improve phagocytic and macrophage function; reduce inflammation and exhibit strong antioxidant activity.12

In a systematic review, Astragalus granules, given at 2.25 grams (equivalent to 15 gram crude Astragalus) twice per day, for at least 3–6 months was found to reduce the incidence of upper respiratory tract infections in children with nephrotic syndrome.13

Mushroom Combination

Mushrooms have been used for millennia because of their nutritional and medicinal properties.17 Mushroom beta-glucans have been shown to activate the innate immune system, increasing production of dendritic cells, NK cells, macrophages, lymphocytes and neutrophils via dectin-1 receptors. These fungal beta-glucans have also been shown to enhance phagocytosis and trigger cytokine release, such as TNF-α and various interleukins.18

Reishi

Patients with advanced cancer receiving chemotherapy were treated with Reishi mushrooms (4-8 grams per day for 15-20 days). Reishi treatment resulted in reduced nausea and vomiting, and improved WBC count compared to controls.19

Shiitake

In healthy young adults who consumed 5 or 10 grams of Shiitake mushrooms a day for 4 weeks, consumption of mushrooms:20

• Improved immune function, as seen by increased proliferation and activation of lymphocytes (gamma delta T cells and natural killer T cells) after stimulation (ex vivo) and produced significantly higher levels of secretory immunoglobulin A in saliva.

• Reduced inflammation during the elicited immune response, as seen by the expression of activation markers on the T cells (ex vivo), the pattern of cytokines secreted by peripheral blood mononuclear cells (ex vivo) and a significant reduction of C-reactive protein in serum.

Maitake

A double-blind, placebo-controlled trial conducted in Japan found that intake of 6.8 grams/day of Maitake mushrooms for 12 weeks enhanced antibody production in response to influenza vaccination in healthy adult volunteers while reducing the occurrence of cold symptoms compared to placebo. Based on study results, researchers suggest that Maitake may activate both innate and adaptive immune responses to help prevent viral infection.21


Tinospora

Tinospora is a succulent, climbing shrub used extensively in Ayurveda to clear heat, reduce fever, tonify the reproductive system and for the relief of hot skin conditions. Clinical trials have found Tinospora to be beneficial in supporting healthy immune function (modulates eosinophil and leukocyte function), as an adaptogen to improve resistance to stress and reduce fatigue, to improve antioxidant capacity as well as regulating pro-inflammatory cytokines.14

In a randomised placebo-controlled trial, HIV-positive patients received either 900 mg of Tinospora extract per day or placebo. Tinospora was found to prevent reductions in leukocyte count as well as reducing eosinophil counts which can be raised in HIV infection. Furthermore, 60% of the Tinospora group reported a decrease in the incidence of symptoms compared to 20% in the placebo group.15

To study Tinospora’s adaptogenic activity, 10 people (aged between 25 and 60 years) with signs and symptoms of premature ageing due to stress received Tinospora extract (1 gram/ day) for 3 months.16

Results found significant improvement in the following parameters compared to baseline values:

• Fatigue, general weakness, loss of appetite, aching muscles, and dizziness.

• Several aspects of the Hamilton Anxiety Rating Scale: tension, fear, anxious mood, depressed mood, intellectual (concentration, memory).

• Haemoglobin, total leukocyte count, lymphocytes, eosinophils, and fasting blood glucose.

Conclusion

In summary, a fundamental part of reducing the incidence of bacterial and viral infections is to support the body’s innate immune response. Herbal medicine in combination with correct hand washing and sneezing/coughing hygiene can be an effective way to support innate immune function and help reduce the contraction and spread of various contagious pathogens.

References

1: Parkin J, Cohen B. An overview of the immune system. The Lancet. 2001;357(9270):1777-89, 2: Catanzaro M, Corsini E, Rosini M, Racchi M, Lanni C. Immunomodulators inspired by nature: A review on curcumin and echinacea. Molecules. 2018;23(11):2778, 3: Raduner S, Majewska A, Chen J-Z, Xie X-Q, Hamon J, Faller B, et al. Alkylamides from Echinacea are a new class of cannabinomimetics Cannabinoid type 2 receptor-dependent and-independent immunomodulatory effects. Journal of Biological Chemistry. 2006;281(20):14192-206, 4: Matovic N, Matthias A, Gertsch J, Raduner S, Bone K, Lehmann R, et al. Stereoselective synthesis, natural occurrence and CB 2 receptor binding affinities of alkylamides from herbal medicines such as Echinacea sp. Organic & biomolecular chemistry. 2007;5(1):169-74, 5: Gertsch J, Schoop R, Kuenzle U, Suter A. Echinacea alkylamides modulate TNF‐α gene expression via cannabinoid receptor CB2 and multiple signal transduction pathways. FEBS letters. 2004;577(3):563-9, 6: Agnew L, Matthias A, Shipp C, Kauter K, Bone K, Watson K, et al. Echinacea induced hsp70 alterations in leukocytes. Planta Medica. 2010;76(12):1354-, 7: Manayi A, Vazirian M, Saeidnia S. Echinacea purpurea: Pharmacology, phytochemistry and analysis methods. Pharmacognosy reviews. 2015;9(17):63, 8: Schapowal A, Klein P, Johnston SL. Echinacea reduces the risk of recurrent respiratory tract infections and complications: a meta-analysis of randomized controlled trials. Advances in therapy. 2015;32(3):187-200, 9: Jawad M, Schoop R, Suter A, Klein P, Eccles R. Safety and efficacy profile of Echinacea purpurea to prevent common cold episodes: a randomized, double-blind, placebo-controlled trial. Evidence-Based Complementary and Alternative Medicine. 2012;2012 10: Sinclair S. Chinese herbs: a clinical review of Astragalus, Ligusticum, and Schizandrae. Alternative Medicine Review. 1998;3:338-44, 11: Weng X. Treatment of leucopenia with pure Astragalus preparation--an analysis of 115 leucopenic cases. Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi= Chinese journal of integrated traditional and Western medicine. 1995;15(8):462-4,

12: Liu Q-y, Yao Y-m, Zhang S-w, Sheng Z-y. Astragalus polysaccharides regulate T cell-mediated immunity via CD11chighCD45RBlow DCs in vitro. Journal of ethnopharmacology. 2011;136(3):457-64, 13: Zou C, Su G, Wu Y, Lu F, Mao W, Liu X. Astragalus in the prevention of upper respiratory tract infection in children with nephrotic syndrome: evidence-based clinical practice. Evidence-Based Complementary and Alternative Medicine. 2013;2013 14: Yadav K. Tinospora cordifolia an Augmenting Agent for Quality of Life in Cancer: an Overview. Asian J Biomed Pharmaceut Sci. 2017;7(60):16, 15: Kalikar M, Thawani V, Varadpande U, Sontakke S, Singh R, Khiyani R. Immunomodulatory effect of Tinospora cordifolia extract in human immuno-deficiency virus positive patients. Indian journal of pharmacology. 2008;40(3):107, 16: Pal S, Ramamurthy A, Rath S, Mahajon B. Healing Role of Guduchi [Tinospora cordifolia (Willd.) Miers] and Amalaki (Emblica officinalis Gaertn.) Capsules in Premature Aging Due to Stress: A Comparative Open Clinical Trial. European Journal of Medicinal Plants. 2017:1-13, 17: Gargano ML, van Griensven LJ, Isikhuemhen OS, Lindequist U, Venturella G, Wasser SP, et al. Medicinal mushrooms: Valuable biological resources of high exploitation potential. Plant Biosystems-An International Journal Dealing with all Aspects of Plant Biology. 2017;151(3):548-65, 18: Chan GC-F, Chan WK, Sze DM-Y. The effects of β-glucan on human immune and cancer cells. Journal of hematology & oncology. 2009;2(1):25, 19: Lin ZB. 16th World Congress of Basic and Clinical Pharmacology. Basic & Clinical Pharmacology & Toxicology. 2010;107(s1):7-70, 10.1111/j.1742-7843.2010.00598_2.x.20: Dai X, Stanilka JM, Rowe CA, Esteves EA, Nieves Jr C, Spaiser SJ, et al. Consuming Lentinula edodes (Shiitake) mushrooms daily improves human immunity: A randomized dietary intervention in healthy young adults. Journal of the American College of Nutrition. 2015;34(6):478-87, 21: Nishihira J, Sato M, Tanaka A, Okamatsu M, Azuma T, Tsutsumi N, et al. Maitake mushrooms (Grifola frondosa) enhances antibody production in response to influenza vaccination in healthy adult volunteers concurrent with alleviation of common cold symptoms. Functional Foods in Health and Disease. 2017;7(7):462-82,


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