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Herbal medicine Gamgungtang down-regulates autoimmunity through induction of TH2

cytokine production by lymphocytes in experimental thyroiditis model

Eun-Ho Saa, b, Un-Ho Jina, Dong-Soo Kimc, Bong-Seok Kanga, 1, Ki-Tae Hab, June-Ki
Kimb, Won-Hwan Parkb and Cheorl-Ho Kima,

Department of Biological Science, Sungkyunkwan University, Chunchun-Dong 300,

Jangan-Gu, Suwon City, Kyunggi-Do 440-746, Republic of Korea


Department of Oriental Medicine, Dongguk University and Cardiovascular MRC,

Kyungju 780-714, Republic of Korea


Department of Food Science and Technology, Kyungsung University, Nam-Gu, Busan

608-736, Republic of Korea

Received 18 July 2005; revised 31 July 2006; accepted 22 August 2006. Available
online 26 August 2006.

The crude herbal formulation, Gamgungtang (GGT), has been shown to protect animals
against a wide range of spontaneously developing or induced autoimmune diseases. We
have previously reported that GGT shows marked down-regulation of several
experimental autoimmune diseases. Although very effective at preventing thyroid
infiltrates in mice immunized with mouse deglycosylated thyroglobulin and complete
Freund's adjuvant and in spontaneous models of thyroiditis, it completely failed to
modify experimental autoimmune thyroiditis (EAT) induced in mice immunized with
mouse thyroglobulin and lipopolysaccharide. In this study, in an effort to elucidate the
mechanisms by which GGT suppresses EAT, and autoimmunity in general, we
investigated the in vivo effects of this drug on the Th1/Th2 lymphocyte balance, which is
important for the induction or inhibition of autoreactivity. Naive SJL/J mice were treated
orally for 5 days with GGT (80 mg/(kg day)). Spleen cells were obtained at various time
points during the treatment period and were stimulated in vitro with concanavalin A.
Interleukins IL-4, IL-10 and IL-12, transforming growth factor- (TGF-) and interferon (IFN-) cytokine production was evaluated at the protein levels of the cytokines in the
medium and mRNA expressions. A significant upregulation of IL-4, IL-10 and TGF-

was observed following treatment with GGT, which peaked at day 5 (IL-10) or day 10
(IL-4). On the other hand, IL-12 and IFN- production were either unchanged or
decreased. It seems therefore that GGT induces in vivo a shift towards Th2 lymphocytes
which may be one of the mechanisms of down-regulation of the autoimmune reactivity in
EAT. Our observations indicate that down-regulation of TH1 cytokines (especially IL-12)
and enhancement of Th2 cytokine production may play an important role in the control of
T-cell-mediated autoimmunity. These data may contribute to the design of new
immunomodulating treatments for a group of autoimmune diseases.

Alternative Herbal Immunomodulators and Drug


Authors: Actor J.K.; Dasgupta A.

Source: Journal of Clinical Ligand Assay, Volume 26, Number 3, 1 September 2003 , pp.
Publisher: Clinical Ligand Assay Society
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Herbal medicines are widely used as immunomodulators. The number
of reported clinical complications from incidental use is on the
increase. Similarly, there are increasing reports for specific drug
interactions with many common herbal medicines. As the frequency of
herbal medicine use increases, physicians must be constantly aware of
potential interactions and interference caused by these natural
compounds. This report focuses on a panel of immunomodulatory
herbal medicines that exhibit drug-herb interactions and potential
interference with standard pharmaceuticals. We also address potential
interference of the herbal medicines with therapeutic drug monitoring.
Awareness of these interactions will allow physicians to make informed
decisions when treating patients using alternative therapeutics.

Herbal Medicine and Treatments for ADHD

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Herbal Treatments & Increased Medical Use of Stimulants

Why are Stimulants Useful in ADD and ADHD?

The Use of Herbal Stimulants in ADHD

Other Herbal Stimulants, Brain Antioxidants, and Nerve Tonics:

Ginkgo (Ginkgo biloba)

Brahmi (Bacopa monniera)

Siberian Ginseng (Eleutherococcus senticosis)

Gotu Kola (Centella asiatica, Hydrocotyle asiatica)

Green Oats (Avena sativa)

Herbal Formulas for ADHD

Chinese Herbs and the Treatment of ADHD

Recommended Chinese Herbal Formulas

Other Commonly Recommended Herbal Formulas

Sharol Tilgner's "Liquid Serenity"

David Winston's "Focus Formula"

Mary Bove's "Componded Melissa"

Herb - Drug Interactions

Precautions about Discontinuing Stimulant Drugs for ADHD

Finding a Practitioner Familiar with Herbal Therapies



List of Articles and Information concerning this treatment

What others in the field think of this specific treatment

What you think of this specific treatment [Web-Forum Discussions]

There is a great need to explore alternative treatments for ADHD. As the use of
Ritalin and amphetamine in children have increased to alarming proportions,
parents and professionals alike are searching for effective alternatives to
stimulant drugs. Herbal medicines may offer a safe alternative, especially in
combination with complementary therapies.
Although more research is necessary to confirm the implied benefits of
commercially available herbal formulas, there are at least a few clinical trials of
herbs and herbal extracts, notably Chinese herbal formulas, that have shown
promising results in this arena.
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Anti-inflammatory Herbs
Healing with Herbal Medicine and Phytochemicals
Elaine Moore
Oct 21, 2006

This article describes the use of plant chemicals with anti-inflammatory properties
as complementary therapies for patients with autoimmune disease.
Inflammation is a key feature in autoimmune disease. In some conditions, such
as Hashimoto's thyroiditis, inflammation contributes to the disease process. In
other conditions, such as Crohn's disease, inflammation may occur as a result of
the disease. Inflammation occurs as the immune system reacts to injury,
infection, environmental agents, malignancy, and cellular changes. In skin,
inflammation is most visible because it causes noticeable swelling, redness,
discomfort and pain. The process leading to inflammation, which is known as the
inflammatory response, also induces changes that aren't seen but influence the
effects of inflammation and their severity.
The inflammatory response is a complex cascade of steps that include an
activation of white blood cells, the release of immune system chemicals such as
complement and cytokines, and the production and release of inflammatory
mediators and prostaglandins. Inflammation may be acute or chronic or
relapsing-remitting depending on the disease course. Most conventional

treatments for autoimmune disease, including corticosteroids, work by reducing

or suppressing inflammation.
Many herbs also possess anti-inflammatory (also known as antiphlogistic)
characteristics. Herbs can be used as the sole therapy in autoimmune disease or
as complementary corticosteroid-sparing therapies allowing patients to take
smaller doses or shorter courses of corticosteroids. Treatment protocols today
often rely on both alternative and conventional treatment options in a discipline
known as integrative medicine.
Herbal medicine relies on active plant chemicals with biological properties. Many
conventional medicines are synthetic compounds designed to mimic the action of
plant chemicals. For instance, the heart medication digoxin is derived from the
foxglove plant. In herbal medicine, active chemicals are extracted from the plant
parts (stems, seeds, roots, or leaves) that are the richest sources. The active
chemicals can be quantitatively measured and prepared in the form of capsules,
tinctures, teas, tonics, oils, or poultices. Aromatic herbs such as lavender can
also benefit the immune system when used topically or as healing oils.
Other herbs known to reduce inflammation include ginger, turmeric, pokeroot,
cleavers, devil's claw, licorice, autumn saffron, boswellin, curcumin, arnica,
bromelain, German chamomile, licorice, white willow, witch hazel, and capsaicin.
Many plant chemicals are known to reduce inflammation, including the omega-3
essential oils, which can also be derived from marine sources. Other plant
chemicals, which are also known as phytochemicals, that are known to reduce
inflammation include carotenoids and catechins, which belong to the plant
chemical family known as bioflavinoids bioflavinoids.

The medicinal effects of plant chemicals are referred to as phyotherapy. The

various plant chemicals found in plant and herbal sources all have different
properties as they go about their business of reducing inflammation. For
instance, spice components, such as curcurmin, turmeric, and capsaicin from red
pepper reduce inflammation by influencing arachidonic acid metabolism and also
the secretion of lysosomal enzymes by macrophages. Curcumin and capsaicin
also inhibited the secretion of collagenase, elastase and hyaluronidase
demonstrating that they can control the release of pro-inflammatory mediators
such as eicosanoids.
Cytokines are chemicals that modulate the immune response. High levels of
cytokines cause many of the detrimental consequences in autoimmune disease.
Many plant chemicals have effects on at least one of the following cytokines:
interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF), and
interferon (IFN). Herbs that reduce or modulate the secretion of one or more of
these cytokines include Acalypha wilkesiana, Acanthopanax gracilisylus, Allium
sativum (garlic), curcurmin, Echinacea purpurea, Grifola frondosa, Panax
ginseng, Olygala tunuifolia, Silybum marianum (milk thistle), Tinospora cordifolia,
Uncaria tomentosa, and Withania somnifera.
Herbs should never be added to a healing protocol without first consulting with
one's integrationist physician. Besides their anti-inflammatory properties, some
herbs such as German chamomile also have sedative and spasmolytic properties
that could interfere with the effects of other medications or cause undesirable
side effects.
Antoine Al-Achi, Anti-inflammatory Herbs, U.S. Pharmacist, March 15, 2004.
Kenneth Proefrock, Latest Updates in the Botanical Treatment of Autoimmune
Diseases, Southwest Conference on Botanical Medicine 2003.

K. Spellman, Modulation of cytokine expression by traditional medicines: a

review of herbal immunomodulators, Alternative Medicine Review, June 2006;
11(12): 128-50.

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Adverse Reactions to Herbal Therapy in Dermatology

R.B. Vender, MD, FRCPC
Dermatrials Research and Faculty of Medicine, McMaster University,
Hamilton, Ontario, Canada
There are many herbal therapies available for dermatological
diseases that patients have already begun to discover.

Fungal Treatment Psoriasis

Treatment Psoriatic Arthritis
Treatment Rosacea Treatment
Skin Cancer Treatment Skin
Care Treatments Bacterial
Infection Treatment Lice
Treatment Herpes Treatment
Lupus Treatment Wart

Dermatologists must be educated not only in the benefits of

these therapies, but must also be aware of some of the risks and
adverse effects. They need information about the effects of
herbal remedies in order to better serve their patients who may
be using herbs to treat their dermatological conditions. This brief
review summarizes some of the more common herbal therapies
used by many dermatology patients for their skin diseases, and
the adverse reactions and drug interactions that may occur.
Key Words: herbal remedies, adverse effects, dermatology, antiinflammatory
The use of herbal therapy by dermatology patients is on the rise.
Because of their convenient availability, many patients with
chronic dermatological diseases have attempted to take more
control over their health by using herbal remedies along with or
instead of conventional treatments. Some patients have lost
hope; standard treatments have failed to be effective for them. As
a result, they seek newer therapies in an attempt to find a "cure"
for their problems.
Government Regulations
The exact frequency of herbal use is not known because of its
non-regulatory status. However, some regulations do exist at the
federal level in Canada with the Natural Health Products
Directorate (est. 03-99). Most of these regulations are still under
review. However, regulations do exist with regard to definitions,
product licensing, adverse reaction reporting, site licensing, good
manufacturing practices, clinical trials, and labeling/packaging.
These are pursuant to the subsection of the Food and Drugs Act
entitled Natural Health Products Regulations. Some of these are
expected to be phased in over the next two years. At the

provincial level, British Columbia established the College of

Traditional Chinese Medicine (TCM) Practitioners and
Acupuncturists of B.C., becoming the first province in Canada to
regulate the practice of TCM.1 No other province thus far has a
similar regulatory body.
There are many herbal remedies that have scientific merit; they
may be of clinical benefit and provide safe, effective and reliable
alternatives to conventional medicine. However, herbal products
cannot be patented.2 They are intended for the self-treatment of a
self-diagnosed, selflimiting condition. Although there are
numerous herbal therapies that are relevant to the specialty of
dermatology, many of these have not been studied in proper
randomized, double-blind, placebo controlled trials. Most herbal
treatments have evidence that is based on sparse anecdotal
reports and word of mouth.
Drug Interactions and Side-Effects
Many of these therapies are considered "natural" and therefore
harmless. However, because of the poor regulations that exist in
monitoring these drugs, adverse reactions do occur.3 Herbal
therapy, therefore, should be avoided in pregnancy, infants and
children because of the uncertainty of adverse reactions that
could occur. There is little incentive for pharmaceutical
companies to investigate or standardize these preparations
because it is unlikely patents would be applicable.
Because of the assumed safety of natural products, many

patients believe these products have "fewer" side-effects. Herbal

therapies should be regarded as drugs. Since drugs have sideeffects, such events can be seen with herbals. Drug interactions
although infrequent, can also occur with herbal therapies and
conventional medications.4,8 This may be due to altered
absorption, distribution, biotransformation and/or excretion. 6
These interactions are often patientinitiated because of the lack
of consultation with a physician. These effects can increase or
decrease the activity of the corresponding drugs and lead to
untoward or unexpected adverse events or changes in drug
efficacy.5 Some herbals may be contaminated with toxic
substances or the herbal can be toxic alone. Others may have
traces of potent topical steroids.7 This makes it even more
important for physicians to take a proper and complete drug
history, including herbal medications.





(Chinese Herbal

Anti-inflammatory, Atopic Dermatitis Yes


Evening Primrose
Oil (EPO)


Acne, atopic



Borage Oil15

Anti-pruritic, antiinflammatory

Atopic Dermatitis No

Aloe Vera4,6,8,9,16


Abrasions, acne,


(promotes wound

aphthous ulcers,
AD, bites, burns,
frostbite, leg
ulcers, poison
ivy, psoriasis,



Boils, burns,
eczema, herpes
simplex or zoster, healing)
mouth irritations,
ulcers, wounds


Deplete neuronal
stores of substance

Pityriasis Rubra
Yes (re:
Pilaris, post
neuralgia (PHN),
prurigo nodularis,
associated with
psoriasis (Ps) and




glabralensis or

Anti-inflammatory, Eczema,
antiviral, demulcent melasma, "sore
(mucous membrane mouth"


Purple Cone Flower

angustifolia or


burns, herpes
simplex, ulcers
internalPrevention of
yeast infections





Slippery Elm Bark


(Ulmas fulva)


Abscesses, boils,
herpes simplex,
skin irritations,

St. Johns Wort



external- Burns, No

Thyme (Thymus


Combined with
herbs for


Ginkgo (Ginkgo
Garlic, Ginger,
Ginseng (Panax




Tea Tree Oil



Acne, impetigo,
mouth ulcers,
psoriasis, tinea


BromelainPineapple (Ananas


Wound healing,
postsurgical pain


Yarrow (Achillea


Compress for
weeping lesions,


Compress for
weeping lesions


(Trigonella foenumgraecum)16
(Matricaria recuita

Anti-bacterial, anti- AD, Candida

albicans, gramfungicidal


Arnica (A


Acne, boils,
insect bites


Horse Chestnut
seed extract


Chronic venous


Table 1: A review of some herbal remedies.



Drug Interactions

Zemaphyte (Chinese
Herbal Therapy)6,10-14

Diarrhea, increased liver Methotrexate

function tests, reversible
dilated cardiomyopathy,
reversible acute hepatic
illness, fatal hepatic
necrosis, symptomatic
nephropathy & bladder
carcinoma, worsening of
atopic dermatitis, acute

Evening Primrose Oil


GI upset, headaches

seizure threshold of

Borage Oil15

Potential for
hepatotoxicity orally, no
toxicity data for topical

None Known (NK)

Aloe Vera4,6,8,9,16

Contact dermatitis


Calendula (Calendula Allergic reactions, ACD




Severe burning,
intolerability, allergy:
can cross react with
latex, bananas, kiwi,
chestnut, avocado


Goldenseal (Hydratis

Allergic Contact


Licorice (Glycyrrhiza
glabralensis or

Contraindicated in
hypertension, diabetes
mellitus, hypokalemia,
liver/kidney disorders

Cyclosporin A (CyA) ,
digoxin, prednisone,

Purple Cone Flower

angustifolia or

Recurrent erythema
TB, MS, ragweed,
sunflower allergies

and CyA,

Slippery Elm Bark

(Ulmas fulva)

CAUTION! Oral form
induces miscarriage


St. Johns Wort


Oral form can cause

photosensitivity, erectile

amitriptyline CyA ,
digoxin, paroxetine,
HIV protease
inhibitors, oral

Thyme (Thymus

Essential oils can be a

mucous membrane


Ginkgo (Ginkgo
Garlic, Ginger,
Ginseng (Panax

Can cause spontaneous


Can potentiate aspirin,

NSAIDs, warfarin,

Tea Tree Oil


ext- ACD, burning,

dryness, itching, 5
irritation, systemic
allergic reactions, can
cross react with
colophony. int- TOXIC


(Ananas comosus)16

ACD, GI upset, diarrhea

Ethyl acrylate

Yarrow (Achillea



(Trigonella foenumgraecum)16

ext-Skin irritation intHypoglycemia


(Matricaria recuita

ACD, anaphylaxis

Hypersensitivity crossreactions to ragweed,

(Compositae family)

Arnica (A Montana)8,9 ext-ACD int-TOXIC


Horse Chestnut seed

extract (Aesculus


ext-ACD int-Dizziness,
drug induced lupus, GI
upset, headache,

Table 2: Side-effects and drug interactions of some herbal remedies

The most common dermatologic reaction from herbal therapies is allergic
contact dermatitis.8 Herbs that are known for causing this condition
include: aloe, arnica, bromelain, calendula, chamomile, goldenseal, tea
tree oil and yarrow.6,4,9 However, more serious events have occurred

including erythroderma and Stevens-Johnson syndrome from

combination herbal preparations.8 Serious systemic adverse events have
been reported with herbal therapies for the treatment of dermatological
diseases as well.7 Most are hepatotoxic effects and some have been fatal
although this is rare.8 Herbals that are recommended for topical use
should not be ingested and vice-versa. Drug interactions that most
commonly occur are due to immunomodulatory reactions, however
effects on anticonvulsants and anticoagulants can occur.5
A brief search of the literature reveals many therapies used for
dermatological disease however there are fewer reports of their side
effects in dermatologic or medical literature. Only those therapies
relevant to the specialty of dermatology that also have had reports of
side-effects are discussed. Those therapies without known side-effects
are excluded from this manuscript. It is important for dermatologists to
become aware of these adverse events and interactions in order to better
educate their patients and possibly prevent potential and unexpected
adverse reactions.8
1. Wong HGC. Chinese Patent Medicines of Herbal and Unknown
Used for Allergic and other Condidtions. Can J Allergy Clin
Immunol 6(4):77-9 (2001).
2. Neldner KH. Complementary and Alternative Medicine. Dermatol
Clin 18(1):189-93 (2000 Jan).
3. Gold JL, Laxer DA, Rochon, PA. Herbal Remedies: A Critical
Perspective. Ann RCPSC 33(8):497-8 (2000 Dec).
4. Gardiner P, Kemper KJ. Herbs in pediatric and adolescent
medicine. Pediatr Rev 21(2):44-57 (2000 Feb).

5. Sitar DS. Important Drug Interactions. Can J CME pp:77-87

(2002 Feb).
6. Dinehart SM, Hordinsky MK, Jaworsky C. Alternative Medicine
and the Skin. Presented at: the American Academy of
Dermatology Annual General meeting, Washington DC, March
7. Keane FM, du Vivier AW, et al. Analysis of Chinese herbal creams
prescribed for dermatological conditions. BMJ 318(7183):563-4
(1999 Feb).
8. Bedi MK, Shenefelt PD. Herbal Therapy in Dermatology. Arch
Dermatol 138(2):232-42 (2002 Feb).
9. Norman R, Nelson D. Do Alternative & Complementary Therapies
work for common Dermatologic Conditions? Skin & Aging 8:2833 (2000 Feb).
Ferguson JE, Chalmers RLG, Rowlans DJ. Reversible dilated
cardiomyopathy following treatment of atopic eczema with
Chinese herbal medicine. Br J Dermatol 136(4):592-3 (1997
Vender RB. Alternative treatments for Atopic Dermatitis: A
Selected Review. Skin Therapy Lett 7(2):1-5 (2002 Feb).
Rustin MH, Poulter L. Chinese Herbal Therapy in atopic
dermatitis. Dermatol Ther 1:83-93 (1996).
Perharic-Walton L, Murray V. Toxicity of Chinese herbal
remedies. Lancet 340(8820):674 (1992 Sep).
Luciuk G. Chinese Herbal Medicines. Allergy & Asthma
13(4):1-2 (2000 Aug/Sep).
Levin Cl, Maibach H. Exploration of "Alternative" and
"Natural" Drugs in Dermatology. Arch Dermatol 138(2):207-11
Graf J. Herbal anti-inammatory agents for skin disease.
Skin Therapy Lett 5(4):3-5 (2000).
Generali, JA. Keeping Up Alternative Medicines: Year in
Review Druglink. pp12-14 (2001 Feb).
Patzelt-Wenczler R. Proof of efficacy of Kamillosan(R)
cream in atopic eczema. Eur J Med Res 5(4): 171-5 (2000 Apr).
Wong HCG. Allergic Reactions Associated with Chinese
Herbal Medicine. Allergy & Asthma 13(4):13-8 (2000 Aug/Sep).
Wong HGC. Acute Urticaria associated with Chinese Herbal
Medicine Used for Atopic Dermatitis. Can J Allergy & Clin
Immunol 6(2):162-5 (2001).
Wong HGC. Acute Generalized Maculopapular Eruption,
Abnormal Liver Function, and elevated Blood Mercury Level

Associated with Chinese Herbal Medicine. Can J Allergy & Clin

Immunol 7(5/6):92-6 (2002 July-Aug).
Tanaka A, Nishida R, Sawai K, et al. [Traditional remedyinduced Chinese herbs nephropathy showing rapid deterioration
of renal function] Nippon Jinzo Gakkai Shi 39(8):794-7 (1997
Graham-Brown R. Toxicity of Chinese Herbal remedies.
Lancet 340(8820):673-4 (1992 Sep).
Kane JA, Kane SP, Jain S. Hepatitis induced by traditional
Chinese herbs; possible toxic components. Gut 36(1):146-7
(1995 Jan).
Giordano-Labadie F, Schwarze HP, Buzex J. Allergic contact
dermatitis from camomile used in phytotherapy. Contact
Dermatitis 42(4):247 (2000 Apr).
Gordon LA. Compositae dermatitis. Australas J Dermatol
40(3):123-8;quiz 129-30 (1999 Aug).

1. Cutaneous Cleansers
2. Adverse Reactions to Herbal Therapy in Dermatology
3. Important Safety Information About DIANE-35 and the Risk of
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Echinacea spp.
David L. Hoffmann B.Sc. (Hons), M.N.I.M.H.

Echinacea spp.
Names: Purple Coneflower

Habitat: Throughout North American prairies, plains, and open woodlands.

Part Used: The root.

Echinacoside, in E. angustifolia but not E. purpurea.Research suggests

that the echinacosides glycosides appear to be primary anti-microbial
constituents in Echinacea. However there are many other biologically
active substances present, and there is evidence that they work
synergistically. The polysaccharides, for example, possess the best
immune stimulating properties and are also antiviral.
Unsaturated isobutyl amides, echinacin and others, in E. angustifolia and
E. pallida.
Polysaccharides; a heteroxylan and an arabinorhamnogalactan
Polyacetylenes, at least 13 of which have been isolated. It has been
postulated that these are artifacts formed during storage, since they are
found in dried but not fresh roots of E. pallida.
Essential oil, containing humulene, caryophyllene and its epoxide,
germacrene D and methyl-p-hydroxycinnamate
Miscellaneous; vanillin linolenic acid derivatives, a labdane derivative,
alkanes and flavonoids and the alkaloids tussilagine and isotussilagine.

Note: Sesquiterpene esters which were originally identified in commercial

samples of E. purpurea have since been shown to be due to the presence of an
adulterant, Parthenium integrifolium L. (American Feverfew). It appears that this
adulteration may be widespread in commercial samples.
Actions: Anti-microbial, immunomodulator, anti-catarrhal, alterative.
Indications: Echinacea is one of the primary remedies for helping the body rid
itself of microbial infections. It is often effective against both bacterial and viral
attacks, and may be used in conditions such as boils, septicaemia and similar
infections. In conjunction with other herbs it may be used for any infection
anywhere in the body. For example in combination with Yarrow or Bearberry it
will effectively stop cystitis. It is especially useful for infections of the upper
respiratory tract such as laryngitis, tonsillitis and for catarrhal conditions of the
nose and sinus. In general it may be used widely and safely. The tincture or
decoction may be used as a mouthwash in the treatment of pyorrhoea and
gingivitis. It may be used as an external lotion to help septic sores and cuts.
Much research is focussing upon this plant, providing important insights into its
activity and potential uses. Glycosides from the roots have mild activity against
Streptococci and Staphylococcus aureus. Echinacoside was the most active with
about 6 mg being equivalent to one unit of penicillin. The tincture was able to
reduce both the rate of growth and the rate of reproduction of Trichomonas
vaginalis, and was found to be effective in halting the recurrence of Candida
albicans infection. It seems to prevent infection and repair tissue damaged by
infection, partially through inhibiting the activity of the enzyme hyaluronidase.
The hyaluronidase system is a primary defense mechanism, involving connective
"ground" substance, or hyaluronic acid, acting as a barrier against pathogenic
organisms. Some pathogens activate an enzyme, hyaluronidase, which once

activated destroys the integrity of the ground substance. This causes the barrier
to become leaky, allowing pathogens to invade, attach themselves to exposed
cells, penetrate the membrane and kill the cell. The result as an inflammatory
infection. Echinacea inhibits the action of hyaluronidase by bonding with it in
some way, resulting in a temporary increase in the integrity of the barrier. Fewer
pathogens are able to stimulate the destruction of the ground substance. A range
of constituents mediate this process, especially a complex polysaccharide called
echinacin B. This anti-hyaluronidase action is involved in regeneration of
connective tissue destroyed during infection and in the elimination of pathogenic
organisms creating the infection. Purified polysaccharides prepared from
Echinacea possess a strong activating force on the body's macrophagemediated defense system. These macrophages initiate the destruction of
pathogens and cancer cells. Echinacea activates macrophages by itself,
independent of any effect with T-cells. A tumor-inhibiting principle has been
found, a oncolytic lipid-soluble hydrocarbon from the essential oil. The
echinacosides glycosides appear to be the primary `antibiotics', but there are
many other active substances present which probably function synergistically.
The polysaccharides possess the best immune stimulating properties and are
also antiviral. Other constituents have been shown to possess good anti-tumor,
bacteriostatic, and anesthetic activity.
This all points to the conclusion that its actions relate to immune system
functioning on some level, helping deal with infections and stimulating the
immune response. It activates the macrophages that destroy both cancerous
cells and pathogens, increases the level of phagocytosis by raising levels of
white blood cells such as the neutrophils, monocytes, eosinophils, and B
lymphocytes. It also has an effect on properidin levels, indication an activation of
the complement system.
Preparations & Dosage: Decoction: put 1-2 teaspoonfuls of the root in one cup
of water and bring it slowly to boil. Let it simmer for 10-15 minutes. This should
be drunk three times a day. Tincture: take 1-4 ml of the tincture three times a
day. Echinacea is often, inappropriately, used as a daily `immune support'
(whatever that is!). A quote from Dr. Daniel Mowrey's excellent review of
Echinacea in Next Generation Herbal Medicine is pertinent here:
"Daily intake should be restricted to what is deemed necessary. During cold and
flu season, two to four capsules per day is sufficient. In the presence of acute
infection, that dosage may be increased, without danger, to more than 8
capsules. In the presence of chronic infections, such as chronic hepatitis,
echinacea may be used continuously for several months. However, for the
maintenance of a healthy immune system, echinacea is most wisely used
periodically--a few weeks on, and a few weeks off, throughout the year.
Echinacea is not a tonic in all aspects; granted that it has been observed to
stabilize the production of neutrophils, such tonic action has not been observed
on other immune factors, such as properdin production. In the absence of
conclusive experimental findings, it is both safe and wise to assume that the
constant, unremitting use of echinacea could be stressful on certain aspects of
the immune system. During breaks, the immune system will adapt and increase
in natural strength."

Citations from the Medline database for the genus Echinacea

Echinacea Bauer R Foster S Analysis of alkamides and caffeic acid
derivatives from Echinacea simulata and E. paradoxa roots.
Planta Med 1991 Oct;57(5):447-9 Bauer VR Jurcic K Puhlmann J Wagner H
[Immunologic in vivo and in vitro studies on Echinacea extracts]
Arzneimittelforschung 1988 Feb;38(2):276-81 (Published in German)
Ethanolic extracts of Echinacea purpurea, E. pallida and E. angustifolia roots
were examined for immunological activity in the carbon clearance test with mice
and in the granulocyte test. In the in vivo experiment all extracts, administered
orally, were found to enhance phagocytosis significantly. These results correlate
with the stimulation of phagocytosis in the in vitro granulocyte test. The lipophilic
fractions of the extracts appeared to be more active than the polar fractions. All
extracts were analyzed by HPLC in order to correlate the chemical constituents
with the immunological activities. Coeugniet EG Elek E Immunomodulation
with Viscum album and Echinacea purpurea extracts.
Onkologie 1987 Jun;10(3 Suppl):27-33
Extracts of Viscum album (Plenosol) and Echinacea purpurea (Echinacin) are
used clinically for their non-specific action on cell- mediated immunity. In vitro we
could prove that these two extracts have a stimulating effect on the production of
lymphokines by lymphocytes and in the transformation test. A toxic effect on cells
was produced only with very high, clinically irrelevant concentrations. Clinical
application of these extracts can produce a stimulation of cell-mediated immunity
(one therapeutic administration followed by a free interval of one week) or can
have a depressive action (daily administrations of higher doses). These
observations were confirmed by lymphokine production and assay, 3H-thymidine
incorporation and a skin test with recall antigens (Multitest Merieux). Gaisbauer
M Schleich T Stickl HA Wilczek I [The effect of Echinacea purpurea Moench
on phagocytosis in granulocytes measured by chemiluminescence]
Arzneimittelforschung 1990 May;40(5):594-8 (Published in
German)Chemiluminescence was used as an indicator for phagocytic activity of
granulocytes induced by zymosan in whole blood. Luminol was used to amplify
the luminescence measured. Methods and conditions of the trial were varied and
the dependence on the methods applied became evident. The effects of
echinacea-extract (Echinacin) and phorbolester (PMA) in various concentrations
on phagocytic activity of whole blood heparinized with 10 I.E./ml heparin as well
as on phagocytic activity of erytrocytolized blood were investigated. The reaction
of the granulocytes--phagocytis and therefore chemilumenescence--under the
influence of echinacea extract depends on the doses and methods applied.
Therefore standardized methods and investigations of various
immunoparameters as well as clinical investigations are necessary to prove the
immunostimulative effect of socalled immunotherapeutics. This has not been
undertaken up to now. Dose and method dependent single results cannot be a
convincing justification for specific therapeutic medication. Heinzer F Chavanne
M Meusy JP Maitre HP Giger E Baumann TW [The classification of

therapeutically used species of the genus Echinacea]

Pharm Acta Helv 1988;63(4-5):132-6 (Published in German) Lersch C Zeuner M
Bauer A Siebenrock K Hart R Wagner F Fink U Dancygier H Classen M
Stimulation of the immune response in outpatients with hepatocellular
carcinomas by low doses of cyclophosphamide (LDCY), echinacea
purpurea extracts (Echinacin) and thymostimulin.
Arch Geschwulstforsch 1990;60(5):379-83
Outpatients with inoperable far advanced hepato-cellular carcinomas (n = 5)
were treated with LDCY--300 mg/m2 i.v. every 28 days-, echinacin--60 mg/m2
i.m.--and thymostimulin--30 mg/m2 i.m., day 3-10 after LDCY, then twice a week.
Therapy was well tolerated by all patients. Their Karnofsky' index increased for
10% in the mean. A stable disease for more than 8 weeks was documented by
abdominal ultrasonography in one patient. Serum levels of Alpha-Fetoprotein
(AFP), Carcinoembryonic Antigen (CEA) and Tissue Polypeptide Antigen (TPA)
did not increase in 2 patients. Median survival time was 2.5 months. One patient
is still alive after 8 months. Absolute numbers of CD8+ cells significantly (p less
than 0.02) decreased for 7% 1 day after LDCY, whereas CD4+ cells increased (p
less than 0.02) from day 1-7. Numbers of natural killer (NK-) cells increased for
17% (p less than 0.05), their activity for 90% (p less than 0.05). Activities of
peripheral polymorphs (p less than 0.05) increased for 27% and of Lymphokine
Activated Killer (LAK-) cells for 180% (p less than 0.05). Luettig B Steinmuller
C Gifford GE Wagner H Lohmann-Matthes ML Macrophage activation by
the polysaccharide arabinogalactan isolated from plant cell cultures of
Echinacea purpurea.
J Natl Cancer Inst 1989 May 3;81(9):669-75
In this study, acidic arabinogalactan, a highly purified polysaccharide from plant
cell cultures of Echinacea purpurea, with a molecular weight of 75, 000, was
effective in activating macrophages to cytotoxicity against tumor cells and microorganisms (Leishmania enriettii). Furthermore, this polysaccharide induced
macrophages to produce tumor necrosis factor (TNF-alpha), interleukin-1 (IL-1),
and interferon-beta 2. Arabinogalactan did not activate B cells and did not induce
T cells to produce interleukin-2, interferon-beta 2, or interferon-gamma, but it did
induce a slight increase in T-cell proliferation. When injected ip, this agent
stimulated macrophages, a finding that may have therapeutic implications in the
defense against tumors and infectious diseases.
Mose J
Effect of echinacin on phagocytosis and natural killer cells.
Med Welt 34: 1463-7, 1983 Orinda D Diederich J Wacker A [Antiviral activity
of components of Echinacea purpurea]
Arzneimittelforschung 1973 Aug;23(8):1119-20 (Published in German) Roesler J
Emmendorffer A Steinmuller C Luettig B Wagner H Lohmann-Matthes ML
Application of purified polysaccharides from cell cultures of the plant

Echinacea purpurea to test subjects mediates activation of the phagocyte

Int J Immunopharmacol 1991;13(7):931-41
Polysaccharides purified from large-scale cell cultures of the plant Echinacea
purpurea were tested for their ability to activate human phagocytes in vitro and in
vivo. These substances enhanced the spontaneous motility of PMN under soft
agar and increased the ability of these cells to kill staphylococci. Monocytes were
activated to secrete TNF-alpha, IL-6 and IL-1 whereas class II expression was
unaffected. Intravenous application of the polysaccharides to test subjects
immediately induced a fall in the number of PMN in the peripheral blood,
indicating activation of adherence to endothelial cells. This fall was followed by a
leukocytosis due to an increase in the number of PMN and a lesser increase of
monocytes. The appearance of stab cells and some juvenile forms and even
myelocytes indicated the migration of cells from the bone marrow into the
peripheral blood. The acute phase C-reactive protein (CRP) was induced,
probably due to activation of monocytes and macrophages to produce IL-6. In
addition a moderate acceleration of the erythrocyte sedimentation rate was
observed. Altogether, as in mice, the polysaccharides could induce acute phase
reactions and activation of phagocytes in humans. The possibility of clinical use
is discussed. Roesler J Steinmuller C Kiderlen A Emmendorffer A Wagner H
Lohmann-Matthes ML Application of purified polysaccharides from cell
cultures of the plant Echinacea purpurea to mice mediates protection
against systemic infections with Listeria monocytogenes and Candida
Int J Immunopharmacol 1991;13(1):27-37
Purified polysaccharides from cell cultures of the plant Echinacea purpurea were
investigated for their ability to enhance phagocytes' activities regarding
nonspecific immunity in vitro and in vivo. Macrophages (M phi) from different
organ origin could be activated to produce IL-1, TNF alpha and IL-6, to produce
elevated amounts of reactive oxygen intermediates and to inhibit growth of
Candida albicans in vitro. Furthermore, in vivo the substances could induce
increased proliferation of phagocytes in spleen and bone marrow and migration
of granulocytes to the peripheral blood. These effects indeed resulted in
excellent protection of mice against the consequences of lethal infections with
one predominantly M phi dependent and one predominantly granulocyte
dependent pathogen, Listeria monocytogenes and C. albicans, respectively.
Specific immune responses to sheep red blood cells (antibody production) and to
listeria (DTH) were not affected by the polysaccharides. The possibility of clinical
use is discussed. Samochowiec E Urbanska L Manka W Stolarska E
[Evaluation of the effect of Calendula officinalis and Echinacea angustifolia
extracts of Trichomonas vaginalis in vitro]
Wiad Parazytol 1979;25(1):77-81 (Published in Polish) Schumacher A
Friedberg KD [The effect of Echinacea angustifolia on non-specific cellular
immunity in the mouse]

Arzneimittelforschung 1991 Feb;41(2):141-7 (Published in German)

Echinacea belongs to the most usable plants in medical treatment since many
years. It is applicable in the fields of homoepathy and allopathy, however, there
are many different ways of treatment. Two species are listed in the European
Pharmacopoea: Echinacea angustifolia and Echinacea purpurea. They differ in
morphology and their chemical composition. There have been chemical and
biological analyses of Echinacea for about 80 years. After exact investigations of
these reports, the following result were found: Most chemical analyses were
done with Echinacea angustifolia, especially the older ones, whereas biological
activity was tested with Echinacea purpurea. In almost all of these experiments,
proprietaries were preferred to use in contrast to any plant extracts. Most of the
reports, which declared the stimulating biological activity of Echinacea could not
resist any critical opinion. So the frequency of medical application of this drug is
mainly due to delivered practical knowledge. The experiments described in this
study were practised with a water- soluble plant extract of Echinacea
angustifolia. Echinacosid one of its low-molecular compounds and proprietaries
which contains this plant. Their influence on the unspecified cellular immunity of
the mouse after intraperitoneal, intravenous or peroral application was
investigated. Under various conditions no effects on the immuno system could
be found using the carbon clearance test. Stimpel M Proksch A Wagner H
Lohmann-Matthes ML Macrophage activation and induction of macrophage
cytotoxicity by purified polysaccharide fractions from the plant Echinacea
Infect Immun 1984 Dec;46(3):845-9
Purified polysaccharides (EPS) prepared from the plant Echinacea purpurea are
shown to strongly activate macrophages. Macrophages activated with these
substances develop pronounced extracellular cytotoxicity against tumor targets.
The activation is brought about by EPS alone and is independent of any
cooperative effect with lymphocytes. Also the production and secretion of oxygen
radicals and interleukin 1 by macrophages is increased after activation with EPS.
Cells of the macrophages lineage seem to be the main target for the action of
these polysaccharides. EPS has no effect on T lymphocytes. B lymphocytes
show a comparatively modest proliferation after incubation with E. purpurea
EPS. Thus, these compounds, which are at least in tissue culture completely
nontoxic, may be suited to activate in vivo cells of the macrophage system to
cytotoxicity. They may therefore be of relevance in tumor and infectious systems.
Tragni E Galli CL Tubaro A Del Negro P Della Loggia R Anti-inflammatory
activity of Echinacea angustifolia fractions separated on the basis of
molecular weight.
Pharmacol Res Commun 1988 Dec;20 Suppl 5:87-90
Five fractions of an aqueous extract obtained from the roots of Echinacea
angustifolia were separated on the basis of molecular weight. The topical antiinflammatory activity of the fractions has been evaluated in mice using the
Croton oil ear test. The fraction with a molecular weight between 30, 000 and
100, 000 was the most active in inhibiting the oedema; it also reduced the
infiltration of inflammatory cells. The activity of this fraction was comparable with

that of a raw polysaccharidic extract obtained from E. angustifolia roots by

differential solubility. The high-molecular weight polysaccharides are therefore
proposed as the anti-inflammatory principles of the plant. Tubaro A Tragni E Del
Negro P Galli CL Della Loggia R Anti-inflammatory activity of a
polysaccharidic fraction of Echinacea angustifolia.
J Pharm Pharmacol 1987 Jul;39(7):567-9
The anti-inflammatory activity of a polysaccharidic fraction (EPF) obtained from
Echinacea angustifolia roots has been examined using the carrageenan paw
oedema and the croton oil ear test. EPF (0.5 mg kg-1 i.v.) almost inhibited the
carrageenan-induced oedema over 8 h and furthermore, EPF, topically applied,
inhibited mouse ear oedema induced by croton oil. EPF also reduced the
leukocytic infiltration of the croton oil dermatitis, evaluated both as peroxidase
activity and histologically. After topical application EPF appears to be slightly
inferior in potency to indomethacin. The results suggest that the antiinflammatory activity of E. angustifolia resides in its polysaccharidic content.
Voaden D and Jacobson M:
Tumor inhibitors. 3. Identification and synthesis of an oncolytic hydrocar
bon from American coneflower roots.
J Med Chem 15:619-23, 1972 Wacker A Hilbig W [Virus-inhibition by
echinacea purpurea (author's transl)]
Planta Med 1978 Feb;33(1):89-102 (Published in German)
Wagner V, Proksch A, Riess-Maurer, et al:
Immunostimulating polysaccharides (heteroglycanes) of higher plants preliminary communications. Arzneim Forsch 34:659-660, 1984
[Proceedings: Echinacea activates the properdin system] Echinacea
aktiviert das Properdinsystem
Med Monatsschr 1976 Jan;30(1):32-3 (Published in German)

Modulation of cytokine expression by traditional

medicines: a review of herbal immunomodulators.
Spelman K, Burns J, Nichols D, Winters N, Ottersberg S, Tenborg M.
Clinical Division, Department of Herbal Medicine, Tai Sophia Institute, 7750
Montpelier Road, Laurel, MD 20723, USA.

Modulation of cytokine secretion may offer novel approaches in the treatment of a

variety of diseases. One strategy in the modulation of cytokine expression may be
through the use of herbal medicines. A class of herbal medicines, known as
immunomodulators, alters the activity of immune function through the dynamic
regulation of informational molecules such as cytokines. This may offer an
explanation of the effects of herbs on the immune system and other tissues. For
this informal review, the authors surveyed the primary literature on medicinal
plants and their effects on cytokine expression, taking special care to analyze
research that utilized the multi-component extracts equivalent to or similar to
what are used in traditional medicine, clinical phytotherapy, or in the marketplace.
METHODOLOGY: MEDLINE, EBSCO, and BIOSIS were used to identify
research on botanical medicines, in whole or standardized form, that act on
cytokine activity through different models, i.e., in vivo (human and animal), ex
vivo, or in vitro. RESULTS: Many medicinal plant extracts had effects on at least
one cytokine. The most frequently studied cytokines were IL-1, IL-6, TNF, and
IFN. Acalypha wilkesiana, Acanthopanax gracilistylus, Allium sativum, Ananus
comosus, Cissampelos sympodialis, Coriolus versicolor, Curcuma longa,
Echinacea purpurea, Grifola frondosa, Harpagophytum procumbens, Panax
ginseng, Polygala tenuifolia, Poria cocos, Silybum marianum, Smilax glabra,
Tinospora cordifolia, Uncaria tomentosa, and Withania somnifera demonstrate
modulation of multiple cytokines. CONCLUSION: The in vitro and in vivo
research demonstrates that the reviewed botanical medicines modulate the
secretion of multiple cytokines. The reported therapeutic success of these plants
by traditional cultures and modern clinicians may be partially due to their effects
on cytokines. Phytotherapy offers a potential therapeutic modality for the
treatment of many differing conditions involving cytokines. Given the activity
demonstrated by many of the reviewed herbal medicines and the increasing
awareness of the broad-spectrum effects of cytokines on autoimmune conditions
and chronic degenerative processes, further study of phytotherapy for cytokinerelated diseases and syndromes is warranted.

Modulation of cytokine expression by traditional medicines: a review of

herbal immunomodulators.
Submitted by Site Editor on Wed, 2006-10-04 18:55.

Modulation of cytokine expression by traditional medicines: a review of herbal immunomodulators.: Altern Med Rev.
2006 Jun; 11(2): 128-50 Spellman K, Burns J, Nichols D, Winters N, Ottersberg S, Tenborg M
Modulation of cytokine secretion may offer novel approaches in the treatment of a variety of diseases. One strategy in
the modulation of cytokine expression may be through the use of herbal medicines. A class of herbal medicines, known
as immunomodulators, alters the activity of immune function through the dynamic regulation of informational

molecules such as cytokines. This may offer an explanation of the effects of herbs on the immune system and other
tissues. For this informal review, the authors surveyed the primary literature on medicinal plants and their effects on
cytokine expression, taking special care to analyze research that utilized the multi-component extracts equivalent to or
similar to what are used in traditional medicine, clinical phytotherapy, or in the marketplace. METHODOLOGY:
MEDLINE, EBSCO, and BIOSIS were used to identify research on botanical medicines, in whole or standardized
form, that act on cytokine activity through different models, i.e., in vivo (human and animal), ex vivo, or in vitro.
RESULTS: Many medicinal plant extracts had effects on at least one cytokine. The most frequently studied cytokines
were IL-1, IL-6, TNF, and IFN. Acalypha wilkesiana, Acanthopanax gracilistylus, Allium sativum, Ananus comosus,
Cissampelos sympodialis, Coriolus versicolor, Curcuma longa, Echinacea purpurea, Grifola frondosa, Harpagophytum
procumbens, Panax ginseng, Polygala tenuifolia, Poria cocos, Silybum marianum, Smilax glabra, Tinospora cordifolia,
Uncaria tomentosa, and Withania somnifera demonstrate modulation of multiple cytokines. CONCLUSION: The in
vitro and in vivo research demonstrates that the reviewed botanical medicines modulate the secretion of multiple
cytokines. The reported therapeutic success of these plants by traditional cultures and modern clinicians may be
partially due to their effects on cytokines. Phytotherapy offers a potential therapeutic modality for the treatment of
many differing conditions involving cytokines. Given the activity demonstrated by many of the reviewed herbal
medicines and the increasing awareness of the broad-spectrum effects of cytokines on autoimmune conditions and
chronic degenerative processes, further study of phytotherapy for cytokine-related diseases and syndromes is
herbal | immunity | review | traditional

Immunomodulating Compounds from Traditional

Chinese Herbs.
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Issue: 41 Page: 19
Immunomodulating Compounds from Traditional Chinese Herbs.
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HerbalGram. 1997;41:19 American Botanical Council

Immunomodulators are agents that exert a general net effect (positive or negative) on
the activity of the immune system or on a specific immune function.
Immunomodulators have the potential to be of clinical use in the enhancement (e.g., for
treating AIDS) or therapeutic suppression (e.g., for treating organ transplant rejection or
autoimmune disease) of immune function. Some compounds that have been isolated

from herbs used in traditional Chinese medicine (TCM) have been shown to have
immunomodulating activity.
More than 70 compounds have been isolated from the poisonous liana Tripterygium
wilfordii Hook.f., Celastraceae, largely alkaloids and terpenoids. Many have been
shown to be immunosuppressors in vitro and in vivo. T. wilfordii has been used in TCM
to treat fever, chills, edema, and inflammation, and extracts of the plant's xylem have
been used for rheumatoid arthritis, chronic nephritis, skin diseases, and immunological
Artemisinin, known as qing haosu in TCM, a sesquiterpene lactone isolated from
Artemisia annua (Sweet Annie, Artemisia annua "Qing-Hao" L., Asteraceae), is an
antimalarial drug. Recent clinical studies have found it to be an immunomodulator, and
that it can be effective in the treatment of systemic lupus erythematosis, psoriasis, and
other autoimmune-related disorders. Arteether, a semisynthetic analogue of
dihydroartemisinin (an artemisinin derivative), is being developed by the World Health
Organization to treat malaria. Another compound, artemether (a homologue of
arteether), is proving to have more potent antimalarial activity than artemisinin.
The fruits of Sophora alopecuoides (Fabaceae) and the roots of S. flavescens are used in
TCM for their antipyretic (fever reducing) effects. Alkaloids isolated from these plants
have been shown both to be immunosuppressors (at high doses) and immunostimulators
(at low doses). Diterpenoid alkaloids isolated from the axial roots of Aconitum species
used in TCM have shown anti-inflammatory, analgesic, antipyretic and
immunomodulatory activity. The sinomenine alkaloids, derived from Sinomenium
acutum Diels. (Menispermaceae), have been shown to be clinically effective in arthritis
and rheumatoid arthritis.
In addition to these compounds, several polysaccharides, such as those from the fruiting
bodies of Ganoderma lucidum (Reishi mushroom), ling chih (Leyss. ex Fr., P. Karst.,
Ganodermataceae), the fruits of Lycium barbarum L. Solanaceae, the whole plants of
Epimedium koreanum Berberidaceae nec pubescens, the roots of Panax ginseng C. A.
Mey., Araliaceae, Acanthopanax obovatus nec senticosus, and Achyranthes bidentata L.,

Amaranthaceae, have been found to be immunostimulators.

[Zhang, Ling-Hua, Yi Huang, Li-Wei Wang, and Pei-Gen Xiao. 1995. Several
Compounds from Chinese Traditional and Herbal Medicine as Immunomodulators.
Phytotherapy Research, Vol. 9, 315-322.]
Article copyright American Botanical Council.