Immunity: The New Priority
for the Modern Patient
Kerry Bone
Co-Founder and Director Research and Development
MediHerb
Adjunct Associate Professor,
University of New England, Australia
The Immune Challenge
• Modern epidemics, viruses jumping species
• Antibiotic-resistant bacteria
• High costs, long lead times for new antibiotic
drugs
• Antibiotic-induced changes in human flora and
the modern epidemic of Clostridium perfringens
• The rising incidence of atopic allergy, for example
anaphylaxis to peanuts
• The rising incidence of many autoimmune
diseases, including type 1 diabetes
• Immunosenescence
2
Antibiotic Resistance
• According to the World Health Organization
(March 2012), “Antimicrobial resistance threatens a
return to the pre-antibiotic era”
• 440,000 new cases of multidrug-resistant
tuberculosis (MDR-TB) emerge annually (150,000
deaths). MDR-TB reported in 64 countries to date
• Resistance to earlier generation
antimalarial medicines is widespread in
most malaria-endemic countries
http://www.who.int/mediacentre/factsheets/fs194/en/index/html
3
Antibiotic Resistance
• Many hospital-acquired infections are caused
by highly resistant bacteria such as methicillinresistant S. aureus (MRSA) and
vancomycin-resistant enterococci
(VRE)1
• In the US, more than 18000 people
die each year (50 every day!) from MRSA2 and up to
30000 from antibiotic-resistant Clostridium3
1
2
3
http://www.who.int/mediacentre/factsheets/fs194/en/index/html
Klevens RM et al. JAMA 2007; 298(15): 1763-1771
Tenover FC. http://www.hhs.gov/asl/testify/2008/06/t20080624e.html accessed July 4,
2012
4
The Post-Antibiotic Era
• Dr Margaret Chan, director general of WHO:
“A post-antibiotic era means, in effect, an end to
modern medicine as we know it. Things as common
as Strep. throat or a child’s scratched knee could
once again kill.
We are losing our first-line antimicrobials.
Replacement treatments are more costly, more
toxic, need much longer durations of treatment, and
may require treatment in intensive care units.”
http://www.who.int/dg/speeches/2012/amr_20120314/en/index.html access July 4 2012
5
Three Key Immune Herbs
• Echinacea angustifolia and/or Echinacea purpurea
root, mainly for prevention and to counter
immunosenescence
• Andrographis paniculata for acute viral or bacterial
infections
• Astragalus membranaceus for chronically depleted
immunity and supporting the immune system
under adverse conditions, especially the immune
cells themselves. Also for immunosenescence
6
My Favorite Herb
• Echinacea root has much to offer the modern
naturopathic physician, but it is so confused and
misunderstood
• There are a multitude of products using different
species, plant parts and manufacturing methods
• A lack of consensus over what phytochemicals in
Echinacea are responsible for its immune activity
• A rudimentary understanding of its exact mode of
action on the immune system, but with intriguing
new developments
• Many myths about how Echinacea should and
should not be used
7
A Brief History of Echinacea
• Information about the therapeutic value of
Echinacea first came from Native American tribes
• Their use of Echinacea was then adopted by the
Eclectic physicians
• By 1921 Echinacea (specifically
the root of E. angustifolia) was
by far the most popular
treatment prescribed by
Eclectic physicians
Wagner H. Z Phytother 1996; 17(2): 79-95
8
Lloyd JU. Echinacea angustifolia.
Lloyd Brothers, Cincinnati, 1923.
In: Bauer R, Wagner H.
Echinacea: Handbuch für Ärzte,
Apotheker und andere
Naturwissenschaftler. WVG,
Stuttgart, 1990, p 16.
9
A Brief History of Echinacea
• The Eclectics were responsible for Echinacea’s
reputation as an immune herb and they used the root
extracted in a high percentage of alcohol (lipophilic
extracts or tinctures)
• They felt that the tingling (due to alkylamides) was
the indicator of good quality
• In Europe during the 1930s the German herbalist
Madaus introduced E. purpurea tops as a stabilized
fresh juice (hydrophilic tincture)
• This eventually led to the investigation of
polysaccharides as Echinacea active components
Bauer R, Wagner H. In Wagner H, Farnsworth NR eds. Economic and Medicinal Plant
Research, Vol 5, Academic Press, London, 1991.
10
How the Eclectics
Used Echinacea Root
Abscesses
Alopecia
Anthrax
Appendicitis
Bed sores
Bee sting
Boils, Carbuncles
Cancer
Chicken-pox
Cholera
Chronic bronchitis
Chronic glandular indurations
Chronic malaria
Chronic ulcerations
Diabetes mellitus
Diphtheria
Dysentery
Eczema
Empyema
Epidemic influenza
Erysipelas
Exophthalmic goitre
Fevers
Gangrene
Gonorrhea
Impetigo
Impotence
Intestinal indigestion
Leg ulcers
Leucorrhea
11
How the Eclectics
Used Echinacea Root
Malaria
Mastitis, acute and chronic
Measles
Meningitis
Psoriasis
Puerperal infection
Pulmonary gangrene
Purulent salpingitis
Quinsy
Rabies
Renal hemorrhage
Respiratory catarrh
Scarlet fever
Scorpion sting
Septic injuries
Septicemia
Small pox
Snake bite
Spider bite
Syphilis
Tetanus
Tonsillitis
Tubercular abscesses
Typhoid fever
Ulcerative stomatitis
Urethral infection
Vulvitis
Wasp sting
Wounds
12
How the Eclectics
Used Echinacea Root
References for the previous slides
• Felter HW, Lloyd JU. King’s American Dispensatory. 18th
Edn, 3rd revision, Volume 1. First published 1905, reprinted
Eclectic Medical Publications, Portland, 1983.
• Ellingwood F, Lloyd JU. American Materia Medica,
Therapeutics and Pharmacognosy. 11th Edn. Naturopathic
Medical Series: Botanical Volume 2. First published 1898,
reprinted Eclectic Medical Publications, Portland, 1983.
13
How the Eclectics
Used Echinacea Root
Points of Note
• The Eclectics often used quite high doses of Echinacea
root
• They were not adverse to using Echinacea root longterm
• For example according to Ellingwood, Echinacea was
recommended for the following chronic conditions:
cancer, chronic mastitis, chronic ulceration, tubercular
abscesses, chronic glandular indurations and syphilis
• With regard to syphilis, Ellingwood writes: “The longest
time of all cases yet reported, needed to perfect the
cure, was nine months.”
Ellingwood F. American Materia Medica, Therapeutics and Pharmacognosy, Eclectic
Medical Publications, Portland, 1993.
14
Early Encounters with
Echinacea: Real or Not?
• As a student at the Jacka’s Naturopathy clinic,
Melbourne, Australia 1976
• As a herbal student, Tunbridge Wells, UK 1982
• At a US herbal trade show, 1987
• Real Echinacea gives you “asthma”, 1988
15
Learning the Power of
Real Echinacea
• The Eclectic writings in King’s Dispensatory and
Ellingwood, early 1990s
• Teaching Echinacea to
naturopathy undergraduates
and student feedback, early 1990s
• Feedback from patients and
learning the power of prevention,
early 1990s
16
The Four Key Echinacea Myths
1. Echinacea can only be taken for short periods.
Long-term use will wear out the immune system
(tachyphylaxis)
2. The polysaccharides are the true active
constituents, hence the root must be extracted
with water, or better still use only the tops
3. Echinacea is the best herb to treat winter viral
infections once they have occurred
4. Echinacea is dangerous in autoimmune disease
17
Echinacea Root: Short
or Long-Term
% Phagocytos is
160
140
Echinacea
120
Placebo
100
80
60
40
20
Tim e
(days)
0
-20
2
3
4
5
6
7
8
-40
Jurcic K et al. Z Phytother 1989; 10: 67-70
9
10
11
Active or placebo
3 x 30 drops per day
18
Problems with Polysaccharides
• Polysaccharides (PS) in Echinacea (tops or root)
have received research attention as active
components
• However, much of this research is in vitro and has
been confounded by endotoxin (lipopolysaccharide)
contamination of the samples used1
• The term “polysaccharide” is generic and includes
starches and other potentially inert plant
compounds, but these are often measured by the
crude analytical techniques used
1
Tamta H et al. J Agric Food Chem 2008; 56(22): 10552-10556
19
Problems with Polysaccharides
• Hence commercial Echinacea products claiming
quantified levels of PS should be viewed with
considerable caution
• Research has found that true polysaccharides are
extremely difficult to extract from Echinacea (top or
root) and they are unstable in the harvested dried
plant
• Ethanol strengths 40% or higher cannot extract the
PS from Echinacea, while less than 4% of PS1 and
17% of PS2 was extracted by hot water from any
dried plant part
Stuart DL et al. Optimisation of polysaccharides in processed Echinacea purpurea. RIRDC
Publication No. 04/118, 2004.
20
Problems with Polysaccharides
• PS are common to all plants, being components of
plant cell walls
• PS are large molecules with limited bioavailability
• The Eclectics never gave Echinacea
PS to patients, since they only
used high ethanol extracts
21
Echinacea Root:
What is Active?
• Echinacea root extracted with alcohol mainly
contains alkylamides and caffeic acid derivatives
• Herbal in vitro research is meaningless if the
extracts being tested do not contain bioavailable
phytochemicals
• What is active must be bioavailable, what is
bioavailable must be active: the model of
undertaking all quality research on herbs
• But subsequent clinical proof of activity of any
product optimized to these phytochemicals is
paramount
22
Echinacea Root: Pharmacokinetics
Study Design:
11 healthy individuals
Age: 18 to 26 years
BMI: 19 to 30
Blood samples taken
over 12 hours
Dose:
4 Echinacea root tablets as a single dose
23
What Compounds Were
Found in Bloodstream
• No caffeic acid conjugates
• No caffeic acid conjugate degradation products
• No alkylamide degradation products
• No polysaccharides
The only compounds identified in human
plasma were alkylamides from the
Echinacea ingested, at approximately the
same ratio as the initial product tested
Matthias A, Addison RS, Penman KG, Bone KM et al. Life Sci 2005; 77:
2018-2029
24
Echinacea - Liquid vs Solid Dose
Diene (ng/mL plasma)
Pharmacokinetics
200
150
100
50
0
0
60
120
180
240
300
360
Time (m in)
Matthias A, Addison RS, Agnew L, Bone KM et al, Phytomedicine 2007;
14(9): 587-590
25
Liver First Pass Metabolism
• The pharmacokinetic study suggested that
alkylamides were being degraded by the liver on first
pass after absorption in the GIT
• When liver decomposition of alkylamides was
investigated a surprising
fact was found
• Some alkylamides in
E. angustifolia are
degraded at a slower
rate and protect other
alkylamides (found in
E. angustifolia and E. purpurea) from degrading
26
Enhancing Bioavailability
100
% Original [247]
• 2-ene protects the
2,4-diene
• increasing amounts
of 2-ene alkylamide
gives less
degradation of the
2,4-diene
80
60
0.00
0.05
0.50
1.26
2.08
5.00
40
20
0
0
20
40
60
80
Time (min)
Matthias A, Gillam EMJ, Penman KG, Bone KM et al. Chem Biol Interact 2005; 155: 62-70
27
What Do Echinacea Alkylamides Do?
• Exert anti-inflammatory effects
• Some bind strongly to cannabinoid receptors
• Others may inhibit breakdown of endogenous
cannabinoids
• Possibly upregulate dendritic cell maturation
• Possibly responsible for positive effects on natural
killer (NK) cell function and numbers and increased
white cell phagocytic activity seen in several in vivo
studies
• Possibly responsible for effects on heat shock
proteins seen in human studies
Bone KM, Mills SY. Principles and Practice of Phytotherapy: Modern Herbal Medicine.
Elsevier, UK. 2nd Edition, In press.
28
Cannabinoid Receptors
• CB1 receptors are highly localized in the central
nervous system (CNS) and are believed to primarily
modulate behavior
• CB2 receptors predominate in
immune tissues outside the
CNS, especially the spleen,
and are believed to modulate
immune function
• Echinacea alkylamides mainly
bind to CB2 receptors
Ralevic V. Cannabinoid modulation of peripheral autonomic and sensory neurotransmission.
29
Eur J Pharmacol 2003; 472(1-2): 1-21
CB2 Binding of Alkylamide Isomers
 Using alkylamides supplied from Australia it has been
found that the tetraene isomers vary in terms
binding to CB receptors, with the ZZ isomer showing
a higher affinity than anandamide
Isomer
ZZ
ZE
EZ
EE
Ki CB2 (nM)
57 ± 8.5
9044 ± 2985
4535 ± 711
> 100000
 Alkylamides from other plants do NOT bind to CB2
Matovic N, Matthias A, Gertsch J, Bone KM et al. Org Biomol Chem 2007; 5(1): 169-174
30
Alkylamides and Anandamide
O
OH
NH
CH3
Anandamide: an endogenous cannabinoid
O
CH3
NH
CH3
CH3
Z,Z tetraene alkylamide from Echinacea
31
CB2 Activation: Subtle but Profound
• A lipophilic extract of E. purpurea strongly
stimulated TNF mRNA synthesis in peripheral
monocytes in vitro
• TNF mRNA was upregulated (around 8-fold) by the
Echinacea extract over a time-span of 24 hours, but
the constituent protein level (of TNF) was not
changed
• However, LPS-stimulated TNF production was
potently modulated by Echinacea, with inhibition
(around 40%) during the first 20 hours, and a
subsequent prolongation of TNF production
Gertsch J, Schoop R, Kuenzle U et al. FEBS Letters 2004; 577(3): 563-569
32
CB2 Activation: Subtle but Profound
• These effects were produced by the interaction of
Echinacea alkylamides with the CB2 receptors on
the monocytes
• The results of this study suggest that Echinacea
works more as a facilitator of the immune response.
In resting monocytes it prepares them for a quicker
response by inducing TNF mRNA
• However, in overstimulated monocytes (as in the
case of LPS) it first reduces, but then extends their
response in terms of TNF production
33
Echinacea: A Miracle Herb?
• In an extraordinarily entitled paper:
“Echinacea: a Miracle Herb against Aging and
Cancer?”, Canadian scientist Dr Sandra Miller
reviewed her research on Echinacea, specifically
Echinacea purpurea root1
• In healthy young adult mice, oral doses of
Echinacea purpurea root (0.45 mg per 25 g body
weight, similar to human dose rates) stimulated NK
cell production by bone marrow in the first 7 days
which resulted in significantly higher levels (around
25% more) of NK cells in the spleen by 2 weeks2
1
2
Miller SC. eCAM 2005; 2(3): 309-314
Sun LZ-Y, Currier NL, Miller SC. J Altern Complement Med 1999; 5: 437-446
34
Echinacea Boosts NK Cells
• In addition, the ‘helper’ or accessory cells
for NK cells, the monocytes, were also increased by
25%
• The Echinacea treatment influenced no other white
blood cell counts
• Polysaccharides, even by injection, were not
responsible for this effect
• Dr Miller feels that alkylamides are largely
responsible for the effect (personal communication)
• This research tends to shift the focus for Echinacea
to innate immunity and emphasizes its preventative
role
Currier NL, Lejtenyi D, Miller SC. Phytomedicine 2003; 10: 145-153
35
Echinacea Reverses Aging
of Innate Immunity
• NK cells decline in number and function with age
and this is thought to be one factor behind the
increase of various cancers with age
• Experiments conducted in healthy, elderly mice
found that 2 weeks of oral doses of Echinacea
returned NK cell numbers in bone
marrow and spleen to the levels of
young adults and also resurrected
the functional capacity (target cell
binding, lysis) of these cells1
1
Currier NL, Miller SC. Exp Gerontol 2000; 35: 627-639
36
Echinacea Reverses Aging
of Innate Immunity
• On this result Dr Miller writes1:
“These observations appear to apply uniquely to this
herb since we could never rejuvenate the NK cellmediated component of the immune system in
elderly mice by any of the other typical NK cell
enhancers….”
• In addition for mice fed Echinacea purpurea root
from 7 weeks of age to 13 months lifespan was
significantly extended compared to controls2
1
2
Miller SC. eCAM 2005; 2(3): 309-314
Brousseau M, Miller SC. Biogerontology 2005; 6: 157-163
37
Heat Shock Proteins
• Heat shock proteins (HSPs) are molecular
chaperones that bind to large proteins to facilitate
their folding (during synthesis) and to prevent misfolding (after synthesis)
• While basal levels of HSPs exist within cells, they
are further induced by temperature shock or other
stressors
• They act to protect cells from protein denaturation
and possible death under hostile conditions
• Certain HSPs within immune cells also appear to
facilitate the immune response (antigen
presentation)
38
Heat Shock Proteins
• Extracellularly, HSPs appear to act like cytokines
(as “moonlighting proteins”) and can modulate
immune responses
Chen T, Cao X. Eur J Immunol 2010; 40(6): 1541-1544
Henderson B. Cell Biochem Funct 2010; 28(1): 1-14
39
Echinacea Root and HSPs
• In an open-label pilot trial, 11 healthy volunteers
were evaluated at baseline (day 1) and on day 15
after consuming 2 Echinacea root tablets/day
(standardized to 4.4 mg alkylamides) for 14 days1
• Echinacea root markedly enhanced (by about 50%)
the increase in white cell heat shock protein (hsp70)
expression after mild heat shock (p=0.029)
• White cell counts were mildly increased (p=0.043)
and there was a preventative effect against free
radical induced erythrocyte hemolysis (p=0.006)
1
Agnew LL et al. J Clin Pharm Ther 2005; 30(4): 363-369
40
Echinacea Root and HSPs
• A follow-up open-label trial in 24 healthy volunteers
used the same design, except the Echinacea root
dose was twice the above1
• While Echinacea did not significantly change basal
hsp70 expression in lymphocytes, it increased CD4,
CD8 and NK cell stress-induced hsp70 expression
• The effect was most marked in NK cells (p<0.05)
• This implies that Echinacea root may play a role in
activating and protecting the immune system via
HSPs when the body encounters a challenge, such
as a virus
1
Agnew L et al. Planta Med 2010; 76(12): P629, 1354
41
The Four Key Echinacea Myths
1. Echinacea can only be taken for short periods.
Long-term use will wear out the immune system
(tachyphylaxis)
2. The polysaccharides are the true active
constituents, hence the root must be extracted
with water, or better still use only the tops
3. Echinacea is the best herb to treat winter viral
infections once they have occurred
4. Echinacea is dangerous in autoimmune disease
42
Echinacea Root for the Common Cold
• In a large and well-designed US trial, the impact of
taking Echinacea root shortly after common cold
onset was investigated
• The active intervention was
10.2 g of dried Echinacea
root during the first 24 h,
and then 5.1 g/day for the
next 4 days
• Primary outcomes assessed
were global severity
throughout the illness and duration of infection
Barrett B, Brown R, Rakel D et al. Ann Intern Med 2010; 153(12): 769-777
43
Echinacea Root for the Common Cold
No Pill
Group
Unblinded
Echinacea
Group
Blinded
Placebo
Group
Blinded
Echinacea
Group
Participants (n)
173
181
176
183
Median global
severity
220
195
206
193
Median duration (d)
6.42
6.16
6.87
6.34
Participants (n)
80
97
79
95
Median global
severity
221
177
199
196
Median duration (d)
6.66
6.15
6.38
6.07
Whole Group
Herbs within 24 h
Barrett B, Brown R, Rakel D et al. Ann Intern Med 2010; 153(12): 769-777
44
Prevention is Better Than Cure
• In a study presented by the late Dr Anna Macintosh
at the 1999 Convention of the American Association
of Naturopathic Physicians, an Echinacea root
formulation was compared against a herbal
adaptogenic formulation and a placebo in the
prevention of winter colds over a 90-day period1
• The trial recruited 260 medical students who were
under stress from their studies
• The placebo group averaged an infection rate of
10%, whereas this dropped to as low as 2% by day
70 (p=0.013) in the Echinacea group
1
McIntosh A et al. AANP Convention, Coeur d’ Arlene, 1999.
45
Echinacea and Long-haul Flights
• A randomized, double blind, placebo-controlled
clinical trial was undertaken with 175 participants
travelling return from Australia to North America,
Europe or Africa for 1 to 5 weeks
• Active tablets each contained extract from 1.275 g
Echinacea root (4.4 mg alkylamides)
• Priming dose was 2/day, travel dose was 4/day and
dose when ill was 6/day
• The placebo group exhibited significantly higher
average respiratory infection symptom score
(around double) compared with the Echinacea
group (p<0.05) after return from travel
Tiralongo E et al. Evid Based Complement Alternat Med 2012; 2012: 417267
46
Echinacea Root and Air Travellers
Tiralongo E et al. Evid Based Complement Alternat Med 2012; 2012: 417267
47
The Four Key Echinacea Myths
1. Echinacea can only be taken for short periods.
Long-term use will wear out the immune system
(tachyphylaxis)
2. The polysaccharides are the true active
constituents, hence the root must be extracted
with water, or better still use only the tops
3. Echinacea is the best herb to treat winter viral
infections once they have occurred
4. Echinacea is dangerous in autoimmune disease
48
Echinacea and Autoimmunity
• The caution for Echinacea in autoimmunity
was based on theoretical grounds and the few
isolated adverse events hardly provide reasonable
grounds for a contraindication
• Mice with autoimmune diabetes did not show
adverse effects when fed Echinacea purpurea root1
• In a controlled clinical trial, patients with
autoimmune uveitis were able to reduce their time
on prednisone when given Echinacea purpurea2
• The role of immune herbs in autoimmunity will be
revisited later in this seminar
1
2
Delorme D, Miller SC. Autoimmunity 2005; 38(6): 453-461
Neri PG et al. J Ocul Pharmacol Ther 2006; 22(6): 431-436
49
Echinacea: Conclusions and
Recommendations
Preferred Preparations and Key Quality Markers
• The preferred parts of Echinacea to use are the
roots of E. angustifolia combined with E. purpurea
• The alkylamides are the important quality marker
compounds (even active constituents) and MUST be
present in adequate quantities
• Doses must be adequate: at least 2.5 g of a root
combination per day (temporarily  to ward off
infection)
50
Echinacea: Conclusions and
Recommendations
The Mode of Action
• Alkylamides are bioavailable, importantly tablet and
liquid preparations are equipotent if appropriately
formulated
• Alkylamides in E. angustifolia help inhibit the rapid
liver breakdown of alkylamides from E. purpurea
• Echinacea root boosts innate immunity with
continued use and modulates immune activity during
an acute phase response
• Mechanisms are complex but probably involve
(among others) CB2 agonism and HSP induction
51
Echinacea: Conclusions and
Recommendations
Best Clinical Practice
• Echinacea root is better used as a preventative for
infections, although traditionally it does have a role
for resolving chronic infections
• Long-term use of Echinacea root is in fact not only
beneficial, it is necessary for its full immune effects
• There is no reason why Echinacea root should be
contraindicated in autoimmune disease, in fact it
may be beneficial (see later in this seminar)
52
Andrographis and Winter Infections
• Two systematic reviews of the role of Andrographis
in the clinical management of upper respiratory tract
infections have been published
• In one review, 7 double blind, controlled trials
(n=896) that met inclusion criteria for evaluation of
efficacy were considered
• All trials scored at least 3
(out of a maximum of 5)
for methodological quality
on the Jadad scale
53
Andrographis and Winter Infections
• Collectively, the data suggested that Andrographis
was superior to placebo in alleviating the subjective
symptoms of uncomplicated upper respiratory tract
infection. There was also preliminary evidence of a
preventative effect
• Adverse events reported following
the herb administration were
generally mild and infrequent1
• In the second review, 433 patients
from 3 trials were included in the
meta-analysis
1
Coon JT, Ernst E. Planta Medica 2004; 70(4): 293-298
54
Andrographis and Winter Infections
• Andrographis either alone or in combination with
Eleutherococcus was more effective than placebo in
the treatment of uncomplicated acute upper
respiratory tract infection1
• Doses used were typically up
to 1000 mg/day of extract
(about 6 g of herb) delivering
50 to 60 mg/day andrographolides
1 Poolsup N, Suthisisang C, Prathanturarug S et al. J Clin Pharm Ther 2004; 29(1): 37-45
55
Andrographis and Autoimmunity
• A 14-week randomized, double blind, placebocontrolled clinical trial in 60 patients examined the
impact of a 75% ethanolic extract of Andrographis
(300 mg/day corresponding to 3 g of herb and
containing 90 mg of andrographolides) in active
rheumatoid arthritis1
• All trial patients were given methotrexate and were
allowed to take prednisone or chloroquine in stable
doses if already prescribed
1 Burgos RA, Hancke JL, Bertoglio JC et al. Clin Rheumatol 2009; 28(8): 931-946
56
Andrographis and Autoimmunity
• Compared with baseline there were significant
improvements observed in the Andrographis group
by week 14
• However, compared with the placebo group these
changes in RA were not statistically significant
57
Andrographis and Autoimmunity
• A randomized, double blind trial (n=108) was
conducted at five centers in Shanghai to compare a
standardized extract of Andrographis with the
nonsteroidal anti-inflammatory drug mesalazine
(4.5 g/day, in slow release form) in patients with
mildly to moderately active ulcerative colitis
(confirmed by colonoscopy)1
• Treatment with Andrographis extract demonstrated
similar efficacy to mesalazine but with fewer
adverse events
1 Tang T, Targan SR, Li ZS et al. Aliment Pharmacol Ther 2011; 33(2): 194-202
58
Astragalus and Immunity
• In an open, randomized clinical trial, 115 patients
with leucopenia received a high dose of a
concentrated Astragalus preparation (equivalent to
30 g/day of Astragalus) or a low dose (equivalent to
10 g/day) over a period of 8 weeks
• There was a significant rise of average white blood
cell (WBC) counts in both groups after treatment
(p<0.001)
• The average WBC count for the high-dose group
was significantly higher than for the low-dose group
(p<0.05)
Weng XS. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih 1995; 15(8): 462-464
59
Astragalus and Cancer Therapy
• A meta-analysis of 34 randomized clinical trials
involving patients with non-small-cell lung cancer
treated with platinum-based chemotherapy and
Astragalus-based Chinese herbs suggested a benefit
from the combination1
• Most trials involved formulas featuring Astragalus,
but two were of Astragalus alone. The herbs were
administered by injection in around one third of the
trials
1
McCulloch M, See C, Shu XJ et al. J Clin Oncol 2006; 24(3): 419-430
60
Astragalus and Cancer Therapy
• 12 trials measuring such outcomes reported
significantly lower mortality rates after 12 months
when Astragalus was combined with chemotherapy
(risk ratio 0.67)
• 9 studies reported significantly lower mortality rates
after 24 months when Astragalus
was combined with chemotherapy
(risk ratio 0.73)
• Most of the studies included were
of low methodological quality
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Astragalus and Cancer Therapy
• A Cochrane review identified four relevant trials
where a decoction of Astragalus and a formulation
featuring Astragalus was combined with
chemotherapy in patients with colorectal cancer
• Chemotherapy-induced nausea, vomiting, and
leucopenia were all decreased by concomitant
administration of Astragalus decoction, and immune
function was improved
• The trials were of low quality, suggesting larger,
more rigorous trials are needed to confirm these
results
Taixiang W, Munro AJ, Guanjian L. Cochrane Database Syst Rev (1):CD004540, 2005
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Astragalus and Autoimmunity
• A US group of doctors described 2 separate cases
(published 3 years apart) of complete remission of
idiopathic membranous nephropathy (IMN,
probably autoimmune in origin) after therapy with
Astragalus
• The first case described a 77-year-old woman with
nephrotic syndrome secondary to IMN who was
largely unresponsive to conventional treatments.
After beginning Astragalus (15 g/day as part of the
formulation Shen-Yan Siwei Pian) there was a
marked decrease in proteinuria
Ahmed MS, Hou SH, Battaglia MC et al. Am J Kidney Dis 2007; 50(6): 1028-1032
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Astragalus and Autoimmunity
• Nephrotic syndrome recurred after a temporary
cessation of the formulation, with complete
remission after its reintroduction
• Remission persisted even after stopping the herbal
treatment
• The second case was a 63-yearold man with nephrotic syndrome
due to IMN who took 15 g/day
Astragalus on its own1
1
Leehey DJ, Casini T, Massey D. Am J Kidney Dis 2010; 55(4): 772
64
Overall Conclusions
• The post-antibiotic era is coming
• Immune herbs have much to offer the modern
patient and if used in appropriate doses of quality
preparations can achieve dramatic results
• The main value of Echinacea root is as a
preventative, and its informed use can be practice
building
• Astragalus and Andrographis also have important
roles, the latter for acute infections and the former
for chronically depressed immunity
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Echinacea Research Collaborators
University of Queensland research groups
• Prof Istvan Toth
• Dr JJ De Voss
• Dr E Gillam
• Prof R Dickenson and Prof W Hooper
Southern Cross University research groups
• A/Prof D Leach
• Prof S Meyers
University of New England research group
• Prof K Watson
Swiss Federal Institute of Technology
• Dr J Gertsch
University of Wisconsin
• Dr Bruce Barrett
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Acknowledgments with Thanks
Echinacea research team
• A/Prof Reg Lehmann
• Dr Anita Matthias
• Dr Kerry Penman
Contribution to presentation
• Berris Burgoyne ND
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