Available online at www.sciencedirect.
com
Use of natural products in gastrointestinal therapies
Stuart M Brierley1,2,3 and Olaf Kelber4
Altered motility, discomfort and pain are common debilitating
symptoms of patients with functional gastrointestinal
disorders. However, these conditions represent a significant
and unmet need for mainstream medical treatment, particularly
after high profile therapeutic drug withdrawals due to safety
concerns. As such an increasing number of sufferers are
turning to alternative medicines in an effort to seek relief from
their symptoms. Alternative medicines have traditionally been
looked at by mainstream medicine with cynicism. However,
new evidence demonstrates that the active components in
natural products have actions on specific ion channels and
receptors, many of which are located in sensory systems
distributed throughout the body. These findings may not only
explain the symptomatic benefit of these alternative medicines
but also provide novel therapeutic targets for mainstream drug
development. As such natural products represent a wealth of
untapped potential which is waiting to be unlocked.
Addresses
1
Nerve-Gut Research Laboratory, Discipline of Medicine, Faculty of
Health Sciences, The University of Adelaide, Adelaide, South Australia
5000, Australia
2 classes of specific taste receptors and taste receptor cells are
Department of Gastroenterology & Hepatology, Hanson Institute, Royal
Adelaide Hospital, Adelaide, South Australia 5000, Australia
3
Discipline of Physiology, Faculty of Health Sciences, The University of
Adelaide, Adelaide, South Australia 5000, Australia
4
Scientific Department, Steigerwald Arzneimittelwerk GmbH,
Darmstadt, Germany
Corresponding author: Brierley, Stuart M
(stuart.brierley@adelaide.edu.au)
Current Opinion in Pharmacology 2011, 11:604–611
This review comes from a themed issue on
Gastrointestinal
Edited by L Ashley Blackshaw and Qasim Aziz
Available online 11th October 2011
1471-4892/$ – see front matter
# 2011 Elsevier Ltd. All rights reserved.
DOI 10.1016/j.coph.2011.09.007
Introduction
Functional Dyspepsia (FD) and Irritable Bowel Syndrome
(IBS) are highly prevalent functional gastrointestinal dis-
orders affecting up to 30% of the population. Although
their aetiologies are different, altered motility, discomfort
and pain are common symptoms, as are a lack of effective
mainstream medical therapies. Increased recognition by
patients of the current limits of conventional mainstream
medicine has helped drive growing interest in alternative
natural product therapies. However, such therapies are
Current Opinion in Pharmacology 2011, 11:604–611
viewed by many in mainstream medicine with scepticism.
There are many reasons for this including a historical lack
of rigorous clinical trials and a perception that these ‘natural
therapies’ are just non-specific actions. However, over the
last decade an enormous amount of evidence in a variety of
fields has indicated that natural products are a valuable
source of pharmacological tools, as they have actions on
specific ion channels and receptors, and are therefore
potentially useful leads in the development of new human
therapeutics.
Selectivity of natural products
Natural products comprise compounds that have been
extracted from botanical sources through to all manner
of organisms (for probiotics see review by Eamon Quigley
in this edition). Such compounds have allowed major
mechanistic breakthroughs in physiology and disease in
other fields. For example, recent advances in taste mod-
alities, a fundamental process we take for granted every-
day, reveal complex mechanisms whereby several distinct
required to distinguish between sweet, sour, bitter, umami
(savoury) and salty compounds [1]. By contrast, more
brutal natural products have evolved for prey capture and
defence. Cone snails, snakes, spiders and scorpions utilise
venoms containing diverse bioactive compounds to
immobilise or kill their prey. In fact, many of these venom
peptides have been shown to act on specific ion channels
(particularly voltage-gated sodium/potassium/calcium
channels) and other cellular receptors to impair their
normal functioning [2,3]. Such studies have utilised
high-throughput screening methods to identify venoms
with a desired activity to allow subsequent isolation of
bioactive molecules [4]. The successfulness of this
approach has led to several different venom peptide deriva-
tives receiving FDA approval for clinical use in hyperten-
sion (Captopril), unstable angina (Eptifibatide), Type 2
diabetes mellitus (Exenatide) and highly selective use in
chronic pain (Ziconotide) [4]. These drug treatments are
synthetic versions of active compounds identified from the
pit viper (Bothrops jararaca), rattle snake (Sistrurus miliarius
barbouri), Gila monster (Heloderma suspectum) and cone
snail (Conus magus), respectively.
In the GI field we have yet to scratch the surface of
mechanistic insight to be gleamed from these developing
venomous compounds. To date the best insight has been
gained from the neurotoxin tetrodotoxin (TTX; isolated
from the puffer fish) where animal studies have shown
that sodium currents that are TTX-resistant (thought to
be mediated by NaV1.8) are enhanced in gut innervating
sensory neurons in inflammatory, nematode or bacterial
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 Use of natural products in gastrointestinal therapies Brierley and Kelber 605
models, leading to neuronal hyper-excitability [5].
These TTX-resistant sodium currents are also enhanced
by the pro-inflammatory cytokine Tumour Necrosis Fac-
tor-a (TNFa) [6], the levels of which are increased in
ulcerative colitis, FD and IBS patients. Family members
of NaV1.8 have also been implicated in human gut syn-
dromes, as IBS patients with mutations in SCN5A (the
gene encoding NaV1.5) are more likely to report gastro-
intestinal symptoms, especially abdominal pain [7]. A
NaV1.7 gain-of-function mutation in SCN9A underlies
the human condition ‘familial rectal pain syndrome’,
now renamed ‘paroxysmal extreme pain disorder’ [8].
Overall, there is a cornucopia of unexploited promise
waiting to be unlocked from venomous compounds,
which will be extremely useful in regulating sensory
afferent and enteric neuromuscular function.
Clearly taste modalities and venomous compounds have
specific mechanisms of action but what about botanical
compounds such as herbs and spices? This is an important
question as herbal preparations are some of the most
popular alternate therapies for gastrointestinal symptoms.
In the last 5 years significant progress has been made in
this regard, particularly with the discovery that numerous
herbs and spices activate members of the Transient Re-
ceptor Potential (TRP) family of ion channels (Table 1).
TRPs are non-selective cation channels comprising 5
subfamilies: TRPA (ankyrin), TRPC (canonical), TRPM
(melastatin), TRPP (polycystin) and TRPV (vanilloid)
(for details see [9]). TRPs are now regarded as being at
the ‘frontline’ of sensory transduction as they are
expressed in sensory nerve endings throughout the body
and underlie our ability to detect thermal, chemical and
mechanical stimuli. To date probably the most studied
natural compound is capsaicin (Table 1), the main pun-
gent ingredient in ‘hot’ chilli peppers (Capsicum annuum),
and the channel it acts on TRPV1 [10]. Other highly
Table 1
Herbal components identified to act on TRP channels.
Natural compound Botanic origin
Capsaicin Hot chilis (Capsicum annuum)
Resiniferatoxin Plant (Euphorbia resinifera)
Bisandrographolide Chinese Herb (Andrographis paniculata)
Allyl-isothiocyanate Mustard and wasabi
Allicin Garlic (Allium sativum)
Cinnamaldehyde Cinnamon (Cinnamomum cassia)
Menthol Peppermint (Mentha piperita)
Eucalyptol Eucalyptus oil (Eucalyptus polybractea)
Hyperforin St. John’s wort (Hypericum perforatum)
Vanillin Vanilla (Vanilla planifolia)
Eugenol Clove oil (Eugenia carophyllata)
Gingerol Ginger oil (Zingiber officinale)
Camphor Camphor tree (Cinnamomum camphora)
Carvacrol Oregano (Origanum genus)
Citral Lemongrass (Cymbopogon)
Curcumin Turmeric (Curcuma longa)
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specific natural TRPV1 agonists include Resiniferatoxin,
from the plant Euphorbia resinifera, which is several times
more potent than capsaicin, and the venom from the West
Indian tarantula Psalmopoeus cambridgei (see [10] for
details). We can all appreciate that chillis elicit burning
pain and as such has been an area widely studied in the GI
field. Human studies indicate increased expression or
function of TRPV1 in a number of GI diseases including
Gastro-Oesophageal Reflux Disease, FD, Inflammatory
Bowel Disease (IBD) and IBS (see [11] for details).
More recently a compound called Bisandrographolide
contained in extracts of the Chinese Herbal plant Andro-
graphis paniculata has been shown to activate TRPV4
[12], a channel which has been shown in animal studies
to contribute to mechanically evoked visceral pain [13].
Another channel implicated in visceral signalling and pain
is TRPA1 [14], which is activated by the pungent
chemicals allyl-isothiocyanate (mustard oil and wasabi)
and allicin (from garlic). In terms of analgesic effects
menthol, a compound obtained from peppermint oil
(Mentha piperita), which is known for its cooling and
soothing effects activates TRPM8 [9] but also inhibits
TRPA1 [15], whilst hyperforin, a key anti-inflammatory
constituent of St. John’s wort, activates TRPC6 [16].
Other herbal extracts can also act across a variety of
TRP channels, for example, eugenol (from clove oil)
activates TRPM8, TRPA1 and TRPV1 [10], whilst
gingerol (from ginger) activates TRPV1 and TRPA1
[10]. Camphor, from the Cinnamomum camphora tree,
activates TRPV3 and TRPV1 but intriguingly sub-
sequently desensitises TRPV1 and inhibits TRPA1
[10,17]. Similarly, carvacrol, the major ingredient of
oregano (Origanum genus), activates TRPV3 and TRPA1,
but then rapidly desensitises TRPA1 [10,18]. Other
herbs block TRP channels, with citral, the active ingre-
dient of lemongrass, blocking the agonist-evoked activity
Primary effect
Activates TRPV1
Potently activates TRPV1
Activates TRPV4
Activates TRPA1
Activates TRPA1
Activates TRPA1
Activates TRPM8 but also inhibits TRPA1
Activates TRPM8
Activates TRPC6
Weak activator of TRPV3
Activates TRPM8, TRPA1 and TRPV1
Activates TRPV1 and TRPA1
Activates TRPV3 and TRPV1, then desensitizes TRPV1.
Also inhibits TRPA1
Activates TRPV3 and TRPA1, then rapidly desensitizes TRPA1
Blocks TRPV1, TRPV2, TRPV3, TRPV4, TRPM8, and TRPA1
Blocks TRPV1
Current Opinion in Pharmacology 2011, 11:604–611
606 Gastrointestinal
of TRPV1, TRPV2, TRPV3, TRPV4, TRPM8, and
TRPA1 [19] whilst curcumin, the major component of
turmeric, blocks capsaicin-induced TRPV1 activation
[20]. Although this is not an exhaustive list and new
interactions are being discovered rapidly these studies
indicate how herbs can provide potential therapeutic
benefit through activation or inhibition of individual or
multiple channels. It may also explain why synergistic
effects are observed in some herbal treatments with
multiple components (see below). Furthermore, a recent
meta-analysis also concluded that the therapeutic benefit
of alternative products is not due to an enhanced placebo
effect [21]. To date the best studied herbal treatments for
GI therapy are Iberogast1 and peppermint oil, with the
later studied either alone or in combination with caraway
oil. Other potential natural product treatments for GI
therapy include curcumin, artichoke leaf extract and
various Chinese, Japanese, Tibetan and African Herbal
remedies which are discussed below.
IberogastW
Is the trading name of STW 5 a fixed combination of a fresh
plant extract from bitter candytuft (Iberis amara) and drug
extracts from greater celandine herb, angelica root, lemon
balm leaves, peppermint leaves, caraway fruit, liquorice
root, chamomile flower and milk thistle fruit [22]. STW 5 is
best known for its beneficial effect in FD, for a detailed
review of the clinical evidence see [23], and has also been
shown to be beneficial in IBS [24,25]. In a meta-analysis,
STW 5 has also been shown to be effective in treating
heartburn as a symptom of functional dyspepsia [26] and
due to its proven tolerability, it is also successfully used by
children [27]. Overall, STW 5 has a remarkable set of
effects on motility, sensory afferents, and secretion, in
addition to anti-inflammatory and anti-oxidant properties.
In terms of specificity, STW 5 selectively inhibits binding
to 5-HT4 and muscarinic M3-receptors, whilst affinity to
5-HT3 receptors is low [28]. In addition, STW 5 has
affinity to the adenosine A2A receptor. These effects
result from the properties of the individual components,
with the fresh plant extract of bitter candy tuft (I. amara)
selectively inhibiting binding to muscarinic M3 receptors,
extracts of celandine herb and chamomile flower to 5-
HT4 receptors, and liquorice root to 5-HT3 receptors [28].
STW 5 and its components have region-specific effects on
muscle from the gastric fundus, corpus and antrum. In the
corpus and fundus, STW 5 has a significant, concen-
tration-dependent muscle relaxant effect, whilst in antral
muscle STW 5 stimulates phasic contractility, with find-
ings consistent across guinea-pig [29] and human muscle
[30]. These region-specific effects were also confirmed in
a clinical pharmacological study, where STW 5 (single
oral dose) has a relaxing effect in the proximal stomach,
together with a significant and long lasting stimulation of
antral motility starting 10 min after administration [31].
Current Opinion in Pharmacology 2011, 11:604–611
This region-specific action is thought to be mediated by
actions on different types of calcium channels.
STW 5 also has contrasting effects on intestinal muscle
function depending on the location and experimental
conditions. In intestinal muscle, STW 5 has a relaxant
effect on contraction stimulated by different agents
(acetylcholine, prostaglandin F2a and substance P)
[32], in which all constituent extracts of STW 5 are
involved. These spasmolytic effects from mouse ileum
are also apparent in guinea-pig ileum and colon [33] and
in human colonic tissue [30]. These effects are likely
mediated by inhibition of action potentials and slow
waves, which was observed in mouse ileum in vitro,
and an inhibitory effect on fast and slow inhibitory
junction potentials, which was observed in colon
[34,35]. By contrast, in relaxed ileal preparations tonicis-
ing effects are observed, which point to a partial agonist
action in addition to the inhibitory action, and may result
in a normalizing effect on muscle activity [33,36]. Sim-
ilarly, in vitro studies on guinea-pig lower oesophageal
sphincter show STW 5 has tonicising effects, whilst not
influencing pyloric tone [30].
An important mechanism by which STW 5 can relieve
dyspeptic and bowel symptoms in patients is by its action
on sensory afferents innervating the gut. Oral adminis-
tration of STW 5 reduces rat jejunal afferent sensitivity to
mechanical distension, serotonin and bradykinin [37,38],
an effect partially mediated by the component I. amara
[39]. STW 5 also influences secretion. In a model of
indomethacin-induced gastric hyperacidity, STW 5
decreases acid secretion, whilst stimulating mucin
secretion [40]. In human colonic preparations STW 5
also enhances chloride secretion via a direct effect on
epithelial chloride channels [41], suggesting STW 5 is a
secretogogue in the human intestine.
Subclinical inflammation is a potential aetiological factor
for functional gastrointestinal disorders [36] and STW 5
has significant anti-inflammatory effects [42,43], redu-
cing; first, reflux-induced oesophagitis, second, gastric
ulcers and third, TNBS-induced or DSS-induced colitis
[40,44–46]. In the case of colitis, STW 5 has comparable
effects to sulfasalacin [44]. In another study of TNBS-
induced inflammation, STW 5 administration decreases
TNF-a expression and restores disturbed acetylcholine-
induced contraction, whilst its component I. amara stimu-
lates Interleukin-10 mediated anti-inflammatory effects.
Additionally, STW 5 decreased TNFa release in Escher-
ichia coli lipopolysaccharide-stimulated human mono-
cytes [47]. Several in vitro and in vivo models show
STW 5 has anti-oxidant effects, which may also contrib-
ute to its anti-inflammatory effects [46,48,49,50].
Overall, STW 5 appears well tolerated in humans and due
to its combination of extracts has numerous mechanisms of
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 Use of natural products in gastrointestinal therapies Brierley and Kelber 607
action in symptom relief, which appears to be advantageous
for heterogeneous conditions such as FD and IBS with
complex aetiologies [42,43].
Peppermint oil
Peppermint oil is an extract of peppermint (M. piperita),
which has long been thought to act as an intestinal
smooth muscle relaxant [51]. As such peppermint oil
has been the subject of study as an attractive therapy for
GI symptom relief, where it is commonly commercially
available in an enteric-coated preparation for the treat-
ment of IBS. Systematic reviews and meta-analyses of
earlier placebo-controlled randomised trials supported
peppermint oil’s effectiveness in relieving IBS symp-
toms; although some trials had methodological flaws,
weakening the findings (for detailed reviews see [52–
55]). Recent, more stringent clinical studies have shown
a clear benefit of daily use enteric-coated peppermint
oil capsules in improving IBS symptoms [56,57]. One
randomised, double blind, placebo controlled study of
57 IBS patients showed two enteric coated peppermint
oil capsules, twice a day, for 4 weeks led to significantly
higher response rates and a significant reduction in
bloating, abdominal distension, difficulty at evacuation,
pain at evacuation and the feeling of incomplete
evacuation [56]. Another randomised, double-blind,
placebo controlled study of 90 outpatients with IBS
one capsule of enteric-coated, delayed-release pepper-
mint oil three times daily for 8 weeks led to a significant
reduction in symptoms (including abdominal pain) and
improvement in quality of life compared to placebo
[57].
Since these studies were conducted menthol, a major
component of peppermint oil, has been identified as a
potent activator of TRPM8 [9]. This mechanism is respon-
sible for the cooling or soothing sensation of menthol when
inhaled, eaten or applied topically to the skin. Recently,
TRPM8 has been located on a select population of
nociceptive neurons innervating the colon [58]. This
study also showed incubating colonic nociceptive endings
with icilin, a synthetic more potent version of menthol,
reduced nociceptor mechanosensitivity. Furthermore, a
subpopulation of TRPM8 colonic nociceptors also co-
expressed TRPV1 and TRPA1, two major TRP channels
implicated in colonic pain [11]. Pre-incubation of these
colonic nociceptive endings with icilin subsequently
reduced the magnitude of response elicited by the TRPV1
agonist capsaicin, whilst preventing the mechanical hyper-
sensitivity evoked by the TRPA1 agonist mustard oil
[58]. Therefore, this study identified three novel mech-
anisms by which TRPM8 activation can reduce colonic
pain. As menthol also inhibits TRPA1 [15], which plays a
key role in colonic pain [14], there are a variety of
mechanisms responsible for the visceral anti-nociceptive
properties of peppermint oil in animal models and human
studies.
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Overall, peppermint oil appears to be well tolerated and
effective in relieving symptoms in IBS patients. It is
readily available making it an appealing cost-efficient
treatment [59]. However, as with many herbs metabolites
[60] and bio-activation [61] must be considered, whilst
enteric-coated capsules may be preferential as they con-
trol the release of peppermint oil to the bowel reducing
the risk of heartburn. Because of its muscle relaxant
effects peppermint oil may induce gastro-oesophageal
reflux due to relaxation of the lower oesophageal sphinc-
ter [55]. Some studies have also shown that peppermint
oil provides therapeutic benefit in combination with car-
away oil, providing global symptom improvement for
patients with FD [62,63], whilst in an animal model of
IBS oral treatment with peppermint oil and caraway oil
reduces post-inflammatory colonic hyperalgesia synergis-
tically [64].
Artichoke leaf extract
Cynara scolymus has traditionally been used to treat dys-
peptic symptoms and has been shown to increase bile flow
and have antioxidant effects. In a double-blind, random-
ised controlled trial of 247 patients with FD those orally
administered a commercial artichoke leaf extract prep-
aration showed a significantly greater improvement of
dyspeptic symptoms and global quality-of-life scores
during a 6-week treatment period when compared with
placebo [65]. Although potentially promising for FD
treatment this is a single study and the precise mechan-
ism of action needs to be elucidated. In a more recent
animal study two specific artichoke extracts were tested
on rat ileum contractility. One extract, a hydrophilic
component termed 36_U evoked ileal contraction, whilst
a lipophilic extract termed 36_EB relaxed rat ileum [66].
Curcumin
Curcumin is a constituent of the spice turmeric (Curcuma
longa), one of the principal ingredients found in curry
powder. It has multiple identified biological targets and
cellular effects and in cell line studies has numerous anti-
inflammatory, anti-oxidant and anti-cancer properties
(see [67] for detailed review). Potentially the most
notable for GI disease are curcumin’s ability to reduce
the pro-inflammatory cytokines TNF-a, IL-1b, IL-6, IL-
8 [67] and as such has been of interest as an IBD
treatment. In animal models curcumin attenuates colitis
in a variety of inflammatory models [67] and in one
human study significantly reduced clinical relapse in
patients with quiescent IBD [68]. Curcumin’s therapeutic
value in IBS remains unclear with contrasting reports of
efficacious outcomes in human studies [69,70]. As with
many other natural compounds randomised controlled
clinical studies with large patient cohorts are needed
to fully determine clinical efficacy. Most recently curcu-
min has been shown to block capsaicin-induced TRPV1
activation [20] and therefore may be useful in FD where
patients are hypersensitive to capsaicin challenge [71,72]
Current Opinion in Pharmacology 2011, 11:604–611
608 Gastrointestinal

and a TRPV1 G315C polymorphism increases the Table 2

susceptibility of developing FD [73]. List of the individual components contained within combined
herbal preparations used in gastrointestinal therapy.
Chinese herbs Combined herbal Individual components
Traditional Chinese Medicine is probably the most preparation
widely known and practised of all the natural alternate Iberogast1 bitter candytuft (Iberis amara)
therapies. Numerous formulations have been documen- greater celandine herb
ted for treating GI symptoms. The first mainstream angelica root
clinical study utilised a capsule containing 20 individual lemon balm leaves
peppermint leaves
Chinese herbs (for details see Table 2), which when taken
caraway fruit
(5 capsules, 3 times a day) had significant global im- liquorice root
provement and improved IBS symptom scores [74]. A chamomile flower
recent meta-analysis reviewed the effectiveness of milk thistle fruit
another Chinese herbal medicine Tong-Xie-Yao-Fang Tong-Xie-Yao-Fang rhizoma atractylodis macrocephalae
(TXYF; a combination of 4 herbs, Table 2) in 12 clinical radix paeoniae alba
studies. It concluded although there was some evidence pericarpium citri reticulatae
radix saposhnikoviae
to indicate the potential usefulness of TXYF for IBS
patients, results were limited by the poor quality and Tong-xie-ning rhizoma atractylodis macrocephalae
heterogeneity of these studies and further carefully radix paeoniae alba
pericarpium citri reticulatae viride
designed, randomised double-blinded placebo-controlled bulbus allii macrostemoni
studies were needed to determine TXYF effectiveness
Padma1 Lax Aloes extractum siccum normatum
for IBS [75]. A more recent randomised, double-blind Kaolinum ponderosum
placebo-controlled trial of 60 diarrhea-predominant IBS Calumbae radix
patients determined the effectiveness of another very Condurango cortex
similar preparation Tong-xie-ning (TXNG; a combi- Helenii rhizome
nation of 4 herbs Table 2) in symptom relief. Oral Gentianae radix
Myrobalani fructus
administration of 5.0 g of TXNG 3 times daily for 3 Natrii hydrogenocarbonas
weeks significantly reduced the frequency and duration Natrii sulfas
of pain and reduced stool frequency compared with Piperis longi fructus
placebo [76]. In contrast, another randomised placebo- Frangulae cortex
Rhamni purshianae cortex
controlled trial of 119 diarrhea-predominant-IBS patients
Rhei radix
found that an 11 Chinese herb formulation did not lead to Strychni semen
global symptom improvement after 8 or 16 weeks of Zingiberis rhizome
treatment [77]. Rikkunnshi-to Atractylodes Lancea Rhizome
Ginseng
Tibetan herbs Pinellia Tuber
Padma1 Lax is a Tibetan herbal formula comprising 15 dry Poria Sclerotium
Jujube
extracts (Table 2), which has been manufactured and used
Citrus Unshiu Peel
in Europe for several decades. In a randomised, double- Glycyrrhiza
blind placebo-controlled pilot study of 61 constipation- Ginger
predominant-IBS patients significant improvements were Dai-kenchu-to Ginseng
demonstrated after 3 months in the Padma1 Lax group Zanthoxylum Fruit
compared to placebo in constipation, severity of abdominal Dried Ginger
pain and its effect on daily activities, incomplete evacua- Hangeshasin-to Pinellia Tuber
tion, abdominal distension and flatulence [78], but further Scutellaria Root
studies are needed. In a recent animal study Padma1 Lax Processed Ginger
Glycyrrhiza
altered the contractile properties of smooth muscle strips of
Jujube
rat proximal colon via a cholinergic mechanism. However, Ginseng
Padma1 Lax did not alter small bowel, distal colon or rectal Coptis Rhizome
contractility and did not affect visceral sensitivity as the Combined Chinese Codonopsis pilosulae, radix
visceromotor response to colorectal distension was unal- herbal treatment Agastaches seu pogostemi, herba
tered in healthy rats [79]. (from [74]) Ledebouriellae sesloidis, radix
Coicis lachryma-jobi, semen
Bupleurum chinense
Japanese herbs
Artemesiae capillaris, herba
Numerous herbal medicines are prescribed in Japan for a Atractylodis macrocephalae, rhizoma
variety of GI complaints (see [80] for detailed review). Magnoliae officinalis, cortex
One such preparation Rikkunnshi-to is prepared from Citri reticulatae, pericarpium

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 Use of natural products in gastrointestinal therapies Brierley and Kelber 609
Table 2 (Continued )
Combined herbal Individual components
preparation
Zingiberis offinicinalis, rhizoma
Fraxini, cortex
Poriae cocos, sclerotium (Hoelen)
Angelicae dahuricae, radix
Plantaginis, semen
Phellodendri, cortex
Glycyrrhizae uralensis, radix
Paeoniae lactiflorae, radix
Saussureae seu vladimirae, radix
Coptidis, rhizoma
Schisandrae, fructus
8 crude herbs (Table 2) and is reported to be beneficial for
nausea and vomiting. Dai-kenchu-to prepared from 3
crude herbs (Table 2) is beneficial for constipation, as
it accelerates intestinal motility [80], whilst Hangeshasin-
to prepared from 7 herbs (Table 2) is used as an anti-
diarrhoeal [80]. However, randomised controlled clinical
studies with large patient cohorts are needed to fully
determine clinical efficacy.
Garcinia buchananii
The bark extract from Garcinia buchananii tree is a
traditional African remedy for diarrhea, dysentery,
abdominal discomfort and pain. In a recent animal study
the aqueous bark extract was shown to inhibit pellet
propulsion in the guinea-pig colon in a concentration-
dependent manner and reversibly reduced the amplitude
of evoked fast excitatory post-synaptic potentials in
myenteric neurons via non-opiate, non-adrenergic, non-
GABAergic mechanisms [81]. However, further studies
are required to characterise the bioactive components and
elucidate the mechanisms of action, whilst clinical studies
are required to determine efficacy and safety.
Conclusions
Natural herbal preparations offer considerable potential
in the alternate and mainstream treatment of functional
gastrointestinal disorders. In general, more stringent
clinical studies are needed, in addition to isolating and
identifying the bioactive components, the receptors/
channels they act on and the overall mechanism of action
in symptom relief. In the case of Iberogast1 and pep-
permint oil an increasing body of literature now exists
to support their use in FD and/or IBS, although their
full mechanisms of action need to be determined. Per-
haps the overriding lesson for mainstream medicine is the
clinical efficacy of these multi-component preparations,
suggesting multi-target therapy may be prudent for multi-
factorial disorders.
Acknowledgements
SMB is supported by a NHMRC Australian Biomedical Fellowship and by
NHMRC Australia Project grants (1008100 and 626960).
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References and recommended reading
Papers of particular interest, published within the period of review,
have been highlighted as:
 of special interest
 of outstanding interest
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Bingham et al. (2010). Excellent review illustrating how such a seemingly
simple snail has yielded a highly effective clinical drug.
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