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© 2015 Hellenic Society of Gastroenterology www.annalsgastro.gr
Annals of Gastroenterology (2015) 28, 210-220
Herbal and plant therapy in patients with inammatory
Aikaterini Triantafyllidia, Theodoros Xanthosa, Apostolos Papaloisb, John K. Triantallidisc
University of Athens Medical School; ELPEN Pharma; Iaso General Hospital, Athens, Greece
Abstract e use of herbal therapy in inammatory bowel disease (IBD) is increasing worldwide. e aim
of this study was to review the literature on the ecacy of herbal therapy in IBD patients. Studies
on herbal therapy for IBD published in Medline and Embase were reviewed, and response to
treatment and remission rates were recorded. Although the number of the relevant clinical studies
is relatively small, it can be assumed that the ecacy of herbal therapies in IBD is promising. e
most important clinical trials conducted so far refer to the use of mastic gum, tormentil extracts,
wormwood herb, aloe vera, triticum aestivum, germinated barley foodstu, and boswellia serrata.
In ulcerative colitis, aloe vera gel, triticum aestivum, andrographis paniculata extract and topical
Xilei-san were superior to placebo in inducing remission or clinical response, and curcumin was
superior to placebo in maintaining remission; boswellia serrata gum resin and plantago ovata seeds
were as eective as mesalazine, whereas oenothera biennis had similar relapse rates as ω-3 fatty
acids in the treatment of ulcerative colitis. In Crohn’s disease, mastic gum, Artemisia absinthium,
and Tripterygium wilfordii were superior to placebo in inducing remission and preventing clinical
postoperative recurrence, respectively. Herbal therapies exert their therapeutic benet by dierent
mechanisms including immune regulation, antioxidant activity, inhibition of leukotriene B4 and
nuclear factor-kappa B, and antiplatelet activity. Large, double-blind clinical studies assessing the
most commonly used natural substances should urgently be conducted.
Keywords Alternative medicine, inammatory bowel disease, herbal medicine, Crohn’s disease,
Ann Gastroenterol 2015; 28 (2): 210-220
Crohn’s disease (CD) and ulcerative colitis (UC) are chronic
idiopathic inammatory bowel diseases (IBD) involving
the large bowel (UC) or the small and large bowel (CD),
in which patients require both induction and maintenance
treatment . e conventional treatment of IBD includes the
use of corticosteroids, immunosuppressants, antibiotics, and
biologic agents (anti-tumor necrosis factor (TNF)-α). However,
the use of these drugs is accompanied by a certain number of
side eects, with some of them being quite severe .
e term complementary or alternative medicine (AM)
refers to both diagnostic and therapeutic strategies existing
outside medical centers where conventional medicine is
practiced . Natural products, e.g. products derived from
plants and herbals, are increasingly used by IBD patients.
In this review, the authors evaluate the clinical studies
concerning the natural products used by IBD patients as
an alternative treatment method for either induction or
A computerized search strategy using Medline and
Embase databases up to April 2014 was implemented.
The medical subject headings applied were: “alternative
medicine” or “herbal medicine” and “inflammatory
bowel disease”, or “Crohn’s disease”, or “ulcerative colitis”.
In order to obtain information concerning the physical
characteristics of the herbal investigated in the clinical
studies, relevant reviews published in the international
scientific literature were used. All full-length randomized,
aMSc Cardiopulmonary Resuscitation, University of Athens Medical
School (Aikaterini Triantafyllidi, eodoros Xanthos); bExperimental-
Research Laboratory ELPEN Pharma (Apostolos Papalois);
cInammatory Bowel Disease Unit, “IASO General” Hospital (John K.
Triantallidis), Athens, Greece
Conict of Interest: None
Correspondence to: Prof. John K. Triantallidis,
354 Iera Odos, Haidari, 12461, Greece,
Received 14August 2014; accepted 3November 2014
Herbal therapy of IBD 211
Annals of Gastroenterology 28
placebo-controlled or controlled against a conventional
treatment clinical studies were included in the analysis.
Then, studies deemed eligible for inclusion were manually
searched. Studies were divided into those that have assessed
the use of herbal therapy for the induction of remission
and maintenance of remission in UC, and the induction
of remission and prevention from operative recurrence for
CD. Data collection included types of herbal administered,
treatment duration, length of follow up, remission and
response rates, and adverse effects.
From 1993 to April 2014, we identied 27 clinical studies
dealing with herbal therapy in IBD. ere were 17 studies of
herbal therapy in UC and 10 studies in CD, including 1,874
individuals in total (Table1). e mean age of subjects was
43 years. No signicant dierences concerning the number
of male and female patients participating in the trials was
e most important of the available data concerning the
use of herbals and plants in the treatment of IBD patients are
So far a total number of 17 clinical studies related to the
treatment of either active or inactive UC with the use of herbal
products have been published. e total number of patients
included was 1421. ese studies compared the eectiveness
of herbal treatment with either drugs used regularly by
patients with UC or placebo. In a minority of studies, herbal
treatment was tested while the patients were receiving their
regular treatment. e number of patients included in each
study varied between a few dozen to more than 200. In
studies dealing with induction treatment of active disease, the
duration of treatment varied between 4 and 12weeks, while
in studies dealing with maintenance treatment uctuated
between 6 and 12months.
Treatment of active disease
e total number of studies referring to the treatment of
active UC was 11 and the number of patients included was
Aloe vera (Xanthorrhoeaceae)
Aloe vera is a herbal preparation with signicant anti-
inammatory eects. e leaves of the plant contain an
abundance of phytochemical substances including acetylated
mannans, polymannans, anthraquinone C-glycosides,
anthrones, anthraquinones (emodin), and lectins, most of
which are under intense search.
In a double-blind, randomized, placebo-controlled trial, 44
hospital outpatients with mild to moderately active UC were
randomly given oral aloe vera gel or placebo, 100 mL b.i.d. for
4weeks, in a 2:1 ratio. Oral administration of aloe vera produced
a clinical response more oen than placebo; it also reduced the
histological disease activity and appeared to be safe .
is herbal seems to be eective in some proportion of
patients with active UC. Further studies are necessary using
dierent doses in larger number of patients.
Triticum aestivum (Poaceae)
Triticum aestivum, common as bread wheat, is an annual
grass belonging to the Poaceae family. It can be found in the
form of liquid or powder. It contains chlorophyll, aminoacids,
vitamins and various enzymes. e plant can be used as food,
or as a drug with unique therapeutic potentials for which,
however, there is no strong scientic support. It can be found
as a fresh product, tablets, frozen juice, or powder.
In a randomized, double-blind, placebo-controlled study,
23 patients with active distal UC were allocated to receive
either 100 mL of wheat grass juice (Triticum aestivum), or
placebo, daily, for 1month. Ten of 11patients in the active
treatment showed endoscopic improvement in comparison
with 3 of 10 in the placebo group. Treatment was associated
with signicant reduction in the overall disease activity index
and in the severity of rectal bleeding. Apart from nausea, no
other serious side eects were noticed .
Andrographis paniculata (Acanthaceae)
Andrographis paniculata, a plant belonging to the family of
Acanthaceae, grows mainly in India και Sri Lanka, as well as in
South and South-Eastern Asia.
A recent randomized, double-blind, placebo-controlled
study compared the extract of Andrographis paniculata
(HMPL-004) with placebo in 224 adult patients with mild to
moderately active UC. Treatment with HMPL-004 in a dose of
1800mg per day resulted in a statistically signicantly better
clinical response compared to placebo (60% vs. 40%; P=0.018),
although the proportion of remission aer 8 weeks did not
dier in the two groups .
e second study was also a randomized, double-blind,
multicenter study of an 8-week duration with parallel groups.
e study showed that HMPL-004 had similar eectiveness
with mesalazine (response 76% vs. 82%; remission 21% vs.
Table 1 Number of clinical studies performed so far and number of
UC (active disease) 11 1008
UC (maintenance treatment) 6 413
CD (active disease) 6 222
CD (post-operative maintenance treatment) 4 231
Tot al 27 1874
UC, ulcerative colitis; CD, Crohn’s disease
212 A. Triantafyllidi et al
Annals of Gastroenterology 28
16%) in patients with mild to moderate UC. In this study, there
was no dierence in the proportion of endoscopic remission in
the two groups aer 8weeks (28% vs. 24%) .
Boswellia serrata (Burseraceae)
Boswellia (Boswellia serrata) belongs to the family of trees
producing resin that are well-known for their good-smelling
oil. Boswellia trees have a thick trunk that produces juice rich
in carbohydrates, essential oils and acids called “boswellic
acids”. ese acids seem to be the active component of the plant
being responsible for its therapeutic capabilities.
e initial clinical studies suggested that Boswellia serrata
resin could be eective in IBD. In 2002, the European
Medicines Agency categorized Boswellia serrata gum resin
extract in the category of “orphan drugs”. Serrata gum resin
extracts could inuence the immune system in many ways.
Boswellia serrata represses the formation of leukotriene via
inhibition of 5-lipoxygenase with the action of two boswellia
acids, namely 11-keto-β-boswellic acid and acetyl-11-keto-β-
boswellic acid .
In the only available study, 30 patients with UC were
randomized to receive either Boswellia serrata resin (900mg/d
in 3 doses, n=20) or sulfasalazine (3 g/d in 3 doses, n=10)
for 6weeks. Remission of the disease was achieved in 14 of
20patients who received Boswellia gum resin, compared with 4
of 10 who received sulfasalazine . Larger studies are urgently
Jian Pi Ling (JPL)
JPL is considered as one of the current plant treatments in
patients with UC. It consists of 9 components and is available
in the form of tablets containing 0.75 g of dry herbal.
In a relevant study, 153patients with UC were randomized
in 3 groups. GroupI: JPL tablet with Radix Sophorae avescentis
and Flos sophorae decoction; Group II: sulfasalazine and
dexamethasone; GroupIII: placebo and enema decoction as in
groupI. e rate of remission aer 3months in group1 was
signicantly higher (53%) compared with the rate of remission
in the two other groups (28% and 19% respectively) .
However, the low rate of remission achieved in the two control
groups raises questions about the real value of this study’s
Tormentil extracts (Tormentilla erecta-Rosaceae) Potentilla
erecta (Tormentilla erecta, Potentilla tormentilla widely known
as tormentil or septfoil) is a plant belonging to the family of
Tormentil extracts have antioxidative properties and thus,
it might be used as a complementary therapy for chronic
IBD. In a relevant study, 16patients with active UC received
Tormentil extracts in escalating doses of 1200, 1800, 2400 and
3000 mg/d for 3 weeks each. During therapy with 2400mg
Tormentil extracts per day, median clinical activity index and
CRP improved from 8(6 to 10.75) and 8(3 to 17.75) mg/L at
baseline to 4.5(1.75 to 6) and 3 (3 to 6) mg/L, respectively.
During therapy, clinical activity index decreased in all patients,
whereas it increased during the washout period . Tormentil
extracts appeared safe up to 3000mg/d.
Xilei-san is a mixture of herbs of Chinese medicine that
harbors signicant anti-inammatory properties. It seems to
be eective in a number of inammatory conditions including
digestive disorders such as esophagitis.
In an 8-week randomized, double-blind study, the Xilei-
san mixture was compared with dexamethasone enema in
35patients with mild to moderately severe ulcerative proctitis
for 12weeks. A similarly signicant clinical, histological and
endoscopic response compared with the baseline values in the
two groups was achieved .
In another controlled study, 30patients with intractable
ulcerative proctitis were randomized to receive either Xilei-san
or placebo suppositories for 2weeks. e number of patients
who achieved an improvement in the clinical activity index as
well as in the endoscopic and histological index, was higher
in the group of Xilei-san compared with the group of placebo
(P<0.04) . e rate of recurrence aer 6months was lower
in the arm of active treatment.
No signicant side eects were observed in both studies.
Anthocyanin-rich bilberry preparation
Anthocyanins, which can be found in large quantities
in bilberries (Vaccinium myrtillus) were shown to have
antioxidative and anti-inammatoryeects.
In the only available study Biedermann et al  explored
the possible therapeutic potential of bilberries in active UC.
irteen patients with mild to moderate UC were treated with
a daily standardized anthocyanin-rich bilberry preparation for
9weeks. At the end of the 6thweek 63.4% of patients achieved
remission and 90.9% showed a response. Asignicant decrease
in the Mayo score was also detected in all patients. Interestingly,
the fecal calprotectin levels signicantly decreased during
treatment phase although an increase in the calprotectin levels
and disease activity was observed aer cessation of bilberry
intake. No serious adverse events were observed. e results
clearly indicate a therapeutic potential of bilberries in UC.
Fufangkushen colon-coated capsule (FCC)
FCC is a newly developed herbal drug for the treatment
of UC patients with Chinese medicine pattern of damp-heat
accumulating in the interior, consisted of Sophorae avescentis,
Sanguisorba ocinalis L., Indigo naturalis, Bletilla striata and
In order to test the ecacy and safety of FCC in patients
with active UC Gong et al  recently performed a double-
blinded, randomizedclinical trial comparing FCC with Huidi
(HD, mesalazine enteric-coated tablets). In this study 320
active UC patients were assigned to two groups: 240 treated
with FCC plus HD placebo treatment and 80 with HD plus
FCC placebo for 8weeks. At the 8thweek, 72.5% of patients
in FCC group and 65.0% of patients in HD group achieved a
clinical response and 41.5% in FCC group vs. 41.25% in HD
group clinical remission (no signicant dierences). e rate of
mucosal healing at week 8 was also similar in the two groups.
Similar safety proles in the 2 groups were also seen. FCC
seems to be equally eective and safe in the treatment of active
UC compared with mesalazine.
Herbal therapy of IBD 213
Annals of Gastroenterology 28
Table2 shows the results of the eectiveness of herbal and
plant products administration in the response and remission
rate of patients with active UC.
Maintenance treatment of UC
So far, a small number of clinical trials have been published
concerning the role of plant products in the maintenance
treatment of UC patients. ese studies are analyzed
Curcumin is a biologically active phytochemical substance
showing antioxidant, anti-inammatory, anticarcinogenic,
hypocholesterolemic, antibacterial, wound-healing,
antispasmodic, anticoagulant, antitumor and hepatoprotective
activities. Curcumin inhibits many cytokine pathways
including interleukin (IL)-6, concurrently having a favorable
safety prole. Its anti-inammatory and antioxidant eect has
been shown in numerous animal models.
Table 2 Studies on herbal and plant product treatment of patients with active ulcerative colitis
CAM No of
rate in the active
in the control
HMPL-004 224 Placebo 8 weeks 45 & 60
34 & 38
HMPL-004 at a dose of
1,800 mg/d achieved
clinical response better
13 No comparative
9 weeks 63.4% remission,
e results indicate a
therapeutic potential of
bilberries in UC
Xilei-san enema 35 Dexamethasone
8 weeks - - Xilei-san enemas
are comparable to
An alternative drug in the
treatment of active UP
2 weeks Higher number
of patients in
remission vs placebo
Signicant clinical and
endoscopic ecacy of
Xilei San in patients with
intractable U proctitis
tablets 80 with HD
plus FCC placebo
8 weeks 72.5% of patients
in FCC group
65.0% of patients
in HD group
achieved a clinical
Compared with HD, FCC
is similarly eective and
safe in the treatment of
Tan g etal,
HMPL-004 120 Mesalazine 8 weeks 21 & 76 respectively 16 & 82
Ecacious alternative to
mesalazine in active UC
in escalating doses
of 1200, 1800, 2400
and 3000 mg/d
16 - 3 weeks During therapywith
2400 mg TE/d, CAI
and CRP improved
and CAI decreased
in all patients
- TE appeared safe up to
Aloe vera 44 Placebo 4 weeks 30 7 Oral aloe vera produced
a clinical response more
oen than placebo and
reduced the histological
Triticum aestivum 23 Placebo 4 weeks 91 42 Eective and safe as a single
or adjuvant treatment of
active distal UC
Boswellia serrata 30 Sulfasalazine 6 weeks 70 40 Boswellia serrata gum resin
could be eective in the
treatment of UC
Jian Pi Ling (JPL)
153 Sulfasalazine (S),
90 days 53 28 (S)
JPL seems to be the best
FCC, fufangkushen colon-coated capsule; JPL, Jian Pi Ling tablet; UC, ulcerative colitis; CRP, C-reactive protein; CDAI, Crohn’s disease activity index
214 A. Triantafyllidi et al
Annals of Gastroenterology 28
Hanai et al  evaluated the usefulness of curcumin in
89 patients with quiescent UC. Forty-ve patients received
1 g curcumin b.i.d. along with sulfasalazine or mesalamine,
and 44 received placebo plus sulfasalazine or mesalamine for
6months. Curcumin signicantly improved both the clinical
activity index and the endoscopic index. Recurrence rates
were signicantly lower in the curcumin group compared with
placebo. Curcumin seems to be promising and safe medication
for maintaining remission in patients with quiescent UC.
Plantago ovata (Plantaginaceae)
Plantago ovata is a small plant with characteristic owers.
e juice derived from the plant leaves, has been used
in the treatment of peptic ulcer and pain accompanying
inammatory conditions. e plant has anti-inammatory
and anti-oxidative properties. It inhibits the protein kinase
C, it down-regulates the expression of intercellular adhesion
molecule-1 and inhibits the inammation produced from
5-hydroxy-6,8,11,14-eicosatetraenoic acid and leukotriene B4.
e enzymatic dissolution of the seeds of Plantago ovata results
in the production of short chain fatty acids that have favorable
eects in patients with patients with UC.
In an open clinical study, 105patients with UC in remission
were randomized to receive either Plantago ovata seeds (10g
b.i.d.), mesalazine (500 mg t.i.d.), and Plantago ovata seeds
with mesalazine in the same doses. e rate of recurrence aer
6months did not dier in the three groups (40% vs. 35% vs.
30%) . ere were few side eects mainly constipation and
Oenothera biennis belongs to the group of Oenothera
which can be found in North America and other tropical and
subtropical countries. e evening primrose oil is the main
product of the plant. e main constituent of Oenothera biennis
seeds is the γ-linolenic acid.
e plant has been used as maintenance treatment
in patients with UC with moderate results. In a placebo-
controlled study, 43 patients with UC were randomized to
receive MaxEPA (n=16), super evening primrose oil (n=19),
or olive oil as placebo (n=8) for 6months plus their regular
maintenance treatment with 5-aminosalicylates (5-ASA).
Treatment with super evening primrose oil increased the
concentrations of dihomogamma-linolenic acid (DGLA) of
red cell membrane (P<0.05) and the stool form during the
rst 6 months, compared to MaxEPA and placebo and this
dierence was continued 3months aer cessation of treatment
(P<0.05). Evening primrose oil could oer some benet in
patients with UC .
Germinated barley foodstu (GBF)
GBF represents the nal product of dryness and fermentation
of barley. It is based on recipes of traditional Chinese medicine
having many benecial physiological eects. GBF, which
mainly consists of dietary ber and glutamine-rich protein, is
essentially a prebiotic that can reduce the clinical activity of
UC over long-term as well as short-term administration .
In a relevant study, 59patients with UC in remission were
divided into two groups, control group (n=37) who received
conventional treatment for 12months and GBF group (n=22)
who received conventionaltreatmentplus 20 g of GBF daily.
Signicantly better activity index values were seen in the GBF
group at 3, 6, and 12months compared with control group.
e cumulative recurrence rate in the GBF group with steroid
tapering treatment was signicantly lower compared with the
value in the control group. No side eects related to GBF were
It seems that GBF is an eective and safe herbal in the
maintenancetreatment of UC having also the abilityto taper
Extract of myrrh, dry extract of chamomile owers and coee
It is well known that theherbal mixture of myrrh, dry
extract of chamomile owers and coee charcoal has anti-
inammatoryand antidiarrheal properties.
In the only one so far available randomized, double-
blind, double-dummy study 96 patients with inactive UC
were randomized to receive either the herbal preparation or
mesalazine over a 12-month period. ere was no signicant
dierence in the relapse rate between the two groups (45%
in the mesalazine group and 53% in theherbal group). No
signicant dierences were also shown in relapse-free time,
endoscopy and fecal biomarkers . eherbalpreparation
was well tolerated and showed a good safety prole.
Table3 shows the results of clinical trials with plant products
of patients with UC in remission.
Although the number of studies concerning the role of
natural products in the treatment of active CD is quite small,
their results are interesting. ese studies are subsequently
Chios mustic gum (Pistacia lentiscus-Anacardiaceae)
Pistacia lentiscus var Chia belongs to the family of Pistacia.
is tree is unique in the world because it produces a special
resin (mastic gum). e mastic tree belongs to the family of
Anacardiaceae. Mastic gum is a natural product produced
by trees growing exclusively in the Greek island of Chios. Its
aromatic and therapeutic characteristics are well-known for
centuries. It contains a large number of antioxidant substances,
most of which have been recently identied.
In a relevant study, the eectiveness of mastic on the clinical
course and plasma inammatory mediators of patients with
active CD was evaluated. Recruited to a 4-week treatment
with mastic caps (6 caps/d, 0.37g/cap) were 10patients and
8 controls. It was found that mastic treatment signicantly
Herbal therapy of IBD 215
Annals of Gastroenterology 28
decreased the CD activity index (CDAI) and the plasma levels
of IL-6 and CRP .
In a subsequent study, the same group of investigators
noticed that treating CD patients with mastic resulted in the
reduction of TNF-α secretion. Migration inhibitory factor
release was also signicantly increased, meaning that random
migration and chemotaxis of monocytes/macrophages were
inhibited. It seems that mastic acts as an immunomodulator
on peripheral blood mononuclear cells, acting as a TNF-α
inhibitor and a migration inhibitory factor stimulator .
We strongly suggest that larger, double-blind, placebo-
controlled studies are required in order to further clarify the
role of this signicant natural product in the treatment of
patients with active CD.
Wormwood herb (Artemisia absinthium-Asteraceae)
Absinth wormwood is a herbaceous perennial plant with
a distinctive smell of sage. It has traditionally been used to
treat various digestive disorders. It is traditionally made by a
distillation of neutral alcohol, various herbs, spices and water.
e European Union permits a maximum thujone level of
35mg/kg in alcoholic beverages where Artemisia species is a
listed ingredient, and 10mg/kg in other alcoholic beverages.
So far, two studies have been published concerning the
possible therapeutic results of this herbal in patients with
active CD. In the rst one, 40patients with CD receiving 40mg
of prednisone daily for at least 3weeks were administered a
herbal blend containing wormwood herb (3x500mg/day) or
placebo for 10weeks. Aer 8weeks, there was almost complete
clinical remission in 65% patients as compared to none in the
placebo group. is remission persisted until the end of the
observation period. It was also noticed that wormwood had a
steroid sparing eect and a positive eect on the quality of life
of patients .
In the second study, 20patients with active CD received dry
powder of wormwood or placebo while being on their previous
regular treatment. Aer 6weeks, 8 of 10 (80%) of patients
receiving wormwood and 2 of 10 (20%) receiving placebo
achieved remission. Clinical response was noticed in 6 of 10
of the group of wormwood compared to none of the group of
placebo . e available data so far concerning this plant
seem to be promising.
Cannabis (Cannabis sativa L.-Cannabaceae)
Cannabis sativa is an annual herbaceous plant in
the Cannabis genus, a species of the Cannabaceae family.
Although the main psychoactive constituent
ofCannabisistetrahydrocannabinol, the plant contains almost
60 cannabinoids. Dierences in the chemical composition
of Cannabis varieties may produce dierent eects in
Table 3 Clinical trials with plant products in patients with ulcerative colitis in remission
CAM No of patients Comparisons Treatment
active drug (%)
myrrh, dry extract
owers and coee
96 Mesalazine 12 months 25/47 (53) 22/49 (45)
Ecacy non-inferior to
Curcumin 89 Placebo 6 months 95 79 Promising and safe for
in quiescent UC
(GBF) 20 g of
for 12 months
12 months Signicantly better
CAI values in the
GBF group at 3, 6,
and 12 months
with the values
in the control
GBF appeared to be
eective and safe as a
to taper steroids and
prolong remission in UC
21 No placebo
6 months Signicant decrease
in clinical activity
with control group
No placebo arm GBFmay have a place in
105 Mesalazine 12 months 60 65 Similarly eective to
mesalazine. Side eects:
etal, 1993 Oenothera biennis 43
primrose oil &
6 months – –
Evening primrose oil
could oer some benet
in patients with UC
CAM, complementary or alternative medicine; CD, Crohn’s disease; UC, ulcerative colitis; GBF, germinated barley foodstuff
216 A. Triantafyllidi et al
Annals of Gastroenterology 28
humans. e marijuana plant cannabis is known to improve
inammatory processes, while experimental evidence suggests
that the endogenous cannabinoid system inhibits colonic
inammation, leading to the conclusion that cannabis may
have a therapeutic role in IBD.
In a retrospective observational study, disease activity, use
of medication, need for surgery and hospitalization rate before
and aer cannabis use in 30patients (26males) with CD was
investigated. Of the 30 patients, 21 signicantly improved
aer treatment while the need for other medication was
signicantly reduced. Fieen of the patients had 19 surgeries
during an average period of 9years before cannabis use, but
only 2 required surgeries during an average period of 3years of
cannabis use . In another study, a comparable proportion
of UC and CD patients reported lifetime or current cannabis
During the forthcoming years, the plant might be widely
used in the treatment of IBD patients. Changes in the relevant
legislation, as well as the use of the plant aer the patients’
informed consent, would play a signicant role in the adoption
of this kind of treatment. It is, however, necessary to accurately
conrm the safety and eectiveness of the plant by performing
large clinical studies.
Boswellia serrata extract
Pilot clinical studies support the potential of Boswellia
serrata gum resin extract for the treatment of IBD. Extracts from
the gum resin of Boswellia serrata aect the immune system
in dierent ways. It could suppress leukotriene formation via
inhibition of 5-lipoxygenase by two boswellic acids, 11-keto-β-
boswellic acid and acetyl-11-keto-β-boswellic acid.
In a randomized double-blind study, 102 patients with
active CD randomized to receive Boswellia serrata extract
(H15) or mesalazine. e mean reduction in the CDAI was 90
for H15 and 53 for mesalazine .
Tripterygium wilfordii Hook F
Τhe traditional Chinese drug Tripterygium wilfordii Hook F
(TWHF), a diterpene triepoxide, represents the main constituent
of an extract obtained from Tripterygium wilfordii. Triptolide
has multiple pharmacological properties (anti-inammatory,
immune modulating, antiproliferative and antiapoptotic).
In a study exploring the potential benet of Tripterygium
wilfordii, 20patients with active CD received tablets containing
T2 for 12weeks. CDAI was signicantly reduced during the
rst 8weeks, while endoscopic improvement was noticed aer
12weeks. e inammatory indices including CRP were also
Table4 shows the results of the clinical studies regarding the
role of plant therapy of active CD.
CD: maintenance treatment
Again a small number of studies have investigated the role
of plant treatment in the prevention of recurrences in patients
In a double-blind, placebo controlled study investigating the
ecacy of Boswelan in maintaining remission in CD, 82patients
were randomized to either Boswelan (n=42, 3×2 capsules/day;
400mg each) or placebo (n=40). No dierences in the two
groups concerning the remission rates were noticed. Regarding
safety, no disadvantages of taking the drug compared to placebo
were observed . is trial conrmed the good tolerability of
Boswelan, although there were no signicant dierences versus
placebo in maintenance of remission.
Two placebo controlled studies and one prospective, single-
blind study, investigated the role of Tripterygium wilfordii in
the prevention of postsurgical relapses in patients with CD.
In the rst one 45patients with CD were randomized to
receive either Tripterygium wilfordii or mesalazine. No relapse
Table 4 Clinical studies of plant treatment of patients with active Crohn’s disease
Author/year CAM Number
Comparison Duration Remission with CAM
control agent (%)
102 Mesalazine - 36% 31% Better results compared
Kaliora et al,
Mastic gum 10 Healthy
4 weeks Signicant reduction of
CDAI and of plasma pro-
Not applied Eective and safe
Ren et al,
20 Placebo 12 weeks – – Eective for the
treatment of mild or
moderately active CD
Omer et al,
40 Placebo 10 weeks 65% 0% e available data seem
to be promising
Krebs et al,
20 Placebo 6 weeks 80% 20% Promising results
Naali et al,
2011 Cannabis 30 No 3 months
to 9years 70% - Positive eect on
CDAI, Crohn’s disease activity index; CAM, complementary or alternative medicine; CD, Crohn’s disease
Herbal therapy of IBD 217
Annals of Gastroenterology 28
was noticed three months aer operation. Again in 6 and
12 months aer the operation the clinical relapse rate did
not dier in the two groups (18% vs. 22% and 32% vs. 39%,
respectively). No signicant dierences were observed in
the rate of endoscopic recurrence aer 12months (46% vs.
In the second study, 39patients with CD were randomized
two weeks aer enterectomy to receive either Tripterygium
wilfordii (n=21) or sulfasalazine (n=18). Clinical recurrence
was noticed in 6% in the Tripterygium w ilfordii group compared
with 25% in the group of sulfasalazine. Again, endoscopic
recurrence was observed in 22% in the group of Tripterygium
wilfordii compared with 56% in the group of sulfasalazine.
It seems that at least numerically, Tripterygium wilfordii is
superior compared with sulfasalazine in the prevention from
postsurgical recurrences of CD .
In the third study postoperative CDpatients in remission
were randomized to receive 1mg/kg Tripterygium wilfordii
polyglycoside daily, orally, or 4 g 5-ASA daily, orally, for
52weeks. Twenty-one patients received Tripterygium wilfordii
polyglycoside and 18 5-ASA . e results showed that
clinical and endoscopic recurrences were less common in the
Tripterygium wilfordii polyglycoside group (n=4) versus the
5-ASA group (n=9).
Taking into account the results of the above mentioned
studies it seems that Tripterygium wilfordii polyglycoside
appears to be an eective, well-tolerated drug superior to oral
5-ASA, for preventing clinical and endoscopic recurrence in
Table5 shows the results of the studies investigating the role
of herbal treatment in the prevention of relapses of CD.
Use of AM by the patients with IBD at least for a short
period of time is quite frequent reaching a proportion of
50% while the use of herbals as treatment of either active or
quiescent disease exceeds the proportion of 58% .
e available clinical studies showed that herbal treatment
produces clinical remission or improvement in patients with
mild or moderate IBD at least similar to that of drugs already
used in the treatment of IBD patients, although a minority
of studies did not noticed benecial eects. For example,
curcumin showed better results compared to placebo in the
maintenance treatment of patients with UC. Other herbals,
such as Aloe vera and Boswellia serrata, were eective in
patients with active UC. In cases of proctitis, the wheat
grass juice showed excellent results, while HMPL-004 was
superior to placebo and equally eective with mesalazine in
the prevention from recurrences in patients with UC. Patients
with UC showed better results compared with patients with
CD, although the number of clinical studies in patients with
CD was quite smaller .
However, there are studies showing no positive results. e
reasons are probably related to the poor design of studies, the
small number of patients included, the variety of substances
tested, the inadequate dose of the herbals, and the improper
analysis and description of the results .
Treatment of patients with IBD either for active disease or
maintenance is quite expensive. is cost could be unsustainable
for most people in many countries. On the other hand, the cost
of herbal therapy is probably similar or even smaller to the cost
of conventional treatment of IBD.
Cellular/molecular/systemic eects of described plant
A lot of clinical and especially experimental work has
suggested that, individual chemical substances derived from
the described plants and herbals may have antibacterial,
antioxidant, antiinammatory, and immunoreguratory
properties. For example curcumin has antioxidant, anti-
inammatory, anticarcinogenic, hypocholesterolemic,
antibacterial, wound-healing, antispasmodic, anticoagulant,
Table 5 Clinical studies of plant treatment of patients with Crohn’s disease in remission
Authors/year CAM No of
Remission on placebo
or active drug (%)
Tao et al,
45 Mesalazine 6 months
Eective and safe
Liao et al,
39 Sulfasalazine – 94% 75% Eective and safe
Holtmeier et al,
Boswellia serrata extract
108 Placebo 52 weeks 60% 55% Good tolerability.
placebo remission is not
Ren et al,
(post-op CD) 39 Mesala zine 52 weeks 79% 53%
Eective, superior to oral
5-ASA, for preventing
clinical and endoscopic
recurrence in post-op CD
CD, Crohn’s disease
218 A. Triantafyllidi et al
Annals of Gastroenterology 28
antitumor and hepatoprotective activities . Boswellia
serrata has signicant immunoregulatory properties.
Boswellic acids (the active moiety of Boswellia) reduces
the levels of TNF-α by suppressing the biosynthesis of
leukotrienes via inhibition of 5-lipoxygenase [37,38]. e
extracts of wormwood (Artemisia absinthium) could reduce
TNF-α and other proinammatory cytokines. Andrographis
paniculata inhibits in vitro the production of TNF-α, IL-1β
and nuclear factor-κB. Moreover, the polysaccharide content
of herbal and plant preparations suggests that they might
also have prebiotic properties. Other herbal preparations
such as GBF have prebiotic characteristics that could increase
luminal butyrate production by modulating the microoral
However, we must bear in mind that the results obtained
from in vitro studies of an herbal preparation are not equally
eective in vivo. is is because many factors including the
amount of the active substance contained in the extract as well
as interactions between individual constituents could interfere
with the results obtained in IBD patients.
A summary of cellular and systemic eects of the described
herbal and plants are shown in Table6.
Safety of herbal treatment
Most of the published trials showed no side eects. In fact,
the number and type of side eects were similar to those of
placebo or mesalazine. is is quite important in patients with
previous operations or patients who experienced signicant
side eects being on conventional treatment.
Curcumin and mastic gum probably represent the safest
herbals. Curcumin is well tolerated without any serious
toxicity and side eects. Several clinical studies have conrmed
its safety in humans with no treatment-related toxicity up
to 8,000 mg/day for 3 months. Only minor gastrointestinal
adverse events, such as nausea and diarrhea, have been
reported . On the other hand, no side eects related to
mastic gum consumption even aer long-term use has been
Again, we must bear in mind that herbal therapy, in general,
could carry risks and produce side eects similar to other
forms of alternative therapy. Liver and renal failure has been
described with some of them, fortunately not with those used
in the treatment of IBD patients.
Toxic eects could also be associated with the inclusion of
prescription medicines in some herbal preparations including
corticosteroids, and glibenclamide . Toxic products such
as mercury, arsenic, and lead, can be found in some plant
However, the most important side eect of the use of
herbal preparations is the abandonment of the drugs used
in the treatment of IBD, a fact that may lead to severe or
complicated IBD. On the other hand, patients with IBD
initially consulting alternative doctors may be erroneously
diagnosed as suering from irritable bowel syndrome or
other disease Finally, it must be stressed that the long-term
safety of herbal treatment including possible mutagenicity
and carcinogenicity has not adequately be explored. We
suggest that future trials could combine a safe herbal product
with conventional drugs thus improving treatment outcome
without increasing toxicity.
A summary of the most important side eects reported so
far are mentioned in Table7.
Table 6 Cellular, molecular and systemic eectsof described plant
and herbal preparations
Herbal and plant Cellular, molecular and systemic eects
Selective inhibition of 5-lipoxygenase
Direct inhibition of intestinal motility
Reduction of chemically induced edema and
inammation in the intestine in rodents
Tormentil extracts Antioxidative properties
Curcumin Decreased activity
Mitogen-activated protein kinase
IL-1, IL-4, IL-5, IL-6, IL-12
Tumor necrosis factor-α
Lipid peroxidase activity
Ιnducible nitric oxide synthase
Toll-like receptor- 4
Binds to thioredoxin reductase and
irreversibly changes its activity
Increases luminal butyrate production by
modulating the microoral distribution
High water holding capacity
Oenothera biennis e mature seeds contain 7-10%γ-linolenic
acid (essential fatty acid)
Plantago ovata Anti-inammatory and anti-oxidative
Inhibits protein kinase C
Down-regulates the expression of
intercellular adhesion molecule-1
Inhibits the inammation produced from
and leukotriene B4
Anthocyanins Antioxidative eects
Xilei San Anti-inammatory eects
Aloe vera In vitro inhibition of prostaglandin E2 and
Triticum aestivum Antioxidant properties
Mastic gum Anti-inammatory
Herbal therapy of IBD 219
Annals of Gastroenterology 28
e available data concerning the administration of extracts
derived from plants and herbals give the gastroenterologist the
excuse to explain to our patients the benets of this therapy,
concurrently providing evidence-based information about their
use . Pharmaceutical companies must aid to the current
knowledge by supporting relevant studies even if their nancial gain
would be much lower compared to other kinds of treatment. Both
international scientic societies and government organizations
should take seriously the locally available opportunities of drug
development by nancially supporting relevant clinical studies. It
is true that the cost of treatment of IBD patients is continuously
raising and herbal treatment might represent a new eective
and cheap treatment method . Doctors must become more
tolerant and open-minded about the benets of AM. Finally, there
is a need for more essential representation of AM in under-and
postgraduate medical education.
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Table 7 Safety of the main herbal and plants used in inammatory bowel disease treatment
Herbal and plant Side eects Safety
Mild or moderate degree of nausea, fatigue, abdominal pain and
distension, anal pain, upper respiratory tract infection, dyspepsia, fever.
Similar in active substance and mesalazine [15.9% vs. 12.5]
Boswellia serrata Boswellia serratais rich in guggalsterones, that increase the thyroid
function, leading to weight loss
Tormentil extracts Mild upper abdominal discomfort
Incidence of side eects: 38%
No discontinuation of the medication was needed
Safe up to 3000 mg/d
Wheat grass juice No serious side eects were reported Excellent
Safe as a single or adjuvant
treatment of active distal UC
Germinated barley foodstu (GBF) No side eects related to GBF were observed Excellent
Oenothera biennis Safety has not been evaluated in pregnant or nursing women Satisfactory
Plantago ovata Hypersensitivity, aer inhaled or ingested psyllium
Temporary gas and/or bloating
Anthocyanins No serious adverse events have been described Satisfactory
Xilei San Well tolerated topically without safety concerns Satisfactory
Jian Pi Pian (Wan) Safely used with few adverse eects Satisfactory
Andrographis Headache, fatigue, rash, bitter/metallic taste, diarrhea, pruritus, and
decreased sex. Anaphylactic reaction in an HIV-positive patient
Triticum aestivumL e grain could cause poisoning in stock, though no toxic substance
has been found
Wheat can absorb toxic concentrations of selenium. However,
“selenium” wheat rarely causes poisoning
Mastic gum No side eects have been reported Excellent
Satisfactory: Side effects not different from an established active drug, Moderate: Larger number of side effects requiring close follow up during treatment,
Excellent:No difference from placebo, UC, ulcerative colitis
220 A. Triantafyllidi et al
Annals of Gastroenterology 28
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