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Effects of Herbal Medicines in Patients with Irritable Bowel Syndrome

Hirotada Akiho

Hirotada Akiho, MD, PhD, Department of Gastroenterology, Kitakyushu Municipal Medical Center, 2-1-1 Bashaku, Kokura-kitaku, Kitakyushu 802-0077, Japan

Correspondence: Hirotada Akiho, MD, PhD, Department of Gastroenterology, Kitakyushu Municipal Medical Center, 2-1-1 Bashaku, Kokura-kitaku, Kitakyushu 802-0077, Japan.
akiho@med.kyushu-u.ac.jp
Telephone: +081-93-541-1831
Fax: +081-93-533-8691
Received: August 17, 2012
Revised: September 5, 2012
Accepted: September 6, 2012
Published online: February 21, 2013

ABSTRACT

Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder associated with alterations in motility, secretion and visceral sensation. Pharmacologic agents used to treat IBS include antispasmodics, 5-hydroxytryptamine-3 receptor (5-HT3) antagonists, 5-hydroxytryptamine-4 (5-HT4) agonists, antibiotics, probiotics, antidepressants and herbal medicines. No single therapy is reliably effective, and an increasing number of patients are taking herbal medicines worldwide. This review describes the effectiveness of herbal medicines in patients with IBS. Of single preparations, peppermint oil has shown the most evidence for efficacy, whereas, of compound preparations, most randomized controlled trials (RCTs) have been performed with TongXieYaoFang (TXYF). Daikenchuto (DKT) appears to be safe and well tolerated, and RCTs of DKT for functional constipation and IBS are now ongoing or being planned. No serious adverse events have been reported, but this may be due to publication bias or the lack of proper monitoring. Although herbal medicines may have therapeutic benefit in patients with IBS, further studies are needed to determine their efficacy and safety.

Key words: Herbal medicine; IBS

© 2013 The Author. Published by ACT Publishing Group Ltd.

Akiho H. Effects of Herbal Medicines in Patients with Irritable Bowel Syndrome. Journal of Gastroenterology and Hepatology Research 2013; 2(2): 387-390 Available from: URL: http://www.ghrnet.org/index./joghr/

INTRODUCTION

Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder associated with alterations in motility, secretion and visceral sensation. Its symptoms include abdominal pain or discomfort associated with changes in bowel habits for which no obvious cause can be found on routine investigations, and its diagnosis is commonly dependent on the symptom based Rome criteria. The pathogenesis of IBS is considered multifactorial and includes psychosocial factors, GI dysmotility, enhanced perception of sensory stimuli, stress, corticotrophin-releasing factor, infection, microbiota, genetics and gut wall immune activation[1].

Several ongoing clinical trials in IBS are testing agents that target visceral hypersensitivity, motility, neurotransmitters, microbiota and immune systems, acting peripherally and/or centrally. Pharmacological therapy of IBS includes antispasmodics, 5-hydroxytryptamine-3 receptor (5-HT3) antagonists, 5-hydroxytryptamine-4 (5-HT4) agonists, antibiotics, probiotics, antidepressants, herbal medicines[2] and melatonin[3]. Herbal medicines have been used to treat GI symptoms for centuries and have provided effective relief of symptoms in patients with IBS.

The multi-herbal medicine daikenchuto (DKT), which originated in ancient China, has been extensively modified/modernized and is now established as a pharmaceutical-grade drug for ethical use in Japan. DKT is widely prescribed for patients with gut dysfunction disorders, such as IBS, postoperative ileus and adhesive bowel obstructions following abdominal surgery[4].

In this, review, herbal medicines are defined as products derived from plants or parts of plants.

The references were collected from randomized controlled trials (RCT) recently published English manuscripts, although studies of artichoke[5,6] and turmeric extract were case control studies.

This review describes the effectiveness of herbal medicines for IBS patients, explores the mechanisms of actions of these agents and highlights the implications of herbal medicines for understanding the management of IBS.

THERAPEUTIC EFFECTS OF HERBAL MEDICINES FOR IBS

Artichoke

Artichoke (Cynara scolymus) is a plant native to southern Europe and northern Africa and is thought to be one of the oldest medicinal plants still in use. A post marketing surveillance study of 279 IBS patients treated for 6 weeks with artichoke leaf extract showed significant reductions in the severity of symptoms[5]. Moreover, a post hoc analysis of 208 IBS patients treated with artichoke leaf extract for 2 months showed a 26.4% decrease in IBS incidence (P<0.001) after treatment[6]. There was a significant shift in self-reported usual bowel pattern, from “alternating constipation/diarrhea” toward “normal”, as well as a 41% decrease in total symptom score[6]. Furthermore, artichokes have been reported to exert a pronounced prebiotic effect on the composition of human fecal microbiota[7].

A hydrophilic artichoke extract 36_U mainly containing luteolin-7-glycoside, luteolin-7-O-glucoside, small amounts of cynarin and luteolin increased contraction of rat ileum. This is mainly mediated by 5-HT3 and 5-HT2 receptors but not 5-HT4 receptors[8].

Fumaria officinalis

Fumaria officinalis is the most common species of the genus Fumaria in Western and Central Europe. One RCT showed that neither Fumaria officinalis nor F. curcuma had any therapeutic advantage over placebo in patients with IBS[9].

Turmeric extract

Turmeric has been traditionally used to manage patients with abdominal pain and bloating. The ability of one or two tablets of a standardized turmeric extract, taken daily for 8 weeks, to improve IBS symptoms and QOL was investigated in 207 patients[10]. Both groups showed significant improvements, between 5% and 36%, in all but one of the IBSQOL scales.

The literature showed that turmeric extract, curcuminoid produced a smooth muscle, relaxation effect on isolated guinea-pig ileum and rat uterus by acetylcholine dependent and independent mechanism[11].

Hypericum perforatum

Hypericum perforatum (St. John’s wort) has been shown effective in the treatment of patients with mild-to-moderate depression[12]. A 12-week RCT found that H. perforatum was a less effective treatment for IBS than placebo[12]. Another study showed, however, that H. perforatum significantly relieved intestinal symptoms, as well as improving psychological conditions and autonomic nervous system reactivity to stress, in patients with IBS[13]. H. perforatum has anti-inflammatory activity[14], but mechanism of GI motility is not certain.

Peppermint oil

Peppermint oil has been used to treat stomach upsets for thousands of years. An RCT assessing the efficacy of enteric-coated peppermint oil capsules (Colpermin) in 110 outpatients with IBS showed that symptom improvements were significantly better after Colpermin than after placebo[15]. Another RCT in 90 IBS outpatients found that the severity of abdominal pain was significantly lower in the Colpermin than in the control group[16]. In a trial involving 57 IBS patients, in whom small intestinal bacterial overgrowth, lactose intolerance and celiac disease had been excluded, 4 weeks of treatment with peppermint oil resulted in greater symptom improvement than in controls[17]. An older RCT showed the opposite results, but that trial involved only 33 patients[18]. The peppermint oil relaxes gastrointestinal smooth muscle by reducing calcium influx[19].

Plantago psyllium

Seeds of Plantago ovata (psyllium) are widely used in the manufacture of bulk laxatives, as well as being added to breakfast cereals to increase dietary fiber and reduce serum cholesterol concentrations. An RCT in patients with IBS showed that the proportion of responders was significantly greater in the psyllium than in the placebo group during the first and second months of treatment[20].

COMPOUND PREPARATIONS

Carmint

Carmint contains total extracts of Melissa officinalis, Mentha spicata, and Coriandrum sativum, which have antispasmodic, carminative, and sedative effects. An RCT in 32 patients with IBS showed that the severity and frequency of abdominal pain/discomfort were significantly lower in the Carmint than in the placebo group at the end of treatment[21]. The pharmaceutical effect of Carmint is similar to that of peppermint oil.

Tong-Xie-Yao-Fang (TXYF)

TongXieYaoFang (TXYF) is composed of four Chinese herbal medicines, Rhizoma atractylodis Macrocephalae, Radix paeoniae alba, Pericarpium citri reticulatae, and Radix saposhnikoviae. A meta-analysis of 12 RCTs, involving 1125 patients with IBS, showed that TXYF was more effective than placebo (RR 1.35, 95% CI 1.21 to 1.50), but these results were limited by the poor quality and heterogeneity of the RCTs analyzed[22]. An RCT evaluating the effectiveness of TXYF in patients with diarrhea-predominant IBS (D-IBS) found that TXYF improved IBS symptoms, by decreasing the number of activated mast cells in the colon[23].

Another RCT evaluated a modified version of traditional TXYF, involving 11 herbal extracts[24]. After a 2-week run-in period, 119 patients were randomized to 8 weeks of treatment with traditional Chinese medicine (TCM) (n=60) or placebo (n=59). The proportions of patients with global symptom improvement were similar in the TCM and placebo groups at 8 (35% vs 44.1%, p=0.38) and 16 (31.7% vs 33.9%, p=0.62) weeks. Moreover, there were no between group differences in individual symptom scores and quality-of-life assessments at any time point. Pan et al[23] mentioned that its mechanism of action might be through the adjustment of mast cells activation to decrease visceral hypersensitivity.

Tong-xie-ning (TXNG)

The efficacy of TXNG was evaluated in an RCT in 60 patients with D-IBS[25]. IBS-related pain, measured using the numeric pain intensity scale, was significantly lower in the TXNG than in the placebo group by the end of therapy. Moreover, 82.7% of TXNG-treated patients reported a reduction in IBS-related pain, compared with 39.3% in the placebo group. Stool frequency at the end of treatment was significantly lower in the TXNG than in the control group, with 86.2% and 42.9% of patients, respectively, showing observable improvements in IBS-related diarrhea[25].

Chinese herbal medicine (CHM)

An RCT in 116 IBS patients was performed to determine whether CHM is of any benefit in the treatment of IBS[26]. Compared with patients in the placebo group, patients in the active treatment groups (standard and individualized CHM) had significant improvements in bowel symptom scores, as rated by patients (P=0.03) and gastroenterologists (P=0.001); and significant global improvement, as rated by patients (P=0.007) and gastroenterologists (P=0.002). Patients reported that treatment significantly reduced the degree that IBS symptoms interfered with activities of daily life. Although CHMs individually tailored to each patient were no more effective than standard CHM, follow-up 14 weeks after completion of treatment showed that only the individualized CHM treatment group maintained improvement. Thus, Chinese herbal formulations appear to offer symptom improvement in some patients with IBS[26].

Padma Lax Tibetan herbal formula

Padma Lax is a complex formula, consisting of 15 herbs and minerals, based on a Tibetan recipe used traditionally to treat constipation and as an aid to digestion. In a 3 month RCT evaluating 80 patients with constipation predominant IBS (IBS-C), with symptom severity evaluated monthly using categorical and numerical rating scales, the Padma Lax group showed significant improvements, compared with placebo, in constipation, severity of abdominal pain and its effect on daily activities, incomplete evacuation, abdominal distention and flatus/flatulence[27]. In a rat model, cholinergic mechanisms appear to be important on the modulation of proximal colon contractility orally and directly applied Padma Lax[28].

STW5 (Iberogast)

An RCT involving 208 patients with IBS evaluated the effectiveness of STW 5 (an extract of 9 plants) and STW-II (an extract of 6 plants)[29]. STW and STW-II were significantly better than placebo in reducing total abdominal pain and IBS symptom scores at 4 weeks[29]. STW 5 may be a secretagogue in the human intestine, with secretion caused by direct epithelial action and through activation of enteric neurons[30]. The prosecretory effect is due to increased epithelial Cl(-) fluxes via a cystic fibrosis transmembrane conductance regulator and Ca-dependent ClCa channels. Thus, STW 5 may be a novel option to treat secretory disorders associated with IBS and constipation[30].

Clinical studies have indicated that the fixed herbal combination product STW 5 (Iberogast) has an efficacy comparable to that of metoclopramide (a 5-HT3 antagonist) and cisapride (a 5-HT4 agonist) in functional gastrointestinal diseases, including functional dyspepsia (FD) and IBS. In vitro data have indicated that 5-HT4 receptors, and, to a lesser degree, 5-HT3, muscarinic M3, and opioid receptors, represent target sites for STW 5 in the treatment of FD and IBS[31].

Daikenchuto (DKT; Figure 1)

DKT, a traditional herbal medicine, is composed of four medicinal herbs, Zanthoxylum fruit, processed ginger, ginseng, and maltose syrup. In Japan, DKT is widely prescribed for patients with GI obstructions, including postoperative ileus and adhesive bowel obstructions[4]. A double-blind, placebo-controlled RCT in healthy human subjects, in which gastrointestinal and colonic transit were measured by scintigraphy, found that DKT had promotility effects, especially in accelerating the emptying half-time of the ascending colon. DKT appears to be safe and well tolerated and is a potential treatment for patients with C-IBS and functional constipation[32]. RCTs evaluating DKT in patients with functional constipation and IBS are now either ongoing or being planned.

In experimental studies, DKT was found to modulate gut motor function by cholinergic and serotonergic mechanisms, and to ameliorate gastrointestinal motility in patients with postoperative ileus[33]. DKT acts by stimulating acetylcholine release from cholinergic nerve terminals, with 5-HT4 receptors involved in this activity[34].

CONCLUSIONS

The use of herbal medicine to treat IBS is increasing throughout the world. Most of the studies described in this review showed that herbal medicines were effective in relieving the symptoms of IBS. The single preparation with the most evidence for efficacy in IBS patients to date is peppermint oil. Limited evidence is available on the efficacy of other herbal formulas. Also the pharmaceutical mechanisms of formulas are not well evaluated yet. No serious adverse events have been reported, but this may be due to publication bias or a lack of proper monitoring. Moreover, the methodological quality of these studies was not always satisfactory. And the mechanisms of action of herbal medicines have been studied, so far cholinergic, 5-HT, Ca, and anti-inflammatory pathways are involved. Although herbal medicines likely have therapeutic benefits in IBS, further studies are required.

REFERENCES

1 Barbara G, De Giorgio R, Stanghellini V, Cremon C, Salvioli B, Corinaldesi R. New pathophysiological mechanisms in irritable bowel syndrome. Aliment Pharmacol Ther 2004; 20 Suppl 2: 1-9

2 American College of Gastroenterology Task Force on Irritable Bowel Syndrome, Brandt LJ, Chey WD, Foxx-Orenstein AE, Schiller LR, Schoenfeld PS, Spiegel BM, Talley NJ, Quigley EM. An evidence-based position statement on the management of irritable bowel syndrome. Am J Gastroenterol 2009; 104 Suppl 1: S1-35

3 Mozaffari S, Rahimi R, Abdollahi M. Implications of melatonin therapy in irritable bowel syndrome: a systematic review. Curr Pharm Des 2010; 16: 3646-3655

4 Kono T, Kanematsu T, Kitajima M. Exodus of Kampo, traditional Japanese medicine, from the complementary and alternative medicines: is it time yet? Surgery 2009; 146: 837–840

5 Walker AF, Middleton RW, Petrowicz O. Artichoke leaf extract reduces symptoms of irritable bowel syndrome in a post-marketing surveillance study. Phytother Res 2001; 15: 58-61

6 Bundy R, Walker AF, Middleton RW, Marakis G, Booth JC. Artichoke leaf extract reduces symptoms of irritable bowel syndrome and improves quality of life in otherwise healthy volunteers suffering from concomitant dyspepsia: a subset analysis. J Altern Complement Med 2004; 10: 667-669

7 Costabile A, Kolida S, Klinder A, Gietl E, Bäuerlein M, Frohberg C, Landschütze V, Gibson GR. A double-blind, placebo-controlled, cross-over study to establish the bifidogenic effect of a very-long-chain inulin extracted from globe artichoke (Cynara scolymus) in healthy human subjects. Br J Nutr 2010; 104: 1007-1017

8 Verspohl EJ, Ploch M, Windeck T, Klaes M, Schmidt T, Bauer K. Effect of two artichoke extracts (36_U and 36_EB) on rat ileum (with respect to bowel syndrome) and the peristaltic threshold. Phytomedicine 2008; 15: 1002-1009

9 Brinkhaus B, Hentschel C, Von Keudell C, Schindler G, Lindner M, Stützer H, Kohnen R, Willich SN, Lehmacher W, Hahn EG. Herbal medicine with curcuma and fumitory in the treatment of irritable bowel syndrome: a randomized, placebo-controlled, double-blind clinical trial. Scand J Gastroenterol 2005; 40: 936-943

10 Bundy R, Walker AF, Middleton RW, Booth J. Turmeric extract may improve irritable bowel syndrome symptomology in otherwise healthy adults: a pilot study. J Altern Complement Med 2004; 10: 1015-1018

11 Itthipanichpong C, Ruangrungsi N, Kemsri W, Sawasdipanich A. Antispasmodic effects of curcuminoids on isolated guinea-pig ileum and rat uterus. J Med Assoc Thai 2003; 86 Suppl 2: S299-309

12 Saito YA, Rey E, Almazar-Elder AE, Harmsen WS, Zinsmeister AR, Locke GR, Talley NJ. A randomized, double-blind, placebo-controlled trial of St John's wort for treating irritable bowel syndrome. Am J Gastroenterol 2010; 105: 170-177

13 Wan H, Chen Y. Effects of antidepressive treatment of Saint John's wort extract related to autonomic nervous function in women with irritable bowel syndrome. Int J Psychiatry Med 2010; 40: 45-56

14 Hu ZP, Yang XX, Chan SY, Xu AL, Duan W, Zhu YZ, Sheu FS, Boelsterli UA, Chan E, Zhang Q, Wang JC, Ee PL, Koh HL, Huang M, Zhou SF.St. John's wort attenuates irinotecan-induced diarrhea via down-regulation of intestinal pro-inflammatory cytokines and inhibition of intestinal epithelial apoptosis. Toxicol Appl Pharmacol 2006; 216: 225-237

15 Liu JH, Chen GH, Yeh HZ, Huang CK, Poon SK. Enteric-coated peppermint-oil capsules in the treatment of irritable bowel syndrome: a prospective, randomized trial. J Gastroenterol 1997; 32: 765-768

16 Merat S, Khalili S, Mostajabi P, Ghorbani A, Ansari R, Malekzadeh R. The effect of enteric-coated, delayed-release peppermint-oil on irritable bowel syndrome. Dig Dis Sci 2010; 55: 1385-1390

17 Cappello G, Spezzaferro M, Grossi L, Manzoli L, Marzio L. Peppermint oil (Mintoil) in the treatment of irritable bowel syndrome: a prospective double blind placebo-controlled randomized trial. Dig Liver Dis 2007; 39: 530-536

18 Nash P, Gould SR, Bernardo DE. Peppermint oil does not relieve the pain of irritable bowel syndrome. Br J Clin Pract 1986; 40: 292-293

19 Hills JM, Aaronson PI. The mechanism of action of peppermint oil on gastrointestinal smooth muscle. An analysis using patch clamp electrophysiology and isolated tissue pharmacology in rabbit and guinea pig. Gastroenterology 1991; 101: 55-65

20 Bijkerk CJ, de Wit NJ, Muris JWM, Whorwell PJ, Knottnerus JA, Hoes AW. Soluble or insoluble fibre in irritable bowel syndrome in primary care? Randomised placebo controlled trial. BMJ 2009; 339: b3154

21 Vejdani R, Shalmani HR, Mir-Fattahi M, Sajed-Nia F, Abdollahi M, Zali MR, Mohammad Alizadeh AH, Bahari A, Amin G. The efficacy of an herbal medicine, Carmint, on the relief of abdominal pain and bloating in patients with irritable bowel syndrome: a pilot study. Dig Dis Sci 2006; 51: 1501-1507

22 Bian Z, Wu T, Liu L, Miao J, Wong H, Song L, Sung JJY. Effectiveness of the Chinese herbal formula TongXieYaoFang for irritable bowel syndrome: a systematic review. J Altern Complement Med 2006; 12: 401-407

23 Pan F, Zhang T, Zhang YH, Xu JJ, Chen FM. Effect of Tongxie Yaofang Granule in treating diarrhea-predominate irritable bowel syndrome. Chin J Integr Med 2009; 15: 216-219

24 Leung WK, Wu JC, Liang SM, Chan LS, Chan FK, Xie H, Fung SS, Hui AJ, Wong VW, Che CT, Sung JJ. Treatment of diarrhea-predominant irritable bowel syndrome with traditional Chinese herbal medicine: a randomized placebo-controlled trial. Am J Gastroenterol 2006; 101: 1574-1580

25 Wang G, Li TQ, Wang L, Xia Q, Chang J, Zhang Y, Wan MH, Guo J, Cheng Y, Huang X, Zhang RM. Tong-xie-ning, a Chinese herbal formula, in treatment of diarrhea-predominant irritable bowel syndrome: a prospective, randomized, double-blind, placebo-controlled trial. Chin Med J 2006; 119: 2114-2119

26 Bensoussan A, Talley NJ, Hing M, Menzies R, Guo A, Ngu M. Treatment of irritable bowel syndrome with Chinese herbal medicine: a randomized controlled trial. JAMA 1998; 280: 1585-1589

27 Sallon S, Ben-Arye E, Davidson R, Shapiro H, Ginsberg G, Ligumsky M. A novel treatment for constipation-predominant irritable bowel syndrome using Padma Lax, a Tibetan herbal formula. Digestion 2002; 65: 161-171

28 Gschossmann JM, Krayer M, Flogerzi B, Balsiger BM. Effects of the Tibetan herbal formula Padma Lax on visceral nociception and contractility of longitudinal smooth muscle in a rat model. Neurogastroenterol Motil 2010; 22: 1036-1041

29 Madisch A, Holtmann G, Plein K, Hotz J. Treatment of irritable bowel syndrome with herbal preparations: results of a double-blind, randomized, placebo-controlled, multi-centre trial. Aliment Pharmacol Ther 2004; 19: 271-279

30 Krueger D, Gruber L, Buhner S, Zeller F, Langer R, Seidl S, Michel K, Schemann M. The multi-herbal drug STW 5 (Iberogast) has prosecretory action in the human intestine. Neurogastroenterol Motil 2009; 21: 1203-e110

31 Simmen U, Kelber O, Okpanyi SN, Jaeggi R, Bueter B, Weiser D. Binding of STW 5 (Iberogast) and its components to intestinal 5-HT, muscarinic M3, and opioid receptors. Phytomedicine 2006; 13 Suppl 5: 51-55

32 Manabe N, Camilleri M, Rao A, Wong BS, Burton D, Busciglio I, Zinsmeister AR, Haruma K. Effect of daikenchuto (TU-100) on gastrointestinal and colonic transit in humans. Am J Physiol Gastrointest Liver Physiol 2010; 298: G970–G975

33 Tokita Y, Yuzurihara M, Sakaguchi M, Satoh K, Kase Y. The pharmacological effects of Daikenchuto, a traditional herbal medicine, on delayed gastrointestinal transit in rat postoperative ileus. J Pharmacol Sci 2007; 104: 303–310

34 Satoh K, Hayakawa T, Kase Y, Ishige A, Sasaki H, Nishikawa S, Kurosawa S, Yakabi K, Nakamura T. Mechanisms for contractile effect of Dai-kenchu-to in isolated guinea pig ileum. Dig Dis Sci 2001; 46: 250–256

Peer reviewers: Masahiro Yamamoto, PhD, Tsumura Laboratories, Tsumura & Co. Yoshiwara 3586, Ami, IBARAKI 300-1192, Japan; Jean-Eric GHIA, Msc, PhD, HDR, Assistant Professor, Department of Immunology, Internal Medicine Section of Gastroenterology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.

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