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Research Article
 

Management of Human Ulcerative Colitis by SaturexTM: A Randomized Controlled Trial



Mansoor Rastegarpanah, Naghmeh Omidzohour, Homayoon Vahedi, Reza Malekzadeh, Farshad Hashemian, Tahereh Safarnavadeh and Mohammad Abdollahi
 
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ABSTRACT

To evaluate clinical benefit of Satureja Khuzestanica (SK) trade named Saturex in Ulcerative Colitis (UC). A randomized controlled trial was conducted in UC patients. Patients with proliferative retinopathy, significant renal impairment (serum creatinine>3 mg dL-1), documented coronary artery disease, chronic liver disease, diabetic foot ulceration and gangrene and pulmonary infection were excluded from the study. The patients were administered 500 mg SK or placebo supplements once daily while they were maintained on their current treatment for UC. After 4 months, frequency difference of the disease flare up was compared between study and placebo groups. 12/14 (85.5%) of SK patients were in complete remission after 4 months as compared to 6/13 (46.2%) of the patients on placebo. The flare up frequency difference (0.07-0.73) between two groups was significant. Supplementing with SK by preventing disease flare up and keeping the patients in remission state would give the opportunity to physicians to reduce the dose of chemical drugs resulting in lower side effects and better compliance of patients.

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Mansoor Rastegarpanah, Naghmeh Omidzohour, Homayoon Vahedi, Reza Malekzadeh, Farshad Hashemian, Tahereh Safarnavadeh and Mohammad Abdollahi, 2011. Management of Human Ulcerative Colitis by SaturexTM: A Randomized Controlled Trial. International Journal of Pharmacology, 7: 516-521.

DOI: 10.3923/ijp.2011.516.521

URL: https://scialert.net/abstract/?doi=ijp.2011.516.521
 
Received: February 28, 2011; Accepted: April 02, 2011; Published: June 14, 2011



INTRODUCTION

Ulcerative Colitis (UC) is kind of chronic Inflammatory Bowel Disease (IBD) that causes many disabling symptoms. It is specified by an inappropriate immune response that causes distinctive inflammatory lesions in the colon. Over production of free radicals (Rezaie et al., 2007a; Hosseini-Tabatabaei and Abdollahi, 2008), imbalance of pathogenic and normal flora of the bowel (Rahimi et al., 2006, 2007a; Elahi et al., 2009) and dysregulation of immune system (Nikfar et al., 2010a) are involved in induction and aggravation of the disease. Currently, pharmacological management of UC is done by use of aminosalicylate derivatives (Nikfar et al., 2009; Rahimi et al., 2009a), tumor necrosis factor antibodies (Rahimi et al., 2007b, c), probiotics (Elahi et al., 2008; Rahimi et al., 2008a, b; Nikfar et al., 2010b), immunoregulators (Nikfar et al., 2010a) and miscellaneous drugs like nicotine (Nikfar et al., 2010c), ATP donors (Salari and Abdollahi, 2009) and phosphodiesterase inhibitors (Salari-Sharif and Abdollahi, 2010). Almost all of these compounds have limited use because of their serious adverse effects. For instance, use of aminosalicylate derivatives during pregnancy may be associated with adverse pregnancy outcomes (Rahimi et al., 2008c). Due to side effects that are commonly seen with current treatments, new investigations have focused on safe effective compound like those obtained from herbal sources (Rahimi et al., 2009b) or traditional medicine (Rahimi et al., 2010).

Satureja Khuzestanica (SK) in Traditional Iranian medicine (TIM) has been used for its antiseptic, analgesic and anti-inflammatory effects. The herb is distributed in the Southern part of the Iran belonging to the family Lamiaceae, subfamily Nepetoideae.

The biological activities and effects of SK have been extensively reviewed by Momtaz and Abdollahi (Momtaz and Abdollahi 2008, 2010). Antioxidative effects of SK have been well confirmed because of its main components such as carvacrol and flavonoids. Carvacrol could prevent prostaglandin synthesis by inhibiting cycloxygenase-2 biosynthesis. Carvacrol also disrupts cell wall of gram negative bacteria and destroys Escherichia coli, Listeria monocytogenes and Lactobacillus sakei. Regarding the role of oxidative inflammation and overgrowth of microbes in pathogenesis of IBD, SK was studied in experimental colitis by our team and found that SK relieves rat IBD through its antioxidant, antimicrobial and anti-inflammatory properties very comparable to prednisolone (Ghazanfari et al., 2006). Safety profile of SK has been studied and completed in animals (Abdollahi et al., 2003) and this herbal compound has been examined and found effective in human diabetes (Vosough-Ghanbari et al., 2010), rat diabetes (Saadat et al., 2004), rat hemorrhagic cystitis Rezvanfar et al., 2008, 2010), rat male infertility (Haeri et al., 2006) and human periodontitis (Shahab et al., 2011).

Therefore, in the present study we evaluated clinical effects in UC patients for the first time.

MATERIALS AND METHODS

The plant was cultivated in Khorramabad and the aerial parts of the plant were collected during the flowering stage. The aerial parts were air dried at ambient temperature in the shade. Tablets were prepared from dried leaves of plant (each tablet contained 500 mg of dried leaves) as described previously (Vosough-Ghanbari et al., 2010). The tablets and placebo were provided by Khorraman Herbal Pharmaceutical Co. (Khorramabad).

This study was a randomized, double blind, placebo controlled trial conducted at the clinic of Digestive Diseases Research Center (DDRC) of Tehran University Teaching Hospital between May 2008 and May 2009. UC patients whom their disease had been already confirmed by colonic features (Table 1) and were in remission were included.

Table 1: Criteria used to Score disease activity index (DAI)
Image for - Management of Human Ulcerative Colitis by SaturexTM: A Randomized Controlled Trial

Exclusion criteria were the followings: proliferative retinopathy, significant renal impairment (serum creatinin>3 mg dL-1), coronary artery disease, chronic liver disease, diabetic foot ulceration/gangrene and pulmonary infection. The DDRC review board approved the study protocol and all participants were asked to sign a written consent before recruiting into study.

Scoring for Disease Activity Index (DAI) was done according to standard measures (Rezaie et al., 2006, 2007b) as described in Table 1 on the basis of disease severity in three categories of mild (grade 1, total score = 8-11), moderate (grade 2, total score = 12-15) and severe (grade 3, total score = 16-19). The patients were simply randomized to receive 500 mg SK or placebo supplements once daily for 4 months.

Baseline characteristics of the patients are shown in Table 2. The patients were maintained on their current treatment for UC.

To measure the outcome, frequency of the disease flare up (intermittent periods of active disease) was evaluated and compared between study and placebo groups by the use of two sample z test and was considered to be significant at a p-value of 0.05, or a confidence interval of 95%.

RESULTS

Thirty patients who met the eligibility criteria were enrolled in the study. They were in the age of 22 to 73 years old. Three patients (one in control and two in placebo patients) left the study because of disease flare-up. Baseline characteristics of the patients are summarized in Table 2. As shown, 12/14 (85.5%) of SK treatment when compared to 6/13 (46.2%) of the patients on placebo. The flare up frequency (Fig. 1) difference (0.07-0.7) between the two groups was significant.

Image for - Management of Human Ulcerative Colitis by SaturexTM: A Randomized Controlled Trial
Fig. 1: Frequency of flare up observed in the placebo and SK groups m: months; SK: Satureja khuzestanica

Table 2: Baseline characteristics of the patients
Image for - Management of Human Ulcerative Colitis by SaturexTM: A Randomized Controlled Trial

Only three patients (one in the control group and two in the placebo group) withdrew from the study. One patient in control group withdrew due to UC flare-up (severe bloody diarrhea, high fever and abdominal pain). Two patients in placebo group withdraw, one due to severe nausea and one because of abdominal pain.

DISCUSSION

Our study showed SK could help UC patients to remain in remission state and reduced flare up rate. This finding appears to be due to its potent antioxidant components including carvacrol (Momtaz and Abdollahi 2008, 2010). In support, there are many studies indicating usefulness of herbal antioxidants like Zataria (Ashtaral-Nakhai et al., 2007), Ziziphora (Ghafari et al., 2006; Amini-Shirazi et al., 2009), Silymarin (Esmaily et al., 2009), Teucrium (Abdolghaffari et al., 2010), IMOD (Baghaei et al., 2010) or even those synthetized like N-acetyl-cysteine (Ebrahimi et al., 2008) and pentoxifylline (Khoshakhlagh et al., 2007). In animal studies, SK reduced bowel biomarkers of free radical damage including myeloperoxidase and lipid peroxidation and improved cellular histology and the inflammatory process (Ghazanfari et al., 2006). SK when tested in human diabetic patients reduced blood markers of oxidative stress and increased body total antioxidant capacity without occurrence of any toxic or adverse effects (Vosough-Ghanbari et al., 2010). Fortunately, no significant adverse effect was recorded in the present study patients and the compound was well tolerated. In another study, the essential oil from SK prevented from malathion-induced free radical damage and toxicity (Rezvanfar et al., 2008, 2010) and even improved blood acetylcholinesterase activity, improved hepatic mitochondrial glycogenolysis and gluconeogenesis in subchronically-exposed rats to the toxin malathion (Saadat et al., 2004; Basiri et al., 2007). Very interestingly, SK improved reproductive potential of normal (Abdollahi et al., 2003; Haeri et al., 2006) and cyclophosphamide-treated (Haeri et al., 2006) male rats through enhancement of body antioxidant potential. These all explains antioxidant potential of SK as one of the mechanisms of actions of SK in management of UC patients (Hasani-Ranjbar et al., 2009).

On the other hand, the role of microbes in induction and development of IBD has been confirmed well and there are strong meta-analysis studies indicating that antibiotics can control human IBD (Rahimi et al., 2007a; Elahi et al., 2009; Nikfar et al., 2010a, b). In support as mentioned in introduction, SK has been traditionally used as antiseptic. Interestingly new study indicated that use of SK irrigation reduces human periodontitis (Shahab et al., 2011) even better than chlorhexidine. Therefore, another explanation for efficacy of SK in human UC is its antimicrobial effects.

CONCLUSION

To keep patients in remission, derivatives of aminosalicylates are conventionally and chronically used but their use is limited with various side effects. Supplementing with SK by preventing disease flare up and keeping the UC patients in remission state would give the opportunity to physicians to reduce the dose of aminosalicylates and other side effects full drugs, thus would result in better compliance of patients. To our best of knowledge, SK gives its benefit in human UC through its potent antioxidant and antimicrobial properties.

ACKNOWLEDGMENT

This study was partially supported by a DDRC of TUMS. Authors declare no conflict of interest. Authors thank Mrs Azadeh Mohammadirad for her assistance in updating references.

REFERENCES

1:  Abdolghaffari, A.H., A. Baghaei, F. Moayer, H. Esmaily and M. Baeeri et al., 2010. On the benefit of Teucrium in murine colitis through improvement of toxic inflammatory mediators. Human Exp. Toxicol., 29: 287-295.
CrossRef  |  

2:  Abdollahi, M., A. Salehnia, S.H.R. Mortazavi, M. Ebrahimi and A. Shafiee et al., 2003. Antioxidant, antidiabetic, antihyperlipidemic, reproduction stimulatory properties and safety of Satureja khuzestanica essential oil as in rat in vivo: A toxicopharmacological study. Med. Sci. Monit., 9: 331-335.
PubMed  |  Direct Link  |  

3:  Amini-Shirazi, N., A. Hoseini, A. Ranjbar, A. Mohammadirad, N. Yasa and M. Abdollahi, 2009. Inhibition of tumor necrosis factor and nitrosative/oxidative stresses by Ziziphora clinopoides (Kahlioti); A molecular mechanism of protection against dextran sodium sulfate-induced colitis in mice. Toxicol. Mech. Methods, 19: 183-189.
CrossRef  |  PubMed  |  Direct Link  |  

4:  Baghaei, A., H. Esmaily, A.H. Abdolghaffari, M. Baeeri, F. Gharibdoost and M. Abdollahi, 2010. Efficacy of Setarud (IMOD®), a novel drug with potent anti-toxic stress potential in rat inflammatory bowel disease and comparison with dexamethasone and infliximab. Indian J. Biochem. Biophys., 47: 219-226.
PubMed  |  Direct Link  |  

5:  Ebrahimi, F., H. Esmaily, M. Baeeri, A. Mohammadirad, S. Fallah and M. Abdollahi, 2008. Molecular evidences on the benefit of N-acetylcysteine in experimental colitis. Central Eur. J. Biol. 3: 135-142.
CrossRef  |  Direct Link  |  

6:  Elahi, B., S. Nikfar, S. Derakhshani, M. Vafaie and M. Abdollahi, 2008. On the benefit of probiotics in the management of pouchitis in patients underwent ileal pouch anal anastomosis: A meta-analysis of controlled clinical trials. Dig. Dis. Sci., 53: 1278-1284.
CrossRef  |  PubMed  |  Direct Link  |  

7:  Elahi, B., S. Nikfar, S. Derakhshani, M. Vafaie and M. Abdollahi, 2009. Benefit of antibiotic therapy on pouchitis after ileal pouch anal anastomosis: A systematic review and meta-analysis of clinical trials. Cent. Eur. J. Med., 4: 164-170.
CrossRef  |  

8:  Esmaily, H., A. Hosseini-Tabatabaei, R. Rahimian, R. Khorasani and M. Baeeri et al., 2009. On the benefits of silymarin in murine colitis by improving balance of destructive cytokines and reduction of toxic stress in the bowel cells. Cent. Eur. J. Biol., 4: 204-213.
CrossRef  |  

9:  Ghafari, H., N. Yasa, A. Mohammadirad, G. Dehghan and M.J. Zamani et al., 2006. Protection by Ziziphora clinopoides of acetic acid-induced toxic bowel inflammation through reduction of cellular lipid peroxidation and myeloperoxidase activity. Hum. Exp. Toxicol., 25: 325-332.
Direct Link  |  

10:  Hasani-Ranjbar, S., B. Larijani and M. Abdollahi, 2009. A systematic review of the potential herbal sources of future drugs effective in oxidant-related diseases. Inflamm. Allergy Drug Targets, 8: 2-10.
PubMed  |  Direct Link  |  

11:  Hosseini-Tabatabaei, A. and M. Abdollahi, 2008. Potassium channel openers and improvement of toxic stress: Do they have role in the management of inflammatory bowel disease? Inflamm. Allergy Drug Targets, 7: 129-135.
Direct Link  |  

12:  Khoshakhlagh, P., M. Bahrololoumi-Shapourabadi, A. Mohammadirad, L. Ashtaral-Nakhai, B. Minaie and M. Abdollahi, 2007. Beneficial effect of phosphodiesterase-5 inhibitor in experimental inflammatory bowel disease: Molecular evidence for involvement of oxidative stress. Toxicol. Mech. Methods, 17: 281-288.
CrossRef  |  

13:  Momtaz, S. and M. Abdollahi, 2008. A systematic review of the biological activities of Satureja L. species. Pharmacologyonline, 2: 34-54.

14:  Momtaz, S. and M. Abdollahi, 2010. An update on pharmacology of Satureja species; From antioxidant, antimicrobial, antidiabetes and anti-hyperlipidemic to reproductive stimulation. Int. J. Pharmacol., 6: 346-353.
CrossRef  |  Direct Link  |  

15:  Nikfar, S., R. Rahimi, A. Rezaie and M. Abdollahi, 2009. A Meta-Analysis of the efficacy of sulfasalazine in comparison with 5-aminosalicylates in the induction of improvement and maintenance of remission in patients with ulcerative colitis. Dig. Dis. Sci., 54: 1157-1170.
CrossRef  |  PubMed  |  

16:  Nikfar, S., H. Mirfazaelian and M. Abdollahi, 2010. Efficacy and tolerability of immunoregulators and antibiotics in fistulizing crohn's disease: A systematic review and meta-analysis of placebo-controlled trials. Curr. Pharm. Des., 16: 3684-3698.
CrossRef  |  

17:  Nikfar, S., M. Darvish-Damavandi and M. Abdollahi, 2010. A review and meta-analysis of the efficacy of antibiotics and probiotics in management of pouchitis. Int. J. Pharmacol., 6: 826-835.
CrossRef  |  Direct Link  |  

18:  Nikfar, S., S. Ehteshami-Ashar, R. Rahimi and M. Abdollahi, 2010. Systematic review and meta-analysis of the efficacy and tolerability of nicotine preparations in active ulcerative colitis. Clin. Ther., 32: 2304-2315.
CrossRef  |  

19:  Rahimi, R., S. Nikfar, A. Rezaie and M. Abdollahi, 2006. A meta-analysis of broad spectrum antibiotic therapy in patients with active Crohn's disease. Clin. Therapeutics, 28: 1983-1988.
CrossRef  |  Direct Link  |  

20:  Rahimi, R., S. Nikfar and M. Abdollahi, 2007. Meta-analysis technique confirms the effectiveness of anti-TNF-alpha in the management of active ulcerative colitis when administered in combination with corticosteroids. Med. Sci. Monit., 13: 13-18.
PubMed  |  Direct Link  |  

21:  Rahimi, R., S. Nikfar and A. Rezaie, 2008. A meta-analysis of the benefit of probiotics in maintaining remission of human ulcerative colitis: Evidence for prevention of disease relapse and maintenance of remission. Arch. Med. Sci., 4: 185-190.

22:  Rahimi, R., S. Nikfar, A. Rezaie and M. Abdollahi, 2008. Pregnancy outcome in women with inflammatory bowel disease following exposure to 5-aminosalicylic acid drugs: A meta-analysis. Reprod. Toxicol., 25: 271-275.
CrossRef  |  Direct Link  |  

23:  Rahimi, R., S. Nikfar, A. Rezaie and M. Abdollahi, 2009. Comparison of mesalazine and balsalazide in induction and maintenance of remission in patients with ulcerative colitis: A meta-analysis. Dig. Dis. Sci., 54: 712-721.
CrossRef  |  

24:  Rahimi, R., S. Mozaffari and M. Abdollahi, 2009. On the use of herbal medicines in management of inflammatory bowel diseases: A systematic review of animal and human studies. Dig. Dis. Sci., 54: 471-480.
CrossRef  |  Direct Link  |  

25:  Rahimi, R., M.R. Shams-Ardekani and M. Abdollahi, 2010. A review of the efficacy of traditional Iranian medicine for inflammatory bowel disease. World J. Gastroenterol., 16: 4504-4514.
CrossRef  |  PubMed  |  

26:  Rezaie, A., F. Ghorbani, A. Eshghtork, M.J. Zamani and G. Dehghan et al., 2006. Alterations in salivary antioxidants, nitric oxide and transforming growth factor-β1 in relation to disease activity in Crohn's disease patients. Ann. N.Y. Acad. Sci., 1091: 110-122.
CrossRef  |  Direct Link  |  

27:  Rezaie, A., S. Khalaj, M. Shabihkhani, S. Nikfar, M.J. Zamani, A. Mohammadirad and N.E. Daryani 2007. Study on the correlations among disease activity index and salivary transforming growth factor-β1 and nitric oxide in ulcerative colitis patients. Ann. N.Y. Acad. Sci., 1095: 305-314.
CrossRef  |  Direct Link  |  

28:  Rezvanfar, M.A., R.A. Sadrkhanlou, A. Ahmadi, H. Shojaei-Sadee and M.A. Rezvanfar et al., 2008. Protection of cyclophosphamide-induced toxicity in reproductive tract histology, sperm characteristics and DNA damage by an herbal source; evidence for role of free-radical toxic stress. Hum. Exp. Toxicol., 27: 901-910.
CrossRef  |  PubMed  |  Direct Link  |  

29:  Rezvanfar, M.A., A.A. Farshid, R.A. Sadrkhanlou, A. Ahmadi, M.A. Rezvanfar, A. Salehnia and M. Abdollahi, 2010. Benefit of Satureja khuzestanica in subchronically rat model of cyclophosphamide-induced hemorrhagic cystitis. Exp. Toxicol. Pathol., 62: 323-330.
PubMed  |  

30:  Saadat, M., S. Pournourmohammadi, M. Donyavi, R. Khorasani, G. Amin, A.N. Salehnia and M. Abdollahi, 2004. Alteration of rat hepatic glycogen phosphorylase and phosphoenolpyruvate carboxykinase activities by Satureja khuzestanica Jamzad essential oil. J. Pharm. Pharmaceut. Sci., 7: 327-331.
Direct Link  |  

31:  Salari, P. and M. Abdollahi, 2009. Current opinion in the pharmaceutical management of irritable and inflammatory bowel diseases: Role of ATP. Rec. Pat. Endoc. Metab. Immune Drug Disc., 3: 69-75.
CrossRef  |  

32:  Salari-Sharif, P. and M. Abdollahi, 2010. Phosphodiesterase 4 inhibitors in inflammatory bowel disease: A comprehensive review. Curr. Pharm. Des., 16: 3661-3667.
CrossRef  |  

33:  Shahab, A., F. Haghighati, M. Baeeri, H. Jamalifar and M. Abdollahi, 2011. A clinical, microbiological and immunological comparison between subgingival irrigation with DentolTM and chlorhexidine in advanced periodontitis. Arch. Med. Sci., 7: 154-160.
CrossRef  |  

34:  Vosough-Ghanbari, S., R. Rahimi, S. Kharabaf, S. Zeinali and A. Mohammadirad et al., 2010. Effects of Satureja khuzestanica on serum glucose, lipids and markers of oxidative stress in patients with type 2 diabetes mellitus: A double-blind randomized controlled trial. Evid. Based Complement. Alternat. Med., 7: 465-470.
CrossRef  |  PubMed  |  Direct Link  |  

35:  Rezaie, A., R.D. Parker and M. Abdollahi, 2007. Oxidative stress and pathogenesis of inflammatory bowel disease: An epiphenomenon or the cause. Dig. Dis. Sci., 52: 2015-2021.
CrossRef  |  PubMed  |  

36:  Rahimi, R., S. Nikfar, A. Rezaie and M. Abdollahi, 2007. A meta‐analysis of antibiotic therapy for active ulcerative colitis. Dig. Dis. Sci., 52: 2920-2925.
CrossRef  |  Direct Link  |  

37:  Rahimi, R., S. Nikfar, F. Rahimi, B. Elahi, S. Derakhshani, M. Vafaie and M. Abdollahi, 2008. A meta-analysis on the efficacy of probiotics for maintenance of remission and prevention of clinical and endoscopic relapse in Crohn's disease. Dig. Dis. Sci., 53: 2524-2531.
CrossRef  |  PubMed  |  

38:  Rahimi, R., S. Nikfar and M. Abdollahi, 2007. Do anti-tumor necrosis factors induce response and remission in patients with acute refractory Crohns disease? A systematic meta-analysis of controlled clinical trials. Biomed. Pharmacother., 61: 75-80.
CrossRef  |  Direct Link  |  

39:  Haeri, S., B. Minaie, G. Amin, S. Nikfar and R. Khorasani et al., 2006. Effect of Satureja khuzestanica essential oil on male rat fertility. Fitoterapia, 77: 495-499.
CrossRef  |  PubMed  |  Direct Link  |  

40:  Nakhai, L.A., A. Mohammadirad, N. Yasa, B. Minaie and N. Nikfar et al., 2007. Benefits of Zataria multiflora Boiss. in experimental model of mouse inflammatory bowel disease. Evid. Based Complement. Alternat. Med., 4: 43-50.
CrossRef  |  Direct Link  |  

41:  Basiri, S., H. Esmaily, S. Vosough‐Ghanbari, A. Mohammadirad, N. Yasa and M. Abdollahi, 2007. Improvement by Satureja khuzestanica essential oil of malathion-induced red blood cells Pesticide Biochem. Physiol., 89: 124-129.
CrossRef  |  Direct Link  |  

42:  Ghazanfari, G., B. Minaie, N. Yasa, L.A. Nakhai and A. Mohammadirad et al., 2006. Biochemical and histopathological evidences for beneficial effects of Satureja khuzestanica jamzad essential oil on the mouse model of inflammatory bowel diseases. Toxicol. Mech. Methods, 16: 365-372.
CrossRef  |  PubMed  |  Direct Link  |  

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