DISCUSSION: IBD Relief is traditionally used in Herbal medicine to help relieve digestive upset/disturbances including lack of appetite, nausea, digestive spasms, indigestion, dyspepsia and flatulent colic. IBD Relief contains digestive enzymes that help digest proteins and a probiotic that forms part of a natural healthy gut flora and helps reduce the risk of antibiotic-associated diarrhea.
|NPN (what's this?)||Product Code||Size||Per Capsule||Vegetarian|
|80036184||AOR04307||120 Vegi-Caps||420 mg|
|Serving Size: 4 Capsules|
|ANPEP™ [protease from A. niger & A. flavus var. oryzae]||13.64 mg / 1,900 HUT*|
|Ginger (Zingiber officinale, 10:1)||300 mg|
|Saccharomyces boulardii||1.33 x 1010 cfu|
|Boswellia serrata (40% boswellic acids)||600 mg|
|Vitamin D3||25 mcg / 1000 IU|
|Withania somnifera (10:1)||100 mg|
|Non-medicinal ingredients: microcrystalline cellulose, maltodextrin, potato starch, beta-cyclodextrin, dextrin, sodium stearyl fumarate. Capsule: hypromellose.*FCC-approved units|
AOR Guarantees: that no ingredients not listed on the label have been added to the product. Contains no wheat, gluten, peanuts, mustard or shellfish.
Adult Dosage: Take 3 capsules daily or 2 capsules twice daily, with meals of your choice, or as directed by a qualified health care professional.
Cautions: Consult a health care practitioner prior to use if you have gastrointestinal lesions/ulcers, are taking anticoagulant agents, anti-inflammatory agents or other enzyme products, are having surgery, or if you have nausea, fever, vomiting, bloody diarrhea or severe abdominal pain. Consult a healthcare practitioner for prolonged use. Discontinue use and consult a health care practitioner if symptoms (e.g. digestive upset, diarrhea) occur, worsen, or persist beyond 3 days. Hypersensitivity/allergy has been known to occur in which case discontinue use. Consumption with alcohol, other drugs or natural health products with sedative properties is not recommended. Do not use if you have an immune-compromised condition (e.g. AIDS, lymphoma, patients undergoing long-term corticosteroid treatment). This product has come into contact with soy; do not use if you have a soy allergy.
Pregnancy/Nursing: Do not use
Proteases – Bacterial fermentation; Vitamin D3 – Lanolin (sheep’s wool); Boswellia, Ashwagandha, Ginger – Natural botanical extracts; Saccharomyces boulardii –Probiotic yeast
The information and product descriptions appearing on this website are for information purposes only, and are not intended to provide or replace medical advice to individuals from a qualified health care professional. Consult with your physician if you have any health concerns, and before initiating any new diet, exercise, supplement, or other lifestyle changes.
Read More ...
IBD and Celiac Disease
Ulcerative colitis (UC) and Crohn’s disease (CD) are the most common forms of inflammatory bowel diseases (IBD) in humans. These diseases are characterized by cycles of chronic relapses and remissions. These cycles are associated with chronic inflammation of the intestinal mucosa and an abnormal gut microflora. Celiac disease is caused by an immune response to the protein gluten. It is believed to affect 1 in 200 people in the modernized world, and results in a decreased ability of the body to absorb nutrients. Symptoms of Celiac disease include diarrhea, weight loss, anemia as well as other complications.
A Successful Combination
IBD Relief provides an innovative and effective combination of ingredients to help those with IBD or celiac disease manage and prevent inflammation and exacerbation of the condition.
Research has shown that prolyl endopeptidases (PEPs) which contain DPP-IV also help to break down gluten, reducing the occurrence of gluten-induced intestinal inflammation. IBD Relief includes PEPs derived from the fungus Aspergillus niger (AN-PEP). AN-PEP is superior to other gluten-digesting enzymes because it remains active over a wide pH range (2-8), and is not destroyed by stomach acidity.Not only does AN-PEP work at stomach’s natural pH, but it has been shown to degrade gluten proteins 60 times faster than other enzymes commonly used. This faster degradation allows gluten molecules to leave the stomach cleaved into smaller fragments before reaching the small intestine where gluten causes the problems associated with Celiac disease.
DPP IV for Inflammation & Auto-immunity
Over-activation of the immune system during an infection can drive the immune system into a state of autoimmunity, which leads to cellular damage and chronic inflammation. Autoimmunity can be promoted through the inappropriate activation of the immune system by certain proteins in the diet. This is the underlying mechanism behind celiac disease, where the immune system inappropriately targets the gliadin proteins in gluten. The problem can be aggravated by a lack of dipeptidyl peptidase IV (DPP-IV) enzyme activity in certain gastrointestinal conditions.
DPP-IV is an enzyme whose activity is required to break down proteins linked to the exacerbation of conditions such as IBD (such as Crohn’s and ulcerative colitis) and celiac disease. DPP IV promotes a normal immune response and is important for the modulation of immune messengers that regulate immunity and inflammation. Low DPP-IV levels results in the accumulation of undigested protein fragments, which are thought to elicit an immune response that can inflame the lining of the gastrointestinal tract. Supplementation with enzymes having DPP-IV activity prevents the activation of the immune system by breaking down dietary proteins like gluten before they activate an immune response – a significant benefit for those suffering from autoimmune disorders like IBD or celiac disease.
Is a probiotic yeast which is useful for fighting off disease causing organisms in the intestinal tract. It is used for fighting inflammation and infection in the intestinal tract as a result of microbial imbalances. Some studies indicate that it is useful in inflammatory bowel diseases for reducing inflammation and inducing remission.
Vitamin D and Autoimmune Diseases
The evidence linking vitamin D and the prevalence of autoimmune diseases continues to grow. There is clear evidence that vitamin D is needed for the proper functioning of the immune system. This has been demonstrated in studies using the development of animal models of human autoimmune diseases including experimental inflammatory bowel disease.
Withania somnifera for Stress
There is significant psychological stress in dealing with any chronic disease. Chronic stress may lead to a breakdown in coping mechanisms and worsen the course of IBD.Withania somnifera is well known for its ability to enhance the body’s response to stress. This traditional ayurvedic herb can also help support the immune system, liver function and normal blood parameters.
Ginger is one of the first treatments that come to mind for an upset stomach, but it also has anti-inflammatory effects in the intestines besides its ability to calm the stomach. Ginger or Zingiber officinale has long been used in Traditional Chinese Medicine for the relief of digestive complaints including nausea and intestinal cramps. Ginger helps to improve digestion by reducing inflammation, improving intestinal motility and toning the muscles of the wall of the gut.
Boswellia is well known for its anti-inflammatory effects. In clinical trials, promising results were obtained in UC patients using Boswellia. All parameters studied improved with boswellia supplementation, including stool properties, rectal biopsies, blood parameters, serum iron, calcium, proteins and eosinophils. Furthermore, 82% of the patients treated with boswellia went into remission whereas only 75% of the patients receiving sulfasalazine (an anti-inflammatory drug used to treat UC) experienced a remission. Similar results have also been shown for patients with Crohn’s disease. It is not surprising that according to the latest survey, 36% of German IBD patients surveyed use boswellia as part of their treatment protocol. Animal experiments have showed that boswellia modulates some components of the immune system, thereby reducing inflammation.
Vitamin D has been shown to inhibit the induction of auto-immune diseases such as systemic lupus erythematosus, type-1 diabetes and IBD. The vitamin D receptor also appears to have a critical role in the control and response of the colon to chemical injury as has been observed in studies using the development of animal models of human autoimmune diseases including experimental inflammatory bowel disease.
A study from the University of Michigan and funded by the National Cancer Institute found that taking ginger root supplements reduced intestinal inflammation by 28%. Ginger also has an excellent safety profile.
S. boulardii is a probiotic yeast that is useful for fighting off disease-causing organisms in the intestinal tract. It is used for fighting inflammation and infection in the intestinal tract as a result of microbial imbalances. In an animal study, S. boulardii reduced the inflammation associated with irritable bowel syndrome (IBD), which suggests that Saccharomyces could play a role in reducing the symptoms of IBD. In a human study on ulcerative colitis, results indicated that it was is useful for fighting the inflammatory effects of the disease, and in some patients was even able to induce remission.
Research has shown that prolyl endopeptidases (PEPs) can reduce the antigen toxicity of gluten, by cleaving proline-rich gluten peptides. PEP cleaves the gluten peptide into two shorter peptides that are cleaved further by brush-border enzymes at the intestinal microvilli. This reduces the vulnerability to gluten induced intestinal inflammation and reduces the immune response that leads to the inflammation of the lining of the gastrointestinal tract.
Preliminary research has shown that DPP IV, one of the activities of AN-PEP, also cleaves and inactivates tumor necrosis factor alpha (TNF-α), regulating the extracellular TNF-α concentration. TNF-α is an immune messenger that promotes inflammation and plays a significant part in autoimmune disorders such as inflammatory bowel disease.
Inflammatory bowel problems and disease are an increasingly common and serious medical problem, which in some cases can have many underlying complexities associated with them. Some of the most common treatments for IBD include adhering to certain dietary protocols, taking medications that suppress the immune system and or downgrade the inflammatory mechanisms in the bowel and in serious cases, removing damaged sections of the bowel by surgical means. Many IBD medications can cause side effects and also do not treat the underlying causes of the disorder. With regards to celiac disease alone, currently the only treatment is life-long avoidance of wheat, rye, barley and other gluten containing foods. In terms of enzymatic therapy, previous gluten digesting enzymes studied, most notably, FM-POP (a prolyl oligopeptidases), were inactivated by the acidic environment of the stomach.
The key to the successfully managing conditions like IBD is intervention based on a multiple-mechanism approach. AOR’s IBD Relief combines research-based ingredients shown to act upon different physiological targets to help manage the symptoms of IBD & celiac disease, offering a natural formula to help treat the underlying causes of inflammatory bowel disorders without the negative side effects that are associated with conventional treatments. The effectiveness of IBD Relief can be further enhanced if combined with additional vitamin D3 supplementation as well as a complete probiotic supplement, like ProBiotic 3, to help normalize the intestinal flora.
Ammon HP. Boswellic acids in chronic inflammatory diseases. Planta Med. 2006 Oct;72(12):1100-16.
Archana R, Namasivayam A. Antistressor effect of Withania somnifera. J Ethnopharmacol 1999 Jan; 64(1): 91-3.
Froicu M, Cantorna MT. Vitamin D and the vitamin D receptor are critical for control of the innate immune response to colonic injury. BMC Immunol. 2007 Mar 30;8:5.
Geier, M., Butler, R., Howarth, G. Inflammatory bowel disease: Current insights into pathogenesis and new therapeutic options; probiotics, prebiotics and synbiotics. International J of Food Microbiology, 115 (2007), pp1-11.
Gerhardt H, Seifert F, Buvari P, Vogelsang H, Repges R. Therapy of active Crohn disease with Boswellia serrata extract H 15. Z Gastroenterol. 2001 Jan;39(1):11-7.
Goodhand J, Rampton D. Psychological stress and coping in IBD. Gut. 2008 Oct;57(10):1345-7.
Gupta I, Parihar A, Malhotra P, Singh GB, Lüdtke R, Safayhi H, Ammon HP. Effects of Boswellia serrata gum resin in patients with ulcerative colitis. Eur J Med Res. 1997 Jan;2(1):37-43.
Guslandi M, Giollo P and Testoni PA. A pilot trial of Saccharomyces boulardii in ulcerative colitis. Eur J Gastroenterol Hepatol 2003; 15:697-698
Hoffman JC, et al. [Diagnosis and therapy of ulcerative colitis: results of an evidence based consensus conference by the German society of Digestive and Metabolic Diseases and the competence network on inflammatory bowel disease]. Z Gastroenterol 2004, 42:979-983.
Joos S, Rosemann T, Szecsenyi J, Hahn EG, Willich SN, Brinkhaus B. Use of complementary and alternative medicine in Germany – a survey of patients with inflammatory bowel disease. BMC Complement Altern Med. 2006 May 22;6:19.
Mach, T. Clinical usefulness of probiotics in inflammatory bowel diseases. J of Physiol and Pharm. 2006, 57, Suppl 9, pp23-33.
Sedo A, Malik R. Dipeptidyl peptidase IV-like molecules: homologous proteins or homologous activities? Biochim Biophys Acta. 2001 Dec 17;1550(2):107-16. Review.
Siegel, M., et al. Rational design for combination enzyme therapy for celiac sprue. Chemistry & Biology. 13, June 2006, pp649-658.
Stepniak, D., et al. Highly efficient gluten degradation with a newly identified prolyl endoprotease: implications for celiac disease. The American Physiological Society. [Online] http://www.the-aps.org/press/journal/06/13.htm 2006.
Tiruppathi C, Miyamoto Y, Ganapathy V, Leibach FH. Genetic evidence for role of DPP IV in intestinal hydrolysis and assimilation of prolyl peptides. Am J Physiol. 1993 Jul;265(1 Pt 1):G81-9.
Vojdani A, Bazargan M, Vojdani E, Samadi J, Nourian AA, Eghbalieh N, Cooper EL. Heat shock protein and gliadin peptide promote development of peptidase antibodies in children with autism and patients with autoimmune disease. Clin Diagn Lab Immunol. 2004 May;11(3):515-24.
Zick SM, Turgeon DK, Vareed SK et al. Phase II Effects of Ginger Root Extract on Eicosanoids in Colon Mucosa in People at Normal Risk For Colorectal Cancer. Journal on Cancer Prevention Research. 2011 Nov;4(11):1929-37.
Effect of ginger on gastric motility and symptoms of functional dyspepsia.
World J Gastroenterol. 2011 Jan 7;17(1):105-10.
Hu ML, Rayner CK, Wu KL, Chuah SK, Tai WC, Chou YP, Chiu YC, Chiu KW, Hu TH.
AIM: To evaluate the effects of ginger on gastric motility and emptying, abdominal symptoms, and hormones that influence motility in dyspepsia.
METHODS: Eleven patients with functional dyspepsia were studied twice in a randomized double-blind manner. After an 8-h fast, the patients ingested three capsules that contained ginger (total 1.2 g) or placebo, followed after 1 h by 500 mL low-nutrient soup. Antral area, fundus area and diameter, and the frequency of antral contractions were measured using ultrasound at frequent intervals, and the gastric half-emptying time was calculated from the change in antral area. Gastrointestinal sensations and appetite were scored using visual analog questionnaires, and blood was taken for measurement of plasma glucagon-like peptide-1 (GLP-1), motilin and ghrelin concentrations, at intervals throughout the study.
RESULTS: Gastric emptying was more rapid after ginger than placebo [median (range) half-emptying time 12.3 (8.5-17.0) min after ginger, 16.1 (8.3-22.6) min after placebo, P≤0.05]. There was a trend for more antral contractions (P=0.06), but fundus dimensions and gastrointestinal symptoms did not differ, nor did serum concentrations of GLP-1, motilin and ghrelin.
CONCLUSION: Ginger stimulated gastric emptying and antral contractions in patients with functional dyspepsia, but had no impact on gastrointestinal symptoms or gut peptides.
Inflammatory bowel disease: current insights into pathogenesis and new therapeutic options; probiotics, prebiotics and synbiotics.
Int J Food Microbiol. 2007 Apr 1;115(1):1-11.
Geier MS, Butler RN, Howarth GS.
Inflammatory bowel disease (IBD) is a chronic relapsing disorder involving a dysregulated host-microbiota interaction. IBD patients have been shown to possess an increased risk for the development of colorectal cancer. Recently, focus has been placed on probiotic and prebiotic therapies, which aim to restore balance to the gastrointestinal microbiota, and reduce intestinal inflammation. Probiotics have been assessed extensively in animal models, with a number of clinical trials also demonstrating potential therapeutic benefits. However, it is widely accepted that more double-blind randomised placebo-controlled trials are required. Future research also needs to focus on determining which probiotics are the most efficacious in the IBD setting, and how the genetic and bacterial profiles of the patient will influence treatment responsiveness. Prebiotics have been studied less extensively, however, they may become an ideal treatment or co-treatment option due to their capacity to increase endogenous lactobacillus and bifidobacteria. Probiotics and prebiotics may offer a new therapeutic option for the treatment of IBD, however, a greater understanding of the mechanisms behind their action on the gastrointestinal microbiota is required in order to determine which probiotic, prebiotic or combinations thereof are the most beneficial.
Vitamin D and the vitamin D receptor are critical for control of the innate immune response to colonic injury.
BMC Immunol. 2007 Mar 30;8:5.
Froicu M, Cantorna MT.
BACKGROUND: The active form of vitamin D (1,25(OH)2D3) has been shown to inhibit development of inflammatory bowel disease (IBD) in IL-10 KO mice. Here, the role of the vitamin D receptor (VDR) and 1,25(OH)2D3 in acute experimental IBD was probed.
RESULTS: VDR KO mice were extremely sensitive to dextran sodium sulfate (DSS) and there was increased mortality of the VDR KO mice at doses of DSS that only caused a mild form of colitis in wildtype (WT) mice. DSS colitis in the VDR KO mice was accompanied by high colonic expression of TNF-alpha, IL-1 alpha, IL-1beta, IL-12, IFN-gamma, IL-10, MIP-1alpha and KC. DSS concentrations as low as 0.5% were enough to induce bleeding, ulceration and weight loss in VDR KO mice. VDR KO mice failed to recover following the removal of DSS, while WT mice showed signs of recovery within 5 days of DSS removal. The early mortality of DSS treated VDR KO mice was likely due to perforation of the bowel and resulting endotoxemia. VDR KO mice were hyper-responsive to exogenously injected LPS and cultures of the peritoneal exudates of moribund DSS treated VDR KO mice were positive for bacterial growth. 1,25(OH)2D3 in the diet or rectally decreased the severity and extent of DSS-induced inflammation in WT mice.
CONCLUSION: The data point to a critical role for the VDR and 1,25(OH)2D3 in control of innate immunity and the response of the colon to chemical injury.
Use of complementary and alternative medicine in Germany – a survey of patients with inflammatory bowel disease
Alternative Medicine; 2006, 6: 19
Joos S, Rosemann T, Szecsenyi J, Hahn EGn , Willich SN and Brinkhaus B. BMC Complementary and
Background: Previous studies have suggested an increasing use of complementary and alternative medicine (CAM) in patients with inflammatory bowel disease (IBD). The aim of our study was to evaluate the use of CAM in German patients with IBD.
Methods: A questionnaire was offered to IBD patients participating in patient workshops which were organized by a self-help association, the German Crohn’s and Colitis Association. The self-administered questionnaire included demographic and disease-related data as well as items analysing the extent of CAM use and satisfaction with CAM treatment. Seven commonly used CAM methods were predetermined on the questionnaire.
Results: 413 questionnaires were completed and included in the analysis (n = 153 male, n = 260 female; n = 246 Crohn’s disease, n = 164 ulcerative colitis). 52 % of the patients reported CAM use in the present or past. In detail, homeopathy (55%), probiotics (43%), classical naturopathy (38%), Boswellia serrata extracts (36%) and acupuncture/Traditional Chinese Medicine (TCM) (33%) were the most frequently used CAM methods. Patients using probiotics, acupuncture and Boswellia serrata extracts (incense) reported more positive therapeutic effects than others. Within the statistical analysis no significant predictors for CAM use were found. 77% of the patients felt insufficiently informed about CAM.
Conclusion: The use of CAM in IBD patients is very common in Germany, although a large proportion of patients felt that information about CAM is not sufficient. However, to provide an evidence-based approach more research in this field is desperately needed. Therefore, physicians should increasingly inform IBD patients about benefits and limitations of CAM treatment.
Vitamin D Status in Children and Young Adults With Inflammatory Bowel Disease
Pediatrics; 2005, 118( 5): 1950-1961
Pappa HM, Gordon CM, Saslowsky TM, Zholudev A, Horr B, Shih M, Grand RJ.
OBJECTIVES: Previous studies of vitamin D status in pediatric patients with inflammatory bowel disease have revealed conflicting results. We sought to report (1) the prevalence of vitamin D deficiency (serum 25-hydroxy-vitamin D concentration 15 ng/mL) in a large population with inflammatory bowel disease, (2) factors predisposing to this problem, and (3) its relationship to bone health and serum parathyroid hormone concentration.
PATIENTS AND METHODS: A total of 130 patients (8-22 years of age) with inflammatory bowel disease, 94 with Crohn disease and 36 with ulcerative colitis, had serum 25-hydroxy-vitamin D, intact parathyroid hormone, and lumbar spine bone mineral density (using dual-energy x-ray absorptiometry) measured at Children’s Hospital Boston.
RESULTS: The prevalence of vitamin D deficiency was 34.6%. Mean serum 25-hydroxy-vitamin D concentration was similar in patients with Crohn disease and ulcerative colitis, 52.6% lower among patients with dark skin complexion, 33.4% lower during the winter months (December 22 to March 21), and 31.5% higher among patients who were taking vitamin D supplements. Serum 25-hydroxy-vitamin D concentration was positively correlated with weight and BMI z score, disease duration, and serum albumin concentration and negatively correlated with erythrocyte sedimentation rate. Patients with Crohn disease and upper gastrointestinal tract involvement were more likely to be vitamin D deficient than those without it. Serum 25-hydroxy-vitamin concentration was not associated with lumbar spine bone mineral density z score or serum parathyroid hormone concentration.
CONCLUSIONS: Vitamin D deficiency is highly prevalent among pediatric patients with inflammatory bowel disease. Factors predisposing to the problem include having a dark-skin complexion, winter season, lack of vitamin D supplementation, early stage of disease, more severe disease, and upper gastrointestinal tract involvement in patients with Crohn disease. The long-term significance of hypovitaminosis D for this population is unknown at present and merits additional study
A pilot trial of Saccharomyces boulardii in ulcerative colitis.
Eur J Gastroenterol Hepatol. 2003 Jun;15(6):697-8.
Guslandi M, Giollo P, Testoni PA.
OBJECTIVES: Probiotics can be useful in the treatment of inflammatory bowel disease. In a previous report, the non-pathogenic yeast Saccharomyces boulardii was found to be beneficial in the maintenance treatment of Crohn’s disease. The aim of this study was to assess the efficacy of S. boulardii in ulcerative colitis patients.
METHODS: A group of 25 patients with a mild to moderate clinical flare-up of ulcerative colitis received additional treatment with S. boulardii 250 mg three times a day for 4 weeks during maintenance treatment with mesalazine. These patients were unsuitable for steroid therapy. Before and after treatment, Rachmilewitz’s clinical activity index was calculated. The probiotic treatment was considered a therapeutic success only when the final score was lower than 6.
RESULTS: Of the 24 patients who completed the study, 17 attained clinical remission; this was confirmed endoscopically.
CONCLUSIONS: Our preliminary results suggest that S. boulardii can be effective in the treatment of ulcerative colitis. Controlled studies with this probiotic agent are warranted.
Therapy of active Crohn disease with Boswellia serrata extract H 15.
Z Gastroenterol. 2001 Jan;39(1):11-7.
Gerhardt H, Seifert F, Buvari P, Vogelsang H, Repges R.
BACKGROUND: The purpose of this clinical trial was to compare efficacy and safety of the Boswellia serrata extract H15 with mesalazine for the treatment of active Crohn’s disease.
PATIENTS AND METHODS: Randomised, double-blind, verum-controlled, parallel group comparison for which 102 Patients were randomised. The per protocol population included 44 patients treated with H15 and 39 patients treated with mesalazine. As primary outcome measure the change of the Crohn Disease Activity Index (CDAI) between the status of enrolment and end of therapy was chosen. H 15 was tested on non-inferiority compared to standard treatment with mesalazine.
RESULTS: The CDAI between the status of enrolment and end of therapy after treatment with H15 was reduced by 90 and after therapy with mesalazine by 53 scores in the mean. In this non-inferiority-trial the test hypothesis was confirmed by the statistical analysis. The difference between both treatments could not be proven to be statistically significant in favor to H15 for the primary outcome measure. The secondary efficacy endpoints confirm the assessment of the comparison of H15 and mesalazine. The proven tolerability of H15 completes the results of the shown clinical efficacy.
CONCLUSIONS: The study confirms that therapy with H15 is not inferior to mesalazine. This can be interpreted as evidence for the efficacy of H15 according to the state of art in the treatment of active Crohn’s disease with Boswellia serrata extract, since the efficacy of mesalazine for this indication has been approved by the health authorities. Considering both safety and efficacy of Boswellia serrata extract H15 it appears to be superior over mesalazine in terms of a benefit-risk-evaluation.
Dipeptidyl peptidase IV-like molecules: homologous proteins or homologous activities?
2001 Dec 17;1550(2):107-16.
Sedo A, Malík R. Biochim Biophys Acta.
Membrane-bound proteases are widely distributed among various cell systems. Their expression in a particular cell type is finely regulated, reflecting the specific functional cell implications and engagement in defined physiological pathways. Protein turnover, ontogeny, inflammation, tissue remodeling, cell migration and tumor invasion are among the many physiological and pathological events in which membrane proteases play a crucial role, both as effector as well as regulatory molecules. The presence of proline residues gives unique structural features to peptide chains, substantially influencing the susceptibility of proximal peptide bond to protease cleavage. Among the rare group of proline-specific proteases, dipeptidyl peptidase IV (DPP-IV, EC 22.214.171.124) was originally believed to be the only membrane-bound enzyme specific for proline as the penultimate residue at the amino-terminus of the polypeptide chain. However, other molecules, even structurally non-homologous with the DPP-IV but bearing corresponding enzyme activity, have been identified recently. This review summarizes the present knowledge of “DPP-IV activity- and/or structure-homologues” (DASH) and provides some insight into their multifunctional roles.
Antistressor effect of Withania somnifera.
J Ethnopharmacol. 1999 Jan;64(1):91-3.
Archana R, Namasivayam A.
Withania somnifera is an Indian medicinal plant used widely in the treatment of many clinical conditions in India. Its antistressor properties have been investigated in this study using adult Wistar strain albino rats and cold water swimming stress test. The results indicate that the drug treated animals show better stress tolerance.
Effects of Boswellia serrata gum resin in patients with ulcerative colitis.
Eur J Med Res. 1997 Jan;2(1):37-43.
Gupta I, Parihar A, Malhotra P, Singh GB, Lüdtke R, Safayhi H, Ammon HP.
Ulcerative colitis is a chronic inflammatory disease of the colon where leukotrienes are suggested to play an important role for keeping inflammation active. Boswellic acids, the biologically active ingredients of the gum resin of Boswellia serrata (Sallai guggal), have been shown to be specific, nonredox and noncompetitive inhibitors of 5-lipoxygenase, the key enzyme of leukotriene biosynthesis. In patients suffering from ulcerative colitis grade II and III the effect of Boswellia serrata gum resin preparation (350 mg thrice daily for 6 weeks) on stool properties, histolopathology and scan microscopy of rectal biopsies, blood parameters including Hb, serum iron, calcium, phosphorus, proteins, total leukocytes and eosinophils was studied. Patients receiving sulfasalazine (1 g thrice daily) served as controls. All parameters tested improved after treatment with Boswellia serrata gum resin, the results being similar compared to controls: 82% out of treated patients went into remission; in case of sulfasalazine remission rate was 75%.
Genetic evidence for role of DPP IV in intestinal hydrolysis and assimilation of prolyl peptides.
Am J Physiol. 1993 Jul;265(1 Pt 1):G81-9.
Tiruppathi C, Miyamoto Y, Ganapathy V, Leibach FH.
The functional role of dipeptidyl peptidase IV (DPP IV) in the intestinal hydrolysis and assimilation of prolyl peptides was investigated using Japan F344 rats, which genetically lack this enzyme. USA F344 rats possess normal activity of this enzyme and served as matched controls. Intestinal brush-border membranes from the control rats were able to hydrolyze several proline-containing peptides. The hydrolytic ability of the brush-border membranes from the Japan rats against these peptides was markedly low. The difference in the hydrolytic activities between the two groups of rats was solely due to the absence of DPP IV in the Japan rats. There was no difference in the growth rate between the two groups of rats fed a reference diet whose protein constituents were not rich in proline. When the protein source was changed to gliadin, a proline-rich protein, USA F344 rats maintained their body weight for a 4-wk period on this diet, whereas the Japan rats experienced a significant weight loss under similar conditions. In situ perfusion experiments in intact animals revealed that the ability of morphiceptin (a peptide primarily hydrolyzable by DPP IV), when administered into the intestinal lumen, to block the cholera toxin-induced water secretion was significantly greater in Japan F344 rats than in USA F344 rats, indicating the resistance of morphiceptin to hydrolytic breakdown in the intestinal lumen of the Japan rats. It is concluded that the intestinal DPP IV plays a significant role in the hydrolysis of prolyl peptides and assimilation of proline-rich proteins.