What is the significance of 2-styryl chromones in CD?

"Anti-inflammatory potential of 2-styrylchromones regarding their interference with arachidonic acid metabolic pathways " in Biochemical Pharmacology (2009)
"The aim of the present work was to evaluate the anti-inflammatory potential of 2-styrylchromones (2-SC), a chemical family of oxygen heterocyclic compounds, vinylogues of flavones (2-phenylchromones), by studying their COX-1 and COX-2 inhibitory capacity as well as their effects on the LTB₄ [leukotrene B4] production by stimulated human polymorphonuclear leukocytes (PMNL). [granulocytes].
Some of the tested 2-SC were able to inhibit both COX-1 activity and LTB₄ production which makes them dual inhibitors of the COX and 5-LOX pathways. The most effective compounds in this study were those having structural moieties with proved antioxidant activity (3′,4′-catechol and 4′-phenol substituted B-rings).
This type of compounds may exhibit anti-inflammatory activity with a wider spectrum than that of classical non-steroidal anti-inflammatory drugs (NSAIDs) by inhibiting 5-LOX product-mediated inflammatory reactions, towards which NSAIDs are ineffective."

"Biological activities of 2-styrylchromones" in Mini Rev Med Chem (2010)
"2-Styrylchromones (2-SC) are chromone derivatives characterized by the attachment of a styryl group to the 2-position of the chromone structure. The 2-styrylchromone structure has been demonstrated to bear important biological activities such as antiallergic, antitumor, affinity and selectivity for A(3) adenosine receptors, antiviral, antioxidant and anti-inflammatory. The aim of the present paper was to review the available information on this field."

How does 5-LOX influence Crohn's?

Lipoxygenase Inhibitors

Vaxamine

Does pycnogenol reduce Crohn's symptoms?

Proanthocyanidin
"Proanthocyanidin (PA or PAC), also known as procyanidin, oligomeric proanthocyanidin (OPC), leukocyanidin, leucoanthocyanin and condensed tannins, is a class of flavanols. ...

Proanthocyanidins represent a group of condensed flavan-3-ols, such as procyanidins, prodelphinidins and propelargonidins, that can be found in many plants, most notably apples, maritime pine bark, cinnamon, cocoa beans, grape seed, grape skin (procyanidins and prodelphinidins), and red wines of Vitis vinifera (the common grape). However, bilberry, cranberry, black currant, green tea, black tea, and other plants also contain these flavonoids. Cocoa beans contain the highest concentrations . Proanthocyanidins can also be isolated from Quercus petraea and Q. robur heartwood (wine barrel oaks).

Apples contain on average per serving about eight times the amount of proanthocyanidin found in wine, with some of the highest amounts found in the Red Delicious and Granny Smith varieties.

A patented extract of maritime pine bark called Pycnogenol bears 65-75 percent proanthocyanidins (procyanidins). Thus a 100 mg serving would contain 65 to 75 mg of proanthocyanidins (procyanidins).

Proanthocyanidin glycosides can be isolated from cocoa liquor.

The seed testas of field beans (Vicia faba) contain proanthocyanidins that affect the digestibility in piglets and could have an inhibitory activity on enzymes.

Proanthocyanidins have strong anti-oxidant properties. Foods rich in proanthocyanidins have high oxygen radical absorbance capacity which has been linked to numerous health benefits such as weight management, cell health, and cardiovascular health. Scientists continue to research the relevance of proanthocyanidins' strong anti-oxidant properties in vivo for such applications as cancer prevention and cardiovascular health. USDA does maintain a database of proanthocyanidin content and structure for many foods, but dietary supplements proanthocyanidin content has not been well documented."

See Maritime Pine on Wikipedia

Pycnogenol







cox 2 suppression at root

Can curcumin reduce Crohn's symptoms?

Curcumin on Wikipedia
"Curcumin is the principal curcuminoid of the popular Indian spice turmeric, which is a member of the ginger family (Zingiberaceae). ... At present, these effects have not been confirmed in humans. However, as of 2008, numerous clinical trials in humans were underway, studying the effect of curcumin on various diseases, including multiple myeloma, pancreatic cancer, myelodysplastic syndromes, colon cancer, psoriasis, and Alzheimer's disease. In vitro and animal studies have suggested curcumin may have antitumor, antioxidant, antiarthritic, antiamyloid, anti-ischemic, and anti-inflammatory properties. ... Curcumin acts as a free radical scavenger and antioxidant, inhibiting lipid peroxidation[19] and oxidative DNA damage."

Tumeric from the world's healthiest foods

"A Potent, Yet Safe Anti-Inflammatory: The volatile oil fraction of turmeric has demonstrated significant anti-inflammatory activity in a variety of experimental models. Even more potent than its volatile oil is the yellow or orange pigment of turmeric, which is called curcumin. Curcumin is thought to be the primary pharmacological agent in turmeric. In numerous studies, curcumin's anti-inflammatory effects have been shown to be comparable to the potent drugs hydrocortisone and phenylbutazone as well as over-the-counter anti-inflammatory agents such as Motrin. Unlike the drugs, which are associated with significant toxic effects (ulcer formation, decreased white blood cell count, intestinal bleeding), curcumin produces no toxicity.

An Effective Treatment for Inflammatory Bowel Disease: Curcumin may provide an inexpensive, well-tolerated, and effective treatment for inflammatory bowel disease (IBD) such as Crohn's and ulcerative colitis, recent research suggests. In this study, mice given an inflammatory agent that normally induces colitis were protected when curcumin was added to their diet five days beforehand. The mice receiving curcumin not only lost much less weight than the control animals, but when researchers checked their intestinal cell function, all the signs typical of colitis (mucosal ulceration, thickening of the intestinal wall, and the infiltration of inflammatory cells)were all much reduced. While the researchers are not yet sure exactly how curcumin achieves its protective effects, they think its benefits are the result of not only antioxidant activity, but also inhibition of a major cellular inflammatory agent called NF kappa-B. Plus, an important part of the good news reported in this study is the fact that although curcumin has been found to be safe at very large doses, this component of turmeric was effective at a concentration as low as 0.25 per cent&mash;an amount easily supplied by simply enjoying turmeric in flavorful curries.

Relief for Rheumatoid Arthritis: Clinical studies have substantiated that curcumin also exerts very powerful antioxidant effects. As an antioxidant, curcumin is able to neutralize free radicals, chemicals that can travel through the body and cause great amounts of damage to healthy cells and cell membranes. This is important in many diseases, such as arthritis, where free radicals are responsible for the painful joint inflammation and eventual damage to the joints. Turmeric's combination of antioxidant and anti-inflammatory effects explains why many people with joint disease find relief when they use the spice regularly. In a recent study of patients with rheumatoid arthritis, curcumin was compared to phenylbutazone and produced comparable improvements in shortened duration of morning stiffness, lengthened walking time, and reduced joint swelling."

For ideas on how to increase bioavailability, see "Make Mincemeat of Cancer Cells With This Breakthrough Spice" from Mercola.com
"One work-around is to use the curcumin powder and make a microemulsion of it by combining a tablespoon of the powder and mixing it into 1-2 egg yolks and a teaspoon or two of melted coconut oil. Then use a high speed hand blender to emulsify the powder.
Another strategy that can help increase absorption is to put one tablespoon of the curcumin powder into a quart of boiling water. It must be boiling when you add the powder as it will not work as well if you put it in room temperature water and heat the water and curcumin. After boiling it for ten minutes you will have created a 12 percent solution that you can drink once it has cooled down. It will have a woody taste. The curcumin will gradually fall out of solution however. In about six hours it will be a 6 percent solution, so it's best to drink the water within four hours. Dr. LaValley is also helping us beta test new curcumin preparations that will radically simplify this process."

"Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets" in Trends in Pharmcological Targets (2009)
"Extensive research within the past two decades has shown that curcumin mediates its anti-inflammatory effects through the downregulation of inflammatory transcription factors (such as nuclear factor κB), enzymes (such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6)."

"Dietary polyphenols can modulate the intestinal inflammatory response" in Nutrition Reviews (2009)
"Studies, conducted using in vivo and in vitro models, provide evidence that pure polyphenolic compounds and natural polyphenolic plant extracts can modulate intestinal inflammation."

"Anti-Inflammatory Effects of Resveratrol, Curcumin and Simvastatin in Acute Small Intestinal Inflammation " in PLoS ONE (2010)

"In a recent study, Curcumin has been shown to inhibit oxidative stress [36] that in turn has been associated with tight junction opening, thereby modifying intestinal permeability [37]. In the present study, bacterial translocation rates (due to compromised epithelial barrier function) into spleen and cardiac blood after treatment with either compound were lower as compared to the Placebo group. Therefore, Resveratrol, Simvastatin, and Curcumin might modulate tight junction protein expression and function." [See my post entitled "Does Resveratol lessen the symptoms of CD?"]

"Curcumin: Getting Back to the Roots" by Shishodia et al., Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas
"Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors (e.g., NF- B, AP-1, Egr-1, -catenin, and PPAR- ), enzymes (e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g., cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors (e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can modulate the expression of these targets, curcumin is now being used to treat cancer, arthritis, diabetes, Crohn’s disease, cardiovascular diseases, osteoporosis, Alzheimer’s disease, psoriasis, and other pathologies."

"Curcumin has Bright Prospects for the Treatment of Inflammatory Bowel Disease" in Current Pharmaceutical Design (2009)
"... [I]n recent years, a large number of research papers have reported intriguing pharmacologic effects associated with curcumin. These include inhibitory effects on cyclooxygenases 1, 2 (COX-1, COX-2), lipoxygenase (LOX), TNF-α, interferon γ (IFN-γ), inducible nitric oxide synthase (iNOS), and the transcriptional nuclear factor kappa B (NF-κB), in addition to a strong anti-oxidant effect. NF-κB is a key factor in the upregulation of inflammatory cytokines that have a high profile in inflammatory diseases, suggesting that curcumin could be a novel therapeutic agent for patients with IBD. Therefore, in recent years, the efficacy of curcumin has been investigated in several experimental models of IBD. The results indicate striking suppression of induced IBD colitis and changes in cytokine profiles, from the pro-inflammatory Th1 to the anti-inflammatory Th2 type. In human IBD, up to now, only one open study has achieved encouraging results. In this study, patients were given curcumin (360mg/dose) 3 or 4 times/day for three months. Further, curcumin significantly reduced clinical relapse in patients with quiescent IBD. The inhibitory effects of curcumin on major inflammatory mechanisms like COX-2, LOX, TNF-α, IFN-γ, NF-κB and its unrivalled safety profile suggest that it has bright prospects in the treatment of IBD. However, randomized controlled clinical investigations in large cohorts of patients are needed to fully evaluate the clinical potential of curcumin."

"Curcumin for inflammatory bowel disease: a review of human studies" in Alt Med Rev (2011)
"Although two small studies have shown promising results, all authors conclude that larger-scale, double-blind trials need to be conducted to establish a role for curcumin in the treatment of ulcerative colitis. In addition to improving results when used in conjunction with conventional medications for UC, curcumin may pose a less-expensive alternative."

"Novel formulation of solid lipid microparticles of curcumin for anti-angiogenic and anti-inflammatory activity for optimization of therapy of inflammatory bowel disease" in Journal of Pharmact and Pharmacology (2010)
"Objectives This project was undertaken with a view to optimize the treatment of inflammatory bowel disease through a novel drug delivery approach for localized treatment in the colon. Curcumin has poor aqueous solubility, poor stability in the gastrointestinal tract and poor bioavailability. The purpose of the study was to prepare and evaluate the anti-inflammatory activity of solid lipid microparticles (SLMs) of curcumin for the treatment of inflammatory bowel disease in a colitis-induced rat model by a colon-specific delivery approach. ...

Conclusions The degree of colitis caused by administration of DSS was significantly attenuated by colonic delivery of SLMs of curcumin. Being a nontoxic natural dietary product, curcumin could be useful in the therapeutic strategy for inflammatory bowel disease patients."

"Molecular Targets of Dietary Polyphenols with Anti-inflammatory Properties" in Yonsei Med J (2005)
"Studies using isolated bovine COX-1 and COX-2 enzymes showed that curcumin had significantly higher inhibitory effects on the peroxidase activity of COX-1 than that of COX-2"

"Bioavailability of curcumin" post on Margaret's Corner, section on "My Discovery of Curcumin" and her journey with Multiple Myeloma"Pre-, "Pro-, Synbiotics and Human Health"in Symbiotics and Human Health (2010)
"... eating substantial amounts of foods with documented anti-inflammatory effects such as turmeric/curcumin, molecules which might be included in future synbiotic compositions."
See my post "Can ginger reduce the symptoms of CD?"

Does boswellia serrata reduce Crohn's symptoms?

"Therapy of active Crohn disease with Boswellia serrata extract H 15" in Z Gastroenterol (2001)
"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."

"Dietary Factors in the Modulation of IBD: Boswellia Serrat/Indian Frankincense" from Medscape Today News
"A randomized, double-blind controlled study comparing Boswellia serrata extract H15 with mesalamine in patients with Crohn's disease demonstrated no statistical difference in the Crohn's Disease Activity Index, indicating that Boswellia serrata may play a helpful role in Crohn's disease. Other studies have shown possible effectiveness of Boswellia serrata gum resin in patients with ulcerative colitis. Proposed mechanisms of effect of Boswellia serrata include inhibition of 5-lipoxygenase."

"Effects of Boswellia serrata in mouse models of chemically induced colitis" in Am J Physiol Gastrointest Liver Physio (2004) [link is for a full text version]
"The most striking finding in our studies was increased liver size and clear evidence of steatosis, particularly in mice fed the higher dose of methanolic extract of B. serrata. This observation was further confirmed in vitro with human HepG2 cells as a model. Although microarray analyses of hepatic gene expression cannot fully explain this phenomenon, it gives important clues to the potential hepatotoxic effects of Boswellia. ...

Although the results presented in this short report may or may not directly translate into human pathophysiology, this compelling evidence should be a cause for concern and will hopefully prompt more scrupulous toxicological assessment of liver functions in patients participating in clinical trials with B. serrata. Contrary to the widespread popular view that "because it is natural, it is safe," herbal therapy carries more risks and produces more serious side effects than any other form of alternative therapy. Unfortunately, there are no formal data on the ineffectiveness of certain compounds and on the incidence even of acute, severe side effects, such as liver failure, after taking certain herbal medications. This is primarily due to the approach of investigators to negative data and to the skewed peer review process, which favors positive and promising results. Although the pharmaceutical industry recently agreed to give physicians and patients full access to both positive and negative results of clinical trials, a systematic reporting of the collection of ineffective trials and adverse responses to herbs is still missing." [emphases mine]

Boswellia serrata in Alternative Medicine Review (2008)