There may be certain herbs that have compound that could act as COX-2 inhibitors, but more research is needed. One such herb could be hops.
Inhibition of COX isoforms by nutraceuticals.
J Herb Pharmacother. 2004.
Humans have two isoforms of Prostaglandin H Synthase or cyclooxygenase: COX-1 and COX-2. COX-1 is cytoprotective. COX-2 inhibitors reduce inflammation without the risk of ulceration and kidney damage. The ideal nutraceutical would inhibit COX-2 synthesis while preserving COX-1 synthesis. The hypothesis for this research was that COX inhibitors would fall primarily into three categories: COX-2 specific inhibition, non-specific inhibition (COX-1 and COX-2), and minimal inhibition. For comparison, ibuprofen, rofecoxib, naproxen, and indomethacin were used. Positive results were seen for ipriflavone, resveratrol, amentoflavone, ruscus extract and notoginseng. Glucosamine, nexrutine, and berberine did not inhibit either isoform.
COX-2 and Natural Supplements
In vitro and ex vivo cyclooxygenase inhibition by a hops extract.
Access Business Group LLC, California, USA. Asia Pac J Clin Nutr. 2004.
While there has been much research on botanical materials as potential pain-relieving Cox inhibitors, it has not yet been demonstrated that oral consumption of botanical agents can inhibit Cox2 activity in humans. In particular it would be of interest to determine whether any botanical anti-inflammatory has Cox-1-sparing activity, in order to reduce the risk of gastrointestinal side effects. This two-stage study was designed to first screen a variety of botanicals in vitro, and then to select one or more promising agents to test in human volunteers. Method: Seventeen botanical agents, putative anti-inflammatories or pain-relievers all, were evaluated in vitro for Cox-1 and -2 inhibitory potency and selectivity using a caco-2 cell line with ibuprofen as an active control. A promising compound, a hops extract high in alpha acids, showed a Cox-2/Cox-1 IC50 selectivity ratio of 0.06, compared to 4.2 for ibuprofen. Two different formulations of a standardized hops extract (resin and powder) were compared with ibuprofen in a double-blind, randomized, ex vivo study. Subjects consumed hops powder extract, hops resin extract, or ibuprofen, and provided blood samples before and at intervals for 9 h following the first dose. Plasma was extracted and analyzed in a validated Cox-1 and -2 inhibition assay. Results: There were no differences between active treatments or ibuprofen control in Cox-2 inhibitory action, as indicated by 9-hour Cox-2 Area over the Inhibition Curve (AOC); however, hops powder or hops resin extract produced a 9-hour Cox-1 / Cox-2 AOC ratio of about 0.4 (i.e., some degree of Cox-1 sparing), compared to 1.5 for ibuprofen (i.e. no Cox-1 sparing). Conclusion: Hops exhibited Cox-2 inhibition over 9 hours equivalent to ibuprofen 400 mg but had significant Cox-1 sparing activity relative to ibuprofen. Hops extracts may represent a safe alternative to ibuprofen for non-prescription anti-inflammation.
Q. I have a question about natural cox-2 inhibitors. There are many products on
the market that claim natural inhibition of the cox-2 enzyme such as turmeric,
resveratrol, boswellia etc. As you will be aware pharmaceutical cox-2 inhibitors
have been found to cause increased risk of stroke, and cardiovascular events. If
this is due to the inhibition of the cox-2 enzyme then surely natural ones
should be just as dangerous?
A. The chemical structure of cox-2 inhibiting drugs is quite different from the chemical structure of the compounds in the herbs you mention. An herb has dozens of compounds in it whereas the drug has only one chemical structure. Curcumin and the other herbs influence the body, or influence inflammation in a number of ways. Therefore, even if certain herbs have cox-2 inhibition effect, they will not be as direct or as specific as the drugs. Plus, most of these herbs have been used for hundreds or thousands of herbs and no major ill effect has been determined thus far.
Nutr Cancer. 2015. Cell cycle regulation and apoptotic cell death in experimental colon carcinogenesis: intervening with cyclooxygenase-2 inhibitors. Relative imbalance in the pathways regulating cell cycle, cell proliferation, or cell death marks a prerequisite for neoplasm. C-phycocyanin, a biliprotein from Spirulina platensis and a selective COX-2 inhibitor along with piroxicam, a traditional nonsteroidal antiinflammatory drug was used to investigate the role of cell cycle regulatory proteins and proinflammatory transcription factor NFκB in 1,2-dimethylhydrazine dihydrochloride (DMH)-induced rat colon carcinogenesis. Cell cycle regulators [cyclin D1, cyclin E, cyclin dependent kinase 2 (CDK2), CDK4, and p53], NFκB (p65) pathway, and proliferating cell nuclear antigen (PCNA) were evaluated by gene and protein expression, whereas apoptosis was studied by terminal deoxynucleotidyl transferase dUTP nick end labeling and apoptotic bleb assay. Molecular docking of ligand protein interaction was done to validate the in vivo results. Cyclin D1, cyclin E, CDK2, and CDK4 were overexpressed in DMH, whereas piroxicam and c-phycocyanin promoted the cell cycle arrest by downregulating them. Both drugs mediated apoptosis through p53 activation. Piroxicam and c-phycocyanin also stimulated antiproliferation by restraining PCNA expression and reduced cell survival via inhibiting NFκB (p65) pathway. Molecular docking revealed that phycocyanobilin (a chromophore of c-phycocyanin) interact with DNA binding site of NFκB. Inhibition of cyclin/CDK complex by piroxicam and c-phycocyanin affects the expression of p53 in colon cancer followed by downregulation of NFκB and PCNA levels, thus substantiating the antineoplastic role of these agents.
COX-2 inhibitors and heart disease
The link between COX-2 inhibitors and increased risk of heart attack is now well established. COX-2 inhibitors increase the risk of heart attack by raising blood pressure and making the blood more likely to clot. They do so by the same mechanisms that they use to reduce pain and inflammation.
A large study confirms that Cox -2 Vioxx ( rofecoxib ), but not Celebrex ( celecoxib ), is associated with increased risk of a first heart attack. However, people with a prior heart attack may be at increased risk for experiencing another if they use either selective COX-2 inhibitor. While Vioxx was pulled from the US market due to an elevated risk of heart attacks and stroke in adults, Celebrex remains on the US market. Heart, 2007.
The risk of taking the painkiller Vioxx is more acute than previously thought. One quarter of patients who suffer a heart attack did so within the first 2 weeks of taking their first Vioxx prescription. Merck & Co. Inc. pulled the $2.5 billion-a-year drug from the market in September 2004 after a study showed Vioxx doubled heart attack and stroke risk for patients who took it for 18 months or longer. A Texas jury found in April, 2006 that the COX-2 painkiller caused the death of a 71-year-old man who had taken the drug for less than 1 month, and awarded his family damages of $32 million. Merck faces about 10,000 Vioxx COX-2 related lawsuits.
Arachidonic acid metabolism is involved in acute ischemic syndromes affecting the coronary or cerebrovascular territory. In particular, the efficacy of low-dose aspirin in reducing the complications of acute ischemic syndromes has focused attention on the cyclooxygenase (COX) pathway of arachidonic acid metabolism and its products, collectively termed prostanoids. Two COX isozymes have been characterized, COX-1 and COX-2, that differ in terms of regulatory mechanisms of expression, tissue distribution, substrate specificity and preferential coupling to upstream and downstream enzymes. While the role of platelet COX-1 in acute ischemic diseases is firmly established, the role of COX-2 in atherothrombosis is still uncertain.
2006 - The use of COX2 inhibitor Vioxx (rofecoxib), the anti-inflammatory drug at the center of many high-profile lawsuits, does, in fact, increase the risk of heart attacks and strokes and may also adversely affect kidney function, according to the results of two studies released early by the Journal of the American Medical Association. Both reports suggest that only Vioxx, not other COX-2 inhibitors, markedly raises the risk of these events. Dr. Jingjing Zhang, from Harvard Medical School in Boston, and colleagues conducted an analysis of data from clinical trials to compare the kidney and heart rhythm risks associated with COX-2 inhibitors, including Vioxx, Celebrex (celecoxib), and others. A total of 6,394 adverse kidney events and 286 heart rhythm disturbances occurred in the study group. Statistical analysis suggested no evidence that all COX-2 inhibitors produced these side effects. Compared with inactive "placebo" drug, COX-2 inhibitor Vioxx was associated with a nearly threefold increased risk of heart rhythm disturbances, or "arrhythmias." In addition, use of the drug was tied to elevated risks of kidney problems.
Short term risk of Cox-2
Merck & Co. Inc. provided new data showing that all patients who took the arthritis medicine Vioxx were at increased risk of heart attacks, strokes and other complications. This was reported by National Public Radio in May 2006. Merck, which disputed the report, withdrew Vioxx from the market in September 2004 after a study showed the drug doubled the chances of heart attacks and strokes in patients who took it for at least 18 months. A 107-page report provided to the Food and Drug Administration by Merck included data from a four-year study suggesting the risk started much earlier. Merck is facing thousands of lawsuits alleging harm from the Co-2 inhibitor. A study published online in May 2006 by the Canadian Medical Association Journal said Vioxx may elevate heart-related risks early in treatment. Researchers at McGill University Health Center said their review of three years of data on Vioxx users found one-quarter of patients who suffered a heart attack did so within the first two weeks of taking their first Vioxx prescription. That study showed the cardiovascular risk actually decreased with longer duration of use.
Update August 2006 - Merck failed to warn doctors about the risks of its COX2 painkiller Vioxx and must pay a retired FBI agent $50 million to compensate for the heart attack he suffered after taking the drug. The jury also found that Merck & Co. "knowingly misrepresented or failed to disclose" information about the drug to retired FBI agent Gerald Barnett's doctors. On its verdict sheet, the jury had the chance to assign percentages of fault to Merck and various physicians, but assigned blame only to Merck.
COX-2 and Gastric Ulcer
COX-2 are two cyclooxygenase enzymes responsible for prostanoid
production. COX-2 is expressed in inflammatory cells and fibroblasts of
the gastric mucosa, and through the production of various growth factors
including hepatocyte growth factor (HGF) and vascular endothelial growth
factor (VEGF), plays a key role in the tissue repair process. Aspirin
induces and acetylates COX-2 to produce 15-(R)-epi-lipoxinA4, an
anti-inflammatory mediator thought to protect the gastric mucosa against
aspirin-induced injury. Recently, three different PGE synthases have been
identified, that convert COX-2 metabolites into PGE2. mPGE synthase (mPGES)-1
has been shown to be inducible, and to colocalize with COX-2 in
fibroblasts and macrophages infiltrating the gastric ulcer bed. cPGES and
mPGES-2 have been found expressed in normal gastric mucosa, with no change
in expression levels seen in gastritis or gastric ulcer tissue.
CoX-2 Inhibition and Cancer
Since up to 50% of polyps and 85% of colonic tumors in humans overexpress cyclooxygenase, COX-2 inhibitors have been considered in the treatment of colon cancer.