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COX-2, Inflammation, Potential Natural Inhibitors & Genes

Written by Ana Aleksic, MSc (Pharmacy) | Last updated:
Puya Yazdi
Medically reviewed by
Puya Yazdi, MD | Written by Ana Aleksic, MSc (Pharmacy) | Last updated:

COX-2 is an inflammatory enzyme that many drugs target, including Celebrex and NSAIDs like Motrin. Learn about its link to inflammatory diseases, genetics, and whether researchers have discovered any noteworthy natural COX-2 inhibitors.

What is COX-2?


COX-2 is an enzyme used by the body to produce a family of inflammatory messengers called prostaglandins [1].

Blocking or inhibiting COX-2 reduces prostaglandins, and thus, decreases inflammation [2].

Scientists found that COX-2 is produced by the body as part of an inflammatory response. But similar to many other molecules that play roles in both inflammation and normal states, COX-2 is thought to protect the brain and support cognition. COX-1 is a similar enzyme that can produce inflammatory prostaglandins, but it also protects the stomach lining [3, 1, 4].

Pharmaceutical COX-2 Inhibitors

These anti-inflammatory medications should only be used under medical guidance.

Non-steroidal anti-inflammatory drugs (NSAIDs) and newer coxib drugs like celecoxib (Celebrex) work to lower pain and swelling by blocking COX-2. Typical NSAIDs, such as ibuprofen or aspirin, also block COX-1, however [2, 5]

Since COX-1 protects the stomach, long-term use of NSAIDs may increase the risk of stomach ulcers [5].

Although limited studies have linked the use of coxibs with an increased risk of heart attacks and strokes, the FDA concluded that Celebrex doesn’t pose a greater risk of these complications than typical NSAIDs like ibuprofen. The main safety concerns were centered around a drug called Vioxx that was withdrawn from the market in 2004 [6].

Contact your doctor or pharmacist if you notice side effects from NSAIDs or Celecoxib.

In the US, you may also report side effects to the FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch. In Canada, you may report side effects to Health Canada at 1-866-234-2345.

COX-2 Associated Diseases

Diseases shown here have only been associated with high COX-2 activity in limited studies. A cause-and-effect relationship hasn’t been established in most cases. Work with your doctor or other health care professional for an accurate diagnosis.


COX-2 has been linked with many inflammatory conditions, including rheumatoid arthritis and osteoarthritis. Since COX-2 is suspected to be active in the brain, its overactivity has been linked with neurodegenerative disorders like multiple sclerosis, amyotrophic lateral sclerosis, Parkinson’s disease, and Alzheimer’s disease in limited studies [7, 3].

Cancer Research

It’s still unknown how and whether COX-2 affects cancer risk.

The expression of one COX-2 variant in the Han Chinese has been associated with gastric cancer [4].

Increased expression of COX-2 was associated with melanoma, a form of skin cancer, in another study [8].

Some scientists think that COX-2’s role in regulating cell death may explain the enzyme’s association with cancer, but this is still far from certain. More research is needed to understand these associations [4].

Have in mind that complex inflammatory diseases and cancer always involve multiple possible factors – including biochemistry, environment, health status, and genetics – that may vary from one person to another.

Factors that Increase COX-2

  • Arachidonic acid – arachidonic acid (AA) is a precursor for the inflammatory prostaglandins COX2 produces. That’s why AA increases COX-2 activity and may worsen inflammation [9].
  • Diets high in omega-6 fatty acids may increase arachidonic acid and have proinflammatory effects by raising COX-2, according to some studies [10].
  • Stress [11]

Many other factors that increase inflammation are likely to increase COX-2 [11].

Potential COX-2 Inhibitors List

Research Limitations

Researchers have suggested that several natural compounds may act as COX-2 inhibitors, but their effectiveness and safety haven’t been confirmed in proper clinical trials [12, 13].

Therefore, this list contains preliminary research information that should not be taken to explain any health effects in humans.

When to See a Doctor

If your goal is to inhibit COX-2 to improve your inflammation-related issues, it’s important to talk to your doctor, especially your symptoms are significantly impacting your daily life.

Your doctor should diagnose and treat the condition causing your symptoms.

You may try the complementary approaches listed below if you and your doctor determine that they could be appropriate. Remember that none of them should ever be done in place of what your doctor recommends or prescribes.

Foods & Spices

  1. Fish and seafood (omega-3 fatty acids) [14]
  2. Olive Oil [15]
  3. Grape polyphenols [16]
  4. Mangosteen/Gamma-mangosteen [17]
  5. Berries/Anthocyanins [18]
  6. Avocado/persenone A [19]
  7. Bananas [20]
  8. Citrus Fruits [21]
  9. Mushrooms [22]
  10. Turmeric/curcumin [23]
  11. Ginger [24]
  12. Cinnamon [25]
  13. Cardamon [26]
  14. Fennel [27]
  15. Nutmeg [28]
  16. Aloe vera [29]
  17. Flaxseed [30]
  18. Honey [31]
  19. Soy [32]
  20. Garlic [33]
  21. Bilberry [34]
  22. Keto diet [35]


Supplement-drug interactions can be dangerous and, in rare cases, even life-threatening. Remember to speak with your doctor before taking any supplements. Let them know about any prescription or over-the-counter medication you may be taking, including vitamins and herbal supplements.

If you and your doctor agree that supplementing is a good idea, choose products made by a trusted and reliable manufacturer.

Remember that dietary supplements have not been approved by the FDA for medical use. Supplements generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective.

  1. Fish oil [36]
  2. Pterostilbene [37, 38]
  3. Caffeic acid [39]
  4. Butyrate [40]
  5. Resveratrol [41, 42, 43]
  6. PQQ [44]
  7. Retinoic acid or carnosol [45]
  8. Quercetin [46]
  9. Pomegranate extract [47]
  10. Pycnogenol [48]
  11. Rosmarinic acid [49]
  12. Glucosamine [50, 51]
  13. Chinese skullcap [52]
  14. Oroxylin A, a component of skullcap [53]
  15. Spirulina [54]
  16. Astaxanthin [55]
  17. Bromelain [56]
  18. Chrysin [57]
  19. Pomegranate [58]
  20. Curcumin [59]
  21. Ginger [60]
  22. Boswellia [61]
  23. Honokiol [62]
  24. White willow [63]
  25. Black Cumin [64]
  26. Rooibos [65]
  27. Nettle [66]
  28. Hydroxytyrosol [67]
  29. Anthocyanins (from red raspberries) [68]
  30. Bitter melon [69]
  31. Olive leaf [70]
  32. Tulsi [71]
  33. Amla [72]
  34. NAC
  35. Danshen [73]
  36. Lipoic acid [74]
  37. Astragalus [75]
  38. Rehmannia [76]
  39. Berberine [77]
  40. Reishi [78]
  41. Sulforaphane [79]
  42. Milk Thistle [80]
  43. Zinc [81]
  44. Theanine [82]
  45. Grape seed extract [83]
  46. Lycopene [84]
  47. Epimedium [85]
  48. Emodin [86]
  49. Ursolic acid [87]
  50. Sodium benzoate [88]
  51. Capsicum [63]
  52. Perilla [89]
  53. Black cohosh [90]
  54. Echinacea [91, 92]
  55. St. Johns wort [91]
  56. Wormwood extract [93]
  57. Thunder god vine/Triptolide [94]
  58. Andrographis/Andrographolide [95]
  59. Ginseng [96]
  60. Tea/EGCG [97]
  61. Chamomile [98]
  62. Selenium [99]


Progesterone, the “pregnancy hormone,” is being researched for inhibiting NF-kappaB activation of COX-2 gene production and uterine contractility during pregnancy. It is sometimes used to prevent preterm labor. Progesterone should only be used with a doctor’s prescription for specific, approved indications [100]

COX-2 Genes

SelfDecode has the COX2/PTGS2 Gene and the following SNPs

  1. RS20417 (COX2) GG
  2. RS5275 (COX2) GG

Certain variations in these SNPs have been associated with a couple of diseases. That does not mean having them will increase your risk of the diseases discussed below – data are lacking to make such claims.

PTGS2 (recommended name) or COX-2 (common name) is a gene that codes for the COX-2 enzyme. It is mainly associated with responses to physiological stresses such as infection and inflammation [101, 102].

Limited studies point to associations between certain PGTS2 variations and colorectal [103, 104, 105], prostate [106], and breast cancer risk [107, 101, 108, 105], and type 2 diabetes [109, 110]. The data are still inconclusive and far more research is needed.

About the Author

Ana Aleksic

Ana Aleksic

MSc (Pharmacy)
Ana received her MS in Pharmacy from the University of Belgrade.
Ana has many years of experience in clinical research and health advising. She loves communicating science and empowering people to achieve their optimal health. Ana spent years working with patients who suffer from various mental health issues and chronic health problems. She is a strong advocate of integrating scientific knowledge and holistic medicine.


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