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All About COX-2 + Natural Inhibitors List & Genes

Written by Helen Quach, BS (Biochemistry) | Last updated:

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COX-2 is a molecule commonly targeted by anti-inflammatory medications. Learn about the risks and benefits of COX-2 inhibition, the role of COX-2 in the body, and more below.

What is COX-2?

COX-2 is a molecule used by the body to produce a type of inflammatory hormone called prostaglandin [1]. Blocking or inhibiting the COX-2 molecule prevents the creation of prostaglandins, and thus decreases inflammation [2].

COX-2 is only produced by the body as part of an inflammatory response, as opposed to many other molecules with a role in the immune system, which are continually produced to some degree [1].

The COX-2 pathway is also involved in the regulation of cell growth, programmed cell death, and cytokine expression [3].

Inhibition of COX-2 is the mechanism by which traditional non-steroidal anti-inflammatories (NSAIDs), such as ibuprofen or aspirin, reduce sensations of swelling and pain [2].

Inhibiting COX-2

Pharmaceutical COX-2 Inhibitors

Inhibition of COX-2 is the mechanism by which traditional non-steroidal anti-inflammatories (NSAIDs), such as ibuprofen or aspirin, reduce sensations of swelling and pain [2].

NSAIDs typically inhibit both COX-2 and also COX-1, a similarly structured enzyme which helps protect the mucosal lining of the stomach [4]. Long-term use of NSAIDs causes reduced immunity and increases the risk of ulcers due to their inhibition of COX-1 [4].

Relatively recently, drugs that are able to target COX-2 have been created, but the long-term safety of prolonged COX-2 inhibition is uncertain [4].

Medical COX-2 inhibitors also stress the cardiovascular system and increase the risk of heart attack, high blood pressure, heart failure, or kidney failure [5].

NSAID inhibitors of COX-2 decrease the ability of the blood to clot and are a risk for those with bleeding disorders [6]. Increased susceptibility to bleeding caused by NSAIDs can also worsen stomach ulcers [7].

COX-2 and Disease


Because it activates inflammatory pathways, COX-2 is linked to inflammation.

Inhibition of COX-2 has been identified as a potential therapeutic target to treat brain inflammation during a stroke [8].


Expression of a COX-2 variant in the Han Chinese is associated with gastric cancer [3].
Increased expression of a COX-2 is associated with melanoma, a form of skin cancer [9].
COX-2’s role in regulating cell death may explain the enzyme’s association with cancer [3].

Factors that Increase COX-2

  • Arachidonic acid – Arachidonic acid (AA) is a precursor for COX2. Supplementation with AA increases COX2 activity.
  • Diet could affect responses to inhibitor-COX drugs. Diets high in omega-6 would cause more arachidonic acid and have an improved response with COX-2 inhibitors [10].

COX-2 Inhibitors List

Researchers have suggested that several natural alternatives to COX-2 inhibitors have a preferable safety profile compared with NSAID drugs [7].

COX-2 is only produced by the body as part of an inflammatory response [1]. Rather than suppressing the inflammatory response, removal of the underlying inflammation can thus decrease the expression of COX-2 in most cases.

Researchers have suggested that several natural alternatives to COX-2 inhibitors have a preferable safety profile compared with NSAID drugs [711].



  1. Olive Oil: Foods high in polyphenol content are good anti-inflammatory sources. They suppress the production of the protein for COX-2 [13].
  2. Grape – Grape polyphenols were also shown to inhibit the increase in COX-2 due to alcohol treatment in a test done on rats [14].
  3. Mangosteen/Gamma-mangostin [15]
  4. Berries/Anthocyanins [16]
  5. Avocado/persenone A [17]
  6. Banana [18]
  7. Citrus Fruits [19]
  8. MushroomFood high in Vitamin D like mushroom are good inhibitors of COX-2 and are anti-inflammatory [20].
  9. Turmeric: Dietary curcumin (found in turmeric) stopped protein production of COX-2, preventing transcription [21].
  10. Ginger (strong) [22]
  11. Nutmeg: Myristinins isolated from nutmeg selectively inhibited the enzyme COX-2 [23].
  12. Aloe vera: Aloesin derivatives in Aloe vera were found to inhibit COX-2 [24].


  1. Fish oil [25]
  2. Pterostilbene [2627]
  3. Caffeic acid [28]
  4. Butyrate [29]
  5. Resveratrol [303132]
  6. PQQ [33]
  7. Retinoic acid or carnosol [34]
  8. Quercetin [35]
  9. Pomegranate extract [36]
  10. Pycnogenol [37]
  11. Rosmarinic acid (strong) [38]
  12. Ketosis [39]
  13. Glucosamine [4041]
  14. Chinese skullcap [42]
  15. Oroxylin A, a component of skullcap, also prevents COX-2 gene production [43]
  16. Spirulina [44]
  17. Astaxanthin [45]
  18. Bromelain [46]
  19. Chrysin [47]
  20. Pomegranate [48]
  21. Curcumin [49]
  22. Cinnamon [50]
  23. Ginger [51]
  24. Boswellia [52]
  25. Honokiol [53]
  26. White willow [54]
  27. Black Cumin [55]
  28. Rooibos [56]
  29. Nettle [57]
  30. Hydroxytyrosol [58]
  31. Anthocyanins (from red raspberries) [59]
  32. Bitter melon [60]
  33. Cardamonin [61]
  34. Olive leaf [62]
  35. Tulsi [63]
  36. Fennel [64]
  37. Amla [65]
  38. NAC
  39. Danshen [66]
  40. Lipoic acid [67]
  41. Astragalus [68]
  42. Rehmannia [69]
  43. Berberine [70]
  44. Reishi [71]
  45. Sulforaphane [72]
  46. Milk Thistle [73]
  47. Flaxseed [74]
  48. Zinc [75]
  49. Honey [76]
  50. Soy [77]
  51. Theanine [78]
  52. Garlic [79]
  53. Grape seed extract [80]
  54. Lycopene [81]
  55. Epimedium [82]
  56. Emodin [83]
  57. Bilberry [84]
  58. Ursolic acid [85]
  59. Sodium benzoate [86]
  60. Capsicum [54]
  61. Perilla [87]
  62. Black cohosh [88]
  63. Echinacea purpurea [89]
  64. Cichoric acid (from Echinacea) [90]
  65. St. Johns wort [89]
  66. Emodin [91]
  67. Wormwood extract [92]
  68. Thunder god vine/Triptolide [93]
  69. Andrographis/Andrographolide [94]
  70. Ginseng [95]
  71. Tea/EGCG [96]
  72. Chamomile [97]
  73. Selenium [98]


  • NSAIDs such as Ibuprofen, Aspirin, and Bromfenac [99]
  • COX-2 specific inhibitors such as Celecoxib and Lumiracoxib [100, 101]

COX-2 Genes

SelfDecode has the COX2/PTGS2 Gene:

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

PTGS2 (recommended name) or COX-2 (common name) is a gene that codes for the enzyme Prostaglandin-endoperoxide synthase 2 also called cyclooxygenase-2. It is mainly associated with responses to physiological stresses such as infection and inflammation [102, 103].

Several studies indicate that PGTS2 is associated with an increase in colorectal [104, 105, 106], prostate [107] and breast cancer risk [108]. In particular, PTGS2 is probably involved in tumor proliferation and growth, in the formation of metastases and in the resistance of cancer cells to programmed death [102, 109, 106].

Recent studies suggest that PTGS2 is linked with the development of type 2 diabetes [110] and with the promotion of eye disease in diabetes [111].

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About the Author

Helen Quach

BS (Biochemistry)

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