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Nonsteroidal anti-inflammatory drugs (NSAIDs)

Cyclooxygenases (COX, COX-1, COX-2) are enzymes that are responsible for the formation of prostanoids, including prostaglandins, prostacyclins and thromboxane. Prostaglandins are mediators of inflammatory and anaphylactic reactions, and thromboxanes are mediators of vasoconstriction. Cyclooxygenases (COXs) catalyze the conversion of free fatty acids to prostanoids in two steps.

Mechanism of action

The mechanism of the anti-inflammatory action of NSAIDs is based on blocking the enzyme cycloxygenase, which is a mediator of one of the links in the inflammatory reaction cascade.

The analgesic effect of NSAIDs is based on reducing the sensitization of nerve endings to prostaglandins, which reduces the effect of irritants.

The antipyretic effect is associated with a decrease in the synthesis of prostaglandins, due to which they have less influence on the thermoregulation center of the hypothalamus.

What increases COX-2

Factors that increase the production of COX-2 include the following substances:

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  • Arachidonic acid . This acid is a precursor for COX-2, so foods or dietary supplements containing arachidonic acid increase COX-2 activity.(15)
  • Foods high in omega-6 unsaturated fatty acids may help produce more arachidonic acid. Such products may reduce the effectiveness of COX-2 inhibitors, both medicinal and natural.(16)


METABOLISM PATHWAYS OF OMEGA-6 AND OMEGA-3 POLYUNSATURATED FATTY ACIDS AND THE DEVELOPMENT OF INFLAMMATORY AND ANTI-INFLAMMATORY PROCESSES

NSAID groups

NSAIDs are classified according to their chemical structure, effectiveness of average doses, etc.

From a practical point of view, NSAIDs are currently mainly divided into non-selective COX1 and COX2 inhibitors and selective COX2 inhibitors.

As stated above, the anti-inflammatory effect of NSAIDs is based on the inhibition of the enzyme cycloxygenase (COX), which stimulates the inflammatory response. Until the recent past, the action of all manufactured NSAIDs was based on the suppression of COX1 and COX2. Relatively recently (1994) it was found that COX has two varieties - COX1 and COX2. It was found that most of the side effects of NSAIDs are associated with the suppression of COX1, and the anti-inflammatory effect itself is associated with the suppression of COX2. Following this discovery, drugs that selectively inhibit COX2 were synthesized, effectively suppressing inflammation while minimizing side effects.

It should be noted that the anti-inflammatory, analgesic and antipyretic effects of non-selective NSAIDs are still somewhat higher than those of selective ones, and therefore they are still widely used in clinical practice.

COX-2: what is it?

COX-2 is an enzyme used by our body to produce one of the inflammatory proteins called prostaglandin. Blocking or suppressing the production of COX-2 stops the production of prostaglandin, thereby reducing inflammation.

The COX-2 production pathway is also involved in the regulation of cell growth, triggering programmed cell death, and cytokine expression.(1)


COX-2 INHIBITORS AS ANTI-CANCER DRUGS

Factors that reduce COX-2

Scientists suggest that several natural alternative COX-2 inhibitors have a preference for long-term use over NSAIDs.(17)

Hormones

The hormone progesterone NF-kB factor , which is responsible for the activation of the COX-2 gene. Thus, the hormone progesterone can reduce uterine contractility.(18)


SCHEME OF INHIBITION OF COX-1 AND COX-2 BY SOME FLAVONOIDS FROM PLANTS

Food

Science includes food products that can reduce the production of COX-2:

  1. Olive oil . Foods high in polyphenols are good anti-inflammatory sources. Polyphenols can inhibit the production of COX-2.(19)
  2. Grape. Grape polyphenols can also suppress the increase in COX-2 production (tested in mice).(20)
  3. Mangosteen (gamma mangosteen) from Garcinia (21)
  4. All berries are rich in anthocyanins (especially raspberries) (22)
  5. Avocado (Persenone A) (23)
  6. Banana (24)
  7. Citrus (25)
  8. Foods High in Vitamin D (26)
  9. Mushrooms. Considered to be good COX-2 inhibitors with general anti-inflammatory properties (27)
  10. Turmeric (curcumin) is able to stop the production of COX-2, preventing transcription (28)
  11. Ginger is considered one of the most powerful COX-2 suppressors (29)
  12. Nutmeg. The substance myristinis from nutmeg selectively inhibits COX-2 (30)
  13. Aloe vera. The substance aloesin from aloe vera inhibits COX-2 (31)

Substances or biological additives

This list contains substances that, in food or in the form of biological additives, can reduce the production of COX-2:

  1. Fish oil (32)
  2. Pterostilbene (33)
  3. Caffeic acid (34)
  4. Butyrate (35)
  5. Resveratrol (36,37,38)
  6. Pyrroloquinoline quinone (vitamin B14) (39)
  7. Retinoic acid (40)
  8. Quercetin (41)
  9. Pomegranate extract, pomegranate (42, 53)
  10. Pycnogenol (43)
  11. Rosmarinic acid. Considered a potent COX-2 inhibitor (44)
  12. Glucosamine (45.46)
  13. Chinese skull cap (47, 48)
  14. Spirulina (49)
  15. Astaxanthin (50)
  16. Bromelain (51)
  17. Chrysin (52)
  18. Cinnamon (54)
  19. Boswellia (55)
  20. White willow (close to the effect of aspirin) (56)
  21. Black cumin (57)
  22. Rooibos (58)
  23. Nettle (59)
  24. Bitter melon (60)
  25. Cardomonin from Alpinia katsumadai (61)
  26. Olive Leaf Extract (62)
  27. Tulsi (63)
  28. Fennel (64)
  29. Lipoic Acid (65)
  30. Salvia miltiorrhiza (Danshen) (66)
  31. Astragalus (67)
  32. Rehmannia adhesive (68)
  33. Berberine (69)
  34. Sulforaphane (70)
  35. Milk thistle (71)
  36. Reishi (72)
  37. Linen (73)
  38. Zinc (74)
  39. Honey (75)
  40. Soybeans (76)
  41. Theanine from tea (77)
  42. Garlic (78)
  43. Lycopene (79)
  44. Epimedium (80)
  45. Emodin (81)
  46. Blueberries (82)
  47. Ursulic acid (83)
  48. Sodium benzoate (84)
  49. Paprika (85)
  50. Perilla (86)
  51. Black cohosh (87)
  52. Echinacea purpurea (88)
  53. Wormwood extract (89)
  54. Thunder God Vine (90)
  55. Andrographis (91)
  56. Ginseng (92)
  57. EGCG (from tea, especially green) (93)
  58. Chamomile (94)
  59. Selenium (95)

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