Flavanol anti-inflammatory properties and Chronic Inflammaory Disease

Osteoarthritis (OA)

The anti-inflammatory properties of flavanols are particularly interesting in the management of chronic inflammatory diseases, such as osteoarthritis (OA). see Video.

Prostaglandins are produced following the sequential oxidation of arachidonic acid (AA), DGLA or EPA by cyclooxygenases (COX-1 and COX-2) and terminal prostaglandin synthases.

COX-1 is responsible for the baseline levels of prostaglandins while COX-2 produces prostaglandins through stimulation. However, while COX-1 and COX-2 are both located in the blood vessels, stomach and the kidneys, prostaglandin levels are increased by COX-2 related inflammation. 

Osteoarthritis can be initiated following trauma. Metabolic processes play an important role in pathophysiology resulting in progressive cartilage degradation and joint pain. For instance, high levels of  AA are generated from damaged cell membrane phospholipids by the action of phospholipase A2. AA is then further metabolized by the cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) enzyme systems to a variety of mediator molecules, including prostaglandin (PG) E2, thromboxanes (TXs) (TXA2), prostacyclins (PGI2), and highly inflammatory leukotrienes such as leukotriene (LT) B4, LTC4, and LTD4.

Conventional pharmacological management of osteothritis involves treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or selective COX-2 inhibitors that block the formation of PGs without modulating 5-LOX enzyme activity. Inhibition of one or both of the COX enzymes may “shunt” AA metabolism down the 5-LOX pathway, which can aggravate toxicity associated with the lack of PGs and excess production of LTs. For example, NSAID-induced gastric ulcers have been shown to have high concentrations of LTB4 in their walls, which attracts leukocytes to the stomach and may contribute to ulceration.

Recently, reports have appeared regarding so-called “dual inhibitors,” flavanol-based agents that co-mediate COX-1 and COX-2, along with 5-LOX. These agents may be particularly effective for managing the metabolic processes underlying osteoarthritis and reducing both gastric and cardiovascular side effects by balancing AA metabolism in the body.

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