In this blog post, we will take a broad look at aspirin, from its basic function to its prevention of cardiovascular disease and its recently discovered anti-cancer effects.

Aspirin: Medical possibilities beyond a simple fever reducer

In 1899, German pharmaceutical company Bayer launched aspirin, a drug with antipyretic and analgesic properties. Over the next century, aspirin became one of the most widely used medicines in the world. Aspirin is more than just a pain reliever; it is widely used in the prevention and treatment of various diseases.
Its mechanism of action lies in the inhibition of cyclooxygenase (COX), an enzyme found in cells. COX enzymes break down phospholipids in cell membranes and are involved in the production of physiologically active substances such as prostaglandins and thromboxanes.
Aspirin irreversibly binds to COX enzymes, permanently blocking their activity. This inhibits the production of substances that would otherwise be produced by COX, thereby suppressing various physiological responses such as inflammation, pain, fever, and blood clot formation.

Three types of COX enzymes

COX is classified into three main types.

1. COX-1: An enzyme that is always expressed in most normal cells and plays an important role in maintaining physiological homeostasis, such as protecting the stomach lining, maintaining kidney function, and regulating platelet function.
2. COX-2: Normally, it is rarely expressed, but during inflammatory responses, it is induced by stimuli from immune cells and vascular endothelial cells.
3. COX-3: Mainly expressed in the central nervous system, especially in the hypothalamus, it is involved in nerve responses related to body temperature regulation and pain.

When COX is activated in this way, various bioactive substances are produced depending on the characteristics and conditions of each tissue. For example

• Prostaglandin E2 (PGE2) is produced in the gastric mucosal cells to protect the mucosa from stomach acid.
•  PGE2, which is associated with inflammatory responses, is produced in immune cells, causing pain and fever.
• Blood vessel endothelial cells produce prostacyclin (PGI2), which inhibits blood clotting.
• Platelets produce thromboxane A2 (TXA2), which induces blood clotting.

Main effects of aspirin: analgesia, antipyresis, anticoagulation

The clinical effects of aspirin can be broadly divided into two categories.
First, it has analgesic and antipyretic effects. When inflammation occurs, COX-2 in immune cells is activated, producing prostaglandins that cause pain. Aspirin inhibits this process, thereby exerting its analgesic effect. It also has an antipyretic effect by inhibiting COX-3 in the central nervous system, especially in the hypothalamus.
Second, it inhibits blood clotting. When bleeding occurs, COX-1 in platelets is activated, producing thromboxane A2, which induces blood clotting. Aspirin irreversibly inhibits COX-1, blocking this process and thereby exerting an antithrombotic effect. In particular, platelets do not have nuclei and cannot regenerate COX-1 once it has been inhibited, so the effect of a single dose of aspirin lasts until the platelets reach the end of their lifespan.
However, this effect can be safely utilized by adjusting the dosage appropriately. For example, low doses of aspirin (75 to 350 mg per day) are effective in reducing the risk of blood clots by decreasing COX-1 activity in platelets, without significantly affecting the ability to stop minor bleeding.
The results of several clinical trials conducted in the 1970s showed that long-term use of low-dose aspirin in patients with cardiovascular disease significantly reduced the incidence of thrombotic events such as myocardial infarction and stroke. As a result, aspirin has expanded its use from a simple antipyretic to a drug for the prevention of cardiovascular disease.

Side effects of aspirin and alternative drugs

However, aspirin also has side effects. The most common side effects are gastrointestinal symptoms.
Prostaglandins produced in the stomach protect the stomach lining, but aspirin reduces this protective function by inhibiting COX-1.
Furthermore, aspirin itself is an acidic substance, which can directly irritate the stomach lining. This can cause problems such as gastritis, stomach ulcers, and stomach bleeding, and caution is required when using aspirin in patients with gastrointestinal diseases or rheumatism who require long-term medication.
In addition, due to its anticoagulant effect, it can have harmful effects on patients at high risk of bleeding, such as those undergoing surgery or those with hemophilia.
To overcome these disadvantages, alternative drugs with the same analgesic mechanism as aspirin but with relatively fewer side effects have been developed.

• Ibuprofen: Acts by reversibly binding to COX enzymes.
• Celecoxib and Rofecoxib: These drugs selectively inhibit COX-2, reducing gastrointestinal side effects. These drugs are used as alternatives to aspirin, maintaining its analgesic and antipyretic effects while minimizing side effects such as gastrointestinal disorders.

New possibilities for aspirin

Recent studies have expanded the scope of aspirin’s effects. Representative examples include

• Cancer prevention and suppression. Some cancer cells increase COX expression during growth, and aspirin suppresses this expression, thereby preventing the growth and metastasis of cancer cells.
• Aspirin also promotes the production of nitric oxide (NO), which suppresses inflammatory responses, and
• NF-κB, thereby suppressing immune responses.

These mechanisms suggest that aspirin has potential as more than just a pain reliever, but also as an anti-inflammatory, anti-cancer, and immune-regulating drug. Accordingly, aspirin is expected to be clinically useful in the prevention of various chronic inflammatory diseases, autoimmune diseases, cardiovascular diseases, and cancer in the future.

Conclusion

Aspirin started out as a simple antipyretic and analgesic in the late 19th century, but today it is recognized for its medical value in various fields, including the prevention of cardiovascular disease, cancer suppression, and inflammation and immune regulation. Of course, it is a drug that requires caution due to its side effects, but with the correct dosage and appropriate patient selection, it can be one of the most inexpensive and effective drugs available.
Aspirin, which was once a “basic medicine,” is now one of the important treatment strategies in modern medicine, and its clinical applications are expected to expand further through various studies in the future.