Understanding Harpagoside: The Devil that I Came to Adore

Harpagoside: A Natural Anti-Inflammatory Powerhouse
Mechanisms and Safety Profile of Harpagoside
Personal Insights and Practical Advice on Using Devil’s Claw


Harpagoside is a natural compound found in plants like Harpagophytum procumbens, commonly known as devil’s claw. It is known for its anti-inflammatory properties, which are primarily attributed to its ability to inhibit enzymes involved in inflammation pathways, such as cyclooxygenase (COX) and lipoxygenase (LOX). This makes harpagoside a subject of interest in the treatment of conditions like arthritis and other inflammatory disorders.

Ever wonder why they call it the devil’s claw?

Mechanism of Action: Comparison with Aspirin and Steroids

Harpagoside acts more like aspirin rather than steroids. Aspirin belongs to a class of drugs known as nonsteroidal anti-inflammatory drugs (NSAIDs), which work by inhibiting the enzymes COX-1 and COX-2 to reduce inflammation and pain. Similarly, harpagoside inhibits these enzymes (COX and possibly LOX), thereby exerting its anti-inflammatory effects. Steroids, on the other hand, work by suppressing the immune system and inflammation through different mechanisms, primarily by affecting gene expression and protein synthesis. Therefore, harpagoside’s mode of action aligns more closely with aspirin and other NSAIDs rather than steroids.

COX Inhibition

Harpagoside primarily inhibits cyclooxygenase (COX) enzymes rather than lipoxygenase (LOX) enzymes. COX enzymes (specifically COX-1 and COX-2) are involved in the production of prostaglandins from arachidonic acid, which play key roles in inflammation, pain, and fever pathways. By inhibiting COX enzymes, harpagoside reduces the production of these inflammatory mediators, contributing to its anti-inflammatory effects.

Selectivity for COX-2

Harpagoside, derived from the plant Harpagophytum procumbens (devil’s claw), primarily inhibits cyclooxygenase-2 (COX-2) rather than cyclooxygenase-1 (COX-1). COX-1 and COX-2 are enzymes involved in the production of prostaglandins, which are mediators of inflammation and pain. COX-1 is constitutively expressed and plays a role in maintaining normal physiological functions, such as protecting the stomach lining. COX-2, on the other hand, is induced during inflammation and is primarily responsible for producing prostaglandins that contribute to inflammation, pain, and fever.

Harpagoside’s selective inhibition of COX-2 suggests it may provide anti-inflammatory and analgesic effects without affecting the protective functions of COX-1 in the stomach lining. This selective inhibition is similar to some modern NSAIDs (Non-Steroidal Anti-Inflammatory Drugs), which aim to minimize gastrointestinal side effects associated with COX-1 inhibition.

Safety Profile and Side Effects

Gastrointestinal Side Effects: Harpagoside, like aspirin and other NSAIDs, can potentially cause gastrointestinal side effects such as irritation, ulceration, and bleeding in some individuals. These effects are primarily due to the inhibition of COX enzymes, which are involved in the production of protective prostaglandins in the stomach lining. When these prostaglandins are reduced, it can lead to increased susceptibility to irritation and ulceration in the gastrointestinal tract.

Mucus Secretion: Regarding mucus secretion, aspirin and NSAIDs are known to inhibit the production of mucus in the stomach, which can further exacerbate the risk of gastrointestinal side effects. While specific studies on harpagoside’s effects on mucus secretion are limited, its similarity in action to aspirin suggests that it may also have similar impacts on mucus production. However, since harpagoside primarily targets COX-2, it may have a potentially more favorable gastrointestinal safety profile compared to non-selective NSAIDs that inhibit both COX-1 and COX-2. Individual responses to harpagoside may vary, and it’s always recommended to use such supplements under medical supervision, especially for those with underlying health conditions or taking other medications.

Pharmaceutical Comparisons: Common COX-2 Inhibitors

Harpagoside itself is a natural compound and is not marketed under specific brand names like pharmaceutical drugs. However, specific brands of COX-2 inhibitors used in clinical practice are typically synthetic drugs rather than natural compounds like harpagoside. Some well-known pharmaceutical COX-2 inhibitors include:

  • Celecoxib (Celebrex): Celecoxib is a selective COX-2 inhibitor commonly used for the treatment of arthritis and other inflammatory conditions. It reduces pain and inflammation by selectively inhibiting COX-2 enzymes.
  • Rofecoxib (Vioxx): Rofecoxib was a COX-2 inhibitor that was withdrawn from the market due to concerns over cardiovascular risks associated with long-term use.
  • Valdecoxib (Bextra): Valdecoxib was another COX-2 inhibitor that was withdrawn from the market due to safety concerns similar to rofecoxib.

These drugs were developed to provide the anti-inflammatory and analgesic benefits of COX-2 inhibition while minimizing gastrointestinal side effects associated with traditional non-selective NSAIDs (which inhibit both COX-1 and COX-2).

The indigenous peoples of South Africa, particularly the Khoisan, have used devil’s claw for its medicinal effects for many years.

Personal Experience: The Devil that I Came to Adore

Being physically active and competitively partaking in many sports, I’ve sustained my share of musculoskeletal injuries. As a result, I’ve frequently used NSAIDs, particularly indomethacin, for their anti-inflammatory effects. However, I must confess that I have been extremely concerned about the tinnitus (ringing in my ears), disturbing gastrointestinal acid secretion, predisposition to ulcers, and most importantly, their impact on my kidney function. For me, the devil’s claw did magic. It isn’t only the COX-2-like inhibition effects of harpagoside that have won me over; there’s an overall feeling that it’s doing something right for me.

Do I take a high dose of it? Absolutely not! Do I look like a harpagoside addict to you? I only use it extremely moderately and based on need.

Are there any drug interactions we should be aware of? Well, many doctors may not be familiar with the interaction between devil’s claw and commonly used medications, as they are mainly trained to work with classic pharmaceutical compounds and are not generally familiar with herbal and traditional medicinal compounds. On the other hand, those who are familiar with naturopathy and non-FDA-approved supplements may not have the same knowledge as physicians. However, based on my recent literature research, I’d say this: if you’re on blood thinners like warfarin or aspirin, the devil’s claw may increase the risk of bleeding. Similarly, if you’re taking NSAIDs such as ibuprofen or aspirin, it could promote gastrointestinal bleeding. For those on diabetic medications, devil’s claw may further lower blood sugar levels.

My best advice? Avoid polypharmacy and excessive medication use. In my experience, fewer meds often lead to better outcomes. A good doctor will likely agree: less is often more when it comes to medication! If you are not taking any medications whatsoever, including over-the-counter preparations, and you have an inflammatory condition, I would recommend the devil’s claw to you without any hesitation. Otherwise, I highly suggest that you consult your primary healthcare provider or pharmacist, as they are more familiar with drug interactions.

The fact that it’s an herb doesn’t mean you can take it like candy!


While harpagoside from devil’s claw acts similarly to COX-2 inhibitors in terms of COX-2 inhibition, it is generally used as a dietary supplement or herbal remedy. Its effects and safety profile may differ from those of pharmaceutical COX-2 inhibitors. It’s important to note that just because a medication is available over the counter or a compound is labeled as a supplement does not guarantee its safety in all circumstances, whether used alone or in combination with other preparations. Consulting with a healthcare professional before starting any new supplement or medication is always prudent, especially considering potential interactions, side effects, and individual health conditions such as a history of bleeding disorders, gastrointestinal issues, or kidney dysfunctions.

Appendix: Understanding LOX, COX, and Steroids

COX (Cyclooxygenase): There are two main types of COX enzymes: COX-1 and COX-2. These enzymes help produce substances in your body called prostaglandins, which cause pain and swelling (inflammation).

  • COX-1: This enzyme works all the time and helps protect your stomach lining and supports blood clotting.
  • COX-2: This enzyme gets activated when you’re injured or have an infection, leading to pain and inflammation.

LOX (Lipoxygenase): This enzyme also helps create substances that cause inflammation. It works a bit differently from COX but has the same goal: to respond to injury or infection.

Steroids: These are powerful drugs that reduce inflammation by slowing down your immune system. They work differently from COX and LOX inhibitors by going straight into your cells and changing how they produce certain proteins.

In Summary: COX and LOX inhibitors like aspirin and harpagoside reduce inflammation by blocking the enzymes that create inflammatory substances. Steroids also reduce inflammation but work at a deeper level by affecting how your cells produce proteins.

Dr. Eftekar (Dr. E) is the founder and head coach of the Center for Conquest of Longevity and Northwestern Medical Review. A unique attribute of Dr. E is his well-rounded academic background that, in addition to the science of medicine, extends over several other disciplines such as physiology of aging and longevity, philosophy of science and medicine, and integrated kinesiology.

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