Osteoarthritis is a metabolic disease. It is not just a degenerative joint condition.

This small distinction might seem trivial, but it is far from it. Instead, this change in classification will revolutionize the way that we look and treat Osteoarthritis.

Recent scientific breakthroughs have finally identified the missing piece of the arthritis puzzle. Like an unfinished jigsaw puzzle, Osteoarthritis has long been associated with words like: joint pain, inflammation and cell damage. Individually, these symptoms make sense but they were never linked together. However, a link has been established with this re-classification from degenerative joint condition to metabolic disease. This new distinction acts as the final piece of the puzzle that provides a complete picture of Osteoarthritis.

Joints with OA display two major side effects : chronic inflammation and apoptosis (cell death). However, neither side effect is efficiently attacked with current treatment options. Toll-Like-Receptor 4 (TLR4) is a molecule that is one of the largest drivers of inflammation in arthritic joints. Being able to stop or suppress the TLR4 damage will have a dramatic effect on improving joint function. Furthermore, OA increases the rate of cell death in joints and an anti-oxidant that slows down this process could reduce or stop joint degradation at its source. Until recently, trying to find a treatment that can simultaneously target TLR4 and also slow down the degradation of a joint has never been achieved. However, Wogonin has been found to treat both.

A breakthrough in Osteoarthritis research 

Osteoarthritis (OA) has always been known as a ‘wear-and-tear’ or ‘degenerative joint’ disease. Our understanding of the condition has centered on the belief that factors like obesity, joint injury, and age were the sole driving forces behind it. A promising scientific breakthrough has altered this way of thinking.

Studies have now shown that OA is more than just a ‘wear-and-tear’ disease. The Osteoarthritis Research Society International (OARSI) has classified OA as a metabolic disease linked to metabolic processes like diabetes, metabolic syndrome, heart disease, high blood pressure, Alzheimer’s and obesity.

Meta-inflammation caused by some of these factors results in stress and inflammation of the cells. This stress triggers a vicious cycle that leads to cell dysfunction which itself can eventually result in joint damage [2].

The most prominent symptoms of Osteoarthritis are pain and stiffness, and there is a complex web of molecules that increase the inflammatory process. One of these molecules is known as ‘Toll-like receptor-4’ (TLR4). It is one of the biggest culprits of inflammation [3]. So stopping (or suppressing) the actions of TLR4 will stop the inflammation from osteoarthritis.

Studies are being carried out on many different fronts to further our understanding of the link between OA and metabolic processes and to take a closer look at the molecules behind the inflammatory pathway. This means by targeting the cellular level, like TLR4, could be the most promising path. These types of breakthroughs are changing the way we view Osteoarthritis and are helping to craft a better understanding of it.

The treatment of OA

In 2016 the Osteoarthritis Research Society International (OARSI) released a document that read in part: ‘Presently there are NO drugs approved that can prevent, stop, or even restrain progression of OA. Moreover, the available medications that promise to mitigate the pain of OA have a number of risk/benefit considerations.’[4]

But since then, a lot has changed.

Traditionally, Osteoarthritis has been treated with over-the-counter (OTC) anti-inflammatory drugs like Ibuprofen, Aspirin or Acetaminophen. While these drugs have a role to play in the management of OA symptoms, unfortunately, a systemic approach with these drugs and other anti-inflammatory agents can have serious adverse side effects. For example, long-term use of Ibuprofen can lead to severe problems with the liver and kidneys or even an erosion of the stomach lining (known as gastritis). This last symptom can result in internal bleeding [5].

Other available drugs on the market run into different problems.

Treatments such as menthol, camphor, wintergreen or capsaicin work by stimulating nerves in the applied area but the result is a temporary cessation of pain that keeps coming back. Other technologies like Lidocaine and skin patches only mask the symptoms of OA.

The general management of Osteoarthritis has revolved around suppressing its symptoms and keeping the pain at bay. But this has meant dealing with medications that provide temporary pain relief at the cost of unwanted side effects. Without addressing the root cause of the pain, the chronic inflammation of OA is lessened but never gone.

Wogonin is a new supplement that is being used in the revolution against OA. It is a natural compound found in the root of the Skullcap Baicalensis plant and is thought to be a safe and highly effective natural anti-inflammatory [6].

Skullcap Baicalensis has been used for centuries as a Chinese herbal medicine. Over the past 10 years scientists have been studying Wogonin to understand how it reacts with an arthritic joint. Wogonin could be a potential therapeutic agent for diseases such as Osteoarthritis and unlike other over-thecounter products; Wogonin is one of the first treatments of its kind to target the TRL4 receptor to reduce inflammation at its source.

Wogonin and joint inflammation 

The story of joint pain and inflammation is a common one. Joints that experience chronic inflammation will eventually lead to a reduction in joint function, movement and mobility. This is in part due to death of cartilage cells at the joint. Cell death, also known as apoptosis is part of a normal physiological process. The cells naturally go through a cycle of birth, growth and death but in OA, cartilage cells are lost at a faster rate than they are being created. The loss of cells due to cell death leads to the characteristic features of OA including loss of cartilage and abnormal tissue remodeling [7].

As time goes on and the cell death continues unopposed, there is further deterioration of the joint to the point where a joint replacement ends up being the final solution for millions of people. Current medications have not been able to stop this breakdown of the joint or to halt its progression.

However, if the inflammation can be controlled at its source before the process of cell death begins, there is hope that this cycle may be interrupted or even slowed down. This is where Wogonin becomes a game-changer.

Wogonin disrupts the workings of the molecule TLR4, which is involved in this inflammatory process. As a major player in the inflammation pathway, using Wogonin to help stop the actions of TLR4 should see a reduction in the pain and stiffness caused by inflammation.

However, managing inflammation is only one hurdle of OA. Wogonin also works as an anti-oxidant. Anti-oxidants function as the body’s clean-up service. They remove free-radicals which are toxic byproducts of oxygen metabolism. Free radicals can damage sensitive parts of a cell such as proteins, DNA, and cell membranes. Wogonin behaves like an anti-oxidant and a study carried out in 2017 found that Wogonin could also act as a chondroprotective agent and an anti-inflammatory [8].

Unlike other over-the-counter pills that have undesirable side effects or topical applications that temporarily mask symptoms, Wogonin can play a big role in helping manage OA.

Not unsurprisingly, the joint pain of Osteoarthritis can push those with the condition towards a sedentary lifestyle. OA can be a debilitating disease that stops people from performing even the most basic tasks. This promotes further weight gain and exacerbates the factors that worsen OA. The benefits of Wogonin are two-fold: a reduction in joint pain and inflammation and the ability to help OA sufferers maintain a much more active lifestyle.

Summary 

Osteoarthritis is no longer seen as just a simple ‘wear-and-tear’ disease. The Osteoarthritis Research Society International (OARSI), a leading authority in Osteoarthritis research recently classified Osteoarthritis as a ‘serious disease.’ The consideration of osteoarthritis as a serious disease by the Food & Drug Administration (FDA) would allow greater speed in the approval process of a drug that “treats a serious condition and generally provides a meaningful advantage over other available therapies.”

Because OA affects more than 240 million people worldwide and because its prevalence continues to rise, finding new ways to treat this growing problem is a goal that many researchers are working on. Wogonin, which suppresses TLR4 (a prominent molecule in joint inflammation) is a promising new supplement on the horizon. As an anti-oxidant and anti-inflammatory, it is thought to slow down cell death and may also reduce the progression of OA.

Wogonin might well revolutionize the management of OA.

References

1) American Academy of Orthopaedic Surgeons (AAOS). Projected volume of primary and revision total joint replacement in the U.S. 2030 to 2060. March 2018 http://aaos-annualmeeting-presskit.org/2018/research-news/sloan_tjr/

2)Wang, X., Hunter, D., Xu, J., & Ding, C. (2015). Metabolic triggered inflammation in osteoarthritis. Osteoarthritis and Cartilage, 23(1), 22-30. https://www.sciencedirect.com/science/article/pii/S1063458414012801

3) Gómez, R., Villalvilla, A., Largo, R., Gualillo, O., & Herrero-Beaumont, G. (2015). TLR4 signalling in osteoarthritis—finding targets for candidate DMOADs. Nature Reviews Rheumatology, 11(3), 159. https://www.nature.com/articles/nrrheum.2014.209

4) Osteoarthritis: A Serious Disease, Submitted to the U.S. Food and Drug Administration December 1, 2016. https://www.oarsi.org/sites/default/files/docs/2016/oarsi_white_paper_oa_serious_disease_121416_1.p df

5) Matsui H, Shimokawa O, Kaneko T, Nagano Y, Rai K, Hyodo I. The pathophysiology of non-steroidal anti-inflammatory drug (NSAID)-induced mucosal injuries in stomach and small intestine. Journal of Clinical Biochemistry and Nutrition. 2011;48(2):107-111. doi:10.3164/jcbn.10-79. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3045681/

6) Tai, M. C., Tsang, S. Y., Chang, L. Y., & Xue, H. (2005). Therapeutic potential of Wogonin: a naturally occurring flavonoid. CNS drug reviews, 11(2), 141-150. https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1527-3458.2005.tb00266.x

7,8) Khan, N. M., Haseeb, A., Ansari, M. Y., Devarapalli, P., Haynie, S., & Haqqi, T. M. (2017). Wogonin, a plant derived small molecule, exerts potent anti-inflammatory and chondroprotective effects through the activation of ROS/ERK/Nrf2 signaling pathways in human Osteoarthritis chondrocytes. Free Radical Biology and Medicine, 106, 288-301.