Autoimmune diseases occur when the body's immune system attacks healthy cells instead of protecting them. Systemic sclerosis (SSc) is one such autoimmune disease characterized by impaired circulation and immune system function, which leads to fibrosis (hardening and scarring of healthy tissue) of the skin and internal organs.
ScS is known to affect patients throughout their lives, thereby impairing their quality of life. Although the exact mechanisms of development and progression of ScS are not fully understood, a complex interrelated mechanism of immune, hormonal, environmental and genetic factors is usually involved.
In addition, about 90% of patients with ScS experience a phenomenon known as "Raynaud's phenomenon (RP)." It is associated with spasms of small blood vessels, which leads to decreased blood flow. RF, in turn, can help increase the generation of molecules called reactive oxygen species (ROS). The resulting oxidative environment causes cell damage and fibrosis, which further aggravates the disease.
In this regard, the use of antioxidants to combat oxidative stress is being actively investigated as a therapeutic strategy. However, antioxidant alone may not be sufficiently effective in reducing oxidative stress.
To this end, a team of researchers from Japan, led by Professor Haruhiko Inufusa, chief scientist at the Louis Pasteur Center for Medical Research and distinguished fellow at the Center for Antioxidant Research at Gifu University, investigated the effectiveness of Twendee X (TwX), a dietary supplement consisting of a combination of eight active antioxidants - in reducing oxidative stress in mouse models of ScS.
Explaining the logic behind their work, published March 6, 2024 in the International Journal of Molecular Sciences, Professor Inufusa says: “Research has shown that TwX reduces ROS levels, protects mitochondrial function and improves cognitive performance and memory. Daily management of oxidative stress with this supplement may help not only maintain health and prevent disease, but also improve the symptoms of difficult-to-treat diseases such as Sc.
The eight components of TwX include vitamin C, L-glutamine, niacin, L-cystine, coenzyme Q10, vitamin B2, succinic acid and fumaric acid. The combined antioxidant effect is likely more powerful than the activity of each compound alone. Previous studies have shown improvements in cognitive performance, memory, and motor coordination in mice with dementia, as well as reductions in lesion size, oxidative stress, and inflammation in mouse models of ischemic stroke after treatment with TwX.
Based on these results, the researchers conducted a study on the effects of TwX in a mouse model of ScS using hypochloritic acid (HOCl).
HOCl induction resulted in a significant increase in serum levels of advanced oxidation protein products (AOPP), mimicking the features of ScS. Further induction of HOCl caused thickening of skin tissues along with local and systemic inflammation, fibrosis and vascular damage.
Notably, AOPP levels in mice treated with TwX were significantly lower than in healthy animals. In addition, TwX treatment significantly reduced skin thickness, collagen accumulation, skin levels of hydroxyproline, a marker of oxidative stress, and skin and lung fibrosis.
Additionally, TwX treatment significantly decreased levels of α-smooth muscle actin (α-SMA), a protein that was increased in response to HOCl induction and which has been shown to activate ROS in fibrotic diseases. Animals subjected to HOCl induction and treated with TwX also showed a trend toward decreased levels of inflammatory cytokines and activated immune cells involved in inflammatory responses.
Overall, these results suggest that TwX may treat ScS by regulating oxidative stress and reducing skin and lung fibrosis. Because these results were observed in a mouse model, further studies will be required to confirm the effectiveness of TwX in patients with ScS. However, given the benefits of TwX in other diseases associated with oxidative stress, as well as the lack of side effects, TwX represents significant potential as an antioxidant therapy against ScS.
Professor Inufusa says: "Although TwX is a dietary supplement, it has been tested for drug-level safety and can be used by a wide range of people, from children to adults. In addition, our results suggest that TwX may potentially relieve symptoms intractable diseases associated with oxidative stress, such as ScS."