NMN Ameliorates DNFB-induced Atopic Dermatitis(AD)-Like Symptoms

NMN Ameliorates DNFB-induced Atopic Dermatitis(AD)-Like Symptoms



The inflammation reaction and disruption of the skin barrier caused by oxidative stress play a crucial role in the process of Atopic Dermatitis (AD). Lipid peroxidation levels are often higher in AD patients, while antioxidant levels like Vitamin A, C, and E tend to be lower. Therefore, scientists speculate that reducing oxidative stress might be a strategy in treating AD. It could suppress the release of inflammatory cytokines, alleviate inflammation, and at the same time, reduce the damage caused by reactive oxygen species to the skin barrier, aiding in its repair.
NMN(Nicotinamide Mononucleotide), as one of the precursors to NAD+, effectively activates Sirtuins proteins. SIRT3 enhances the efficiency of electron transfer in respiration, reducing the generation of reactive oxygen species. Moreover, the Sirtuins family can regulate the levels and activity of antioxidant enzymes to decrease oxidative stress. Hence, NMN can be regardede as a potential substance for treating AD.

1. NMN Alleviates Symptoms of AD

Researchers induced Atopic Dermatitis in mice using DNFB. The results showed that compared to the normal group, mice in the DNFB group displayed severe Atopic Dermatitis symptoms on their back skin, characterized by redness, thickening, and scaling. Additionally, the severity of dermatitis, as reflected in the dermatitis score, significantly increased. However, mice treated with 5% NMN or Dex exhibited noticeable alleviation of symptoms on their back skin(as shown in Figure 1).

Figure 1 

Interestingly, the NMN-treated mice showed a significant decrease in dermatitis scores, while the Dex-treated group showed a decreasing trend but not significantly. These findings suggest that NMN effectively alleviates symptoms of AD, with its effects surpassing those of dexamethasone.

2. NMN Reduces Skin Swelling And Itching

Apart from causing prominent skin symptoms, AD also leads to skin swelling and itching, especially itching, significantly affecting the daily lives of patients, notably sleep, consequently inducing negative emotions like depression and anxiety.

Figure 2 

Skin thickness is an important indicator reflecting skin swelling. Results showed that compared to the normal group, mice in the DNFB group exhibited significantly increased skin thickness, while mice treated with NMN or Dex displayed markedly reduced skin thickness(as shown in Figure 2).
Scratching frequency is an indicator that reflects the severity of itching. As expected, compared to the DNFB group, mice treated with NMN and Dex exhibited a significant decrease in scratching frequency.

3. NMN Inhibits the Production of Inflammatory Factors And Restores the Skin Barrier

To better understand the reasons behind NMN's alleviation of AD symptoms, researchers measured levels of IgE, IL-4, and IFN-γ, associated with inflammation. IgE is closely related to allergies, IFN-γ is an anti-inflammatory cytokine produced by Th1 cells, while IL-4 is a pro-inflammatory cytokine produced by Th2 cells.
Results showed that compared to the normal group, DNFB-induced mice displayed significantly elevated levels of IgE, IL-4, and IFN-γ. However, mice treated with NMN and Dex exhibited markedly decreased levels of these markers, indicating that AD activates the immune system and induces allergic reactions. NMN and dexamethasone help to calm down an overactive immune system(as shown in Figure 3).


Figure 3 

Simultaneously, researchers also measured Filaggrin and E-cadherin, closely related to the skin barrier. The results revealed increased expression of these proteins in mice treated with NMN or Dex, indicating the effective protection and restoration of the impaired skin barrier by NMN or dexamethasone.

4. NMN Inhibits the JAK2/STAT5 Pathway, Reducing Oxidative Stress

Researchers speculated that NMN's inhibition of inflammation and restoration of the skin barrier are associated with decreased levels of oxidative stress, which was their primary intent. The findings showed that DNFB-induced mice displayed a significant increase in the phosphorylation of JAK2 and STAT5, indicating the activation of this pathway, leading to inflammation and oxidative stress, resulting in symptoms like skin redness and itching. NMN and Dex effectively inhibited the JAK2/STAT5 pathway, consequently reducing symptoms of Atopic Dermatitis(as shown in Figure 4).

Figure 4

In summary, this study demonstrates that NMN can alleviate symptoms of Atopic Dermatitis by inhibiting the JAK2/STAT5 pathway, reducing oxidative stress levels, subsequently decreasing the production of inflammatory cytokines, and restoring the abnormal differentiation of skin cells. This suggests that maintaining the oxidative-antioxidant balance within patients might be a promising treatment strategy for AD. However, further basic research and clinical trials are needed to validate these findings.
Dexamethasone (Dex) and NMN exhibited comparable efficacy in relieving symptoms of Atopic Dermatitis. Each has its advantages, but long-term use of dexamethasone, as a corticosteroid, tends to have more noticeable side effects, potentially leading to issues like steroid-induced dermatitis. On the other hand, numerous clinical studies indicate that NMN has no significant toxic side effects. If further research evidence supports NMN's efficacy in treating Atopic Dermatitis, NMN might become a mainstream drug for future Atopic Dermatitis treatments.


Reference: 
Gao J., Tang L., et, Nicotinamide mononucleotide ameliorates DNFB-induced atopic dermatitis-like symptoms in mice by blocking activation of ROSmediated JAK2/STAT5 signaling pathway, International Immunopharmacology, 2022.

 

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