Feb 21, 2023 / Author: China Glutathione suppliers & NMN manufacturers
Recently, a team of scientists from Sichuan University published an article on Nutrients. They found that after NMN treatment, there were positive changes in lung tissue, and inflammatory cells and inflammatory infiltration were significantly reduced, confirming that NMN can indeed reduce lung injury in mice. Supplementation of NMN may be an effective therapeutic strategy to alleviate silicosis.
To mimic silicosis, the researchers induced silicosis by introducing silica powder directly into the airways of mice. Then perfuse the trachea with normal saline, low-dose NMN (500mg/kg) and high-dose NMN (1000mg/kg) every day. Another two control groups were set up, neither of which was treated with silicosis, one with normal saline and one with NMN (1000 mg/kg). The details are shown in Table 1, which are divided into Sham, Vehicle, NMN-H, NMN-L, and NMN-con.
Table 1: Grouping of animal experiment designs
1. NMN can alleviate lung damage caused by silica
Compared with the mice in the Sham group, the lung weight coefficient, pathological score and collagen volume fraction of the mice in the Vehicle group were significantly increased after 28 days of exposure to silica, the lung tissue structure was severely damaged, and the collagen fibers in the interstitial tissue deposition increased significantly. This suggests that silica powder can indeed cause lung damage.
In contrast, the lung tissue structure of the mice in the NMN-H group was relatively complete, and only a small number of small inflammatory cell nodules appeared. The degree of lung injury in the NMN-L group was also lower than that in the Vehicle group, indicating that NMN significantly alleviated the silica-induced lung injury.
Figure 1: Lung weight coefficient, pathological score, and collagen volume fraction of mice in 5 groups after 28 days of exposure to silica powder
2. NMN relieves silica-induced oxidative stress and immune disorders
In order to explore how NMN alleviates silica-induced lung injury, the scientists conducted in-depth research. Since previous studies had identified oxidative stress as a mechanism by which silica causes lung damage, the researchers measured ROS levels in lung cells.
The results were as expected, the ROS level in the lung tissue of the mice in the Vehicle group was significantly increased, and the NMN-H group supplemented with 1000 mg/kg NMN significantly reduced the ROS level. However, the addition of 500 mg/kg NMN-L group did not reduce the ROS level at 7 days, and it was still reduced at 28 days, and the reduction effect was not as good as that of the NMN-H group.
Figure 2: ROS expression (fluorescence intensity) of five groups of mice on day 7 and day 28
Since glutathione (GSH) is one of the main substrates for ROS scavenging, the researchers also measured glutathione levels in lung tissue. The results showed that, compared with the Sham group, the expression of GSH in the lung tissue of the mice in the Vehicle group exposed to silica decreased, while the expression of GSH in the lung tissue increased in a dose-dependent manner after NMN supplementation. Both of these indicators indicated that NMN alleviated the silica-induced lung oxidative stress injury.
In addition, the researchers also examined the immune status of the lung tissue due to the inflammation. The results showed that the proportions of macrophages, CD4+CD69+ T cells and CD8+CD69+ T cells were abnormally increased no matter on day 7 or day 28. This suggests that silica can disrupt the immune balance of lung tissue, leading to inflammatory damage.
However, both 500 mg/kg and 1000 mg/kg NMN could reduce the proportions of macrophages, CD4+CD69+ T cells and CD8+CD69+ T cells in the lung tissue, almost returning to the level of the Sham group. This indicated that NMN relieved the inflammatory damage caused by silica and corrected the immune disorder of lung tissue.
3. NMN up-regulates the expression of antioxidant genes, promotes the synthesis of GSH, and reduces oxidative damage
It is not enough to know that NMN reduces oxidative stress and corrects immune disorders. In order to further understand the protective mechanism of NMN against silicosis, the researchers measured the expression of related genes. Among them, the expressions of Gstm1, Gsto1, Gsta4, and Mgst1 have significant changes, and they are jointly involved in the regulation of various signaling pathways, which have become the focus of research.
Figure 3: Expression of Gstm1, Gsto1, Gsta4, and Mgst1 genes in five groups of mice
Gstm1 and Mgst1 are the target genes of the antioxidant pathway Nrf2, and the expression of Nrf2 mRNA and Nrf2 protein was subsequently measured, and it was found that silica decreased the expression of both, while NMN supplementation increased the expression of both. Through observation, they found that NMN can promote the entry of Nrf2 into the nucleus, which means that NMN may regulate the expression of antioxidant-related genes by promoting Nrf2 expression and nuclear translocation.
After querying the gene interaction network, it was finally found that NMN promoted the synthesis of GSH by up-regulating the expression of Nrf2 and other antioxidant genes, thereby clearing ROS and reducing oxidative damage in the lungs.
Silicosis is a rapidly progressive and incurable disease in which oxidative damage is a typical manifestation of silicosis, which is characterized by elevated ROS levels and decreased GSH. Therefore, reducing oxidative damage is an effective measure to delay the course of silicosis. From this study, we found that NMN ameliorates silica-induced oxidative damage in silicosis by reducing inflammatory cell infiltration, reducing ROS production, and promoting GSH synthesis.
This shows that NMN is a promising method for the treatment of silicosis. Other lung-damaging diseases, such as sepsis-induced lung injury and cigarette-induced lung fibrosis, have also been shown to be positively affected by NMN treatment. Studies have also shown that NMN helps reduce signs of aging and functional decline in the lungs of aged mice.
This suggests that NMN holds promise for the treatment of both those affected by lung injury and those affected by aging lung tissue. But long-term clinical studies are still needed before the benefits of NMN on human lungs can be determined.
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Oct 20, 2023