NMN Stifles Mouse Inflammation Response Like NSAIDs

NMN Stifles Mouse Inflammation Response Like NSAIDs

NMN has been found to help prevent cancer and insulin resistance by treating macrophages, which are immune cells that are similar to anti-inflammatory medications.

Highlights

• The anti-inflammatory effects of NMN are thought to be due to its ability to counteract the pro-inflammatory effects of oxidants. It is possible that NMN treatment reduces the inflammatory response in macrophages, an immune cell type called macrophages.
• NAG inhibits the formation of inflammatory proteins, such as COX-2, by acting on the body's natural barrier, which is responsible for regulating inflammation.
• NMN inhibits inflammation by inhibiting COX-2 accumulation, which is similar to non-steroidal anti-inflammatory drugs (NSAIDs).

In a vicious circle, inflammatory cells called macrophages that produce more inflammatory stimuli cause chronic inflammation in any region of the body. This continuous inflammation might lead to insulin resistance and atherosclerosis, the formation of plaque in blood vessels. People use non-steroidal anti-inflammatory medications (NSAIDs) such as aspirin or ibuprofen to combat this negative chain reaction.

Prolonged NSAID use, on the other hand, can result in severe consequences such as intestinal bleeding. As a result, people who have persistent inflammation and want to prevent harmful NSAID reactions should look for non-injurious alternatives to relieve it.

Research

According to a recent study published in Epilepsia, nicotinamide mononucleotide (NMN) reverses inflammation-associated molecules, including proteins and byproducts of metabolism, when used on mouse macrophage immune cells. The Tsinghua University researchers reveal that NMN inhibits macrophage inflammatory response in a Frontiers in Molecular Biosciences article.

Future clinical trials might establish that NMN inhibits macrophage-perpetuating inflammation in humans, allowing supplementation to provide a means to avoid side effects of NSAIDs.

Inflammation Alters Metabolic Byproduct Abundance

Previously, NMN has been shown to prevent the development of several ailments in rodents, prompting the study team to examine if it could inhibit widespread inflammation. Long-term use of NMN has already been proven to reduce fat tissue inflammation in mice. Understanding whether NMN therapy inhibits macrophage inflammatory response is a key first step toward seeing if patients might utilize it instead of or in combination with NSAIDs for general discomfort one day.

The scientists at Tsinghua University began their study by looking at metabolic byproduct molecule (metabolite) levels in macrophages during inflammation. The Tsinghua-based team applied big molecules from bacteria called lipopolysaccharides to the immune cells in order to induce a macrophage inflammatory state. Their metabolite measurements before and after the inflammatory stimulation indicated that roughly 22% of the 458 molecules evaluated increased, whereas approximately 23% decreased.

After lipopolysaccharide stimulation, the levels of one of the metabolites measured, NAD+, decreased. Its amounts plummeted after LPS inflammatory activation. The decreasing NAD+ levels associated with inflammation prompted researchers to investigate whether increasing NAD+ would have an effect on inflammatory processes.

NMN Reverses Inflammatory Metabolite Signature

To see whether increasing NAD+ effectively reduces inflammation, the researchers next treated macrophages with NMN and lipopolysaccharide, a pro-inflammatory cytokine that induces an inflammatory response. To determine whether NMN increases NAD+ in macrophages, the team went on to show that it inhibits inflammation-induced metabolite changes. In other words, it reversed some of the metabolite abnormalities caused by inflammation. These findings suggest that NMN supplementation can lower inflammation.

NMN Reverts Inflammation-Associated Protein Levels

To see whether NMN therapy reduces inflammation, the researchers measured pro-inflammatory proteins. With NMN treatment, all of the inflammatory proteins measured were decreased, further proving that NMN decreases the macrophage inflammatory condition.

NMN Dampens NSAID Target Protein Accumulation

In a recent study, researchers led by Professor Seung-Hui Cho at the University of Colorado's Center for Bioinformatics found that mice given NMN had decreased expression of COX-2, an enzyme involved in inflammation and pain that is a target of NSAIDs. By lowering COX-2 levels, NMN may recapitulate some of the pharmacological effects of NSAIDs without producing unwanted side effects.

NMN Dosages and Efficacy

How can we be sure that taking NMN is a safer alternative to lengthy NSAID usage? Up to 1200 mg per day was well tolerated in a study demonstrating that supplementing with NMN encourages greater oxygen utilization in runners. The other two NMN human studies, one which found improved insulin sensitivity and the other improved muscular function, used 250 mg per day. Thus far, the data suggest that while NMN may have better tolerability than NSAIDs, it still has some issues.

Will Future Studies Help Designate NMN to Replace NSAIDs?

“We revealed that the NMN supplementation decreased COX-2 expression,” said Deng and colleagues. “These results suggest NMN replenishment is an effective approach for chronic inflammation treatment.”

The most significant barrier left is to see whether supplementing people with NMN dampens the macrophage inflammatory response since this research was done on mouse macrophages. The next step could be testing NMN in human macrophages and seeing its effects when inflammation is provoked. Only then can we start considering using NMN as an NSAID replacement seriously.