Melatonin shows promise as a natural treatment for Sjögren’s syndrome

The activity of certain ‘clock genes’ – those involved in the body’s internal clock or circadian rhythm – is significantly dysregulated in the salivary glands of people with primary Sjögren’s syndrome (PSS) and a model murine of the disease, according to a study.

Treatment with melatonin, a hormone that regulates circadian rhythm and sleep in humans, has been shown to significantly reduce pro-inflammatory immune responses and improve salivary gland function in the mouse model.

These benefits were accompanied by a general restoration of clock gene activity and daily oscillations, supporting a potential link between circadian rhythm abnormalities and pSS – and highlighting melatonin as a potential therapy for this. patient population.

“Our study suggested that… melatonin may be a potential candidate for the prevention and treatment of pSS,” the researchers wrote.

The study, titled “Melatonin dampens immune response and improves salivary gland function in primary Sjögren’s syndromeand conducted by a team of researchers in China, was published in the journal Biochemical pharmacology.

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Sjögren’s syndrome is an autoimmune disorder characterized by abnormal immune attacks on the body’s secretory glands, primarily the lacrimal and salivary glands. It reduces the production of tears and saliva, leading to dry eyes and mouth, also known as dryness symptoms.

A growing body of evidence suggests that circadian clock problems contribute to the onset and progression of autoimmune diseases. However, whether this is true of Sjögren remains largely uncertain.

The circadian rhythm “orchestras the daily rhythms of many physiological, behavioral and molecular processes,” including the production of immune cells and molecules, the researchers wrote.

Melatonin, commonly known as the “sleep hormone,” is primarily produced by the small, pea-shaped pineal gland in the brain. In addition to regulating sleep-wake cycles, it “plays an important role in maintaining circadian rhythm and immunomodulation.”

Additionally, melatonin treatment has shown promise in certain autoimmune diseases, while being safe and well-tolerated, with almost no side effects – features needed in Sjögren’s therapeutic area, the scientists say.

Sjögren’s current first-line treatments typically involve immunosuppressive drugs, but these “inevitably induce a range of side effects” that can be serious, they noted.

“It is imperative to identify a new safe and effective treatment for [successfully] administer pSS patients,” the team wrote.

Their study now assessed whether the activity of circadian clock genes in the salivary glands was dysregulated in pSS patients and mouse models. The team also examined the therapeutic potential of melatonin in these mice.

A total of 10 women were recruited for the study. Seven had pSS but had not received any previous treatment for the disease. The other three were healthy women who served as controls. The median age of the patients was 48.7 years (range 39-58 years) and the control group had a median age of 45.3 years (range 37-53 years). The samples were taken between 9 a.m. and 10 a.m.

The results showed the activity of clock genes with anti-inflammatory effects – in particular, BMAL1, CRY1and CRY2 — were significantly reduced in the salivary glands of pSS patients and mice with pSS-like disease compared to their healthy counterparts.

In turn, pSS was associated with significantly higher activity of genes known to increase inflammation: CLOCK, PER1, PER2and MMR-alpha.

Additionally, differences in 24-hour oscillations were noted for several of these clock genes, particularly CRY2 and ROR-alpha, which showed reversed diurnal patterns between the pSS mouse model and healthy mice.

These data supported a potential link between circadian clock dysregulation and pSS.

The team then assessed the effects of a four-week daily treatment with melatonin in mice with pSS-like disease.

Melatonin treatment nearly restored clock gene activity and daily oscillations in the salivary glands, while significantly improving gland function and reducing immune cell infiltration.

This was accompanied by a significant drop in levels of pro-inflammatory immune cells and molecules and an increase in those with anti-inflammatory effects. In addition, melatonin treatment significantly reduced levels of abnormal antibodies associated with Sjögren’s disease, approaching those seen in healthy mice.

These results highlight the role of the circadian clock in pSS and indicate that melatonin is a “potential approach for the prevention and treatment of pSS,” the researchers wrote.

Notably, since inflammatory molecules can also disrupt the activity and oscillations of clock genes, the observed abnormalities “could not only be the cause but also the consequence of pSS,” the team added.

The researchers noted that further research is needed to clarify “the specific contributions of these clock genes or melatonin-related receptors involved in the effects of melatonin on pSS,” as well as future studies designed appropriately to to assess the effectiveness of melatonin in people with pSS.

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