Highlights

  • Naringin protects mouse lungs from aging with less destruction of the lung structure as compared to an induced-aging mouse model.
  • Mice treated with naringin had less cellular stress and increased antioxidant proteins.
  • SIRT1 increased with naringin treatments in an induced-aging mouse model.

Aging is a degenerative condition,associated with failing organs and diminished organ function. The lungs are often among the organs heavily affected by aging and injury, leading to reduced capacity and function. Multiple studies have shown that naringin – a compound found in plant pigments – may have positive effects on the body, including increasing antioxidant defenses and reducing reactive oxygen species (harmful compounds known to cause cellular stress). A new study shows that naringin’s positive effects may also include reducing lung aging and enhancing overall longevity.

The study, out of Egypt and published as a preprint in Life Sciences, focused on mice given D-galactose (a type of sugar) known to create cellular stress to induce lung aging. The scientists assessed whether naringin could help prevent lung aging. Naringin was found to reduce multiple pathways of tissue aging, including programmed cell death (apoptosis) in the lungs, the destruction of the alveoli (the air sacs in the lungs where oxygen is exchanged), and the thickening of the air passage walls (the bronchi). Salama and colleagues also found that naringin may enhance longevity through its stimulation of SIRT1, a protein activated by NAD+ which helps with reducing cellular stress and mitochondrial functioning. The mitochondria is the powerhouse of the cell and is known to be a key player in antioxidant pathways for reducing cellular stress and delaying the aging process. 

“Naringin exerts protective effects against D-galactose-induced lung aging and enhances longevity by activating SIRT1,” the scientist wrote.

Naringin Prevents Lung Aging 

In an effort to tease out how naringin may affect D-galactose induced lung aging, the scientists separated the mice into five groups: untreated, treated with D-galactose alone, treated with 300 mg/kg naringin alone, treated with D-galactose + 150 mg/kg naringin, and treated with D-galactose + 300 mg/kg naringin. The researchers found that the group treated with D-galactose had unhealthy lung tissue with destroyed alveoli, bronchial wall thickening, and increased number of cells undergoing apoptosis, which would likely affect lung function. Meanwhile, those treated with D-galactose + naringin showed gradual improvement across all these lung health parameters as the naringin dose increased.

Naringin Reduces Oxidative Stress

Oxidative stressis a known cause of tissue and organ aging, so the researchers looked at the oxidative stress in the treated mice. They found that the mice treated with naringin and D-galactose had less oxidative stress than those treated with D-galactose alone, while the D-galactose + 300 mg/kg group had less oxidative stress than the D-galactose + 150 mg/kg group. D-galactose also reduced two proteins known to reduce oxidative stress, Nrf2 and NQO1, while naringin increased both proteins. The higher naringin dose, 300 mg/kg, increased the proteins to nearly control levels. This data suggests that naringin may reduce oxidative stress by increasing antioxidant proteins.

(Salama et al., 2023 | Life Sciences) Naringin Reduces Oxidative Stress in Mouse Lungs Mice given D-galactose alone (middle bar – D-gal control) had increased oxidative stress based on MDA levels (left) – an assay for measuring oxidation in tissues and cells – as compared to the untreated, control mice (black – normal control). Additionally, the mice treated with D-galactose and naringin had increased Nrf2, a known antioxidant protein, as compared to those treated with D-galactose alone. a – as compared to the normal control group; b – as compared to the D-gal control; c – as compared to the D-gal + naringin (150 mg/kg) group.

SIRT1 is another protein that has been shown to interact with Nrf2 and reduce oxidative stress by increasing antioxidant activity. SIRT1, and other members of the SIRT family, known as sirtuins, have been shown to help ameliorate various symptoms of aging. When the mice were given D-galactose, the SIRT1 levels in their lungs were significantly reduced. However, when the mice were treated with naringin in addition to D-galactose, their SIRT1 levels were not as reduced. Additionally, naringin was shown to bind to SIRT1 with modeling studies. 

(Salama et al., 2023 | Life Sciences) Naringin Increases SIRT1 in Mouse Lungs Mice given D-galactose alone (middle bar – D-gal control) had decreased SIRT1 levels in their lungs as compared to the untreated, control mice (black – normal control). The addition of naringin helped to increase the SIRT1 levels a bit, although not to the levels of the untreated control mice.
a – as compared to the normal control group; b – as compared to the D-gal control; c – as compared to the D-gal + naringin (150 mg/kg) group.

Naringin and Aging

Salama and colleagues show here how naringin can work to prevent lung aging through its effects on SIRT1 and, subsequently, oxidative stress, a leading cause of aging. Other researchers have shown that naringin has positive effects on the longevity of worms, as well as a beneficial role in delaying Alzheimer’s and Parkinson’s diseases. It has also been shown to positively affect fat and sugar metabolism in mice on Western diets and prevent ovarian aging in chickens. Many other studies have looked at one of the components of naringin, naringenin, and it too has positive effects on aging, ranging from preventing vision loss in mice to increasing worm longevity. 

Overall, naringin has been shown to have beneficial anti-aging effects across multiple organ systems in different species, at least in part due to its effects on SIRT1 and other antioxidant pathways. However, there is still not enough data to say that supplementing with naringin can delay aging. There have been minimal clinical trials with long-term follow-up to assess whether naringin is a useful and effective antiaging therapy. Clinical trials looking at naringenin have shown that it is safe, but its efficacy has also not been determined. More research is needed before naringin can be considered an effective antiaging tool.