MgIG-Salmeterol Combo Fares Well in Rat Study

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by Steve Bryson, PhD |

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Salmeterol, combined with the root extract derivative magnesium isoglycyrrhizinate (MgIG), eased the signs and symptoms of chronic obstructive pulmonary disease (COPD) in rats, a study demonstrated.

Salmeterol-MgIG combination therapy was more effective than the approved salmeterol-fluticasone combination in improving lung function and reducing inflammation.

The researchers suggested the MgIG-salmeterol combination therapy might be a potential alternative to fluticasone-salmeterol, which is associated with adverse side effects brought on by long-term use.

The study “Efficacy of salmeterol and magnesium isoglycyrrhizinate combination treatment in rats with chronic obstructive pulmonary disease,” was published in the journal Scientific Reports.

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Salmeterol, sold as Serevent, is an approved therapy for breathing difficulties such as wheezing and coughing caused by COPD. Salmeterol is a long-acting bronchodilator that opens the airways and makes breathing easier.

The therapy often is prescribed with anti-inflammatory glucocorticoids, such as the inhaled medicine fluticasone. However, long-term use of this combination may cause adverse events and further aggravation of COPD.

Magnesium isoglycyrrhizinate (MgIG), a derivative of glycyrrhizic acid extracted from the roots of a plant, has been used to treat chronic inflammatory diseases due to its glucocorticoid-like chemical structure.

A team of researchers at the Jiangsu Vocational College of Medicine in China Previously, showed that MgIG as a single treatment reduced lung inflammation in a rat model of COPD.

Now, the team evaluated the combination of salmeterol plus MgIG in COPD rats to determine MgIG’s potential as a COPD add-on therapy.

To induce disease, COPD rats first were exposed to lipopolysaccharide, a potent activator of inflammation, followed by intervals of passive cigarette smoke exposure for up to 45 days. Healthy controls were a group of unexposed rats.

From days 30 to 45, COPD rats were treated with salmeterol or MgIG alone, alongside the combinations of salmeterol-MgIG and salmeterol-fluticasone.

The body weight of control rats typically increased, while the untreated COPD rats lost weight and showed a decline in lung function.

Although all four treatment groups showed significant improvements in body weight and lung function compared to the untreated COPD rats, those treated with the salmeterol-MgIG combination had the best recovery.

In COPD animals, tissue analysis revealed thickening of the airway walls and the formation of mucus plugs, whereas all treatments reduced these features. Notably, COPD rats receiving the salmeterol-MgIG combination demonstrated a “marked improvement” in airway wall thickness and the number of the lung’s tiny air sacs (alveoli).

The team also assessed the levels of certain pro-inflammatory immune-signaling proteins called cytokines in the bloodstream, as well as three types of inflammatory immune cells in the rats’ bronchoalveolar lavage fluid (BALF) — obtained by rinsing the lungs with a salt solution.

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Consistently, untreated rats had significantly more immune cells in the BALF than healthy rats. Likewise, all four treated groups showed significantly reduced cell levels. Moreover, increases in the levels of cytokines — IL-6, IL-1beta and TNF-alpha — in the bloodstream were eased by all four treatments. Salmeterol-MgIG, however, demonstrated the most potent anti-inflammatory effect.

Exposure to cigarette smoke is known to activate the pro-inflammatory signaling pathway called JAK2/STAT3. Again, all treatments reduced the production of JAK2, p-JAK2, STAT3, and p-STAT3 in lung tissue compared to untreated COPD animals, with the most significant effect in those treated with salmeterol-MgIG.

The researchers noted that rats were treated with a dose of salmeterol less than the equivalent dose in humans and thus “safe.”

“Overall, our studies suggested that MgIG might be a potential alternative adjuvant drug for fluticasone for the clinical treatment of patients with COPD,” the authors concluded.