Red ginseng extract reduces signs of CF in rat lungs: Study

Effect believed to enhance activity of chloride transport protein TMEM16A

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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An illustration of a rat in a lab.

Oral red ginseng extract eased the signs of cystic fibrosis (CF) in the lungs of rats, a study reports.

The extract’s effect was thought to enhance the activity of TMEM16A, a chloride transport protein similar to CFTR, which is defective in CF. The treatment improved chloride flow and reduced mucus secretions.

“Therapeutic strategies utilizing TMEM16A potentiators to treat CF airway disease are appropriate and provide a new avenue for mutation-independent therapies,” the researchers wrote in “Red ginseng aqueous extract improves mucociliary transport dysfunction and histopathology in CF rat airways,” a study published in the Journal of Cystic Fibrosis.

CF is caused by inherited defects in CFTR, which regulates the flow of chloride into and out of cells, preventing them from adequately controlling the flow of salt and water. This results in a thick and sticky mucus being produced.

Although CFTR modulator therapies can partially rescue CFTR defects, lung function isn’t fully restored, and not all patients are genetically amenable to these treatments. This makes “effective, mutation-independent therapeutics” urgently needed, wrote researchers associated with the University of Alabama at Birmingham.

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Testing red ginseng extract in rats

Red ginseng aqueous extract (RGAE) enhanced the activity of TMEM16A in cell-based studies. It also improved the flow of mucus, a process referred to as mucociliary transport, which is responsible for clearing particulates and microorganisms from the lungs. The medicinal ingredient in RGAE is thought to be a class of biochemicals called ginsenosides, a type of steroid glycoside.

In this study, the research team tested RGAE in a CF rat model lacking the gene that carries instructions for CFTR. Four-month-old CF rats were randomly assigned to receive daily oral RGAE at a dose of 0.4mg/kg of ginsenosides, or a placebo, for four weeks.

As expected, there was no flow of chloride in the upper airways in untreated CF animals, even when stimulated to enhance CFTR-mediated chloride transport. CF rats treated with RGAE showed significantly more chloride flow when TMEM16A was stimulated by uridine 5-triphosphate (UTP) than untreated CF rats.

RGAE also significantly improved parameters associated with microstructures within airway tissue, as measured by micro-optical coherence tomography. This included airway surface liquid, the distance between the air-mucus interface and the surface of the epithelial layer, and the periciliary liquid, the distance between the mucus layer and the epithelial surface.

The ciliary beat frequency, the motion of hair-like cilia on cell surfaces that propels mucus from the airways, was improved with RGAE. Consistently, the mean mucociliary transport rate was three times faster with treatment than without (1.45 vs. 0.45 mm per minute).

Treatment was found to reduce the number of goblet cells, the primary mucus-secreting cell that lines the airways, and lacked the mucus-distended appearance seen in untreated controls. The thickness of the layer of cells that line the airways, the epithelial layer, was also thinner with treatment, “presumably due to the “loss” of distended goblet cells,” the researchers wrote.

At the same time, the RGAE-treated rats showed a marked decrease in total intracellular mucus levels within nasal cavities. Also, no changes in TMEM16A production (expression) resulted from treatment. Thus, “RGAE did not confer its effect through overexpression of TMEM16A,” the researchers said.

“RGAE is the first known orally bioavailable compound capable of potentiating TMEM16A,” they concluded. “A therapeutic strategy utilizing TMEM16A potentiators to treat CF airway disease is promising and provides a new avenue for mutation-independent therapies that target the [cholride] transport defect in CF.”