Written by Tatjana Djakovic, Staff Writer. A study in mice showed an improvement in the symptoms, using curcumin.
Cystic fibrosis is a genetic disorder that affects approximately 30,000 Americans and 1,000 new cases are diagnosed each year. The defective gene results in the body accumulating abnormally thick, sticky mucus that builds up in the lungs and in the pancreas (1). The most common cause of cystic fibrosis is a deletion of a single amino acid, phenylalanine at position 508 of a protein called “cystic fibrosis regulatory protein”(CFTR), which account for about 69% of all cases of cystic fibrosis (2). This protein is involved in the transport of chloride ions into and out of the cell. CFTR is found in the epithelial cells of the lung, pancreas, sweat glands, vas deferens, and its defect results in varying clinical signs, such as ion transport which does not affect all organs in the same way (3).
The movement of chloride out of the cell is lowered due to the defective CFTR protein, while more sodium ions are absorbed. An ionic gradient develops because the concentration of sodium (positive charge) outside the cell, in mucus increases, while inside of the cell is more negative due to higher concentration of chloride (negative charge) (3). In cystic fibrosis patients, the defective protein is still partially functional as a chloride channel (4). However, it gets degraded in the endoplasmic reticulum (part of the cell responsible for protein production) and therefore does not make it to the cellular membrane (a biological membrane that controls the type of molecules that enter or exit the cell).
Many proteins in the endoplasmic reticulum that are in charge of degrading defective proteins use calcium (5). This suggests the possibility that treatments capable of reducing the concentration of calcium in the endoplasmic reticulum might interfere with the degradation of the protein and therefore allow it to move to the cellular membrane (6).The scientists in this study aimed to identify nontoxic compounds that may work by inhibiting calcium in the endoplasmic reticulum. They tested curcumin, which is the principal component of turmeric, an Indian spice that has been believed to have anti-inflammatory, antioxidant, and perhaps even anticancer properties (7). Curcumin was tested because it inhibits the transport of calcium ions from the cytoplasm into the endoplasmic reticulum (8).
The study was conducted in mice that had cystic fibrosis. The mice were given 45 mg of curcumin per kilogram of body weight by mouth daily for 3 days. Following treatment, the function of CFTR channel across the nasal epithelia was measured using nasal potential difference test. This test measures the salt (sodium and chloride) transport in and out of the cells in the nose. Patients with cystic fibrosis have a greater nasal potential difference, because too much sodium is absorbed into the mucus while the chloride is inside the cell (9).
In the untreated mice with cystic fibrosis, there was a large negative potential. After amiloride (a substance that blocks the sodium channels) was added there was a decreased in nasal potential difference, possibly due to both the sodium and chloride channels not functioning completely. The researchers also added isoproterenol (as substance that stimulates CFTR), but there was no change seen. These signs are all indicative of cystic fibrosis (9).
After curcumin treatment, the average potential difference decreased from -27.9 +/- 0.77 millivolts to -10.8 +/- 0.62 millivolts, (p<0.05) which is an improvement in the function of the CFTR protein by 61.3%. In addition, treating the mice with isoproterenol resulted in a more positive nasal potential difference similar to those in healthy animals (9). These results suggest that symptoms of cystic fibrosis can be improved by the intake of curcumin, although a study in humans would be most beneficial.
Posted July 10, 2013.
References:
- Cystic Fibrosis Foundation. About Cystic Fibrosis: What You Need to Know.
- P.B. Davis, Pediatr. Rev. 22, (2001) 257.
- Domingo-Ribas, C., and M. Bosque-García. “Nasal potential difference test to diagnose cystic fibrosis.” Archivos de Bronconeumología ((English Edition)) 42.1 (2006): 33-38.
- G.M. Denning et al., Nature. (1992). 358, 761.
- S.K. Nigam et al., J Biol. Chem. (1994) 269, 1744.
- M.E. Egan et al., Nature Med. (2002) 8, 485.
- Bengmark, S., and M. D. Mesa. “Gil,(2009). A. plant-derived health—The effects of turmeric and curcuminoids.” Nutricion Hospitalaria 24: 273-281.
- J.G. Bilmen et al., Eur. J. Biochem. (2001) 268, 6318.
- Egan, Marie E., et al. “Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects.” Science 304.5670 (2004): 600-602
