Forskolin trumps antibiotics for bladder infection

http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/tb/5404


DURHAM, N.C., April 9 -- A common herbal extract may alleviate the pain of a recurrent bladder infection, suggest experiments on mice. Action Points

Explain to interested patients that many bladder infections recur even after apparently successful treatment with Antibiotics .


Explain that this study suggests that some bacteria infect vesicles in the bladder epithelium, and are not affected by Antibiotic therapy, but can remerge, alter and cause a recurrent infection.


Explain that a common herbal extract, forskolin, appears to flush out the vesicles, potentially allowing more complete Antibiotic treatment.


Caution that the experiments are preliminary and were carried out in mice. More research is needed.
The most common cause of a bladder infection is uropathogenic Escherichia coli, and the painful condition often recurs even after apparently successful treatment with Antibiotics , according to Soman Abraham, Ph.D., of Duke University Medical Center.


In experiments in mice, Dr. Abraham and colleagues found that the bacteria appear to hide in vesicles on bladder epithelial cells, where they are protected from Antibiotics , the investigators reported online in Nature Medicine.


But the cells can be flushed out by forskolin, an extract from the Indian coleus plant, which is widely available in health food stores and is used in bodybuilding products, Dr. Abraham and colleagues found.


The key is that forskolin is a powerful elevator of cyclic AMP, which is also a regulator of exocytosis of the bladder epithelial cells, they wrote.


"After customary Antibiotic treatment, the vast majority of the bacteria are either killed by the antibiotics or eliminated during urination," Dr. Abraham said.


"However, there are small numbers of bacteria that survive antibiotic treatment because they sneak into the lining of the bladder," he said, "waiting for the opportunity, after antibiotic treatment, to come out and start multiplying again."


Part of the bladder epithelium is composed of fusiform vesicles that distend as the organ fills with urine, the researchers noted, and experiments in mice showed that E. coli invades bladder epithelial cells using these vesicles.


Treating bladder epithelium with forskolin eliminated more than 99% of the E. coli in the cells, Dr. Abraham and colleagues said.


To test the effect in vivo, the researchers infected female Balb/c mice with E. coli and treated them with either forskolin or saline 24 hours later. The forskolin-treated mice had a 79.4% reduction in the number of bacteria in their bladders, compared with those given saline, a difference that was significant at P≤0.033.


Balb/c mice are naturally resistant to urinary tract infection, the researchers said, but, even so, a day later 33% of the control mice harbored more than 100,000 bacteria in their bladders, versus only 4.1% of the forskolin-treated animals, a difference that was significant at P≤0.01.


In animals prone to urinary tract infections, the effect of forskolin treatment was also significant, reducing bacterial load by 56% (P≤0.03), they said. Also, forskolin significantly reduced (P≤0.0003) the level of interleukin-6 -- a marker of the inflammation associated with urinary tract infections -- in the urine of treated mice.


Taken together, the researchers said, the experiments allow the conclusion that "cAMP regulation may be a new target for future therapies against (urinary tract infection)."


In these experiments, Dr. Abraham said, the animals were given the herbal extract either by injection directly into the bladder or intravenously. The next step is to see whether the extract is effective when mice receive it orally, since that is how it would be used in humans.


"This type of treatment strategy may prove to be beneficial for patients with recurrent urinary tract infections," Dr. Abraham said. "Ideally, use of this herb would expel the bacteria, where it would then be hit with antibiotics. With the reservoir of hiding bacteria cleared out, the infection should not recur."
Tweet