Ginger Compounds May Be Effective in Treating Asthma Symptoms

GingerGourmands and foodies everywhere have long recognized ginger as a great way to add a little peppery zing to both sweet and savory dishes; now, a study from researchers at Columbia University shows purified components of the spicy root also may have properties that help asthma patients breathe more easily.

The results of the study was presented at the American Thoracic Society International Conference (May 17 to 22, 2013) in Philadelphia.

Asthma is characterized by bronchoconstriction, a tightening of the bronchial tubes that carry air into and out of the lungs. Bronchodilating medications called beta-agonists (β-agonists) are among the most common types of asthma medications and work by relaxing the airway smooth muscle (ASM) tissues. This study looked at whether specific components of ginger could help enhance the relaxing effects of bronchodilators.

“Asthma has become more prevalent in recent years, but despite an improved understanding of what causes asthma and how it develops, during the past 40 years few new treatment agents have been approved for targeting asthma symptoms,” said lead author Elizabeth Townsend, PhD, post-doctoral research fellow in the Columbia University Department of Anesthesiology. “In our study, we demonstrated that purified components of ginger can work synergistically with β-agonists to relax ASM.”

To conduct their study, the researchers took human ASM tissue samples and caused the samples to contract by exposing them to acetylcholine, a neurotransmitting compound that causes bronchoconstriction. Next, the researchers mixed the β-agonist isoproterenol with three separate components of ginger: 6-gingerol, 8-gingerol or 6-shogaol. Contracted tissue samples were exposed to each of these three mixtures as well as unadulterated isoproterenol and the relaxation responses were recorded and compared.

At the conclusion of their study, the researchers found that tissues treated with the combination of purified ginger components and isoproterenol exhibited significantly greater relaxation than those treated only with isoproterenol; of the three ginger components, 6-shogaol appeared most effective in increasing the relaxing effects of the β-agonist.

Once they were able to demonstrate that the ginger components enhanced the relaxing effects of the β-agonist, they turned their attention to learning why. First, the researchers wanted to determine if the ginger components might work by affecting an enzyme called phosphodiesterase4D (PDE4D). Previous studies have shown that PDE4D, which is found in the lungs, inhibits processes that otherwise help relax ASM and lessen inflammation. Using a technique called fluorescent polarization, they found that all three components significantly inhibited PDE4D.

Next, the study looked at F-actin filaments, a protein structure which previous studies have shown plays a role in the constriction of ASM, and found that 6-shogaol was effective in speedily dissolving these filaments.

“Taken together, these data show that ginger constituents 6-gingerol, 8-gingerol and 6-shogaol act synergistically with the β-agonist in relaxing ASM, indicating that these compounds may provide additional relief of asthma symptoms when used in combination with β-agonists,” Dr. Townsend noted.”By understanding the mechanisms by which these ginger compounds affect the airway, we can explore the use of these therapeutics in alleviating asthma symptoms.”

Dr. Townsend and her colleague, Dr. Charles Emala, hope future studies will enable them to gain a better understanding of the cellular mechanisms that facilitate ASM relaxation and to determine whether aerosol delivery of these purified constituents of ginger may have therapeutic benefit in asthma and other bronchoconstrictive diseases.

 

ABSTRACT

Active Constituents of Ginger Potentiate β-Agonist-Induced Relaxation of Airway Smooth Muscle
E.A. Townsend, Y. Zhang, C. Xu, R. Wakita, C. Emala
Columbia University – New York, NY/US

Rationale: Asthma prevalence has steadily increased and is characterized by bronchoconstriction. Bronchodilators are the first-line therapy to reverse airway obstruction by relaxing airway smooth muscle (ASM). Asthma therapies include β-agonists that induce bronchodilation by activating adenylyl cyclase, increasing cAMP and activating protein kinase A. Despite improved understanding of the pathogenesis of asthma, few novel therapeutics have been approved for targeting asthma symptoms in the last 40 years. This highlights the need for new therapies that relax contracted airways while also augmenting traditional therapies. We demonstrated that purified components of ginger can relax ASM. By understanding the mechanisms by which these compounds exert their effects on the airway, we can explore the use of these phytotherapeutics in alleviating asthma symptoms. We hypothesized that unique chemical components of ginger have bronchorelaxant properties and work synergistically with β-agonist signaling to relax ASM.

Methods and Results: Epithelial-denuded human ASM tissue (deidentified; exempt from Columbia’s IRB) was contracted with acetylcholine in organ baths. ASM tissues were then relaxed dose-dependently with β-agonist, isoproterenol (100 pM – 10 μM, half-log increments). The tissues were treated concurrently at 300 pM isoproterenol with vehicle, 6-gingerol, 8-gingerol, or 6-shogaol (100 μM). Significant potentiation of isoproterenol-induced relaxation was observed with each of the ginger constituents. 6-shogaol showed the largest leftward shift in the EC50 for isoproterenol. Purified phosphodiesterase 4D enzyme, the prominent isoform in the lung, was used to assess PDE inhibitory action of the ginger constituents using fluorescent polarization analyses. 6-gingerol, 8-gingerol, and 6-shogaol (100 μM, 15 min) significantly inhibited PDE4D compared to vehicle control (0.2% DMSO), the PDE4-selective inhibitor, rolipram (10 μM) and non-selective PDE inhibitor, IBMX (250 μM) were used as positive controls. β-agonist induced depolymerization of actin via a PKA-HSP20-dependent pathway contributes to ASM relaxation. In primary human ASM cells transiently transfected with RFP-actin, treatment with 6-gingerol, 8-gingerol, or 6-shogaol showed acute (within seconds) dissolution of F-actin filaments. This was not due to PKA phosphorylation of HSP20.

Conclusions: Taken together, these data show synergistic effects of ginger constituents 6-gingerol, 8-gingerol, and 6-shogaol with β-agonist in relaxing ASM. This may be attributed to increased cAMP due to PDE4D inhibitory activity. Additionally, these compounds stimulate actin depolymerization through a novel PKA-independent pathway, providing another pathway for potentiation with β-agonists. These compounds may provide additional relief of asthma symptoms when used in combination with β2-agonists and highlight novel use of phytotherapeutics in the treatment of obstructive lung disease.

 

Vitamin D Deficiency Linked With Airway Changes In Children With Severe Asthma

Children with severe therapy-resistant asthma (STRA) may have poorer lung function and worse symptoms compared to children with moderate asthma, due to lower levels of vitamin D in their blood, according to researchers in London. Lower levels of vitamin D may cause structural changes in the airway muscles of children with STRA, making breathing more difficult. The study provides important new evidence for possible treatments for the condition.

The findings were published online ahead of the print edition of the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

“This study clearly demonstrates that low levels of vitamin D are associated with poorer lung function, increased use of medication, worse symptoms and an increase in the mass of airway smooth muscle in children with STRA,” said Atul Gupta, MRCPCH, M.D., a researcher from Royal Brompton Hospital and the National Heart and Lung Institute (NHLI) at Imperial College and King’s College London. “It is therefore plausible that the link between airway smooth muscle mass and lung function in severe asthma may be partly explained by low levels of vitamin D.”

While most children with asthma can be successfully treated with low doses of corticosteroids, about 5 to 10 percent of asthmatic children do not respond to standard treatment. These children have severe therapy-resistant asthma, or STRA, experience more asthma episodes and asthma-related illnesses, and require more healthcare services, than their treatment-receptive peers.

Although previous studies of children with asthma have linked increases in airway smooth muscle mass with poorer lung function and in vitro studies have established a connection between levels of vitamin D and the proliferation of airway smooth muscle, this is the first study to evaluate the relationship between vitamin D and the pathophysiology of children with STRA.

“Little is known about vitamin D status and its effect on asthma pathophysiology in these patients,” Dr. Gupta noted. “For our study, we hypothesized that children with STRA would have lower levels of vitamin D than moderate asthmatics, and that lower levels of vitamin D would be associated with worse lung function and changes in the airway muscle tissue.”

The researchers enrolled 86 children in the study, including 36 children with STRA, 26 with moderate asthma and 24 non-asthmatic controls, and measured the relationships between vitamin D levels and lung function, medication usage and symptom exacerbations.The researchers also examined tissue samples from the airways of the STRA group to evaluate structural changes in the airway’s smooth muscle.

At the conclusion of the study the researchers found children with STRA had significantly lower levels of vitamin D, as well as greater numbers of exacerbations, increased use of asthma medications and poorer lung function compared to children with moderate asthma and non-asthmatic children. Airway muscle tissue mass was also increased in the STRA group.

“The results of this study suggest that lower levels of vitamin D in children with STRA contribute to an increase in airway smooth muscle mass, which could make breathing more difficult and cause a worsening of asthma symptoms,” Dr. Gupta said.

The findings suggest new treatment strategies for children suffering from difficult-to-treat asthma, he added.

“Our results suggest that detecting vitamin D deficiency in children with STRA, and then treating that deficiency, may help prevent or reduce the structural changes that occur in the airway smooth muscle, which in turn may help reduce asthma-related symptoms and improve overall lung function,” Dr. Gupta said.

Before any widespread treatment recommendations can be made, however, larger studies will

“The determination of the exact mechanism between low vitamin D and airway changes that occur in STRA will require intervention studies,” Dr. Gupta said. “Hopefully, the results of this and future studies will help determine a new course of therapy that will be effective in treating these children.”

 

Reference

Gupta A, Sjoukes A, Richards D, Banya W, Hawrylowicz C, Bush A, Saglani S. Relationship Between Serum Vitamin D, Disease Severity and Airway Remodeling in Children with Asthma. Am J Respir Crit Care Med. 2011 Sep 15. [Epub ahead of print]

 

Mother’s Diet Influences Baby’s Allergies — New Research

A possible link between what a mother eats during pregnancy and the risk of her child developing allergies has been identified in new research published in this month’s The Journal of Physiology.

The research found that if a mother’s diet contains a certain group of polyunsaturated fatty acids (PUFAs) – such as those found in fish, walnut oil or flaxseed – the baby’s gut develops differently. The PUFAs are thought to improve how gut immune cells respond to bacteria and foreign substances, making the baby less likely to suffer from allergies.

Until now, several clinical trials have shown that fish and walnut oil supplementation in pregnant women reduces the risk of allergy in their children, but the mechanism was unknown.

“There is intense research interest in maternal diet during pregnancy. In the western diet, the group of polyunsaturated fatty acids that we have shown to help gut function are actually disappearing – our dietary intake of fish and nut oils is being replaced by corn oils which contain a different kind of fatty acid”. Said Dr Gaëlle Boudry, of the INRA research institute in Rennes, France.

“Our study identifies that a certain group of polyunsaturated fatty acids – known as n-3PUFAs – causes a change in how a baby’s gut develops, which in turn might change how the gut immune system develops. These changes are likely to reduce the risk of developing allergies in later life.”

The team found that supplementing a mother’s diet with n-3PUFA caused the new-born’s gut to become more permeable. A more permeable gut enables bacteria and new substances to pass through the lining of the gut into the bloodstream more easily. These new substances then trigger the baby’s immune response and the production of antibodies.

“The end result is that the baby’s immune system may develop and mature faster – leading to better immune function and less likelihood of suffering allergies,” added Dr Boudry.

This research adds to previous studies which have shown that an intake of n-3 PUFAs during pregnancy increases gestational length and maturation of the central nervous system of a baby and that their performance on mental tasks also seemed to be improved in childhood.

“Other studies have found that a diet containing fish or walnut oil during pregnancy may make your baby smarter – our research adds to this, suggesting such supplements also accelerate the development of a healthy immune system to ward off food allergies.”

In terms of next steps, the team’s findings were based on piglets so research will continue to see if they translate to humans. The porcine intestine is an excellent model of the human gut however, so they are hopeful that the findings can be extrapolated. The team also plans to investigate whether the apparent gut function-boosting effects of n-3PUFA that they have identified in new-borns extends into later life.

 

Reference

De Quelen F, Chevalier J, Rolli-Derkinderen M, Mourot J, Neunlist M, Boudry G. n–3 polyunsaturated fatty acids in the maternal diet modify the postnatal development of nervous regulation of intestinal permeability in piglets J Physiol 2011; 589 (17): 4341-4352.

 

Vitamin C May Be Beneficial For Asthmatic Children

Depending on the age of asthmatic children, on their exposure to molds or dampness in their bedroom, and on the severity of their asthma, vitamin C has greater or smaller beneficial effect against asthma, according to a study published in the Clinical and Translational Allergy.

Proposals that vitamin C might be beneficial in the treatment of asthma date back to the 1940s, but the findings from controlled trials have been conflicting.

Drs Mohammed Al-Biltagi from the Tanta University in Egypt and Harri Hemila from the University of Helsinki in Finland analyzed the effect of 0.2 grams per day of vitamin C on 60 asthmatic children aged 7 to 10 years. The effect of vitamin C on the forced expiratory volume per one second (FEV1) was modified by age and exposure to molds or dampness. In the younger children aged 7.0 to 8.2 years with no exposure to molds or dampness, vitamin C administration increased the FEV1 level by 37%. In the older children aged 8.3 to 10 years with exposure to molds or dampness in their bedroom more than one year before the study, vitamin C increased the FEV1 level by only 21%.

The effect of vitamin C on the asthma symptoms was modified by age and the severity of asthma symptoms. In the younger children aged 7.0 to 8.2 years with mild asthma symptoms, the benefit of vitamin C was greatest. In the older children aged 8.3 to 10 years who had severe asthma symptoms, the benefit of vitamin C was smallest.

Drs Al-Biltagi and Hemila conclude that there is strong evidence that the effect of vitamin C on asthmatic children is heterogeneous. They consider that it is important to carry out further research to confirm their findings and to more accurately identify the groups of children who would receive the greatest benefit from vitamin C supplementation.

 

Reference 

Hemila H, Al-Biltagi M, Baset A. Vitamin C and asthma in children: modification of the effect by age, exposure todampness and the severity of asthma. Clinical and Translational Allergy 2011; 1: 9.

 

Allergy Planet

We are in the grip of an allergy epidemic. 50 years ago one in 30 were affected, but in Britain today it is closer to one in three. Why are allergies one of the biggest puzzles of modern medicine? Are we creating a world in which people can’t live?

In search of answers, Horizon travels round the globe, from the remotest inhabited island to the polluted centers of California and the UK. We meet sufferers and the scientists who have dedicated their lives trying to answer the mystery of why we are becoming allergic to our world.

 

 “Allergy Planet” (2008) is a BBC documentary produced and directed by Naomi Austin.  

 

Vitamin A Deficiency Does Not Affect Onset of Asthma

Vitamin A deficiency does not increase the risk of asthma, according to new research published online in the European Respiratory Journal.

In developing countries, vitamin A deficiency is particularly common and previous research has shown that it harms the development of the lungs.

This study aimed to assess whether vitamin A deficiency influences the development of asthma later in life.

The research, which was carried out by scientists at Johns Hopkins University in the USA and Nepalese scientists, analysed over 5,000 people living in a rural area of Nepal, where many people suffer from chronic malnutrition. They assessed whether taking vitamin A supplements at an early age altered the risk of developing of asthma.

The participants were children who had participated in two different studies. In the first, half the children were given vitamin A supplements during their pre-school years and half received a placebo. In the second study, one-third of the mothers of the children each received vitamin A supplements before, during and after pregnancy, and one-third received no supplements.

Ten to fifteen years after the studies were completed, the researchers used questionnaires and a spirometry test, which measures the amount of air in your lungs and how quickly you can breathe out, to assess lung function and whether or not the children had asthma.

The results showed that there was no difference between the children receiving supplements and those that did not receive them, in both groups of participants. The results from the spirometry tests also showed that vitamin A deficiency did not impact upon the risk of wheezing, cough, phlegm and obstructive airways.

Dr William Checkley, lead author from the John Hopkins University, said: “Contrary to what has previously been thought, our findings show that vitamin A deficiency does not lead to an increased risk of asthma. If vitamin A status was linked to asthma, the supplement taken by the study participants, would have led to some reduction in the risk of developing the condition, which we did not see.

“Whilst vitamin A deficiency does affect lung development adversely, we have found no evidence that it is linked with the development of asthma.”