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Treat Your Asthma Gingerly

ginger-rootIf numbers can be trusted (99% of all statistics being made up on the spot), there are almost 25 million cases of asthma in the United States. Out of almost 314 million people in the country, that equates to almost 8% of the population. More than 3,000 Americans die from asthma each year. The annual cost for prescription drugs exceeds 6 billion dollars, and, as reported in 2012, asthma cases have increased 48% in the last ten years. (http://www.statisticbrain.com/asthma-statistics/, from the American Lung Association). Wow, that’s quite an indictment.

Asthma is a condition in which airways become narrowed, swell and produce extra mucus, making it difficult to breathe. It triggers coughing, wheezing and shortness of breath. For the lucky few, it’s only a minor nuisance; for others, it can be a major problem that interferes with daily life and might lead to a life-threatening asthma attack. Although asthma has no cure, it can be controlled. Once in a while symptoms flare up in certain situations, such as the exercise-induced asthma that worsens when the air is cool and dry, or the occupational asthma that assaults people in a workplace where exposure to fumes, chemicals or gases are the norm.

The odds of developing the condition increase among smokers, those whose mothers smoked during pregnancy, those assailed by second-hand smoke, people having other allergic conditions, or those having a blood relative with asthma. Symptoms that interfere with sleep, work or recreational activities need serious attention and a visit to a physician.

The inhaled corticosteroids commonly prescribed to treat asthma claim to have fewer adverse effects than the oral steroids used for other inflammatory conditions, such as arthritis and allergies. But that is purely subjective. These medications are used for the long haul, as are the oral leukotriene modifiers that include Singulair and its kin. Leukotrienes are endogenous chemicals that mediate responses in allergic reactions and inflammation, and their modification with drugs is linked, albeit weakly, to psychological reactions characterized by aggression, agitation, hallucinations, depression and suicidal thoughts. No completed suicides have been reported, however (Philip, 209). That’s reassuring. Yep. Other medications are used in combination with inhaled corticosteroids, but have the nasty habit of occasional exacerbation of symptoms. A drug seldom used nowadays is theophylline, a pill that relaxes the muscles around the airways to keep them open. Originally extracted from tea leaves and later found in cocoa, theophylline is one hundred percent bioavailable, but its side effects are equally disturbing, and are worsened in the presence of fatty meals.

But the future is bright. On the horizon are compounds extracted from ginger, the zingy spice that livens up our baked goods. Traditionally used to treat stomach upset, including that from motion sickness (Langner, 1998), ginger has found its way into the grab bag of integrative medicine, where its anti-inflammatory nature finds favor with sufferers of arthritis, hypercholesterolemia (Madkor, 2011), elevated glucose (Akhani, 2004), and even hypertension (Ghayur, 2005) and worms (Mostafa, 2011) (Lin, 2010).

Researchers at Columbia University have discovered that the bronchoconstriction of asthma can be attenuated with ginger compounds that work synergistically with  medications called beta-agonists, the best-known probably being Albuterol. The relaxation of airway smooth muscle is the goal. When the drug and the natural components were combined, relaxation response was remarkable (Townsend, 2013). Of the ginger isolates, one called 6-shogaol was most effective in its relaxing effects. This constituent of ginger is similar in structure to the better-known gingerol, the most active ingredient of the herb which is related to compounds appearing in chilies and black pepper, capsaicin and piperine respectively. Shogaol is produced when ginger is dried or cooked. As far as pungency, it falls between capsaicin and piperine on the heat scale.

In the lungs there is an enzyme called PDE4D which interferes with the relaxation of the airways. The elements of ginger stop this enzyme from flaunting its attributes. To further aggravate asthma, there also exists a protein structure that plays a role in the constriction of airways and the contraction of muscles, named F-actin filament.
6-shogaol dissolves these filaments rapidly. While there is support for the idea that asthma can be outgrown as musculature matures (Chitano, 2005), there is comfort in knowing that management of the disease is readily obtainable and that all-natural adjuvants are in the offing. Calcium signaling is part of the muscle contraction process. With some blood pressure medicines, calcium is inhibited and vessels relax to allow the smooth passage of blood. It was found that ginger has an activity like that of verapamil, a calcium-channel blocker, in that it can ease the contraction of the smooth muscle that controls airways (Ghayur, 2008).

In the decade preceding the 21st century, plants have been documented to be useful in the treatment of various respiratory disorders, including asthma. In fact, the use of natural products has increased dramatically all over the world. Not only have they affected bronchodilation, but also mast cell stabilization, anaphylaxis, and overall leukotriene modulation (Mali, 2011). (Mast cells, by the way, are those that release histamine in response to injury, allergy or inflammation.) To the delight of alternative-minded practitioners, many of these medicinal plants provide relief of symptoms equal to allopathic medicines (Bielory, 1999).

We might be reminded to enjoy our spices, especially those with anti-inflammatory characteristics, such as ginger and its close cousin, turmeric, but to be prudent if taking blood thinners. That the therapeutic value of ginger is enhanced by its mineral constituents (Latona, 2012) adds another dimension to the study of its universal appreciation.

References

Akhani SP, Vishwakarma SL, Goyal RK.
Anti-diabetic activity of Zingiber officinale in streptozotocin-induced type I diabetic rats.
J Pharm Pharmacol. 2004 Jan;56(1):101-5.

Bielory L, Lupoli K.
Herbal interventions in asthma and allergy.
J Asthma. 1999;36(1):1-65.

Chitano P, Wang L, Murphy TM.
Mechanisms of airway smooth muscle relaxation during maturation.
Can J Physiol Pharmacol. 2005 Oct;83(10):833-40.

Ghayur MN, Gilani AH.
Ginger lowers blood pressure through blockade of voltage-dependent calcium channels.
J Cardiovasc Pharmacol. 2005 Jan;45(1):74-80.

Ghayur MN, Gilani AH, Janssen LJ.
Ginger attenuates acetylcholine-induced contraction and Ca2+ signalling in murine airway smooth muscle cells.
Can J Physiol Pharmacol. 2008 May;86(5):264-71.

Hirst SJ.
Airway smooth muscle as a target in asthma.
Clin Exp Allergy. 2000 Jun;30 Suppl 1:54-9.

Langner E, Greifenberg S, Gruenwald J.
Ginger: history and use.
Adv Ther. 1998 Jan-Feb;15(1):25-44.

Latona DF, Oyekele GO, Olayiwola OA
Chemical analysis of Ginger Root
IOSR Journal of Applied Chemistry (IOSRJAC). Volume 1, Issue 1; May/June 2012: 47-49

Levy AS, Simon O, Shelly J, Gardener M.
6-Shogaol reduced chronic inflammatory response in the knees of rats treated with complete Freund’s adjuvant.
BMC Pharmacol. 2006 Oct 1;6:12.

Lin RJ, Chen CY, Lee JD, Lu CM, Chung LY, Yen CM.
Larvicidal constituents of Zingiber officinale (ginger) against Anisakis simplex.
Planta Med. 2010 Nov;76(16):1852-8.

H Ling, H Yang, S-H Tan, W-K Chui, E-H Chew
6-Shogaol, an active constituent of ginger, inhibits breast cancer cell invasion by reducing matrix metalloproteinase-9 expression via blockade of nuclear factor-κB activation
British Journal of Pharmacology. Volume 161, Issue 8, pages 1763–1777, December 2010

Madkor HR, Mansour SW, Ramadan G.
Modulatory effects of garlic, ginger, turmeric and their mixture on hyperglycaemia, dyslipidaemia and oxidative stress in streptozotocin-nicotinamide diabetic rats.
Br J Nutr. 2011 Apr;105(8):1210-7.

Mali RG, Dhake AS.
A review on herbal antiasthmatics.
Orient Pharm Exp Med. 2011 Aug;11(2):77-90.

Mostafa OM, Eid RA, Adly MA.
Antischistosomal activity of ginger (Zingiber officinale) against Schistosoma mansoni harbored in C57 mice.
Parasitol Res. 2011 Aug;109(2):395-403.

Philip G, Hustad C, Noonan G, Malice MP, Ezekowitz A, Reiss TF, Knorr B.
Reports of suicidality in clinical trials of montelukast.
J Allergy Clin Immunol. 2009 Oct;124(4):691-6.e6.

Ramji, Divya; ho, chi; Huang, Qingron; Rafi, Mohamed; Huang, Mou
Isolation of gingerols and shogaols from ginger and evaluation of their chemopreventive activity on prostate cancer cells and anti-inflammatory effect on 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear inflammation
RUcore – Rutgers University Community Repository. 2007
http://mss3.libraries.rutgers.edu/dlr/showfed.php?pid=rutgers-lib:21328

Sehwan Shima, Sokho Kima, Dea-Seung Choia, Young-Bae Kwonb, Jungkee Kwona
Anti-inflammatory effects of [6]-shogaol: Potential roles of HDAC inhibition and HSP70 induction
Food and Chemical Toxicology. Volume 49, Issue 11, November 2011, Pages 2734–2740

Townsend EA, Yim PD, Gallos G, Emala CW.
Can we find better bronchodilators to relieve asthma symptoms?
J Allergy (Cairo). 2012 ;2012:321949. doi: 10.1155/2012/321949. Epub 2012 Oct 2.

Townsend EA, Siviski ME, Zhang Y, Xu C, Hoonjan B, Emala CW.
Effects of ginger and its constituents on airway smooth muscle relaxation and calcium regulation.
Am J Respir Cell Mol Biol. 2013 Feb;48(2):157-63.

Wang L, Pozzato V, Turato G, Madamanchi A, Murphy TM, Chitano P.
Reduced spontaneous relaxation in immature guinea pig airway smooth muscle is associated with increased prostanoid release.
Am J Physiol Lung Cell Mol Physiol. 2008 May;294(5):L964-73.

Wu H, Hsieh MC, Lo CY, Liu CB, Sang S, Ho CT, Pan MH.
6-Shogaol is more effective than 6-gingerol and curcumin in inhibiting 12-O-tetradecanoylphorbol 13-acetate-induced tumor promotion in mice.
Mol Nutr Food Res. 2010 Sep;54(9):1296-306.

Zick SM, Djuric Z, Ruffin MT, Litzinger AJ, Normolle DP, Alrawi S, Feng MR, Brenner DE.
Pharmacokinetics of 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol and conjugate metabolites in healthy human subjects.
Cancer Epidemiol Biomarkers Prev. 2008 Aug;17(8):1930-6.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

What Gets YOU Inflamed?

knee-inflammationAre you an adult? Would you prefer the pound(s) of cure to the ounce of prevention? One of the sad commentaries about adulthood is that we don’t take care of ourselves until something hurts, the detection of which relies on the nervous system. The nervous system is plastic, meaning that it exhibits a wide range of responses according to different conditions. The perception of pain depends on more than one factor, the environment included. With inflammation, however, there exists a hypersensitivity state that makes us aware of what’s going on. This realization is called nociception, involving a network that identifies a noxious condition that evokes responses ranging from mild to severe. Once the pain message is recognized by the nervous system it registers as an “ouch.” The greater the intensity of the stimulus, the greater is the perception of pain. In some cases, no external trigger is needed, such as one would experience with arthritis pain.

Inflammation is the body’s attempt at self-protection, the intention of which is to remove the harmful stimuli, including damaged cells, irritants or pathogens. If the stimulus comes from outside, it can be removed, although pain may linger. If it comes from inside, the body is left to its own devices. In either instance, tissue repair is the ultimate goal. To our dismay, inflammation may beget further inflammation in a self-perpetuating cascade. This occurs because of cellular alterations that cause mediator chemicals to be released and certain white cells, called macrophages, to become activated. The job of the macrophage is to swallow (-phage) the debris that comes from, or causes, tissue damage. Without inflammation, infections and wounds would never heal. In fact, too much anti-inflammatory medication, such as cortisone, slows wound healing (Goforth, 1980). The innate immunity with which we were born is always at the ready to start the inflammatory cascade and to bring healing.

Signs of overt inflammation include pain, redness, immobility (as in loss of function), swelling, and heat (more blood to the area makes it feel warm). Covert inflammation, occurring with internal organs, does not necessarily present with all these signs. Pain arises when swelling pushes on nerves, but sometimes the brain gets used to it and ignores the stimulus. The risk for inflammatory conditions rises with weight gain, as determined by an increase in white blood cells. Regardless of body mass index, C-reactive protein and homocysteine are markers for the presence of inflammatory state, which is at the center of many disorders, from arthritis, through Crohn’s disease, to various allergies and vitamin deficiencies.

Treatment for inflammation abounds in the world of allopathic medicine. Most of us know about NSAIDS, non-steroidal anti-inflammatory drugs, among which Tylenol is not, but aspirin, naproxen and ibuprofen are. Then, there are the corticosteroids—or just plain steroids—that are naturally made by the body in the adrenal glands. But these guys, given as drugs, prevent phospholipid release, and that undermines the activity of eosinophils, which are designed to fight back against allergy, for example, by releasing histamine.

Of the alternative modalities to address inflammation, ginger has accrued quite a following. For hundreds of years it’s been used to treat gastric distress, including dyspepsia and constipation. Recent research points to ginger’s role as an anti-inflammatory agent in the prevention of colon cancer, where inflammation has been identified as a precursor to the disease (Zick, 2011), the markers of which are pro-inflammatory prostaglandins—primarily PGE2—produced by cyclooxygenase (COX) as an early event in the course of the condition (Jiang, 2012).

In a British examination of pain studies, those suffering from osteoarthritis, dysmenorrhea, and acute muscle pain had been administered ginger as the sole treatment. Though additional rigorous trials are anticipated, these subjects reported a reduction in pain, as cited on subjective assessment tools (Terry, 2011). Even before interest in alternative medicine was accelerated to its present status, scientists scrutinized ginger’s reputation in the Ayurvedic community among people treated with the herb for rheumatic concerns, finding efficacy that paralleled traditional interventions (Srivastava, 1989). Applying oral powdered ginger to generalized musculoskeletal discomfort, Danish physicians realized that the safety factor of ginger far exceeded that of any known drugs, while presenting significant efficacy in the relief of pain and swelling via the inhibition of pro-inflammatory prostaglandins (Srivastava, 1992).

By sequestering these incendiary prostaglandins (PG’s), ginger proves itself to be on a par with NSAIDS, minus the concerns of adverse side effects. Similar to prostaglandins in promoting physical aberrations are leukotrienes, products of an enzyme called lipoxygenase (LOX), like COX an offspring of arachidonic acid metabolism. Leukotrienes generally work within the immune system, while PG’s almost always play a role in pure inflammation and pain. (There are beneficent PG’s, by the way.)  Leukotrienes are signaling molecules that call immune cells to the site of infiltration, as from airborne allergens. Bluntly, ginger suppresses the synthesis of leukotrienes (Grzanna, 2005), a property that separates it from NSAIDS. Other of ginger’s attributes point to an anti-oxidant character in the interruption of free radical generation (Ali, 2008), which is helpful in the fight against allergens and pain.

Nitric Oxide (NO) is one of the few signaling gases in the body. The smooth muscle that lines blood vessels is told by NO to relax, thus dilating the vessels and lowering blood pressure. In excessive concentrations, though, NO becomes a pro-oxidant as a naturally unstable free radical, especially when made by white cells (monocytes and macrophages)  during their battle against an infective agent. One logistician that maintains regulation of NO is ginger, where it was shown to control white cell activation as part of its job as an anti-inflammatory vehicle (Shimoda, 2010). Modulating inflammation is what ginger does, and not so gingerly, at that.

References

Ali BH, Blunden G, Tanira MO, Nemmar A.
Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research.
Food Chem Toxicol. 2008 Feb;46(2):409-20. Epub 2007 Sep 18.

ltman RD, Marcussen KC.
Effects of a ginger extract on knee pain in patients with osteoarthritis.
A Arthritis Rheum. 2001 Nov;44(11):2531-8.

Drozdov VN, Kim VA, Tkachenko EV, Varvanina GG.
Influence of a specific ginger combination on gastropathy conditions in patients with osteoarthritis of the knee or hip.
J Altern Complement Med. 2012 Jun;18(6):583-8. doi: 10.1089/acm.2011.0202.

Frondoza CG, Sohrabi A, Polotsky A, Phan PV, Hungerford DS, Lindmark L.
An in vitro screening assay for inhibitors of proinflammatory mediators in herbal extracts using human synoviocyte cultures.
In Vitro Cell Dev Biol Anim. 2004 Mar-Apr;40(3-4):95-101.

Goforth P, Gudas CJ.
Effects of steroids on wound healing: a review of the literature.
J Foot Surg. 1980 Spring;19(1):22-8.

Grzanna R, Lindmark L, Frondoza CG
Ginger–an herbal medicinal product with broad anti-inflammatory actions.
J Med Food. 2005 Summer;8(2):125-32.

Jiang Y, Turgeon DK, Wright BD, Sidahmed E, Ruffin MT, Brenner DE, Sen A, Zick SM.
Effect of ginger root on cyclooxygenase-1 and 15-hydroxyprostaglandin dehydrogenase expression in colonic mucosa of humans at normal and increased risk for colorectal cancer.
Eur J Cancer Prev. 2012 Dec 6.

Levy AS, Simon O, Shelly J, Gardener M.
6-Shogaol reduced chronic inflammatory response in the knees of rats treated with complete Freund’s adjuvant.
BMC Pharmacol. 2006 Oct 1;6:12.

Lu H, Huang D, Saederup N, Charo IF, Ransohoff RM, Zhou L.
Macrophages recruited via CCR2 produce insulin-like growth factor-1 to repair acute skeletal muscle injury.
FASEB J. 2011 Jan;25(1):358-69.

Ramji, Divya; ho, chi; Huang, Qingron; Rafi, Mohamed; Huang, Mou
Isolation of gingerols and shogaols from ginger and evaluation of their chemopreventive activity on prostate cancer cells and anti-inflammatory effect on 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear inflammation
RUcore – Rutgers University Community Repository. 2007
http://mss3.libraries.rutgers.edu/dlr/showfed.php?pid=rutgers-lib:21328

Shen CL, Hong KJ, Kim SW.
Effects of ginger (Zingiber officinale Rosc.) on decreasing the production of inflammatory mediators in sow osteoarthrotic cartilage explants.
J Med Food. 2003 Winter;6(4):323-8.

Sehwan Shima, Sokho Kima, Dea-Seung Choia, Young-Bae Kwonb, Jungkee Kwona
Anti-inflammatory effects of [6]-shogaol: Potential roles of HDAC inhibition and HSP70 induction
Food and Chemical Toxicology. Volume 49, Issue 11, November 2011, Pages 2734–2740

Shimoda H, Shan SJ, Tanaka J, Seki A, Seo JW, Kasajima N, Tamura S, Ke Y, Murakami N.
Anti-inflammatory properties of red ginger (Zingiber officinale var. Rubra) extract and suppression of nitric oxide production by its constituents.
J Med Food. 2010 Feb;13(1):156-62.

Srivastava KC, Mustafa T.
Ginger (Zingiber officinale) and rheumatic disorders.
Med Hypotheses. 1989 May;29(1):25-8.

Srivastava KC, Mustafa T.
Ginger (Zingiber officinale) in rheumatism and musculoskeletal disorders.
Med Hypotheses. 1992 Dec;39(4):342-8.

Terry R, Posadzki P, Watson LK, Ernst E.
The use of ginger (Zingiber officinale) for the treatment of pain: a systematic review of clinical trials.
Pain Med. 2011 Dec;12(12):1808-18.

Tripathi S, Maier KG, Bruch D, Kittur DS.
Effect of 6-gingerol on pro-inflammatory cytokine production and costimulatory molecule expression in murine peritoneal macrophages.
J Surg Res. 2007 Apr;138(2):209-13. Epub 2007 Feb 8.

Tripathi S, Bruch D, Kittur DS.
Ginger extract inhibits LPS induced macrophage activation and function.
BMC Complement Altern Med. 2008 Jan 3;8:1. doi: 10.1186/1472-6882-8-1.

Zick SM, Turgeon DK, Vareed SK, Ruffin MT, Litzinger AJ, Wright BD, Alrawi S, Normolle DP, Djuric Z, Brenner DE.
Phase II study of the effects of ginger root extract on eicosanoids in colon mucosa in people at normal risk for colorectal cancer.
Cancer Prev Res (Phila). 2011 Nov;4(11):1929-37.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.