A Short Review on Management of Asthma Through Alternative Therapies

Int. J. LifeSc. Bt & Pharm. Res. 2012 Ladde Shivakumar and Shalam, 2012

Ladde Shivakumar1* and Shalam2

*Corresponding Author: Ladde Shivakumar,  [email protected]

Asthma, a common, chronic lung disease in industrialized countries, is characterized by the production of large quantities of IgE antibody by B cells and a decrease of the IFN-g /IL-4 (Th1/ Th2) ratio. Based on various research articles on management of asthma, we reviewed some alternative techniques for management of asthma. Various herbal and Chinese medicine possess their antisthamic activity by reversing histamine induced anaphylactic response, decreased the levels of reactive oxygen species (ROS), T helper (Th)2 cytokines, the total IgE produced by B cells and OVA. Also asthma can prevent through nutritional, life style, Acupuncture technique and Bronchial thermoplasty.

Keywords: Asthma, Herbal remedies, Acupuncture, Thermoplasty.

INTRODUCTION exposure is the generation of free radicals which Asthma can be defined as a lung disorder in which are the culprits causing oxidative damage leading spasms of the bronchial passages restrict the to shortness in breathing. One of the other flow of air in and out of the lungs. In today’s common causes of asthma may be hereditary. stressful life there is an increased exposure to Commonly Leukotriene modifiers include number of immunological agents like allergens, montelukast (Singulair), zafirlukast (Accolate) and dust, pollens, viruses, chemicals that acts as zileuton (Zyflo, Zyflo CR) and Long-acting beta stimuli to liberate mediators these mediators agonists (LABAs) include salmeterol (Serevent which include leukotrienes, prostaglandins, Diskus) and formoterol (Foradil Aerolizer) used histamine, IgE etc. are the endogenous chemicals in management of asthma, but some severe produced in the body which in turn cause broncho- unwanted reaction are associated with them are constriction (www.sciencedaily.com, J P psychological reactions such as agitation, Kowalak et al 2001). Another consequence of this aggression, hallucinations, depression and

1 Department of Pharmacology, Shivlingeshwar College of Pharmacy, Amit Nagar, Hasegaon 413512, Dist-Latur (MH). 2 Department of Pharmacology, College of Pharmacy, Al Qassim University, Buraidah, KSA.

16 Int. J. LifeSc. Bt & Pharm. Res. 2012 Ladde Shivakumar and Shalam, 2012 suicidal thinking. However, they’ve been linked to no detectable effect on mobilization of intracellular severe asthma attacks. LABAs should be taken calcium. These results coupled with the in vivo only in combination with an inhaled corticosteroid effects of ethanol extract reveal that the Alstonia (Litonjua AA, et al. 2010). Based on various scholaris leaves possess broncho-vasodilatory research articles on management of asthma, we activity mediated presumably by prostaglandins, reviewed some alternative techniques for calcium antagonism and endothelium-derived management of asthma. relaxing factor(s) (Shabana Channa et al. 2005). HERBAL THERAPY Amomum compactum soland ex Maton: It is widely distributed in Korea, and has been Number of herbs are reported in Ayurveda that commonly used in Korean traditional medicine provides as a whole protection against asthmatic to resolve dampness, disperse stuffiness, move attacks naturally without any side effects and qi, warm the middle, increase appetite, and gradually helps you to recover from asthma. promote digestion. A. compactum treatment Aegle Marmelos Bael or Bengal quince is a markedly decreased the number of infiltering deciduous sacred tree, associated with Gods eosinophils and the hypersecretion of mucus having useful medicinal properties, especially as when compared with the effects on mice treated a cooling agent. with OVA alone. The A. compactum treatment Albizzia lebbeck The decoction of Shirish dose-dependently decreased the levels of (Albizzia lebbeck) stem bark was found to be Reactive Oxygen Species (ROS) and T helper effective against bronchospasm induced by (Th)2 cytokines, including interleukin (IL)-4 and histaminic acid phosphate and shown to exert IL-5, in the bronchoalveolar lavage fluid (BALF), disodium cromoglycate like action on mast cells. and a high dose of A. compactum effectively Aqueous extract of both stem bark and flowers reduced the level of total immunoglobulin (Ig)E in significantly reduced (P<0.01) bronchospasm the serum. A. compactum may have a therapeutic induced by micro-aerosols of histamine acid effect on allergic asthma or inflammatory disease phosphate (1% solution) and acetycholine (Jin-Ah LEE et al. 2010). chloride (1% solution in guinea pig bronchi) (Nisha Andrographolide: It is traditional Chinese herbal Ojha 2011) medicines has been shown to possess a strong Alstonia scholaris: The extract of Alstonia anti-inflammatory activity and has the potential to scholaris inhibited the spontaneous movements be used in allergic lung inflammation. of rabbit jejunum and contractile effects of Andrographolide could inhibit extensive infiltration acetylcholine and histamine on guinea-pig ileum. of inflammatory cells in lung and decrease airway Additionally, the extract caused marked reduction hyperreactivity. Andrographolide could inhibit NF- of barium chloride-, potassium chloride- and kB expression in lung and suppress NF-kB calcium chloride-induced contraction on guinea- translocation from the cytoplasm to the nucleus pig ileum and pulmonary artery, implying a direct of airway epithelial cells. Results implicate the interference of plant extract with the influx of anti-inflammatory mechanisms of Andrographolide calcium ions into cells. However, the extract has are associated with NF-kB expression in lung and

17 Int. J. LifeSc. Bt & Pharm. Res. 2012 Ladde Shivakumar and Shalam, 2012 suppress NF-kB translocation from the cytoplasm bronchodilator (Bauer K1993). Another Ayurvedic to the nucleus of airway epithelial cells (Jing Li herbal remedy, Tylophora indica, has proven et al. 2009). beneficial in controlled, double-blind cross-over Asystasia gangetica: The terpenoid compounds studies, but the most effective dosages and long- in the leaves of A. gangetica are likely responsible term effects on children are unknown (Gupta S for the usefulness of the plant’s leaves in the 1979). management of asthma in traditional medicine Euphorbia lunulata (Euphorbiaceae): It practice (Ezike AC et al. 2008). is found in the southeast of China. The Benincasa hispida (Thunb.) Cogn: Commonly whole plants of E. lanulata have yielded known as ash gourd belonging to Cucurbitaceae kaempferol, quercetin, kaempferol 3-O- family, is employed as a main ingredient in Lrhamnoside, quercetin 3-O-L-rhamnoside, 6,7- Kusmanda lehyam in Ayurvedic system of dihydroxycoumarinand maoyancaosu. It has long medicine. Methanol extract of Benincasa hispida been used as a traditional crude drug for the (MEBH) showed excellent protection in guinea treatment of bronchial asthma and chronic pigs against the histamine-induced bronchospasm bronchitis (Tadahiro Nishimura et al. 2005). (D. Anil kumar et al. 2002). Gingko biloba: This is one of the most widely Coffee and tea: In the 1800s coffee was the used herbal remedies in Europe. Standardized treatment of choice for asthma. Epidemiologic extract of Gingko biloba (EGb), is sold under data support a relationship between coffee intake several different brand names: Ginkgobil, Rokan, and reduced respiratory symptoms that may be Tanakan, Tebonin, and Kaveri. Ginkgo’s active mediated through coffee’s xanthine content. ingredient, ginkgolide, antagonizes Platelet Caffeine is chemically related to theophylline. Like Activating Factor (PAF), and may decrease theophylline, it increases intracellular cyclic airway inflammation. Ginkgo is also a powerful adenosine monophosphate (cAMP) and thereby antioxidant. Although Gingko biloba has a long relaxes bronchial smooth muscles. In a large history and a reasonable biochemical rationale, Italian study, adults who drank two to three only one small pilot study has evaluated its cups of coffee daily had about 25% less asthma effectiveness as an asthma remedy. That study than adults who abstained (Schwarz J 1992). found it protective against exercise-induced American data support a dose-effect association bronchospasm; it also decreased participants’ between coffee intake and a reduced risk of reactivity to house dust mite antigen (Guinot P et asthmatic symptoms. There are no recent, al. 1987). randomized controlled trials evaluating the effects Gyokuheifusan (GHS): Gyokuheifusan (GHS) of caffeine on childhood asthma symptoms, nor is a classical formulation of traditional Chinese on the interaction between coffee, tea, colas, and medicine (TCM) that is usually prescribed to modern asthma medications. prevent or treat respiratory tract diseases, such Coleus forskohlii: This herb is used in Ayurvedic as respiratory infection and bronchial asthma. medicine to treat asthma. Like theophylline, it GHS down-regulates the over-production of IgE increases intracellular cAMP and is an effective and IL-4 via a significant and persistent increase

18 Int. J. LifeSc. Bt & Pharm. Res. 2012 Ladde Shivakumar and Shalam, 2012 of IFN-g. Yang et al., found that Astragalus Root components from HCWE may be beneficial in (a main material of GHS) reduced the secretion the treatment of mast cell-mediated allergic of IL-4 by regulating the shift of Th1 to Th2, and diseases(Guang Zhao LI et al., 2005, Li GZ et al. the total IgE produced by B cells decreased 2005). accordingly. Zhao et al. also reported that Kampo medicine Shoseiryuto (Xiao-Qing- Astragalus root can significantly promote IFNg , Long-Tang in Chinese): Kampo is a traditional IgG1, IgG2 and IgG3 production from peripheral Japanese medicine originating from ancient blood monocyte (PBMC) in vitro, but had no Chinese medicine. Orally administered Kampo significant effect on the production of IL-4 or IgG4, prescriptions are believed to be influenced by diet suggesting that it can modulate Th1/Th2 function and intestinal microbiota. However, reports on the and enhance the immuno-function of asthma Kampo administration effects are still limited. sufferers by improving Th1-deficiency. GHS is Shoseiryuto (TJ-19), which has anti-allergic and commonly used to treat respiratory diseases in anti-inflammatory properties, is a Kampo clinical practice in oriental countries, and there is prescription used clinically for the treatment of currently much interest in the mechanisms of its allergic bronchial asthma. The accumulation of effects on the immune system. An understanding eosinophils were significantly reduced by 30 mg/ of these may provide a pharmacological basis day doses of Shoseiryuto. The results indicate a for more effective clinical application of GHS (Su- synergistic effect of a Kampo medicine (Shoseiryuto, ping FANG et al. 2005). Xiao-Qing-Long-Tang in Chinese) and lysed Houttuynia cordata: Houttuynia cordata Thunb, Enterococcus faecalis FK-23 on allergic well known as ‘E-Sung-Cho’in Korea, has been responses in mice (Shimada T et al., 2010). used for the treatment of Herpes simplex, chronic Licorice root (Glycyrrhiza glabraradix): Folk sinusitis and nasal polyps. Recently, a few papers medicines around the world use licorice root to reported the antileukemic activity, anticancer treat coughs. The herb’s active compounds, activity, adjuvanticity, and antioxidant action of glycyrrhetinic acid and carbenoxolone, are potent Houttuynia cordata Thunb water extract (HCWE). inhibitors of cortisol metabolism, thereby The results suggest that Houttuynia cordata enhancing endogenous and exogenous steroid Thunb water extract (HCWE) may containthe benefits, this led most clinicians to as an adjunct bioactive compounds that inhibit the compound in asthma treatment. Glycyrrhiza glabra (10 mg/ 48/80- or anti-DNP IgE-induced mast cell kg/ body wt.) was fed to sensitized mice and activation and anaphylactic reactions by blocking measured ova-induced Early Airway Response of calcium uptake into mast cells, or increasing (EAR) and Late Asthmatic Response (LAR). At the cAMP level in mast cells. HCWE also inhibited the end of experiment, the animals were the local allergic reaction, PCA, activated by anti- sacrificed and measured OVA specific serum IgE dinitrophenyl (DNP) IgE antibody in rats. HCWE levels. The feeding of Glycyrrhiza glabra inhibited reduced the compound 48/80-induced mast cell significantly both EAR as well as LAR as degranulation and colchicine-induced deformation compared to vehicle treated sensitized mice. OVA of rat peritoneal mast cells (RPMC). The specific serum IgE levels were also reduced purification of the exact anti-anaphylactic significantly by the treatment of Glycyrrhiza glabra.

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NSL, New Delhi (Ram A et al., 2003, Nisha Ojha effectively reduce passive cutaneous anaphylaxis 2011). in rats and protect guinea pigs against antigen- Ma huang (Ephedra sinica): This herb has been induced bronchospasm; a 30% protection of mast an asthma remedy in China for over 5,000 years. cells was observed in an in vitro study (Chatterjee, Ephedrine, ma huang’s principle active ingredient, 1999; Dahanukar et al., 1984). Aller-7, a was included in mainstream medical therapies combination from seven medicinal plants for pediatric asthma until the mid-1980s when it including Long pepper is used for allergic rhinitis, was replaced by more specific b-agonist as antihistaminic and as antispasmodic (Amit et medications that had fewer cardiovascular side al., 2003; P. Manoj, 2004). In a study involving effects. It continues to be a mainstay of natural 240 children of different age groups suffering from herbal asthma remedies when used in combination frequent asthma attacks, long-term administration with anti-inflammatory herbs such as licorice root. of long pepper fruits significantly, reduced the Ocimum sanctum: The anti-asthmatic activity frequency and severity of attacks. In another study of the extract of dried and fresh leaves, and the 20 pediatric patients with asthma received long volatile and fixed oils of Ocimum sanctum was pepper in dosages ranging from 935-1575 gm, evaluated against histamine and acetylcholine- daily for several weeks as a result of this treatment induced pre-convulsive dyspnea (PCD) in guinea all patients showed clinical improvement. Piper pigs. The extract of fresh leaves, volatile oil longum has been shown to reduce the passive extracted from fresh leaves and fixed oil from the cutaneous anaphylaxis in rats and protect guinea seeds significantly protected the guinea pigs pigs against antigen-induced bronchospasm against histamine- and acetylcholine-induced (Dahanukar S A et al., 1984; Nisha Ojha et al., 2011). PCD (P Prakash et al., 2005). Ryokan-kyomi-shinge-nin-to (RKS): It is a Onions (Allium cepa): Nine different traditional oriental herbal (Kampo) medicine compounds isolated from this common folk which has been used for the treatment of allergic remedy inhibit leukotriene synthesis in vitro. Crude asthma and rhinitis, were investigated. These onion extracts reduce experimentally induced results suggest that RKS has antiallergic activity bronchoconstriction in guinea pigs. Onions are in animals, by significantly inhibited an increase extremely safe and well tolerated in normal diets. in vascular permeability induced by histamine and Hypersensitivity is rare. Additional research is serotonin. In addition, RKS prevented histamine needed to determine the best dose and frequency hypersensitivity in actively sensitized mice. of onion supplements for asthmatic children Because RKS did not affect sleeping time (Dorsch W et al., 1984). induced by pentobarbital in mice and did not Piper longum Linn: The fruits of Piper longum inhibit gastric emptying in rats, the drug appears contain 1% volatile oil, resin, alkaloids piperine to be useful for treating allergic patients suffering and piperlonguminine, a waxy alkaloid N- from classical antihistamines side effects such isobutyldeca-trans-2-trans-4-dienamide and a as stomach discomfort or relative drowsiness terpenoid substance. Dried ripe fruits; the fruit (Masaru Sakaguchi et al. 2002).

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SHATI (Hedychium spicatum): The powdered Solanum xanthocarpum, Tylophora asthmatica, rhizome given in divided doses of 10gm to 25 and Curcuma caesia significantly prolonged the patients with recurrent paroxysmal attacks of latent period of convulsions followed by exposure dyspnoea for 4 weeks (Bronchial asthma), to histamine aerosol at the dose of 500 mg/kg, completely relieved dyspnoea, cough and 100 mg/kg, 100 mg/kg and 500 mg/kg restlessness in all patients. The bronchi respectively. The results of the study confirmed completely disappeared in 36% of the patients. the bronchodilator properties of the plants, The mean R/R was reduced by 25% and the vital justifying their traditional claims in the treatment capacity increased by 20%. The mean absolute of asthma. Adhatoda vasica mainly consists of pyrroquinazoline alkaloids viz. vasicine, vasicol, count also decreased by 55.6% (Chaturvedi GN vasicinone, peganine along with other minor et al., 1974; Nisha Ojha et al., 2011). constituents. Vasicine is a major bioactive Shinpi-to and saiboku-to: Clinical trials indicate pyrroquinazoline alkaloid of vasaka present in the some steroid-sparing effects of the ancient concentration of 1.3%. Minor alkaloids include Chinese herbal combination remedy, saiboku-to, adhatonine, vasicinol and vasicinolone (Pritesh reducing the need for anti-inflammatory Paliwal et al., 2011; Sayeed Ahmad et al., 2009). medications in adult asthmatics taking it over Xincang Decoction was composed of Flos several months. Saiboku-to contains five herbs Magnoliae (Xinyi) and Fructus Xanthii (Cang’erzi), that slow steroid breakdown, possibly increasing the traditional Chinese herbs for expelling wind. the risk of side effects (or decreasing dosage In three months treatment, Xincang Decoction requirements) in patients dependent on oral showed that the levels of EOS and IL-5 were steroids. Like the new asthma drug zileuton, obviously decreased after the treatment, and the saiboku-to and shinpi-to, another Chinese herbal levels of EOS and IL-5 of the patients in the asthma remedy, inhibit 5-lipoxygenase and thus treatment group were lower than those in the the synthesis of the pro-inflammatory leukotrienes control group. Meanwhile the forced expiratory (Hamasaki Y et al., 1997). The ethanolic extract volume in one second (FEV1) was improved after (50%) of fresh leaves, volatile oils (from fresh the treatment, and the FEV1 of the patients in the leaves) and fixed oil (from seeds) has shown anti treatment group was higher than that of the asthmatic activity and significantly protected patients in the control group. Hence Xincang guinea pigs against histamine and acetylcholine Decoction can decrease the levels of EOS and induced preconvulsive dyspnoea Kathi J Kemper IL-5 and improve the pulmonary function in et al., 1999; Nisha Ojha et al., 2011). treating chronic airway inflammation in children with bronchial asthma in remission stage (Yu Jian- Solanum xanthocarpum, Tylophora Er 2005). asthmatica, and Curcuma caesia. Histamine induced bronchoconstriction is the traditional NUTRITIONAL THERAPY immunological model of antigen induced airway Antioxidant vitamins are commonly suggested obstruction. In Pritesh Paliwal1 et al., 2011 study complementary therapies for asthma. Pyridoxine find that Methanolic extracts of Adhatoda vasica, supplements of 200 mg per day reduced the

21 Int. J. LifeSc. Bt & Pharm. Res. 2012 Ladde Shivakumar and Shalam, 2012 number of asthma attacks, the severity of symptoms under control. A few things you can symptoms, and the need for medications in a do include: double-blind study of 76 asthmatic children • Regular exercise can strengthen your heart (Collipp PJet al. 1975). Side effects are rare with and lungs, which helps relieve asthma these doses. In some children, 500 mg of oral symptoms. Keep in mind that exercising in vitamin C has a protective effect against exercise- cold weather may trigger asthma symptoms. induced asthma (Cohen HA et al. 1997). Oral magnesium supplementation (400 mg daily) in • Eating plenty of fruits and vegetables may adults, there was a statistically significant increase lung function and reduce asthma improvement in asthma symptoms and a small symptoms. These foods are rich in protective reduction in bronchodilator requirements, but no nutrients (antioxidants) that boost the immune significant change in pulmonary function tests system. during the three weeks of treatment (Hill J et al., • Control heartburn and gastroesophageal reflux 1997). Omega-3 fatty acids limit leukotriene disease (GERD) may damage lung airways synthesis by blocking arachidonic acid and worsen asthma symptoms. metabolism. Eating fresh oily fish (cod, mullet, Alternative Medicine: There’s some evidence orange roughy, salmon, tuna, mackerel and that certain alternative treatments may help with rainbow trout) is associated with a significantly asthma symptoms. However, keep in mind that reduced risk of asthma and improved pulmonary these treatments are not a replacement for function in large epidemiologic studies in both medical treatment especially if you have severe adults and children (Hodge L et al. 1996). asthma. Alternative asthma treatments include: LIFESTYLE THERAPY • Breathing techniques: The Papworth Although many people with asthma rely on method and yoga breathing (pranayama) may medications to prevent and relieve symptoms, reduce the amount of medication you need to you can do several things on your own to maintain keep your asthma symptoms under control. your health and lessen the possibility of asthma Yoga classes increase fitness and reduce attacks. stress, which may help with asthma as well(Nagarathna R et al 1985). • Use air conditioner, it reduces the amount of airborne pollen from trees, grasses and weeds • Acupuncture. This technique involves placing that finds its way indoors and Keep indoor air very thin needles at strategic points on your clean body. It’s safe and generally painless (Jobst K A,1995). • Maintain optimal humidity Bronchial thermoplasty is a novel therapy that • Reduce pet dander uses radiofrequency energy to heat the airways • If your asthma is worsened by cold, dry air, in order to reduce excess smooth muscle mass wearing a face mask can help. in the airways. Patients with chronic asthma have • Taking care of yourself and treating other more airway smooth muscle than non-asthmatics conditions linked to asthma will help keep your (Bergeron C et al., 2006; Carroll N et al., 1993).

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Beta-agonist therapy temporarily reduces heating the smooth muscle walls of the airway to bronchoconstriction, but bronchial thermoplasty approximately 149° F. This temperature is is the first therapeutic attempt to achieve a long- sufficient to thin the smooth airway wall muscles term reduction in airway smooth muscle mass without scarring or damaging them (www.tree. and potentially reduce asthma severity. The com). thermal energy is hypothesized to disrupt the interaction between actin and myosin and to The Alair ®Bronchial Thermoplasty System is denature muscle proteins (Dyrda P et al. 2001). indicated for the treatment of severe persistent asthma in patients 18 years and older whose Working: During the procedure, a small, flexible asthma is not well controlled with inhaled catheter is guided into the lung using a corticosteroids and long acting beta agonists. bronchoscope accessed through the nose or mouth. No incision is required. The tip of the Contraindications catheter is expanded to touch the walls of the Patiens with the following conditions should not airway. The catheter delivers controlled be treated: radiofrequency energy along the length of the Presence of a pacemaker, internal defibrillator, airway walls in 10 second bursts. The heat or other implantable electronic devices. reduces the amount of excess airway smooth muscle and limits its ability to constrict, making it Known sensitivity to medications required to less sensitive to irritants in the air. Traditionally, perform bronchoscopy, including lidocaine, living with asthma has meant patients have to atropine, and benzodiazepines. avoid “triggers,” use medications religiously to Patients previously treated with the Alair prevent flare-ups and have an inhaler handy at all System should not be retreated in the same times. This kind of treatment goes right to the area(s). No clinical data are available studying source of the problem, hopefully offering a way the safety and/or effectiveness of repeat of life less dependent on having to avoid triggers treatments. to reduce the occurrence of asthma attacks Patients should not be treated while the (www.texashealth.org ). following conditions are present: Bronchial thermoplasty uses radio frequency Active respiratory infection energy to relieve asthma symptoms. Because Asthma exacerbation or changing dose of the procedure requires only light anesthesia, it systemic corticosteroids for asthma (up or down) can be performed on an outpatient basis. A small, in the past 14 days flexible tube called a bronchoscope is inserted through the nose or mouth and guided into the Known coagulopathy lungs. Once the bronchoscope is situated in the As with other bronchoscopic procedures, desired airway; a catheter is inserted through the patients should stop taking anticoagulants, bronchoscope. The tip of the catheter is inflated antiplatelet agents, aspirin and NSAIDS before until it touches the sides of the airway wall. Radio the procedure with physician guidance. frequency energy is then sent through the catheter,

23 Int. J. LifeSc. Bt & Pharm. Res. 2012 Ladde Shivakumar and Shalam, 2012

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