Posted in May 2010

Phytotherapy for the Management of Asthma
Part 2: Materia Medica and Therapeutics

Treatment Goals for Phytotherapy of Asthma

Treatment goals will obviously vary according to the needs of the individual case at the particular time of treatment. However, based on the considerations discussed in Part 1 of this article (April 2006), they can be divided into two main categories (see Tables 1 and 2). The required actions related to the treatment goals are also provided. Some treatment goals, such as resolving sinusitis, are complete therapeutic subjects in themselves.

Materia Medica of Herbs to Control Inflammation and Allergy
A complete review of the materia medica for asthma is beyond the scope of this discussion. However, some plants have specialized effects on the inflammatory or allergic mechanisms known to occur in asthma. Since some of these effects have only recently been discovered or studied, a discussion of the research findings follows.  

a.   Inhibitors of Prostaglandin and Leukotriene Production
Cepaenes and thiosulfinates from Allium cepa (onion) are dual inhibitors of AA metabolism, as are the gingerols from Zingiber officinale (ginger; see also the information on turmeric below). Boswellia serrata, a potent inhibitor of leukotriene production, has been successful in a clinical trial with asthmatic patients. In a double-blind, placebo-controlled clinical study, 80 patients with chronic asthma were treated with 900 mg/day of Boswellia gum resin or placebo for six weeks.¹ Only 27% of patients in the control group showed improvement, whereas 70% of patients taking Boswelliaimproved. After taking Boswellia, improvements were observed for shortness of breath, number of attacks, and respiratory capacity, as well as indicators of inflammation. Comparing the Boswellia group to the placebo group, there was a significant improvement in FEV1, a measure of bronchial obstruction (p = 0.0001). PEFR, a measure of lung capacity was also significantly increased (p = 0.0001). The number of attacks was lower in the Boswellia group (p = 0.0001). Additionally, Boswellia showed substantial (p < 0.05) improvements compared to placebo in secondary outcome parameters such as rhonchi, eosinophil count, ESR, and respiratory rate. Two patients who received Boswellia complained of epigastric pain and nausea. Research with leukotriene modifiers suggest that they will work best in ASA and exercise-induced asthma.²

• inhibited weal and flare responses to subcutaneously applied PAF in healthy volunteers^7,8 and in atopic volunteers (late-onset response only)⁹;
• reduced the bronchoconstriction caused by inhalation of PAF (healthy volunteers)¹⁰ or by inhalation of dust mites and pollen (atopic asthmatics);¹¹
• and inhibited exercise-induced bronchospasm in asthmatic volunteers.¹²

Pretreatment with an oral dose of standardized Ginkgo extract (600 mg) also protected asthmatic patients exposed to challenge with an inhaled allergen.⁵

In small, uncontrolled trials, oral administration of standardized Ginkgo extract

• normalized pulmonary function in children with atopic asthma, which was correlated with a significant improvement in flow parameters;
• and improved asthma in adults, some of whom were able to stop corticosteroid therapy.

Concentrated Ginkgo leaf liquid (orally administered for eight weeks) reduced airway hyperreactivity and improved clinical symptoms and pulmonary functions in asthmatic patients. These improvements were significantly greater than placebo.^13,14

Tylophora indica (Tylophora asthmatica) is a well-known antiasthmatic herb which depresses cell-mediated immunity.¹⁵ It also stimulates the adrenal cortex, increasing plasma steroid levels and antagonizing steroid-induced suppression of adrenal activity.¹⁶ Several clinical trials using Tylophora have shown benefits.¹⁷

c.   Antiallergic Effects
The antiallergic mast cell stabilizing effect of Picrorrhiza was confirmed in several studies. Mast cell stabilisation appeared gradually on repeated administration in vivo.¹⁸ To study this effect further, rat mast cells were treated with Picrorrhiza extract in vitro.¹⁹ This experiment suggests that alteration of the mast cell membrane structure or function provided the stabilizing effect. Mast cell binding of IgE was not affected. Picrorrhiza also enhances the bronchodilating effects of sympathicomimetic amines used as asthma drugs.²⁰

Flavonoids from Scutellaria baicalensis have marked antiallergic activity. Baicalin and baicalein demonstrated antiallergic and antiasthmatic activity in several animal models.²¹ For example, oral administration of baicalin to egg-white-sensitized guinea pigs protected them against allergic reaction from reinhalation of the antigen. Both compounds suppressed cutaneous allergy in guinea pigs.²¹

A soluble derivative of baicalein was antiallergic after oral administration and demonstrated more extensive antiallergic activity than DSCG in vitro.^22,23 Other flavonoids from Baical skullcap were active in inhibiting the histamine release from rat peritoneal mast cells in vitro, and baicalein inhibited basophil histamine content and growth in vitro.^24,25

Saiboku-To (TJ-96) is a Kampo (Japanese botanical) medicine comprising 10 herbs, including Baical skullcap. It has been used in Japan for glucocorticoid-dependent asthmatic patients with the aim of reducing the dose of administered glucocorticoids. The antiallergic action of Saiboku-To is based on the suppression of type I and IV allergic reaction, which has been confirmed in animal studies.²⁶

Albizzia lebbeck has mast cell stabilizing activity.²⁷ Its antiallergic effects may also be mediated by suppression of lymphocyte function.²⁸  

d.   Turmeric
Curcuma longa is a member of the Zingiberaceae (ginger) family and has been used as a medicine, spice, and coloring agent for thousands of years. The medicinal part is the oblong or cylindrical rhizome, which has an internal color ranging from yellow to yellow-orange. The rhizome contains yellow pigments known as diarylheptanoids and includes curcumin and methoxylated curcumins. These constituents, as well as the essential oil, are regarded as important for the therapeutic activity of Turmeric.⁴ In an uncontrolled trial conducted in India, 60% of asthma patients administered plain or ghee-fried Turmeric powder (6–12 g) showed a response in relief of symptoms.²⁹

Curcumin may exert its anti-inflammatory activity by the inhibition of a number of factors that play a role in inflammation. In vitro studies have identified several agents involved in inflammation that are inhibited by curcumin. including phospholipase, lipoxygenase, cyclooxygenase 2, leukotrienes, thromboxane, prostaglandins, nitric oxide, collagenase, elastase, hyaluronidase, monocyte chemoattractant protein-1, interferon-inducible protein, tumor necrosis factor alpha, and interleukin-12. High oral doses of curcumin have demonstrated anti-inflammatory activity in acute and chronic models of inflammation. In some models, at the tested dosage, curcumin had similar efficacy to cortisone and phenylbutazone.^30,31

Curcumin is a dual inhibitor of arachidonic acid (AA) metabolism in that it inhibits both the enzymes 5-lipoxygenase and cyclooxygenase. Dual inhibitors of AA metabolism are attracting interest as anti-inflammatory agents since they prevent the potentially damaging effects of increased leukotriene production, which can result from only using cyclooxygenase inhibitors such as aspirin. In addition, leukotrienes may play an important role in some inflammatory processes. Curcumin is probably only a mild inhibitor of cyclooxygenase in vivo since, unlike aspirin and phenylbutazone, it lacks analgesic and antipyretic activities.⁴

A high oral dose of curcumin (20 mg/kg) significantly inhibited allergen-induced airway constriction and airway hyperreactivity to histamine in guinea pigs. The effective test dose was comparable to many of the anti-inflammatory compounds already tested in this model.³² An in vitro study suggests that curcumin may have an effect on allergic diseases through inhibiting the production of cytokines affecting eosinophil function and IgE synthesis.³³

Important Herbs in Overall Asthma Management
a.   Adhatoda
Adhatoda vasica is a small evergreen, subherbaceous bush that grows on the plains of India in the lower Himalayan ranges and in Sri Lanka, Burma, and Malaysia. Adhatoda leaf has been used extensively in the Ayurvedic system for over 2000 years.³⁴ It has antiasthmatic, bronchodilating, and expectorant activities and is traditionally used for the treatment of asthma, bronchitis cough, and common cold.³⁵ In the World Health Organization publication The Use of Traditional Medicine in Primary Health Care: A Manual for Health Workers in South-East Asia, Adhatoda is said to facilitate breathing and to make sputum more fluid, thereby facilitating its removal. Adhatoda preparations are recommended for long-term use in adults and children.³⁶ However, it is contraindicated during pregnancy.

Key constituents of Adhatoda leaf are the quinazoline alkaloids (0.5–2%). The major alkaloid is vasicine, present at levels of 45–95%. Minor alkaloids include vasicinine, vasicinone, oxyvasicinine, deoxyvasicine, deoxyvasicinone, and vasicinol.^37,38 The drug bromhexine was developed from vasicine in Europe prior to the 1960s and is still used as an aid to expectoration by reducing the viscosity of secretions.³⁹

A number of in vitro and in vivo studies were conducted from the 1920s to the early 1970s and produced conflicting results for the bronchial activity of vasicine, vasicinone, and vasicinol. The conflicting results may have been due to the use of impure active constituents. Investigation in 1977 indicated that vasicine showed bronchodilatory activity and vasicinone showed bronchoconstriction in vivo. The two alkaloids in combination showed more bronchodilatory activity than equivalent doses of either vasicine or theophylline (a bronchodilator) in vivo. (In these in vivo studies, the compounds were administered by injection.) Vasicine also stimulated respiration following its experimentally induced suppression. Application of vasicine to isolated tissue increased ciliary movement and inhibited bronchial secretions.⁴⁰

Oral administration of a mixture of vasicine and vasicinone (25 mg, three times per day) showed good bronchodilating activity in asthma patients. Seventy percent demonstrated clinical improvement and improvement in spirometry.⁴¹

Uncontrolled clinical trials conducted in India as early as 1925 suggested that Adhatoda had an expectorant action. In acute bronchitis, Adhatoda provided relief, especially where the sputum was thick and tenacious. In patients with chronic bronchitis, cough was relieved and the sputum thinned, which facilitated removal. Mild relief was achieved for asthma.³⁵

b.   Grindelia
There are 40 to 60 species of Grindelia native to temperate, mostly arid and semiarid regions of North and South America. Species of Grindelia (commonly called gumweeds) are often poorly differentiated, and the taxonomy of the genus is still poorly understood. The resins produced by Grindelia consist mostly of labdane-type diterpenoid resin acids, similar in chemistry and physical properties to those obtained from pine trees. Resins from various species of Grindelia have been patented for use in adhesives, rubber, coatings, and textiles.⁴²

Several species of Grindelia are used in herbal medicine including Grindelia camporum, G. robusta, G. squarrosa, and G. humilis. Constituents of the medicinal Grindelia spp. include a resin containing diterpenoid acids, phenolic acids, flavonoids, an essential oil, and small amounts of saponins.⁴³

Grindelia is an expectorant herb with bronchospasmolytic activity. It is traditionally recommended for the treatment of spasmodic respiratory conditions such as asthma and bronchitis. The British Herbal Pharmacopoeia 1983 lists the specific indication as bronchial asthma with tachycardia.⁴⁴ Eclectic physicians also utilized Grindelia for asthma.⁴⁵ Californian Native Americans used Grindelia not only for skin infections but also for bronchial conditions. They brought Grindelia to the attention of the Catholic missionaries. Hispanics used Grindelia species in a similar way to the Native American use – that is, primarily for asthma, neuralgia, bladder infections, and, externally, for skin eruptions. The dried leaf and flowering tops of Grindelia were listed officially in the United States Pharmacopoeia 1882–1926 and have been in the National Formulary, 1926–1960.^46,47

Table 3 lists important herbs for use in asthma management, many of which have already been discussed. The relevant actions of each herb are also provided.

Prescription Construction
Asthma is a deep-seated protracted condition that requires herbal treatment in pharmacological doses. Hence, a high dosage protocol is proposed. Based on the treatment goals outlined in Tables 1 and 2, it is suggested that two formulae, each composed of four to six herbs, be developed for the individual patient. Otherwise, one formulation and an herbal tablet should be used.

One is a long-term treatment aimed at treating the underlying factors behind the asthmatic condition. The second is aimed at the symptoms and sustaining causes. (A third formula could be developed, to be taken only to alleviate acute attacks, but these days, most patients will resort to a bronchodilating drug in these circumstances.)

The herbs in the two formulae should be chosen so that there is as much overlap of the required actions as possible. This reduces the number of herbs needed to give a broad range of required actions. For example, ginger has expectorant, digestive-stimulant, and anti-inflammatory activities, and Adhatoda is expectorant and bronchodilating.

The adult patient is then prescribed a 5 mL dose of each formula two to three times a day. Dosages are adjusted for children, based on their body weight. The treatment should be varied over time, depending on the patient's response. Also, not every factor can necessarily be treated at the one time, so particular treatment goals may need to be changed from time to time. This should be a dynamic and interactive approach.

Case Histories

Case History 1

Susie, aged 3½ on presentation, was diagnosed as asthmatic 18 months before, after an unresolved viral infection that started as a persistent cough. Sodium cromoglycate was ineffective, and she was currently taking six puffs of inhaled steroids a day and using ipratropium bromide by nebulizer three times a day. She was always tired, due to a nocturnal cough that interfered with her sleep. She often complained of a "sore tummy," which probably indicated GER. Her father had asthma. On examination, she was underweight, she looked devitalized, her nose was constantly blocked, and she was mouth-breathing. Chest examination revealed the presence of wheezes and considerable respiratory congestion. She had swollen neck lymph glands.

         Elecampane                                      1:2                    20 mL
         Ginkgo biloba standardized extract    2:1                    25 mL
         Eyebright                                          1:2                    20 mL
         Echinacea angustifolia                        1:2                    35 mL
                                                                                         100 mL
         Dose:   2.5 mL with water twice a day

B.  For Night Cough/GER
        
         Licorice                                             1:1                    20 mL
         Meadowsweet                                   1:2                    25 mL
         Marshmallow root glycetract              1:5                    55 mL
                                                                                         100 mL
         Dose:   2 mL with a small quantity of water two to three times in the evening

Susie's mother was also advised to reduce her daughter's dairy intake.

Four weeks later
The day after initial presentation Susie had a bad time, with increased need for conventional medication. This settled down once she took her normal medication. Her sleep at night was better, and the night mixture was helping her cough. She was mouth-breathing less. Repeat prescription.

Four weeks later
Susie had been well. No acute problems. Conventional medication reduced to inhaled steroids only. Susie's mother asked if she could use night mixture during the day as it seemed to help considerably. Repeat prescription, but increase second mixture to 2 mL three to four times to include the daytime hours.

Four weeks later
One aggravation where the nebulizer was used for two days, but the problem cleared up quickly.

Twelve weeks later
Inhaled steroids dose reduced substantially. No need for other conventional medication. People comment how well she looks. Attacks of nocturnal coughing were infrequent and mild.

The following case of a 16-year-old teenage girl illustrates how herbal tablets can be effectively used to manage asthma in patients who have difficulty negotiating tinctures and liquid extracts. Here the tablets were largely aimed at controlling inflammation and allergy and supporting immune function.

This patient had asthma since the age of 6. She had been hospitalized several times, including recently. She had marked upper respiratory allergy and "had a constant cold all last year." Medication was inhaled bronchodilators and steroids. The patient was advised to eliminate all dairy products from her diet.

The following herbal tablets were prescribed:

• A tablet containing Echinacea angustifolia extract 4:1 125 mg, Ocimum tenuiflorum leaf extract 4:1 125 mg, Andrographis paniculata extract10:1 100 mg, and Ocimum tenuiflorum leaf essential oil 10 mg. Dose four per day.
• A tablet containing Boswellia serrata 4:1 extract 300 mg, Apium graveolens 6:1 extract 166.7 mg, Zingiber officinale 5:1 extract 60 mg, and Curcuma longa 25:1 extract 80 mg. Dose two per day.
• A tablet containing Echinacea angustifolia 4:1 extract 150 mg, and Echinacea purpurea 6:1 extract 112.5 mg. Dose one per day.
• A tablet containing Scutellaria baicalensis 3:1 extract 267 mg, Albizia lebbek 4:1 extract 200 mg, and Tanacetum parthenium 6:1 extract 8.33 mg. Dose two per day.

Over a six-month treatment period, the patient's condition improved dramatically. Her need for inhaled conventional drugs was reduced to almost zero and her sinuses cleared, and she experienced a considerable enhancement of general well-being.

A 75-year-old female patient developed late onset asthma following a bout of lower-respiratory infections and was prescribed prednisone by her medical doctor (now stopped). She also had pronounced sinus congestion and was under stress because of selling and moving house.

The following herbal treatments were instituted:

         Eyebright                                               1:2               25 mL
         Ginkgo biloba standardized extract         2:1               25 mL
         Echinacea angustifolia/purpurea root       1:2               25 mL
         Eleutherococcus                                     1:2               25 mL
                                                                                        100 mL
         Dose:   8 mL with water twice a day

B.     Three herbal tablets per day containing the following:

Scutellaria baicalensis 3:1 extract 166.7 mg, Adhatoda vasica 5:1 extract 150 mg, Grindelia camporum 4:1 extract 75 mg, Curcuma longa 25:1 extract 40 mg, Ginkgo biloba leaf 50:1 extract 20 mg, and Foeniculum vulgare essential oil 5 mg.

After four weeks, the patient reported that the asthma had improved substantially. This improvement was also sustained by the next consultation four weeks later. The patient was then subsequently maintained with just the herbal tablets which, according to her reports, provided substantial relief for her asthma on an ongoing basis.

Notes
1. Gupta I, Gupta V, Parihar A et al. Eur J Med Res. 1998;3(11):511–514
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3. Dorsch W et al. Folia Allergol Immunol Clin. 1983;30, 17.
4. Mills S, Bone K. Principles and Practice of Phytotherapy: Modern Herbal Medicine. Edinburgh: Churchill Livingstone; 2000:405
5. Braquet P. Adv Prostaglandin Thromboxane Leukot Res 1986;16:179–180
6. Braquet P, ed. Ginkgolides: Chemistry, Biology, Pharmacology and Clinical Perspectives, vol. 1. Barcelona: JR Prous Science; 1988.
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21. Chang HM, But PP. Pharmacology and Applications of Chinese Materia Medica. Singapore: World Scientific; 1987.
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24. Kubo M, Matsuda H, Tanaka M, Kimura Y, Okuda H, Higashino M, Tani T, Namba K, Arichi S. Studies on Scutellariae radix. VII. Anti-arthritic and anti-inflammatory actions of methanolic extract and flavonoid components from Scutellariae radix. Chem Pharm Bull. 1984;32(7):2724–2729
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28. Tripathi RM, Sen PC, Das PK. Further studies on the mechanism of the anti-anaphylactic action of Albizzia lebbeck, an Indian indigenous drug. J Ethnopharmacol. 1979a;1(4):397–400.
29. Aulakh GS, Mahadevan G. Indian Drugs. 1989;26:593
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34. Atal CK. Chemistry and Pharmacology of Vasicine: A New Oxytocic and Abortifacient. Jammu-Tawi: Regional Research Laboratory; 1980.
35. Chopra RN et al. Chopra's Indigenous Drugs of India, 2nd ed. Calcutta, India: Academic Publishers; 1982.
36. World Health Organization. The Use of Traditional Medicine in Primary Health Care: A Manual for Health Workers in South-East Asia. New Delhi: WHO Regional Office for South-East Asia; 1990.
37. Wagner H, Bladt S. Plant Drug Analysis: A Thin Layer Chromatography Atlas, 2nd ed. Berlin: Springer-Verlag; 1996.
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42. McLaughlin SP. Grindelia New Crop Factsheet. Office of Arid Lands Studies, University of Arizona; 1995.
43. Mills S, Bone K. The Essential Guide to Herbal Safety. Churchill Livingstone; 2005:457–458.
44. British Herbal Medicine Association's Scientific Committee. British Herbal Pharmacopoeia. Bournemouth, England: BHMA; 1983.
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Kerry Bone, as cofounder and director of research and development, is the innovation driver at MediHerb. He is a practicing herbalist (24 years' experience) and maintains a busy practice in Toowoomba, Australia. He is also associate professor at the University of New England in Armidale, Australia, and a prolific author with six published herbal medicine books that are renowned as defining herbal texts in natural medicine schools throughout the world. His latest book, written with Rob Santich, is Healthy Children: Optimising Children's Health with Herbs. Kerry has also published 20 scientific papers in the field of herbal research.