New herbal leads for asthma management.

Given that asthma occurs with such a high frequency in children and adults, it should not be surprising that herbs to assist in its management are being actively researched. Previous Phytotherapy Review columns (Townsend Letter, April 2006;273, May 2006; 274) provided a comprehensive exploration of phytotherapy for asthma. In this current column, new developments in the research on Chinese, Ayurvedic, and Western herbs for the management of asthma will be discussed.

Leads from Traditional Chinese Medicine 

The Chinese herb Sophora flavescens, both on its own and in a formulation, has yielded promising results in asthma management. Sophora has a long history of traditional use and recently has been the subject of pharmacological and clinical research into a wide range of conditions. (1) Its pharmacological properties include diuretic, antiviral, antitumor, sedative, and anti-inflammatory activities. The main active components are matrine-type alkaloids, particularly matrine and oxymatrine. (1)

It has been suggested that the Sophora alkaloids can act as modulators of cell membrane excitability. This is based on its central nervous system (CNS) effects, anti-arrhythmic activity, and inhibition of glutamate-induced responses. (1) On the hypothesis that an excitatory modulator (especially in the context of glutamate responses) may be beneficial in asthma, an open trial of Sophora in refractory asthma was initiated. (1)

From February 1997 to December 2005, 14 patients with moderate to severe asthma (six men and eight women) aged 22 to 70 years old were treated. These patients had been diagnosed with asthma by their allergists and had been on medication for asthma for three to six years. Despite years of moderate to high doses of inhaled corticosteroids and beta-2 agonists, they still suffered episodes of dyspnea, expectoration, coughing, wheezing, chest tightness more than two times a week, and waking up at night with asthma symptoms more than two times a week. (1)

The patients were given a dried powder of a hot water extract of S. flavescens root, which contained a high content of matrine and oxymatrine (1.8%-3.2%). The extract was provided in capsules, with a dose equal to 4 g of dried root, three times daily for three months, two times daily for six months, and once daily for 27 months thereafter. Since the study was open, non-randomized, and selective, the results below are summarized based on the records of the diary card of symptoms, peak expiratory flow (PEF), medication use, and quality of life. (1)

After four weeks, the daytime asthma symptoms were reduced by 78% and the night-time symptoms by 75%. The beta-2 agonist dose was reduced by 72% and the dose of corticosteroid inhaler reduced by 45%. The mean PEF rate improved by 12%. Two patients had remarkable improvements of eczema symptoms. No side effects were observed. (1)

At one year, the daytime symptoms of asthma reduced by 94% and night-time symptoms by 95%. The beta-2 agonist use was reduced by 95%, and the corticosteroid inhaler was reduced by 92%. The mean PEF had increased by 18%. After three years, the daytime symptoms of asthma were reduced by 97% and night-time symptoms by 98%. The dose of beta-2 agonist was reduced by 97%, and no patients inhaled corticosteroids. The mean PEF had increased by 21%.

At three years, nine of the patients had achieved a symptom-free, medication-free, and also an asthma-free condition, meaning they did not develop asthma symptoms when they were exposed to the previous triggers of their asthma attacks. Two of the patients with functional and radiological evidence of emphysema achieved an improvement in both breathing capacity and airway fibrosis (emphysema) to the extent that they were no longer considered to have emphysema. Two patients had complete remission of their eczema. (1)

Despite these striking results, they must be viewed with caution, since this was an open label trial and there was no placebo group. So it is encouraging to learn that Sophora in conjunction with two other traditional Chinese herbs (Glycyrrhiza uralensis [licorice] and Ganoderma lucidum) was found to be active in a controlled trial. (2) The efficacy and tolerability of this formula was investigated in 91 patients with moderate to severe asthma in a double-blind, randomized, controlled trial. The herbal treatment was compared to oral prednisone therapy. (2)

Patients in the herbal group received oral capsules (four capsules, three times daily, 0.3 g/capsule) and placebo tablets similar in appearance to prednisone. Those in the prednisone group received oral prednisone tablets (20 mg, once daily in the morning) and "herbal placebo capsules," for four weeks. Treatment was administered daily over a period of four weeks, and all subjects, 18 to 65 years old, remained in the hospital for the duration of the study. No medications other than rescue beta-2 agonists were allowed. Spirometry measurements, symptom scores, side effects, and serum cortisol, cytokine, and IgE levels were evaluated pretreatment and post-treatment. This study found that post-treatment lung function (FEV and PEF values) was significantly improved in both herbal (64.9 [+ or -] 3.6 to 84.2 [+ or -] 5.0; p < 0.001) and prednisone (65.2 [+ or -] 3.7 to 88.4 [+ or -]8.0; p < 0.001) groups. The improvement was slightly but significantly greater in the prednisone group (p < 0.05). There was a significant and a similar degree of reduction in clinical symptom scores in both treated groups. (2)

Th2 cytokines IL-5 and IL-13 were significantly reduced in both treated groups (p < 0.001 for each). Strikingly, serum IFN-[gamma] and cortisol levels were significantly decreased in the prednisone group (p < 0.001) but significantly increased in the herbal group (p < 0.001). In addition, the herbal treatment had no significant effect on body weight (increases in body weight post-therapy: 2.8 kg in the prednisone group vs. 0.8 kg in the herbal group). No significant side effects were observed. All hematologic, electrocardiogram, and liver and kidney functions were normal in both groups. Thus, the herbal appeared to be effective and well-tolerated and may offer benefits comparable to standard corticosteroid therapy without undesirable side effects. (2)

Leads from Ayurvedic Medicine

Although the research is not that recent, dating from 1998, it is worthwhile reiterating that Boswellia is a significant anti-inflammatory herb that has shown clinical benefit in asthma. 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. (3) Only 27% of patients in the control group showed improvement, whereas 70% of patients taking Boswellia improved. 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 [FEV.sub.1], a measure of bronchial obstruction (p = 0.0001). Peak expiratory flow rate (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.

Two plants belonging to Solanaceae, namely Solanum trilobatum and S. xanthocarpum, are widely used in South Indian traditional medicine to treat respiratory diseases. In a pilot study conducted earlier, a single dose of either S. xanthocarpum or S. trilobatum was found to offer significant relief from bronchospasm in asthmatic patients. (4) Because of the encouraging results obtained in the single-dose study, it was considered worthwhile to investigate these herbs in a more substantial study. (5) The clinical efficacy of either S. xanthocarpum (n = 20) or S. trilobatum (n = 20) each in a dose of 900 mg/day dried aerial parts for three days was investigated in mild to moderate bronchial asthma. Their effect was compared with standard bronchodilator drugs, salbutamol (4 mg x 3) and deriphylline (200 mg x 3). Respiratory function was assessed by measuring the PEFR using a mini peak flow meter. In addition, improvement in lung function was assessed by physical examination (rhonchi and crepitation) and other symptoms such as cough, breathlessness, and sputum. Both herbs produced a progressive improvement in the ventilatory function of asthmatic individuals over three days. The scores for rhonchi, cough, breathlessness, and sputum were all decreased by these treatments. Results were significant at p < 0.001. The improvement in PEFR and the reduction in other symptom scores clearly indicate a bronchodilator effect, a decrease of edema and secretions in the airway lumen. The response to these herbs was considered to be equivalent to that of deriphylline but less than salbutamol. No untoward effects were reported during the study. (5)

Leads from Western Herbal Medicine 

Ivy leaves (Hedera helix) are a rich source of saponins and as such have been traditionally used as an expectorant in the management of bronchial conditions. A review of the published research was undertaken to explore if extracts from dried ivy leaves are effective in the management of chronic airway obstruction in children suffering from bronchial asthma. (6) A systematic review identified three trials that were conducted in children and met the selection criteria. The data from these three trials, published in German medical journals, were subjected to reanalysis. (6)

The authors concluded that the data from the eligible studies show that the three formulations used in the trials (drops, syrup, suppositories) can be safe and effective in improving the respiratory function (as measured by body-plethysmography and spirometry) in children suffering from mildly to moderately severe, reversible chronic respiratory tract diseases (obstructive or non-obstructive). These findings are consistent with the results of another trial in adults with simple or obstructive chronic bronchitis. (6)

They also suggested that a major limitation of their analysis is that there is only one placebo-controlled trial, which, furthermore, has only a small sample size (n = 24 patients evaluable for efficacy). However, the trial was adequately powered to demonstrate superiority of the herbal extract. The same applies to the two reference-controlled trials, which established non-inferiority of ivy leaf extract syrup (n = 25) and suppositories (n = 26) to drops. The three trials reviewed were comparable in design, outcome measures, and study populations so that a direct comparison of the results (as performed in the estimation of the "indirect" effect sizes for syrup and suppositories against placebo) appears to be justified. (6) However, they cautioned that additional placebo-controlled trials with appropriate methodology and larger patient numbers are required.

Euphorbia hirta (asthma weed) is not really a new lead for asthma, having been traditionally used in the west for this condition for over 100 years. Clinical studies are lacking, and any understanding of its effects in asthma has been fairly rudimentary at best. However, a recent pharmacological study suggests that the herb could have pronounced antiallergic activity. (7) A 95% ethanol extract of Euphorbia aerial parts showed antihistaminic, anti-inflammatory, and immunosuppressive properties in various animal models. Both early and late phase allergic reactions were inhibited at oral doses ranging from around 1 to 20 g/kg equivalent of the dried herb. These are high doses, but they do suggest that the activity of Euphorbia in asthma could be based in part on anti-allergic and immune-modulating effects.

Notes

1. Hoang BX, Shaw DG, Levine S, et al. New approach in asthma treatment using excitatory modulator. Phytother Res. 2007; 21: 554-557.

2. Li X-M. Traditional Chinese herbal remedies for asthma and food allergy. J Allergy Clin Immunol. 2007; 120: 25-31.

3. Gupta I, Gupta V, Parihar A, et al. Effects of Boswellia serrata gum resin in patients with bronchial asthma: results of a double-blind, placebo-controlled, 6-week clinical study. Eur J Med Res. 1998; 3(11): 511-514.

4. Govindan S, Viswanathan S, Vijayasekaran V, et al. A pilot study on the clinical efficacy of S. xanthocarpum and S. trilobatum in bronchial asthma. J Ethnopharmacol. 1999; 66: 205-210.

5. Govindan S, Viswanathan S, Vijayasekaran V, et al. Further studies on the clinical efficacy of solanum xanthocarpum and solanum trilobatum in bronchial asthma. Phytother Res. 2004; 18: 805-809.

6. Hofmann D, Hecker M, Volp A. Efficacy of dry extract of ivy leaves in children with bronchial asthma--a review of randomized controlled trials. Phytomed. 2003; 10: 213-220.

7. Singh GD, Kaiser P, Youssouf MS, et al. Inhibition of early and late phase allergic reactions by euphorbia hirta L. Phytother Res. 2006; 20: 316-321.

by Kerry Bone, FNIMH, FNHAA

www.mediherb.com

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