New Studies Confirm the Power of Three Chinese Herbs for Asthma

If you’ve ever tried to breathe through a straw or felt as if an invisible gorilla had your chest in a vice, or simply had to focus all your will and attention on drawing each breath—if you’ve ever had a bad asthma attack, you know how frightening asthma can be.

One in every 13 Americans suffers from this chronic lung disease characterized by ongoing airway inflammation, episodes of bronchoconstriction, and trouble breathing.[1] An estimated 39.5 million people (12.9%), including 10.5 million (14.0%) children in the United States have been diagnosed with asthma in their lifetimes.[2] Asthma is the top reason for missed school days in children.[3] In 2008, the group of children aged 5–17 years who each had one or more asthma attacks in the previous 12 months missed, in total, 10.5 million days of school. Adults who were employed and who each had one or more asthma attacks during the previous 12 months missed, in total, 14.2 million days of work due to asthma.[4] Researchers estimate the annual cost of asthma in the United States is around $56 billion.[5]

The standard medications for asthma include inhaled corticosteroids and beta-2 agonists, leukotriene modifiers, oral corticosteroids, and theophylline.[6] Steroids, however, can suppress endogenous cortisol production[7] and immune function.[8] Even inhaled steroids can suppress adrenal function, cause mucosal immunosuppression, and increase risk of respiratory infections.[9] In spite of their risks, they are being overprescribed: “Inhalers have become almost a fashion accessory”, write two respiratory specialists in a 2015 editorial.[10]

Children under five, in particular, may be at risk of being overprescribed potent oral steroids, when less potent inhaled steroids or beta agonist sprays would suffice, according to a 2017 study. The study analysed the computerised databases of Texas Children’s Health Plan between January 2011 and January 2016.[11] “Over the past 30 years, [oral corticosteroid] prescribing for children with asthma has gone from underuse to what now appears to be substantial overprescribing”! the authors write.

Even” safer” medications such as beta-agonists can lead to tolerance and can actually increase airway inflammation.[12] Long-acting beta-agonists may actually increase the risk for fatal and nonfatal asthma exacerbations.[13]

A Natural Alternative as Effective as Steroids— Without the Side Effects?

For the last 17 years, paediatric immunologist Xiu-Min Li, MD, and her team at the Icahn School of Medicine at Mount Sinai in New York have been proving the efficacy of a novel, nonsteroidal blend of traditional Chinese herbs for asthma.14 The formula is called ASHMI (anti-asthma herbal medicine intervention) and blends the three most effective herbs found in a traditional 14-herb formula15 with a long history of human use in China: lingzi (Ganoderma lucidum, commonly known as reishi), gancao (Glycyrrhiza uralensis, commonly known as Chinese liquorice) and ku shen (Sophora flavescens, commonly known as shrubby sophora).16 ASHMI has broad therapeutic effects on the major pathogenic mechanisms of asthma, including inflammation and bronchoconstriction, and it also raises endogenous cortisol production instead of suppressing it as steroid medications do. In vitro studies conducted by the team have unravelled the ways in which the herbs function—modulating the activity of immune cells, inhibiting smooth muscle contraction, and increasing the production of cortisol. Human studies, in turn, have demonstrated the formula’s power and gentleness.

In our March 2008 edition of FOCUS, we reported on the team’s first human study, an FDA-approved Phase I and Phase II trial involving 13 researchers—11 of them physicians—from the Weifang Asthma Hospital, the Weifang School of Medicine, and the Mount Sinai School of Medicine. This study found ASHMI as effective as prednisone, without suppressing cortisol or immune function.[14]

During the four-week, double-blind, randomized placebo-control trial, 45 individuals with moderate to severe asthma received oral ASHMI capsules and placebo prednisone tablets (ASHMI group) and 46 matched individuals received oral prednisone tablets (20 mg) and placebo ASHMI capsules (prednisone group). The ASHMI group received four capsules three times a day, with each capsule containing 0.3 g of a dried aqueous extract of the three herbs. Placebo capsules were similar in appearance to prednisone. The prednisone group received oral tablets of 20 mg once a day in the morning.[15]

Post-treatment lung function significantly improved in both groups, with the steroid group showing only a slightly greater benefit. Clinical symptom scores, use of beta agonist bronchodilators, and serum IgE levels were also reduced significantly in both groups. However, a key difference emerged: though both groups had low cortisol levels before the study, cortisol was even further suppressed in the prednisone group, while in the ASHMI group, levels increased into the normal range. And while prednisone decreased the secretion of interferon (IFN-γ), ASHMI increased it, improving immune function.[16]

A second randomized, double-blind, placebo-controlled, dose-escalation study followed in 2009 to assess safety. 20 allergic individuals were included, to test three different doses of ASHMI: 600 mg, 1200 mg, or 1800 mg. For each test dose, four individuals were treated, and two individuals were given the placebo.[17] All three doses were well tolerated.^18[18] Vital signs, electrocardiogram findings, and laboratory results obtained at pre-and post-treatment visits remained within normal range. No abnormal immunologic alterations were detected.

How ASHMI Works at the Cellular Level

Studies in mice reveal how ASHMI might work. First, it appears to prevent early reactivity to allergen exposure.^19[19] It also reduces late airway reactions, and reduces airway inflammation and remodelling (the long-term thickening of the smooth muscles of the bronchi). Levels of collagen in lung fluid—which are associated with airway remodelling—are also reduced. In addition, ASHMI also helps inhibit constriction caused by the neurotransmitter acetylcholine and increase levels of smooth-muscle relaxants such as prostaglandins.  It reduces lung inflammation and mucus in mice bred for late-onset asthma.[20] A single dose of ASHMI dramatically reduces airway hyperresponsiveness in response to challenge with the neurotransmitter acetylcholine, which can contribute to asthma.[21]Treatment of mice with ASHMI in drinking water for four weeks prevents the development of asthma, and this therapeutic effect remains at eight weeks post-therapy.[22]

At the same time, in vitro studies reveal intriguing mechanisms underlying the formula’s effectiveness. In vitro studies using cells from human lungs found that one of the extracts, gancao (Chinese liquorice), decreased levels of inflammatory chemicals such as interleukin (IL)-8.[23] Other in vitro studies found that the formula decreased inflammatory molecules such as tumor necrosis factor (TNF) and nuclear factor kappa B (NF-κB).[24] ASHMI also inhibited production of the inflammatory interleukins IL-4 and IL-5 as well as a molecule called eotaxin-1, which stimulates the migration of inflammatory white blood cells from blood into the lungs.[25]

A 2013 editorial in Clinical & Experimental Allergy, entitled Chinese Herbal Anti-asthma Tea to Go!, reviews the work by Li and her colleagues and concludes: “Experimental and clinical evidence suggests that ASHMI may be an effective future modality for treatment and/or prevention for allergic asthma.[26] In sum, ASHMI improves lung function, reduces symptom scores in asthma, and leads to decreased beta2-agonist use -and does so without prednisone’s adverse effect on adrenal function, and with no overall immune suppression.

References

[1] Centers for Disease Control and Prevention (US). Asthma [Internet]. Atlanta (GA): U S Department of Health and Human Services; updated 2016 [cited 2017 Jul 22]. Available from:  http://www.cdc.gov/asthma/default.htm

[2] Centers for Disease Control and Prevention (US). Asthma facts [Internet]. Atlanta (GA): U S Department of Health and Human Services; 2013 [cited 2017 Jul 22]. Available from:

http://www.cdc.gov/nchs/fastats/asthma.htm

[3] Moorman JE, Akinbami LJ, Bailey CM, et al. National surveillance of asthma: United States, 2001-2010. Vital Health Stat 3. 2012;(35):1-58. PMID: 24252609

[4] Akinbami LJ, Moorman JE, Liu X. Asthma prevalence, healthcare use, and mortality: United States, 2005-2009. Natl Health Stat Report. 2011;(32):1-14. PMID: 21355352

[5] United States Environmental Protection Agency. Asthma facts [Internet]. Washington, DC: United States Environmental Protection Agency; 2013 [cited 2017 Jul 22]. Available from:  https://www.epa.gov/sites/production/files/2017-08/documents/2017_asthma_fact_sheet.pdf

[6] Mayo Clinic staff. Asthma treatment and drugs [Internet]. Mayo Foundation for Medical Education and Research, Mayo Clinic; 2016 [cited 2017 Jul 22]. Available from:

http://www.mayoclinic.org/diseases-conditions/asthma/basics/treatment/con-20026992

[7] The Asthma Center. Steroid dependence [Internet]. Philadelphia (PA): The Asthma Center Education and Research Fund [cited 2017 Jul 22]. Available from:

http://www.theasthmacenter.org/index.php/disease_information/asthma/medical_treatment_of_asthma/corticosteroids/corticosteroid_risks/steroid_dependance

[8] Fuenfer MM, Olson GE, Polk HC Jr. Effect of various corticosteroids upon the phagocytic bactericidal activity of neutrophils. Surgery. 1975;78(1):27-33. PMID: 1138397

[9] Sabroe I, Postma D, Heijink I, et al. The yin and the yang of immunosuppression with inhaled corticosteroids. Thorax. 2013;68:1085-7. PMID: 23929790

[10] Bush A, Fleming L. Is asthma overdiagnosed? Arch Dis Child. 2016;101(8):688-9. PMID: 27049005

[11] Farber HJ, Silveira EA, Vicere DR, et al. Oral corticosteroid prescribing for children with asthma in a medicaid managed care program. Pediatrics. 2017;139(5). PMID: 28557753

[12] Salpeter SR, Ormiston TM, Salpeter EE. Meta-analysis: respiratory tolerance to regular beta2-agonist use in patients with asthma. Ann Intern Med. 2004;140(10):802-13. PMID: 15148067

[13] Salpeter SR, Buckley NS, Ormiston TM. Meta-analysis: effect of long-acting beta-agonists on severe asthma exacerbations and asthma-related deaths. Ann Intern Med. 2006;144(12):904-12. PMID: 16754916

[14] Wen MC, Wei CH, Hu ZQ, et al. Efficacy and tolerability of anti-asthma herbal medicine intervention in adult patients with moderate-severe allergic asthma. J Allergy Clin Immunol. 2005;116(3):517-24. PMID: 16159618

[15] Li XM, Huang CK, Zhang TF, et al. The Chinese herbal medicine formula MSSM-002 suppresses allergic airway hyperreactivity and modulates TH1=TH2 responses in a murine model of allergic asthma. J Allergy Clin Immunol. 2000;106:660-8. PMID: 11031336

[16]N/A

[17] Note: Although the protocol specified enrollment of 18 individuals in the study (six per dose level), because of an error in randomizing, two additional individuals were recruited in order to complete the experiment while maintaining blinding.

[18] Kelly-Pieper K, Patil SP, Busse PJ. Safety and tolerability of an antiasthma herbal Formula (ASHMI) in adult subjects with asthma: a randomized, double-blinded, placebo-controlled, dose-escalation phase I study. Altern Complement Med. 2009;15(7):735-43. PMID: 19586409

[19] Zhang T, Srivastava K, Wen MC, et al. Pharmacology and immunological actions of a herbal medicine ASHMI on allergic asthma. Phytother Res. 2010;24:1047-55. PMID: 19998324

[20] Busse PJ, Schofield B, Birmingham N, et al. The traditional Chinese herbal formula ASHMI inhibits allergic lung inflammation in antigen-sensitized and antigen-challenged aged mice. Ann Allergy Asthma Immunol. 2010;104:236-46. PMID: 20377113

[21] Srivastava K, Sampson HA, Emala CW, et al. The anti-asthma herbal medicine ASHMI acutely inhibits airway smooth muscle contraction via prostaglandin E2 activation of EP2/EP4 receptors. J Physiol Lung Cell Mol Physiol. 2013;305(12):L1002-10. PMID: 24163140

[22] Srivastava K, Sampson HA, Li X. The anti-asthma Chinese herbal formula ASHMI provides more persistent benefits than dexamethasone in a murine asthma model. J All Clin Immun. 2011;2(127),p AB261

[23] Matsui S, Matsumoto H, Sonoda Y, et al. Glycyrrhizin and related compounds down-regulate production of inflammatory chemokines IL-8 and eotaxin 1 in a human lung fibroblast cell line. Int Immunopharmacol. 2004;4:1633-44. PMID: 15454116

[24] Li XM. Treatment of asthma and food allergy with herbal interventions from traditional Chinese medicine. Mount Sinai J Med. 2011;78:697-716. PMID: 21913200

[25] Jayaprakasam B, Yang N, Wen MC, et al. Constituents of the anti-asthma herbal formula ASHMI(TM) synergistically inhibit IL-4 and IL-5 secretion by murine Th2 memory cells, and eotaxin by human lung fibroblasts in vitro. J Integr Med. 2013;11(3):195-205. PMID: 23743163

[26] Wang YH, Hogan SP. Chinese herbal anti-asthma tea to go! Clin Exp Allergy. 2010;40(11):1590-2. PMID: 21039969