Wednesday, 9 April 2014

Asthma in Herbs' points of view

Kyle J. Norton

Respiratory Disease is defined as medical conditions which affect the breathing organ and tissues including Inflammatory lung disease, Obstructive lung diseases, Restrictive lung diseases, Respiratory tract infections, trachea, bronchi, bronchioles, alveoli, the nerves and  muscles breathing , etc.
 Asthma is a chronic inflammatory disease affecting the air way of the lung with recurring symptoms, such as wheezing, chest tightness, shortness of breath, and coughing. The disease affects people of all ages, and mostly starts during childhood. According to American academy, allergy, asthma and immunology, about 1 in 10 children (10%) had asthma and 1 in 12 adults (8%) had asthma in 2009. (about 25 million, or 8% of the U.S. population)(1).
Epidemiological studies, linking herbs in reduced risk and treatment have been inconclusive(a)(b)(c)(d), but certain herbs have been found to be effectively in some studies.
1. Angelica sinensis (Oliv.)
Dang Qui (Angelica sinensis) is a herb of Genus Angelica from the family Apiaceae, indigenous to China. The herb has been used as a Queen herb in traditional Chinese medicine as an antispasmodic and vasodilatory agent, and to balance the hormones in women for a normal menstrual cycle and menstruation and strengthen heart, spleen, kidneys, and liver for both men and women, etc. In other words, it is used to treat gynecological ailments, fatigue, mild anemia and high blood pressure. It has analgesic, anti-inflammatory, etc..  Ethanolic extract (AD of Angelica in the study at Korea Institute of Oriental Medicine, showed to suppress airway allergic inflammation, by significantly lower airway eosinophilia, cytokine levels, including interleukin (IL)-4, IL-5, and tumor necrosis factor (TNF)-alpha levels, mucus production and immunoglobulin (Ig)E in mice(1). Danggui Buxue Tang, a composition of Angelica sinensis (AS) and Astragalus membranaceus (AM),  in OVA-sensitized mice, its DBT2 or DBT3 showed no improved effects relative to DBT1 in treating asthmatic symptoms but DBT1 showed to suppress airway hyperresponsiveness and OVA-immunoglobulin E (IgE) in serum(2). According to Thammasat University, ethanol found in of Angelica sinensis exerted its anti-inflammatory activity through antioxidant effects(3).

2. Ginkgo biloba
Ginkgo biloba is oldest living tree species, genus Ginkgo, belonging to the family Ginkgoaceae, native to China, from temperate zone to subtropical zone and some parts of north America. It Has been used in traditional herbal medicine in treating impotence, memory loss, respiratory diseases, circulatory disorders and deafness as well as preventing drunkenness, and bedwetting.
Ginkgolide B (GKB), a major chemical compound of ginkgo biloba, in BALB/c mice exerted its anti asthmatic activity through inhibited the increase of T-helper 2 cytokines, such as interleukin (IL)-5 and IL-13 in bronchoalveolar lavage fluid (BALF) and decreased eosinophil count via inhibition of the ERK/MAPK signaling pathway(4). The composition of Ginkgo biloba leaf extract (EGb761),  astaxanthin (ASX) and vitamin C, also showed to exhibit the inhibition of asthma-associated inflammation in asthmatic guinea-pigs(5) and Ginkgo biloba extracts showed to inhibit asthmatic disorder through suppression tof NF-kappaB gene expression actively in HL-60 cells(6). Accordiong to Dokuz Eylul University Hospital, biloba alleviates all established chronic histological changes of lung except smooth muscle thickness in a mouse model of asthma(7).

3. Licorice
Licorice (Glycyrrhiza Glabra) also known as sweetwood, is the genus Glycyrrhiza, belonging to the family Fabaceae, native to the Mediterranean and certain areas of Asia. The herb has been used in traditional medicine to treat skin diseases, coughs, constipation, bronchitis, inflammation, arthritis, etc. Licochalcone A (Lico A) isolated from the root of Xinjiang liquorice, exerted its anti-inflammatory activity on a non-infectious mouse model of asthma, through inhibition of the increase in T-helper type 2 cytokines and reduced serum levels of OVA-specific IgE and IgG(8). ASHMI, the composition of aqueous extracts of Lingzhi (Ganoderma lucidum), Kushen (Sophora flavescens) and Gancao (Glycyrrhiza uralensis), showed to be effective on allergic asthma, through inhibition of production of interleukin (IL)-4 and IL-5 by murine memory Th2 cells and eotaxin-1 production by HLF-1 cells(9).
Other study in a murine model also suggested that ASHMI not only significantly reduce eosinophilic pulmonary inflammation, serum IgE levels, IL-4 and IL-13 levels, but also increase IFN-γ production in lung cell cultures in response to antigen stimulation(10).

4. Chamomile
Chamomile is also known as camomile, common name of many species daisy-like plants in the family Asteraceae. The herb has been used in traditional medicine as antispasmodic and anti-inflammatory constituents and to treat menstrual cramps and sleep disorders, reduce cramping and spastic pain in the bowels, relieve excessive gas and bloating in the intestine, etc. Water composition extract of a mixture of eight herbs (chamomile, saffron, anise, fennel, caraway, licorice, cardomom and black seed), showed to alleviate the symptoms of asthma, through inhibition of histamine released from chemically- and immunologically-induced cells(11).

5. Garlic
Garlic (Allium sativum) is a species in the onion genus, belonging to family Amaryllidaceae, native to central Asia. It has been used popularly in traditional and Chinese medicine in treating common cold and flu to the Plague, blood pressure cholesterol levels, natural antibiotic, etc.
Diallyl disulfide (DADS), a major organosulfur compound found in garlic, in an ovalbumin-induced model of allergic asthma and RAW264.7 cells, showed to inhibit the proinflammatory proteins, through up regulation of Nrf-2/HO-1 and down regulation of NF-κB pathways(12). According to the study by Tarbiat Modares University, purified aged garlic extract exhibited the protective effect of asthma through a significant decrease in the hallmark criteria of allergic airway inflammation levels(13).

6. Grape seed extract
Grapefruit seed extract (GSE) is a liquid extracted from the seeds, pulp, and white membranes of grapefruit. The herb has been used in traditional medicine as an anti bacterial, viral, fungal, parasites and to enhance immune system, protect against colds and flu and malignant disease. Grape seed extract (GSPE) may alleviate the symptoms od asthma through its antioxidant activities. According to the study of University of Ulsan College of Medicine, GSPE effectively suppressed inflammation in both acute and chronic mouse models of asthma, through reduced airway hyperresponsiveness (AHR), decreased inflammatory cells in the BAL fluid, reduced lung inflammation and and decreased IL-4, IL-5, IL-13, and eotaxin-1 expression(14) by downregulating the iNOS expression(15). Other study suggested that GSE significantly ameliorated of the pathological changes of ovalbumin-induced asthma, through inhibition of altered the lung parenchyma pathology and inflammation in ovalbumin-induced murine asthma model(16).

7. Green Tea
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world.
According to teh study at State University of New York Downstate Medical Center, green tea extract (GTE), and its major catechin, consisted an immunoregulatory effects through suppression of IgE production by peripheral blood mononuclear cells of allergic asthmatic patinets(17) and B cell production of IgE without inducing apoptosis(18). Other study suggested an anti asthmatic effect of aqueous extract of Camellia sinensis through increasing the expression level of tumor necrosis factor-beta and interferon-gamma and decreasing the expression of anti-asthmatic cytokines in the lung(19).

8. Ephedra sinica
Ephedra prepared from Ephedra sinica has been used in traditional Chinese medicine for 5,000 years to treat asthma, hypotension and fatigue, etc. In testing the effect of Ma huang water decoction, EWD and cough tablets containing ephedra and liquorice, MXCT, with theophylline (one of the most popular antiasthmatic drugs and a typical substrate of cytochrome P450 (CYP) 1A2, a enzyme in metabolism of xenobiotics), in rat, found the effectiveness of EWD or MXCT in pretreatment in induced CYP1A2 activity, thus speeding up the metabolism of theophylline(20). Modified Shegan Mahuang Decoction (SGMH), in the study of a total of 154 children with cough and variant asthma (C&VA), exhibited the regulation of the serum levels of TNF-alpha (in the regulation of immune cells with function involved in induced fever, apoptotic cell death, cachexia, inflammation and to inhibit tumorigenesis and viral replication and respond to sepsis via IL1 & IL6 producing cells), IL-10( an anti-inflammatory cytokine) and IL-13(associated primarily with the induction of airway disease, and anti-inflammatory properties)(21), Other compositions of Herba Ephedrae decoction showed a strong effect in  antianaphylaxis asthma(22).

9. Stinging nettle (Urtica dioica)
Sting Nettle is a flower plant in the genus Urtica, belonging tothe family Urticaceae, native to Europe, Africa, Asia, and North America.The herb has been used in traditional medicine as diuretic and laxative agent and to treat diarrhea and urinary disorders, to relieve pain, treat arthritis, asthma, bronchitis, sinusitis, etc. According to the Penn State University College of Medicine, extracts from the stinging nettle may provide therapeutic value for some inflammatory medical conditions, due to its released chemicals act to cause itching, dermatitis, and urticaria within moments of contact(23).

10. Boswellia
 B. serrata gum resin extract (BSE) may be potential for the treatment of a variety of inflammatory diseases including inflammatory bowel disease, rheumatoid arthritis, osteoarthritis and asthma, according to Central Laboratory of German Pharmacists, Eschborn,(24), same as boswellic acids in some autoimmune diseases including rheumatoid arthritis, Crohn's disease, ulcerative colitis and bronchial asthma, according to University of Tuebingen(25). The compositions of Boswellia serrata, licorice root (Glycyrrhiza glabra) and Tumeric root (Curcuma longa), in a total of 63 patients with bronchial asthma study, significantly decreased the plasma levels of Plasma leukotriene C(4) (LTC(4))(,) nitric oxide (NO) and malondialdehyde (MDA) in target therapy group when compared with placebo group(26).

11. kava kava (Piper)
Kava Kava is a tall shrub, genus Piper, belonging to family Piperaceae, native to western Pacific. The herb has been used in traditional medicine as a drink for sedative and anesthetic effects and to treat anxiety, insomnia, etc.
Kava kava (Piper) one most commonly used as complementary and alternative medicine (CAM) for treatment of asthma, allergy, and immunologic conditions, may display some adverse effects in the form of a hypersensitivity reaction(27). According to University of Aberdeen, kavain and flavokavains A and B treatment in asthmatic subjects enhanced anti-inflammatory mechanisms, through inhibition of both inhibitor of kappaB (IkappaB) degradation and subsequent translocation of p50 and p65 NF-kappaB subunits from the cytoplasm to the nucleus(28).

12. peppermint oil and leaf (Mentha)
Peppermint is a hybrid mint with small purple or white flowers and downy leaves, in the genus Mentha, belonging to the family Lamiaceae, native to to Europe. The herb has been used in folk medicine as analgesic, antiseptic, antispasmodic, decongestant, agent and to relieve gas, nausea, and stomach pain due to an irritable bowel, intestinal cramps, or indigestion, infecttion, etc.
Mentha, a major chemical constituent found in peppermint, its haplocalyx ethanol extract (MH), showed to inhibit inflammation of the airway in an asthmatic model, through inhibited increases in immunoglobulin (Ig) E and T-helper 2 (Th2)-type cytokines such as IL-4 and IL-5 in bronchoalveolar lavage fluid (BALF) and lung tissue(29).

13. Ginseng (Panax)
Ginseng is a slow-growing perennial plants with fleshy roots, the genus Panax, belonging to the family Araliaceae. Depending to the climate where it grows, ginseng can be classified mainly into Panax ginseng Asian ginseng (root), Red ginseng, wild ginseng, American ginseng (root).
According to Gachon University, Korean. red ginseng (KRG) was found effectively in treating nasal allergic inflammatory reaction in an allergic murine model by reducing Th2 cytokines(30). RG-II, isolated from Panax ginseng, inhibited asthmatic reaction of an ovalbumin-induced murine model, through regulated the T(H)1/T(H)2 immune response(31). Other researchers suggested that Panax ginseng ameliorates airway inflammation through inhibited the numbers of goblet cells and further small G proteins and increased MAP kinases in bronchoalveolar lavage cells and lung tissues, in ovalbumin-induced allergic asthma in mice(32)

14. The compositions
14.1. Sho-seiryu-to (Xiao-Qing-Long-Tang)
 Sho-seiryu-to (Xiao-Qing-Long-Tang) is a herbal composition included Chi Fu Ling, Gui Zhi, Bai Shao, Gan Jiang, Gan Cao, Zhi Ban Xia and Wu Wei Zi. According to the China Medical University, Xiao-Qing-Long-Tang (XQLT), inhibited the allergic inflammation including AHR, IgE elevation and eosinophil infiltration in Der p stimulated mice through regulating neurotrophin and reducing TARC(33) and also exhibited anti-airway inflammatory, anti-airway remodeling, and specific immunoregulatory effects in a chronic asthmatic mice model, through downregulated IL-10, IL-13, RANTES, Eotaxin, and MCP-1 mRNA expression in the lung(34). In the comparison of oral administration of 3 mg/day Shoseiryuto, 30 mg/day LFK, 3 mg/day of Shoseiryuto co-administered with 30 mg/day of LFK, and saline showed a significant  reduction in the accumulation of eosinophils  at 3 mg/day Shoseiryuto co-administered with 30 mg/day of LFK(35).

14.2. Ma-Xing-Gan-Shi-Tang (MXGST)
Ma-Xing-Gan-Shi-Tang (MXGST) is a Chinese herbal formula, included Ephedra, Apricot seed, R.Gypsum and Licorice frequently used in traditional Chinese medicine for asthmatic children in nationwide clinical database in Taiwan(36). According to the Institute of Chinese Medical Science, China Medical, College, Taichung, Taiwan,  in actively sensitized guinea pig study, administration of MXGST (10 g/kg) extracts significantly inhibited the antigen induced immediate asthmatic responses(IAR), through stimulation of beta2-adrenoceptors on bronchial smooth muscle and its anti-inflammatory ability to inhibit the neutrophil into the airway(37).

Taken altogether, herbal medicine list above may be effective in prevention and treatment of asthma disorder, through reduction of air way inflammation via inhibition of histamine released from chemically- and immunologically-induced cells, etc. Some researchers suggested that large sample size and muticenter studies are necessary with identification of the active principle in order to improve the validation of the clinical trial. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying.

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(1) Anti-asthmatic effects of Angelica dahurica against ovalbumin-induced airway inflammation via upregulation of heme oxygenase-1 by Lee MY1, Seo CS, Lee JA, Lee NH, Kim JH, Ha H, Zheng MS, Son JK, Shin HK.(PubMed)
(2) Danggui Buxue Tang attenuates eosinophil infiltration and airway hyperresponsiveness in asthmatic mice by Lin CC1, Liou CJ, Chiang CY, Huang WY, Huang WC.(PubMed)
(3) Antioxidant and nitric oxide inhibition activities of Thai medicinal plants by Makchuchit S1, Itharat A, Tewtrakul S.(PubMed)
(4) A novel anti-inflammatory role for ginkgolide B in asthma via inhibition of the ERK/MAPK signaling pathway by Chu X1, Ci X, He J, Wei M, Yang X, Cao Q, Li H, Guan S, Deng Y, Pang D, Deng X.(PubMed)
(5) Summative interaction between astaxanthin, Ginkgo biloba extract (EGb761) and vitamin C in suppression of respiratory inflammation: a comparison with ibuprofen by Haines DD1, Varga B, Bak I, Juhasz B, Mahmoud FF, Kalantari H, Gesztelyi R, Lekli I, Czompa A, Tosaki A(PubMed)
(6) [Studies on the effect of Ginkgo biloba extracts on NF-kappaB pathway].[Article in Chinese] by Li GH1, Lei XX, Yi YM, Xu BL, Wang HP, Du J.(PubMed)
(7) Effects of Ginkgo biloba on airway histology in a mouse model of chronic asthma by Babayigit A1, Olmez D, Karaman O, Ozogul C, Yilmaz O, Kivcak B, Erbil G, Uzuner N.(PubMed)
(8) Attenuation of allergic airway inflammation in a murine model of asthma by Licochalcone A by Chu X1, Jiang L, Wei M, Yang X, Guan M, Xie X, Wei J, Liu D, Wang D.(PubMed)
(9) 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 by Jayaprakasam B1, Yang N, Wen MC, Wang R, Goldfarb J, Sampson H, Li XM.(PubMed)
(10) Glycyrrhiza uralensis flavonoids present in anti-asthma formula, ASHMI™, inhibit memory Th2 responses in vitro and in vivo by Yang N1, Patil S, Zhuge J, Wen MC, Bolleddula J, Doddaga S, Goldfarb J, Sampson HA, Li XM.(PubMed)
(11) The effect of a herbal water-extract on histamine release from mast cells and on allergic asthma by Haggag EG1, Abou-Moustafa MA, Boucher W, Theoharides TC.(PubMed)
(12) Diallyl-disulfide, an organosulfur compound of garlic, attenuates airway inflammation via activation of the Nrf-2/HO-1 pathway and NF-kappaB suppression by Shin IS1, Hong J, Jeon CM, Shin NR, Kwon OK, Kim HS, Kim JC, Oh SR, Ahn KS.(PubMed)
(13) Purified aged garlic extract modulates allergic airway inflammation in BALB/c mice by Zare A1, Farzaneh P, Pourpak Z, Zahedi F, Moin M, Shahabi S, Hassan ZM.(PubMed)
(14) Grape seed proanthocyanidin extract attenuates allergic inflammation in murine models of asthma by Lee T1, Kwon HS, Bang BR, Lee YS, Park MY, Moon KA, Kim TB, Lee KY, Moon HB, Cho YS.(PubMed)
(15) Grape seed proanthocyanidin extract attenuates airway inflammation and hyperresponsiveness in a murine model of asthma by downregulating inducible nitric oxide synthase by Zhou DY1, Du Q, Li RR, Huang M, Zhang Q, Wei GZ.(PubMed)
(16) Grape seed extract attenuates lung parenchyma pathology in ovalbumin-induced mouse asthma model: an ultrastructural study by Mahmoud YI.(PubMed)
(17) Green tea (Camelia sinensis) mediated suppression of IgE production by peripheral blood mononuclear cells of allergic asthmatic humans by Wu SY1, Silverberg JI, Joks R, Durkin HG, Smith-Norowitz TA.(PubMed)
(18) Green tea (Camelia sinensis) suppresses B cell production of IgE without inducing apoptosis by Hassanain E1, Silverberg JI, Norowitz KB, Chice S, Bluth MH, Brody N, Joks R, Durkin HG, Smith-Norowitz TA.(PubMed)
(19) An aqueous extract of green tea Camellia sinensis increases expression of Th1 cell-specific anti-asthmatic markers by Heo JC1, Rho JR, Kim TH, Kim SY, Lee SH.(PubMed)
(20) Effects of ephedra water decoction and cough tablets containing ephedra and liquorice on CYP1A2 and the pharmacokinetics of theophylline in rats by Tang J1, Zhou X, Ji H, Zhu D, Wu L.(PubMed)
(21) [Effect of modified shegan mahuang decoction on cytokines in children patients with cough and variant asthma].[Article in Chinese]by Chen ZX1, Hu GH.(PubMed)
(22)[Effects of among compositions of Herba Ephedrae decoction on genic xpression of 5-lipoxygenase activating protein, IL-4 and leukotriene C4 in asthmatic mice].[Article in Chinese]by Liu YG1, Luo JB.(PubMed)
(23) Stinging nettle dermatitis by Anderson BE1, Miller CJ, Adams DR(PubMed)
(24) Boswellia serrata: an overall assessment of in vitro, preclinical, pharmacokinetic and clinical data by Abdel-Tawab M1, Werz O, Schubert-Zsilavecz M.(PubMed)
(25) Boswellic acids in chronic inflammatory diseases by Ammon HP.(PubMed)
(26) Natural anti-inflammatory products and leukotriene inhibitors as complementary therapy for bronchial asthma by Houssen ME1, Ragab A, Mesbah A, El-Samanoudy AZ, Othman G, Moustafa AF, Badria FA.(PubMed)
(27) Complementary and alternative interventions in asthma, allergy, and immunology by Bielory L.(PubMed)
(28) Inhibition of TNFalpha-induced activation of nuclear factor kappaB by kava (Piper methysticum) derivatives by Folmer F1, Blasius R, Morceau F, Tabudravu J, Dicato M, Jaspars M, Diederich M.(PubMed)
(29) Protective effects of Mentha haplocalyx ethanol extract (MH) in a mouse model of allergic asthma by Lee MY1, Lee JA, Seo CS, Ha H, Lee NH, Shin HK.(PubMed)
(30) The effect of Korean red ginseng on allergic inflammation in a murine model of allergic rhinitis by Jung JH1, Kang IG, Kim DY, Hwang YJ, Kim ST.(PubMed)
(31) RG-II from Panax ginseng C.A. Meyer suppresses asthmatic reaction by Jung ID1, Kim HY, Park JW, Lee CM, Noh KT, Kang HK, Heo DR, Lee SJ, Son KH, Park HJ, Shin SJ, Park JH, Ryu SW, Park YM.(PubMed)
(32) Panax ginseng ameliorates airway inflammation in an ovalbumin-sensitized mouse allergic asthma model by Kim DY1, Yang WM.(PubMed)
(33) Xiao-Qing-Long-Tang shows preventive effect of asthma in an allergic asthma mouse model through neurotrophin regulation by Chang RS1, Wang SD, Wang YC, Lin LJ, Kao ST, Wang JY.(PubMed)
(34) Xiao-Qing-Long-Tang attenuates allergic airway inflammation and remodeling in repetitive Dermatogoides pteronyssinus challenged chronic asthmatic mice model by Wang SD1, Lin LJ, Chen CL, Lee SC, Lin CC, Wang JY, Kao ST.(PubMed)
(35) Enhancement of anti-allergic effects mediated by the Kampo medicine Shoseiryuto (Xiao-Qing-Long-Tang in Chinese) with lysed Enterococcus faecalis FK-23 in mice by Shimada T1, Kondoh M, Motonaga C, Kitamura Y, Cheng L, Shi H, Enomoto T, Tsuruta D, Ishii M, Kobayashi H.(PubMed)
(36) Identifying core herbal treatments for children with asthma: implication from a chinese herbal medicine database in Taiwan by Chen HY1, Lin YH, Thien PF, Chang SC, Chen YC, Lo SS, Yang SH, Chen JL.(PubMed)
(37) The effects of Ma-Xing-Gan-Shi-Tang on respiratory resistance and airway leukocyte infiltration in asthmatic guinea pigs by Kao ST1, Yeh TJ, Hsieh CC, Shiau HB, Yeh FT, Lin JG.

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