Herbal Remedies To Manage Asthma

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Allergic asthma is defined as a disease of the respiratory passages characterized by airway hyperresponsiveness (an exaggerated airway-narrowing response) to specific triggers such as viruses, allergens and exercise that leads to increased mucus production, reversible airway obstruction, infiltration of T helper cells (Th2) eosinophils and nonspecific airway hyper responsiveness (bronchial constriction) resulting in expiratory dysponea of an obstructive type with recurrent episodes of wheezing, breathlessness, chest tightness and/or coughing that can vary in intensity and duration, this condition is usually reversible either spontaneously or with appropriate asthma treatments such as a fast-acting bronchodilators. Asthma affects people of all ages and the most common trigger is continuous exposure to allergens.  Recently it has been proposed that asthma may result from an imbalance between T helper 1 (Th1) and T helper type 2 (Th2) cells,  mediated by the overexpression of (T helper cells) Th2-mediated or Th1-mediated cytokines, including interleukin (IL)-4, IL-5, IL-9 and IL-13. Present therapies like that of steroids , bronchodilators and anti-Ig E antibodies have failed to control the symptoms of asthma completely and even shortcoming side effects and cost effectiveness is less. Therefore alternative methods such as Indian herbal medication in association with acupuncture have been used for treating asthma.

HOW TO TREAT ASTHMA:

Correction of the Th1/Th2 Imbalance. The secretion of IFN-????, IL-12, tumor necrosis factor-???? (TNF-????) by Th1 cells and secretion of IL-4, IL5, IL-13. IL-4 together with IL-13 by Th2 cells causes isotype class switching of B cells towards Immunoglobulin-E (IgE) synthesis, which can bind to high-affinity receptors on mast cells and basophils, leading to their subsequent activation. IL-5 activates eosinophils which are further attracted to the lungs, where they secrete numerous inflammatory cytokines and chemokines. IL-13 directly affects the airway epithelium by increasing goblet cell differentiation, activation of fibroblasts, and bronchial hyper-responsiveness. These cytokines and two transcription factors, that is, T-bet and GATA-3 affect the Th1/Th2 balance. GATA-3 and T-bet are further influenced by IL-12, IFN-????, or IL-4 via the signal transducers and  transcription activators (STAT), that is, STAT4, STAT1, and STAT6.

Masking MAPK and NF-????B Signaling Pathways: Mitogen-activated protein kinases (MAPKs), which comprise three major subgroups, that are extracellular signal related kinase 1/2 (ERK1/2), p38, and c-Jun N-terminal kinase 1/2 (JNK1/2), which play critical roles in the activation of inflammatory cells. Nuclear factor kappa B (NF-????B) is an important transcription factor involved in the expression of various pro-inflammatory genes. The allergen activates NF- ????B in the lungs and in airway epithelial cells and macrophages in asthmatic patients.

Targeting the Treg/Th17 Cells. T-regulatory cells (Tregs) are a heterogeneous group of cells that maintains the homeostasis of pulmonary immunity by establishing immune tolerance to non-harmful antigens or suppressing effectors of T cell immunity. The specification of Treg subset is driven by transcription factor fork head box P3 (Foxp3). Th17 cells are main players in chronic lung inflammation. Steroid-resistant asthma and neutrophil-mediated asthma have been proved to be related to Th17 cells which are further involved in the production of IL-17 that directly affects the airway smooth muscle by inducing allergen-induced airway hyper-responsiveness. ROR????t is the transcription factor related to Th17, which increases IL-17 production in Th17 cells. The lung tissue showed increased expressions of IL-17A and IL-17F. Most CD11c+ myeloid DCs (Dendritic cells) in the lung are immature, which express relatively low levels of major histocompatibility complex (MHC) class II, and have a high capacity of antigen uptake but poor T cell stimulating activity. Thus, inhibiting functional differentiation of pulmonary immature DC to mature DC may be a useful strategy to restrict the activation of T cells in the treatment of allergic asthma.

Inhibition of Mast Cell Degranulation. Mast cell degranulation, is enhanced by antigen-mediated crosslinking of IgE which is bound to Fc????R1 surface receptors or alterations in the adjacent local tissue environment resulting in discharge of the mediators that are stored or newly synthesized by the mast cells which additionally attracts leukocytes (eosinophils, basophils, Th2 lymphocytes, and neutrophils) to the site of inflammation and exaggerate the inflammatory response.

Targeting HO-1 and Nrf-2. Oxidative stress performs an important role in the pathogenesis of most airway diseases. Heme oxygenase-1 (HO-1) is produced in the airways of patients with asthma as a natural antioxidant, it exerts its cytoprotective effect against oxidative cell injury. It suppress the production of IL-13-induced goblet cell hyperplasia and MUC5AC. Hence, HO-1 with its transcription factor, nuclear factor E2-related factor 2 (Nrf-2) is a efficient strategy for  control of asthma.

 Relaxing Airway Smooth Muscle. Relax airway smooth muscle by antihistaminics and anticholinergic and ????2-adrenoreceptors stimulation and Ca2+ signaling blocking.

Alteration of TGF-????1/Smad signal pathway was found to be one of the important mechanisms for signal conduction in asthma airway remodeling through inhibition of Th2 cytokines and TGF-????1. Transforming growth factor β1 (TGF-β1), a growth factor elevated in the airway of patients with asthma, plays a role in airway remodeling and in the shortening of various airway structural cells. TGF-β1 signaling begins when activated TGF-β1 binds to the serine-threonine kinase TGF-β type II receptor (TβR-II) then TβR-II recruits and phosphorylates TGF-β type I receptor (TβR-I) at serine/threonine residues. Activated TβR-I induces the phosphorylation of Smad2 and Smad3 (Smad2/3) transcription factors. Smad4 after the association, the translocates to the nucleus and promote the transcription of target genes. The Smad complex binds to DNA directly or indirectly via interaction with other proteins, recruiting coactivators to mediate the transcription of genes involved in a variety of pathways mediating airways remodeling.TGF-β1 stimulates the recruitment of inflammatory cells to the airway and promotes the secretion of additional growth factors and inflammatory cytokines and suppress lymphocyte proliferation. TGF-β1 may participate in airway narrowing by increasing ASM (airway smooth muscle) contractile protein expression that alters airway structural cell size or accumulation can influence AHR (airway hyper-responsiveness.) TGF-β1 promotes airway structural cell fibrosis in asthma through various mechanisms. TGF-β1 mediates the expression of genes implicated in fibrosis, including collagen, proteases, and fibronectin, through a Smad-dependent mechanism. In addition, TGF-β1 may mediate a subset of its fibrotic effects through the production of ROS generated by the mitochondrial electron transport chain and the ROS-producing enzyme nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4).

Management of the Arachidonic Acid Metabolism Pathway (AAMP). Arachidonic acid (AA) from the diet or after synthesis is stored in membrane phospholipids and is liberated under appropriate stimulatory conditions by the enzyme phospholipase A2 (PLA2). Arachidonic acid is then metabolized by three main classes of enzymes (cyclooxygenases (COX), lipoxygenases (LOX), and p450 epoxygenases) and all products of these three pathways like prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), leukotrienes (LTs), and so forth are related to inflammatory and anaphylactic reaction. PGE2 has been the potent proinflammatory mediator and has many beneficial functions, such as the inhibition of inflammatory cell recruitment, reduction of leukotrienes and PGD2, and decrease of Th2 differentiation, thereby modulating inflammation and tissue repair. LTs (LTB4, LTC4, LTD4, etc.) are also thought to be important mediators of airway inflammation and airway obstruction in asthma. LTB4 can act as a neutrophil chemoattractant. Thus, strategies targeting AA metabolism are effective in many inflammatory diseases.

HOW THE PLANTS BENEFIT THE ASTHMATIC PATIENT:

Boswellia serrata: The gum resin of B serrata is known in the Indian Ayurvedic system of medicine as Salai guggal and contains boswellic acids which have been shown to inhibit leukotriene biosynthesis and a significant increase in forced expiratory volume in one second (FEV1). Tylophora indica (T indica) Antamool is a plant indigenous to India and reputed to be able to provide relief to patients with bronchial asthma. Tylophora seems to increases airflow and reduce allergic reactions. It clear the lungs from the excess mucus. Being mucolytic and a good expectorant , it is useful in cases of asthma and bronchitis when excessive mucus production is the main underlying cause of a cough, shortness of breath, and wheezing. Ganoderma lucidem (Reishi mushroom) suppresses the inflammation and allergy in asthma patients. Sophora flavescentis (shrubby sophora) the flavinoid rich fraction of plant root inhibits Ig E synthesis. Glycyrhhiza uralensis, (liquorice) reduces airway responses in asthma patients Inhibit Memory Th2 Responses thus inhibitory effects on antigen mediated asthma. Aleurites moluccana (candlenut tree) the leaf extract has potent anti-hypersensitivity effects. Nigella sativa is known for its relaxant effect on smooth muscle tissue the extracts and oils from N. sativa have inhibitory effects on histamine (H1) receptors and stimulatory effects on β-adrenergic receptors and used in the prevention of cough. Astragalus membranaceus (Mongolian milkvetch)leaf extract modulates Th1 and Th2 cytokines. It regulates relative contents of CD4+, CD25, CD127 and Treg cells which secrete a variety of cytokines that can suppress the proliferation of T cells and the synthesis of IgE by the transmission of inflammatory cells, such as IL-10 and TGF-β.  Panax ginseng  inhibited the numbers of goblet cells and further small G proteins and MAP kinases in bronchoalveolar cells and lung tissues and restored the expression of EMBP, Muc5ac, CD40, and CD40L, as well as the mRNA and protein levels of interleukin (IL)-1β, IL-4, IL-5, and tumor necrosis factor (TNF)-α. Saururus chinensis inhibits eicosanoid (Eicosanoids,   which   include   prostaglandins(PGs)  and  leukotrienes  (LTs)  are  inflammatory  mediators that  are  biosynthesized  in  many  cell  types  by  cyclo-oxygenases  (COX)  and  lipoxygenases  (LOX)  and  are  strongly  associated  with bronchial asthma) generation, inhibition of COX-2, degranulation as well as the down regulation of IL-4 and eotaxin (a  potent  eosinophil chemotactic  factor  that  plays  a  central  role  in  eosinophilic airway  inflammation  in  asthma) mRNA expression.
Psoralea, corylifolia (babchi), P.fructus Psoralen, a major constituent of PF, has immunomodulatory properties on Th2 response, reduced airway hyperresponsiveness (AHR) to aerosolized methacholine and decreased IL-4 and IL-13 levels and inhibitory effects on the accumulation of eosinophills into airways and blood. The immune balance controlled by T helper 1 (Th1) and T helper 2 (Th2) is crucial for immunoregulation and its imbalance causes various immune diseases including allergic disorders and asthma. Ligustrazine were reported a similar mechanism of decreasing the ratio of GATA3/T-bet expression level. ligustrazine can modulate the expression of transcription factors for Th1 (T-bet) and Th2 (Gata-3) in asthma thus reducing the influx of eosinophils and neutrophils in airways. Scutellaria baicalensis and Cnidii monnieri fructus extract Osthol suppressed IL-4-induced eotaxin (a key mediator in allergic diseases with eosinophilic infiltration) in epithelial cells via inhibition of STAT6 expression. Taraxacum officinale extract, Duchesnea chrysantha , Echinacea purpurea, Zingiber officinale (ginger) Actinidia polygama fructus maintain Th1 and Th2 imbalance. Crocus sativus: Active constituents of saffron (safranal and crocin) have  antioxidant and anti-inflammatory effects and so have beneficial effects on asthma. This is reported that saffron supplementation in animals with allergic asthma decreased eosinophils, basophils, and total white blood cells, and some of these effects were found to be equal to dexamethasone. saffron had a potent relaxant effect on tracheal chains of guinea pigs which was comparable to or even higher than that of theophylline. T
he hemp plant, Cannabis sativa , which contains the psychoactive principle Δ9-tetrahydrocannabinol (Δ9-THC), produce a pleasant intoxicating effect. has a bronchodilator effect. 

Acupuncture:

a classic prevention treatment for asthma is Tianjiu Therapy in Sanfu Days. the three hottest days in a year which are calculated by ancient calendar are the Sanfu Days. Both Positive-qi in human body and nature are in a most energetic status in Sanfu Days so this is best time for cold-insufficiency patients to boost Positive-qi. As a result, patients can have a strong body-resistance  to combat extrinsic pathogens because they have already gathered enough Positive-qi intrinsicly. This Therapy means applying herbs patches on special acupoints in order to stimulate skin to form blisters, hyperemia, and even suppuration. This improve the body immunity which in turn can get a purpose of preventing and decreasing respiratory viral or bacterial infection, reducing airway inflammation and damage, and reducing airway hyperresponsiveness which in turn reduces the chances of asthma attacks.

First, herbal formula is singly used to relieve asthmatic symptom on intermittent asthmatic children contained Radix Astragali Mongolici 10 g, Rhizoma Polygonati Odorati 10 g, Fructus Ligustri Lucidi 10 g, Fructus Psoraleae 10 g, Radix Pseudostellariae 3 g, Fructus Schisandrae Chinensis 3 g, Fructus Jujubae 10 g, Concha Ostreae 10 g, and Endoconcha Sepiellae 10 g. Their results showed that the formula reduced the number of intermittent asthma attacks, decreased the syndrome scores, and reduced the airway resistance in the children.

All these complimentary therapeutic approaches have been regarded as having less side effects and being used as the adjuvant therapy for the diseases. Furthermore, many researchers also aim to identify the active components of herb medicine for the purification and development of drugs.

References:                                                                                        

  1. Kjell A. (1969) Allergic asthma in childhood.  Arch. Dis. Childh. 44; 1-10.
  2. Jaclyn Q, Kyla J. H, Jorge M, Francisco N, Harold K (2018).Allergy Asthma Clin Immunol. ; 14(2): 50. 
  3. Herbal Remedies for Asthma –A Review: /J. Pharm. Sci. & Res. Vol. 8(6), 2016, 431-433.
  4. Urata Y, Yoshida S, Irie Y, Tanigawa T ,Amayasuw H , Nakabayashiz M and K. Akahoriz K.(2002) Treatment of asthma patients with herbal medicine TJ-96: a randomized controlled trial. Respiratory Medicine Vol. 96 (2002) 469^ 474.
  5. Irwin Z, Donald P. Tashkin(2000) Alternative medicine for allergy and asthma. Journal of allergy and clinical immunology Volume 106, Issue 4, Pages 603–614t.
  6. Liu, Fang et al. (2016) “Herbal Medicines for Asthmatic Inflammation: From Basic Researches to Clinical Applications.” Mediators of inflammation  vol.: 6943135. doi:10.1155/2016/6943135

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