# Systematic Review: Guideline-Based Approach for the Management of Asthma and Subtypes via Chinese Medicine

Authors: Lin Ho Wong; Louisa Tay; Robby Miguel W. J. Goh; Tai Joum Tan; Ruishu Zhou; Aaron Kwun Hang Ho; Pang Ong Wong
Journal: Evidence-Based Complementary and Alternative Medicine
 (2021)

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## Abstract

Background. Asthma is a chronic condition that results in the inflammation and narrowing of airways, often clinically presenting as wheeze and shortness of breath. Little is known of the mechanisms of action (MOA) of herbs used to treat asthma. The aim of this study is to review existing data regarding known MOA of traditional Chinese medicine which will aid in the understanding of possible interactions between Western drugs and Chinese herbs as well as the standardization of management via a proposed guideline to improve patient safety and possible synergism in the long term. Methods. We searched through 5 databases for commonly prescribed herbs and formulas for asthma and narrowed down the search to identify the underlying MOA of individual herbs that could specifically target asthma symptoms. We included studies that stated the MOA of individual herbs when used for treating symptoms of asthma, excluding them if they are described as part of a formula. Results. A total of 26 herbs commonly prescribed for asthma with known mechanism of action were identified. Herbs used for asthma were found to have similar MOA as that for drugs. Based on existing GINA guidelines, a guideline is proposed which includes a total of 5 steps depending on the severity of asthma and the herbs’ MOA. 16 formulas were subsequently identified for the management of asthma, which consist of 12 “stand-alone” and 4 “add-on” formulas. “Stand-alone” formulas used independently for asthma generally follow the GINA guidelines but do not proceed beyond step 3. These formulas consist mainly of beta-agonist and steroid-like effects. “Add-on” formulas added as adjunct to “stand-alone” formulas, however, mainly act on T helper cells or have steroid-like effects. Conclusion. Through the understanding of MOA of herbs and their respective formulas, it will ensue greater patient safety and outcomes.


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## Body

## 1. Introduction

There has been an increasing trend in the use of complementary and alternative medicine (CAM) [1] since its acknowledgement by the World Health Organization (WHO) in 2018 [2]. Herbs are being used by 75% of the people in the world for their basic healthcare needs [3]. Despite the dominance of Western evidence-based medicine in healthcare settings, people occasionally seek traditional Chinese medicine (TCM) treatments, a widely used form of CAM, for medical conditions such as chronic pain and allergies, including, but not limited to, asthma.Asthma is a heterogeneous disease that is characterized by chronic, reversible airway inflammation that involves eosinophil granulocytes, mast cells, T cells, and an array of cytokines. As curative treatments for asthma are still not available, patients are increasingly seeking CAM for add-on treatments, resulting in growing concerns over the concomitant use of Western medicine and CAM herbs [4]. Furthermore, most CAM herbs used for asthma have unknown mechanism of actions (MOA). This could potentially lead to dangerously high concentration of constituents with the same MOA, which may lead to severe side effects.While Western doctors typically manage asthma using the Global Initiative for Asthma (GINA) guidelines based on the disease severity, TCM adopts a less guideline-based and more individualized therapy via a holistic view of the patient’s pathophysiology, resulting in a discrepancy in herbal prescribing between TCM physicians [5]. With increasing scientific evidence to support the use of TCM for asthma [6], it is crucial for both medical doctors and TCM physicians to be aware of the potential risks that come with the simultaneous use of prescribed drugs and herbal medicine.This review aims to categorise commonly used herbs and empirical prescriptions of TCM based on known MOA of Western medicines to allow both Western and TCM physicians to have a better understanding of how drugs and herbs interact. This will hopefully lead to increased patient safety and possible synergism in the long run, giving patients more choices for an individually tailored treatment and better treatment outcomes.


## 2. Methods

### 2.1. Criteria for considering Studies for This Review

#### 2.1.1. Types of Studies

All studies eliciting the mechanism of action of a specific herb in the context of asthma, regardless of the model. Studies which involved the use of multiple herbs simultaneously (i.e., formulas) were excluded.


### 2.2. Search Methods for Identification of Studies

#### 2.2.1. Electronic Searches

For this review, we searched EMBASE, PubMed, CENTRAL, Wanfang, and China National Knowledge Infrastructure (CNKI).


### 2.3. Identifying the Herbs

We first conducted a search to identify herbs which are currently commonly prescribed by TCM physicians by identifying systematic reviews on frequently used herbs or formulas and extracted the relevant herbs from the formulas, using the terms “asthma AND TCM OR Traditional Chinese Medicine OR alternative medicine” in EMBASE, PubMed, CENTRAL, Wanfang, and CNKI (Figure1). The list was subsequently confirmed with a senior TCM physician specialising in TCM Formula-logy.Figure 1
Study flow diagram of the identification of commonly used herbs for asthma.We then extracted the Latin and Mandarin names of the herbs used and identified those used primarily for the treatment of asthma, before searching electronic databases for their mechanisms of action (Figure2). Herbs prescribed for supportive treatment were excluded.Figure 2
Study flow diagram for the identification of articles of commonly used herbs.


### 2.4. EMBASE, PubMed, and Cochrane

#### 2.4.1. CNKI (Overseas CNKI) and Wanfang (Based on the Translations of the Keywords Used in English Medium)

(1)
“Glycyrrhiza uralensis” AND “asthma”(2)
“Prunus armeniaca” AND “asthma”(3)
“Pinellia ternata” AND “asthma”(4)
“Asarum sieboldii” AND “asthma”(5)
“Pheretima aspergillum” AND “asthma”(6)
“Aster tataricus” AND “asthma”(7)
“Fritillaria cirrhosa” AND “asthma”(8)
“Lepidium apetalum” AND “asthma”(9)
“Pericarpium Citri Reticulatae” AND “asthma”(10)
“Cortex Mori” AND “asthma”(11)
“Ephedra sinica” AND “asthma”(12)
“Zingiber officinale” AND “asthma”(13)
“Tussilago farfara” AND “asthma”(14)
“Platycodon grandifloras” AND “asthma”(15)
“Fritillaria thunbergii” AND “asthma”(16)
“Paeonia lactiflora” AND “asthma”(17)
“Magnolia officinalis” AND “asthma”(18)
“Bupleurum chinense” AND “asthma”(19)
“Scutellaria baicalensis” AND “asthma”(20)
“Perilla frutescens” AND “asthma”(21)
“Anemarrhena Rhizoma” AND “asthma”(22)
“Gypsum fibrosum” AND “asthma”(23)
“Eriobotryae Folium” AND “asthma”(24)
“Cinnamomi Ramulus” AND “asthma”(25)
“Zingiberis rhizoma” AND “asthma”(26)
“Schisandra Fructus” AND “asthma”We did not impose any language or publication restrictions.


### 2.5. Data Collection and Analysis

#### 2.5.1. Selection of Studies

Four review authors (TJ, L, RS, and RM) independently reviewed the titles, abstracts, and keywords of all records retrieved to determine the studies to be assessed. We retrieved full articles for further assessment if the information given suggested that the study:(1)
Discussed asthma(2)
And administered any of 26 Chinese herbs identified through the initial searchA fifth review author (LH) acted as arbiter and resolved any differences in opinion.


#### 2.5.2. Data Analysis

We first identified the herbs relevant to treating asthma by the formulas which contain them, for reference purposes (Table1). We then categorised the herbs according to their mechanisms of action (Table 2), plotted a schematic representation of the herbs on the asthma immunopathological pathway (Figure 3), and then compared them against GINA guidelines to identify clinical situations where herbs could see the potential use (Figure 4).Table 1
Summary of MOA of herbs frequently used in asthma.
Herb speciesMechanism of actionGlycyrrhiza uralensisIn murine models(1) BronchodilationLPS-induced NO productionAttenuates acetylcholine- and carbachol-induced contractions(2) Anti-inflammatoryInhibit T lymphocytes, eosinophils, IgE, IL-13, and TNF-aUpregulate caspase-3 and BaxSteroid-like activitiesDownregulate Bcl-2(3) MucolyticInhibit MUC5AC gene expression, production and secretion via regulation of NF-κB, STAT6, and HDAC2In guinea pig models(1) BronchodilationActivate c-GMP and open calcium channelsHuman airway epithelial cells(1) MucolyticInhibit PMA-induced MUC5AC mucin production(2) Anti-inflammatoryInhibit Th2-associated cytokinesHuman peripheral blood mononuclear cells(1) Anti-inflammatoryPhytohaemagglutinin-induced proliferation and inhibition of TNF-alpha, IFN-gamma, and IL-10 productionIn vitro(1) Anti-inflammatoryInhibit memory Th2 responsesInhibit IL-4 and Eotaxin-1 secretionPrunus armeniacaIn murine models(1) Anti-inflammatoryReduce recruitment of eosinophils, macrophages, and lymphocytesInhibit MAPK signalling and IL-4 activationActivate IFN-yPinellia ternataIn murine models(1) Anti-inflammatoryReduce recruitment of eosinophilsReduce IL-4 activation and IFN-y activationAsarum sieboldiiIn guinea pig models(1) Anti-inflammatoryInhibit IL-4 activation and histamine release(2) Signalling pathway regulationRegulate MMP-9 and TIMP-1 signallingPheretima aspergillumIn murine models(1) Anti-inflammatoryInhibit IL-4, IL-5, IgE, and TNF-α activationInhibit eosinophil activationRegulate Th1/Th2 balanceInhibit NF-kB activationInhibit production of NO, PGE2, TNF-a, iNOS, and COX-2Inhibit release of IL-1B and IL-6(2) MucolyticDecrease collagen depositionDecrease mucin glycogen expressionIn guinea pig models(1) Anti-inflammatoryRegulate IFN-y, IL-4, and LTB4 productionIn human models(1) Anti-inflammatoryInhibit TGF-B1 and SMAD2Aster tataricus L. f.In vitro(1) Anti-inflammatorySuppress NO productionInhibit production of PGE2, IL-6, IL-1BInhibit expression of iNOS and COX-2 by inhibition of NF-KB activation(2) Signalling blockadePrevent activation of MAPK signalling cascade via inhibition of phosphorylation of c-Jun N-terminal kinases, extracellular signal-regulated kinases, and p38(3) BronchodilationActivate of B2-adrenoceptorsFritillaria cirrhosa D. DonIn murine models(1) Anti-inflammatorySuppress TH2 cytokines (IL-4, IL-5, and IL-13)Suppress IgE, histamine productionReduce eosinophilic accumulationIncrease IFN-γ production(2) Block signalling pathwaysInhibit ERK/MAPK signalling activation(3) Downregulate NOTCH 2 expression(4) Inhibit MMP-2, MMP-9, and TIMP-1Lepidium apetalumIn murine models(1) Anti-inflammatoryReduce expression of type 2 cytokinesInhibit differentiation and activation of Th2 cytokinesPericarpium Citri ReticulataeIn murine models(1) Anti-inflammatorySuppress eosinophil productionIn guinea pig models(1) Anti-inflammatoryDownregulate expression of eosinophils and serum IgE, IL-4, and IL-5 levels(2) BronchodilationActivation of B2-adrenoceptorsCortex MoriIn murine models(1) Anti-inflammatoryEnhancement of CD4(+)CD25(+)Foxp3(+) regulatory T cells and inhibition of Th2 cytokines such as interleukin (IL)-4, -5 and -13(2) AnticholinergicEphedra sinica StapfIn murine models(1)Anti-inflammatoryReduce infiltration of inflammatory cells in the lungRegulate levels of inflammatory factors such as OVA-IgE, IL-4, and IL-13 and downregulate the expression of p65 NF-k B protein(2) BronchodilatorActivate a-, B1-, and B2-adrenoceptorsZingiber officinale RoscoeIn murine models(1) Anti-inflammatoryInhibit Th2-mediated immune response(2) BronchodilationReduce Ca2+ influx in smooth muscle and promoteβagonist-induced relaxation in human airway smooth muscle by suppressing phosphodiesterase 4DTussilago farfaraIn murine models(1) Anti-inflammatoryRegulate IgE, IL-4, and IL-13 levelsDownregulate the expression of p65 NF-kB proteinInhibit NO, MAPKs, and NF-kBSuppress expression of PGE2, TNF-α, and HMGB1Reduce production of IL-4, IL-5, IL-13, and IL-17Reduce IgE in serum by regulating Th1/Th2 cellsIncrease HO-1 levels affecting Nrf2/HO-1 pathway(2) MucolyticDecrease mucin production by regulating NF-kBPlatycodon grandiflorasIn murine modelsSerum concentrations of NF-κB, MMP-9, and TIMP-1 decreased significantlyIn guinea pig models(1) Anti-inflammatoryPromote and regulate release of LXA4Reduce oxygen-free radicalsPromote secretion of IFN-γRegulate Th1/Th2 balanceFritillaria thunbergiiIn guinea pig modelsInhibit PDE and prevent inactivation of cAMPPaeonia lactifloraIn murine models(1) Anti-inflammatoryInhibit IL-22 and IL-13Magnolia officinalisIn murine models(1) Anti-inflammatoryInhibit IL-4, IL-6, and IL-17Decrease serum MDA levelIncrease SOD and GSH-Px/p-JNK, NF-κB, caspase-3, and γH2 Ax levelsInhibition of the PI3 K/Akt signalling pathway by TLR2 and TLR4 receptors-Steroid-like activitiesBupleurum chinenseIn guinea pig models(1) Anti-inflammatoryReduce eosinophil levelsReduce serum levels of IL-5 and TNF-αScutellaria baicalensisIn murine models(1) Anti-inflammatoryInhibit TGF-β1 and α-SMA, and decrease p-ERK1/2Inhibit phosphorylated p38 proteinInhibit IgE, IL-4, IL-5, IL-6, IL-17AReduce STAT3 protein levelPromote expression of FOXP3 proteinIncrease serum MDA levelsPromote expression of FOXP3 proteinInhibit HMGB1Inhibit protein expression ofα-SMA and TLR4Expression of GATA-3 and STAT6Suppress Th2 responseIncrease IL-10 levelsPerilla frutescensNone foundAnemarrhena RhizomaIn guinea pig modelsReduce serum NO, BALF, and ET-1Gypsum fibrosumNone foundEriobotryae FoliumIn murine modelsReduce CD4+Increase CD 8+Regulate CD4+/CD8+ dysfunctionCinnamomi RamulusIn murine models(1) Anti-inflammatoryInhibition of eosinophils, IFN-γ, IL-4, IgE, histamine, and β-hexosaminidase releaseZingiberis rhizomaNone foundSchisandra FructusIn murine models(1) Anti-inflammatoryReduce EOSIncrease SOD in serumReduce MDAInhibit TNF-α, IL-1β, and IL-6 expressionRegulate the HMGB1/TLR4/NF-κB signalling pathwayTable 2
Phenotype specific asthma therapeutic targeting of herbs.
Chinese nameLatin nameMOA targeting asthmatic subgroupsTargeted asthmatic phenotypeβ-Adrenergic agonistZi WanAster tataricus L. f.N/AN/AChen PiPericarpium Citri Reticulatae(1) Inhibits IL-5 and reduction of eosinophil(2) Inhibits IgE and IL-4(1) Idiopathic eosinophilic asthma(2) Allergen exacerbated asthmaMa HuangEphedra sinica StapfInhibits IL-4 and IL-13Allergen exacerbated asthmaSheng JiangZingiber officinale RoscoeN/AN/AKuan Dong HuaTussilago farfara(1) Inhibits IL-4, IL-13, and IgE(2) Inhibits IL-5(3) Inhibits IL-17(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthma(3) Neutrophilic asthmaHuang QinScutellaria baicalensis(1) Inhibits IL-4, IL-13, and IgE(2) Inhibits IL-5(3) Inhibits IL-17A(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthma(3) Neutrophilic asthmaSteroidal effectsHou PoMagnolia officinalis(1) Inhibits IL-4 and IL-13(2) Inhibits IL-5(3) Inhibits IL-17A(4) Inhibits leukotriene release(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthma(3) Neutrophilic asthma(4) Aspirin induced asthmaPDE inhibitorZhe BeiFritillaria thunbergiiN/AN/Aβ-Adrenergic and steroidal effectsGan CaoGlycyrrhiza uralensis(1) Inhibits IgE and IL-13(2) Steroidal effects and inhibits IL-5 antagonist(3) Steroidal effects(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthma(3) Neutrophilic asthmaAnticholinergicSang Bai PiCortex Mori(1) Inhibits IL-4 and IL-13(2) Inhibits IL-5(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthmaLeukotriene antagonistDi LongPheretima aspergillum(1) Leukotriene antagonist(2) Inhibits IgE and IL-4(3) Reduces eosinophils and inhibits IL-5(1) Aspirin induced asthma(2) Allergen exacerbated asthma(3) Idiopathic eosinophilic asthmaInhibition of IL-4Xi XinAsarum sieboldiiInhibits IL-4 and histamine releaseAllergen exacerbated asthmaBan XiaPinellia ternataInhibits IL-4Allergen exacerbated asthmaKu Xing RenPrunus armeniacaInhibits IL-4Allergen exacerbated asthmaInhibition of IL-17Wu Wei ZiSchisandra FructusInhibits IL-17Neutrophilic asthmaRegulation of T helper cellsTing Li ZiLepidium apetalumReduces the expression of Th2 cytokines and inhibits differentiation and activation of Th2 cells.Allergen exacerbated asthmaSu ZiPerilla frutescensSuppression of allergen-specific Th2 responseAllergen exacerbated asthmaPi Pa YeEriobotryae FoliumReduction of CD4+, rises CD 8+, and alters CD4+/CD8+ dysfunctionAllergen exacerbated asthmaMultiple monoclonal effects for asthmaZhi MuAnemarrhena Rhizoma(1) Inhibits IL-5 and reduction of eosinophil(2) Inhibits histamine release, IgE, IL-4, and IL-13(1) Idiopathic eosinophilic asthma(2) Allergen exacerbated asthmaJie GengPlatycodon grandifloras(1) Inhibits IL-4 and IL-13(2) Inhibits IL-5(3) Inhibits IL-17(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthma(3) Neutrophilic asthmaShao YaoPaeonia lactiflora(1) Inhibits IL-4 and IL-13(2) Inhibits IL-5 and reduces eosinophil(3) Inhibits IL-17 and reduces neutrophil count(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthma(3) Neutrophilic asthmaChai HuBupleurum chinense(1) Inhibits IL-4 and IgE(2) Inhibits IL-5(3) Inhibits IL-17A(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthma(3) Neutrophilic asthmaGui ZiCinnamomi Ramulus(1) Inhibits IgE and IL-4Allergen exacerbated asthmaAlteration of genetic expression/signaling pathwayBei MuFritillaria cirrhosa D.DonNANAFigure 3
Chinese medicine targeted therapy on immunopathological pathways of asthma.Figure 4
Proposed guideline for traditional Chinese medicine based on existing GINA.


## 2.1. Criteria for considering Studies for This Review

### 2.1.1. Types of Studies

All studies eliciting the mechanism of action of a specific herb in the context of asthma, regardless of the model. Studies which involved the use of multiple herbs simultaneously (i.e., formulas) were excluded.


## 2.1.1. Types of Studies

All studies eliciting the mechanism of action of a specific herb in the context of asthma, regardless of the model. Studies which involved the use of multiple herbs simultaneously (i.e., formulas) were excluded.


## 2.2. Search Methods for Identification of Studies

### 2.2.1. Electronic Searches

For this review, we searched EMBASE, PubMed, CENTRAL, Wanfang, and China National Knowledge Infrastructure (CNKI).


## 2.2.1. Electronic Searches

For this review, we searched EMBASE, PubMed, CENTRAL, Wanfang, and China National Knowledge Infrastructure (CNKI).


## 2.3. Identifying the Herbs

We first conducted a search to identify herbs which are currently commonly prescribed by TCM physicians by identifying systematic reviews on frequently used herbs or formulas and extracted the relevant herbs from the formulas, using the terms “asthma AND TCM OR Traditional Chinese Medicine OR alternative medicine” in EMBASE, PubMed, CENTRAL, Wanfang, and CNKI (Figure1). The list was subsequently confirmed with a senior TCM physician specialising in TCM Formula-logy.Figure 1
Study flow diagram of the identification of commonly used herbs for asthma.We then extracted the Latin and Mandarin names of the herbs used and identified those used primarily for the treatment of asthma, before searching electronic databases for their mechanisms of action (Figure2). Herbs prescribed for supportive treatment were excluded.Figure 2
Study flow diagram for the identification of articles of commonly used herbs.


## 2.4. EMBASE, PubMed, and Cochrane

### 2.4.1. CNKI (Overseas CNKI) and Wanfang (Based on the Translations of the Keywords Used in English Medium)

(1)
“Glycyrrhiza uralensis” AND “asthma”(2)
“Prunus armeniaca” AND “asthma”(3)
“Pinellia ternata” AND “asthma”(4)
“Asarum sieboldii” AND “asthma”(5)
“Pheretima aspergillum” AND “asthma”(6)
“Aster tataricus” AND “asthma”(7)
“Fritillaria cirrhosa” AND “asthma”(8)
“Lepidium apetalum” AND “asthma”(9)
“Pericarpium Citri Reticulatae” AND “asthma”(10)
“Cortex Mori” AND “asthma”(11)
“Ephedra sinica” AND “asthma”(12)
“Zingiber officinale” AND “asthma”(13)
“Tussilago farfara” AND “asthma”(14)
“Platycodon grandifloras” AND “asthma”(15)
“Fritillaria thunbergii” AND “asthma”(16)
“Paeonia lactiflora” AND “asthma”(17)
“Magnolia officinalis” AND “asthma”(18)
“Bupleurum chinense” AND “asthma”(19)
“Scutellaria baicalensis” AND “asthma”(20)
“Perilla frutescens” AND “asthma”(21)
“Anemarrhena Rhizoma” AND “asthma”(22)
“Gypsum fibrosum” AND “asthma”(23)
“Eriobotryae Folium” AND “asthma”(24)
“Cinnamomi Ramulus” AND “asthma”(25)
“Zingiberis rhizoma” AND “asthma”(26)
“Schisandra Fructus” AND “asthma”We did not impose any language or publication restrictions.


## 2.4.1. CNKI (Overseas CNKI) and Wanfang (Based on the Translations of the Keywords Used in English Medium)

(1)
“Glycyrrhiza uralensis” AND “asthma”(2)
“Prunus armeniaca” AND “asthma”(3)
“Pinellia ternata” AND “asthma”(4)
“Asarum sieboldii” AND “asthma”(5)
“Pheretima aspergillum” AND “asthma”(6)
“Aster tataricus” AND “asthma”(7)
“Fritillaria cirrhosa” AND “asthma”(8)
“Lepidium apetalum” AND “asthma”(9)
“Pericarpium Citri Reticulatae” AND “asthma”(10)
“Cortex Mori” AND “asthma”(11)
“Ephedra sinica” AND “asthma”(12)
“Zingiber officinale” AND “asthma”(13)
“Tussilago farfara” AND “asthma”(14)
“Platycodon grandifloras” AND “asthma”(15)
“Fritillaria thunbergii” AND “asthma”(16)
“Paeonia lactiflora” AND “asthma”(17)
“Magnolia officinalis” AND “asthma”(18)
“Bupleurum chinense” AND “asthma”(19)
“Scutellaria baicalensis” AND “asthma”(20)
“Perilla frutescens” AND “asthma”(21)
“Anemarrhena Rhizoma” AND “asthma”(22)
“Gypsum fibrosum” AND “asthma”(23)
“Eriobotryae Folium” AND “asthma”(24)
“Cinnamomi Ramulus” AND “asthma”(25)
“Zingiberis rhizoma” AND “asthma”(26)
“Schisandra Fructus” AND “asthma”We did not impose any language or publication restrictions.


## 2.5. Data Collection and Analysis

### 2.5.1. Selection of Studies

Four review authors (TJ, L, RS, and RM) independently reviewed the titles, abstracts, and keywords of all records retrieved to determine the studies to be assessed. We retrieved full articles for further assessment if the information given suggested that the study:(1)
Discussed asthma(2)
And administered any of 26 Chinese herbs identified through the initial searchA fifth review author (LH) acted as arbiter and resolved any differences in opinion.


### 2.5.2. Data Analysis

We first identified the herbs relevant to treating asthma by the formulas which contain them, for reference purposes (Table1). We then categorised the herbs according to their mechanisms of action (Table 2), plotted a schematic representation of the herbs on the asthma immunopathological pathway (Figure 3), and then compared them against GINA guidelines to identify clinical situations where herbs could see the potential use (Figure 4).Table 1
Summary of MOA of herbs frequently used in asthma.
Herb speciesMechanism of actionGlycyrrhiza uralensisIn murine models(1) BronchodilationLPS-induced NO productionAttenuates acetylcholine- and carbachol-induced contractions(2) Anti-inflammatoryInhibit T lymphocytes, eosinophils, IgE, IL-13, and TNF-aUpregulate caspase-3 and BaxSteroid-like activitiesDownregulate Bcl-2(3) MucolyticInhibit MUC5AC gene expression, production and secretion via regulation of NF-κB, STAT6, and HDAC2In guinea pig models(1) BronchodilationActivate c-GMP and open calcium channelsHuman airway epithelial cells(1) MucolyticInhibit PMA-induced MUC5AC mucin production(2) Anti-inflammatoryInhibit Th2-associated cytokinesHuman peripheral blood mononuclear cells(1) Anti-inflammatoryPhytohaemagglutinin-induced proliferation and inhibition of TNF-alpha, IFN-gamma, and IL-10 productionIn vitro(1) Anti-inflammatoryInhibit memory Th2 responsesInhibit IL-4 and Eotaxin-1 secretionPrunus armeniacaIn murine models(1) Anti-inflammatoryReduce recruitment of eosinophils, macrophages, and lymphocytesInhibit MAPK signalling and IL-4 activationActivate IFN-yPinellia ternataIn murine models(1) Anti-inflammatoryReduce recruitment of eosinophilsReduce IL-4 activation and IFN-y activationAsarum sieboldiiIn guinea pig models(1) Anti-inflammatoryInhibit IL-4 activation and histamine release(2) Signalling pathway regulationRegulate MMP-9 and TIMP-1 signallingPheretima aspergillumIn murine models(1) Anti-inflammatoryInhibit IL-4, IL-5, IgE, and TNF-α activationInhibit eosinophil activationRegulate Th1/Th2 balanceInhibit NF-kB activationInhibit production of NO, PGE2, TNF-a, iNOS, and COX-2Inhibit release of IL-1B and IL-6(2) MucolyticDecrease collagen depositionDecrease mucin glycogen expressionIn guinea pig models(1) Anti-inflammatoryRegulate IFN-y, IL-4, and LTB4 productionIn human models(1) Anti-inflammatoryInhibit TGF-B1 and SMAD2Aster tataricus L. f.In vitro(1) Anti-inflammatorySuppress NO productionInhibit production of PGE2, IL-6, IL-1BInhibit expression of iNOS and COX-2 by inhibition of NF-KB activation(2) Signalling blockadePrevent activation of MAPK signalling cascade via inhibition of phosphorylation of c-Jun N-terminal kinases, extracellular signal-regulated kinases, and p38(3) BronchodilationActivate of B2-adrenoceptorsFritillaria cirrhosa D. DonIn murine models(1) Anti-inflammatorySuppress TH2 cytokines (IL-4, IL-5, and IL-13)Suppress IgE, histamine productionReduce eosinophilic accumulationIncrease IFN-γ production(2) Block signalling pathwaysInhibit ERK/MAPK signalling activation(3) Downregulate NOTCH 2 expression(4) Inhibit MMP-2, MMP-9, and TIMP-1Lepidium apetalumIn murine models(1) Anti-inflammatoryReduce expression of type 2 cytokinesInhibit differentiation and activation of Th2 cytokinesPericarpium Citri ReticulataeIn murine models(1) Anti-inflammatorySuppress eosinophil productionIn guinea pig models(1) Anti-inflammatoryDownregulate expression of eosinophils and serum IgE, IL-4, and IL-5 levels(2) BronchodilationActivation of B2-adrenoceptorsCortex MoriIn murine models(1) Anti-inflammatoryEnhancement of CD4(+)CD25(+)Foxp3(+) regulatory T cells and inhibition of Th2 cytokines such as interleukin (IL)-4, -5 and -13(2) AnticholinergicEphedra sinica StapfIn murine models(1)Anti-inflammatoryReduce infiltration of inflammatory cells in the lungRegulate levels of inflammatory factors such as OVA-IgE, IL-4, and IL-13 and downregulate the expression of p65 NF-k B protein(2) BronchodilatorActivate a-, B1-, and B2-adrenoceptorsZingiber officinale RoscoeIn murine models(1) Anti-inflammatoryInhibit Th2-mediated immune response(2) BronchodilationReduce Ca2+ influx in smooth muscle and promoteβagonist-induced relaxation in human airway smooth muscle by suppressing phosphodiesterase 4DTussilago farfaraIn murine models(1) Anti-inflammatoryRegulate IgE, IL-4, and IL-13 levelsDownregulate the expression of p65 NF-kB proteinInhibit NO, MAPKs, and NF-kBSuppress expression of PGE2, TNF-α, and HMGB1Reduce production of IL-4, IL-5, IL-13, and IL-17Reduce IgE in serum by regulating Th1/Th2 cellsIncrease HO-1 levels affecting Nrf2/HO-1 pathway(2) MucolyticDecrease mucin production by regulating NF-kBPlatycodon grandiflorasIn murine modelsSerum concentrations of NF-κB, MMP-9, and TIMP-1 decreased significantlyIn guinea pig models(1) Anti-inflammatoryPromote and regulate release of LXA4Reduce oxygen-free radicalsPromote secretion of IFN-γRegulate Th1/Th2 balanceFritillaria thunbergiiIn guinea pig modelsInhibit PDE and prevent inactivation of cAMPPaeonia lactifloraIn murine models(1) Anti-inflammatoryInhibit IL-22 and IL-13Magnolia officinalisIn murine models(1) Anti-inflammatoryInhibit IL-4, IL-6, and IL-17Decrease serum MDA levelIncrease SOD and GSH-Px/p-JNK, NF-κB, caspase-3, and γH2 Ax levelsInhibition of the PI3 K/Akt signalling pathway by TLR2 and TLR4 receptors-Steroid-like activitiesBupleurum chinenseIn guinea pig models(1) Anti-inflammatoryReduce eosinophil levelsReduce serum levels of IL-5 and TNF-αScutellaria baicalensisIn murine models(1) Anti-inflammatoryInhibit TGF-β1 and α-SMA, and decrease p-ERK1/2Inhibit phosphorylated p38 proteinInhibit IgE, IL-4, IL-5, IL-6, IL-17AReduce STAT3 protein levelPromote expression of FOXP3 proteinIncrease serum MDA levelsPromote expression of FOXP3 proteinInhibit HMGB1Inhibit protein expression ofα-SMA and TLR4Expression of GATA-3 and STAT6Suppress Th2 responseIncrease IL-10 levelsPerilla frutescensNone foundAnemarrhena RhizomaIn guinea pig modelsReduce serum NO, BALF, and ET-1Gypsum fibrosumNone foundEriobotryae FoliumIn murine modelsReduce CD4+Increase CD 8+Regulate CD4+/CD8+ dysfunctionCinnamomi RamulusIn murine models(1) Anti-inflammatoryInhibition of eosinophils, IFN-γ, IL-4, IgE, histamine, and β-hexosaminidase releaseZingiberis rhizomaNone foundSchisandra FructusIn murine models(1) Anti-inflammatoryReduce EOSIncrease SOD in serumReduce MDAInhibit TNF-α, IL-1β, and IL-6 expressionRegulate the HMGB1/TLR4/NF-κB signalling pathwayTable 2
Phenotype specific asthma therapeutic targeting of herbs.
Chinese nameLatin nameMOA targeting asthmatic subgroupsTargeted asthmatic phenotypeβ-Adrenergic agonistZi WanAster tataricus L. f.N/AN/AChen PiPericarpium Citri Reticulatae(1) Inhibits IL-5 and reduction of eosinophil(2) Inhibits IgE and IL-4(1) Idiopathic eosinophilic asthma(2) Allergen exacerbated asthmaMa HuangEphedra sinica StapfInhibits IL-4 and IL-13Allergen exacerbated asthmaSheng JiangZingiber officinale RoscoeN/AN/AKuan Dong HuaTussilago farfara(1) Inhibits IL-4, IL-13, and IgE(2) Inhibits IL-5(3) Inhibits IL-17(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthma(3) Neutrophilic asthmaHuang QinScutellaria baicalensis(1) Inhibits IL-4, IL-13, and IgE(2) Inhibits IL-5(3) Inhibits IL-17A(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthma(3) Neutrophilic asthmaSteroidal effectsHou PoMagnolia officinalis(1) Inhibits IL-4 and IL-13(2) Inhibits IL-5(3) Inhibits IL-17A(4) Inhibits leukotriene release(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthma(3) Neutrophilic asthma(4) Aspirin induced asthmaPDE inhibitorZhe BeiFritillaria thunbergiiN/AN/Aβ-Adrenergic and steroidal effectsGan CaoGlycyrrhiza uralensis(1) Inhibits IgE and IL-13(2) Steroidal effects and inhibits IL-5 antagonist(3) Steroidal effects(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthma(3) Neutrophilic asthmaAnticholinergicSang Bai PiCortex Mori(1) Inhibits IL-4 and IL-13(2) Inhibits IL-5(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthmaLeukotriene antagonistDi LongPheretima aspergillum(1) Leukotriene antagonist(2) Inhibits IgE and IL-4(3) Reduces eosinophils and inhibits IL-5(1) Aspirin induced asthma(2) Allergen exacerbated asthma(3) Idiopathic eosinophilic asthmaInhibition of IL-4Xi XinAsarum sieboldiiInhibits IL-4 and histamine releaseAllergen exacerbated asthmaBan XiaPinellia ternataInhibits IL-4Allergen exacerbated asthmaKu Xing RenPrunus armeniacaInhibits IL-4Allergen exacerbated asthmaInhibition of IL-17Wu Wei ZiSchisandra FructusInhibits IL-17Neutrophilic asthmaRegulation of T helper cellsTing Li ZiLepidium apetalumReduces the expression of Th2 cytokines and inhibits differentiation and activation of Th2 cells.Allergen exacerbated asthmaSu ZiPerilla frutescensSuppression of allergen-specific Th2 responseAllergen exacerbated asthmaPi Pa YeEriobotryae FoliumReduction of CD4+, rises CD 8+, and alters CD4+/CD8+ dysfunctionAllergen exacerbated asthmaMultiple monoclonal effects for asthmaZhi MuAnemarrhena Rhizoma(1) Inhibits IL-5 and reduction of eosinophil(2) Inhibits histamine release, IgE, IL-4, and IL-13(1) Idiopathic eosinophilic asthma(2) Allergen exacerbated asthmaJie GengPlatycodon grandifloras(1) Inhibits IL-4 and IL-13(2) Inhibits IL-5(3) Inhibits IL-17(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthma(3) Neutrophilic asthmaShao YaoPaeonia lactiflora(1) Inhibits IL-4 and IL-13(2) Inhibits IL-5 and reduces eosinophil(3) Inhibits IL-17 and reduces neutrophil count(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthma(3) Neutrophilic asthmaChai HuBupleurum chinense(1) Inhibits IL-4 and IgE(2) Inhibits IL-5(3) Inhibits IL-17A(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthma(3) Neutrophilic asthmaGui ZiCinnamomi Ramulus(1) Inhibits IgE and IL-4Allergen exacerbated asthmaAlteration of genetic expression/signaling pathwayBei MuFritillaria cirrhosa D.DonNANAFigure 3
Chinese medicine targeted therapy on immunopathological pathways of asthma.Figure 4
Proposed guideline for traditional Chinese medicine based on existing GINA.


## 2.5.1. Selection of Studies

Four review authors (TJ, L, RS, and RM) independently reviewed the titles, abstracts, and keywords of all records retrieved to determine the studies to be assessed. We retrieved full articles for further assessment if the information given suggested that the study:(1)
Discussed asthma(2)
And administered any of 26 Chinese herbs identified through the initial searchA fifth review author (LH) acted as arbiter and resolved any differences in opinion.


## 2.5.2. Data Analysis

We first identified the herbs relevant to treating asthma by the formulas which contain them, for reference purposes (Table1). We then categorised the herbs according to their mechanisms of action (Table 2), plotted a schematic representation of the herbs on the asthma immunopathological pathway (Figure 3), and then compared them against GINA guidelines to identify clinical situations where herbs could see the potential use (Figure 4).Table 1
Summary of MOA of herbs frequently used in asthma.
Herb speciesMechanism of actionGlycyrrhiza uralensisIn murine models(1) BronchodilationLPS-induced NO productionAttenuates acetylcholine- and carbachol-induced contractions(2) Anti-inflammatoryInhibit T lymphocytes, eosinophils, IgE, IL-13, and TNF-aUpregulate caspase-3 and BaxSteroid-like activitiesDownregulate Bcl-2(3) MucolyticInhibit MUC5AC gene expression, production and secretion via regulation of NF-κB, STAT6, and HDAC2In guinea pig models(1) BronchodilationActivate c-GMP and open calcium channelsHuman airway epithelial cells(1) MucolyticInhibit PMA-induced MUC5AC mucin production(2) Anti-inflammatoryInhibit Th2-associated cytokinesHuman peripheral blood mononuclear cells(1) Anti-inflammatoryPhytohaemagglutinin-induced proliferation and inhibition of TNF-alpha, IFN-gamma, and IL-10 productionIn vitro(1) Anti-inflammatoryInhibit memory Th2 responsesInhibit IL-4 and Eotaxin-1 secretionPrunus armeniacaIn murine models(1) Anti-inflammatoryReduce recruitment of eosinophils, macrophages, and lymphocytesInhibit MAPK signalling and IL-4 activationActivate IFN-yPinellia ternataIn murine models(1) Anti-inflammatoryReduce recruitment of eosinophilsReduce IL-4 activation and IFN-y activationAsarum sieboldiiIn guinea pig models(1) Anti-inflammatoryInhibit IL-4 activation and histamine release(2) Signalling pathway regulationRegulate MMP-9 and TIMP-1 signallingPheretima aspergillumIn murine models(1) Anti-inflammatoryInhibit IL-4, IL-5, IgE, and TNF-α activationInhibit eosinophil activationRegulate Th1/Th2 balanceInhibit NF-kB activationInhibit production of NO, PGE2, TNF-a, iNOS, and COX-2Inhibit release of IL-1B and IL-6(2) MucolyticDecrease collagen depositionDecrease mucin glycogen expressionIn guinea pig models(1) Anti-inflammatoryRegulate IFN-y, IL-4, and LTB4 productionIn human models(1) Anti-inflammatoryInhibit TGF-B1 and SMAD2Aster tataricus L. f.In vitro(1) Anti-inflammatorySuppress NO productionInhibit production of PGE2, IL-6, IL-1BInhibit expression of iNOS and COX-2 by inhibition of NF-KB activation(2) Signalling blockadePrevent activation of MAPK signalling cascade via inhibition of phosphorylation of c-Jun N-terminal kinases, extracellular signal-regulated kinases, and p38(3) BronchodilationActivate of B2-adrenoceptorsFritillaria cirrhosa D. DonIn murine models(1) Anti-inflammatorySuppress TH2 cytokines (IL-4, IL-5, and IL-13)Suppress IgE, histamine productionReduce eosinophilic accumulationIncrease IFN-γ production(2) Block signalling pathwaysInhibit ERK/MAPK signalling activation(3) Downregulate NOTCH 2 expression(4) Inhibit MMP-2, MMP-9, and TIMP-1Lepidium apetalumIn murine models(1) Anti-inflammatoryReduce expression of type 2 cytokinesInhibit differentiation and activation of Th2 cytokinesPericarpium Citri ReticulataeIn murine models(1) Anti-inflammatorySuppress eosinophil productionIn guinea pig models(1) Anti-inflammatoryDownregulate expression of eosinophils and serum IgE, IL-4, and IL-5 levels(2) BronchodilationActivation of B2-adrenoceptorsCortex MoriIn murine models(1) Anti-inflammatoryEnhancement of CD4(+)CD25(+)Foxp3(+) regulatory T cells and inhibition of Th2 cytokines such as interleukin (IL)-4, -5 and -13(2) AnticholinergicEphedra sinica StapfIn murine models(1)Anti-inflammatoryReduce infiltration of inflammatory cells in the lungRegulate levels of inflammatory factors such as OVA-IgE, IL-4, and IL-13 and downregulate the expression of p65 NF-k B protein(2) BronchodilatorActivate a-, B1-, and B2-adrenoceptorsZingiber officinale RoscoeIn murine models(1) Anti-inflammatoryInhibit Th2-mediated immune response(2) BronchodilationReduce Ca2+ influx in smooth muscle and promoteβagonist-induced relaxation in human airway smooth muscle by suppressing phosphodiesterase 4DTussilago farfaraIn murine models(1) Anti-inflammatoryRegulate IgE, IL-4, and IL-13 levelsDownregulate the expression of p65 NF-kB proteinInhibit NO, MAPKs, and NF-kBSuppress expression of PGE2, TNF-α, and HMGB1Reduce production of IL-4, IL-5, IL-13, and IL-17Reduce IgE in serum by regulating Th1/Th2 cellsIncrease HO-1 levels affecting Nrf2/HO-1 pathway(2) MucolyticDecrease mucin production by regulating NF-kBPlatycodon grandiflorasIn murine modelsSerum concentrations of NF-κB, MMP-9, and TIMP-1 decreased significantlyIn guinea pig models(1) Anti-inflammatoryPromote and regulate release of LXA4Reduce oxygen-free radicalsPromote secretion of IFN-γRegulate Th1/Th2 balanceFritillaria thunbergiiIn guinea pig modelsInhibit PDE and prevent inactivation of cAMPPaeonia lactifloraIn murine models(1) Anti-inflammatoryInhibit IL-22 and IL-13Magnolia officinalisIn murine models(1) Anti-inflammatoryInhibit IL-4, IL-6, and IL-17Decrease serum MDA levelIncrease SOD and GSH-Px/p-JNK, NF-κB, caspase-3, and γH2 Ax levelsInhibition of the PI3 K/Akt signalling pathway by TLR2 and TLR4 receptors-Steroid-like activitiesBupleurum chinenseIn guinea pig models(1) Anti-inflammatoryReduce eosinophil levelsReduce serum levels of IL-5 and TNF-αScutellaria baicalensisIn murine models(1) Anti-inflammatoryInhibit TGF-β1 and α-SMA, and decrease p-ERK1/2Inhibit phosphorylated p38 proteinInhibit IgE, IL-4, IL-5, IL-6, IL-17AReduce STAT3 protein levelPromote expression of FOXP3 proteinIncrease serum MDA levelsPromote expression of FOXP3 proteinInhibit HMGB1Inhibit protein expression ofα-SMA and TLR4Expression of GATA-3 and STAT6Suppress Th2 responseIncrease IL-10 levelsPerilla frutescensNone foundAnemarrhena RhizomaIn guinea pig modelsReduce serum NO, BALF, and ET-1Gypsum fibrosumNone foundEriobotryae FoliumIn murine modelsReduce CD4+Increase CD 8+Regulate CD4+/CD8+ dysfunctionCinnamomi RamulusIn murine models(1) Anti-inflammatoryInhibition of eosinophils, IFN-γ, IL-4, IgE, histamine, and β-hexosaminidase releaseZingiberis rhizomaNone foundSchisandra FructusIn murine models(1) Anti-inflammatoryReduce EOSIncrease SOD in serumReduce MDAInhibit TNF-α, IL-1β, and IL-6 expressionRegulate the HMGB1/TLR4/NF-κB signalling pathwayTable 2
Phenotype specific asthma therapeutic targeting of herbs.
Chinese nameLatin nameMOA targeting asthmatic subgroupsTargeted asthmatic phenotypeβ-Adrenergic agonistZi WanAster tataricus L. f.N/AN/AChen PiPericarpium Citri Reticulatae(1) Inhibits IL-5 and reduction of eosinophil(2) Inhibits IgE and IL-4(1) Idiopathic eosinophilic asthma(2) Allergen exacerbated asthmaMa HuangEphedra sinica StapfInhibits IL-4 and IL-13Allergen exacerbated asthmaSheng JiangZingiber officinale RoscoeN/AN/AKuan Dong HuaTussilago farfara(1) Inhibits IL-4, IL-13, and IgE(2) Inhibits IL-5(3) Inhibits IL-17(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthma(3) Neutrophilic asthmaHuang QinScutellaria baicalensis(1) Inhibits IL-4, IL-13, and IgE(2) Inhibits IL-5(3) Inhibits IL-17A(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthma(3) Neutrophilic asthmaSteroidal effectsHou PoMagnolia officinalis(1) Inhibits IL-4 and IL-13(2) Inhibits IL-5(3) Inhibits IL-17A(4) Inhibits leukotriene release(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthma(3) Neutrophilic asthma(4) Aspirin induced asthmaPDE inhibitorZhe BeiFritillaria thunbergiiN/AN/Aβ-Adrenergic and steroidal effectsGan CaoGlycyrrhiza uralensis(1) Inhibits IgE and IL-13(2) Steroidal effects and inhibits IL-5 antagonist(3) Steroidal effects(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthma(3) Neutrophilic asthmaAnticholinergicSang Bai PiCortex Mori(1) Inhibits IL-4 and IL-13(2) Inhibits IL-5(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthmaLeukotriene antagonistDi LongPheretima aspergillum(1) Leukotriene antagonist(2) Inhibits IgE and IL-4(3) Reduces eosinophils and inhibits IL-5(1) Aspirin induced asthma(2) Allergen exacerbated asthma(3) Idiopathic eosinophilic asthmaInhibition of IL-4Xi XinAsarum sieboldiiInhibits IL-4 and histamine releaseAllergen exacerbated asthmaBan XiaPinellia ternataInhibits IL-4Allergen exacerbated asthmaKu Xing RenPrunus armeniacaInhibits IL-4Allergen exacerbated asthmaInhibition of IL-17Wu Wei ZiSchisandra FructusInhibits IL-17Neutrophilic asthmaRegulation of T helper cellsTing Li ZiLepidium apetalumReduces the expression of Th2 cytokines and inhibits differentiation and activation of Th2 cells.Allergen exacerbated asthmaSu ZiPerilla frutescensSuppression of allergen-specific Th2 responseAllergen exacerbated asthmaPi Pa YeEriobotryae FoliumReduction of CD4+, rises CD 8+, and alters CD4+/CD8+ dysfunctionAllergen exacerbated asthmaMultiple monoclonal effects for asthmaZhi MuAnemarrhena Rhizoma(1) Inhibits IL-5 and reduction of eosinophil(2) Inhibits histamine release, IgE, IL-4, and IL-13(1) Idiopathic eosinophilic asthma(2) Allergen exacerbated asthmaJie GengPlatycodon grandifloras(1) Inhibits IL-4 and IL-13(2) Inhibits IL-5(3) Inhibits IL-17(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthma(3) Neutrophilic asthmaShao YaoPaeonia lactiflora(1) Inhibits IL-4 and IL-13(2) Inhibits IL-5 and reduces eosinophil(3) Inhibits IL-17 and reduces neutrophil count(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthma(3) Neutrophilic asthmaChai HuBupleurum chinense(1) Inhibits IL-4 and IgE(2) Inhibits IL-5(3) Inhibits IL-17A(1) Allergen exacerbated asthma(2) Idiopathic eosinophilic asthma(3) Neutrophilic asthmaGui ZiCinnamomi Ramulus(1) Inhibits IgE and IL-4Allergen exacerbated asthmaAlteration of genetic expression/signaling pathwayBei MuFritillaria cirrhosa D.DonNANAFigure 3
Chinese medicine targeted therapy on immunopathological pathways of asthma.Figure 4
Proposed guideline for traditional Chinese medicine based on existing GINA.


## 3. Results

### 3.1. Results of the Search to Identify Herbs of Interest

Our initial searches in online databases identified 6843 studies, of which 128 systematic reviews were relevant to our topic, yielding 55 herbs (Figure1).


### 3.2. Included Herbs

Of the 55 herbs, 26 were used primarily for asthma treatment.These includedGlycyrrhiza uralensis [7–24], Prunus armeniaca [25, 26], Pinellia ternata [27], Asarum sieboldii [28, 29], Pheretima aspergillum [30–37], Aster tataricus [38, 39], Fritillaria cirrhosa [40–43], Lepidium apetalum [44], Pericarpium Citri Reticulatae [45–47], Cortex Mori [48–52], Ephedra sinica Stapf [53–56], Zingiber officinale Roscoe [57], Tussilago farfara [58–61], Platycodon grandifloras [62–65], Fritillaria thunbergii [66, 67], Paeonia lactiflora [68–71], Magnolia officinalis [72–77], Bupleurum chinense [78, 79], Scutellaria baicalensis [80–86], Anemarrhena Rhizoma [87, 88], Gypsum fibrosum, Eriobotryae Folium [89], Cinnamomi Ramulus [90], Zingiberis rhizoma, Schisandra Fructus [91–93], and Perilla frutescens [94].


### 3.3. Results of the Search for Herb Mechanisms of Action

#### 3.3.1. Included Studies

Searching online databases yielded 8961 studies, of which 149 met the inclusion criteria (Figure2). No studies were found for the herbs Gypsum fibrosum and Zingiberis rhizoma.


#### 3.3.2. Mechanisms of Action

We first extracted the proposed mechanisms of action of the herbs (Table1) and categorised them according to the known main mechanisms of action of Western medicines important in the treatment of asthma. Based on known mechanisms, the herbs were divided broadly into beta-adrenergic agonist, steroid-like, anticholinergics, PDE antagonist, leukotriene antagonist, and herbs with monoclonal effects or those affecting signalling pathways (Table 2). The schematic representation on how herbs act on the immunopathological pathways of asthma is depicted in Figure 3. The herbs act mainly on IL-4, IL-5, IL-13, and IL-17A and T cells on asthmatic pathways, which act to mobilize inflammatory cells, tissue repair, and remodelling, causing bronchial hyperreactivity and induction of chemokines.


### 3.4. Proposed Guidelines in Relation to GINA Guidelines

The proposed guidelines (Figure4), based on existing GINA guidelines, describe a stepwise approach to treating asthma, where increments in medication are made if existing treatment is insufficient for controlling a patient’s symptoms [95].Step 1 involves using a low to moderate dose of beta-2-adrenoreceptor agonist as required. Herbs which work similarly includeAster tataricus, Pericarpium Citri Reticulatae, Ephedra sinica Stapf, Zingiber officinale Roscoe, Tussilago farfara, and Scutellaria baicalensis.Step 2 involves the addition of a low dose of corticosteroids. This can be achieved by addingMagnolia officinalis to the existing herbs or possibly by substituting them with Glycyrrhiza uralensis alone.Step 3 involves increasing the dose of the beta-2-adrenoreceptor agonist to a moderate-high dose and either using a medium dose of corticosteroid or adding a leukotriene receptor antagonist (LTRA) to the low-dose corticosteroid.Pheretima aspergillum is an LTRA and could potentially be useful.Step 4 involves the addition of either an anticholinergic or an LTRA or increasing to a moderate dose of corticosteroid, whichever was not undertaken during step 3. Cortex Mori has anticholinergic effects and could have potential use (Figure4).Step 5 involves switching to a high dose of corticosteroid and the addition of drugs with effects such as inhibiting IgE, IL-4, or IL-5, guided by the phenotypic assessment by an asthma specialist. Herbs that may be useful for these purposes includeAsarum sieboldii, Pinellia ternata, and Prunus armeniaca which inhibit IL-4, Schisandra Fructus which inhibits IL-17, Lepidium apetalum and Perilla frutescens which regulate Th2 helper cell activity, or Anemarrhena Rhizoma, Eriobotryae Folium, Platycodon grandifloras, Paeonia lactiflora, Bupleurum chinense, and Cinnamomi Ramulus which have a range of effects against multiple targets (Table 2).


### 3.5. Frequently Prescribed TCM Formulas in Asthma

A total of 16 formulas were identified as frequently prescribed for asthma (Table3), of which 12 were “stand-alone formulas” which are usually prescribed independently and 4 were “add-on formulas” which are used in addition to “stand-alone formulas” during an acute exacerbation [96]. The MOA of the herbs identified in the formulas was analysed, which demonstrated that “stand-alone formulas” contain herbs with beta-agonist, steroid-like effects or leukotriene antagonist mechanisms, or a combination of beta-agonist and steroid-like effects/leukotriene antagonist. However, “add-on formulas” only had either steroid-like effects or regulated T helper cells.Table 3
Analysis of MOA of commonly used TCM formulas.
Formula (Chinese)FormulasKey ingredientsMain MOAIndividual/add-on formula三子养亲汤San Zi Yang Qin TangPerilla frutescensRegulation of Th2 cellAdd-on三子汤San Zi TangLepidium apetalum and Perilla frutescensRegulation of Th2 cellAdd-on半夏厚朴汤Ban Xia Hou Po TangPinellia ternata and Magnolia officinalisSteroid-like effectsAdd-on桂枝加厚朴杏仁汤Gui Zhi Jia Hou Po Xing Ren TangCinnamomi Ramulus,Magnolia officinalis, Prunus armeniaca, and Glycyrrhiza uralensisSteroid-like effectsAdd-on射干麻黄汤She Gan Ma Huang TangEphedra sinica Stapf, Aster tataricus L. f., Pinellia ternata, Schisandra Fructus, Asarum sieboldii, and Tussilago farfaraβ-AgonistIndividual康连智方Kang Lian Zhi FangEphedra sinica Stapf, Pinellia ternata, Asarum sieboldii, and Schisandra fructusβ-AgonistIndividual董氏治喘基本方Dong Shi Zhi Chuan Ji Ben FangEphedra sinica Stapf, Prunus armeniaca, and Pheretima aspergillumβ-Agonist and leukotriene antagonistIndividual麻杏石甘汤Ma Xing Shi Gan TangEphedra sinica Stapf, Glycyrrhiza uralensis, and Prunus armeniacaβ-Agonist and steroid-like effectsIndividual三拗汤San Ao TangEphedra sinica Stapf, Glycyrrhiza uralensis, and Prunus armeniacaβ-Agonist and steroid-like effectsIndividual茯苓杏仁甘草汤Fu Ling Xing Ren Gan Cao TangPrunus armeniaca and Glycyrrhiza uralensisβ-Agonist and steroid-like effectsIndividual六君子汤Liu Jun Zi TangGlycyrrhiza uralensis, Pinellia ternata, and Pericarpium Citri Reticulataeβ-Agonist and steroid-like effectsIndividual治喘方Zhi Chuan FangEphedra sinica Stapf, Asarum sieboldii, Glycyrrhiza uralensis, Schisandra Fructus, and Pinellia ternataβ-Agonist and steroid-like effectsIndividual苓桂术甘汤Ling Gui Shu Gan TangCinnamomi Ramulus andGlycyrrhiza uralensisβ-Agonist and steroid-like effectsIndividual小柴胡汤Xiao Chai Hu TangBupleurum chinense, Scutellaria baicalensis, Pinellia ternata, and Glycyrrhiza uralensisβ-Agonist and steroid-like effectsIndividual小青龙汤Xiao Qing Long TangEphedra sinica Stapf, Paeonia lactiflora, Asarum sieboldii, Glycyrrhiza uralensis, Cinnamomi Ramulus, Schisandra Fructus, and Pinellia ternataβ-Agonist and steroid-like effectsIndividual芍药甘草汤Shao Yao Gan Cao TangPaeonia lactiflora and Glycyrrhiza uralensisβ-Agonist and steroid-like effectsIndividual


## 3.1. Results of the Search to Identify Herbs of Interest

Our initial searches in online databases identified 6843 studies, of which 128 systematic reviews were relevant to our topic, yielding 55 herbs (Figure1).


## 3.2. Included Herbs

Of the 55 herbs, 26 were used primarily for asthma treatment.These includedGlycyrrhiza uralensis [7–24], Prunus armeniaca [25, 26], Pinellia ternata [27], Asarum sieboldii [28, 29], Pheretima aspergillum [30–37], Aster tataricus [38, 39], Fritillaria cirrhosa [40–43], Lepidium apetalum [44], Pericarpium Citri Reticulatae [45–47], Cortex Mori [48–52], Ephedra sinica Stapf [53–56], Zingiber officinale Roscoe [57], Tussilago farfara [58–61], Platycodon grandifloras [62–65], Fritillaria thunbergii [66, 67], Paeonia lactiflora [68–71], Magnolia officinalis [72–77], Bupleurum chinense [78, 79], Scutellaria baicalensis [80–86], Anemarrhena Rhizoma [87, 88], Gypsum fibrosum, Eriobotryae Folium [89], Cinnamomi Ramulus [90], Zingiberis rhizoma, Schisandra Fructus [91–93], and Perilla frutescens [94].


## 3.3. Results of the Search for Herb Mechanisms of Action

### 3.3.1. Included Studies

Searching online databases yielded 8961 studies, of which 149 met the inclusion criteria (Figure2). No studies were found for the herbs Gypsum fibrosum and Zingiberis rhizoma.


### 3.3.2. Mechanisms of Action

We first extracted the proposed mechanisms of action of the herbs (Table1) and categorised them according to the known main mechanisms of action of Western medicines important in the treatment of asthma. Based on known mechanisms, the herbs were divided broadly into beta-adrenergic agonist, steroid-like, anticholinergics, PDE antagonist, leukotriene antagonist, and herbs with monoclonal effects or those affecting signalling pathways (Table 2). The schematic representation on how herbs act on the immunopathological pathways of asthma is depicted in Figure 3. The herbs act mainly on IL-4, IL-5, IL-13, and IL-17A and T cells on asthmatic pathways, which act to mobilize inflammatory cells, tissue repair, and remodelling, causing bronchial hyperreactivity and induction of chemokines.


## 3.3.1. Included Studies

Searching online databases yielded 8961 studies, of which 149 met the inclusion criteria (Figure2). No studies were found for the herbs Gypsum fibrosum and Zingiberis rhizoma.


## 3.3.2. Mechanisms of Action

We first extracted the proposed mechanisms of action of the herbs (Table1) and categorised them according to the known main mechanisms of action of Western medicines important in the treatment of asthma. Based on known mechanisms, the herbs were divided broadly into beta-adrenergic agonist, steroid-like, anticholinergics, PDE antagonist, leukotriene antagonist, and herbs with monoclonal effects or those affecting signalling pathways (Table 2). The schematic representation on how herbs act on the immunopathological pathways of asthma is depicted in Figure 3. The herbs act mainly on IL-4, IL-5, IL-13, and IL-17A and T cells on asthmatic pathways, which act to mobilize inflammatory cells, tissue repair, and remodelling, causing bronchial hyperreactivity and induction of chemokines.


## 3.4. Proposed Guidelines in Relation to GINA Guidelines

The proposed guidelines (Figure4), based on existing GINA guidelines, describe a stepwise approach to treating asthma, where increments in medication are made if existing treatment is insufficient for controlling a patient’s symptoms [95].Step 1 involves using a low to moderate dose of beta-2-adrenoreceptor agonist as required. Herbs which work similarly includeAster tataricus, Pericarpium Citri Reticulatae, Ephedra sinica Stapf, Zingiber officinale Roscoe, Tussilago farfara, and Scutellaria baicalensis.Step 2 involves the addition of a low dose of corticosteroids. This can be achieved by addingMagnolia officinalis to the existing herbs or possibly by substituting them with Glycyrrhiza uralensis alone.Step 3 involves increasing the dose of the beta-2-adrenoreceptor agonist to a moderate-high dose and either using a medium dose of corticosteroid or adding a leukotriene receptor antagonist (LTRA) to the low-dose corticosteroid.Pheretima aspergillum is an LTRA and could potentially be useful.Step 4 involves the addition of either an anticholinergic or an LTRA or increasing to a moderate dose of corticosteroid, whichever was not undertaken during step 3. Cortex Mori has anticholinergic effects and could have potential use (Figure4).Step 5 involves switching to a high dose of corticosteroid and the addition of drugs with effects such as inhibiting IgE, IL-4, or IL-5, guided by the phenotypic assessment by an asthma specialist. Herbs that may be useful for these purposes includeAsarum sieboldii, Pinellia ternata, and Prunus armeniaca which inhibit IL-4, Schisandra Fructus which inhibits IL-17, Lepidium apetalum and Perilla frutescens which regulate Th2 helper cell activity, or Anemarrhena Rhizoma, Eriobotryae Folium, Platycodon grandifloras, Paeonia lactiflora, Bupleurum chinense, and Cinnamomi Ramulus which have a range of effects against multiple targets (Table 2).


## 3.5. Frequently Prescribed TCM Formulas in Asthma

A total of 16 formulas were identified as frequently prescribed for asthma (Table3), of which 12 were “stand-alone formulas” which are usually prescribed independently and 4 were “add-on formulas” which are used in addition to “stand-alone formulas” during an acute exacerbation [96]. The MOA of the herbs identified in the formulas was analysed, which demonstrated that “stand-alone formulas” contain herbs with beta-agonist, steroid-like effects or leukotriene antagonist mechanisms, or a combination of beta-agonist and steroid-like effects/leukotriene antagonist. However, “add-on formulas” only had either steroid-like effects or regulated T helper cells.Table 3
Analysis of MOA of commonly used TCM formulas.
Formula (Chinese)FormulasKey ingredientsMain MOAIndividual/add-on formula三子养亲汤San Zi Yang Qin TangPerilla frutescensRegulation of Th2 cellAdd-on三子汤San Zi TangLepidium apetalum and Perilla frutescensRegulation of Th2 cellAdd-on半夏厚朴汤Ban Xia Hou Po TangPinellia ternata and Magnolia officinalisSteroid-like effectsAdd-on桂枝加厚朴杏仁汤Gui Zhi Jia Hou Po Xing Ren TangCinnamomi Ramulus,Magnolia officinalis, Prunus armeniaca, and Glycyrrhiza uralensisSteroid-like effectsAdd-on射干麻黄汤She Gan Ma Huang TangEphedra sinica Stapf, Aster tataricus L. f., Pinellia ternata, Schisandra Fructus, Asarum sieboldii, and Tussilago farfaraβ-AgonistIndividual康连智方Kang Lian Zhi FangEphedra sinica Stapf, Pinellia ternata, Asarum sieboldii, and Schisandra fructusβ-AgonistIndividual董氏治喘基本方Dong Shi Zhi Chuan Ji Ben FangEphedra sinica Stapf, Prunus armeniaca, and Pheretima aspergillumβ-Agonist and leukotriene antagonistIndividual麻杏石甘汤Ma Xing Shi Gan TangEphedra sinica Stapf, Glycyrrhiza uralensis, and Prunus armeniacaβ-Agonist and steroid-like effectsIndividual三拗汤San Ao TangEphedra sinica Stapf, Glycyrrhiza uralensis, and Prunus armeniacaβ-Agonist and steroid-like effectsIndividual茯苓杏仁甘草汤Fu Ling Xing Ren Gan Cao TangPrunus armeniaca and Glycyrrhiza uralensisβ-Agonist and steroid-like effectsIndividual六君子汤Liu Jun Zi TangGlycyrrhiza uralensis, Pinellia ternata, and Pericarpium Citri Reticulataeβ-Agonist and steroid-like effectsIndividual治喘方Zhi Chuan FangEphedra sinica Stapf, Asarum sieboldii, Glycyrrhiza uralensis, Schisandra Fructus, and Pinellia ternataβ-Agonist and steroid-like effectsIndividual苓桂术甘汤Ling Gui Shu Gan TangCinnamomi Ramulus andGlycyrrhiza uralensisβ-Agonist and steroid-like effectsIndividual小柴胡汤Xiao Chai Hu TangBupleurum chinense, Scutellaria baicalensis, Pinellia ternata, and Glycyrrhiza uralensisβ-Agonist and steroid-like effectsIndividual小青龙汤Xiao Qing Long TangEphedra sinica Stapf, Paeonia lactiflora, Asarum sieboldii, Glycyrrhiza uralensis, Cinnamomi Ramulus, Schisandra Fructus, and Pinellia ternataβ-Agonist and steroid-like effectsIndividual芍药甘草汤Shao Yao Gan Cao TangPaeonia lactiflora and Glycyrrhiza uralensisβ-Agonist and steroid-like effectsIndividual


## 4. Discussion

### 4.1. Mechanism of Action of Herbs and Concomitant Use of Drugs and Herbs

Despite theoretical differences between TCM and Western medicine, research is increasingly suggesting that herbal medicines have similar MOA to that of Western medicines (Table1). The understanding of MOA allows characterisation of herbs in relation to Western medicines and improves prescription methods of TCM physicians. For example, TCM physicians will be able to select herbs with beta-agonist effects in patients presenting with acute asthma. It also allows minimisation of possible interactions between herbs and drugs if taken concurrently, and the use of readily available antidotes should occur. Recent research showed that up to 33.6% of patients in the United Kingdom consume both herbal and prescription medicine together [97]. This could result in overdose or interactions when herbs and drugs with similar MOA be consumed concurrently [98, 99]. Herbs such as Gypsum fibrosum and Zingiberis rhizoma which have no known MOA should not be used concurrently with Western medicines to prevent the occurrence of any unknown side effects.


### 4.2. Standardization of TCM Management of Asthma

TCM physicians traditionally adopt a “Syndrome-Based” approach in diagnosing patients which is determined by the symptoms of the patient, looks of the tongue, and character of the pulse [100]. “Syndrome-Based” approach means that patients with the same diagnosis given by Western doctors might be diagnosed as different syndromes by TCM physicians, and as such, different management would be given. It is also a relatively subjective approach depending on the consulting physician(s) [101]. It would likely result in differences in outcomes for patients. Through the understanding of the underlying MOA of each herb used for asthma, a proposed guideline (Figure 4) can thus be formulated based on existing GINA guidelines [95]. This would ensure a standardized uniform outcome for patients regardless of “syndromes” characterized by TCM physicians and prevent herbs with repetitive or unknown MOA from being prescribed.Unlike drugs, herbs are usually consumed orally, and their duration of effect has not been elicited. The proposed guideline takes into account the differences in the mode of administration and durations of the effect of herbs despite the similarity in MOA. Similar to existing GINA guidelines, prescription will be stepwise and incremental according to the severity of their asthma, from step 1 to 5. Worsening of symptoms warrants moving up the ladder, and dose reductions can be made if symptoms improve. This will ensure adequate herbs with appropriate MOA and dosage are prescribed.


### 4.3. Phenotype Specific Asthma Therapeutic Targeting of Herbs

In addition to the standard therapeutic MOA for asthma, herbs also seem to regulate the activity of inflammatory cells and cytokines by acting on particular pathways in the immunopathology of asthma (Figure3). This aids not only in understanding of the way herbs work but can also be used to target a particular phenotype of asthma, e.g., downregulation of IgE in allergen-induced asthma. Biologics such as omalizumab, which targets specific cytokines, have long been employed in the management of asthma. Herbs with similar effects could potentially be employed in a similar fashion as biologics.The therapeutic interventions for different phenotypes include IL-17 antagonist (neutrophilic asthma), IL-4/13 antagonist and anti-IgE (allergen-induced asthma), corticosteroids and IL-5 antagonist (idiopathic eosinophilic asthma), and leukotriene antagonist (aspirin exacerbated asthma) [102].Herbs which target certain phenotypes through their effect on cytokines (Table2) should be added after standardized therapy has been given and phenotypic assessment has been conducted, in line with GINA guidelines. This serves as an individualised management for patients with different asthmatic phenotypes and will lead to improved treatment outcomes.


### 4.4. Analysis of TCM Formulas Used for Asthma

Herbs are typically prescribed in various combinations as “TCM formulas,” rather than individually. They can be broadly divided into “Stand-alone formulas” which can be used independently for diseases and “Add-on Formulas” which are usually added as adjuvants to “Stand-alone formulas” to enhance their therapeutic effects (Table3). Interestingly, the analysis of “Stand-alone Formulas” has shown that despite the differences in herbs used, formulas generally consist of herbs with β-agonist and steroid-like effects as recommended by GINA guidelines [95]. On the other hand, “Add-on Formulas” consist of herbs with steroid-like effects or assist in the regulation of T helper cells. However, none of the formulas have proceeded beyond step 3 of the GINA guidelines which could involve the addition of anticholinergics or leukotriene antagonists.In addition, some formulas consist of several herbs with the same MOA, e.g., Ma Xing Shi Gan Tang which comprises ofEphedra sinica Stapf and Glycyrrhiza uralensis, both of which exerts the β-agonistic effect and Gui Zhi Jia Hou Po Xing Ren Tang which is made up of Magnolia officinalis and Glycyrrhiza uralensis, both of which exert steroid-like effects. Unknowingly, Ma Xing Shi Gan Tang could result in arrhythmias as a result of excessive β-adrenergic activity, while Gui Zhi Jia Hou Po Xing Ren Tang could result in iatrogenic-induced Cushing syndrome, one of the well documented side effects of steroids especially in systemic steroids administration [103]. Gui Zhi Jia Hou Po Xing Ren Tang should therefore be avoided and let alone as an “Add-on Formula;” as the “Stand-alone Formula,” it is added onto and might already consist of steroidal elements. In addition, one of the existing formulas (Dong Shi Zhi Chuan Ji Ben Fang) also proceeded to include herbs with leukotriene antagonist activity without first including herbs with steroid-like effects as per GINA guidelines. This will likely result in the suboptimal management of patients with asthma.


## 4.1. Mechanism of Action of Herbs and Concomitant Use of Drugs and Herbs

Despite theoretical differences between TCM and Western medicine, research is increasingly suggesting that herbal medicines have similar MOA to that of Western medicines (Table1). The understanding of MOA allows characterisation of herbs in relation to Western medicines and improves prescription methods of TCM physicians. For example, TCM physicians will be able to select herbs with beta-agonist effects in patients presenting with acute asthma. It also allows minimisation of possible interactions between herbs and drugs if taken concurrently, and the use of readily available antidotes should occur. Recent research showed that up to 33.6% of patients in the United Kingdom consume both herbal and prescription medicine together [97]. This could result in overdose or interactions when herbs and drugs with similar MOA be consumed concurrently [98, 99]. Herbs such as Gypsum fibrosum and Zingiberis rhizoma which have no known MOA should not be used concurrently with Western medicines to prevent the occurrence of any unknown side effects.


## 4.2. Standardization of TCM Management of Asthma

TCM physicians traditionally adopt a “Syndrome-Based” approach in diagnosing patients which is determined by the symptoms of the patient, looks of the tongue, and character of the pulse [100]. “Syndrome-Based” approach means that patients with the same diagnosis given by Western doctors might be diagnosed as different syndromes by TCM physicians, and as such, different management would be given. It is also a relatively subjective approach depending on the consulting physician(s) [101]. It would likely result in differences in outcomes for patients. Through the understanding of the underlying MOA of each herb used for asthma, a proposed guideline (Figure 4) can thus be formulated based on existing GINA guidelines [95]. This would ensure a standardized uniform outcome for patients regardless of “syndromes” characterized by TCM physicians and prevent herbs with repetitive or unknown MOA from being prescribed.Unlike drugs, herbs are usually consumed orally, and their duration of effect has not been elicited. The proposed guideline takes into account the differences in the mode of administration and durations of the effect of herbs despite the similarity in MOA. Similar to existing GINA guidelines, prescription will be stepwise and incremental according to the severity of their asthma, from step 1 to 5. Worsening of symptoms warrants moving up the ladder, and dose reductions can be made if symptoms improve. This will ensure adequate herbs with appropriate MOA and dosage are prescribed.


## 4.3. Phenotype Specific Asthma Therapeutic Targeting of Herbs

In addition to the standard therapeutic MOA for asthma, herbs also seem to regulate the activity of inflammatory cells and cytokines by acting on particular pathways in the immunopathology of asthma (Figure3). This aids not only in understanding of the way herbs work but can also be used to target a particular phenotype of asthma, e.g., downregulation of IgE in allergen-induced asthma. Biologics such as omalizumab, which targets specific cytokines, have long been employed in the management of asthma. Herbs with similar effects could potentially be employed in a similar fashion as biologics.The therapeutic interventions for different phenotypes include IL-17 antagonist (neutrophilic asthma), IL-4/13 antagonist and anti-IgE (allergen-induced asthma), corticosteroids and IL-5 antagonist (idiopathic eosinophilic asthma), and leukotriene antagonist (aspirin exacerbated asthma) [102].Herbs which target certain phenotypes through their effect on cytokines (Table2) should be added after standardized therapy has been given and phenotypic assessment has been conducted, in line with GINA guidelines. This serves as an individualised management for patients with different asthmatic phenotypes and will lead to improved treatment outcomes.


## 4.4. Analysis of TCM Formulas Used for Asthma

Herbs are typically prescribed in various combinations as “TCM formulas,” rather than individually. They can be broadly divided into “Stand-alone formulas” which can be used independently for diseases and “Add-on Formulas” which are usually added as adjuvants to “Stand-alone formulas” to enhance their therapeutic effects (Table3). Interestingly, the analysis of “Stand-alone Formulas” has shown that despite the differences in herbs used, formulas generally consist of herbs with β-agonist and steroid-like effects as recommended by GINA guidelines [95]. On the other hand, “Add-on Formulas” consist of herbs with steroid-like effects or assist in the regulation of T helper cells. However, none of the formulas have proceeded beyond step 3 of the GINA guidelines which could involve the addition of anticholinergics or leukotriene antagonists.In addition, some formulas consist of several herbs with the same MOA, e.g., Ma Xing Shi Gan Tang which comprises ofEphedra sinica Stapf and Glycyrrhiza uralensis, both of which exerts the β-agonistic effect and Gui Zhi Jia Hou Po Xing Ren Tang which is made up of Magnolia officinalis and Glycyrrhiza uralensis, both of which exert steroid-like effects. Unknowingly, Ma Xing Shi Gan Tang could result in arrhythmias as a result of excessive β-adrenergic activity, while Gui Zhi Jia Hou Po Xing Ren Tang could result in iatrogenic-induced Cushing syndrome, one of the well documented side effects of steroids especially in systemic steroids administration [103]. Gui Zhi Jia Hou Po Xing Ren Tang should therefore be avoided and let alone as an “Add-on Formula;” as the “Stand-alone Formula,” it is added onto and might already consist of steroidal elements. In addition, one of the existing formulas (Dong Shi Zhi Chuan Ji Ben Fang) also proceeded to include herbs with leukotriene antagonist activity without first including herbs with steroid-like effects as per GINA guidelines. This will likely result in the suboptimal management of patients with asthma.


## 5. Conclusion

With a rising number of patients seeking TCM [104], it is paramount for TCM physicians to understand the underlying MOA of herbs. This will allow the standardization of prescribing and result in a more guideline-based approach. In line with this approach, herbs with repetitive or unknown MOA should be avoided to reduce the risk of side effects. Both TCM physicians and doctors should also be wary of possible herb-drug interactions. A guideline-based approach will also allow greater continuity of care should a patient wish to transfer between TCM and Western medicine and prevent under or overmedication. However, patients should still seek the advice of their doctors prior to stopping medications.Further research onGypsum fibrosum and Zingiberis rhizoma to identify their underlying MOA is recommended.



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*Source: 4319657-2021-01-08.xml*