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REVIEW ARTICLE

Research progress on icariin, a traditional Chinese medicine extract, in the treatment of asthma

Jia-ying Yuana, Zhi-ying Tongb, Yu-chao Donga, Jia-yi Zhaob*, Yan Shanga, b*

aDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Naval Medical University (Second Military Medical University), Shanghai, China

bDepartment of General Medicine, The First Affiliated Hospital of Naval Medical University (Second Military Medical University), Shanghai, China

Abstract

Bronchial asthma is a common chronic airway disease, and long-term management of asthma is the focus and challenge of clinical treatment. Glucocorticoids are often used as the first choice for the treatment of asthma. However, the occurrence of hormone dependence, hormone resistance, and local and systemic adverse reactions caused by hormone application also creates problems for the treatment of asthma. Finding new, safe, and effective therapeutic drugs is an important research direction at present. Icariin is an effective ingredient of the traditional Chinese medicine, Epimedium. It has various biological attributes such as anti-inflammatory and antioxidative activities, and immune regulation. It has high safety and a wide range of clinical applications. Icariin has the characteristics of multitargeted intervention in the treatment of asthma. Here, we review the specific mechanisms of icariin in treating asthma, and icariin is considered a novel therapy in controlling asthma; however, the mechanism is still worth further investigation.

Key words: asthma, airway inflammation, airway remodeling, Chinese herbal extracts, Icariin

*Corresponding authors: Yan Shang, Doctor, Department of General Practice, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China. Email address: [email protected];

Jia-yi Zhao, Master, Department of General Practice, The First Affiliated Hospital of Naval Medical University (Second Military Medical University), Shanghai 200433, China. Email address: [email protected]

Received 17 August 2021; Accepted 9 October 2021; Available online 1 January 2022

DOI: 10.15586/aei.v50i1.490

Copyright: Yuan J-Y, et al.
License: This open access article is licensed under Creative Commons Attribution 4.0 International (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/

Introduction

Bronchial asthma (asthma) is a group of highly heterogeneous chronic airway diseases with different pathogeneses and various clinical manifestations. The main manifestations are cough, chest tightness, dyspnea, wheezing, and other symptoms.1 Chronic airway inflammation and airway remodeling are key features of the onset of asthma, and they can lead to airway hyperresponsiveness and restricted lung function.2 There are various classifications of asthma. According to its pathogenesis, it can usually be divided into Th2-related asthma and non-Th2-related asthma. The former is mainly characterized by increased airway eosinophils, while the latter mostly manifests as increased airway neutrophils.3,4 At present, there are approximately 300 million asthma patients in the world, and on average, more than 1,000 people die of asthma every day.5 Inhaled corticosteroids (ICSs) are currently recognized as the main treatment for asthma, but approximately 30%–50% of asthma patients still receive hormone therapy, and hormone dependence and multiple side effects caused by hormone use cause difficulties in the long-term management of asthma.6

Traditional Chinese medicine has a history of thousands of years in treating asthma, and it was recorded in the “Treatise on Febrile and Miscellaneous Diseases” written by Zhang Zhongjing of the Eastern Han Dynasty.7 Various traditional Chinese medicines and their extracts have been found to have a significant therapeutic effect in the treatment of asthma in modern medicine, and presently this is an important research direction for asthma treatment. In recent years, many new research advances have been made on the specific mechanism of action of icariin in the treatment of asthma, and they are summarized as follows.

Icariin

The source of icariin

Epimedium pubescens (Epimedium pubescens Maxim), is also known as barren grass. It has three branches on the stem and three leaves in each branch, and it is also called the three-branched, nine-leafed clover. It mainly grows on cliffs near moist forests, streams, and wetlands at altitudes of 200 to 3700 m. It is a perennial temperate and subtropical medicinal plant belonging to the Berberis family.8 Herba Epimedii is the dry leaf of the Epimedium plant. The classic Chinese medicine literature, “Shen Nong’s Materia Medica” recorded more than 400 years ago that Herba Epimedii has the effects of “tonifying kidney yang,” “strengthening muscles and bones,” and “dispelling rheumatism.”9 Modern studies have found that Epimedium and its extracts have a certain therapeutic effect on improving osteoporosis, asthma, and cardiovascular diseases, and have been widely used in clinical treatment in China, South Korea, Japan, and other East Asian countries.1013

The molecular structure and biological activity of icariin

The molecular formula for icariin (2-(4'-methoxylphenyl)- 3-rhamnosido-5-hydroxyl-7-glucosido-8-(3'-methyl- 2-butylenyl))-4-chromanone, ICA), is C33H40O15, and its molecular weight is 676.67. It is a pentenylated flavonoid glycoside monomer extracted from the traditional Chinese medicine, Epimedium, and it is one of the most important pharmacologically active ingredients in Epimedium.14 It has multiple effects such as regulating immunity, exerting anti-inflammatory and antioxidative activities, inhibiting cell apoptosis, and improving endothelial cell function.15 Icariin mainly acts in the body through its metabolites. The main absorption site of icariin is in the small intestine. It can be quickly converted into icariin II (deglucosyl) and absorbed into the blood in the intestine. Bile is in the form of icariin 3-OL-rhamnopyranosyl-7-OD-glucopyranoside. Icariin II that enters the body can regenerate C7-OH glucoaldehydation in the liver.16

A clinical trial of icariin and mood and alcohol use disorders demonstrated that icariin not only effectively improves mood and alcohol use disorders in patients but also is highly safe and well tolerated.17 Icariin has received widespread attention in clinical treatment due to its wide-ranging effects. In research on lung cancer treatment, icariin was found to target the PI3K-Akt signaling pathway; reduce the phosphorylation levels of Bax, Bad, and other factors; and reduce the mitochondrial membrane potential to promote tumor cell apoptosis.18 In the treatment of myocardial damage and heart failure, icariin, as a flavonoid compound, exhibits a strong ability to resist oxidative stress.19 Icariin can also combine with inorganic materials such as hydroxyapatite to form a new type of drug scaffold that can effectively promote bone damage repair.20

The Mechanism of Action of Icariin in the Treatment of Asthma

The mechanism of icariin in inhibiting airway inflammation (Table 1)

Icariin could regulate the expression of eosinophils and basophils

Eosinophils (EOS) are considered key cells and treatment target in asthma, and the eosinophil count is closely related to asthma symptom control.21 Further studies have shown that eosinophils can express leukotriene hydrolase A4 (LTA4H) and generate LTB4, which can enhance asthma inflammation.22 Basophils (Bas) were also identified to generate IL-4 to affect the function of ILC2s in lung inflammation and may act as a potential biomarker.23 BuShenYiQi is a traditional Chinese herbal formula in which Herba Epimedii has been confirmed as one of the main components by high-performance liquid chromatography (HPLC). In the model of RSV-induced asthmatic rats, BuShenYiQi formula (BSYQF) showed a significant effect in reducing excessive infiltration of eosinophils and neutrophils, regulating the balance between Th1 and Th2/Th17 responses to inhibit asthma exacerbation.24 BSYQF also inhibits the expression of inflammatory cells such as neutrophils (Neu), lymphocytes (Lym), monocytes (Mon), and basophils; enhances Tregs; and inhibits Th17 cells function to reduce asthma inflammation.25 Further studies have found that icariin may affect the chemotactic migration of EOS to effectively reduce inflammation in asthma by downregulating the expression of chemokines RANTES and McP-3 in lung and CCR3 and eotaxin on EOS surfaces, inhibiting the expression of bcl-2, which is an anti-apoptotic protein.26

Table 1 The mechanism of icariin in inhibiting airway inflammation to treat asthma.

No Extract/monomer Patients/animal/cell Dose Possible mechanism/function Reference
1 Bu-Shen-Yi-Qi formula ((BSYQF) Mice 2.5, 5, and 10 g/kg/day, po.; for 15 days BSYQF could effectively improve the inflammatory cells’ infiltration such as eosinophils in asthma, and to regulate Th1 and Th2/Th17 balance. [24]
2 BSYQF Mice 5, 10, and 20 g raw herbs/kg body weight, po., for 8 weeks BSYQF could reduce the differentiation of Th17 and improve the enhancement of Treg functions to regulate Th17/Treg imbalance in asthma treatment. [25]
3 Icariin Mice 5, 50, and 100 mg/kg/2 days, ip.; for 6 weeks Icariin could downregulate the expression of Bcl-2 and upregulate the expression of Bax protein, promote the apoptosis of EOS in asthmatic mice, and reduce the EOS infiltration. [26]
4 Icariin Mice 40 µg/single injection/mouse, ip., for day 1 and day 22 Icariin may act as a safe adjuvant in mice and be able to induce both Th1 and Th2 responses. [30]
5 Icariin Rat 5 mg/kg; 10 mg/kg; 20 mg/kg, ig., for 2 weeks Icariin was found to reduce the inflammatory cell infiltration in rat asthmatic bronchi, under the vessel mucosa and in peripheral tissue, with targeting p65 protein to inhibit the differentiation of eosinophile granulocyte and macrophage. [31]
6 Icariin Mice 25 mg/kg, 50 mg/kg, 100 mg/kg, po., for 8 weeks Icariin was found to reduce airway inflammation by reducing the expression of IL-6, IL-17, TGF-β, and inhibiting Th17 functions while improving the enhancement of Treg functions. [34]
7 Icariin HeLa and RAW 264.7 cells Three concentrations (7.5 μM, 15 μM, and 30 μM) for 24 h Icariin was able to enhance the functions of glucocorticoids (GCs) and promote glucocorticoid receptor (GRα) translocate into the nucleus with targeting the NF-κB and STAT3 to reduce LPS-induced inflammation. [39]
8 Fructus Ligustrilucidi extracts; Herbal Epimedii extracts Rat 100 mg/kg, ig., for 4 weeks This study showed that co-combination of HE and FLL seemed to have stronger effects in antioxidant and regulating immunity than single use of extracts with targeting TGF-β/Smads signaling; besides, two extracts combined with budesonide expressed the best effects in regulating the expression of TGF-β1, 2, and Smad2,3 and Smad7 to treat asthma. [40]
9 Icariin Mice 2.5 mg/200 μl normal saline once a week, ip., for 2 weeks Icariin can downregulate the expression of prostaglandin D2 (PGD2) and prostaglandin D2 receptor 2 (CRTH2) to reduce the chemotaxis of eosinophils and to improve Th17/Treg imbalance in asthma. [43]
10 Suhuang antitussive capsule Rat 1.75, 3.5, and 7 g/kg, ig., for 2 weeks Suhuang may regulate TXNIP induction and RIP1-RIP3-DRP1 signaling to inhibit the activation of NLRP3 inflammasome and attenuate endoplasmic reticulum stress to improve pulmonary dysfunction. [44]
11 Icariin Primary hippocampal neurons of rat 10, 20, and 50 nM, for 2 h It was identified that icariin could attenuate CRH-induced ER stress and apoptosis, targeting to upregulate the activation of NF-kB. [46]

ip.: Intraperitoneal Injections; Th: T helper type; ig.: Oral administration; BSYQF: Bu-Shen-Yi-Qi formula; p.o.: per os; Treg: Regulatory cells; GCs: Glucocorticoids; GRα: Glucocorticoid receptor; IL: Interleukin; TGF-β: Transforming growth factor-β; NF-κB: Nuclear factor kappa-B; STAT: Signal transducer and activator of transcription; LPS: Lipopolysaccharide; FLL: Fructus Ligustrilucidi; HE: Herbal Epimedii; PGD2: Prostaglandin D2; CRTH2: Prostaglandin D2 receptor 2; TXNIP: Thioredoxin-interacting protein; RIP: Receptor-interacting protein; DRP: Dystrophin-related protein; NLRP3: NOD-like receptor family, pyrin domain containing 3; CRH: Corticotropin releasing hormone; ER: Endoplasmic reticulum.

Icariin could improve Th1/Th2 cell imbalance

The occurrence and development of asthma is closely related to the participation of a variety of immune cells. Initial CD4+T cells (naive CD4+T Cells) can be differentiated into a subgroup of T helper (Th) cells with diverse functions, among which T helper 2 cells (Th2) are the main response cells for asthma.27 Studies have found that under the stimulation of allergens, Th2 cell subtype differentiation is enhanced and Th1 cell differentiation is inhibited, which leads to an imbalance of Th1/Th2 cells and causes corresponding inflammation.28 Further studies have shown that GATA3 is the main transcription factor involved in Th2 cell differentiation induction, while T-bet and Runx3 mainly control Th1 cell differentiation.29 Some scholars have found that icariin has the immunomodulatory effect of enhancing the Th1-related immune response in rats and inhibiting Th2 cell differentiation.30 In addition, by comparing the expression of corresponding transcription factors in the lung tissues of the rat asthma group and the icariin treatment group, icariin intervention was found to significantly downregulate the expression levels of GATA3 and T-bet, thereby inhibiting Th2 cell differentiation and regulating Th1/Th2 cell imbalance to improve asthma airway inflammation.31

Icariin could improve the imbalance of Th17/Treg cells

Regulatory T cells (Tregs) are CD4+T cells that are critical to the development and homeostasis of Th2 cells.32 The decrease in Treg cells and the increase in the number of Th17 cells in asthma patients are important pathogenic mechanisms of asthma and one of the main research directions for clinical treatment.33 Experiments by Ying Wei et al. suggest that the traditional Chinese medicines Epimedium and Astragalus may play an important role in inhibiting TH17-related inflammatory factors, such as IL-6 and IL-10, and promoting Treg cell-related factors such as FOXP3, providing a new treatment direction to improve the imbalanced ratio of TH17/Treg cells in asthma.25 Further studies have found that IL-6 can combine with TGF-β to promote Th17 differentiation and inhibit Treg cell function, and in an ovalbumin-induced asthma model, icariin was confirmed to effectively inhibit the expression of IL-6, IL-17, TGF-β, and other inflammatory factors to promote FOXP3 expression and Treg cell development and differentiation, significantly improving TH17/Treg cell imbalance and relieving asthma airway hyperresponsiveness and airway inflammation.34

Icariin could regulate the hypothalamic– pituitary–adrenal axis (HPAA)

Hypothalamic–pituitary–adrenal axis dysfunction often occurs in patients with chronic asthma, which affects Th1/Th2 cell imbalance, promotes the secretion of inflammatory factors mediated by eosinophils and TH2 cells, and further promotes airway inflammation, and it is also an important mechanism in asthma treatment.35 Glucocorticoids (GCs) can bind to glucocorticoid receptors (GRs) to inhibit or activate the transcription of genes in the nucleus. GRα is the main mediating receptor that can inhibit nuclear factor kappa-B (NF-κB), signal transducer and activator of transcription (STAT) family, and other inflammatory factors to exert a strong anti-inflammatory effect in vivo, whereas GRβ mainly plays a negative regulatory role.36 However, steroid-resistance commonly occurs in asthma patients, especially in severe asthma patients.37 Traditional Chinese medicine has been found to have potential synergistic effects on enhancing the effects of GC. In an in vitro experiment with HaCaT keratinocytes, icariin was found to inhibit the expression of IL-8 and IL-1b to reduce the inflammatory response. Pretreatment with icariin was also able to promote the activation of GC, and it showed a potential effect in improving insufficient GC secretion in chronic inflammation.38 Icariin can significantly inhibit lipopolysaccharide (LPS)-induced cell inflammation, downregulate the expression of inflammatory factors such as NF-κB, AP-1, and STAT3, and partially restore the expression of GRα to decrease GC-resistance.39 Tang Xiufeng et al. demonstrated that combining the extracts of Herba Epimedii (HE) and Fructus Ligustri Lucidi (FLL) with GC to treat asthma may result in much more efficient treating power, more obviously inhibiting the expression of TGF-β and improving airway remolding in asthma than the single use of GC.40

Icariin could inhibit the expression of prostaglandin D2 (PGD2)

In comparing the sputum and bronchoalveolar lavage fluid (BALF) of asthma patients and healthy people, the level of proinflammatory eicosanoids such as prostaglandin D2 (PGD2) was found to be significantly increased, and this is closely related to the severity of asthma.41 PGD2 is mainly derived from activated mast cells, which can promote bronchoconstriction and activate and recruit a large number of TH2 cells by binding to the TP1 receptor and DP2 receptor (also known as CRTH2), and has become an important intervention target in the treatment of asthma.42 Research conducted by J. Qiao et al. showed that icariin intervention can significantly downregulate the expression levels of PGD2 and CRTH2 in asthmatic mice, thereby effectively improving airway inflammation and airway remodeling.43

Icariin could inhibit endoplasmic reticulum (ER) stress

The endoplasmic reticulum is a multifunctional organelle of eukaryotic cells, and it plays an important role in protein modification, folding, and biosynthesis. Studies have shown that endoplasmic reticulum stress can increase the occurrence of inflammation and lead to chronic respiratory diseases.44 In asthma, phosphoinositol 3-kinase (PI3K) is overactivated under the activation of TOLL-like receptors, leading to the accumulation of a large number of misfolded proteins and reactive oxygen species (ROS), and cell endoplasmic reticulum dysfunction, stimulating the unfolded protein response (UPR), aggravating endoplasmic reticulum stress, airway inflammation, and airway remodeling processes.45 In a model of primary cultured fetal rat hippocampal neurons, icariin not only obviously inhibited the corticotropin-releasing hormone (CRH)-induced ER stress and cell apoptosis but also reduced the activation of NF-κB; in addition, in an in vivo model of OVALPS-OVA-induced asthmatic rats, icariin treatment also showed a strong protective effect, inhibiting ER stress and the expression of the NF-kB pathway, and reducing airway hyperresponsiveness (AHR) in asthmatic rats to protect against ER stress and inflammation.46

The mechanism of icariin in inhibiting airway remodeling (Table 2)

Icariin could inhibit extracellular matrix (ECM) deposition

Airway chronic inflammation can lead to airway remodeling and promote asthma exacerbation, of which extracellular matrix deposition is one of the main manifestations of airway remodeling.47 Transforming growth factor-1 (TGF-β1) is the main regulator that can promote airway fibrosis and collagen deposition by regulating cytokines such as Smads proteins.48 In the treatment of diabetic nephropathy, icariin has been shown to exert antioxidative activity and inhibit extracellular matrix deposition.49 In addition, Herba Epimedii (HE) and Fructus Ligustri Lucidi (FLL) combined with GCs were demonstrated to clearly improve collagen synthesis in respiratory epithelium in asthma model in rats, and the single GC treatment did not show the same effect; the combined treating was also found to reduce the expression of TGF-β1,TGF-β2,Smad2 and Smad3, and promote the expression of Smad7; this may be the main mechanism in improving ECM in asthma.40

Table 2 The mechanism of icariin in improving airway remolding to treat asthma.

NO Extract/monomer Patients/ animal/cell Dose Possible mechanism/function Reference
1 Icariin Rat 20, 40, 80 mg/kg, i.g., for 9 weeks Icariin could reduce the expression of ROS and extracellular matrix deposition partly by influencing p62- Keap1 and Nrf2 signaling. [49]
2 Icariin Human bronchial epithelial cell line 16HBE; mice 16HBE cells: 25 mg/mL; 50 mg/mL; 100 mg/mL; for 6h; Mice: 25 mg/mL; 50 mg/mL; 100 mg/mL; ip., three times a week, for 6 weeks Icariin was identified to attenuate TGF-β-Smads and MAPK signaling to reduce airway remolding; besides, the expression of N-cadherin and α-SMA was also inhibited and E-cadherin was downregulated both in 16HBE and asthma mice. [53]
3 Icariin Rat ASMCs 25 μM, 50 μM, 75 μM, 100 μM, 150 μM, 200 μM, 250 μM, and 300 μM, for 24 h, 48 h, and 72 h Icariin was able to induce S phase acceleration and G2/M phase arrest regulate in ASMCs proliferation in a dose-dependent manner, which may be closely related to caspase pathway. [55]
4 Icariin Mice;
ASMC
Mice: 25, 50, and 100 mg/kg, po., for 28 days;
ASMC: 5, 10, or 100 μM for 24 h
ICA was found to improve the OVA-induced airway remolding via MAPK/Erk signaling pathway in a dose-dependent manner while the expression of TGF-β1, VEGF, IL-13, and ET-1 were obviously reduced [56]
5 Icariin Foam cell 0.8, 4, and 20 mM, for 12 h; The expression of CD36 was downregulated while SR-BI was upregulated in LPS-induced foam cell when treated by Icariin, while p38/MAPK pathway may act as key pathway in this process. [58]

i.g.: Oral administration; ROS: reactive oxygen species; Keap: Kelch-like ECH-associated protein; Nrf: NF-E2-related factor; TGF-β: Transforming growth factor-β; MAPK: Mitogen-activated protein kinase; Cadherin: Ca2+dependent cell adhesion molecule; α-SMA: Alpha Sarcomeric Actin; ASMCs: Airway smooth muscle cells; OVA: Ovalbumin; Erk: Extracellular regulated protein kinases; VEGF: Vascular endothelial growth factor; IL: Interleukin; ET: Endothelin; SR-BI: Scavenger receptor class B type I; LPS: Lipopolysaccharide.

Icariin could inhibit airway epithelial cell-to-mesenchymal transition (EMT)

In the process of airway remodeling, there is a phenotypic transformation of airway epithelial cells to mesenchymal morphology, including E-cadherin reduction and an increase in N-calcium expression, which can lead to a decrease in glucocorticoid sensitivity and severely affect the prognosis.50,51 Studies have shown that TGF-β1 can regulate the miR-203a-3p/SIX1 signaling pathway to regulate the Smad3 pathway and promote the occurrence of epithelial-mesenchymal transition in asthma.52 In vivo and in vitro experiments have found that icariin can significantly inhibit the phosphorylation of cytokines such as Erk, JNK, and p38; inhibit the activation of Smad and MAPK signaling pathways; and reduce the EMT process induced by TGF-β1 to improve airway remodeling.53

Icariin could inhibit airway smooth muscle (ASMC) proliferation

Hyperplasia of airway smooth muscle cells is one of the main manifestations of airway remodeling. The excessive proliferation of ASMC not only promotes the occurrence of airway hyperresponsiveness but also can modify the extracellular matrix and promote the production of inflammatory factors to further aggravate airway inflammation, which seriously affects the prognosis of asthma patients.54 In vitro experiments have shown that icariin can not only induce S phase acceleration and G2/M phase arrest of airway smooth muscle cells to inhibit cell proliferation but also promote the expression of apoptosis-related genes to promote cell apoptosis.55 In addition, a study using ovalbumin (OVA)-induced asthmatic mice conducted by Lingli Hu et al. demonstrated that icariin intervention can significantly downregulate the expression of TGF-β1, vascular endothelial growth factor (VEGF), IL-13 (interleukin-13), endothelin-1 (ET-1), and other important cytokines in airway remodeling, inhibiting the activity of the MAPK/Erk signaling pathway and thereby inhibiting the proliferation of AMSCs and improving the airway remodeling process by affecting multiple targets.56

Icariin could inhibit the proinflammatory effect of macrophages

Studies have shown that macrophages can not only secrete macrophage migration inhibitory factor (MIF) to promote the secretion of inflammatory factors, but also induce autophagy of ASMC and further induce airway remodeling.57 In lipopolysaccharide (LPS)-activated macrophages, icariin was found to target the expression of p38MAPK-related signaling factors and inhibit the proinflammatory effect of macrophages.58 Further studies have shown that macrophages can be further transformed into different phenotypes under the stimulation of different factors. Among them, interferon or lipopolysaccharide (LPS) can induce M1 polarization of macrophages and increase the expression of Th1 proinflammatory factors and corresponding chemokines in the tissue microenvironment; IL-4 or IL-13 can activate the M2 type conversion of macrophages, increasing the expression of anti-inflammatory factors, and promoting tissue repair and anti-inflammatory effects.59

Future perspectives

In a randomized placebo-controlled trial with 30 healthy men as subjects, the main active metabolites of icariin in the human body were found to be desmethylicariin and its precursor, which have good tolerance and almost no adverse reactions, providing favorable evidence for further investment in clinical treatment.60 In addition, in a randomized controlled trial of 100 postmenopausal women, icariin was found to significantly inhibit bone resorption, stimulate bone formation, and effectively delay the occurrence of postmenopausal osteoporosis.61 At present, the traditional Chinese medicine prescription “ChuanKeZhi Injection” with icariin as one of the main components has been widely used in the treatment of clinical respiratory diseases. It has shown many benefits such as antiallergic and anti-inflammatory effects and enhancement of body fluid and cellular immunity.62 This evidence vouches for the high safety of the clinical application of icariin and its feasibility in treating asthma, providing support for further clinical application of icariin. Due to the extensive mechanism of action of icariin, the specific therapeutic mechanism of icariin in the asthmatic population remains to be further clarified.

Conclusion

The pathogenesis of asthma is complicated, and airway inflammation and airway remodeling are the main features of asthma. The use of Epimedium to treat asthma has been proposed in various Chinese medicine prescriptions. Icariin is an effective extract of Epimedium. With its high safety and effective anti-inflammatory, antioxidant, and immune regulation effects, extensive attention has been given to its clinical applications. Icariin can not only effectively inhibit airway inflammation and regulate various immune imbalances in asthma but also effectively improve airway fibrosis and collagen deposition in the airway wall, and reverse the airway remodeling process. In addition, icariin can also cooperate with glucocorticoids to effectively improve the occurrence of hormone resistance and enhance the effect of hormone therapy. More noteworthy is that as a new type of drug carrier, exosomes are being studied extensively. The delivery of icariin through exosomes may effectively enhance drug activity and bioavailability, which can be a promising treatment in future clinical research. Icariin is an effective treatment for asthma, and its specific mechanism and further clinical applications need to be explored continuously.

Conflict of Interest

The authors declare no potential conflicts of interest with respect to research, authorship, and publication of this article.

Funding

Sponsored by National Natural Science Foundation of China (82170033), Natural Science Foundation of Shanghai (21ZR1479200), Shanghai Changhai Hospital Scientific Research Fund (2019SLZ002, 2019YXK018)

Acknowledgments

The authors are responsible for the content and the writing of this paper.

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