Application of network pharmacology in asthma management

Network pharmacology integrates computational and experimental data to reveal the multi-component, multi-target mechanisms of herbal formulations or conventional drugs in asthma (Table 1). It constructs compound-target and PPI networks, uncovering complex interactions among herbal ingredients and asthma-related targets such as IL-6, TNF, IL4, EGFR and HIF1A. It also helps reveal key signalling pathways involved in asthma pathogenesis and treatment, such as PI3K/AKT, MAPK, JAK-STAT, IL-17, TNF and Th17 cell differentiation pathways, thereby showing multi-target and multi-pathway modulation. Molecular docking and dynamics simulations complement network pharmacology by validating the binding affinities and stabilities of active compounds for core asthma targets, thereby supporting proposed mechanisms. Integration with experimental validation (in vitro, in vivo) demonstrates that network pharmacology-predicted compounds reduce airway inflammation and mucus hypersecretion and modulate immune responses, thereby confirming therapeutic effects. It facilitates discovery and mechanistic elucidation of multi-component herbal medicines, advancing traditional treatments toward modern evidence-based asthma therapy [7,20,24].

Scientific name | Common name | Family | Mechanism of action | Figure | Ref.
Acacia nilotica | Gum arabic tree | Fabaceae | The attenuation of the p13AKT signalling cascade, which may play a significant role in alleviating asthma and a multitude of other inflammatory disorders |  | [7]
Pinellia ternata | BanXia | Araceae | Immune response, cytokine signalling, inflammation, reduced allergic responses and downregulating the expression of pivotal inflammatory mediators Mmp2 and IL-4 in lung tissue |  | [8]
Ferula asafoetida | Devil's dung, hing | Umbelliferae | Airway inflammation, remodelling and immune responses |  | [38]
Nepeta bracteata | Bracted catmint | Lamiaceae | Regulating inflammation, oxidative stress and disturbed metabolic pathways |  | [40]
Fructus Xanthii | Cocklebur fruit, xanthium fruit, siberian cocklebur | Asteraceae | Fructus Xanthii demonstrates anti asthmatic properties through the modulation of HSP90AB1/IL6/TNF and PI3K-AKT signalling cascade, thereby influencing inflammation, cell cycle dynamics, apoptosis and the maintenance of immune homeostasis |  | [50]
Marsdenia tenacissima | Rajmahal hemp, devil's tongue | Apocynaceae | Marsdenia tenacissima administers treatment for NA via the IL-6/JAK/STAT and PI3K/AKT/mTOR signalling pathways |  | [51]
Paeoniae radix alba | White peony root | Paeoniaceae | Inhibit airway eosinophil infiltration, inflammatory mediator release, attenuates adipocyte lipolysis. Helped relax bronchial smooth muscle by regulating calcium ion signalling, thereby potentially reducing cough and bronchospasm. |  | [52]

Network pharmacology evidence for anti-asthmatic agents

Bushenyiqi decoction

This investigation examined the therapeutic mechanisms of BYD-a contemporary formulation of TCM for the management of allergic asthma-using network pharmacology, molecular docking and empirical validation in vivo. The analysis conducted via network pharmacology identified 116 bioactive compounds in BYD from the TCMSP database [26], of which 11 key constituents (notably quercetin, kaempferol and luteolin) were most strongly associated with asthma-related pathways. From the intersection of 166 BYD targets and 1,485 asthma-related genes sourced from GeneCards and OMIM [31,33] 75 genes exhibiting overlap were identified. The analysis of the protein-protein interaction (PPI) network was performed using Cytoscape [53], which elucidated IL6, EGFR, HIF1A, HSP90AA1, MAPK8, BCL2, CASP3, MYC and ESR1 as pivotal targets. The subsequent GO and KEGG enrichment analyses indicated that the BYD-asthma targets predominantly focused on PI3K/AKT, TNF, Th17 cell differentiation, HIF-1 and IL-17 signalling pathways, and consistently pointed to the PI3K/AKT signalling pathway as the central mechanism underlying BYD’s anti-asthmatic effects. Molecular docking through Autodock software [41] further confirmed strong binding affinities between the core compounds (quercetin, kaempferol, luteolin) and the core targets (IL6, EGFR, HIF1A), supporting their mechanistic relevance. In vivo experiments using an Ovalbumin-induced allergic asthma mouse strain demonstrated that BYD significantly reduced airway hyperresponsiveness, inflammatory cell infiltration, Th2 cytokines (IL-4, IL-5, IL-13), mucus hypersecretion and collagen deposition. Importantly, Western blot analysis showed that BYD markedly suppressed the phosphorylation of PI3K and AKT, confirming downregulation of the PI3K/AKT pathway in lung tissues. Overall, the study concludes that BYD exerts multi-component, multi-target and multi-pathway therapeutic effects against asthma, primarily by inhibiting PI3K/AKT signalling and consequently reducing airway inflammation and remodelling. These findings provide modern scientific evidence supporting the traditional "Bushenyiqi" therapeutic concept for the management of asthma [24].

Danlong Dingchuan decoction

The study investigated the therapeutic mechanisms of Danlong Dingchuan decoction (DLDD), a traditional Chinese medicine formula, in asthma by integrating network pharmacology, molecular docking, metabolomics and in vivo experiments. A total of 247 active phytoconstituents were found from the TCMSP database and 155 asthma-related targets were identified through OMIM [26,33], TTD and other databases, with quercetin, kaempferol, β-sitosterol, xanthine, lysine and luteolin emerging as key components, alongside IL-6, TNF, CXCL8, VEGFA, MAPK3, IL-1β, IL-4 and TLR4, have been delineated as pivotal therapeutic targets. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) [22,23] enrichment analyses indicated that DCDD may exert anti-asthmatic effects primarily by modulating the cAMP, cGMP-PKG, NF-κB and PI3K-Akt signalling pathways. Molecular docking confirmed high-affinity binding, particularly between quercetin and targets such as TNF, CXCL8 and TLR4. Animal experiments in ovalbumin-induced asthmatic mice demonstrated that DCDD effectively reduced airway inflammation, lowered levels of inflammatory mediators including TNF-α, IL-4, IL-6, IL-8, IL-1β and TGF-β1, and downregulated TLR4 mRNA expression, supporting its role in regulating Th2-mediated inflammation and alleviating asthma pathology. Overall, the findings highlight DLDCD as a multi-constituent, polytarget and multi-pathway intervention with both immunomodulatory and anti-inflammatory benefits in asthma [42].

Conciliatory anti-allergic decoction

The study investigates the therapeutic mechanisms of a multi-herb decoction used in Traditional Chinese Medicine for asthma by integrating network pharmacology, molecular docking and laboratory confirmation. Conciliatory anti-allergic decoction (CAD) comprises 10 herbs with 77 active ingredients screened from the TCMSP database according to the ADME criteria targeting 48 asthma-associated proteins taken from TTD, OMIM and PharmGKB databases, including TNF, IL4, IL5, IL10, IFN-gamma and IL13. Network pharmacology coupled with molecular docking indicated significant involvement of Th1/Th2 differentiation, NF-κB, IL-17, JAK-STAT and T cell receptor signalling pathways. Molecular docking confirmed strong binding affinities between key phytochemicals and hub targets, suggesting potent regulatory interactions. In vivo mouse models confirmed CAD’s efficacy in reducing airway inflammation, goblet cell hyperplasia, mucus secretion and pro-inflammatory cytokines. Major bioactive such as quercetin and kaempferol target multiple cytokines to restore immune balance. Overall, the findings demonstrate that the multi-herb decoction acts through a multi-component, multi-target and multi-pathway mechanism to reduce airway inflammation, modulate immune responses and improve asthma outcomes, supporting its relevance as a complementary therapeutic option [43].

Maxing-Ganshi decoction

The study systematically investigates the mechanisms of Maxing Ganshi decoction (MXGSD), a classical four-herb formula (Mahuang, Xingren, Gancao, Shigao), in the treatment of asthma using a network pharmacology approach. From 600 known herbal constituents, 141 bioactive components were identified and linked to 186 putative targets, of which 52 overlapped with asthma-related genes. Functional enrichment of these shared targets indicated involvement in airway inflammation, airway remodelling, immune regulation and drug-responsiveness pathways, aligning with known asthma pathophysiology. Construction of a comprehensive PPI network followed by topological filtering revealed 138 core targets, which were clustered into functional modules associated with gene expression regulation, DNA/RNA repair, protein synthesis, inflammatory signalling and neuro-immune interactions. KEGG pathway analysis highlighted four major signalling routes-neurotrophin, estrogen, PI3K-Akt and ErbB pathways as central mechanisms through which MXGSD may exert multi-component and multi-target therapeutic effects in asthma. Overall, the findings suggest that asthma is a systemic neuro-immuno-inflammatory disorder and that MXGSD treats the disease holistically by modulating interconnected genetic and signalling networks rather than isolated pathways, providing a basis for future drug development and validation [54].

Jiegeng decoction

The study examines the therapeutic potential and mechanisms of Jiegeng decoction (JGT), a traditional Chinese herbal formula composed of Platycodon grandiflorus and Glycyrrhiza uralensis, in treating allergic asthma. JGT helps improve lung function, clears mucus and reduces inflammation. Using an ovalbumin-induced mouse model, researchers demonstrated that JGT markedly reduced airway inflammation, eosinophil infiltration, Th2-associated cytokines (IL-4, IL-5, IL-13) and serum IgE levels. LC-MS analysis identified 38 phytochemical constituents in JGT. Network pharmacology analysis revealed 320 therapeutic targets, of which 54 core targets were primarily involved in immune regulation and inflammatory pathways. Enrichment analysis highlighted Th2 differentiation and the JAK-STAT signalling axis as key pathways influenced by JGT. Experimental validation (qPCR, flow cytometry, Western blotting) confirmed that JGT inhibits Th2 cell differentiation by suppressing the JAK1-STAT6 pathway in CD4⁺ T cells. Overall, the study provides mechanistic evidence that JGT ameliorates allergic asthma by modulating immune responses, particularly by blocking the IL-4/IL-13-JAK1-STAT6 signalling cascade, offering a promising multi-target herbal strategy for allergic asthma management [55].

Artesunate

This article provides a comprehensive network pharmacology and molecular docking analysis to evaluate the efficacy and safety of artesunate, derived from Artemisia annua, and its active metabolite, dihydroartemisinin (DHA), which show acceptable drug-likeness and safety profiles, as assessed by SwissADME and ADMETlab, for the treatment of asthma. Artesunate, a semisynthetic derivative of artemisinin, has exhibited therapeutic potential, including reversal of bronchial hypersensitivity and steroid resistance, attenuation of inflammation, inhibition of mast cell mediator release and promotion of eosinophil apoptosis. A comprehensive total of 282 targets associated with artesunate/DHA were extracted from the SwissTargetPrediction and PharmMapper databases, while for asthma, 7,997 targets were obtained from the GeneCards and DisGeNET databases. The investigation revealed 172 common targets shared between artesunate/DHA and asthma-related genetic loci, comprising 10 pivotal hub genes, namely CCND1, CASP3, MTOR, ERBB2, MAPK3, EGFR, MAP2K1, PTGS2, JAK2 and CASP8, which were subsequently visualized using Cytoscape software. Enrichment analyses indicated the involvement of pathways related to steroid hormone biosynthesis and metabolism, immune and inflammatory responses, AHR, airway remodelling and regulation of cell survival and apoptosis. Molecular docking confirmed stable interactions between artesunate/DHA and most hub proteins, including PTGS2, MAPK3, JAK2 and mTOR, supporting multiple mechanisms by which these compounds may alleviate asthma pathophysiology. Artesunate modulates airway smooth muscle proliferation, inflammation and glucocorticoid sensitivity, validated by bioinformatics and preclinical data, making it a potential multipotent anti-asthmatic agent [6].

Acacia nilotica

This study investigates the anti-asthmatic potential of Acacia nilotica using a network pharmacology and molecular docking approach. From an initial set of 51 phytochemicals identified in AN, 18 active compounds were selected through ADMET screening. These compounds exhibited good oral bioavailability, skin permeability, BBB/CNS penetration and non-toxicity. Target prediction using the STITCH and BindingDB databases identified 189 constituent-related genes and 2096 asthma-related genes from the DisGeNet database, with 80 overlapping targets identified as potential AN-anti-asthmatic targets. Construction of a compound-target network showed that apigenin and quercetin were the major active constituents with the highest connectivity, each interacting with 35 asthma-related genes. PPI analysis delineated AKT1, EGFR, VEGFA, RELA, ESR1, HDAC1, STAT1, PPARG, AR and HSP90AB1 as pivotal hub genes. GO enrichment analysis underscored their involvement in the regulation of inflammation, hypoxia response and signalling through protein kinase B. KEGG pathway analysis indicated that the PI3K-AKT signalling pathway was the most significantly enriched pathway, suggesting a fundamental mechanism underlying the anti-asthmatic effects of AN. Other significant pathways encompassed MAPK and Ras signalling. To elucidate the mechanism by which AN operates in the context of asthma, network analysis was performed using DAVID and Cytoscape, which identified 18 active components, 80 prospective targets and 10 essential pathways. Apigenin and quercetin showed strong binding affinities to major target proteins (AKT1, EGFR, VEGFA, HSP90AB), indicating their therapeutic relevance. The findings suggest that AN exerts multi-target, multi-component and multi-pathway effects, mainly through immunomodulatory and anti-inflammatory mechanisms. The authors conclude that AN has promising anti-asthmatic potential by modulating pathways central to airway inflammation and remodelling, particularly the PI3K-AKT pathway. However, they note that further in vivo and in vitro validation is required to confirm these computational predictions [7].

Pinellia ternata

This article presents a network pharmacology-based investigation into the mechanisms by which Pinellia ternata (PT), a traditional Chinese medicinal herb, exerts therapeutic effects in asthma. The study combines computational predictions with experimental animal validation to clarify PT’s bioactive components, molecular targets, affected pathways and functional effects in the context of allergic asthma. The authors identified 11 bioactive compounds in PT (mainly sterols, flavonoids and glycosides) with favourable pharmacokinetic profiles using the TCMSP Database. Targets of PT’s compounds were predicted using PharmMapper [29] and compared with asthma-related targets collected from the OMIM database, revealing 57 hub genes central to the putative pharmacological network. GO and KEGG pathway enrichment analyses showed these hubs are primarily involved in immune response, cytokine signalling and inflammation, with key signals mediated via the JAK-STAT pathway, T-cell receptor pathway and cytokine-receptor interactions. Animal experiments using an ovalbumin-induced allergic asthma mouse model revealed that PT treatment significantly reduced allergic responses, in part by decreasing Th2 cell activation and downregulating the expression of pivotal inflammatory mediators, Mmp2 and IL-4 in lung tissue. PT appears to modulate core asthma pathways, specifically by impacting cytokine signalling and matrix remodelling, thus providing a scientific rationale for its clinical application as a complementary or adjunct asthma therapy. These findings support the utility of network pharmacology for dissecting the molecular basis of complex herbal medicines and for driving forward rationale phytopharmacological drug development [8].

Hyssopus cuspidatus Boriss

This article presents a network pharmacology investigation aimed at elucidating the antiasthmatic mechanisms of Hyssopus cuspidatus Boriss. (Shen Xiang Cao, SXC), a traditional herbal remedy employed by ethnic minorities in Xinjiang, China. The researchers discerned eight bioactive compounds from SXC via a comprehensive literature review and the TCMSP database [26], employing criteria based on oral bioavailability and DL score and subsequently predicted 258 potential human target proteins associated with asthma utilizing SwissTargetPrediction. A cumulative total of 1295 asthma-related intersection targets were extracted from DisGeNET, GeneCards and the Herb database. Using a Venn diagram, 135 common genes were identified between SXC and asthma. Notable hub targets included inflammatory cytokines and regulatory proteins, such as IL-6, TNF, IL-10, JUN and CXCL8. Functional enrichment analysis indicated that SXC predominantly influences biological processes pertinent to oxidative stress, reactive oxygen species and immune responses. Significant signalling pathways affected by SXC included MAPK, IL-17, Toll-like receptor (TLR) and TNF pathways, all of which are recognized contributors to the pathogenesis of asthma. Molecular docking studies further illustrated robust binding affinities between principal active compounds (quercetin, luteolin, acacetin and β-sitosterol) and these crucial asthma-related target proteins (TNF, MMP9 and AKT1). The study concludes that SXC manifests anti-asthmatic properties through the action of multiple compounds targeting various pathways, thereby providing scientific substantiation for its traditional application and serving as a basis for future experimental validation and clinical research [20].

Bailing capsule (Cordyceps-based)

Network pharmacology identifies 7 key active ingredients, including cerevisterol and beta-sitosterol, and 294 overlapping targets, including asthma-targeting proteins SRC, STAT3 and TP53. These targets play a pivotal role in inflammatory signalling cascades, including the PI3K-Akt, MAPK and Ras pathways, which are primarily implicated in inflammatory responses, programmed cell death and responses to xenobiotic stimuli. The capsule exhibits anti-inflammatory effects by downregulating inflammatory mediators, including IL-4, TNF-α and IL-6. Molecular docking and molecular dynamics simulations show cerevisterol binds stably to core targets. This suggests Bailing Capsule's efficacy in modulating airway inflammation and immune responses in asthma [36].

Ferula asafoetida

The study investigates the anti-asthmatic potential of Ferula asafoetida using an integrated network pharmacology and molecular docking strategy to elucidate its underlying molecular mechanisms. Among the 63 phytochemicals examined, six principal bioactive constituents, assafoetidin, cynaroside, farnesiferol-B, farnesiferol-C, galbanic acid and luteolin, were discerned based on their advantageous pharmacokinetic attributes (ADMET). The STITCH and Swiss Target Prediction databases revealed a total of 630 prospective target genes for the six bioactive compounds, while an aggregate of 1593 genes associated with asthma was obtained from the GeneCards and DisGeNET databases [31,32]. These compounds were predicted to interact with 177 asthma-associated targets through a Venn diagram. PPI network analysis highlighted AKT1, MAPK3 and TNF as central hub genes involved in airway inflammation, remodelling and immune responses. GO and KEGG enrichment revealed that the therapeutic effects of F. asafoetida are mainly associated with modulation of the PI3K-Akt, MAPK, NF-κB, chemokine signalling and T-cell receptor pathways, key routes implicated in asthma pathophysiology. Molecular docking further validated strong binding affinities between the six active compounds and core targets, supporting their mechanistic relevance. In summary, the results indicate that F. asafoetida manifests its anti-asthmatic properties through a complex mechanism involving multiple components, targets and pathways, thereby establishing a scientific rationale for its historical use and laying the groundwork for subsequent in vitro and in vivo investigations [38].

Nepeta bracteata

The study investigated the anti-asthmatic potential of Nepeta bracteata (DBJJ) using an integrated metabolomics and network pharmacology approach. In an ovalbumin-induced allergic asthma rat model, DBJJ treatment significantly improved lung histopathology, reduced eosinophils and WBCs in BALF, and lowered key inflammatory mediators, including TNF-α, IL-18, IgE, IL-1β, VEGF-A and TGF-β1. Metabolomic profiling identified 21 differential serum metabolites involved in amino acid and energy metabolism, suggesting DBJJ’s role in restoring metabolic disturbances associated with asthma. UPLC-QE-MS/MS analysis identified 29 chemical constituents, of which 13 were active based on oral availability and Caco-2 cell permeability, mapping to 120 core targets and 173 KEGG pathways, including MAPK, PI3K-Akt, Th17 differentiation and oxidative stress-related pathways. Integrated analysis highlighted ferulic acid and ursolic acid as key bioactive compounds targeting DAO and NOS2 and molecular docking confirmed strong binding affinities. Western blot validation showed that DBJJ reduced phosphorylation and expression of NOS2, MAPK1/3 and STAT3, confirming pathway-level modulation. Overall, the findings demonstrate that N. bracteata exerts multi-target, multi-pathway anti-asthmatic effects by regulating inflammation, oxidative stress and disturbed metabolic pathways [40].

Resveratrol

This study employs a network pharmacology and molecular docking approach combined with empirical verification to explore the therapeutic mechanisms of resveratrol in asthma treatment. After intersecting the 236 Res targets obtained from TCMSP, DrugBank and SwissTargetPrediction with the 2,382 asthma targets from DisGeNET, GeneCards and TTD, 120 overlapping genes against asthma were identified, with TNF, IL6, STAT3, TP53 and IL1B as key therapeutic targets. Functional enrichment analyses elucidated the role of resveratrol in various biological processes, including apoptosis and inflammation, as well as in specific signalling pathways such as the TNF and MAPK pathways. Docking studies corroborated the presence of robust binding affinities between resveratrol and critical proteins (TNFα, IL-6, STAT3, p53 and IL-1β). Experimental validation using a house dust mite-induced asthma murine model and airway epithelial cell cultures demonstrated that resveratrol significantly mitigated airway hyperresponsiveness and inflammation by reinstating the dysregulated expression of these targets, with notable improvements in inflammatory infiltration in the peri-bronchial regions, peri-vascular areas and lung parenchyma. This investigation offers a thorough understanding of the multi-targeted anti-asthmatic effects of resveratrol and substantiates its prospective application in asthma management [44].

Fructus Xanthii

This study integrates multi-omics (from GEO datasets GSE63142 and GSE14787), network pharmacology, machine learning (RF, SVM, XGBoost), molecular docking, dynamics simulations, immune infiltration (CIBERSORT) and in vivo validation in an OVA-induced murine asthma model to reveal Fructus Xanthii’s (Cang-Er-Zi) anti-asthmatic mechanisms. Key findings include 3,755 asthma-related DEGs with the MEblack WGCNA module (741 genes) correlating strongly; 1,317 Fructus Xanthii targets intersecting 100 DEGs, yielding hub genes like HSP90AB1, CCNB1, CASP9, CDK6, NR3C1, ERBB2 and CCK via PPI and machine learning, indicating anti-inflammatory, immune-modulatory, cell cycle and apoptosis-regulatory involvement. GO/KEGG enrichment highlighted steroid hormone responses, kinase activities, PI3K-AKT, cellular senescence and p53 pathways; docking showed strong affinities (e.g. carboxyatractyloside-HSP90AB1 at -42.22 kJ mol-1 (-10.09 kcal mol-1)) with stable MD trajectories (RMSD <0.3 nm); immune analysis revealed shifts in M2 macrophages and plasma/ /memory B cells. In vivo, Fructus Xanthii extract (10 to 30 mg kg-1) dose-dependently reduced lung inflammation, BALF cytokines (TNF-α, IL-6, IL-1β, IL-5), histopathology scores and hub gene/protein expression (HSP90AB1, AKT1), comparable to dexamethasone, modulating inflammation, cell cycle, apoptosis and immune homeostasis via HSP90AB1/IL6/TNF and PI3K-AKT pathways. Overall, Fructus Xanthii exhibits a robust multi-target therapeutic mechanism, supporting its potential as an effective complementary herbal intervention in asthma [50].

Marsdenia tenacissima

This study investigated the therapeutic potential of Marsdenia tenacissima (MT) in neutrophilic asthma (NA), a severe asthma subtype characterized by poor glucocorticoid response and elevated neutrophil levels. By employing a comprehensive methodology that integrates network pharmacology, molecular docking, molecular dynamics and experimental validation, the research successfully identified significant bioactive constituents of MT, notably 17β-Tenacigenin B, as the primary pharmacologically active C21 steroid compound that interacts with IL-6 and JAK1, thereby modulating the JAK-STAT signalling pathway and the subsequent PI3K-AKT-mTOR cascade. From 282 MT compounds, 45 drug-like actives intersected with asthma targets yielded 34 genes enriched in leukocyte activation and migration, LPS response, lipoxygenase activity and relevant KEGG pathways; molecular docking showed strong binding affinities (-24.69/-25.94 kJ mol-1 (-5.9/-6.2 kcal mol-1)), confirmed by dynamics simulations (stable RMSD ~0.2 nm) and CETSA (higher Tm). Validation via molecular docking, dynamics simulations, CETSA (cell thermal shift assay), in vitro assays on bronchial epithelial cells showing reduced inflammatory cytokines (IL-1, IL-6, IL-17, IFN-γ, TNF-α) and neutrophil migration, and in vivo NA mouse models (HDM+LPS-induced) demonstrating alleviated airway hyperresponsiveness, neutrophil infiltration, mucus hypersecretion and cytokine levels. MT and 17-Tenacigenin B treatments mirrored the effects of IL-6 inhibitor LMT-28, confirming the IL-6/JAK-STAT axis as central to MT's therapeutic mechanism. Overall, this work demonstrates that Marsdenia tenacissima exerts potent therapeutic effects in neutrophilic asthma by modulating inflammatory signalling cascades, restoring immune balance and overcoming steroid resistance, positioning it as a promising candidate for refractory asthma management [51].

Paeoniae Radix Alba

Paeoniae Radix Alba (PRA), the root of Paeonia lactiflora Pall., is traditionally used in Chinese medicine for asthma treatment. This study employed a systematic network pharmacology approach to identify 21 active phytochemicals in PRA and their 147 associated target proteins relevant to asthma. Key active compounds such as kaempferol, paeoniflorin, beta-sitosterol and sitogluside were linked to critical asthma-related targets, including TNF-α, PGR and NF-Κb pathway components. Gene Ontology and KEGG pathway analyses suggested that PRA’s therapeutic effects involve modulation of inflammatory processes, inhibition of TNF release, ceramide signalling, and regulation of apoptosis. Notably, kaempferol was found to inhibit airway eosinophil infiltration, inflammatory mediator release, IL-4 and ceramide signalling pathway, while Paeoniflorin diminishes lipolytic activity in adipocytes and obstructs the phosphorylation of ERK, JNK, and IKK that is induced by TNF-α. Beta-sitosterol and sitogluside helped relax bronchial smooth muscle by regulating calcium ion signalling, thereby potentially reducing cough and bronchospasm. The study highlights TNF-α as a central target, providing a molecular basis for PRA’s anti-inflammatory and immunomodulatory effects in asthma. Overall, the findings support PRA’s multi-target therapeutic potential, uncovering molecular interactions that warrant further experimental validation and clinical exploration [52].

Andrographolide

This research meticulously investigated the anti-asthmatic mechanisms of andrographolide (AG), a principal bioactive compound derived from Andrographis paniculata, which is widely recognized for its significant anti-inflammatory and immunomodulatory properties, as well as its ability to restore steroid sensitivity. Employing a combination of network pharmacology, molecular docking and experimental validation within a model of ovalbumin-sensitized BALB/c mice, the study identified a total of 57 andrographolide-associated targets, sourced from the Swiss Target Prediction, Drug Bank and STITCH [28,30,34] databases, which were subsequently cross-referenced with 8168 asthma-related targets obtained from the OMIM [31] and Genecards 33] databases. A subset of 38 targets emerged as potential candidates for andrographolide's therapeutic action against asthma. The construction of a PPI network underscored prominent hubs, including IL-6, IL-1B, NFKB1, MMP9, CDK2, CREBBP, MAP2K1, JAK1, AR and PRKCA. GO enrichment analysis highlighted critical biological processes such as protein phosphorylation and kinase activity, along with cellular components like receptor complexes, while KEGG pathway analysis identified Th17 cell differentiation, JAK-STAT signalling, PI3K-Akt pathway and TNF signalling as the primary pathways of interest. Molecular docking studies corroborated the strong binding affinities of AG to various targets, including JAK2 (-21.30 kJ mol-1), MMP9 (-21.63 kJ mol-1), PRKCA (-21.71 kJ mol-1), LRRK2 (-21.92 kJ mol-1) and ITGAL (-23.35 kJ mol-1), with interactions visualized through the formation of hydrogen bonds. In vivo flow cytometry experiments demonstrated that AG (0.5 mg kg-1) significantly reduced Th17 cell differentiation in lung tissue, comparable to dexamethasone (2 mg kg-1), supporting Th17 inhibition as a core mechanism for AG's therapeutic effects against airway inflammation, hyperresponsiveness and remodelling in asthma [56].

Collectively, the body of research elucidates those herbal preparations and their constituent phytochemicals manifest anti-asthmatic properties through multifaceted mechanisms encompassing multiple components, targets and pathways, with a predominant emphasis on the modulation of inflammatory, immunological and airway remodelling pathways. Most traditional decoctions, such as Danlong Dingchuan Decoction, Bushenyiqi Decoction, Maxing-Ganshi Decoction and Jiegeng Decoction, consistently targeted central asthma-related pathways, including PI3K-Akt, MAPK, NF-κB, JAK-STAT, TNF and Th2/Th17 differentiation axes. Similarly, single herbs or phytochemicals such as Acacia nilotica, Pinellia ternata, Ferula asafoetida, Hyssopus cuspidatus Boriss., Resveratrol, Paeonia lactiflora and Andrographolide showed overlapping hub targets such as TNF, IL-6, AKT1, MAPK3, STAT3 and EGFR, reinforcing the concept that asthma is driven by interconnected inflammatory and immune signalling networks. Across studies, network pharmacology combined with molecular docking served as the foundational methodology, while several investigations strengthened predictions through in vivo validation in ovalbumin, HDM, or LPS-induced asthma models. Among them, studies integrating multi-omics, machine learning, molecular dynamics, immune infiltration analysis and experimental validations, such as those on Fructus Xanthii and Marsdenia tenacissima, provided the most comprehensive mechanistic insight, as they moved beyond static network predictions to dynamic simulations and subtype-specific validation (e.g. neutrophilic asthma). Therefore, while classical network pharmacology with docking and animal validation is robust and widely applied, integrative approaches incorporating multi-omics data, machine learning algorithms, molecular dynamics simulations and targeted experimental confirmation appear methodologically superior, offering higher predictive accuracy, more profound mechanistic clarity and stronger translational relevance for future anti-asthmatic drug development (Tables 2 and 3).

No. | Formula/component | Key bioactive | Main targets/pathways | Study design and experimental model | Ref.
1 | Artesunate | Artesunate/DHA | CCND1, MTOR, ERBB2, MAPK3, EGFR, NF-kappa B signalling pathway, Fc epsilon receptor (FCERI) signalling | Network pharmacology, ADMET and molecular docking | [6]
2 | Acacia nilotica | Quercetin, apigenin | AKT1, EGFR, VEGFA, STAT1, HSP90AB1, MAPK, PI3K-Akt, Ras | Network pharmacology and Molecular docking (in silico) | [7]
3 | Pinellia ternata | Flavonoids, sterols, lipids | JAK-STAT, TCR, cytokine-cytokine receptor, IL-4, MMP2 | Animal model, gene/protein expression | [8]
4 | Hyssopus cuspidatus Boriss. | Luteolin, quercetin, acacetin and β-sitosterol | TNF, MAPK, IL-17, MMP9, AKT1, JUN, CXCL8, IL-6, TLR | Network pharmacology and Molecular docking (in silico) | [20]
5 | Bushenyiqi decoction | Quercetin, kaempferol, luteolin | IL-6, EGFR, HIF1A, PI3K-Akt, Th2 cytokines (IL-4, IL-5, IL-13), TNF, HIF-1, Th-17 cell differentiation | Network pharmacology, Mouse model, western blotting, ELISA, molecular docking, cytokine levels | [24]
6 | Bailing capsule | Cerevisterol | SRC, TP53, STAT3, PI3K-Akt, MAPK and Ras pathways | Network pharmacology, molecular docking, in vitro validation, molecular dynamics simulation | [36]
7 | Ferula asafoetida | Assafoetidin, luteolin | AKT1, MAPK3, TNF, NF-κB, PI3K-Akt, Ras, Chemokine signaling | Network pharmacology and molecular docking (in silico) | [38]
8 | Nepeta bracteata (DBJJ) | Ferulic acid, ursolic acid | MAPK, STAT3, NOS2, Th17 differentiation, oxidative stress | Metabolomics, western blot, molecular docking, animal model | [40]
9 | Danlong Dingchuan decoction | Quercetin, xanthine, lysine, kaempferol and ß sitosterol | IL-6, TNF, CXCL8, VEGFA, MAPK3, cAMP, cGMP-PKG, NF-κB and PI3K-Akt signalling pathway | Metabolomics, experimental validation and molecular docking, in vivo studies | [42]
10 | Conciliatory anti-allergic decoction | Quercetin, kaempferol | TNF, IL-4, IL-13, NF-κB, JAK-STAT, Th1/Th2 | Mouse model, molecular docking | [43]
11 | Resveratrol | Resveratrol | TNF, IL6, STAT3, TP53, IL1B, apoptosis, MAPK, TNF signalling pathways | Animal/cell experiments, molecular docking, western blotting | [44]
12 | Fructus Xanthii | sesquiterpene lactones, flavonoids, lignans and coumarin derivatives | HSP90AB1, CCNB1, CASP9, CCK, HSP90AB1/IL6/TNF, PI3K-AKT, cellular senescence, p53 pathways | multi-omics analysis, network pharmacology, molecular docking, machine learning and experimental validation | [50]
13 | Marsdenia tenacissima | 17-Tenacigenin B | IL-6, JAK1, JAK-STAT and PI3K-AKT-mTOR pathways | network pharmacology, molecular docking, MD and experimental validation | [51]
14 | Paeoniae radix Alba | kaempferol, paeoniflorin, beta-sitosterol and sitogluside | TNF-α, PGR, NF-κB, ceramide signalling, Toll-like receptor pathways and apoptosis regulation | Network/enrichment analysis | [52]
15 | Maxing Ganshi decoction | Multiple flavonoids | Neurotrophin, PI3K-Akt, estrogen, immune inflamemation and ErbB pathways | Network/enrichment analysis | [54]
16 | Jiegeng decoction | Platycodon grandiflorus and Glycyrrhiza uralensis | IL-4/IL-13-JAK1-STAT6 | Animal model, network, experimental validation | [55]
17 | Andrographolide | Andrographolide | IL-6, IL-1B, NFKB1, MMP9, CDK2, Th17 cell differrentiation, JAK-STAT, PI3K-Akt and TNF signalling pathways | Network pharmacology, molecular docking, in vitro validation | [56]

No. | Study / herb or formula | Major strengths of the model | Key limitations of the model | Ref.
1 | Artesunate | Incorporates safety and pharmacokinetic prediction; enhances drug repositioning relevance | No experimental asthma model used; therapeutic efficacy remains theoretical | [6]
2 | Acacia nilotica | Efficient identification of multi-target mechanisms; suitable for exploring traditional herbal claims | No biological or experimental validation; predictions rely on database accuracy; limited translational relevance | [7]
3 | Pinellia ternata | Combines computational prediction with in vivo validation; links molecular targets to biological outcomes; confirms anti-allergic activity | Small animal sample size; OVA model reflects acute allergic asthma rather than chronic disease; network pharmacology predictions require further clinical confirmation | [8]
4 | Hyssopus cuspidatus Boriss. | Systematic screening of key inflammatory pathways (MAPK, TNF, IL-17) | Purely predictive; lacks functional immune or airway validation | [20]
5 | Bushenyiqi decoction | Strong causal evidence; links pathway modulation to airway inflammation and lung function | Animal model reflects mainly allergic asthma; limited human translatability | [24]
6 | Bailing capsule | Confirms predicted targets in airway epithelial cells, improves biological relevance | In vitro model cannot replicate full asthma pathology or airway remodelling | [36]
7 | Ferula asafoetida | Highlights multi-component synergy and pathway-level modulation | Absence of in vitro or in vivo confirmation; does not account for pharmacokinetics or immune complexity | [38]
8 | Nepeta bracteata (DBJJ) | Demonstrates direct pharmacological effect of single herb; easier to interpret than polyherbal formulas | Often lacks omics-level validation; preclinical data only; limited pathway confirmation | [40]
9 | Danlong Dingchuan decoction | Demonstrates functional anti-inflammatory effects in whole-organism context | Limited mechanistic depth at cellular immune level; species differences | [42]
10 | Conciliatory anti-allergic decoction | Systems-level approach suitable for complex diseases like asthma; reflects traditional polyherbal therapy | High complexity reduces clarity of causal mechanisms; dosing standardization issues | [43]
11 | Resveratrol | Well-characterized compound with defined molecular targets; strong mechanistic evidence | Non-herbal single compound - may not fully represent TCM complexity; bioavailability concerns limit translational interpretation | [44]
12 | Fructus Xanthii | Most comprehensive approach; captures immune heterogeneity and system-level effects | High complexity; resource-intensive; limited scalability for routine screening | [50]
13 | Marsdenia tenacissima | Whole-organism assessment allows evaluation of airway inflammation and cytokine response | Limited mechanistic depth; often lacks long-term chronic remodelling assessment; translational relevance to humans may be restricted | [51]
14 | Paeoniae radix Alba | Mechanistic insight into active constituents; clearer pharmacological targeting compared with complex decoctions | May not reflect synergistic effects seen in clinical formulas; dose equivalence to human use unclears | [52]
15 | Maxing Ganshi decoction | Classical TCM formula studied in physiological disease context; multi-target approach mirrors clinical usage | Complex multi-component nature makes mechanistic attribution difficult; variability in herbal composition reduces reproducibility | [54]
16 | Jiegeng decoction | High translational strength; validates Th2-JAK-STAT signalling at cellular and tissue levels | Focused on Th2-dominant asthma; may not represent non-allergic phenotypes | [55]
17 | Andrographolide | Strengthened mechanistic credibility; partial immune validation (Th17 differentiation) | Limited to cellular models; lacks airway-level physiological validation | [56]