ArticleChinese medicine2023
Isoforskolin modulates AQP4-SPP1-PIK3C3 related pathway for chronic obstructive pulmonary disease via cAMP signaling.
Article in Chinese medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 10 citations in OpenAlex.
- Pseudoephedrine Improves Chronic Obstructive Pulmonary Disease by Regulating Airway Senescence and Mitochondrial Function through PI3K/AKT/mTOR Axis.Biomolecules & therapeutics · 2026Article
- Gene signature linked to inhaled corticosteroid-induced lung function improvement in COPD: insights from the GLUCOLD Study.ERJ open research · 2026Article
- Isoforskolin inhibits LUBAC/GSDMD/IL-1β cascades in pulmonary fibrosis.Journal of thoracic disease · 2026Article
- Negative Correlation Between Secreted Phosphoprotein 1 and the Treg/Th17 Ratio in Non-Valvular Atrial Fibrillation.Reviews in cardiovascular medicine · 2025Article
- [Therapeutic effects of natural products on animal models of chronic obstructive pulmonary disease].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Integrative network pharmacology, transcriptomics, and proteomics reveal the material basis and mechanism of the Shen Qing Weichang Formula against gastric cancer.Chinese medicine · 2025Article
- Mechanism underlying the therapeutic effects of effective component compatibility of Bufei Yishen formula III combined with exercise rehabilitation on chronic obstructive pulmonary disease.Annals of medicine · 2024Article
- Extracellular vesicle dynamics in COPD: understanding the role of miR-422a, SPP1 and IL-17 A in smoking-related pathology.BMC pulmonary medicine · 2024Article
- Osteopontin/SPP1: a potential mediator between immune cells and vascular calcification.Frontiers in immunology · 2024Review
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCyclic adenosine monophosphate (cAMP) levels are directly activated by adenylate cyclase (AC) and play an anti-inflammatory role in chronic obstructive pulmonary disease (COPD). Previously, we have shown that isoforskolin (ISOF) can effectively activate AC1 and AC2 in vitro, improve pulmonary ventilation and reduce the inflammatory response in COPD model rats, supporting that ISOF may be a potential drug for the prevention and treatment of COPD, but the mechanism has not been explored in detail.
methodsThe potential pharmacological mechanisms of ISOF against COPD were analyzed by network pharmacology and multi-omics based on pharmacodynamic study. To use specific agonists, inhibitors and/or SiRNA for gene regulation function studies, combined qPCR, WB were applied to detect changes in mRNA and protein expression of important targets PIK3C3, AKT, mTOR, SPP1 and AQP4 which related to ISOF effect on COPD. And the key inflammatory factors detected by ELISA.
resultsBioinformatics suggested that the anti-COPD pharmacological mechanism of ISOF was related to PI3K-AKT signaling pathway, and suggested target protein like PIK3C3, AQP4, SPP1, AKT, mTOR. Using the AQP4 inhibitor,or inhibiting SPP1 expression by siRNA-SPP1 could block the PIK3C3-AKT-mTOR pathway and ameliorate chronic inflammation. ISOF showed cAMP-promoting effect then suppressed AQP4 expression, together with decreased level of IL-1β, IL-6, and IL-8.
conclusionsThese findings demonstrate ISOF controlled the cAMP-regulated PIK3C3-AKT-mTOR pathway, thereby alleviating inflammatory development in COPD. The cAMP/AQP4/PIK3C3 axis also modulate Th17/Treg differentiation, revealed potential therapeutic targets for this disease.
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