Inula racemosa ameliorates acute lung injury through integrated modulation of innate immune signalling, inflammation activation and redox homeostasis
DOI:
https://doi.org/10.18203/issn.2454-2156.IntJSciRep20263677Keywords:
Inula racemosa, Cytokines, Lung inflammation, LPS, COVID-19Abstract
Background: Chronic respiratory diseases are associated with persistent inflammation and dysregulated immune responses. Although corticosteroids are widely used, prolonged therapy may cause immunosuppression and increase susceptibility to secondary infections. Inula racemosa (IR) Hook. F. (Pushkarmool), an Ayurvedic medicinal plant traditionally used for respiratory and inflammatory disorders, contains bioactive sesquiterpene lactones, particularly alantolactone and isoalantolactone, with reported anti-inflammatory and immunomodulatory activities.
Methods: The study employed human lung epithelial NCI-H460 cells and an lipopolysaccharide (LPS) induced pulmonary inflammation model in BALB/c mice. Cytotoxicity and inflammatory responses were evaluated following treatment with IR extract. Gene expression of key inflammatory and signalling markers was analysed by RT-qPCR, while protein levels of inflammatory cytokines were quantified using ELISA. Cytokine profiling, BALF cellular analysis, and lung histopathological examination were performed to assess the anti-inflammatory effects of the extract. The expression of genes associated with the TLR4/MyD88/NF-κB, MAPK, NLRP3 inflammasome, and Nrf2/HO-1 pathways was investigated to elucidate the potential molecular mechanisms underlying observed effects.
Results: IR extract attenuated LPS-induced inflammatory responses in NCI-H460 cells, with reduced production of TNF-α, IL-6, IL-1β, IL-8, IL-18, IL-4, and CCL2. In LPS-challenged BALB/c mice, treatment reduced inflammatory cell infiltration, including neutrophils, in BAL fluid and improved inflammation-associated histopathological alterations in lung tissue.
Conclusions: The findings demonstrate that whole IR extract possesses significant anti-inflammatory activity in cellular and experimental pulmonary inflammation models. Its effects may involve modulation of multiple inflammatory and antioxidant signalling pathways. These findings provide experimental support for the traditional use of IR in respiratory inflammatory conditions and warrant further mechanistic and translational investigations.
Metrics
References
Medzhitov R. Inflammation 2010: New adventures of an old flame. Cell. 2010;140(6):771-6. DOI: https://doi.org/10.1016/j.cell.2010.03.006
Nathan C, Ding A. Nonresolving inflammation. Cell. 2010;140(6):871-82. DOI: https://doi.org/10.1016/j.cell.2010.02.029
Gundeti MS, Bhurke LW, Mundkinajeddu D. Traditional medicine in India. J Tradit Chinese Med Sci. 2021;8(4):294-305.
Gundeti MS, Bhurke LW, Mundada PS, Murudkar S, Surve A, Sharma R, et al. AYUSH 64, a polyherbal Ayurvedic formulation in influenza-like illness: Results of a pilot study. J Ayurveda Integrative Med. 2022;13(3):100325. DOI: https://doi.org/10.1016/j.jaim.2020.05.010
Ma S, Wang X, Lai F, Lou C. The beneficial pharmacological effects and potential mechanisms of picroside II: Evidence of its benefits from in vitro and in vivo. Biomed Pharmacother. 2020;130:110421. DOI: https://doi.org/10.1016/j.biopha.2020.110421
Khyade MS, Kasote DM, Vaikos NP. Alstonia scholaris (L.) R.Br. and Alstonia macrophylla Wall. ex G. Don: A comparative review on traditional uses, phytochemistry and pharmacology. J Ethnopharmacol. 2014;153(1):1-18. DOI: https://doi.org/10.1016/j.jep.2014.01.025
Gaffen SL. Recent advances in the IL-17 cytokine family. Curr Opin Immunol. 2011;23(5):613-9. DOI: https://doi.org/10.1016/j.coi.2011.07.006
Agache I, Ciobanu C, Agache C, Anghel M. Increased serum IL-17 is an independent risk factor for severe asthma. Respiratory Medicine. 2010;104(8):1131-7. DOI: https://doi.org/10.1016/j.rmed.2010.02.018
Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133(5):775-87. DOI: https://doi.org/10.1016/j.cell.2008.05.009
Burzyn D, Kuswanto W, Kolodin D, Jennifer LS, Massimiliano C, Young J, et al. A special population of regulatory T cells potentiates muscle repair. Cell. 2013;155(6):1282-95. DOI: https://doi.org/10.1016/j.cell.2013.10.054
Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respiratory Med. 2020;8(4):420-22. DOI: https://doi.org/10.1016/S2213-2600(20)30076-X
Patel VK, Shirbhate E, Patel P, Veerasamy R, Sharma PC, Rajak H. Corticosteroids for treatment of COVID-19: Effect, evidence, expectation and extent. Beni-Suef University J Basic Applied Sci. 2021;10:78. DOI: https://doi.org/10.1186/s43088-021-00165-0
Rizvi SAA, Einstein GP, Tulp OL, Sainvil F, Branly R. Introduction to Traditional Medicine and Their Role in Prevention and Treatment of Emerging and Re-Emerging Diseases. Biomolecules. 2022;12(10):1442. DOI: https://doi.org/10.3390/biom12101442
Rathore S, Raj Y, Debnath P, Kumar M, Kumar R. Ethnopharmacology, phytochemistry, agrotechnology, and conservation of Inula racemosa Hook. f.: A critically endangered medicinal plant of the western Himalaya. J Ethnopharmacol. 2022;283:114613.
Wangchuk P, Jamtsho T. Inula racemosa Hook. f. (Pushkarmool): Its ethnobotanical uses, phytochemicals, and pharmacological activities. James Cook University. 2023.
Yang G, Yang L, Xu F. Isoalantolactone: A review on its pharmacological effects. Front Pharmacol. 2024;15:1372428.
Tan L, Li J, Wang Y, Tan R. Anti-neuroinflammatory effect of alantolactone through the suppression of the NF-κB and MAPK signaling pathways. Cells. 2019;8(7):739.
Dang X, He B, Ning Q, Liu Y, Guo J, Niu G, et al. Alantolactone suppresses inflammation, apoptosis and oxidative stress in cigarette smoke-induced human bronchial epithelial cells through activation of Nrf2/HO-1 and inhibition of the NF-κB pathways. Respiratory Res. 2020;21:95.
Jiang C, Masood M, Rasul A, Wei W, Wang Y, Ali M, et al. Alantolactone inhibits NF-κB and STAT3 activation and induces reactive oxygen species-mediated apoptosis in prostate cancer DU145 cells. Molecules. 2017;22(10):1707. DOI: https://doi.org/10.3390/molecules22020240
Liu X, Bian L, Duan X, Zhuang X, Sui Y, Yang L. Alantolactone: A sesquiterpene lactone with diverse pharmacological effects. Chem Biol Drug Des. 2021;98(6):1131-5. DOI: https://doi.org/10.1111/cbdd.13972
Dang X, He B, Ning Q, Liu Y, Guo J, Niu G, Chen M. Alantolactone suppresses inflammation, apoptosis and oxidative stress in cigarette smoke-induced human bronchial epithelial cells through activation of Nrf2/HO-1 and inhibition of the NF-κB pathways. Respir Res. 2020;21(1):95.
He G, Zhang X, Chen Y, Chen J, Li L, Xie Y. Isoalantolactone inhibits LPS-induced inflammation via NF-κB inactivation in peritoneal macrophages and improves survival in sepsis. Biomed Pharmacother. 2017;90:598-607. DOI: https://doi.org/10.1016/j.biopha.2017.03.095
Sharma RK, Arora R. Herbal Drugs: A Twenty-First Century Perspective. Jaypee Digital. 2006: 688. DOI: https://doi.org/10.5005/jp/books/10352
Kirtikar KR, Basu BD. Indian Medicinal Plants. 2nd ed. Dehradun: International Book Distributors. 1999.
Government of India, Ministry of AYUSH. The Ayurvedic Pharmacopoeia of India. Part I, Vol. II. New Delhi: Ministry of AYUSH; Inula racemosa monograph.
Wangchuk P. Inula racemosa Hook.f. (Pushkarmool): Ethnobotany, phytochemistry and pharmacological activities. Plants. 2024. DOI: https://doi.org/10.1007/978-981-19-9501-9_11
Rathore S, Debnath P, Kumar R. Inula racemosa: A critically endangered medicinal plant with therapeutic potential. J Ethnopharmacol. 2022;283:114613. DOI: https://doi.org/10.1016/j.jep.2021.114613
OECD. Guidance Document on Good in Vitro Method Practices (GIVIMP). Paris: OECD Publishing. 2020.
Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduction and Targeted Therapy. 2017;2:17023. DOI: https://doi.org/10.1038/sigtrans.2017.23
Chen L, Deng H, Cui H, Jing F, Zhicai Z, Junliang D, et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2018;9:7204-18. DOI: https://doi.org/10.18632/oncotarget.23208
Thompson BT, Chambers RC, Liu KD. Acute respiratory distress syndrome. N Eng J Med. 2017;377:562-72. DOI: https://doi.org/10.1056/NEJMra1608077
Yang G, Yang L, Xu F. Isoalantolactone: A review on its pharmacological effects. Front Pharmacol. 2024;15:1453205. DOI: https://doi.org/10.3389/fphar.2024.1453205
Tan L, Li J, Wang Y, Tan R. Anti-neuroinflammatory effect of alantolactone through suppression of NF-κB and MAPK signaling pathways. Cells. 2019;8:739. DOI: https://doi.org/10.3390/cells8070739
Dang X, He B, Ning Q, Ya L, Jianxin G, Gang N, et al. Alantolactone suppresses inflammation, apoptosis and oxidative stress through activation of Nrf2/HO-1 and inhibition of NF-κB pathways. Respiratory Res. 2020;21(1):95. DOI: https://doi.org/10.1186/s12931-020-01358-4
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Phulwanti Kumari Sharma, Gaurav Sharma, Sudipta Kumar Rath

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.