Cosmos caudatus Extract Attenuates Doxorubicin-Associated Lung Injury in Female Wistar Rats: Histopathological and Biomarker Evidence From 4-HNE, IL-6, Bax and Angiopoietin-2
1 Department of Internal Medicine, Faculty of Medicine, Universitas Wijaya Kusuma Surabaya, Surabaya, Indonesia.
2 Department of Pharmacology, Faculty of Medicine, Universitas Wijaya Kusuma Surabaya, Surabaya, Indonesia.
3 Department of Public Health, Faculty of Medicine, Universitas Wijaya Kusuma Surabaya, Surabaya, Indonesia.
4 Department of Biochemistry, Faculty of Medicine, Universitas Wijaya Kusuma Surabaya, Surabaya, Indonesia.
5 Undergraduate Medical Doctor Program, Faculty of Medicine, Universitas Wijaya Kusuma Surabaya, Surabaya, Indonesia.
6 Undergraduate Medical Doctor Program, Faculty of Medicine and Health Sciences, Universitas Muhammadiyah Makassar, Makassar, Indonesia.
Research Article
Open Access Research Journal of Biology and Pharmacy, 2026, 16(01), 029-040.
Article DOI: 10.53022/oarjbp.2026.16.1.0019
Publication history:
Received on 09 January 2026; revised on 14 February 2026; accepted on 17 February 2026
Abstract:
Background: Doxorubicin (DOX) is widely used in chemotherapy but is limited by off-target toxicities, including lung injury driven by oxidative stress, inflammation, apoptosis, and endothelial dysfunction. Cosmos caudatus is a polyphenol-rich medicinal plant with reported antioxidant activity; however, its protective effect against DOX-associated lung injury remains unclear.
Objective: To assess whether C. caudatus extract (CCE) protects against doxorubicin-associated lung injury in female Wistar rats.
Methods: Twenty rats were randomized into four groups (n = 5/group): control (CON), DOX (5 mg/kg i.p. weekly for 4 weeks), DOX+CCE200, and DOX+CCE400. CCE (200 or 400 mg/kg/day, oral gavage) was administered one week prior to DOX and continued throughout the exposure period. Lung injury was evaluated by blinded histopathological scoring (H&E). Lung levels of 4-hydroxynonenal (4-HNE), interleukin-6 (IL-6), Bax, and angiopoietin-2 (Ang-2) were measured by ELISA and normalized to total protein.
Results: DOX significantly reduced body weight gain, increased lung index, worsened histopathological injury, and elevated lung 4-HNE, IL-6, Bax, and Ang-2 compared with CON. CCE improved weight-related outcomes and reduced lung index in a dose-dependent manner. The 400 mg/kg dose significantly reduced histopathological injury scores, while both doses markedly suppressed oxidative, inflammatory, apoptotic, and endothelial injury biomarkers.
Conclusion: C. caudatus extract attenuates DOX-induced lung injury, potentially through modulation of oxidative stress, inflammation, apoptosis, and endothelial activation pathways.
Keywords:
Cosmos caudatus; Doxorubicin; Lung injury; Oxidative stress; Apoptosis; Angiopoietin-2
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