Protective effects of Echinacea extract and hydrocortisone coadministration against sepsis-induced pulmonary lesions in rats
Subject Areas : clinical veterinary science
Reyhane Zendedel
1
,
saeed hesaraki
2
*
1 - Department of Pathobiology, SR.C., Islamic Azad University, Tehran, Iran
2 - Department of Pathobiology, Sc. R, Islamic Azad University, Tehran, Iran
Keywords: echinacea, hydrocortisone, sepsis, pulmonary lesions,
Abstract :
Sepsis is a severe cytokine crisis with the systemic and pulmonary edema, causing death. Corticosteroids are prescribed in sepsis crises to reduce the destructive reactions caused by the exaggerated immune system response, especially in pulmonary edema. This study aimed to investigate the protective effects of Echinacea extract combined with hydrocortisone in reducing edema and inflammation in the lungs of rats that had suffered from sepsis crises. In this study, the rats were split into three groups: one group had sepsis without any treatment, and the other two groups received daily doses of 400 and 800 micrograms/kg of Echinacea extract for two weeks, plus an injection of 8 mg/kg of hydrocortisone on the 14th day after sepsis. Sepsis was induced by CLP on day 14, and rats were sacrificed 24 hours later by pentobarbital (250 mg/kg IP). First, the wet-to-dry weight ratio of the lung was calculated. The neutrophil count in bronchoalveolar lavage fluid was assessed. Half of the lung tissue was allocated for histopathology, and the other half was allocated for evaluating malondialdehyde (MDA) and total antioxidant capacity (TAC) parameters. The wet-to-dry weight ratio of the lung in the sepsis group was found to be higher than the other groups (P<0.01). The amount of malondialdehyde (MDA) was significantly higher in the sepsis group than in the other two groups (P<0.01). However, the antioxidant reserve in the 800 group was significantly higher than in the sepsis and 400 groups (P<0.01). The levels of tissue damage (fluid buildup in the air sacs and airways) were also significantly lower in the sepsis, 400, and 800 groups, respectively. The results of the present study indicated that Echinacea extract plays a role in reducing inflammation caused by sepsis.
1. Kumar V. Pulmonary innate immune response determines the outcome of inflammation during pneumonia and sepsis-associated acute lung injury. Frontiers in immunology. 2020;11:1722.
2. Prauchner CA. Oxidative stress in sepsis: Pathophysiological implications justifying antioxidant co-therapy. Burns. 2017;43(3):471-85.
3. Sharifi-Rad M, Mnayer D, Morais-Braga MFB, Carneiro JNP, Bezerra CF, Coutinho HDM, et al. Echinacea plants as antioxidant and antibacterial agents: From traditional medicine to biotechnological applications. Phytother Res. 2018;32(9):1653-63.
4. Burlou-Nagy C, Bănică F, Jurca T, Vicaș LG, Marian E, Muresan ME, et al. Echinacea purpurea (L.) Moench: Biological and pharmacological properties. A review. Plants. 2022;11(9):1244.
5. Hubbard WJ, Choudhry M, Schwacha MG, Kerby JD, Rue III LW, Bland KI, Chaudry IH. Cecal ligation and puncture. Shock. 2005;24:52-7.
6. Deng Z, He M, Hu H, Zhang W, Zhang Y, Ge Y, et al. Melatonin attenuates sepsis-induced acute kidney injury by promoting mitophagy through SIRT3-mediated TFAM deacetylation. Autophagy. 2024;20(1):151-65.
7. Legras A, Giraudeau B, Jonville-Bera AP, Camus C, François B, Runge I, et al. A multicentre case-control study of nonsteroidal anti-inflammatory drugs as a risk factor for severe sepsis and septic shock. Crit Care. 2009;13(2):R43.
8. Barnes J, Anderson LA, Gibbons S, Phillipson JD. Echinacea species (Echinacea angustifolia (DC.) Hell., Echinacea pallida (Nutt.) Nutt.,Echinacea purpurea (L.) Moench): a review of their chemistry, pharmacology and clinical properties. J Pharm Pharmacol. 2005;57(8):929-54.
9. Guiotto P, Woelkart K, Grabnar I, Voinovich D, Perissutti B, Invernizzi S, et al. Pharmacokinetics and immunomodulatory effects of phytotherapeutic lozenges (bonbons) with Echinacea purpurea extract. Phytomedicine. 2008;15(8):547-54.
10. Tsai MS, Huang CH, Wang CH, Cheng HJ, Wu SN, Chang WT, Chen WJ. Post-Cardiac Arrest Hydrocortisone Use Ameliorates Cardiac Mitochondrial Injury in a Male Rat Model of Ventricular Fibrillation Cardiac Arrest. J Am Heart Assoc. 2021;10(10):e019837.
11. Moorthy AN, Rai P, Jiao H, Wang S, Tan KB, Qin L, et al. Capsules of virulent pneumococcal serotypes enhance formation of neutrophil extracellular traps during in vivo pathogenesis of pneumonia. Oncotarget. 2016;7(15):19327-40.
12. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Jama. 2016;315(8):801-10.
13. Ingbar DH. Mechanisms of repair and remodeling following acute lung injury. Clin Chest Med. 2000;21(3):589-616.
14. Czermak BJ, Breckwoldt M, Ravage ZB, Huber-Lang M, Schmal H, Bless NM, et al. Mechanisms of enhanced lung injury during sepsis. Am J Pathol. 1999;154(4):1057-65.
15. Fein AM, Calalang-Colucci MG. Acute lung injury and acute respiratory distress syndrome in sepsis and septic shock. Crit Care Clin. 2000;16(2):289-317.
16. Tongyoo S, Permpikul C, Mongkolpun W, Vattanavanit V, Udompanturak S, Kocak M, Meduri GU. Hydrocortisone treatment in early sepsis-associated acute respiratory distress syndrome: results of a randomized controlled trial. Crit Care. 2016;20(1):329.
17. Park YJ, Lee MJ, Bae J, Lee JH, Lee HAR, Mun S, et al. Effects of Glucocorticoid Therapy on Sepsis Depend Both on the Dose of Steroids and on the Severity and Phase of the Animal Sepsis Model. Life (Basel). 2022;12(3).
18. Aziz M, Wang P. Glucocorticoid resistance and hyperlactatemia: A tag team to worsen sepsis. Cell Metab. 2021;33(9):1717-8.
19. Chen J, Zhou L, Li X, Wu X, Li Y, Si L, Deng Y. Protective effect of zerumbone on sepsis-induced acute lung injury through anti-inflammatory and antioxidative activity via NF-κB pathway inhibition and HO-1 activation. Naunyn-Schmiedeberg's Archives of Pharmacology. 2024;397(4):2241-55.
20. Aziz M, Ode Y, Zhou M, Ochani M, Holodick NE, Rothstein TL, Wang P. B-1a cells protect mice from sepsis-induced acute lung injury. Molecular Medicine. 2018;24(1):26.
21. Aarland RC, Bañuelos-Hernández AE, Fragoso-Serrano M, Sierra-Palacios ED, Díaz de León-Sánchez F, Pérez-Flores LJ, et al. Studies on phytochemical, antioxidant, anti-inflammatory, hypoglycaemic and antiproliferative activities of Echinacea purpurea and Echinacea angustifolia extracts. Pharm Biol. 2017;55(1):649-56.
22. Duan M, Jie J, Li C, Bai X, Hua S, Tang M, Li D. Echinatin alleviates sepsis severity through modulation of the NF-κB and MEK/ERK signaling pathways. Biomed Pharmacother. 2024;179:117359.
23. Li W, Wu AH, Zhu S, Li J, Wu R, D'Angelo J, Wang H. EGCG induces G-CSF expression and neutrophilia in experimental sepsis. Immunol Res. 2015;63(1-3):144-52.
24. Gharebaghi N, Hasanloei MA, Khalifani A, Pakzad S, Lahooti D. Neutrophil-to-lymphocyte ratio in patients with gram-negative sepsis admitted to intensive care unit. Anaesthesiology Intensive Therapy. 2019;51(1):11-6.