PRE-CLINICAL IN-VIVO ACUTE TOXICITY AND ANTI-INFLAMMATORY EVALUATION OF AURONE DERIVATIVES

Main Article Content

Muhammad Ikram
Ismail Shah
Abdul Saboor Pirzada
Ali Khan
Niamat Ullah Khan
Muhammad Najmus Saqib
Shah Faisal
Fahad Nawaz Khan
Hammad Ullah
Sajjad Ahmad
Tauqeer Ahsan
Muhammad Asif
Zafar Ali

Keywords

Aurone derivatives, anti-inflammatory, Carrageenan, Xylene, Paw edema, Pro-inflammatory mediators

Abstract

This study investigates the acute toxicity and anti-inflammatory potential of aurone derivatives (C-A, M-A and DM-A) using in vivo models. Male Swiss albino BALB/c mice were employed, and ethical clearance was obtained from Abdul Wali Khan University, Mardan. Acute toxicity test was conducted in two Phases. Phase-l for lower dose and Phase-ll for higher doses. For the anti-inflammatory assessment, a carrageenan-induced paw edema and xylene-induced ear edema were performed.


Acute toxicity assay of stated aurones on mice models revealed that these compounds were well-tolerated up to 500 mg/kg, with no observable symptoms of toxicity in terms of mortality and morbidity, thus confirming their safety profile. The aurone derivatives, showed dose dependent potential, particularly DM-A, demonstrated significant anti-inflammatory activity at a dose of 20 mg/kg showing the highest inhibition of paw edema (60.89%)  after 3 hours post-administration as compared to control (3.81±0.07) and standard 1.6±0.15 (58%) in carrageenan assay and reduced significantly (p=0.05) the mice ear edema from 0.301±0.008 to 0.24±0.004 after 40 min of the treatment via xylene induced ear edema assay. This suggests that aurone derivatives may effectively modulate the inflammatory response, likely through the inhibition of pro-inflammatory cytokines or stabilization of cell membranes.


The findings suggest that aurone derivatives possess significant therapeutic potential as anti-inflammatory agents, with a favorable safety profile. These results warrant further investigation into their development as safer alternatives to conventional therapies.


 

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References

1. AHMED, A. U. 2011. An overview of inflammation: mechanism and consequences. Frontiers in Biology, 6, 274.
2. ALI, N., NABI, M., SUBHAN, Z., ULLAH, S., SULTANA, U. & SHAMS, B. 2020. Acute toxicity and antinociceptive activity of saponins rich fraction of Dioscorea deltoidea (wall). Khyber Medical University Journal, 12, 107-12.
3. ASIJA, R., PRAJAPAT, R., VYAS, P. & KUMAR, V. 2014. A brief cause of acute inflammation: an overview. Journal of Drug Discovery and Therapeutics, 2, 31-35.
4. BROOKS, S. K., WEBSTER, R. K., SMITH, L. E., WOODLAND, L., WESSELY, S., GREENBERG, N. & RUBIN, G. J. 2020. The psychological impact of quarantine and how to reduce it: rapid review of the evidence. The lancet, 395, 912-920.
5. CHEN, L., DENG, H., CUI, H., FANG, J., ZUO, Z., DENG, J., LI, Y., WANG, X. & ZHAO, L. 2018. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget, 9, 7204.
6. CHINEDU, E., AROME, D. & AMEH, F. S. 2013. A new method for determining acute toxicity in animal models. Toxicology international, 20, 224.
7. DAVIS III, J. M. & MATTESON, E. L. My treatment approach to rheumatoid arthritis. Mayo Clinic Proceedings, 2012. Elsevier, 659-673.
8. GALLUCCI, S. & MATZINGER, P. 2001. Danger signals: SOS to the immune system. Current opinion in immunology, 13, 114-119.
9. GARDEMANN, A., MEYER, F. & BRAUN-DULLAEUS, R. 2013. What the surgeon needs to know about basic new concepts of inflammation and their therapeutic consequences: sanitation of inflammation is not a passive but rather an active process regulated by lipid mediators. Zentralblatt Fur Chirurgie, 138, 322-330.
10. HARB, H. & RENZ, H. 2015. Update on epigenetics in allergic disease. Journal of Allergy and Clinical Immunology, 135, 15-24.
11. HAYASHI, H., HONDA, M., SHIMOKAWA, Y. & HIRASHIMA, M. 1984. Chemotactic factors associated with leukocyte emigration in immune tissue injury: their separation, characterization, and functional specificity. International Review of Cytology, 89, 179-250.
12. IKRAM, M., SHAH, I., HUSSAIN, H., MUGHAL, E. U., NAEEM, N., SADIQ, A., NAZIR, Y., SHAH, S. W. A., ZAHOOR, M. & ULLAH, R. 2024. Synthesis, molecular docking evaluation for LOX and COX-2 inhibition and determination of in-vivo analgesic potentials of aurone derivatives. Heliyon, 10.
13. JOHNSON, L. A., CLASPER, S., HOLT, A. P., LALOR, P. F., BABAN, D. & JACKSON, D. G. 2006. An inflammation-induced mechanism for leukocyte transmigration across lymphatic vessel endothelium. The Journal of experimental medicine, 203, 2763-2777.
14. LAWRENCE, T., WILLOUGHBY, D. A. & GILROY, D. W. 2002. Anti-inflammatory lipid mediators and insights into the resolution of inflammation. Nature Reviews Immunology, 2, 787-795.
15. LÓPEZ-LÁZARO, M. 2009. Distribution and biological activities of the flavonoid luteolin. Mini reviews in medicinal chemistry, 9, 31-59.
16. MEDZHITOV, R. 2008. Origin and physiological roles of inflammation. Nature, 454, 428-435.
17. MITCHELL, R. N. 2006. Pocket companion to Robbins and Cotran pathologic basis of disease, Elsevier Health Sciences TW.
18. NUGENT, R. 2008. Chronic diseases in developing countries: health and economic burdens. Annals of the New York Academy of Sciences, 1136, 70-79.
19. ORGANIZATION, W. H. 2020. Global health estimates 2020: deaths by cause, age, sex, by country and by region, 2000–2019. WHO Geneva, Switzerland.
20. ROSS, J. A. & KASUM, C. M. 2002. Dietary flavonoids: bioavailability, metabolic effects, and safety. Annual review of Nutrition, 22, 19-34.
21. SERHAN, C. N. & LEVY, B. D. 2018. Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators. The Journal of clinical investigation, 128, 2657-2669.
22. SHANMUGAM, M. K. & SETHI, G. 2012. Role of epigenetics in inflammation-associated diseases. Epigenetics: Development and disease, 627-657.
23. SINGSAI, K., CHAROONGCHIT, P., CHAIKAEW, W., BOONMA, N., FHANJAKSAI, P. & CHAISATAN, K. 2020. Antilipoxygenase and anti‐inflammatory activities of Streblus asper leaf extract on xylene‐induced ear edema in mice. Advances in pharmacological and pharmaceutical sciences, 2020, 3176391.
24. SMEDLEY, B. D., STITH, A. Y. & NELSON, A. R. Committee on Understanding and Eliminating Racial and Ethnic Disparities in Health Care. Unequal treatment: confronting racial and ethnic disparities in health care. National Academy of Science, 2003. National Academies Press Washington, DC, 191.
25. STAWICKI, S. P., JEANMONOD, R., MILLER, A. C., PALADINO, L., GAIESKI, D. F., YAFFEE, A. Q., DE WULF, A., GROVER, J., PAPADIMOS, T. J. & BLOEM, C. 2020. The 2019–2020 novel coronavirus (severe acute respiratory syndrome coronavirus 2) pandemic: A joint american college of academic international medicine-world academic council of emergency medicine multidisciplinary COVID-19 working group consensus paper. Journal of global infectious diseases, 12, 47.
26. SULAIMAN, M., PERIMAL, E., AKHTAR, M., MOHAMAD, A., KHALID, M., TASRIP, N., MOKHTAR, F., ZAKARIA, Z., LAJIS, N. & ISRAF, D. 2010. Anti-inflammatory effect of zerumbone on acute and chronic inflammation models in mice. Fitoterapia, 81, 855-858.
27. Tubaro, E., Borelli, G., Croce, C., Cavallo, G., & Lisciani, R. (1985). Effect of a non-steroidal anti-inflammatory drug, benoxaprofen, on lipoxygenase and cyclooxygenase pathways. Prostaglandins, 30(5), 821-831.
28. UPADHYAY, R. K. 2015. Role of regeneration in tissue repairing and therapies. J Regen Med Tissue Eng, 4, 1.
29. VALKO, M., LEIBFRITZ, D., MONCOL, J., CRONIN, M. T., MAZUR, M. & TELSER, J. 2007. Free radicals and antioxidants in normal physiological functions and human disease. The international journal of biochemistry & cell biology, 39, 44-84.
30. VONKEMAN, H. E. & VAN DE LAAR, M. A. Nonsteroidal anti-inflammatory drugs: adverse effects and their prevention. Seminars in arthritis and rheumatism, 2010. Elsevier, 294-312.
31. WILHELM, D. & MASON, B. 1960. Vascular permeability changes in inflammation: the role of endogenous permeability factors in mild thermal injury. British Journal of Experimental Pathology, 41, 487.
32. WILLIAMS, T. & PECK, M. 1977. Role of prostaglandin-mediated vasodilatation in inflammation. Nature, 270, 530-532.
33. YADAV, T. & ROHANE, S. 2021. Acute toxicity study of synthesized drug and herbal product. Asian Journal of Pharmaceutical Research, 11, 251-256.
34. Young, J. M., Spires, D. A., Bedell, S. A., Swingle, K. F., & De Young, L. M. (1983). The mouse ear oedema assay for topical anti-inflammatory activity. Journal of Investigative Dermatology, 80(1), 47-50

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