Main Article Content

Sania Riaz
Andleeb Zahra
Fatima Haider
Nouman Shahzad Malik
Hafsah Shafique


Paw edema, Agave sisalana, Agave americana, phytochemicals, Aliskiren


Inflammation has been reported as an immune system regulator from the last two decades but cellular and molecular pathways involved in tissue damage has only been established in the recent era. Additionally, it has been involved in the morbidity of different diseases like cancer, diabetes, heart disease, and rheumatoid arthritis. The control of two key players of inflammation i.e., prostaglandins and cytokines activation must be provided with different therapeutic strategies to control all the diseases that have close relationship with inflammatory biomarkers. Use of several pharmaceutical treatments for inflammation is in practice however prolonged usage even with physician supervision may have threat to kidney and liver failure. Researchers from different regions of the world are working on the phytotherapy to lessen the risks that are associated with the use of synthetic drugs. For this purpose, the anti-inflammatory potential of different leaf extracts was investigated via in-vivo study on rat model. With regard to inflammation in carrageenan-induced paw edema in rats, we aim to contrast the leaf extracts of Agave sisalana and Agave americana with standard drug Aliskiren. Twenty-five albino rats were grouped as control, positive control, standard drug, Agave sisalana extract and Agave americana extract treated. To demonstrate acute phase protein activation and a rise in inflammatory biomarkers in the positive control group, serum levels of CRP, TNF-, COX-2, and IL-10 were assessed. Bilirubin levels remain unchanged before and after treatments, however the positive control group has a decline in ALT, AST, Albumin, and A/G ratio. Alkaline phosphatase, total protein, and globulin revealed significant improvements after therapy when compared to the positive control group (p < 0.05). Furthermore, histopathological analysis of paw skin of rats also revealed rete pegs and normal sub-epidermal structures. Edema and inflammatory cells diminished, and the epidermis became reddish. Agave species extract from Agave sisalana and Agave americana raised serum inflammatory indicators and promoted paw skin histology in groups that had been subjected to inflammation.

Abstract 182 | pdf Downloads 86


1. Aziz, T.A., Kareem, A.A., Othman, H.H., and Ahmad, Z.A. (2020). The Anti-Inflammatory Effects of Different Doses of Aliskiren in Rat Models of Inflammation. Drug Design, Development and Therapy, 14, 2841-2851.
2. Ahmed Shah and Saeid Amini-Nik. (2017).The role of phytochemicals in the inflammatory phase of wound healing. International Journal of molecular sciences. 18(5). 1068,
3. Begum, R., Sharma, M., Pillai, K.K., Aeri, V. and Sheliya. (2014). Inhibitory Effects of Careya arborea on Inflammatory Biomarkers in Carrageenan-Induced Inflammation. Pharmaceutical Biology, 53 (3), 437-445.DOI:10.3109/13880209.2014.923005
4. Banu, K.S. and Cathrine, L. (2015). General techniques involved in phytochemical analysis. International journal of advanced research in chemical science, 2 (4), 25-32
5. Cordaro, M., Siracusa, R., Fusco, R., Amico, R.D., Peritore, A.F., Gugliandolo, E., Genovese, T., Scuto, M., Crupi, R., Mandalari, G., Guzzocrea, S., Paola, R.D. and Impellizeri, D. (2020). Cashew (Anacardium occidentale L.) Nuts Counteract Oxidative Stress and Inflammation in an Acute Experimental Model of Carrageenan Induced Paw Edema. Antioxidants, 9 (660), DOI: 10.3390/antiox9080660
6. Chen, L., Deng, H., Cui, H., Fang, J., Zuo, Z., Deng, J., Li, Y., Wang, X., and Zhao, L. (2018). Inflammatory responses and inflammation-associated diseases in organs. Oncotarget, 9 (6), 7204–7218.
7. Dave, O.O., Adebusola, O.T., Nweze, K. and Obinna A. (2020). Effects of Aqueous Extract of Agave sisalana (Perr Syn) Root in Cadmium-Induced Infertility in Male Wistar Rat. Trends Nat Prod Res, 1 (2), 78-86.DOI:10.48245/tnpr-2734391.2021.1202
8. Dunder, R.J., Quaglio, A.E.V., Maciel, R.P., Ferreira, A.L., Almeida, A.C.A., Takyama, C., Faria, F.M.D., Brito, A.R.M.S. (2010). Anti-Inflammatory and Analgesic potential of Hydrolyzed Extract of Agave sisalana Perrine ex Engelm.Asparagaceae. Revista Brasileira de Farmacognosia, Brazilian Journal of Pharmacognosy, 20 (3), 376-381.
9. Dzoyem, J., McGaw, L., Kuete, V., Bakowsky, U. (2017). Anti-inflammatory and anti-nociceptive activities of African medicinal spices and vegetables. In Medicinal Spices and Vegetables from Africa, 239–270.
10. Ekam DE and Udosen EO (2012). Total Protein, Albumin and Globulin Levels following the Administration of Activity Directed Fractions of Vernonia Amygdalina during Acetaminophen induced Hepatotoxicity in Wistar Rats. Global Journal of Pure and Applied Sciences, 18(1,2): 25-29.
11. Haley, R.M., and Recum, H.A.V., (2019). Localized and targeted delivery of NSAIDs for treatment of inflammation. Experimental Biology and Medicine, 244, 433–444. DOI: 10.1177/1535370218787770
12. Kim, K.H., IM, H.W., Karmachary, M.B., Kim, S., Min, B.H., Park, S.R. and Choi, B.H. (2020). Low Intensity Ultrasound Attenuates Paw Edema Formation and Decreases Vascular Permeability Induced by Carrageenan Injection in Rats. Journal of Inflammation, 17 (7).
13. Khedir, B.S., Mzid, M., Bardaa, S., Moalla, D., Sahnoun, Z. and Rebai, T. (2016). In Vivo Evaluation of the Anti-Inflammatory Effect of Pistacia lentiscus Fruit Oil and Its Effects on Oxidative Stress. Evidence – based Complementary and Alternative Medicines, DOI:
14. Mwale, M., Masika, P.J., Francis, J. (2012). Anti- Inflammatory and Analgesic Activities of the Aqueous Leaf Extract of Agave sisalana in Rats. Scientific Research and Essay, 7 (14), 1477-1484. DOI:10.5897//SRE11.660
15. Madariaga, Y.G., Linares, Y.M., Monteagudo, D.M., Diaz, A.V., Leon, J.O.G.D., Reyes, L.N. (2020). In Vivo Anti-Inflammatory Effect of Saponin-Enriched Fraction from Agave brittoniana Trel sub specie brachypus. Ars Pharm, 61 (4), 231-237.
16. Mostafa, R.E., El-Marasy, S.A., Jaleel, G.A.A., Bakeer, R.M. (2020). Protective effect of Royal Jelly against diclofenac-induced hepato-renal damage and gastrointestinal ulcerations in rats.DOI:
17. Misra, A.K., Verma, S.K and Kumar, R. (2018). Anti- inflammatory effect of an extract of Agave americana on experimental animals. Pharmacognosy Research, 10 (1), 104-108.
18. Necas, J., and Bartosikova, L., (2013). Carrageenan: a review. Veterinarni Medicina, 58, (4), 187–205.
19. Ou, Z., Zhaoa, J., Zhu, L., Huang, L., Maa, Y., Maa, C., Luo, C., Zhu, Z., Yuan, Z., Wu, J., Li, R., Yi, J. (2019). Anti-inflammatory effect and potential mechanism of betulinic acid on λ-carrageenan-induced paw edema in mice. Biomedicine & Pharmacotherapy, 118, 109347.
20. Oliveira, S.H.P., Brito, V.G.B., Frasnelli, S.C.T. (2019). Aliskiren attenuates the inflammatory response and wound healing process in diabetic mice with periodontal disease. Front Pharmacol, 10 (1–16), DOI:10.3389/fphar.2019.00708
21. Patel, R.B., Pawar, V.D., Prajapati, K.D. (2013). Anti-nociceptive and anti-allodynic activity of aliskiren in various pain models. Eur J Pharmacol, 708 (1–3), 80–87. DOI:10.1016/j.ejphar.2013.03.036
22. Pacurari, M., Kafoury, R., Tchounwou, P.B., Ndebele, K. (2014). The renin-angiotensin-aldosterone system in vascular inflammation and remodeling. Int J Inflam, 2014, 689360. DOI:10.1155/2014/689360
23. Pineda, D.T.S., Alacron, N.C., Godinez, M.E.M., Toress, M.D.P.N., Hernandez, J.P., Fitz, P.A. (2017). Antibacterial and anti inflammatory activity of extracts and fractions from Agave cupreata. International Journel of Pharmacology, 13 (8), 1063-1070. DOI: 10.3923/ijp.2017.1063.1070
24. Shahzad, S., Hussain, M., Munir, H., Arfan, M. (2017). Proximate Composition and Spatio-Temporal Heterogeneity of Phytochemicals in Agave sisalana adapted in Different Zones of Punjab, Pakistan. Research Square, DOI:
25. Sarwar, M.B., Ahmad, Z., Anicet, B.A., Sajid, M., Rashid, B., Hassan, S., Ahmed, M., Husnain, T. (2020). Identification and validation of superior housekeeping gene (s) for qRT-PCR data normalization in Agave sisalana (a CAM-plant) under abiotic stresses. Physiol Mol Biol Plant, 4 (1-8).
26. Saha, A., Ahmed, M. (2009). The analgesic and anti-inflammatory activities of the extract of Albizia lebbeck in animal model. Pakistan Journal of Pharmaceutical Sciences, 22 (1), 74–77.
27. Saxena, M., Saxena, J., Nema, R., Singh, D., Gupta, A. (2013). Phytochemistry of medicinal plants. Journal of pharmacognosy and phytochemistry, 1 (6), 168-182.
28. Singh, P., Tanwar, N., Saha, T., Gupta, A., Sargam, V. (2018). Phytochemical screening and analysis of Carica papaya, Agave americana and Piper nigrum. International Journal of Current Microbiology and Applied Sciences, 7 (2), 1786-1794
29. Tewari, D., Tripathi, Y.C., Anjum, N. (2014). Agave sisalana: A plant with high chemical diversity and medicinal importance. World Journal of Pharmaceutical Research, 3 (8).
30. Viel, A.M., Pereira, A.R., Neres, W.E., Santos, D.L., Neto, O.P., Souza, E.B., Silva, R.M., Camargo, I.C. (2017). Effect of Agave sisalana Perrine extract on the ovarian and uterine tissues and fetal parameters: Comparative Interventional Study. Int J Multispeciality Health, 3 (5), 129-38.
31. Yoon, J.W., Ham, M.Y., Kim, S.S., Yoo, S.B., Moon, Y.J., Baik, S.J., Lee, H.N., Hyun, G.C. (2009). Suppression of Pro-inflammatory cytokines, INOS and COX-2 expression by brown algae Sargassum micracanthum in RAW 264.7 macrophages. Eur Asian Journal of Biosciences, 3, 130-143.