Author(s):
Mohd Hijaz Mohd Sani, Solihati, Fong Siat Yee Alison, Hartanto Mulyo, Nurry Ayuningtyas Kusumastuti
Email(s):
solihatisadeli@gmail.com
DOI:
10.52711/0974-360X.2026.00681 
Address:
Mohd Hijaz Mohd Sani1, Solihati2*, Fong Siat Yee Alison3, Hartanto Mulyo4, Nurry Ayuningtyas Kusumastuti5
1,3Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Malaysia.
2Faculty of Medicine and Health Sciences, University Malaysia Sabah, Malaysia.
2,5Faculty of Health Science, Yatsi Madani University, Tangerang, Indonesia.
4Faculty of Veterinary Medicine, Airlangga University, Indonesia.
*Corresponding Author
Published In:
Volume - 19,
Issue - 10,
Year - 2026
ABSTRACT:
Inflammation is a complex response involving mediators such as nitric oxide (NO), prostaglandins, and cytokines, which contribute to tissue injury and chronic disease. Aloe vera has long been used in traditional medicine for inflammatory disorders, yet mechanistic evidence supporting its anti-inflammatory activity remains limited. This study aimed to evaluate the anti-inflammatory activity of Aloe vera ethanolic extract (AVEE) in acute and sub chronic rat models, with a focus on NO modulation. Sprague–Dawley rats were treated orally with AVEE (100, 200, and 300mg/kg) or aspirin (100mg/kg) as reference. Anti-inflammatory activity was assessed using carrageenan-induced paw edema (acute) and cotton pellet granuloma pouch (sub chronic) models, while serum NO levels were quantified by Griess assay. AVEE significantly reduced paw edema volume and granuloma formation compared with control (p<0.05). In addition, AVEE produced a dose-dependent reduction in NO, with levels of 174.44±6.36, 160.25±3.76, and 157.44±2.38µmol/L at 100, 200, and 300mg/kg, respectively, compared to 206.25±6.60µmol/L in control and 124.06±3.06µmol/L in aspirin-treated rats. All doses were significantly different from control (p<0.01), while the difference between 200 and 300mg/kg was not statistically significant (p = 0.158), suggesting that 200mg/kg is the optimal effective dose. These findings demonstrate that AVEE exerts anti-inflammatory effects in both exudative and proliferative phases of inflammation, partly through inhibition of iNOS-mediated NO production. The results provide mechanistic support for the ethnomedicinal use of Aloe vera and highlight its potential as a natural anti-inflammatory agent comparable to aspirin.
Cite this article:
Mohd Hijaz Mohd Sani, Solihati, Fong Siat Yee Alison, Hartanto Mulyo, Nurry Ayuningtyas Kusumastuti. Anti-inflammatory Activity of Aloe vera Ethanolic Extract through Nitric Oxide Modulation in Sprague–Dawley Rats. Research Journal Pharmacy and Technology. 2026;19(10):4885-2. doi: 10.52711/0974-360X.2026.00681
Cite(Electronic):
Mohd Hijaz Mohd Sani, Solihati, Fong Siat Yee Alison, Hartanto Mulyo, Nurry Ayuningtyas Kusumastuti. Anti-inflammatory Activity of Aloe vera Ethanolic Extract through Nitric Oxide Modulation in Sprague–Dawley Rats. Research Journal Pharmacy and Technology. 2026;19(10):4885-2. doi: 10.52711/0974-360X.2026.00681 Available on: https://rjptonline.org/AbstractView.aspx?PID=2026-19-10-57
REFERENCES:
1. Bernardette Martínez-Rizo A, Fosado-Rodríguez R, César Torres-Romero J, César Lara-Riegos J, Alberto Ramírez-Camacho M, Ly Arroyo Herrera A, et al. Models in vivo and in vitro for the study of acute and chronic inflammatory activity: A comprehensive review. Int Immunopharmacol. 2024 Jun 30; 135: 112292.
2. P. Pavani, E. Naveena, P. Subhashini, S. Srikanth, K. Thirumala Naik, M. Kishore Babu. A Review on Non-Steroidal Anti-Inflammatory Drugs Induced Kidney Diseases. Res J Pharmacol Pharmacodyn. 2022;
3. Maiuolo J, Carresi C, Gliozzi M, Mollace R, Scarano F, Scicchitano M, et al. The Contribution of Gut Microbiota and Endothelial Dysfunction in the Development of Arterial Hypertension in Animal Models and in Humans. Int J Mol Sci. 2022; 23(7): 1–25.
4. Jijith US, Jayakumari S. An Apparatus for the determination of rat paw Edema during In vivo Evaluation of Anti-inflammatory agents. Res J Pharm Technol. 2020 May 30; 13(5): 2373–5.
5. Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, et al. Oncotarget 7204 www.impactjournals.com/oncotarget Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2018; 9(6): 7204–18.
6. Tahir A, Dar MS. Evaluation of the anti-inflammatory activity of hexane and ethanolic extracts of polyherbal formulation. 2023; 173–80.
7. Pisoschi AM, Pop A, Iordache F, Stanca L, Predoi G, Serban AI. Oxidative stress mitigation by antioxidants - An overview on their chemistry and influences on health status. Eur J Med Chem. 2021 Jan 1; 209: 112891.
8. Liy PM, Puzi NNA, Jose S, Vidyadaran S. Nitric oxide modulation in neuroinflammation and the role of mesenchymal stem cells. Exp Biol Med. 2021; 246(22): 2399–406.
9. Liu C, Lei S, Cai T, Cheng Y, Bai J, Fu W, et al. Inducible-nitric-oxide-synthase-activity-mediates-tnf-α-induced-endothelial-cell-dysfunction.pdf. 2023.
10. Ashwini S. Jadhav, Omkar A. Patil, Sampada V. Kadam DMAB. Review on Aloe Vera is used in Medicinal Plant. Asian J Res Pharm Sci. 2020; 10(1).
11. Varrassi G, Coluzzi F, Fornasari D, Fusco F, Gianni W, Guardamagna VA, et al. New Perspectives on the Adverse Effects of NSAIDs in Cancer Pain: An Italian Delphi Study from the Rational Use of Analgesics (RUA) Group. J Clin Med. 2022; 11(24).
12. Fatma F, Kumar A. A systematic Review of Aloe vera and its Properties. Asian J Pharm Res. 2021; 11(4): 257–9.
13. Sánchez M, González-Burgos E, Iglesias I, Gómez-Serranillos MP. Pharmacological update properties of aloe vera and its major active constituents. Molecules. 2020; 25(6): 1–37.
14. Le HM, Ngo PT, Nguyen AT, Do HTT. Phytochemicals, Antiinflammatory, and Analgesic Effects of the Ethanol Extract From the Leaves of Premna Flavescens Wall. ex C. B. Clarke. Nat Prod Commun. 2022; 17(7): 1–6.
15. Akpinar E. Experimental Inflammation Models Created in Laboratory Animals. Ataturk Univ J Vet Sci. 2021; 16(3): 336–43.
16. Puri M, Walia YK. Analysis of Aspirin (Acetylsalicylic Acid): Development and Validation using RP-HPLC Methods - A Component of Anti-hypertensive Drugs. Res J Pharm Technol. 2024; 17(8): 3963–8.
17. Sanyam Sharma, Rahul Sharma, Kamya Goyal, Shammy Jindal. Potential of herbal treatment of Psoriasis: A Laconic Review. Asian J Res Pharm Sci. 2021; 11(1).
18. Slavkova M, Popova T, Voycheva C, Bozhanov S, Maslarska V, Dimitrov M. Effect of soft beverages on the in vitro dissolution of gastro-resistant tablets containing low dose Acetylsalicylic acid. Res J Pharm Technol. 2021; 14(12): 6345–52.
19. Subedi L, Gaire BP, Parveen A, Kim SY. Nitric oxide as a target for phytochemicals in anti-neuroinflammatory prevention therapy. Int J Mol Sci. 2021; 22(9).
20. Deepa Amminbavi, N Prasanna Lakshmi. Assessment of In vitro wound healing potential of Hibiscus leaf extract Emulgel. Asian J Pharm Res.
21. Eyiiş E, Kaygisiz B, Kiliç FS, Ayhanci A. The in vivo antinociceptive and antiinflammatory effects of verbascum exuberans hub.-mor. Turkish J Pharm Sci. 2020; 17(6): 586–92.
22. Wardhani RG, Yosephi V, Nastiti CT, Budhy TI, Noor TNEBTA, Nugraha AP. Secretome of Adipose-Derived Stem Cells with Aloe Vera Gel in Burn Injury Therapy: A Narrative Review. Res J Pharm Technol. 2025 Apr 12; 18(4): 1913–9.
23. Chismirina S, Hakim RF, Nasution AI, Putri CF, Oktaviary A, Firza IC, et al. Evaluation of the Radiographic and Microscopical Impact of Aloe vera Gel Application on Alveolar Bone in Wistar Rats Exposed to Periodontitis. Res J Pharm Technol. 2025; 18(4): 1544–50.
24. Tazeze H, Mequanente S, Nigussie D, Legesse B, Makonnen E, Mengie T. Investigation of wound healing and anti-inflammatory activities of leaf gel of aloe trigonantha l.C. leach in rats. J Inflamm Res. 2021; 14: 5567–80.
25. Fitri K, Khairani TN, Sianturi KT, Leny L, Hafiz I. Anti-inflammatory Activity of Ethanol Extract of Lotus (Nelumbo nucifera G.) Seed Against White Male Rats Using Paw Edema Method. J Drug Deliv Ther. 2021; 11(4): 1–4.
26. Lim DW, Choi HJ, Park SD, Kim H, Yu GR, Kim JE, et al. Activation of the Nrf2/HO-1 Pathway by Amomum villosum Extract Suppresses LPS-Induced Oxidative Stress in Vitro and Ex Vivo. Evidence-based Complement Altern Med. 2020; 2020.
27. Sherif AE, Alam R, Asif M, Khan K ur rehman, Sajid M, Rehman U. Evaluation of the anti-in fl ammatory, potential of ethanolic extract of Aristida depressa Retz through in vitro, in vivo, and in silico models. 2024; (July):1–18.
28. Calhelha RC, Haddad H, Ribeiro L, Heleno SA, Carocho M, Barros L. Applied Sciences Inflammation : What’s There and What’s New ? Appl Sci. 2023; 13(4): 1–26.
29. Solihati, Hijaz Mohd Sani M, Siat Yee Alison F, Mulyo H. Interleukin-6 Level In Vivo And In Vitro Anti Inflammatory and Anti-Pyretic Evaluation of Aloe Vera Ethanolic Extract in Sprague Dawley. J Neonatal Surg. 2025; 14(21s): 14.
30. Hongzhi D, Xiaoying H, Yujie G, Le C, Yuhuan M, Dahui L, et al. Classic Mechanisms and Experimental Models for the Anti‐Inflammatory Effect of Traditional Chinese Medicine. Anim Models and Exp Med. 2021.