Mechanistic and Pharmacological Evaluation of Cassia rhombifolia Fruit Extract in Murine Models of Pain, Fever, and Acute Inflammation
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Keywords:
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Cassia rhombifolia, Ethanol Extract, Dose-Response Relationship, Analgesic Activity, Antipyretic Activity, Anti-Inflammatory Activity
Abstract
This work investigated the pharmacological profile and dose-response behavior of an ethanol extract prepared from Cassia rhombifolia fruits (EECR) in mouse models of nociception, pyrexia, and short-term inflammatory reactions. Swiss albino mice were given EECR by mouth at 100, 200, or 300 mg/kg. Thermal pain thresholdswere evaluated using the hot plate and tail-flick paradigms. Yeast-induced hyperthermia was employed to assess antipyretic activity, and λ-carrageenan-evoked paw swelling served as an index of acute inflammation. Serum cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were assessed by enzyme-linked immunosorbent assay (ELISA). EECR significantly increased reaction latencies in both nociceptive paradigms and reduced fever and paw edema in a clear dose-related fashion (p < 0.01). At 300 mg/kg, the extract inhibited the tail-flick response by 83.27%, lowered hyperthermia by 68.42%, and diminished paw swelling by 64.25%. These functional benefits were accompanied by a marked suppression of pro-inflammatory mediators, and the EECR dose showed a pronounced negative relationship with cytokine levels (r = −0.98; p < 0.05). Across behavioral and biochemical outcomes, correlation coefficients and determination indices (R2) supported pronounced, almost linear dose-response patterns. Overall, the data indicate that EECR exerts potent pain-relieving, fever-lowering, and inflammation-attenuating effects in animal models and warrant further studies to isolate active principles, clarify molecular mechanisms, and evaluate its translational relevance.
References
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Al AlSheikh, H. M., I. Sultan, V. Kumar, I. A. Rather, H. Al-Sheikh, A. T. Jan, and Q. M. R. Haq (2020). Plant-Based Phytochemicals as Possible Alternative to Antibiotics in Combating Bacterial Drug Resistance. Antibiotics, 9(8); 480
Al-Khayri, J. M., G. R. Sahana, P. Nagella, B. V. Joseph, F. M. Alessa, and M. Q. Al-Mssallem (2022). Flavonoids as Potential Anti-Inflammatory Molecules: A Review. Molecules, 27(9); 2901
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Chavda, V. P., J. Feehan, and V. Apostolopoulos (2024). Inflammation: The Cause of All Diseases. Cells, 13(22); 1906
Della Vedova, L., G. Baron, P. Morazzoni, G. Aldini, and F. Gado (2025). The Potential of Polyphenols in Modulating the Cellular Senescence Process: Implications and Mechanism of Action. Pharmaceuticals, 18(2); 138
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Esh, C. J., B. C. R. C. Chrismas, A. R. Mauger, A. Cherif, J. Molphy, and L. Taylor (2021). The Influence of Environmental and Core Temperature on Cyclooxygenase and PGE2 in Healthy Humans. Scientific Reports, 11; 6531
Fatima, M., M. R. Khan, M. Al-Mutiry, M. Patel, N. Alshammari, and M. Adnan (2025). Modulation of Inflammatory and Oxidative Stress Pathways by Polyphenol-Rich Pleurospermum candollei Extract in Carrageenan-Induced Paw Edema in Rats. Inflammopharmacology, 33(9); 5291–5303
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Li, W., X. Chen, H. Li, J. Zhang, J. An, and X. Liu (2022). Anti-Inflammatory Function of Plant-Derived Bioactive Peptides: A Review. Foods, 11(15); 2361
Mantiniotou, M., V. Athanasiadis, D. Kalompatsios, E. Bozinou, and S. I. Lalas (2025). Therapeutic Capabilities of Triterpenes and Triterpenoids in Immune and Inflammatory Processes: A Review. Compounds, 5(1); 2
Mehmood, K. T., S. Al-Baldawi, G. Z. Salazar, D. Zúñiga, and S. Balasubramanian (2024). Antipyretic Use in Noncritically Ill Patients with Fever: A Review. Cureus, 16(1); e51943
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Nhung, T. T. P. (2025). Correlation-Driven Analysis of Synergistic Effects of Dual Medicinal Mushroom Extracts in a DMBA-Induced Murine Breast Cancer Model. Tropical Journal of Natural Product Research, 9(8); 3496–3504
Nhung, T. T. P. and L. P. T. Quoc (2023). Analgesic and Antipyretic Activities of Ethanol Extract of Gardenia jasminoides Ellis Fruits in Mice. Tropical Journal of Natural Product Research, 7(10); 4902–4907
Nhung, T. T. P. and L. P. T. Quoc (2024a). Efficacy of Black Shallot Extract in Analgesic and Antipyretic Activities in Experimental Mice. Tropical Journal of Natural Product Research, 8(3); 6609–6616
Nhung, T. T. P. and L. P. T. Quoc (2024b). Exploring the Analgesic, Antipyretic, and Anti-Inflammatory Properties of Annona squamosa Linnaeus Fruit Peel Extract in a Mouse Model. Tropical Journal of Natural Product Research, 8(9); 8537–8545
Nurlaili, S., M. Arifa, K. Junaidi, M. Roihatul, and R. Maftuchah (2023). Phytochemical, Metabolite Compound, and Antioxidant Activity of Clinacanthus nutans Leaf Extract from Indonesia. Science and Technology Indonesia, 8(1); 38–44
Oladeji, O. S., F. E. Adelowo, A. P. Oluyori, and D. T. Bankole (2020). Ethnobotanical Description and Biological Activities of Senna alata. Evidence-Based Complementary and Alternative Medicine, 2020; 2580259
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Pant, T., N. Uche, M. Juric, J. Zielonka, and X. Bai (2024). Regulation of Immunomodulatory Networks by Nrf2 Activation in Immune Cells: Redox Control and Therapeutic Potential in Inflammatory Diseases. Redox Biology, 70; 103077
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Raichurkar, A. P. and S. G. H. Reddy (2020). Evaluation of Analgesic Activity of the Methanol Extract from the Galls of Quercus infectoria Alone and as an Adjuvant in Wistar Rats. International Journal of Basic & Clinical Pharmacology, 9(5); 701–705
Rauf, A., A. A. Khalil, S. Awadallah, S. A. Khan, T. Abu-Izneid, M. Kamran, H. A. Hemeg, M. S. Mubarak, A. Khalid, and P. Wilairatana (2023). Reactive Oxygen Species in Biological Systems: Pathways, Associated Diseases, and Potential Inhibitors—A Review. Food Science & Nutrition, 12(2); 675–693
Rudrapal, M., S. J. Khairnar, J. Khan, A. Bin Dukhyil, M. A. Ansari, M. N. Alomary, F. M. Alshabrmi, S. Palai, P. K. Deb, and R. Devi (2022). Dietary Polyphenols and Their Role in Oxidative Stress-Induced Human Diseases: Insights into Protective Effects, Antioxidant Potentials, and Mechanisms of Action. Frontiers in Pharmacology, 13; 806470
Salis, Z. and A. Sainsbury (2024). Association of Long-Term Use of Non-Steroidal Anti-Inflammatory Drugs with Knee Osteoarthritis: A Prospective Multi-Cohort Study over 4-to-5 Years. Scientific Reports, 14; 6593
Saptarini, N. M., R. Mustarichie, S. Hasanuddin, and M. J.-A. T. Corpuz (2024). Cassia alata L.: A Study of Antifungal Activity against Malassezia furfur, Identification of Major Compounds, and Molecular Docking to Lanosterol 14-Alpha Demethylase. Pharmaceuticals, 17(3); 380
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Authors
Tran, T. P. N., Vu, T. H., & Nguyen, T. N. (2026). Mechanistic and Pharmacological Evaluation of Cassia rhombifolia Fruit Extract in Murine Models of Pain, Fever, and Acute Inflammation. Science and Technology Indonesia, 11(1), 366–377. https://doi.org/10.26554/sti.2026.11.1.366-377
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