The Synergistic Role of Curcuma Longa Extract and Resveratrol Against Induced Colorectal Tumor in Rats

Abstract

Background: Colon cancer is considered one of the most common cancer types in both sexes according to the latest reports. The current research tends focus on gen-targeted therapies.

Objectives: The current study aims to investigate the protective effects of Curcuma longa extract and resveratrol, individually and in combination, against 1,2-dimethylhydrazine (DMH)-induced colorectal cancer in female rats, with a particular focus on their influence on KRAS gene expression and histopathological alterations.

Methods: Forty female albino rats were randomly divided into five groups (n = 8 per group): G1 (control), G2 (DMH only), G3 (DMH + Curcuma longa), G4 (DMH + Curcuma longa + resveratrol), and G5 (DMH + resveratrol). Colorectal cancer was induced by DMH administration, followed by daily oral treatments for 16 weeks. At the end of the experiment, colorectal tissues were collected for molecular analysis of KRAS expression using RT-qPCR and for histopathological and immunohistochemical evaluation.

Results: Rats in the DMH group (G2) exhibited marked overexpression of KRAS and severe histopathological changes consistent with colorectal carcinoma. Treatment with Curcuma longa (G3) and resveratrol (G5) significantly reduced KRAS expression and ameliorated tissue alterations, while the combined treatment (G4) demonstrated the greatest protective effect, showing near-normal architecture and the lowest KRAS expression levels

Conclusion: Curcuma longa and resveratrol exert protective effects against DMH-induced colorectal carcinogenesis by downregulating KRAS expression and improving tissue integrity. Their combined use produced synergistic effects, highlighting their potential as complementary chemo-preventive agents in colorectal cancer management.

Keywords:

Curcuma longa, Resveratrol, Colorectal Tumor

References

Bertoncini-Silva, C., Lima, A. S., de Almeida, L. M., & de Oliveira, J. R. (2024). Enhancing the bioavailability and bioactivity of curcumin: Strategies and implications. Antioxidants, 13(3), 331. https://doi.org/10.3390/antiox13030331

Brockmueller, A., & Kessler, M. (2024). Curcumin and its anti-colorectal cancer potential. Phytotherapy Research. https://doi.org/10.1002/ptr.8220

Brockmueller, A., & Kessler, M. (2024). Curcumin and its anti-colorectal cancer potential. Phytotherapy Research. https://doi.org/10.1002/ptr.8220

De, S., Saha, S., & Banerjee, S. (2023). Phenolic phytochemicals for prevention and treatment of colorectal cancer. Cancers, 15(3), 993. https://doi.org/10.3390/cancers15030993

Fan, Y., Wang, Y., Zhang, L., & Li, S. (2022). Curcumin against gastrointestinal cancer: A review of the pharmacological mechanisms. Frontiers in Pharmacology, 13, 990475. https://doi.org/10.3389/fphar.2022.990475

Fernandez-Muñoz, K. V., Sánchez-Barrera, C. Á., Meraz-Ríos, M., Reyes, J. L., Pérez-Yépez, E. A., Ortiz-Melo, M. T., Terrazas, L. I., & Mendoza-Rodriguez, M. G. (2025). Natural alternatives in the treatment of colorectal cancer: A mechanisms perspective. Biomolecules, 15(3), 326. https://doi.org/10.3390/biom15030326

Freeman, W. M., Walker, S. J., & Vrana, K. E. (2018). Quantitative RT-PCR: Pitfalls and potential. Biotechniques, 26(1), 112–125.

Fumarola, S., & Rossi, C. (2025). Polyphenol intake in elderly patients: A novel approach to KRAS-targeted therapies. International Journal of Molecular Sciences.

Gao, D., Liu, J., Yuan, J., Wu, J., Kuang, X., Kong, D., Zheng, W., Wang, G., Sukumar, S., Tu, Y., Chen, C., & Sun, S. (2021). Intraductal administration of N-methyl-N-nitrosourea as a novel rodent mammary tumor model. Annals of Translational Medicine, 9(7), 576. https://doi.org/10.21037/atm-21-1540

Honari, M., Shafabakhsh, R., Reiter, R. J., Mirzaei, H., & Asemi, Z. (2019). Resveratrol is a promising agent for colorectal cancer prevention and treatment: Focus on molecular mechanisms. Cancer Cell International, 19, 90. https://doi.org/10.1186/s12935-019-0906-y

Jayachandran, P., & Kumar, S. (2025). Pan-RAS inhibitors and polo-like kinase 1: Promising targets in colorectal cancer. Oncogene. https://doi.org/10.1038/s41388-025-03484-z

Li, T.-P., Wong, W.-P., Chen, L.-C., Su, C.-Y., Chen, L.-G., Liu, D.-Z., Ho, H.-O., & Sheu, M.-T. (2017). Physical and pharmacokinetic characterizations of trans-resveratrol (t-Rev) encapsulated with self-assembling lecithin-based mixed polymeric micelles. Scientific Reports, 7, 10674. https://doi.org/10.1038/s41598-017-11320-y

Moghadamtousi, S. Z., Fadaeinasab, M., Nikzad, S., Mohan, G., Ali, H. M., & Kadir, H. A. (2015). Annona muricata (Annonaceae): A review of its traditional uses, isolated acetogenins, and biological activities. International Journal of Molecular Sciences, 16(7), 15625–15658.

Moutabian, H., Mahdavi, M., & Khosravi, A. (2022). A systematic review of the therapeutic effects of resveratrol in colorectal cancer. Complementary Therapies in Medicine, 63, 102820. https://doi.org/10.1016/j.ctim.2022.102820

Ochoa-Sanchez, A., Garcia, J., & Martinez, J. (2024). Evaluation of the synergistic effects of curcumin-resveratrol co-loaded biogenic silica on colorectal cancer cells. Journal of Experimental Therapeutics. [Preclinical study]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11196415/

Ojo, O. A., Akinmoladun, A. F., & Akinmoladun, F. O. (2022). Anticancer properties of curcumin against colorectal cancer. Journal of Oncology, 2022, Article 9072734. https://doi.org/10.1155/2022/9072734

Patra, S., Sahoo, S., & Sahoo, S. (2021). Chemotherapeutic efficacy of curcumin and resveratrol: Mechanisms and synergy. Pharmacology & Therapeutics, 225, 107842. https://doi.org/10.1016/j.pharmthera.2021.107842

Roy, S., Levi, E., Majumdar, A. P., & Sarkar, F. H. (2025). An overview of the potential of natural compounds to regulate microRNAs in colorectal cancer. PMC.

Sardou, H. S., & Alavi, S. (2023). Nano-curcumin formulations for targeted therapy of colon cancer models. [Journal].

Weng, W., Zhang, Y., & Zhang, X. (2020). Curcumin and colorectal cancer: An update and current perspectives. Journal of Cellular Biochemistry, 121(7), 2018–2030. https://doi.org/10.1002/jcb.29374

Zeng, L., Li, W., & Chen, C. S. (2020). Breast cancer animal models and applications. Zoological Research, 41(5), 477–494. https://doi.org/10.24272/j.issn.2095-8137.2020.095

Zhu, W., He, X., Huang, Z., Huang, W., Zhang, A., & Huang, B. (2020). Potential enhancement of host immunity and anti-tumor efficacy of nanoscale curcumin and resveratrol in colorectal cancers by modulated electro-hyperthermia. BMC Cancer, 20, Article 763. https://doi.org/10.1186/s12885-020-07072-0