Phytochemical profile and dual anticancer–antilipase activities of Rubus ulmifolius extracts from Jijel, Algeria
Abstract
This study evaluated the in vitro antiproliferative and antilipase activities of ethanolic and methanolic extracts from Rubus ulmifolius (Jijel, Algeria) against obesity‑related colorectal cancer (CRC) cell lines (HT29, HCT116, SW620, CACO2, SW480) and primary human fibroblasts. Cells were treated for 72 h and viability was quantified by SRB assay. The ethanolic extract yielded IC₅₀ (μg mL-1, mean ± SD) values of 73.3 ± 9.9 (HT29), 106.8 ± 8.5 (HCT116), 240.2 ± 16.4 (SW620), 50.5 ± 5.2 (CACO2), 109.8 ± 3.7 (SW480), and 229.2 ± 16.8 (fibroblasts). The methanolic extract gave 121.2 ± 8.4 (HT29), 102.0 ± 3.9 (HCT116), 147.1 ± 10.3 (SW620), 26.2 ± 1.5 (CACO2), 95.0 ± 9.2 (SW480), and 157.3 ± 8.2 (fibroblasts), with activity in CACO2 meeting the NCI threshold for crude extracts (IC₅₀ < 30 μg mL-1). Cisplatin (positive control) showed IC₅₀ values of 19.72 ± 1.62 (HT29), 878.12 ± 105.4 (HCT116), 173.8 ± 21.0 (SW620), 175.41 ± 21.05 (CACO2), 26.9 ± 0.061 (SW480), and 1.52 ± 0.18 (fibroblasts), underscoring the relatively lower cytotoxicity of plant extracts toward normal cells. In pancreatic lipase assays, the ethanolic extract was more potent than the methanolic extract (IC₅₀ 30.2 ± 1.1 vs. 120.2 ± 8.8 μg mL-1), while orlistat gave 0.11 μg mL-1. HPLC‑DAD‑UV profiling identified rutin as the predominant phenolic (6.17–7.09 mg100 mg-1 extract). GC‑MS indicated that the ethanolic extract was enriched in fatty acids (oleic acid 17.62%, Z‑6‑octadecenoic acid 15.36%, methyl linolenate 12.81%), whereas the methanolic extract was rich in monoterpenoids (carvacrol 35.87%, thymol 21.14%, o‑cymene 8.74%). Collectively, these data suggest R. ulmifolius contains constituents with dual anti‑CRC and antilipase potential and merits further bioassay‑guided fractionation.
Downloads
References
Ado, M. A., Abas, F., Mohammed, A. S., & Ghazali, H. M. (2013). Anti and pro lipase activity of selected medicinal, herbal and aquatic plants, and structure elucidation of an anti lipase compound. Molecules, 18(12), 14651–14669. https://doi.org/10.3390/molecules181214651
Arnold, M., Sierra, M. S., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2017). Global patterns and trends in colorectal cancer incidence and mortality. Gut, 66(4), 683–691. https://doi.org/10.1136/gutjnl-2015-310912
Asnaashari, M., Tajik, R., & Khodaparast, M. H. H. (2015). Antioxidant activity of raspberry (Rubus fruticosus) leaves extract and its effect on oxidative stability of sunflower oil. Journal of Food Science and Technology, 52(8), 5180–5187. https://doi.org/10.1007/s13197-014-1564-7
Belhattab, R., Larous, L., Figueirido, A. C., Santos, P. A., Barroso, J. G., & Pedro, L. G. (2005). Origanum glandulosum Desf. grown wild in Algeria: Essential oil composition and glycosidically bound volatiles. Flavour and Fragrance Journal, 20(2), 209–212. https://doi.org/10.1002/ffj.1387
Bensam, M., Rechreche, H., Abdelwahab, A. E., Abu Serie, M. M., & Ali, S. M. (2023). The ethanolic extract of Algerian Ephedra alata inhibits MCF 7 breast cancer cell line growth by inducing apoptosis in a p53 dependent pathway. Saudi Journal of Biological Sciences, 30. https://doi.org/10.1016/j.sjbs.2023.103650
Billington, C. J., Epstein, L. H., Goodwin, N. J., & Harrison, B. (2000). Overweight, obesity, and health risk. Archives of Internal Medicine, 160(7), 898–904. https://doi.org/10.1001/archinte.160.7.898
Cherbal, A., Hireche, S., Kasabri, V., Al Alawi, S. H., Afifi, F. U., Abaza, I., Kebieche, M., & Madani, K. (2022). Pancreatic lipase inhibitory and antiproliferative effects of Oleaeuropaea L., Pistacialentiscus L. and Marrubiumvulgare on obesity related human colorectal cancer cell lines. International Journal of Natural and Engineering Sciences, 16(3), 137–154. https://ijnes.org/index.php/ijnes/article/view/687
Cherbal, A., Kebieche, M., Yilmaz, E. M., Aydoğmuş, Z., Benzaouia, L., Benguessoum, M., Benkedidah, M., & Madani, K. (2017). Antidiabetic and hypolipidemic activities of Algerian Pistacia lentiscus L. leaves extract in alloxan-induced diabetic rats. South African Journal of Botany, 108, 157–162. https://doi.org/10.1016/j.sajb.2016.10.024
Dai, J., & Mumper, R. J. (2010). Plant phenolics: Extraction, analysis and their antioxidant and anticancer properties. Molecules, 15(10), 7313–7352. https://doi.org/10.3390/molecules15107313
Danış, Ö., Ogan, A., Anbar, D., Dursun, B. Y., Demir, S., & Salan, U. (2015). Inhibition of pancreatic lipase by culinary plant extracts. International Journal of Plant Biology & Research, 3(2). https://www.jscimedcentral.com/public/assets/articles/plantbiology-3-1038.pdf
Deng, B., Kong, W., Suo, H., Shen, X., Newton, M. A., Burett, W. C., Zhao, Z., John, C., Sun, W., Zhang, X., Fan, Y., Zhou, C., & Bae Jump, V. L. (2023). Oleic acid exhibits anti proliferative and anti invasive activities via the PTEN/AKT/mTOR pathway in endometrial cancer. Cancers, 15(22). https://doi.org/10.3390/cancers15225407
Farha, A. K., Gan, R. Y., Li, H. B., Wu, D. T., Atanasov, A. G., Gul, K., Zhang, J. R., Yang, Q. Q., & Corke, H. (2020). The anticancer potential of the dietary polyphenol rutin: Current status, challenges, and perspectives. Critical Reviews in Food Science and Nutrition, 62(3), 832–859. https://doi.org/https://doi.org/10.1080/10408398.2020.1829541
Ferdjioui, S., Belhattab, R., Ouhida, S., Khither, H., Saoudi, S., & Mayouf, N. (2024). Hepatoprotective activity of Mentha rotundifolia aqueous extract against hepatocellular damage induced by CCl4 in rats. Natural Product Research, 1–6. https://doi.org/10.1080/14786419.2024.2387252
Gunes Bayir, A., Guler, E. M., Bilgin, M. G., Ergun, I. S., Kocyigit, A., & Dada, A. (2022). Anti inflammatory and antioxidant effects of carvacrol on N methyl N’ nitro N nitrosoguanidine (MNNG) induced gastric carcinogenesis in Wistar rats. Nutrients, 14(14). https://doi.org/10.3390/nu14142848
Hashemipour, H., Kermanshahi, H., Golian, A., & Veldkamp, T. (2013). Effect of thymol and carvacrol feed supplementation on performance, antioxidant enzyme activities, fatty acid composition, digestive enzyme activities, and immune response in broiler chickens. Poultry Science, 92(8), 2059–2065. https://doi.org/10.3382/ps.2012-02685
He, X., Chen, L., Pu, Y., Wang, H., Cao, J., & Jiang, W. (2023). Fruit and vegetable polyphenols as natural bioactive inhibitors of pancreatic lipase and cholesterol esterase: Inhibition mechanisms, polyphenol influences, application challenges. Food Bioscience, 55. https://doi.org/10.1016/j.fbio.2023.103054
Hireche, S., Belhattab, R., Cherbal, A., & Kebieche, M. (2021). Anti coagulant activity of Rubus ulmifolius extracts from Jijel, Algeria. Journal of Applied Biological Sciences, 15(2), 126–136. https://www.jabsonline.org/index.php/jabs/article/view/796
Kang, S. H., Kim, Y. S., Kim, E. K., Hwang, J. W., Jeong, J. H., Dong, X., Lee, J. W., Moon, S. H., Jeon, B. T., & Park, P. J. (2016). Anticancer effect of thymol on AGS human gastric carcinoma cells. Journal of Microbiology and Biotechnology, 26(1), 28–37. https://doi.org/10.4014/jmb.1506.06073
Kimura, Y. (2002). Carp oil or oleic acid, but not linoleic acid or linolenic acid, inhibits tumor growth and metastasis in Lewis lung carcinoma bearing mice. Journal of Nutrition, 132(7), 2069–2075. https://doi.org/10.1093/jn/132.7.2069
Kwon, Y. J., Kwon, G. E., Lee, H. S., Choi, M. H., & Lee, J. W. (2022). The effect of orlistat on sterol metabolism in obese patients. Frontiers in Endocrinology, 13. https://doi.org/10.3389/fendo.2022.824269
Lunagariya, N. A., Patel, N. K., Jagtap, S. C., & Bhutani, K. K. (2014). Inhibitors of pancreatic lipase: State of the art and clinical perspectives. EXCLI Journal, 13, 897–921. https://pmc.ncbi.nlm.nih.gov/articles/PMC4464291/pdf/EXCLI-13-897.pdf
Mączka, W., Twardawska, M., Grabarczyk, M., & Wińska, K. (2023). Carvacrol—A natural phenolic compound with antimicrobial properties. Antibiotics, 12(5). https://doi.org/10.3390/antibiotics12050824
Martínez, J., Gutiérrez, A., Casas, J., Lladó, V., López Bellan, A., Besalduch, J., Dopazo, A., & Escribá, P. V. (2005). The repression of E2F 1 is critical for the activity of minerval against cancer. Journal of Pharmacology and Experimental Therapeutics, 315(1), 466–474. https://doi.org/10.1124/jpet.105.088716
Mauri, G., Gori, V., Bonazzina, E., Amatu, A., Tosi, F., Bencardino, K., Ruggieri, L., Patelli, G., Arena, S., Bardelli, A., Siena, S., & Sartore Bianchi, A. (2020). Oxaliplatin retreatment in metastatic colorectal cancer: Systematic review and future research opportunities. Cancer Treatment Reviews, 91. https://doi.org/10.1016/j.ctrv.2020.102112
Mericli, F., Becer, E., Kabadayı, H., Hanoglu, A., Yiğit Hanoglu, D., Özkum Yavuz, D., Özek, T., & Vatansever, S. (2017). Fatty acid composition and anticancer activity in colon carcinoma cell lines of Prunus dulcis seed oil. Pharmaceutical Biology, 55(1), 1239–1248. https://doi.org/10.1080/13880209.2017.1296003
Mopuri, R., & Meriga, B. (2014). Anti-lipase and anti-obesity activities of Terminalia paniculata bark in high calorie diet-induced obese rats. Global Journal of Pharmacology, 8(1), 114–119. https://doi.org/10.5829/idosi.gjp.2014.8.1.82221
Olas, B. (2018). Berry phenolic antioxidants—Implications for human health? Frontiers in Pharmacology, 9. https://doi.org/10.3389/fphar.2018.00078
Oszmiański, J., Wojdyło, A., Gorzelany, J., & Kapusta, I. (2011). Identification and characterization of low molecular weight polyphenols in berry leaf extracts by HPLC-DAD and LC-ESI/MS. Journal of Agricultural and Food Chemistry, 59(24), 12830–12836. https://doi.org/10.1021/jf203052j
Schulz, M., Seraglio, S. K. T., Della Betta, F., Nehring, P., Valese, A. C., Daguer, H., Gonzaga, L. V., Costa, A. C. O., & Fett, R. (2019). Blackberry (Rubus ulmifolius Schott): Chemical composition, phenolic compounds and antioxidant capacity in two edible stages. Food Research International, 122, 627–634. https://doi.org/10.1016/j.foodres.2019.01.034
Sisti, M., De Santi, M., Fraternale, D., Ninfali, P., Scoccianti, V., & Brandi, G. (2008). Antifungal activity of Rubus ulmifolius Schott standardized in vitro culture. LWT—Food Science and Technology, 41(5), 946–950. https://doi.org/10.1016/j.lwt.2007.05.012
Sobczak, M., Kalemba, D., Ferenc, B., & Żylińska, L. (2014). Limited protective properties of thymol and thyme oil on differentiated PC12 cells with downregulated Mgst1. Journal of Applied Biomedicine, 12(4), 235–243. https://doi.org/10.1016/j.jab.2014.08.002
Zhang, A., Wan, L., Wu, C., Fang, Y., Han, G., Li, H., Zhang, Z., & Wang, H. (2013). Simultaneous determination of 14 phenolic compounds in grape canes by HPLC-DAD-UV using wavelength switching detection. Molecules, 18(11), 14241–14257. https://doi.org/10.3390/molecules181114241
Zhang, C., Xu, C., Gao, X., & Yao, Q. (2022). Platinum-based drugs for cancer therapy and anti-tumor strategies. Theranostics, 12(5), 2115–2132. https://doi.org/10.7150/thno.69424
Zheng, C. D., Duan, Y. Q., Gao, J. M., & Ruan, Z. G. (2010). Screening for anti-lipase properties of 37 traditional Chinese medicinal herbs. Journal of the Chinese Medical Association, 73(6), 319–324. https://doi.org/10.1016/S1726-4901(10)70068-X
Copyright (c) 2025 Saliha Hireche, Rachid Belhattab, Asma Cherbal, Violet Kasabri, Zeinep Aydoğmuş, Sundus H. Al Alawi, Fatma U. Afifi, Mohammed Kebieche, Abderrachid Desdous (Autor)
This work is licensed under a Creative Commons Attribution 4.0 International License.
DECLARATION OF ORIGINALITY AND COPYRIGHTS
I Declare that current article is original and has not been submitted for publication, in part or in whole, to any other national or international journal.
The copyrights belong exclusively to the authors. Published content is licensed under Creative Commons Attribution 4.0 (CC BY 4.0) guidelines, which allows sharing (copy and distribution of the material in any medium or format) and adaptation (remix, transform, and build upon the material) for any purpose, even commercially, under the terms of attribution.
Read this link for further information on how to use CC BY 4.0 properly.
1.png)
3.png){kind=logo}
