In collaboration with Payame Noor University and Iranian Society of Physiology and Pharmacology

Document Type : Article

Authors

1 Department of Biology, University of ‎Shiraz, Shiraz, Iran‎

2 Department of Biology, Payame Noor ‎University, Tehran, Iran

10.30473/eab.2025.75303.2002

Abstract

Natural resources such as plants are a safe therapeutic option in treating cancers and reducing the side effects of current treatments. Sage is an aromatic and medicinal plant known for its antioxidant properties. It has been used as an antispasmodic, astringent, sedative, anti-hyperglycemic, and anti-inflammatory agent in Iranian medicine. In the present study, the anticancer effects of compounds found in sage extracts, such as cineole and camphor, were studied. For this purpose, cancer was first induced in mice by (dimethylbenzanthracene) dissolved in sunflower oil for 4 weeks. Then, different tumor cell lines were exposed to the extracts. For this purpose, the experimental group was treated with a hydroalcoholic extract of sage leaves for 4 weeks. While the control group received distilled water. Then, tissue sections were taken from the samples and the groups were statistically compared with each other. The findings indicate the therapeutic effects of sage. Sage can potentially prevent breast cancer.

Keywords

Main Subjects

Abdallah, E. M. (2011). Plants: An alternative source for antimicrobials. Journal of applied pharmaceutical science, (Issue), 16-20. https://japsonline.com/abstract.php?article_id=118
Afzal-Rafii, M. Z. (1979). Contribution à l'étude cytotaxonomique du groupe Salvia verbenaca L. Bulletin de la Société Botanique de France. Lettres Botaniques, 126(1), 79-86. https://doi.org/10.1080/01811797.1979.10824377
Al‐Jaber, H. I., Obeidat, S. M., Afifi, F. U., & Abu Zarga, M. H. (2020). Aroma profile of two populations of Salvia verbenaca collected from two bio‐geographical zones from Jordan. Chemistry & Biodiversity, 17(2), e1900553. https://doi.org/10.1002/cbdv.201900553
Badisa, R. B., Tzakou, O., Couladis, M., & Pilarinou, E. (2005). Cytotoxic Activities of Salvia. of the Labiatae Family. Pharmaceutical biology42(8), 640-645. https://doi.org/10.1080/13880200490902590
Bang, S., Ha, T. K. Q., Lee, C., Li, W., Oh, W. K., & Shim, S. H. (2016). Antiviral activities of compounds from aerial parts of Salvia plebeia R. Br. Journal of ethnopharmacology192, 398-405. https://doi.org/10.1016/j.jep.2016.09.030
Bang, S., Li, W., Ha, T. K. Q., Lee, C., Oh, W. K., & Shim, S. H. (2018). Anti-influenza effect of the major flavonoids from Salvia plebeia R. Br. via inhibition of influenza H1N1 virus neuraminidase. Natural product research, 32(10), 1224-1228. https://doi.org/10.1080/14786419.2017.1326042
Belkhiri, F., Baghiani, A., Zerroug, M. M., & Arrar, L. (2017). Investigation of antihemolytic, xanthine oxidase inhibition, antioxidant and antimicrobial properties of Salvia verbenaca L. aerial part extracts. African Journal of Traditional, Complementary and Alternative Medicines14(2), 273-281. https://doi.org/10.21010/ajtcam.v14i2.29
Bonesi, M., Loizzo, M. R., Acquaviva, R., Malfa, G. A., Aiello, F., & Tundis, R. (2017). Anti-inflammatory and antioxidant agents from Salvia genus (Lamiaceae): An assessment of the current state of knowledge. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Inflammatory and Anti-Allergy Agents), 16(2), 70-86. https://doi.org/10.2174/1871523016666170502121419
Bonnier, G. (1935). Flore complète illustrée en couleurs de France, Suisse et Belgique. Table Générale.
Bydoun, M., Marcato, P., & Dellaire, G. (2014). Breast cancer genomics. In Cancer genomics (pp. 213-232). Academic Press. https://doi.org/10.1016/B978-0-12-396967-5.00013-X
Canzoneri, M., Bruno, M., Rosselli, S., Russo, A., Cardile, V., Formisano, C., ... & Senatore, F. (2011). Chemical composition and biological activity of Salvia verbenaca essential oil. Natural Product Communications6(7), 1934578X1100600725. https://doi.org/10.1177/1934578X1100600725
Djeridane, A., Yousfi, M., Nadjemi, B., Maamri, S., Djireb, F., & Stocker, P. (2006). Phenolic extracts from various Algerian plants as strong inhibitors of porcine liver carboxylesterase. Journal of Enzyme Inhibition and Medicinal Chemistry, 21(6), 719-726. https://doi.org/10.1080/14756360600810399
Eggermont, A. M., Caldas, C., Ringborg, U., Medema, R., Tabernero, J., & Wiestler, O. (2014). Cancer Core Europe: A consortium to address the cancer care–Cancer research continuum challenge. European Journal of Cancer50(16), 2745-2746. https://doi.org/10.1016/j.ejca.2014.07.025
Esra, M., Cetin, O., Kahraman, A., Celep, F., & Dogan, M. (2011). A cytomorphological study in some taxa of the genus Salvia L. (Lamiaceae). Caryologia, 64(3), 272-287. https://doi.org/10.1080/00087114.2011.10589793
Et-Touys, A., Fellah, H., Sebti, F., Mniouil, M., Aneb, M. H., Elboury, H., ... & Bakri, Y. (2016). In vitro antileishmanial activity of extracts from endemic Moroccan medicinal plant Salvia verbenaca (L.) Briq. ssp verbenaca Maire (S. clandestina Batt. non L). Eur J Med Plants16(1), 1-8. https://doi.org/10.9734/EJMP/2016/27891
Farhat, M. B., Sotomayor, J. A., & Jordán, M. J. (2019). Salvia verbenaca L. essential oil: Variation of yield and composition according to collection site and phenophase. Biochemical Systematics and Ecology82, 35-43. https://doi.org/10.1016/j.bse.2018.12.002
Guaouguaou, F. E., Bebaha, M. A. A., Taghzouti, K., Bouyahya, A., Bakri, Y., Dakka, N., & Es-Safi, N.E. (2018). Cytotoxicological investigation of the essential oil and the extracts of Cotula cinerea and Salvia verbenaca from Morocco. BioMed research international, 2018(1), 7163961. https://doi.org/10.1155/2018/7163961
Giordano, A., & Tommonaro, G. (2019). Curcumin and Cancer. Nutrients, 11(10), 2376. https://doi.org/10.3390/nu11102376
Gupta, P., Wright, S. E., Kim, S. H., & Srivastava, S. K. (2014). Phenethyl isothiocyanate: A comprehensive review of anti-cancer mechanisms. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1846(2), 405-424. https://doi.org/10.1016/j.bbcan.2014.08.003
Jedinák, A., et al. (2010). Antioxidant and Antiprotease Activities of Sage (Salvia officinalis L.) Extracts. Journal of Agricultural and Food Chemistry, 58(12), 7346–7352. https://doi.org/10.1021/jf100518k
Howes, M. J. R. (2018). The evolution of anticancer drug discovery from plants. The Lancet Oncology, 19(3), 293-294. https://doi.org/10.1016/S1470-2045(18)30136-0
Huang, M. Y., Zhang, L. L., Ding, J., & Lu, J. J. (2018). Anticancer drug discovery from Chinese medicinal herbs. Chinese medicine13(1), 35. https://doi.org/10.1186/s13020-018-0192-y
Hamidpour, M., et al. (2014). Chemistry, Pharmacology, and Medicinal Property of Sage (Salvia) to Prevent and Cure Illnesses such as Obesity, Diabetes, Depression, Dementia, Lupus, Autism, Heart Disease, and Cancer. Journal of Traditional and Complementary Medicine, 4(2), 82-88. https://doi.org/10.4103/2225-4110.130373
 
Jang, H. J., Lee, S. J., Kim, C. Y., Hwang, J. T., Choi, J. H., Park, J. H., ... & Rho, M. C. (2017). Effect of Sunlight Radiation on the Growth and Chemical Constituents of Salvia plebeia R. Br. Molecules, 22(8), 1279. https://doi.org/10.3390/molecules22081279
Jang, H. J., Lee, S., Lee, S. J., Lim, H. J., Jung, K., Kim, Y. H., ... & Rho, M. C. (2017). Anti-inflammatory activity of eudesmane-type sesquiterpenoids from Salvia plebeiaJournal of natural products, 80(10), 2666-2676. https://doi.org/10.1021/acs.jnatprod.7b00326
Johnson, J. J. (2011). Carnosol: a promising anti-cancer and anti-inflammatory agent. Cancer letters, 305(1), 1-7. https://doi.org/10.1016/j.canlet.2011.02.005
Jung, H. J., Song, Y. S., Lim, C. J., & Park, E. H. (2009). Anti-inflammatory, anti-angiogenic and anti-nociceptive activities of an ethanol extract of Salvia plebeia R. Brown. Journal of ethnopharmacology, 126(2), 355-360. https://doi.org/10.1016/j.jep.2009.08.031
Kamatou, G. P., Van Vuuren, S. F., Van Heerden, F. R., Seaman, T., & Viljoen, A. M. (2007). Antibacterial and antimycobacterial activities of South African Salvia species and isolated compounds from S. chamelaeagnea. South African Journal of Botany73(4), 552-557.
Kamatou, G. P., Van Zyl, R. L., Davids, H., Van Heerden, F. R., Lourens, A. C. U., & Viljoen, A. M. (2008). Antimalarial and anticancer activities of selected South African Salvia species and isolated compounds from S. radula. South African Journal of Botany, 74(2), 238-243. https://doi.org/10.1016/j.sajb.2007.08.001
Keshavarz, M., et al. (2020). Sage (Salvia officinalis) as a Adjuvant Therapy for Cancer: A Review of the Potential Mechanisms. Iranian Journal of Pharmaceutical Research, 19(1), 1-12. https://doi.org/10.22037/ijpr.2020.1101033
Khouchlaa, A., Et-Touys, A., Lakhdar, F., Laasri, F. E., El Idrissi, A. E. Y., & Zaakour, F. (2021). Ethnomedicinal use, phytochemistry, pharmacology, and toxicology of Salvia verbenaca L.: A review. Biointerface Research in Applied Chemistry12(2), 1437-1469. https://doi.org/10.33263/BRIAC122.14371469
Latif, A., Amer, H. M., Hamad, M. E., Alarifi, S. A. R., & Almajhdi, F. N. (2014). Medicinal plants from Saudi Arabia and Indonesia: In vitro cytotoxicity evaluation on Vero and Hep-2 cells. Journal of Medicinal Plants Research8(34), 1065-1073. https://doi.org/10.5897/JMPR2014.5481
Lin, L. T., Uen, W. C., Choong, C. Y., & Shi, Y. C. (2022). Cinnamaldehyde Induces Apoptosis and reverses epithelial-mesenchymal transition through inhibition of Wnt/β-catenin pathway in non-small cell lung cancer. International Journal of Molecular Sciences, 23(1), 462.
Lu, Y., & Foo, L. Y. (2002). Polyphenolics of Salvia-a review. Phytochemistry59(2), 117-140. https://doi.org/10.1016/S0031-9422(01)00415-0
Mamache, W., Amira, S., Ben Souici, C., Laouer, H., & Benchikh, F. (2020). In vitro antioxidant, anticholinesterases, anti‐α‐amylase, and anti‐α‐glucosidase effects of Algerian Salvia aegyptiaca and Salvia verbenaca. Journal of Food Biochemistry, 44(11), e13472. https://doi.org/10.1111/jfbc.13472
Mukhtar, H. (2012). Chemoprevention: making it a success story for controlling human cancer. Cancer letters, 326(2), 123-127. https://doi.org/10.1016/j.canlet.2012.05.016
Nassar, M. E. R. Y. E. M., Zerizer, S. A. K. I. N. A., Kabouche, Z. A. H. I. A., Kabouche, A. H. M. E. D., & Bechkri, S. A. R. A. (2015). Antioxidant and the immunomodulatory activities exhibited by three plants from Lamiaceae family. Int J Pharm Pharm Sci7(9), 331-334. https://d1wqtxts1xzle7.cloudfront.net/111176666
Nassar, M., Zadri, F., & Slimani, S. (2021). Assessment of Protective Effects of Methanolic Extract of Salvia verbenaca Roots Against Oxidative Damage Induced by Hydrogen Peroxide. Turkish Journal of Pharmaceutical Sciences, 18(3), 360. https://doi.org/10.4274/tjps.galenos.2020.74555
Newman, D. J., & Cragg, G. M. (2012). Natural products as sources of new drugs over the 30 years from 1981 to 2010. Journal of natural products75(3), 311-335. https://doi.org/10.1021/np200906s
Pan, L., Chai, H. B., & Kinghorn, A. D. (2012). Discovery of new anticancer agents from higher plants. Frontiers in bioscience (Scholar edition)4, 142. https://doi.org/10.2741/257
Prasad, S., Yadav, V. R., Sung, B., Reuter, S., Kannappan, R., Deorukhkar, A., ... & Aggarwal, B. B. (2012). Ursolic acid inhibits growth and metastasis of human colorectal cancer in an orthotopic nude mouse model by targeting multiple cell signaling pathways: chemosensitization with capecitabine. Clinical cancer research18(18), 4942-4953.
Rocha, J., et al. (2015). Anti-inflammatory and cytotoxic activities of Salvia officinalis L. Journal of Ethnopharmacology, 167, 1-6.
Reis, F. R., et al. (2016). Carnosic Acid Induces Apoptosis and Inhibits Akt/mTOR Signaling in Human Gastric Cancer Cell Lines. Pharmaceuticals, 9(4), 67.
Russo, A., Cardile, V., Graziano, A. C., Formisano, C., Rigano, D., Canzoneri, M., ... & Senatore, F. (2015). Comparison of essential oil components and in vitro anticancer activity in wild and cultivated Salvia verbenaca. Natural Product Research, 29(17), 1630-1640. https://doi.org/10.1080/14786419.2014.994212
Rastogi, N., Duggal, S., Singh, S. K., Porwal, K., Srivastava, V. K., Maurya, R., & Bhatt, M. L. B. (2015). Proteasome inhibition mediates p53 reactivation and anti-cancer activity of 6-gingerol in breast cancer cells. Oncotarget, 6(41), 43310-43325. https://doi.org/10.18632/oncotarget.6383
Sarac, N., & Uğur, A. (2007). Antimicrobial activities and usage in folkloric medicine of some Lamiaceae species growing in Mugla, Turkey. https://hdl.handle.net/20.500.12809/7732
Viegi, L., & Ghedira, K. (2014). Preliminary study of plants used in ethnoveterinary medicine in Tunisia and in Italy. African Journal of Traditional, Complementary and Alternative Medicines, 11(3), 189-199. http://dx.doi.org/10.4314/ajtcam.v11i3.27
Wang, X., Zhang, F., Yang, L., Mei, Y., Long, H., Zhang, X., ... & Su, X. (2011). Ursolic acid inhibits proliferation and induces apoptosis of cancer cells in vitro and in vivo. BioMed Research International2011(1), 419343. https://doi.org/10.1155/2011/419343
Zou, Y. H., Zhao, L., Xu, Y. K., Bao, J. M., Liu, X., Zhang, J. S., ... & Tang, G. H. (2018). Anti-inflammatory sesquiterpenoids from the Traditional Chinese Medicine Salvia plebeia: Regulates pro-inflammatory mediators through inhibition of NF-κB and Erk1/2 signaling pathways in LPS-induced Raw264. 7 cells. Journal of Ethnopharmacology210, 95-106. https://doi.org/10.1016/j.jep.2017.08.034