Phytochemical composition, antioxidant and antiproliferative activities of Rosmarinus officinalis leaves

Authors

  • Winfred Nassazi Moi University
  • Isaac K’Owino Masinde Muliro University of Science and Technology
  • Jacqueline Makatiani Moi University
  • Sabina Wachira Kenya Medical Research Institute (KEMRI), Centre for Traditional Medicine and Drug Research

DOI:

https://doi.org/10.17721/fujcV8I2P150-167

Keywords:

Polyphenols, cancer, cytotoxicity, prostate adenocarcinoma

Abstract

Phytochemicals in Rosmarinus officinalis leaves, their total phenolic content, antioxidant potential and antiproliferative activity against human prostate (DU145), colon (CT26) and cervical (HeLa 229) cancer cells were investigated. Extraction was done separately using hexane, dichloromethane, ethyl acetate and methanol. A total of 32 compounds were identified, eight of which were reported for the first time. The highest phenolic content was 476.80 ± 0.69 µg/ml for the methanolic extract which also had the highest antioxidant activity with a minimum inhibitory concentration of 5.39 ± 0.09 mg/ml. Extracts exhibited the highest toxicity against prostate cancer cells and the least against cervical cancer cells.

Author Biographies

Winfred Nassazi, Moi University

Postgraduate Researcher, Department of Chemistry and Biochemistry, Moi University, Eldoret, Kenya

Isaac K’Owino, Masinde Muliro University of Science and Technology

Isaac O. Kowino (PhD) is a Senior Chemistry Lecturer, Department of Pure and Applied Chemistry, Masinde Muliro University of Science and Technology, Kakamega, Kenya. Adjunct Chemistry Lecturer at Department of Chemistry and Biochemistry, Moi University, Eldoret, Kenya.

Jacqueline Makatiani, Moi University

Jacqueline Makatiani (PhD) is a Senior Lecturer at Department of Biological Sciences, Moi University, Eldoret, Kenya.

Sabina Wachira, Kenya Medical Research Institute (KEMRI), Centre for Traditional Medicine and Drug Research

Dr. Sabrina Wachira is a principal Reseracher at Kenya Medical Research Institute (KEMRI), Centre for Traditional Medicine and Drug Research, Nairobi, Kenya.

References

Omara T, Kiprop A, Ramkat R, Cherutoi J, Kagoya S, Moraa Nyangena D, Azeze Tebo T, Nteziyaremye P, Nyambura Karanja L, Jepchirchir A, Maiyo A, Jematia Kiptui B, Mbabazi I, Kiwanuka Nakiguli C, Nakabuye B, Chepkemoi Koske M. Medicinal Plants Used in Traditional Management of Cancer in Uganda: A Review of Ethnobotanical Surveys, Phytochemistry, and Anticancer Studies. Evidence-Based Complementary and Alternative Medicine 2020;2020:1-26. https://doi.org/10.1155/2020/3529081

Akter R, Uddin S, Grice I, Tiralongo E. Cytotoxic activity screening of Bangladeshi medicinal plant extracts. Journal of Natural Medicines 2013;68(1):246-252. https://doi.org/10.1007/s11418-013-0789-5

Khalighi-Sigaroodi F, Ahvazi M, Hadjiakhoondi, A, Taghizadeh M, Yazdani D, Khalighi-Sigaroodi S, Bidel S. Cytotoxicity and antioxidant activity of 23 plant species of Leguminosae family. Iranian J Pharmaceut Res. 2012; 11(1): 295-302.

Omara T, Nassazi W, Omute T, Awath A, Laker F, Kalukusu R, Musau B, Nakabuye B, Kagoya S, Otim G, Adupa E. Aflatoxins in Uganda: An Encyclopedic Review of the Etiology, Epidemiology, Detection, Quantification, Exposure Assessment, Reduction, and Control. International Journal of Microbiology 2020;2020:1-18. https://doi.org/10.1155/2020/4723612

Nguyen C, Mehaidli A, Baskaran K, Grewal S, Pupulin A, Ruvinov I, Scaria B, Parashar K, Vegh C, Pandey S. Dandelion Root and Lemongrass Extracts Induce Apoptosis, Enhance Chemotherapeutic Efficacy, and Reduce Tumour Xenograft Growth In Vivo in Prostate Cancer. Evidence-Based Complementary and Alternative Medicine 2019;2019:1-12. https://doi.org/10.1155/2019/2951428

Kaur R, Kapoor K, Kaur H. Plants as a source of anticancer agents. J Nat Prod Plant Resour. 2011; 1(1): 119-124.

Majoumouo M, Tincho M, Morris T, Hiss D, Boyom F, Mandal C. Antiproliferative potential of methanolic and aqueous extracts and their methanolic fractions derived from fruits of Bersama engleriana against a panel of four cancer cell lines. Cogent Biology 2020;6(1):. https://doi.org/10.1080/23312025.2020.1727636

Azwanida NN. A Review on the Extraction Methods Use in Medicinal Plants, Principle, Strength and Limitation. Medicinal & Aromatic Plants 2015;04(03):. https://doi.org/10.4172/2167-0412.1000196

Torres R, Casanova L, Carvalho J, Marcondes M, Costa S, Sola-Penna M, Zancan P. Ocimum basilicum but not Ocimum gratissimum present cytotoxic effects on human breast cancer cell line MCF-7, inducing apoptosis and triggering mTOR/Akt/p70S6K pathway. Journal of Bioenergetics and Biomembranes 2018;50(2):93-105. https://doi.org/10.1007/s10863-018-9750-3

Vinay N, David D. Evaluation and comparison of anti-cancer activity of dapagliflozin and canagliflozin in oral cancer cell line: an in vitro study. International Journal of Basic & Clinical Pharmacology 2019;8(3):473. https://doi.org/10.18203/2319-2003.ijbcp20190459

Prinsloo S, Pieters R, Bezuidenhout C. A cell viability assay to determine the cytotoxic effects of water contaminated by microbes. South African Journal of Science 2013;109(7/8):1-4. https://doi.org/10.1590/sajs.2013/20120069

El-Attar M, Awad A, Abdel-Tawab F, Kamel H, Ahmad S, Hassan A. ASSESSMENT OF CYTOTOXIC AND ANTICANCER ACTIVITY OF Zygophyllum album AND Suaeda palastina EXTRACTS ON HUMAN LIVER CANCER CELL LINES. Arab Universities Journal of Agricultural Sciences 2019;27(1):539-544. https://doi.org/10.21608/ajs.2019.43663

Njuguna D, Mbuthia K, Mutuku C, Jepkorir M, Ndung’u J, Mwangangi R, Chepngetich J, Mwitari P. Phytochemical Composition and In vitro Anti-Proliferative Activity of Oxygonum sinuatum (Meisn.) Dammer on Selected Cancerous Cells. Journal of Complementary and Alternative Medical Research 2018;6(2):1-9. https://doi.org/10.9734/jocamr/2018/44413

Francis M, rew W. Antioxidant activity, nitric oxide scavenging activity and phenolic contents of Ocimum gratissimum leaf extract. Journal of Medicinal Plants Research 2010;4(23):2479-2487. https://doi.org/10.5897/jmpr10.262

Velioglu Y, Mazza G, Gao L, Oomah B. Antioxidant Activity and Total Phenolics in Selected Fruits, Vegetables, and Grain Products. Journal of Agricultural and Food Chemistry 1998;46(10):4113-4117. https://doi.org/10.1021/jf9801973

Krishnaiah D, Devi T, Sarbatly R, Bono A, Sarbatly R. Studies on phytochemical constituents of six Malaysian medicinal plants. J Med Plants Res. 2009; 3(32): 067-072.

Ashokkumar R, Ramaswamy M. Phytochemical screening by FTIR spectroscopic analysis of leaf extracts of selected Indian Medicinal plants. Int J Curr Microbiol Appl Sci. 2014; 3(1): 395-406.

Silva S, Feliciano R, Boas L, Bronze M. Application of FTIR-ATR to Moscatel dessert wines for prediction of total phenolic and flavonoid contents and antioxidant capacity. Food Chemistry 2014;150:489-493. https://doi.org/10.1016/j.foodchem.2013.11.028

Rajauria G. Optimization and validation of reverse phase HPLC method for qualitative and quantitative assessment of polyphenols in seaweed. Journal of Pharmaceutical and Biomedical Analysis 2018;148:230-237. https://doi.org/10.1016/j.jpba.2017.10.002

Quatrin A, Pauletto R, Maurer L, Minuzzi N, Nichelle S, Carvalho J, Maróstica M, Rodrigues E, Bochi V, Emanuelli T. Characterization and quantification of tannins, flavonols, anthocyanins and matrix-bound polyphenols from jaboticaba fruit peel: A comparison between Myrciaria trunciflora and M. jaboticaba. Journal of Food Composition and Analysis 2019;78:59-74. https://doi.org/10.1016/j.jfca.2019.01.018

Zhong L, Wu G, Fang Z, Wahlqvist M, Hodgson J, Clarke M, Junaldi E, Johnson S. Characterization of polyphenols in Australian sweet lupin (Lupinus angustifolius) seed coat by HPLC-DAD-ESI-MS/MS. Food Research International 2019;116:1153-1162. https://doi.org/10.1016/j.foodres.2018.09.061

Ren J, Liao L, Shang S, Zheng Y, Sha W, Yuan E. Purification, Characterization, and Bioactivities of Polyphenols from Platycladus orientalis

(L.) Franco. Journal of Food Science 2019;84(3):667-677. https://doi.org/10.1111/1750-3841.14483

FELHI S, DAOUD A, HAJLAOUI H, MNAFGUI K, GHARSALLAH N, KADRI A. Solvent extraction effects on phytochemical constituents profiles, antioxidant and antimicrobial activities and functional group analysis of Ecballium elaterium seeds and peels fruits. Food Science and Technology 2017;37(3):483-492. https://doi.org/10.1590/1678-457x.23516

Naima R, Oumam M, Hannache H, Sesbou A, Charrier B, Pizzi A, Charrier – El Bouhtoury F. Comparison of the impact of different extraction methods on polyphenols yields and tannins extracted from Moroccan Acacia mollissima barks. Industrial Crops and Products 2015;70:245-252. https://doi.org/10.1016/j.indcrop.2015.03.016

Felhi S, Baccouch N, Ben Salah H, Smaoui S, Allouche N, Gharsallah N, Kadri A. Nutritional constituents, phytochemical profiles, in vitro antioxidant and antimicrobial properties, and gas chromatography–mass spectrometry analysis of various solvent extracts from grape seeds (Vitis vinifera L.). Food Science and Biotechnology 2016;25(6):1537-1544. https://doi.org/10.1007/s10068-016-0238-9

Widyawati PS, Dwi T, Budianta W, Kusuma FA. Difference of solvent polarity to phytochemical content and antioxidant activity of Pluchea indicia Less leaves extracts. Int J Pharmacog Phytochem Res. 2014; 6(4): 850-855.

Hussain A, Anwar F, Chatha S, Jabbar A, Mahboob S, Nigam P. Rosmarinus officinalis essential oil: antiproliferative, antioxidant and antibacterial activities. Brazilian Journal of Microbiology 2010;41(4):1070-1078. https://doi.org/10.1590/s1517-83822010000400027

Yesil-Celiktas O, Sevimli C, Bedir E, Vardar-Sukan F. Inhibitory Effects of Rosemary Extracts, Carnosic Acid and Rosmarinic Acid on the Growth of Various Human Cancer Cell Lines. Plant Foods for Human Nutrition 2010;65(2):158-163. https://doi.org/10.1007/s11130-010-0166-4

González-Vallinas M, Molina S, Vicente G, Zarza V, Martín-Hernández R, García-Risco M, Fornari T, Reglero G, de Molina A. Expression of MicroRNA-15b and the Glycosyltransferase GCNT3 Correlates with Antitumor Efficacy of Rosemary Diterpenes in Colon and Pancreatic Cancer. PLoS ONE 2014;9(6):e98556. https://doi.org/10.1371/journal.pone.0098556

Borrás-Linares I, Pérez-Sánchez A, Lozano-Sánchez J, Barrajón-Catalán E, Arráez-Román D, Cifuentes A, Micol V, Carretero A. A bioguided identification of the active compounds that contribute to the antiproliferative/cytotoxic effects of rosemary extract on colon cancer cells. Food and Chemical Toxicology 2015;80:215-222. https://doi.org/10.1016/j.fct.2015.03.013

Valdés A, Sullini G, Ibáñez E, Cifuentes A, García-Cañas V. Rosemary polyphenols induce unfolded protein response and changes in cholesterol metabolism in colon cancer cells. Journal of Functional Foods 2015;15:429-439. https://doi.org/10.1016/j.jff.2015.03.043

Yan M, Li G, Petiwala S, Householter E, Johnson J. Standardized rosemary (Rosmarinus officinalis) extract induces Nrf2/sestrin-2 pathway in colon cancer cells. Journal of Functional Foods 2015;13:137-147. https://doi.org/10.1016/j.jff.2014.12.038

Valdés A, García-Cañas V, Koçak E, Simó C, Cifuentes A. Foodomics study on the effects of extracellular production of hydrogen peroxide by rosemary polyphenols on the anti-proliferative activity of rosemary polyphenols against HT-29 cells. ELECTROPHORESIS 2016;37(13):1795-1804. https://doi.org/10.1002/elps.201600014

Berrington D, Lall N. Anticancer Activity of Certain Herbs and Spices on the Cervical Epithelial Carcinoma (HeLa) Cell Line. Evidence-Based Complementary and Alternative Medicine 2012;2012:1-11. https://doi.org/10.1155/2012/564927

Ðilas S, Knez Ž, Cetojevic-Simin D, Tumbas V, Škerget M, Canadanovic-Brunet J, et al. In vitro antioxidant and antiproliferative activity of three rosemary (Rosmarinus officinalis L.) extract formulations. Int J Food Sci Technol. 2012; 47: 2052-2062. https://doi.org/10.1111/j.1365-2621.2012.03069.x

Moore J, Yousef M, Tsiani E. Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols. Nutrients 2016;8(11):731. https://doi.org/10.3390/nu8110731

Moore J, Megaly M, MacNeil A, Klentrou P, Tsiani E. Rosemary extract reduces Akt/mTOR/p70S6K activation and inhibits proliferation and survival of A549 human lung cancer cells. Biomedicine & Pharmacotherapy 2016;83:725-732. https://doi.org/10.1016/j.biopha.2016.07.043

Kontogianni V, Tomic G, Nikolic I, Nerantzaki A, Sayyad N, Stosic-Grujicic S, Stojanovic I, Gerothanassis I, Tzakos A. Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity. Food Chemistry 2013;136(1):120-129. https://doi.org/10.1016/j.foodchem.2012.07.091

PENG C, SU J, CHYAU C, SUNG T, HO S, PENG C, PENG R. Supercritical Fluid Extracts of Rosemary Leaves Exhibit Potent Anti-Inflammation and Anti-Tumor Effects. Bioscience, Biotechnology, and Biochemistry 2007;71(9):2223-2232. https://doi.org/10.1271/bbb.70199

Tai J, Cheung S, Wu M, Hasman D. Antiproliferation effect of Rosemary (Rosmarinus officinalis) on human ovarian cancer cells in vitro. Phytomedicine 2012;19(5):436-443. https://doi.org/10.1016/j.phymed.2011.12.012

Petiwala S, Berhe S, Li G, Puthenveetil A, Rahman O, Nonn L, Johnson J. Rosemary (Rosmarinus officinalis) Extract Modulates CHOP/GADD153 to Promote Androgen Receptor Degradation and Decreases Xenograft Tumor Growth. PLoS ONE 2014;9(3):e89772. https://doi.org/10.1371/journal.pone.0089772

Valdés A, Artemenko K, Bergquist J, García-Cañas V, Cifuentes A. Comprehensive Proteomic Study of the Antiproliferative Activity of a Polyphenol-Enriched Rosemary Extract on Colon Cancer Cells Using Nanoliquid Chromatography–Orbitrap MS/MS. Journal of Proteome Research 2016;15(6):1971-1985. https://doi.org/10.1021/acs.jproteome.6b00154

Ekunwe SI, Thomas MS, Luo X, Wang H, Chen Y, Zhang X, Begonia GB. Potential cancer-fighting Ocimum gratissimum (OG) leaf extracts: increased anti-proliferation activity of partially purified fractions and their spectral fingerprints. Ethnicity Dis. 2010; 20: S1-16.

Everette J, Bryant Q, Green A, Abbey Y, Wangila G, Walker R. Thorough Study of Reactivity of Various Compound Classes toward the Folin−Ciocalteu Reagent. Journal of Agricultural and Food Chemistry 2010;58(14):8139-8144. https://doi.org/10.1021/jf1005935

Ainsworth E, Gillespie K. Estimation of total phenolic content and other oxidation substrates in plant tissues using Folin–Ciocalteu reagent. Nature Protocols 2007;2(4):875-877. https://doi.org/10.1038/nprot.2007.102

Omara T, Kagoya S, Openy A, Omute T, Ssebulime S, Kiplagat K, Bongomin O, . Antivenin plants used for treatment of snakebites in Uganda: ethnobotanical reports and pharmacological evidences. Tropical Medicine and Health 2020;48(1):6. https://doi.org/10.1186/s41182-019-0187-0

Sripad G, Prakash V, Rao M. Extractability of polyphenols of sunflower seed in various solvents. Journal of Biosciences 1982;4(2):145-152. https://doi.org/10.1007/bf02702723

Cook N. Flavonoids--Chemistry, metabolism, cardioprotective effects, and dietary sources. The Journal of Nutritional Biochemistry 1996;7(2):66-76. https://doi.org/10.1016/0955-2863(95)00168-9

Tepe B, Daferera D, Sokmen A, Sokmen M, Polissiou M. Antimicrobial and antioxidant activities of the essential oil and various extracts of Salvia tomentosa Miller (Lamiaceae). Food Chemistry 2005;90(3):333-340. https://doi.org/10.1016/j.foodchem.2003.09.013

Fellah O, Bourenane N, Hameurlaine S, Altun M, Gherraf N, Zellagui A, et al. Anticancer Activity of Rosmarinus Officinalis Aqueous Extracts from Three Locations in Algeria. World J Environ Biosci. 2014; 7(3): 39-42.

Garbarino J, Troncoso N, Delpiano P, Carvajal L, Russo A. Antioxidant Activity Analysis for the Selection of Rosmarinus officinalis L. Natural Product Communications 2006;1(12):1934578X0600101. https://doi.org/10.1177/1934578x0600101210

Bourhia M, Laasri F, Aourik H, Boukhris A, Ullah R, Bari A, Ali S, El Mzibri M, Benbacer L, Gmouh S. Antioxidant and Antiproliferative Activities of Bioactive Compounds Contained in Rosmarinus officinalis Used in the Mediterranean Diet. Evidence-Based Complementary and Alternative Medicine 2019;2019:1-7. https://doi.org/10.1155/2019/7623830

Houlihan C, Ho C, Chang S. The structure of rosmariquinone — A new antioxidant isolated fromRosmarinus officinalis L.. Journal of the American Oil Chemists’ Society 1985;62(1):96-98. https://doi.org/10.1007/bf02541500

Wu J, Lee M, Ho C, Chang S. Elucidation of the chemical structures of natural antioxidants isolated from rosemary. Journal of the American Oil Chemists’ Society 1982;59(8):339-345. https://doi.org/10.1007/bf02541016

Souza L, de Gomes M, Goes A, Del Fabbro L, Filho C, Boeira S, Jesse C. Evidence for the involvement of the serotonergic 5-HT1A receptors in the antidepressant-like effect caused by hesperidin in mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry 2013;40:103-109. https://doi.org/10.1016/j.pnpbp.2012.09.003

Yang S, Hong C, Lee G, Kim C, Lee K. The hepatoprotection of caffeic acid and rosmarinic acid, major compounds of Perilla frutescens, against t-BHP-induced oxidative liver damage. Food and Chemical Toxicology 2013;55:92-99. https://doi.org/10.1016/j.fct.2012.12.042

Singh P. Infrared Spectroscopy. J Anal Chem. 2016: 1-85.

Meenakshi S, Umayaparvathi S, Arumugam M, Balasubramanian T. In vitro antioxidant properties and FTIR analysis of two seaweeds of Gulf of Mannar. Asian Pacific Journal of Tropical Biomedicine 2011;1(1):S66-S70. https://doi.org/10.1016/s2221-1691(11)60126-3

Graham J, Quinn M, Fabricant D, Farnsworth N. Plants used against cancer – an extension of the work of Jonathan Hartwell. Journal of Ethnopharmacology 2000;73(3):347-377. https://doi.org/10.1016/s0378-8741(00)00341-x

Mena P, Cirlini M, Tassotti M, Herrlinger K, Dall’Asta C, Del Rio D. Phytochemical Profiling of Flavonoids, Phenolic Acids, Terpenoids, and Volatile Fraction of a Rosemary (Rosmarinus officinalis L.) Extract. Molecules 2016;21(11):1576. https://doi.org/10.3390/molecules21111576

Hossain M, Rai D, Brunton N, Martin-Diana A, Barry-Ryan C. Characterization of Phenolic Composition in Lamiaceae Spices by LC-ESI-MS/MS. Journal of Agricultural and Food Chemistry 2010;58(19):10576-10581. https://doi.org/10.1021/jf102042g

Romo Vaquero M, Yáñez-Gascón M, García Villalba R, Larrosa M, Fromentin E, Ibarra A, Roller M, Tomás-Barberán F, Espín de Gea J, García-Conesa M. Inhibition of Gastric Lipase as a Mechanism for Body Weight and Plasma Lipids Reduction in Zucker Rats Fed a Rosemary Extract Rich in Carnosic Acid. PLoS ONE 2012;7(6):e39773. https://doi.org/10.1371/journal.pone.0039773

Borrás Linares I, Arráez-Román D, Herrero M, Ibáñez E, Segura-Carretero A, Fernández-Gutiérrez A. Comparison of different extraction procedures for the comprehensive characterization of bioactive phenolic compounds in Rosmarinus officinalis by reversed-phase high-performance liquid chromatography with diode array detection coupled to electrospray time-of-flight mass spectrometry. Journal of Chromatography A 2011;1218(42):7682-7690. https://doi.org/10.1016/j.chroma.2011.07.021

Pérez-Fons L, GarzÓn M, Micol V. Relationship between the Antioxidant Capacity and Effect of Rosemary (Rosmarinus officinalis L.) Polyphenols on Membrane Phospholipid Order. Journal of Agricultural and Food Chemistry 2010;58(1):161-171. https://doi.org/10.1021/jf9026487

Nangia-Makker P, Tait L, Shekhar M, Palomino E, Hogan V, Piechocki M, Funasaka T, Raz A. Inhibition of breast tumor growth and angiogenesis by a medicinal herb:Ocimum gratissimum. International Journal of Cancer 2007;121(4):884-894. https://doi.org/10.1002/ijc.22733

Downloads

Published

2020-12-22

Issue

Section

Articles