Phytochemical Profiles and Anti-Glioma Activity of Bearberry Arctostaphylos uva-ursi (L.) Spreng. Leaf Extracts
Source abstract
Abstract
The use of diversified raw materials and various extractant types is justified because the varied chemical composition of extracts obtained via extraction determines their biological activity. Therefore, the objective of this study was (i) to characterize the chemical profile of two types of bearberry extracts (70% ethanolic and water) and (ii) to investigate the biological activity of the analyzed extracts through an assessment of their possible proapoptotic effects on glioma cell lines. The HPLC-UV analysis of individual compounds was performed for the determination of the phytochemical profile of the bearberry extracts, and their total phenolic content (TPC) and total flavonoid content (TFC) were determined spectrophotometrically. The induction of apoptosis, autophagy, and necrosis in anaplastic astrocytoma MOGGCCM and human glioblastoma LN229 cell lines were investigated. The results indicated that the ethanolic (Et) and aqueous (Aq) extracts had different chemical profiles. The TPC in the Et was ca. 60% higher than in the Aq. Similarly, the TFC and methylarbutin (mARB) concentrations were significantly higher in the Et. On the other hand, the concentration of hydroquinone (HQ) was ca. 70% and that of corilagin (COR) was ca. 100% higher in the Aq. In turn, the presence of ursolic acid (UA) and oleanolic acid (OA) was confirmed solely in the Et. In contrast to Aq, Et demonstrated high proapoptotic activity. At the concentration of 2 µL/mL, the level of apoptosis varied between 14.7% and 26% in the case of the MOGGCCM cells and between 12.3% and 33.3% in the case of the LN229 cell line. The knowledge and information obtained in this study indicate a need for further research on the anticancer effect of the studied bearberry phytochemicals on the MOGGCCM and LN229 cell lines and for the elucidation of their molecular anticancer mechanisms.
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Research context
OpenAlex topics: Natural product bioactivities and synthesis · Phytochemistry and Biological Activities · Phytochemical compounds biological activities
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Botany, Mycology and Ecology, Institute of Biological Sciences, Maria Curie-Skłodowska University, 19 Akademicka Street, 20-033 Lublin, Poland
Department of Functional Anatomy and Cytobiology, Institute of Biological Sciences, Maria Curie-Skłodowska University, 19 Akademicka Street, 20-033 Lublin, Poland
Department of Industrial and Medicinal Plants, University of Life Sciences in Lublin, 15 Akademicka Street, 20-950 Lublin, Poland
Department of Plant Physiology and Biophysics, Institute of Biological Sciences, Maria Curie-Skłodowska University, 19 Akademicka Street, 20-033 Lublin, Poland
Department of Zoology and Nature Protection, Institute of Biological Sciences, Maria Curie-Skłodowska University, 19 Akademicka Street, 20-033 Lublin, Poland
Department of Biological Bases of Forestry, Institute of Soil Science and Environmental Engineering and Management, University of Life Sciences in Lublin, 20-069 Lublin, Poland
Funding
Provincial Fund for Environmental Protection and Water Management in Lublin · Polish Ministry of Science and Higher Education
References (64)
Show source-provided references
1. The effect of developmental and environmental factors on secondary metabolites in medicinal plants10.1016/j.plaphy.2020.01.006 ↗
2. Secondary metabolites in the drought stress tolerance of crop plants: A review10.1016/j.genrep.2021.101040 ↗
3. Natural products as sources of new drugs from 1981–201410.1021/acs.jnatprod.5b01055 ↗
4. Seca, A.M.L., and Pinto, D.C.G.A. (2018). Plant secondary metabolites as anticancer agents: Successes in clinical trials and therapeutic application. Int. J. Mol. Sci., 19.10.3390/ijms19010263 ↗
5. Bhattacharya, T., Dutta, S., Akter, R., Rahman, M.H., Karthika, C., Nagaswarupa, H.P., Murthy, H.C.A., Fratila, O., Brata, R., and Bungau, S. (2021). Role of phytonutrients in nutrigenetics and nutrigenomics perspective in curing breast cancer. Biomolecules, 11.10.3390/biom11081176 ↗
6. Asma, S.T., Acaroz, U., Imre, K., Morar, A., Shah, S.R.A., Hussain, S.Z., Arslan-Acaroz, D., Demirbas, H., Hajrulai-Musliu, Z., and Istanbullugil, F.R. (2022). Natural products/bioactive compounds as a source of anticancer drugs. Cancers, 14.10.3390/cancers14246203 ↗
7. Overview of the anticancer activity of withaferin A, an active constituent of the Indian ginseng Withania somnifera10.1007/s11356-020-09028-0 ↗
8. Khan, A.W., Farooq, M., Haseeb, M., and Choi, S. (2022). Role of plant-derived active constituents in cancer treatment and their mechanisms of action. Cells, 11.10.3390/cells11081326 ↗
9. Naeem, A., Hu, P., Yang, M., Zhang, J., Liu, Y., Zhu, W., and Zheng, Q. (2022). Natural products as anticancer agents: Current status and future perspectives. Molecules, 27.10.3390/molecules27238367 ↗
10. Anticancer properties and mechanisms of botanical derivatives10.1016/j.phyplu.2022.100396 ↗
11. Phytochemical profile and pharmacological activity of the dry extract from Arctostaphylos uva-ursi leaves modified with phenylalanine
12. Sustainable wild harvesting of Arctostaphylos uva-ursi in the Pyrenees as a conservation practice10.1080/10496470802341110 ↗
13. Allen, D., Bilz, M., Leaman, D.J., Miller, R.M., Timoshyna, A., and Window, J. (2014). European Red List of Medicinal Plants, Publications Office of the European Union.
14. Kaźmierczakowa, R., Bloch-Orłowska, J., Celka, Z., Cwener, A., Dajdok, Z., Michalska-Hejduk, D., Pawlikowski, P., Szczęśniak, E., and Ziarnek, K. (2016). Polish Red List of Pteridophytes and Flowering Plants, Instytut Ochrony Przyrody Polskiej Akademii Nauk.
15. Hultén, E., and Fries, M. (1986). Atlas of North European Vascular Plants North of the Tropic of Cancer Volumes I–III, Koeltz Scientific Books.
16. Asensio, E., Vitales, D., Pérez, I., Peralba, L., Viruel, J., Montaner, C., Vallès, J., Garnatje, T., and Sales, E. (2020). Phenolic compounds content and genetic diversity at population level across the natural distribution range of Bearberry (Arctostaphylos uva-ursi, Ericaceae) in the Iberian Peninsula. Plants, 9.10.3390/plants9091250 ↗
17. Stefanescu, B.E., Szabo, K., Mocan, A., and Crisan, G. (2019). Phenolic compounds from five Ericaceae species leaves and their related bioavailability and health benefits. Molecules, 24.10.3390/molecules24112046 ↗
18. Natural approach used for urinary tract infections
19. Azman, N.A.M., Gallego, M.G., Segovia, F., Abdullah, S., Shaarani, S.M., and Pablos, M.P.A. (2016). Study of the properties of bearberry leaf extract as a natural antioxidant in model foods. Antioxidants, 5.10.3390/antiox5020011 ↗
20. Dell’Annunziata, F., Cometa, S., Della Marca, R., Busto, F., Folliero, V., Franci, G., Galdiero, M., De Giglio, E., and De Filippis, A. (2022). In vitro antibacterial and anti-inflammatory activity of Arctostaphylos uva-ursi leaf extract against Cutibacterium acnes. Pharmaceutics, 14.10.3390/pharmaceutics14091952 ↗
21. Kravchenko, G., Krasilnikova, O., Raal, A., Mazen, M., Chaika, N., Kireyev, I., Grytsyk, A., and Koshovyi, O. (2022). Arctostaphylos uva-ursi L. leaves extract and its modified cysteine preparation for the management of insulin resistance: Chemical analysis and bioactivity. Nat. Prod. Bioprospect., 12.10.1007/s13659-022-00352-1 ↗
22. Antioxidant activity and phenolic compounds of traditional Chinese medicinal plants associated with anticancer10.1016/j.lfs.2003.09.047 ↗
23. Anticancer effect in human glioblastoma and antioxidant activity of Petroselinum crispum L. methanol extract
24. Sugier, P., Sęczyk, Ł., Sugier, D., Krawczyk, R., Wójcik, M., Czarnecka, J., Okoń, S., and Plak, A. (2021). Chemical characteristics and antioxidant activity of Arctostaphylos uva-ursi L. Spreng. at the southern border of the geographical range of the species in Europe. Molecules, 26.10.3390/molecules26247692 ↗
25. Sugier, P., Sęczyk, Ł., and Sugier, D. (2022). Variation in population and solvents as factors determining the chemical composition and antioxidant potential of Arctostaphylos uva-ursi (L.) Spreng. leaf extracts. Molecules, 27.10.3390/molecules27072247 ↗
26. Phytotherapy for the treatment of glioblastoma: A review10.3389/fsurg.2022.844993 ↗
27. Colorimetry of total phenolics with phospho- molybdicephosphotungstic acid reagents10.5344/ajev.1965.16.3.144 ↗
28. Teneurs en principaux flavonoïdes des fleurs et feuilles de Crataegeus monogyna Jacq. et de Crataegeus laevigata (Poiret) DC
29. Temozolomide and sorafenib as programmed cell death inducers of human glioma cells10.1016/j.pharep.2017.03.008 ↗
30. Kovach, W. (1999). MVSP—A Multivariate Statistical Package for Windows. Ver. 3.1, Kovach Computing Services.
31. Council of Europe (2014). European Pharmacopoeia, 8.1 Supplement, Council of Europe. [8th ed.].
32. Validation of a quantitative assay of arbutin using gas chromatography in Origanum majorana and Arctostaphylos uva-ursi extracts10.1002/pca.1142 ↗
33. Boo, Y.C. (2021). Arbutin as a skin depigmenting agent with antimelanogenic and antioxidant properties. Antioxidants, 10.10.3390/antiox10071129 ↗
34. Variation of the arbutin content in different wild populations of Arctostaphylos uva-ursi in Catalonia, Spain10.1300/J044v09n04_10 ↗
35. Yang, L., Wen, K.-S., Ruan, X., Zhao, Y.-X., Wei, F., and Wang, Q. (2018). Response of plant secondary metabolites to environmental factors. Molecules, 23.10.3390/molecules23040762 ↗
36. Slika, H., Mansour, H., Wehbe, N., Nasser, S.A., Iratni, R., Nasrallah, G., Shaito, A., Ghaddar, T., Kobeissy, F., and Eid, A.H. (2022). Therapeutic potential of flavonoids in cancer: ROS-mediated mechanisms. Biomed. Pharmacother., 146.10.1016/j.biopha.2021.112442 ↗
37. The anti-cancer properties of neem (Azadirachta indica) through its antioxidant activity in the liver: Its pharmaceutics and toxic dosage forms. A literature review10.1515/jcim-2021-0009 ↗
38. Oleanolic acid and ursolic acid: Therapeutic potential in neurodegenerative diseases, neuropsychiatric diseases and other brain disorders10.1080/1028415X.2022.2051957 ↗
39. Antioxidant activities of oleanolic acid in vitro: Possible role of Nrf2 and MAP kinases10.1016/j.cbi.2010.01.034 ↗
40. Oleanolic acid improves hepatic insulin resistance via antioxidant, hypolipidemic and anti-inflammatory effects10.1016/j.mce.2013.06.014 ↗
41. Anti-inflammatory effects of oleanolic acid on LPS-induced inflammation in vitro and in vivo10.1007/s10753-012-9523-9 ↗
42. Antimicrobial activity of oleanolic and ursolic acids: An update10.1155/2015/620472 ↗
43. Efficient synthesis and anti-fungal activity of oleanolic acid oxime esters10.3390/molecules18033615 ↗
44. Anticancer and apoptotic activities of oleanolic acid are mediated through cell cycle arrest and disruption of mitochondrial membrane potential in HepG2 human hepatocellular carcinoma cells10.3892/mmr.2015.4033 ↗
45. Oleanolic acid suppresses the proliferation of lung carcinoma cells by miR-122/Cyclin G1/MEF2D axis10.1007/s11010-014-2228-7 ↗
46. Oleanolic acid and its synthetic derivatives for the prevention and therapy of cancer: Preclinical and clinical evidence10.1016/j.canlet.2014.01.016 ↗
47. Study of the oleanolic and ursolic acid contents of some species of the Lamiaceae10.1016/j.bse.2005.12.004 ↗
48. Microwave assisted extraction of ursolic acid and oleanolic acid from Ocimum sanctum10.1007/s12257-013-0798-y ↗
49. Microwave-assisted extraction of oleanolic acid and ursolic acid from Ligustrum lucidum Ait10.3390/ijms12085319 ↗
50. Determination of betulinic acid, oleanolic acid and ursolic acid from Achyranthes aspera L. using RP-UFLC-DAD analysis and evaluation of various parameters for their optimum yield
51. Quercetin and sorafenib as a novel and effective couple in programmed cell death induction in human gliomas10.1007/s12640-013-9452-x ↗
52. Phase I study of sorafenib and tipifarnib for recurrent glioblastoma: NABTC 05–0210.1007/s11060-017-2624-4 ↗
53. Synergistic anticancer effects of formononetin and temozolomide on glioma C6 cells10.1248/bpb.b18-00002 ↗
54. LY294002 and sorafenib as inhibitors of intracellular survival pathways in the elimination of human glioma cells by programmed cell death10.1007/s00441-021-03481-0 ↗
55. Zając, A., Maciejczyk, A., Sumorek-Wiadro, J., Filipek, K., Deryło, K., Langner, E., Pawelec, J., Wasiak, M., Scibiorski, M., and Rzeski, W. (2023). The role of Bcl-2 and Beclin-1 complex in “switching” between apoptosis and autophagy in human glioma cells upon LY294002 and sorafenib treatment. Cells, 12.10.3390/cells12232670 ↗
56. Selective induction of apoptosis in glioma tumour cells by a Gynostemma pentaphyllum extract10.1016/j.phymed.2009.12.002 ↗
57. A preliminary study of apoptosis induction in glioma cells via alteration of the Bax/Bcl-2- p53 axis by transformed and non-transformed root extracts of Leonurus sibiricus L.10.1007/s13277-015-4714-2 ↗
58. Radan, M., Carev, I., Tesevic, V., Politeo, O., and Culic, V.C. (2017). Qualitative HPLC-DAD/ESI-TOF-MS analysis, cytotoxic, and apoptotic effects of Croatian endemic Centaurea ragusina L. aqueous extracts. Chem. Biodivers., 14.10.1002/cbdv.201700099 ↗
59. Kubik, J., Waszak, Ł., Adamczuk, G., Humeniuk, E., Iwan, M., Adamczuk, K., Michalczuk, M., Korga-Plewko, A., and Józefczyk, A. (2022). Phytochemical analysis and anti-cancer properties of extracts of Centaurea castriferrei Borbás & Waisb genus of Centaurea L.. Molecules, 27.10.3390/molecules27217537 ↗
60. Khwaza, V., Oyedeji, O.O., and Aderibigbe, B.A. (2020). Ursolic acid-based derivatives as potential anti-cancer agents: An update. Int. J. Mol. Sci., 21.10.3390/ijms21165920 ↗
61. Kornel, A., Nadile, M., and Tsiani, E. (2022). Evidence of the beneficial effects of ursolic acid against lung cancer. Molecules, 27.10.3390/molecules27217466 ↗
62. UHPLC-PDA-ESI-TOF/MS metabolic profiling of Arctostaphylos pungens and Arctostaphylos uva-ursi. A comparative study of phenolic compounds from leaf methanolic extracts10.1016/j.phytochem.2015.01.002 ↗
63. Discovery and characterization of phenolic compounds in bearberry (Arctostaphylos uva-ursi) leaves using Liquid Chromatography-Ion Mobility-High-Resolution Mass Spectrometry10.1021/acs.jafc.1c02845 ↗
64. The synergistic and antagonistic antioxidant interactions of dietary phytochemical combinations10.1080/10408398.2021.1888693 ↗