Isolation of Biflavonoids from Indonesian Araucaria Cunninghamii Mudie Leaves and Their Activity Against MCF7 Cells and 20S Proteasome
DOI:
https://doi.org/10.48048/tis.2025.9198Keywords:
Amentoflavone, Biflavonoid, Cupressuflavone, MCF7, Proteasome, RobustaflavoneAbstract
To enhance our survey of Araucaria biflavonoid’s biological activity, Araucaria cunninghamii Mudie dried leaf samples from West Java, Indonesia were extracted using acetone, then purified by Sephadex column and silica gel radial chromatography to give 3 known pure compounds: 7,4′,7″,4‴-tetra-O-methyl cupressuflavone, 7,4′,4‴-tri-O-methylrobustaflavone, and 7,7″-di-O-methylamentoflavone. This is the first report of 7,4′,4‴-tri-O-methylrobustaflavone and 7,7″-di-O-methylamentoflavone isolation from A. cunninghamii Mudie species. Among the isolated compounds, 7,7″-di-O-methylamentoflavone showed the best activity towards the MCF7 cancer cell line (IC50 = 150 μM). The ELISA assay exhibited a 32 % decrease in the detected 20S proteasome concentration level in the MCF7 lysate samples treated with 25 ppm 7,7″-di-O-methylamentoflavone.
HIGHLIGHTS
- This is the first research on the phytochemical composition of Araucaria cunninghamii Mudie leaves from Taman Bunga Nusantara, West Java, Indonesia.
- This is the first report of 7,4′,4‴-tri-O-methylrobustaflavone and 7,7″-di-O-methylamentoflavone isolation from Araucaria cunninghamii Mudie species.
- The isolated biflavonoids show moderate to weak cytotoxic activity towards MCF7 cells.
- Biflavonoids-treated MCF7 cell lysates show lower proteasome levels based on ELISA assay.
GRAPHICAL ABSTRACT
Downloads
References
C Frezza, A Venditti, DD Vita, C Toniolo, M Franceschin, A Ventrone, L Tomassini, S Foddai, M Guiso, M Nicoletti, A Bianco and M Serafini. Phytochemistry, chemotaxonomy, and biological activities of the araucariaceae family—a review. Plants 2020; 9(7), 888.
DD Agusta, H Dianhar, DUC Rahayu, IH Suparto and P Sugita. Anticancer and antivirus activities of two biflavonoids from indonesian araucaria hunsteinii k schum leaves. Journal of Hunan University Natural Sciences 2022; 493(3), 168-177.
P Sugita, DD Agusta, H Dianhar, IH Suparto, Kurniawanti, DUC Rahayu and L Irfana. Biflavonoid derived from araucaria hunsteinii K. schum leaves and their cytotoxicity activity against MCF-7 and HeLa cancer cells. Journal of Applied Pharmaceutical Science 2023; 13(10), 199-209.
Kurniawanti, DD Agusta, P Sugita, IH Suparto, H Dianhar and DUC Rahayu. Bioactive compounds of flavone dimers from indonesian araucaria columnaris leaves. RASAYAN Journal of Chemistry 2023; 16(03), 1872-1882.
W Rahman and SP Bhatnagar. A new biflavonyl AC3 from araucaria cunninghamii. Tetrahedron Letters 1968; 9(6), 675-678.
M Ilyas, JN Usmani, SP Bhatnagar, M Ilyas and W Rahman. WB1 and W11, the first optically active biflavones. Tetrahedron Letters 1968; 9(53), 5515-5517.
NU Khan, WH Ansari, W Rahman, M Okigawa and N Kawano. Two new biflavonyls from araucaria cunninghamii. Chemical and Pharmaceutical Bulletin 1971; 19(7), 1500-1501.
J Chen, ML Yang, J Zeng and K Gao. Antimicrobial activity of araucaria cunninghamii sweet and the chemical constituents of its twigs and leaves. Phytochemistry Letters 2013; 6(1), 41-45.
NU Khan, WH Ansari, JN Usmani, M Ilyas and W Rahman. Biflavonyls of the araucariales. Phytochemistry 1971; 10(9), 2129-2131.
B Sahu, S Chakrabarty, V Saini, M Kandpal, B Goel, S Kumari, I Ahmed, HC Jha and SK Jain. Exploring the cytotoxic potential of biflavones of araucaria cunninghamii: Precise identification combined by LC-HRMS-metabolomics and database mining, targeted isolation, network pharmacology, in vitro cytotoxicity, and docking studies. Chemical Biology & Drug Design 2024; 103(6), e14564.
C Frezza, D De Vita, L Fonti, O Giampaoli, C Dal Bosco, F Sciubba, A Venditti, C Scintu and F Attorre. Secondary metabolites of araucaria cunninghamii mudie from central Italy. Plant Biosystems - An International Journal Dealing with all Aspects of Plant Biology 2024; 158(4), 589-594.
X He, F Yang and X Huang. Proceedings of chemistry, pharmacology, pharmacokinetics and synthesis of biflavonoids. Molecules 2021; 26(19), 6088.
J Tsalikis, M Abdel-Nour, A Farahvash, MT Sorbara, S Poon, DJ Philpott and SE Girardin. Isoginkgetin, a natural biflavonoid proteasome inhibitor, sensitizes cancer cells to apoptosis via disruption of lysosomal homeostasis and impaired protein clearance. Molecular and Cellular Biology 2019; 39(10), e00489-18.
S Sengupta and G Mehta. Non-peptidic natural products as ubiquitin-proteasome inhibitors. Tetrahedron 2019; 75(7), 817-853.
RA Guedes, N Aniceto, MAP Andrade, JAR Salvador and RC Guedes. Chemical patterns of proteasome inhibitors: Lessons learned from two decades of drug design. International Journal of Molecular Sciences 2019; 20(21), 5326.
L Skalniak, M Dziendziel and J Jura. MCPIP1 contributes to the toxicity of proteasome inhibitor MG-132 in HeLa cells by the inhibition of NF-κB. Molecular and Cellular Biochemistry 2014; 395(1), 253-263.
K Mehdizadeh, F Ataei and S Hosseinkhani. Treating MCF7 breast cancer cell with proteasome inhibitor Bortezomib restores apoptotic factors and sensitizes cell to docetaxel. Medical Oncology 2021; 38(6), 64.
F Commo and BM Bot. R package nplr N-Parameter logistic regression, Available at: https://cran.r-project.org/web/packages/nplr/vignettes/nplr.pdf, accessed May 2024.
M Ilyas, O Seligmann and H Wagner. Biflavones from the leaves of araucaria rulei F. Muell. and a survey on biflavanoids of the araucaria genus. Zeitschrift für Naturforschung C 1977; 32(3-4), 206-209.
AM Freitas, MTR Almeida, CR Andrighetti-Frohner, FTGS Cardozo, CRM Barardi, MR Farias and CMO Simoes. Antiviral activity-guided fractionation from araucaria angustifolia leaves extract. Journal of Ethnopharmacology 2009; 126(3), 512-517.
C Frezza, F Sciubba, D De Vita, C Toniolo, S Foddai, L Tomassini, R Petrucci, A Bianco and M Serafini. Non-volatile compounds from araucaria columnaris (G.Forst.) hook leaves. Biochemical Systematics and Ecology 2022; 103, 104430.
N Ilyas, M Ilyas, W Rahman, M Okigawa and N Kawano. Biflavones from the leaves of araucaria excelsa. Phytochemistry 1978; 17(5), 987-990.
Y Gu, Y Xu, S Fang and Q He. The chemical constituents from podocarpus imbricatus. Journal of Integrative Plant Biology 1990; 32(8), 631-636.
LASD Nascimento, GMSP Guilhon, MSP Arruda, LS Santos, AC Arruda, AH Muller, MND Silva, ST Rodrigues and MGD Carvalho. Biflavones and triterpenoids isolated from ouratea castaneifolia (DC.) Engl., ochnaceae. Revista Brasileira de Farmacognosia 2009; 19(4), 823-827.
DJ Ofman, KR Markham, C Vilain and BPJ Molloy. Flavonoid profiles of New Zealand kauri and other species of agathis. Phytochemistry 1995; 38(5), 1223-1228.
H Li, T Nehira, M Hagiwara and N Harada. Total synthesis and absolute stereochemistry of the natural atropisomer of the biflavone 4‘,4‘‘‘,7,7‘‘-Tetra-O-methylcupressuflavone. The Journal of Organic Chemistry 1997; 62(21), 7222-7227.
JC DeForest, L Du and PM Joyner. 4′,4‴,7,7″-Tetra-O-methylcupressuflavone inhibits seed germination of lactuca sativa. Journal of Natural Products 2014; 77(4), 1093-1096.
P Charisiadis, VG Kontogianni, CG Tsiafoulis, AG Tzakos, M Siskos and IP Gerothanassis. 1H-NMR as a structural and analytical tool of intra- and intermolecular hydrogen bonds of phenol-containing natural products and model compounds. Molecules 2014; 19(9), 13643-13682.
J Chen, C Duh and J Chen. New cytotoxic biflavonoids from selaginella delicatula. Planta Medica 2005; 71(7), 659-665.
M Ghasemi, T Turnbull, S Sebastian and I Kempson. The MTT assay: Utility, limitations, pitfalls, and interpretation in bulk and single-cell analysis. International Journal of Molecular Sciences 2021; 22(23), 12827.
S Sharifi, J Barar, MS Hejazi and N Samadi. Doxorubicin changes bax /Bcl-xL ratio, caspase-8 and 9 in breast cancer cells. Advanced Pharmaceutical Bulletin 2015; 5(3), 351-359.
E Gavilan, S Giraldez, I Sanchez-Aguayo, F Romero, D Ruano and P Daza. Breast cancer cell line MCF7 escapes from G1/S arrest induced by proteasome inhibition through a GSK-3β dependent mechanism. Scientific Reports 2015; 5, 10027.
H Sasaki, Y Kitoh, M Tsukada, K Miki, K Koyama, LD Juliawaty, EH Hakim, K Takahashi and K Kinoshita. Inhibitory activities of biflavonoids against amyloid-β peptide 42 cytotoxicity in PC-12 cells. Bioorganic & Medicinal Chemistry Letters 2015; 25(14), 2831-2833.
H Sasaki, K Miki, K Kinoshita, K Koyama, LD Juliawaty, SA Achmad, EH Hakim, M Kaneda and K Takahashi. β-Secretase (BACE-1) inhibitory effect of biflavonoids. Bioorganic & Medicinal Chemistry Letters 2010; 20(15), 4558-4560.
N Sirimangkalakitti, LD Juliawaty, EH Hakim, I Waliana, N Saito, K Koyama and K Kinoshita. Naturally occurring biflavonoids with amyloid β aggregation inhibitory activity for development of anti-Alzheimer agents. Bioorganic & Medicinal Chemistry Letters 2019; 29(15), 1994-1997.
F Hosp, H Vossfeldt, M Heinig, D Vasiljevic, A Arumughan, E Wyler, M Landthaler, N Hubner, EE Wanker, L Lannfelt, M Ingelsson, M Lalowski, A Voigt and M Selbach. Quantitative interaction proteomics of neurodegenerative disease proteins. Cell Reports 2015; 11(7), 1134-1146.
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Walailak University
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
