Home Phytochemical characterization and multi-biological potentials of Inula viscosa: new in vitro evidence
Article
Licensed
Unlicensed Requires Authentication

Phytochemical characterization and multi-biological potentials of Inula viscosa: new in vitro evidence

  • Yasemin Celik Altunoglu ORCID logo EMAIL logo , Mustafa Ocal , Mehmet Cengiz Baloglu , Alsideeq Abdulsalam Ahmed Aboujanah , Erdoğan Horuz , Eulogio J. Llorent-Martínez , Abdullahi Ibrahim Uba , Irina Lazarova , Gökhan Zengin ORCID logo and Kerim Güney
Published/Copyright: October 20, 2025
Become an author with De Gruyter Brill

Abstract

Inula viscosa is a common medicinal plant and is mostly spread in Mediterranean countries. The current study analyses I. viscosa extracts for antimicrobial capacity, phenolic content, antioxidant, enzyme inhibition, and molecular modeling. The extracts’ anticancer potential in prostate and breast cancer cells was evaluated, and their anti-metastatic and molecular activities were analyzed through gene expression. The most prevalent substances in the methanol extract of I. viscosa are phenolic acids, which include derivatives of caffeic acid and mono-, di-, and tri-caffeoylquinic acids. Dicaffeoylquinic acids represented 88 % of the quantified phenolics. The methanol extract showed a 50 % inhibitor concentration (IC50) of 101.4 μg/mL at 48 h in PC3 cells. Autophagy-related genes were found to be down-regulated in all three cancer cells. Regarding antimetastatic activity, the wound width remained ∼96 % at 48 h after ethyl acetate treatment in MCF-7 cells. The water extract had the highest total phenolic content and the strongest antioxidant capacity, followed by the methanol extract. Modest binding potential to B-cell leukemia-2 (Bcl-2) was observed with caffeoylquinic acid and caffeic acid derivatives, which may be related to pro-apoptotic/anticancer effects. Our results suggested that I. viscosa can be considered as an effective raw material for designing health-promoting applications.


Corresponding author: Yasemin Celik Altunoglu, Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Kastamonu University, Plantomics Research Laboratory, 37150, Kastamonu, Türkiye, E-mail:

Acknowledgment

Technical and human support provided by CICT of Universidad de Jaén (UJA, MINECO, Junta de Andalucía, FEDER) is gratefully acknowledged.

  1. Research ethics: Not applicable.

  2. Informed consent: Not applicable.

  3. Author contributions: Yasemin Celik Altunoglu: Writing – review & editing, Writing – original draft, Project administration, Investigation. Mustafa Ocal: Writing – review & editing, Methodology, Investigation. Mehmet Cengiz Baloglu: Writing – review & editing, Validation, Investigation. Alsideeq Abdulsalam Ahmed Aboujanah: Methodology, Investigation. Erdoğan Horuz: Methodology, Investigation. E.J. Llorent-Martínez: Methodology, Investigation. Abdullahi Ibrahim Uba: Methodology, Investigation. Irina Lazarova: Methodology, Investigation. Gökhan Zengin: Writing – review & editing, Writing – original draft, Investigation. Kerim Güney: Investigation, Validation.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: This research has been supported by Kastamonu University Scientific Research Projects Coordination Department (grant number: KÜ-BAP01/2021-29 and KÜ-HIZDES 2018-09).

  7. Data availability: The raw data can be obtained on request from the corresponding author.

References

1. RL Siegel, KD Miller, NS Wagle, A Jemal. Cancer statistics. CA Cancer J Clin 2023;73:17–48. https://doi.org/10.3322/caac.21763.Search in Google Scholar PubMed

2. Giaquinto, AN, Sung, H, Miller, KD, Kramer, JL, Newman, LA, Minihan, A, et al.. Breast-cancer statistics, 2022. CA Cancer J Clin 2022;72:524–41. https://doi.org/10.3322/caac.21754.Search in Google Scholar PubMed

3. Shrihastini, V, Muthuramalingam, P, Adarshan, S, Sujitha, M, Chen, JT, Shin, H, et al.. Plant-derived bioactive compounds as alternative strategies for breast-cancer treatment: an updated overview. Cancers 2021;13:6222. https://doi.org/10.3390/cancers13246222.Search in Google Scholar PubMed PubMed Central

4. Pan, SY, Zhou, SF, Gao, SH, Yu, ZL, Zhang, SF, Tang, MK, et al.. New perspectives on how to discover drugs from herbal medicines: CAM’s outstanding contribution to modern therapeutics. Evid Based Complement Alternat Med 2013;2013:627375. https://doi.org/10.1155/2013/627375.Search in Google Scholar PubMed PubMed Central

5. Laskar, YB, Lourembam, RM, Mazumder, PB. Herbal remedies for breast-cancer prevention and treatment. In: Laskar, YB, Lourembam, RM, Mazumder, PB, editors. Medicinal Plants—Use in Prevention and Treatment of Diseases. London: InTechOpen; 2020. Chap. 3.Search in Google Scholar

6. Baloğlu, MC, Yıldız Özer, L, Pirci, B, Zengin, G, Uba, AI, Çelik Altunoğlu, Y, et al.. Evaluation of the potential therapeutic properties of Liquidambar orientalis oil. Chembiochem 2023;20:e202300291. https://doi.org/10.1002/cbdv.202300291.Search in Google Scholar PubMed

7. Çelik Altunoğlu, Y, Can, TH, Tufekci, EF, Altunoglu, BD, Baloğlu, MC, Llorent-Martínez, EJ, et al.. Comprehensive approaches on chemical composition and biological properties of Daphne pontica L. extracts. Plant Biosyst 2022;156:116–29. https://doi.org/10.1080/11263504.2020.1837282.Search in Google Scholar

8. Yerlikaya, S, Baloğlu, MC, Çelik Altunoğlu, Y, Diuzheva, A, Jekő, J, Cziáky, Z, et al.. Exploring of Coronilla varia extracts as a source of high-value natural agents: chemical profiles and biological connections. South Afr J Bot 2021;143:382–92. https://doi.org/10.1016/j.sajb.2021.02.025.Search in Google Scholar

9. Can, TH, Tufekci, EF, Altunoglu, YC, Baloğlu, MC, Llorent-Martínez, EJ, Stefanucci, A, et al.. Chemical characterization, computational analysis and biological views on Daphne gnidioides jaub. & spach extracts. Comput Biol Chem 2020;87:107273. https://doi.org/10.1016/j.compbiolchem.2020.107273.Search in Google Scholar PubMed

10. Mahomoodally, MF, Ugurlu, A, Llorent-Martínez, EJ, Nagamootoo, M, Picot-Allain, MCN, Baloğlu, MC, et al.. Syzygium coriaceum potentiates conventional antibiotics, inhibits clinical enzymes and induces apoptosis in breast-cancer cells. Ind Crops Prod 2020;143:111948. https://doi.org/10.1016/j.indcrop.2019.111948.Search in Google Scholar

11. Mahomoodally, MF, Picot-Allain, C, Hosenally, M, Ugurlu, A, Mollica, A, Stefanucci, A, et al.. Multi-targeted potential of Pittosporum senacia: HPLC-ESI-MSn analysis, in silico docking, DNA protection, antimicrobial, enzyme-inhibition, anticancer and apoptotic activity. Comput Biol Chem 2019;83:107114. https://doi.org/10.1016/j.compbiolchem.2019.107114.Search in Google Scholar PubMed

12. Yerlikaya, S, Baloğlu, MC, Diuzheva, A, Jekő, J, Cziáky, Z, Zengin, G, et al.. Investigation of chemical profile, biological properties of Lotus corniculatus extracts and apoptotic-autophagic effects on breast-cancer cells. J Pharm Biomed Anal 2019;174:286–99. https://doi.org/10.1016/j.jpba.2019.05.068.Search in Google Scholar PubMed

13. Zengin, G, Uğurlu, A, Baloğlu, MC, Diuzheva, A, Jekő, J, Cziáky, Z, et al.. Chemical fingerprints, antioxidant, enzyme-inhibitory and cell assays of three extracts from Sideritis ozturkii. J Pharm Biomed Anal 2019;171:118–25. https://doi.org/10.1016/j.jpba.2019.04.011.Search in Google Scholar PubMed

14. Mahomoodally, MF, Yerlikaya, S, Llorent-Martínez, EJ, Uğurlu, A, Baloğlu, MC, Çelik Altunoğlu, Y, et al.. Pharmacological and polyphenolic profiles of Phyllanthus phillyreifolius var. commersonii. Food Res Int 2019;115:425–38. https://doi.org/10.1016/j.foodres.2018.10.075.Search in Google Scholar PubMed

15. Locatelli, M, Yerlikaya, S, Baloğlu, MC, Zengin, G, Çelik Altunoğlu, Y, Cacciagrano, F, et al.. Therapeutic potential of Asphodeline liburnica roots: in vitro and in silico biochemical and toxicological perspectives. Food Chem Toxicol 2018;120:172–82. https://doi.org/10.1016/j.fct.2018.07.012.Search in Google Scholar PubMed

16. Hernández, V, Recio, MC, Máñez, S, Giner, RM, Ríos, JL. Effects of naturally occurring dihydroflavonols from Inula viscosa on inflammation and enzymes involved in arachidonic-acid metabolism. Life Sci 2007;81:480–8. https://doi.org/10.1016/j.lfs.2007.06.006.Search in Google Scholar PubMed

17. Talib, WH, Al-Zarga, MH, Mahasneh, AM. Antiproliferative, antimicrobial and apoptosis-inducing effects of compounds isolated from Inula viscosa. Molecules 2012;17:3291–303. https://doi.org/10.3390/molecules17033291.Search in Google Scholar PubMed PubMed Central

18. Rechek, H, Haouat, A, Hamaidia, K, Pinto, DCGA, Boudiar, T, Válega, MSGA, et al.. Inula viscosa (L.) aiton ethanolic extract inhibits the growth of human AGS and A549 cancer cell lines. Chem Biodivers 2023;20:e202200890. https://doi.org/10.1002/cbdv.202200890.Search in Google Scholar PubMed

19. Apaydın Yıldırım, B, Gedikli, S, Kordali, S, Küçükaydin, S. Apoptotic and antiproliferative effects of Inula viscosa L. water extract in the expression of microRNAs on HCT 116 cell line: an in vitro study. Int J Environ Health Res 2023;34:1076–87. https://doi.org/10.1080/09603123.2023.2197641.Search in Google Scholar PubMed

20. Migheli, R, Virdis, P, Galleri, G, Arru, C, Lostia, G, Coradduzza, D, et al.. Antineoplastic properties of Inula viscosa and its sesquiterpene lactones tomentosin and inuviscolide. Biomedicines 2022;10:2739. https://doi.org/10.3390/biomedicines10112739.Search in Google Scholar PubMed PubMed Central

21. El Yaagoubi, OM, Lahmadi, A, Bouyahya, A, Filali, H, Samaki, H, El Antri, S, et al.. Antitumor effect of Inula viscosa extracts on DMBA-induced skin carcinoma are mediated by proteasome inhibition. BioMed Res Int 2021;2021:6687589. https://doi.org/10.1155/2021/6687589.Search in Google Scholar PubMed PubMed Central

22. Colak, DK, Egeli, U, Eryilmaz, IE, Aybastier, O, Malyer, H, Cecener, G, et al.. The anticancer effect of Inula viscosa methanol extract by miRNAs’ re-regulation: an in vitro study on human malignant melanoma cells. Nutr Cancer 2021;74:211–24. https://doi.org/10.1080/01635581.2020.1869791.Search in Google Scholar PubMed

23. P Virdis, R Migheli, G Galleri, S Fancello, MPL Cadoni, G Pintore, et al.. Antiproliferative and pro-apoptotic effects of Inula viscosa extract on a Burkitt-lymphoma cell line. Tumor Biol. 2020;42:1010428319901. https://doi.org/10.1177/1010428319901.Search in Google Scholar

24. Ozkan, E, Karakaş, FP, Yıldırım, AB, Taş, İ, Eker, İ, Yavuz, MZ, et al.. Inula viscosa: antiproliferative, antioxidant, antibacterial activities and phenolic profile. Prog Nutr 2019;21:652–61. https://doi.org/10.23751/pn.v21i3.7186.Search in Google Scholar

25. Bar-Shalom, R, Bergman, M, Grossman, S, Azzam, N, Sharvit, L, Fares, F, et al.. Inula viscosa extract inhibits growth of colorectal cancer cells in Vitro and in Vivo through induction of apoptosis. Front Oncol 2019;9:227. https://doi.org/10.3389/fonc.2019.00227.Search in Google Scholar PubMed PubMed Central

26. Merghouba, N, El Btaouri, H, Benbacerc, L, Gmouhd, S, Trentesaux, C, Brassart, B, et al.. Inula viscosa extracts induce telomere shortening and apoptosis in cancer cells and overcome drug resistance. Nutr Cancer 2016;68:131–43. https://doi.org/10.1080/01635581.2016.1115105.Search in Google Scholar PubMed

27. Messaoudi, M, Chahmi, N, El Mzibri, M, Gmouh, S, Amzazi, S, Benbacer, L, et al.. Cytotoxic effect and chemical composition of Inula viscosa from three different regions of Morocco. Eur J Med Plants 2016;16:1–9. https://doi.org/10.9734/EJMP/2016/28340.Search in Google Scholar

28. Benbacer, L, Merghoub, N, El Btaouri, H, Gmouh, S, Attaleb, M, Morjani, H, et al.. Antiproliferative effect and induction of apoptosis by Inula viscosa L. and Retama monosperma L. extracts in human cervical cancer cells” in topics on cervical cancer with an advocacy for prevention. Intech 2012:1–14.10.5772/30025Search in Google Scholar PubMed

29. Rozenblat, S, Grossman, S, Bergman, M, Gottlieb, H, Cohen, Y, Dovrat, S, et al.. Induction of G2/M arrest and apoptosis by sesquiterpene lactones in human melanoma cell lines. Biochem Pharmacol 2008;75:369–82. https://doi.org/10.1016/j.bcp.2007.08.024.Search in Google Scholar PubMed

30. Kheyar-Kraouche, N, da Silva, AB, Serra, AT, Bedjou, F, Bronze, MR. Characterization by liquid chromatography–mass spectrometry and antioxidant activity of an ethanolic extract of Inula viscosa leaves. J Pharm Biomed Anal 2018;156:297–306. https://doi.org/10.1016/j.jpba.2018.04.047.Search in Google Scholar PubMed

31. Simirgiotis, MJ. Antioxidant capacity and HPLC-DAD-MS profiling of Chilean peumo (Cryptocarya alba) fruits and comparison with German peumo (Crataegus monogyna) from southern Chile. Molecules 2013;18:2061–80. https://doi.org/10.3390/molecules18022061.Search in Google Scholar PubMed PubMed Central

32. Clifford, MN, Knight, S, Kuhnert, N. Discriminating between the six isomers of dicaffeoylquinic acid by LC-MSn. J Agric Food Chem 2005;53:3821–32. https://doi.org/10.1021/jf050046h.Search in Google Scholar PubMed

33. Iqbal, MJ, Kabeer, A, Abbas, Z, Siddiqui, HA, Calina, D, Sharifi-Rad, J, et al.. Interplay of oxidative stress, cellular communication and signaling pathways in cancer. Cell Commun Signal 2024;22:7. https://doi.org/10.1186/s12964-023-01398-5.Search in Google Scholar PubMed PubMed Central

34. Kotha, RR, Tareq, FS, Yildiz, E, Luthria, DL. Oxidative stress and antioxidants – A critical review on in Vitro antioxidant assays. Antioxidants 2022;11:2388. https://doi.org/10.3390/antiox11122388.Search in Google Scholar PubMed PubMed Central

35. Danino, O, Gottlieb, EH, Grossman, S, Bergman, M. Antioxidant activity of 1,3-dicaffeoylquinic acid isolated from Inula viscosa. Food Res Int 2009;42:1273–80. https://doi.org/10.1016/j.foodres.2009.03.023.Search in Google Scholar

36. Iwai, K, Kishimoto, N, Kakino, Y, Mochida, K, Fujita, T. In vitro antioxidative effects and tyrosinase inhibitory activities of seven hydroxycinnamoyl derivatives in green coffee beans. J Agric Food Chem 2004;52:4893–8. https://doi.org/10.1021/jf040048m.Search in Google Scholar PubMed

37. Magaña, A, Kamimura, N, Soumyanath, A, Stevens, JF, Maier, CS. Caffeoylquinic acids: chemistry, biosynthesis, occurrence, analytical challenges, and bioactivity. Plant J 2021;107:1299–319. https://doi.org/10.1111/tpj.15390.Search in Google Scholar PubMed PubMed Central

38. Islam, S, Adam, Z, Akanda, JH. Quinic and caffeic acids derivatives: affecting antioxidant capacities and phenolics contents of certain therapeutic and specialty crops employing water and ethanolic extracts. Food Chem Adv 2024;4:100693. https://doi.org/10.1016/j.focha.2024.100693.Search in Google Scholar

39. Khan, AL, Khan, H, Hussain, J, Adnan, M, Hussain, I, Khan, T, et al.. Sesquiterpenes: the potent antioxidants. Pak J Sci Ind Res 2008;51:343–50.Search in Google Scholar

40. Mouas, TN, Kabouche, Z, Kabouche, A, Khaoula, G, Racha, B. Assessment on α-isocostic acid involvement in the biological activities of Inula viscosa aerial and roots parts. Mater Today Proc 2021;49:976–80. https://doi.org/10.1016/j.matpr.2021.08.102.Search in Google Scholar

41. Lam, TP, Tran, NVN, Pham, LHD, Lai, NVT, Dang, BTN, Truong, NLN, et al.. Flavonoids as dual-target inhibitors against α-glucosidase and α-amylase: a systematic review of in vitro studies. Nat. Prod. Bioprospect. 2024;14:4. https://doi.org/10.1007/s13659-023-00424-w.Search in Google Scholar PubMed PubMed Central

42. Crozier, A, Clifford, MN, Ashihara, H, editors. Plant Secondary Metabolites: Occurrence, Structure and Role in the Human Diet. Oxford: Blackwell Publishing; 2006:208–302 pp.10.1002/9780470988558.ch7Search in Google Scholar

43. Duong, TH, Nguyen, HT, Nguyen, CH, Tran, NMA, Danova, A, Tran, TMD, et al.. Identification of highly potent α-glucosidase inhibitors from Artocarpus integer and molecular-docking studies. Chem Biodivers 2021;18:e2100499. https://doi.org/10.1002/cbdv.202100499.Search in Google Scholar PubMed

44. Quan, YS, Zhang, XY, Yin, XM, Wang, SH, Jin, LL. Potential α-glucosidase inhibitor from Hylotelephium erythrostictum. Bioorg Med Chem Lett 2020;30:127665. https://doi.org/10.1016/j.bmcl.2020.127665.Search in Google Scholar PubMed

45. Zhou, Y, Jiang, Q, Ma, S, Zhou, X. Effect of quercetin on in the vitro tartary-buckwheat starch digestibility. Int J Biol Macromol 2021;183:818–30. https://doi.org/10.1016/j.ijbiomac.2021.05.013.Search in Google Scholar PubMed

46. Kashchenko, NI, Chirikova, NK, Olennikov, DN. Acylated flavonoids from Spiraea genus as inhibitors of α-amylase. Russ J Bioorg Chem 2018;44:876–86. https://doi.org/10.1134/S1068162018070051.Search in Google Scholar

47. NK Vu, CS Kim, MT Ha, QT Ngo, SE Park, H Kwon, et al.. Antioxidant and antidiabetic activities of flavonoid derivatives from the outer skins of Allium cepa L. J Agric Food Chem 2020;68:8797–811. https://doi.org/10.1021/acs.jafc.0c02122.Search in Google Scholar PubMed

48. N Cichon, W Grabowska, L Gorniak, M Stela, P Harmata, M Ceremuga, et al.. Mechanistic and therapeutic insights into flavonoid-based inhibition of acetylcholinesterase: implications for neurodegenerative diseases. Nutrients 2024;17:78. https://doi.org/10.3390/nu17010078.Search in Google Scholar PubMed PubMed Central

49. MA Islam, S Zaman, K Biswas, MY Al-Amin, MK Hasan, AHMK Alam, et al.. Evaluation of cholinesterase-inhibitory and antioxidant activity of Wedelia chinensis and isolation of apigenin as an active compound. BMC Complement Med Ther 2021;21:204. https://doi.org/10.1186/s12906-021-03373-4.Search in Google Scholar PubMed PubMed Central

50. V Rathi, SSK Sagi, AK Yadav, M Kumar, R Varshney. Quercetin prophylaxis protects the kidneys by modulating the renin–angiotensin–aldosterone axis under acute hypobaric-hypoxic stress. Sci Rep 2024;14;7617. https://doi.org/10.1038/s41598-024-58134-3.Search in Google Scholar PubMed PubMed Central

51. N Cichon, J Saluk-Bijak, E Miller, L Gorniak, J Redlicka, M Niwald, et al.. The role of supplementation with natural compounds in post-stroke patients. Int J Mol Sci 2021;22:7893. https://doi.org/10.3390/ijms22157893.Search in Google Scholar PubMed PubMed Central

52. HAS El-Nashar, MIG El-Din, L Hritcu, OA Eldahshan. Insights on the inhibitory power of flavonoids on tyrosinase activity: a survey from 2016 to 2021. Molecules 2021;26:7546. https://doi.org/10.3390/molecules26247546.Search in Google Scholar PubMed PubMed Central

53. V Jacob, T Hagai, K Soliman. Structure–activity relationships of flavonoids. Curr Org Chem 2011;15:2641–57. https://doi.org/10.2174/138527211796367309.Search in Google Scholar

54. M Fan, G Zhang, X Hu, X Xu, D Gong. Quercetin as a tyrosinase inhibitor: inhibitory activity, conformational change and mechanism. Food Res Int 2017;100:226–33. https://doi.org/10.1016/j.foodres.2017.07.010.Search in Google Scholar PubMed

55. YH Choi, JY Lee, JE Lee, YW Jung, W Jeong, SS Hong, et al.. Skin-related properties and constituents from the aerial parts extract of Persicaria senticosa. Oxid Med Cell Longev 2020;2020. Article ID 6627752. https://doi.org/10.1155/2020/6627752.Search in Google Scholar PubMed PubMed Central

56. D Lee, HD Lee, H Kwon, HL Lee, GS Hwang, S Choi, et al.. Insulin secretion and α-glucosidase-inhibitory effects of dicaffeoylquinic-acid derivatives. Appl Biol Chem 2022;65:22. https://doi.org/10.1186/s13765-022-00688-9.Search in Google Scholar

57. Aydın, T, Sağlamtaş, R, Doğan, B, Köstekci, E, Durmuş, R, Çakır, A, et al.. A new specific method for isolation of tomentosin with a high yield from Inula viscosa (L.) and determination of its bioactivities. Phytochem Anal 2022;33:612–18. https://doi.org/10.1002/pca.3114.Search in Google Scholar PubMed

58. Talebi, M, Khoramjouy, M, Feizi, A, Ali, Z, Khan, IA, Ayatollahi, NA, et al.. Multi-target therapeutic potential of the genus Inula: advances and opportunities for neuroprotection. Pharmacol Res Mod Chin Med 2023;7:100263. https://doi.org/10.1016/j.prmcm.2023.100263.Search in Google Scholar

59. Choo, SJ, Ryoo, IJ, Kim, KC, Na, M, Jang, JH, Ahn, JS, et al.. Hypo-pigmenting effect of sesquiterpenes from Inula britannica in B16 melanoma cells. Arch Pharm Res (Seoul) 2014;37:567–74. https://doi.org/10.1007/s12272-013-0302-4.Search in Google Scholar PubMed

60. Lin, G, Gao, S, Cheng, J, Li, Y, Shan, L, Hu, Z, et al.. 1β-Hydroxyalantolactone, a sesquiterpene lactone from Inula japonica, attenuates atopic-dermatitis-like skin lesions induced by 2,4-dinitrochlorobenzene in mouse. Pharm Biol 2016;54:516–22. https://doi.org/10.3109/13880209.2015.1050745.Search in Google Scholar PubMed

61. Colovic, MB, Krstic, DZ, Lazarevic-Pasti, TD, Bondzic, AM, Vasic, VM. Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol 2013;11:315–35. https://doi.org/10.2174/1570159X11311030006.Search in Google Scholar PubMed PubMed Central

62. Giacobini, E. Cholinesterase inhibitors: new roles and therapeutic alternatives. Pharmacol Res 2004;50:433–40. https://doi.org/10.1016/j.phrs.2003.11.017.Search in Google Scholar PubMed

63. Briganti, S, Camera, E, Picardo, M. Chemical and instrumental approaches to treat hyperpigmentation. Pigment Cell Res 2003;16:101–10. https://doi.org/10.1034/j.1600-0749.2003.00029.x.Search in Google Scholar PubMed

64. Tundis, R, Loizzo, MR, Menichini, F. Natural products as α-amylase and α-glucosidase inhibitors and their hypoglycaemic potential in diabetes treatment: an update. Mini Rev Med Chem 2010;10:315–31. https://doi.org/10.2174/138955710791331007.Search in Google Scholar PubMed

65. Cory, S, Adams, JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2002;2:647–56. https://doi.org/10.1038/nrc883.Search in Google Scholar PubMed

66. Saxena, A, Fedorko, JM, Vinayaka, CR, Medhekar, R, Radic, Z, Taylor, P, et al.. Aromatic amino-acid residues at the active and peripheral anionic sites control the binding of E2020 (aricept®) to cholinesterases. Eur J Biochem 2003;270:4447–58. https://doi.org/10.1046/j.1432-1033.2003.03837.x.Search in Google Scholar PubMed

67. Sepehri, N, Khoshneviszadeh, M, Moghadam-Farid, S, Moayedi, SS, Asgari, MS, Moazzam, A, et al.. Design, synthesis, biological evaluation and molecular-docking study of thioxo-2,3-dihydroquinazolinone derivatives as tyrosinase inhibitors. J Mol Struct 2022;1253:132283. https://doi.org/10.1016/j.molstruc.2021.132283.Search in Google Scholar

68. Elks, J, Ganellin, CR. Dictionary of drugs. London: Chapman & Hall; 1990, 2.10.1007/978-1-4757-2085-3Search in Google Scholar

69. Verma, S, Singh, A, Kumari, A, Tyagi, C, Goyal, S, Jamal, S, et al.. Natural polyphenolic inhibitors against the anti-apoptotic BCL-2. J Recept Signal Transduction 2017;37:391–400. https://doi.org/10.1080/10799893.2017.1298129.Search in Google Scholar PubMed

70. Mohti, H, Taviano, MF, Cacciola, F, Dugo, P, Mondello, L, Marino, A, et al.. Inula viscosa (L.) aiton leaves and flower buds: effect ofextraction solvent/technique on their antioxidant ability,antimicrobial properties and phenolic profile. Nat Prod Res 2020;34:46–52. https://doi.org/10.1080/14786419.2019.1569659.Search in Google Scholar PubMed

71. Lamine, BM, Amina, K, Nacera, M, Zohra, EF, Zouaoui, B, Bouziane, A, et al.. Antibacterial activity of essential oils of Inula viscosa against some multiresistant Pseudomonas aeruginosa ATCC 27853 and Staphylococcus aureus ATCC 25923. Egypt Acad J Biol Sci C 2022;14:399–407. https://doi.org/10.21608/eajbsc.2022.236997.Search in Google Scholar

72. Najefi, RB, Asghari, G, Abbas, A. Antimicrobial activities of phenolic and non-phenolic fractions of Inula viscosa (L) extract. J Biol Act Prod Nat 2011;1:325–31. https://doi.org/10.1080/22311866.2011.10719100.Search in Google Scholar

73. Sevgi, E, Dağ, A, Kızılarslan-Hançer, Ç, Atasoy, S, Kurt, BZ, Aksakal, Ö, et al.. Evaluation of cytotoxic and antioxidant potential of Dittrichia viscosa (L.) greuter used in traditional medicine. J Ethnopharmacol 2021;276:114211. https://doi.org/10.1016/j.jep.2021.114211.Search in Google Scholar PubMed

74. Hepokur, C, Budak, Y, Karayel, HB, Selvi, B, Yaylım, İ. Investigation of cytotoxic effects of Inula viscosa extract. Cumhuriyet Sci J 2019;40:578–82. https://doi.org/10.17776/csj.437993.Search in Google Scholar

75. Tepe, HD, Uğurlu, A, Yazgan, İ. Determination of phenolic compounds, organic-volatile molecules and anticancer properties in Inula viscosa, viscum album and raphanus sativus. Sakarya Univ J Sci 2021;25:647–62. https://doi.org/10.16984/saufenbilder.742432.Search in Google Scholar

76. Erdal, B, Yılmaz, B, Baylan, B. Investigation of the antibacterial and anticarcinogenic effects of Inula viscosa methanol and hexane extracts. Turkish Bull Hyg Exp Biol 2022;79:133–44. https://doi.org/10.5505/TurkHijyen.2022.55798.Search in Google Scholar

77. Jafari, N, Zargar, SJ, Delnavazi, MR, Yassa, N. Cell-cycle arrest and apoptosis induction of phloroacetophenone glycosides and caffeoylquinic-acid derivatives in gastric adenocarcinoma (AGS) cells. Anti Cancer Agents Med Chem 2018;18:610–16. https://doi.org/10.2174/1871520618666171219121449.Search in Google Scholar PubMed

78. Palmioli, A, Ciaramelli, C, Tisi, R, Spinelli, M, De Sanctis, G, Sacco, E, et al.. Natural compounds in cancer prevention: effects of coffee extracts and their main polyphenolic component, 5-O-caffeoylquinic acid, on oncogenic ras proteins. Chem Asian J 2017;12:2457–66. https://doi.org/10.1002/asia.201700844.Search in Google Scholar PubMed

79. In, JK, Kim, JK, Oh, JS, Seo, DW. 5-Caffeoylquinic acid inhibits invasion of non-small-cell lung-cancer cells through inactivation of p70S6K and akt: involvement of p53 in differential regulation of signaling pathways. Int J Oncol 2016;48:1907–12. https://doi.org/10.3892/ijo.2016.3436.Search in Google Scholar PubMed

80. Suberu, JO, Romero-Canelón, I, Sullivan, N, Lapkin, AA, Barker, GC. Comparative cytotoxicity of artemisinin and cisplatin and their interactions with chlorogenic acids in MCF-7 breast-cancer cells. ChemMedChem 2014;9:2791–7. https://doi.org/10.1002/cmdc.201402285.Search in Google Scholar PubMed PubMed Central

81. Albrecht, C, Cittadini, MC, Soria, EA. Pharmacological activity of quercetin and 5-caffeoylquinic acid oral intake in male Balb/c mice with lung adenocarcinoma. Arch Med Res 2020;51:8–12. https://doi.org/10.1016/j.arcmed.2019.11.006.Search in Google Scholar PubMed

82. Wu, Q, Kroon, PA, Shao, H, Needs, PW, Yang, X. Differential effects of quercetin and two derivatives, isorhamnetin and isorhamnetin-3-glucuronide, on proliferation of human breast-cancer MCF-7 cells. J Agric Food Chem 2018;66:7181–9. https://doi.org/10.1021/acs.jafc.8b02420.Search in Google Scholar PubMed

83. Sharmila, G, Bhat, FA, Arunkumar, R, Elumalai, P, Singh, PR, Senthilkumar, K, et al.. Chemopreventive effect of quercetin , a natural dietary flavonoid on prostate cancer in in vivo model. Clin Nutr 2014;33:718–26. https://doi.org/10.1016/j.clnu.2013.08.011.Search in Google Scholar PubMed

84. Maurya, AK, Vinayak, M. Anticarcinogenic action of quercetin by downregulation of phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) via induction of p53 in hepatocellular carcinoma (HepG2) cell line. Mol Biol Rep 2015;42:1419–29. https://doi.org/10.1007/s11033-015-3921-7.Search in Google Scholar PubMed

85. Antunes-Ricardo, M, Moreno-García, BE, Gutiérrez-Uribe, JA, Aráiz-Hernández, D, Alvarez, MM, Serna-Saldivar, SO, et al.. Induction of apoptosis in colon cancer cells treated with isorhamnetin glycosides from Opuntia ficus-indica pads. Plant Foods Hum Nutr 2014;69:331–6. https://doi.org/10.1007/s11130-014-0438-5.Search in Google Scholar PubMed

86. Bishayee, K, Ghosh, S, Mukherjee, A, Sadhukhan, R, Mondal, J, Khuda-Bukhsh, AR, et al.. Quercetin induces cytochrome-c release and ROS accumulation to promote apoptosis and arrest the cell cycle in G2/M, in cervical carcinoma: signal cascade and drug-DNA interaction. Cell Prolif 2013;46:153–63. https://doi.org/10.1111/cpr.12017.Search in Google Scholar PubMed PubMed Central

87. Kheyar-Kraouche, N, Boucheffa, S, Bellik, Y, Farida, K, Brahmi-Chendouh, N. Exploring the potential of Inula viscosa extracts for antioxidant, antiproliferative and apoptotic effects on human liver-cancer cells and a molecular-docking study. Biotechnologia 2023;104:183–98. https://doi.org/10.5114/bta.2023.127207.Search in Google Scholar PubMed PubMed Central

88. Das, S, Shukla, N, Singh, SS, Kushwaha, S, Shrivastava, R. Mechanism of interaction between autophagy and apoptosis in cancer. Apoptosis 2021;26:512–33. https://doi.org/10.1007/s10495-021-01687-9.Search in Google Scholar PubMed

89. Llorent-Martínez, EJ, Zengin, G, Lobine, D, Molina-García, L, Mollica, A, Mahomoodally, MF, et al.. Phytochemical characterization, in vitro and in silico approaches for three hypericum species. New J Chem 2018;42:5204–14. https://doi.org/10.1039/C8NJ00347E.Search in Google Scholar

90. Grochowski, DM, Uysal, S, Aktumsek, A, Granica, S, Zengin, G, Ceylan, R, et al.. In vitro enzyme inhibitory properties, antioxidant activities, and phytochemical profile of Potentilla thuringiaca. Phytochem Lett 2017;20:365–72. https://doi.org/10.1016/j.phytol.2017.03.005.Search in Google Scholar

91. Slinkard, K, Singleton, VL. Total phenol analysis: automation and comparison with manual methods. Am J Enol Vitic 1977;28:49–55. https://doi.org/10.5344/ajev.1977.28.1.49.Search in Google Scholar

92. Kurumbail, RG, Stevens, AM, Gierse, JK, McDonald, JJ, Stegeman, RA, Pak, JY, et al.. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature 1996;384:644–8. https://doi.org/10.1038/384644a0.Search in Google Scholar PubMed

93. Dileep, KV, Ihara, K, Yonemochi, M, Mishima-Tsumagari, C, Hanada, K, Kukimoto-Niino, M, et al.. Crystal structure of human acetylcholinesterase in complex with tacrine : implications for drug discovery. Int J Biol Macromol 2022;210:172–81. https://doi.org/10.1016/j.ijbiomac.2022.05.009.Search in Google Scholar PubMed

94. Ielo, L, Deri, B, Germano, MP, Vittorio, S, Mirabile, S, Gitto, R, et al.. Exploiting the 1-(4-fluorobenzyl)piperazine fragment for the development of novel tyrosinase inhibitors as anti-melanogenic agents: design, synthesis, structural insights and biological profile. Eur J Med Chem 2019;178:380–9. https://doi.org/10.1016/j.ejmech.2019.06.019.Search in Google Scholar PubMed

95. Knez, D, Diez-Iriepa, D, Chioua, M, Gottinger, A, Denic, M, Chantegreil, F, et al.. 8-Hydroxyquinolylnitrones as multifunctional ligands for the therapy of neurodegenerative diseases. Acta Pharm Sin B 2023;13:2152–75. https://doi.org/10.1016/j.apsb.2023.01.013.Search in Google Scholar PubMed PubMed Central

96. Nahoum, V, Roux, G, Anton, V, Rougé, P, Puigserver, A, Bischoff, H, et al.. Crystal structures of human pancreatic α-amylase in complex with carbohydrate and proteinaceous inhibitors. Biochem J 2000;346:201–8. https://doi.org/10.1042/bj3460201.Search in Google Scholar

97. Souers, AJ, Leverson, JD, Boghaert, ER, Ackler, SL, Catron, ND, Chen, J, et al.. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med 2013;19:202–8. https://doi.org/10.1038/nm.3048.Search in Google Scholar PubMed

98. Omer, HAA, Caprioli, G, Abouelenein, D, Mustafa, AM, Uba, AI, Ak, G, et al.. Phenolic profile, antioxidant and enzyme inhibitory activities of leaves from two cassia and two senna species. Molecules 2022;27:5590. https://doi.org/10.3390/molecules27175590.Search in Google Scholar PubMed PubMed Central

99. Martínez-Rosell, G, Giorgino, T, De Fabritiis, G. PlayMolecule ProteinPrepare: a web application for protein preparation for molecular dynamics simulations. J Chem Inf Model 2017;57:1511–16. https://doi.org/10.1021/acs.jcim.7b00190.Search in Google Scholar PubMed

100. Pettersen, EF, Goddard, TD, Huang, CC, Couch, GS, Greenblatt, DM, Meng, EC, et al.. UCSF Chimera – A visualization system for exploratory research and analysis. J Comput Chem 2004;25:1605–12. https://doi.org/10.1002/jcc.20084.Search in Google Scholar PubMed

101. Morris, GM, Huey, R, Lindstrom, W, Sanner, MF, Belew, RK, Goodsell, DS, et al.. AutoDock4 and AutoDockTools4: automated docking with flexible receptors. J Comput Chem 2009;30:2785–91. https://doi.org/10.1002/jcc.21256.Search in Google Scholar PubMed PubMed Central

Received: 2025-08-21
Accepted: 2025-10-06
Published Online: 2025-10-20

© 2025 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 14.11.2025 from https://www.degruyterbrill.com/document/doi/10.1515/znc-2025-0189/html
Scroll to top button