Plants of genus Ononis belong to family Fabaceae and are distributed in Europe, Atlantic Islands, West Asia, and North Africa and more than 75 species in the genus have been identified worldwide. Previous phytochemical studies showed a diversity of bioactive constituents, specifically flavonoids and isoflavonoids, that have been responsible for the different actions exerted by plants of this genus. This study represents a comprehensive review of all data present in literature related to the phenolic constituents isolated from Ononis plants and their pharmacological activities. The study revealed also the essential structure-activity relationship of Ononis compounds and briefly highlighted some toxicity studies. Data was collected by searching journals, books, periodicals, and databases. The results demonstrated a wide variety of flavonoids and isoflavonoids, isocoumarins, and resorcinols reported from different Ononis species. Flavonoidal compounds were the main constituents responsible for the various pharmacological activities such as antioxidant, anti-inflammatory, antimicrobial, cytotoxic, enzyme inhibitory, and antidiabetic effects. The reason behind these activities was mainly the degree and position of hydroxylation and methoxylation on the flavonoids’ rings. The findings of this study suggest Ononis plants and/or their components are promising candidates for treatment of wide range of ailments as a preventive measure or in combination with conventional therapies. Further studies would be required to describe the detailed mechanistic pathways for promising compounds and their clinical applications.
Chouman A, El-lakany A, Aboul-ela M, Ali Hijazi M. Review on phenolic constituents and pharmacological activities of genus Ononis. J Appl Pharm Sci. 2025. Online First. http://doi.org/10.7324/JAPS.2025.234398
1. Tekdal D. Plant genes for abiotic stress in legumes. Abiotic Stress and Legumes. Singh VP, Singh S, Tripathi DK, Prasad SM, Bhardwaj R, Chauhan DK, editors. Academic Press; 2021. Pp 291-301. https://doi.org/10.1016/B978-0-12-815355-0.00015-1 | |
2. Gao T, Yao H, Song J, Liu C, Zhu Y, Ma X, et al. Identification of medicinal plants in the family Fabaceae using a potential DNA barcode ITS2. J Ethnopharmacol. 2010;130(1):116-21. https://doi.org/10.1016/j.jep.2010.04.026 | |
3. Xu Z, Deng M, Xu Z, Deng M. Fabaceae or Leguminosae. Identification and Control of Common Weeds. Vol. 2. 2017. Pp 547- 615. https://doi.org/10.1007/978-94-024-1157-7_43 | |
4. Maroyi A. Medicinal uses of the Fabaceae family in Zimbabwe: a review. Plants. 2023;12(6):1255. https://doi.org/10.3390/plants12061255 | |
5. Öz BE, ??can GS, Akkol EK, Süntar ?, Kele? H, Ac?kara ÖB. Wound healing and anti-inflammatory activity of some Ononis taxons. Biomedicine Pharmacother. 2017;91:1096-105. https://doi.org/10.1016/j.biopha.2017.05.040 | |
6. Mhamdi B, Abbassi F, Abdelly C. Chemical composition, antioxidant and antimicrobial activities of the edible medicinal Ononis natrix growing wild in Tunisia. Nat Prod Res. 2015;29(12):1157-60. https://doi.org/10.1080/14786419.2014.981188 | |
7. Mezrag A, Malafronte N, Bouheroum M, Travaglino C, Russo D, Milella L, et al. Phytochemical and antioxidant activity studies on Ononis angustissima L. aerial parts: isolation of two new flavonoids. Nat Prod Res. 2017;31(5):507-14. https://doi.org/10.1080/14786419.2016.1195381 | |
8. Ghribi L, Waffo-Téguo P, Cluzet S, Marchal A, Marques J, Mérillon JM, et al. Isolation and structure elucidation of bioactive compounds from the roots of the Tunisian Ononis angustissima L. Bioorgan Med Chem Lett. 2015;25(18):3825-30. https://doi.org/10.1016/j.bmcl.2015.07.076 | |
9. Al-Snafi AE. The traditional uses, constituents and pharmacological effects of Ononis spinosa. IOSR J Pharm. 2020;10(2):53-9. | |
10. Ullah A, Munir S, Badshah SL, Khan N, Ghani L, Poulson BG, et al. Important flavonoids and their role as a therapeutic agent. Molecules. 2020;25(22):5243. https://doi.org/10.3390/molecules25225243 | |
11. Cañedo LM, del Corral JM, San Feliciano A. 5-Alkylresorcinols from Ononis natrix. Phytochemistry. 1997;44(8):1559-63. https://doi.org/10.1016/S0031-9422(96)00755-8 | |
12. San Feliciano A, del Corral JM, Cañedo LM, Medarde M. 3, 4-Dihydroisocoumarins from Ononis natrix. Phytochemistry. 1990;29(3):945-8. https://doi.org/10.1016/0031-9422(90)80052-I | |
13. Gampe N, Szakács Z, Darcsi A, Boldizsár I, Sz?ke É, Kuzovkina I, et al. Qualitative and quantitative phytochemical analysis of Ononis hairy root cultures. Front Plant Sci. 2021;11:622585. https://doi.org/10.3389/fpls.2020.622585 | |
14. Abu Zarga MH, Al-Jaber HI, Al-Qudah MA, Al-Aboudi AM. A new cyclic polyketide and other constituents from Ononis spinosa growing wildly in Jordan and their antioxidant activity. J Asian Nat Prod Res. 2022;24(3):290-5. https://doi.org/10.1080/10286020.2021.1914597 | |
15. Besbas S, Mouffouk S, Haba H, Marcourt L, Wolfender JL, Benkhaled M. Chemical composition, antioxidant, antihemolytic and anti-inflammatory activities of Ononis mitissima L. Phytochem Lett. 2020;37:63-9. https://doi.org/10.1016/j.phytol.2020.04.002 | |
16. Yerlikaya S, Zengin G, Mollica A, Baloglu MC, Celik Altunoglu Y, Aktumsek A. A multidirectional perspective for novel functional products: in vitro pharmacological activities and in silico studies on Ononis natrix subsp. hispanica. Front Pharmacol. 2017;8:600. https://doi.org/10.3389/fphar.2017.00600 | |
17. Dénes T, Bartha SG, Kerényi M, Varga E, Balázs VL, Csepregi R, et al. Histological and antimicrobial study of Ononis arvensis L. Acta Biol Hung. 2017;68:321-33. https://doi.org/10.1556/018.68.2017.3.9 | |
18. Al-Zereini WA. Ononis natrix and Salvia verbenaca: two Jordanian medicinal plants with cytotoxic and antibacterial activities. J Herbs Spices Med Plants. 2017;23(1):18-25. https://doi.org/10.1080/10496475.2016.1241200 | |
19. Spiegler V, Gierlikowska B, Saenger T, Addotey JN, Sendker J, Jose J, et al. Root extracts from Ononis spinosa inhibit IL-8 release via interactions with toll-like receptor 4 and lipopolysaccharide. Front Pharmacol. 2020;11:889. https://doi.org/10.3389/fphar.2020.00889 | |
20. Al-Mubideen BF, Al-Serhan AA, Amarin JZ, Al-Dweikat A, Al- Muhaisen RA, Shreikh YA, et al. Ononis natrix L. lowers the blood glucose concentration in wistar rats with streptozotocin-induced diabetes mellitus. Endocr Metab Immune Disord Drug Targets. 2021;21(5):854-8. https://doi.org/10.2174/1871530320999200818140359 | |
21. Al-Mterin MA, Aboalhaija N, Zihlif MA, Afifi FU. Effects of Ononis natrix on glucose and lipid metabolism: an in vivo study. J Res Pharm. 2024;28(1):278-88. https://doi.org/10.29228/jrp.695 | |
22. El Khiat A, Bouftini K, Lafhal K, Tastift MA, El-Mansoury B, Ali DA, et al. Evaluation of the Anti-hyperglycemic activity of Ononis natrix aqueous extract against alloxan-induced experimental model of insulinopenic diabetes in albino Swiss mice. Academic J. 2024;39(4):57-64. | |
23. Kanso MA, Hijazi MA, El-Lakany A, Aboul-Ela M. Review on phytochemical constituents and pharmacological activities of genus Galium. J Appl Pharm Sci. 2024;14(9):046-56. | |
24. Al-Khalil S, Masalmeh A, Abdalla S, Tosa H, Iinuma M. N-arachidylanthranilic acid, a new derivative from Ononis natrix. J Nat Prod. 1995;58(5):760-3. https://doi.org/10.1021/np50119a018 | |
25. Wollenweber E, Dörr M, Rivera D, Roitman JN. Externally accumulated flavonoids in three Mediterranean Ononis species. Zeitschrift fuer Naturforschung C. 2003;58(11-12):771-5. https://doi.org/10.1515/znc-2003-11-1202 | |
26. Gampe N, Darcsi A, Lohner S, Béni S, Kursinszki L. Characterization and identification of isoflavonoid glycosides in the root of Spiny restharrow (Ononis spinosa L.) by HPLC-QTOF-MS, HPLC-MS/ MS and NMR. J Pharm Biomed Anal. 2016;123:74-81. https://doi.org/10.1016/j.jpba.2016.01.058 | |
27. Gampe N, Dávid DN, Takács-Novák K, Backlund A, Béni S. In vitro and in silico evaluation of Ononis isoflavonoids as molecules targeting the central nervous system. PLoS One. 2022;17(3):e0265639. https://doi.org/10.1371/journal.pone.0265639 | |
28. Gampe N, Darcsi A, Nagyné Nedves A, Boldizsár I, Kursinszki L, Béni S. Phytochemical analysis of Ononis arvensis L. by liquid chromatography coupled with mass spectrometry. J Mass Spectrometry. 2019;54(2):121-33. https://doi.org/10.1002/jms.4308 | |
29. Abdel-Kader MS. Phenolic constituents of Ononis vaginalis roots. Planta Medica. 2001;67(04):388-90. https://doi.org/10.1055/s-2001-14325 | |
30. Yousaf M, Al-Rehaily AJ, Ahmad MS, Mustafa J, Al-Yahya MA, Al- Said MS, et al. A 5-alkylresorcinol and three3, 4-dihydroisocoumarins derived from Ononis natrix. Phytochem Lett. 2015;13:1-5. https://doi.org/10.1016/j.phytol.2015.05.002 | |
31. Barrero AF, Sánchez JF, Rodríguez I. N-Δ13-Docosenoylanthranilic acid and alkylresorcinols from Ononis natrix subsp. hispanica. Phytochemistry. 1990;29(6):1967-9. https://doi.org/10.1016/0031-9422(90)85049-L | |
32. Jiang D, Rasul A, Batool R, Sarfraz I, Hussain G, Mateen Tahir M, et al. Potential anticancer properties and mechanisms of action of formononetin. BioMed Res Int. 2019;2019(1):5854315. https://doi.org/10.1155/2019/5854315 | |
33. Plochmann K, Korte G, Koutsilieri E, Richling E, Riederer P, Rethwilm A, et al. Structure-activity relationships of flavonoid-induced cytotoxicity on human leukemia cells. Arch Biochem Biophy. 2007;460(1):1-9. https://doi.org/10.1016/j.abb.2007.02.003 | |
34. Tian C, Liu X, Chang Y, Wang R, Lv T, Cui C, et al. Investigation of the anti-inflammatory and antioxidant activities of luteolin, kaempferol, apigenin and quercetin. South African J Bot. 2021;137:257-64. https://doi.org/10.1016/j.sajb.2020.10.022 | |
35. Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. Sci World J. 2013;2013(1):162750. https://doi.org/10.1155/2013/162750 | |
36. Cushnie TT, Lamb AJ. Antimicrobial activity of flavonoids. Int J Antimicrob Agents. 2005;26(5):343-56. https://doi.org/10.1016/j.ijantimicag.2005.09.002 | |
37. Sarian MN, Ahmed QU, Mat So'ad SZ, Alhassan AM, Murugesu S, Perumal V, et al. Antioxidant and antidiabetic effects of flavonoids: a structure-activity relationship based study. BioMed Res Int. 2017;2017(1):8386065. https://doi.org/10.1155/2017/8386065 | |
38. Cunningham P, Patton E, VanderVeen BN, Unger C, Aladhami A, Enos RT, et al. Sub-chronic oral toxicity screening of quercetin in mice. BMC Complementary Med Ther. 2022;22(1):279. https://doi.org/10.1186/s12906-022-03758-z | |
39. Singh P, Sharma S, Rath SK. A versatile flavonoid Quercetin: study of its toxicity and differential gene expression in the liver of mice. Phytomed Plus. 2022;2(1):100148. https://doi.org/10.1016/j.phyplu.2021.100148 | |
40. Dibal NI, Garba SH, Jacks TW. Acute toxicity of quercetin from onion skin in mice. Pharm Biomed Res. 2020;6(4):269-76. https://doi.org/10.18502/pbr.v6i4.5113 | |
41. Li C, Li G, Gao Y, Sun C, Wang X. A 90-day subchronic toxicity study with sodium formononetin-3′-sulphonate (Sul-F) delivered to dogs via intravenous administration. Regul Toxicol Pharmacol. 2016;77:87-92. https://doi.org/10.1016/j.yrtph.2016.02.016 | |
42. Singh KB, Dixit M, Dev K, Maurya R, Singh D. Formononetin, a methoxy isoflavone, enhances bone regeneration in a mouse model of cortical bone defect. Br J Nutr. 2017;117(11):1511-22. https://doi.org/10.1017/S0007114517001556 | |
43. Pingale TD, Gupta GL. Acute and sub-acute toxicity study reveals no dentrimental effect of formononetin in mice upon repeated ip dosing. Toxicol Mech Methods. 2023;33(8):688-97. https://doi.org/10.1080/15376516.2023.2234026 | |
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