Traditional Medicinal Ranunculaceae Species from Romania and Their In Vitro Antioxidant, Antiproliferative, and Antiparasitic Potential
Abstract
1. Introduction
2. Results and Discussion
2.1. Antioxidant Effect
2.2. Anticancer Activity
2.3. Antileishmanial Effect
2.4. Antitrypanosomal Effect
2.5. Combined Antioxidant and Antiproliferative Activity
3. Materials and Methods
3.1. Plant Material
3.2. Sample Preparation
3.3. Chemicals and Reagents
3.4. Cell Cultures
3.5. Parasite Strains and Culture
3.6. Antioxidant Activity
3.6.1. Oxygen Radical Absorbance Capacity (ORAC) Assay
3.6.2. DPPH Radical Scavenging Assay
3.7. Cytotoxicity Activity
3.7.1. Cell Viability Assay
3.7.2. Cell Death Assay
3.8. Antiparasitic Activity
3.8.1. Resazurin Assay
3.8.2. Parasite Rescue Assay
3.9. Statistical Analysis
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Chen, S.-L.; Yu, H.; Luo, H.-M.; Wu, Q.; Li, C.-F.; Steinmetz, A. Conservation and sustainable use of medicinal plants: Problems, progress, and prospects. Chin. Med. 2016, 11, 37. [Google Scholar] [CrossRef] [PubMed]
- Heywood, V.H.; Brummitt, R.K.; Culham, A.; Seberg, O. Flowering Plant Families of the World, 1st ed.; Firefly Books: Richmond Hill, ON, Canada, 2007; pp. 273–276. [Google Scholar]
- Cristea, V. Plante Vasculare: Diversitate, Sistematica, Ecologie Si Importanta; Presa Universitara Clujeana: Cluj Napoca, Romania, 2014; pp. 32–38. [Google Scholar]
- Hao, D.-C.; Xiao, P.-G.; Ma, H.-Y.; Peng, Y.; He, C.-N. Mining chemodiversity from biodiversity: Pharmacophylogeny of medicinal plants of Ranunculaceae. Chin. J. Nat. Med. 2015, 13, 507–520. [Google Scholar] [CrossRef] [PubMed]
- Alexan, M.; Bojor, O.; Craciun, F. Flora Medicinala a Romaniei, 2nd ed.; Ceres: Bucuresti, Romania, 1991; pp. 23–41. [Google Scholar]
- Neblea, M.; Marian, M.; Duţa, M. Medicinal plant diversity in the Flora of the west part of Bucegi mountains (Romania). Acta Hortic. 2012, 955, 41–49. [Google Scholar] [CrossRef]
- Tamas, M. Botanica Farmaceutica: Sistematica-Cormobionta, 3rd ed.; Medicala Universitara: Cluj Napoca, Romania, 2005; pp. 40–44. [Google Scholar]
- Darshan, S.; Doreswamy, R. Patented antiinflammatory plant drug development from traditional medicine. Phytother. Res. 2004, 18, 343–357. [Google Scholar] [CrossRef]
- Salem, M.L. Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int. Immunopharmacol. 2005, 5, 1749–1770. [Google Scholar] [CrossRef]
- Raskin, I.; Ribnicky, D.M.; Komarnytsky, S.; Ilic, N.; Poulev, A.; Borisjuk, N.; Brinker, A.; Moreno, D.A.; Ripoll, C.; Yakoby, N.; et al. Plants and human health in the twenty-first century. Trends Biotechnol. 2002, 20, 522–531. [Google Scholar] [CrossRef]
- Hao, D.C.; He, C.N.; Shen, J.; Xiao, P.G. Anticancer chemodiversity of Ranunculaceae medicinal plants: Molecular mechanisms and functions. Curr. Genom. 2017, 18, 39–59. [Google Scholar] [CrossRef]
- Ren, M.Y.; Yu, Q.T.; Shi, C.Y.; Luo, J.B. Anticancer activities of C18-, C19-, C20-, and bis-diterpenoid alkaloids derived from genus Aconitum. Molecules 2017, 22, 267. [Google Scholar] [CrossRef]
- Bhatti, M.Z.; Ali, A.; Ahmad, A.; Saeed, A.; Malik, S.A. Antioxidant and phytochemical analysis of Ranunculus arvensis L. extracts. BMC Res. Notes 2015, 8, 279. [Google Scholar] [CrossRef]
- Munir, N.; Ijaz, W.; Altaf, I.; Naz, S. Evaluation of antifungal and antioxidant potential of two medicinal plants: Aconitum heterophyllum and Polygonum bistorta. Asian Pac. J. Trop. Biomed. 2014, 4, S639–S643. [Google Scholar] [CrossRef]
- Shoieb, A.M.; Elgayyar, M.; Dudrick, P.S.; Bell, J.L.; Tithof, P.K. In vitro inhibition of growth and induction of apoptosis in cancer cell lines by thymoquinone. Int. J. Oncol. 2003, 22, 107–113. [Google Scholar] [CrossRef] [PubMed]
- Song, J.L.; Zhao, X.; Qian, Y.; Wang, Q. Antioxidant and anticancer activities of methanolic extract of Trollius chinensis Bunge. Afr. J. Pharm. Pharmacol. 2013, 7, 1015–1019. [Google Scholar] [CrossRef]
- Wang, J.L.; Liu, K.; Gong, W.Z.; Wang, Q.; Xu, D.T.; Liu, M.F.; Bi, K.L.; Song, Y.F. Anticancer, antioxidant, and antimicrobial activities of anemone (Anemone cathayensis). Food Sci. Biotechnol. 2012, 21, 551–557. [Google Scholar] [CrossRef]
- Yin, T.; Cai, L.; Ding, Z. A systematic review on the chemical constituents of the genus Consolida (Ranunculaceae) and their biological activities. RSC Adv. 2020, 10, 35072–35089. [Google Scholar] [CrossRef] [PubMed]
- Castano Osorio, J.C.; Giraldo Garcia, A.M. Antiparasitic phytotherapy perspectives, scope and current development. Infectio 2019, 23, 189–204. [Google Scholar] [CrossRef]
- Mishra, B.B.; Singh, R.K.; Srivastava, A.; Tripathi, V.J.; Tiwari, V.K. Fighting against Leishmaniasis: Search of alkaloids as future true potential anti-Leishmanial agents. Mini Rev. Med. Chem. 2009, 9, 107–123. [Google Scholar] [CrossRef]
- Marin, C.; Diaz, J.G.; Maiques, D.I.; Ramirez-Macias, I.; Rosales, M.J.; Guitierrez-Sanchez, R.; Canas, R.; Sanchez-Moreno, M. Antitrypanosomatid activity of flavonoid glycosides isolated from Delphinium gracile, D. staphisagria, Consolida oliveriana and from Aconitum napellus subsp. lusitanicum. Phytochem. Lett. 2017, 19, 196–209. [Google Scholar] [CrossRef]
- Pizzino, G.; Irrera, N.; Cucinotta, M.; Pallio, G.; Mannino, F.; Arcoraci, V.; Squadrito, F.; Altavilla, D.; Bitto, A. Oxidative stress: Harms and benefits for human health. Oxid. Med. Cell Longev. 2017, 2017, 8416763. [Google Scholar] [CrossRef]
- Swiętek, M.; Lu, Y.C.; Konefal, R.; Ferreira, L.P.; Cruz, M.M.; Ma, Y.H.; Horak, D. Scavenging of reactive oxygen species by phenolic compound-modified maghemite nanoparticles. Beilstein J. Nanotechnol. 2019, 20, 1073–1088. [Google Scholar] [CrossRef]
- Rajendran, P.; Nandakumar, N.; Rengarajan, T.; Palaniswami, R.; Gnanadhas, E.N.; Lakshminarasaiah, U. Antioxidants and human diseases. Clin. Chim. Acta 2014, 436, 332–347. [Google Scholar] [CrossRef]
- Taniyama, Y.; Griendling, K.K. Reactive oxygen species in the vasculature. Hypertension 2003, 42, 1075–1081. [Google Scholar] [CrossRef] [PubMed]
- Kumar, N.; Goel, N. Phenolic acids: Natural versatile molecules with promising therapeutic applications. Biotechnol. Rep. 2019, 20, e00370. [Google Scholar] [CrossRef] [PubMed]
- Gill, S.S.; Tuteja, N. Reactive oxygen species and antioxidant machinery in abiotic stress tolerance in crop plants. Plant Physiol. Biochem. 2010, 48, 909–930. [Google Scholar] [CrossRef] [PubMed]
- Rondevaldova, J.; Tauchen, J.; Mascellani, A.; Tulkova, J.; Magdalita, P.M.; Tulin, E.E.; Kokoska, L. Antioxidant activity and total phenolic content of underutilized edible tree species of the Philippines. Horticulturae 2024, 10, 1051. [Google Scholar] [CrossRef]
- Goo, Y.-K. Therapeutic potential of Ranunculus species (Ranunculaceae): A literature review on traditional medicinal herbs. Plants 2022, 11, 1599. [Google Scholar] [CrossRef]
- Ahmad, A.; Husain, A.; Mujeeb, M.; Khan, S.A.; Najmi, A.K.; Siddique, N.A.; Anwar, F. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac. J. Trop. Biomed. 2013, 3, 337–352. [Google Scholar] [CrossRef]
- Mariani, C.; Braca, A.; Vitalini, S.; De Tommasi, N.; Visioli, F.; Fico, G. Flavonoid characterization and in vitro antioxidant activity of Aconitum anthora L. (Ranunculaceae). Phytochemistry 2008, 69, 1220–1226. [Google Scholar] [CrossRef]
- Fico, G.; Braca, A.; Bilia, A.R.; Tome, F.; Morelli, I. New flavonol glycosides from the flowers of Aconitum napellus ssp. tauricum. Planta Medica 2001, 67, 287–290. [Google Scholar] [CrossRef]
- Braca, A.; Fico, G.; Morelli, I.; De Simone, F.; Tome, F.; De Tommasi, N. Antioxidant and free radical scavenging activity of flavonol glycosides from different Aconitum species. J. Ethnopharmacol. 2003, 86, 63–67. [Google Scholar] [CrossRef]
- Malik, J.; Tauchen, J.; Landa, P.; Kutil, Z.; Marsik, P.; Kloucek, P.; Havlik, J.; Kokoska, L. In vitro antiinflammatory and antioxidant potential of root extracts from Ranunculaceae species. S. Afr. J. Bot. 2017, 109, 128–137. [Google Scholar] [CrossRef]
- Sutan, N.A.; Manolescu, D.S.; Fiarescu, I.; Neblea, A.M.; Sutan, C.; Ducu, C.; Soare, L.C.; Negrea, D.; Avramescu, S.M.; Fiarescu, R.C. Phytosynthesis of gold and silver nanoparticles enhance in vitro antioxidant and mitostimulatory activity of Aconitum toxicum Reichenb. rhizomes alcoholic extracts. Mater. Sci. Eng. C-Mater. Biol. Appl. 2018, 93, 746–758. [Google Scholar] [CrossRef] [PubMed]
- Vitalini, S.; Braca, A.; Passarella, D.; Fico, G. New flavonol glycosides from Aconitum burnatii Gayer and Aconitum variegatum L. Fitoterapia 2010, 81, 940–947. [Google Scholar] [CrossRef] [PubMed]
- Jeong, H.J.; Whang, W.K.; Kim, I.H. New flavonoids from the aerial parts of Aconitum chiisanense. Planta Med. 1997, 63, 329–334. [Google Scholar] [CrossRef] [PubMed]
- Fico, G.; Braca, A.; De Tommasi, N.; Tome, F.; Morelli, I. Flavonoids from Aconitum napellus subsp. neomontanum. Phytochemistry 2001, 57, 543–546. [Google Scholar] [CrossRef]
- Neag, T.; Toma, C.C.; Olah, N.; Ardelean, A. Polyphenols profile and antioxidant activity of some Romanian Ranunculus species. Stud. Univ. Babes-Bolyai Chem. 2017, 62, 75–88. [Google Scholar] [CrossRef]
- Khan, M.Z.; Jan, S.; Khan, F.U.; Noor, W.; Khan, Y.M.; Shah, A.; Chaudhary, M.I.; Ali, F.; Khan, K.; Ullah, W.; et al. Phytochemical screening and biological activities of Ranunculus arvensis. Int. J. Biosci. 2017, 11, 15–21. [Google Scholar]
- Rui, W.; Chen, H.; Tan, Y.; Zhong, Y.; Feng, Y. Rapid analysis of the main components of the total glycosides of Ranunculus japonicus by UPLC/Q-TOF-MS. Nat. Prod. Commun. 2010, 5, 783–788. [Google Scholar] [CrossRef]
- Deng, K.Z.; Xiong, Y.; Zhou, B.; Guan, Y.M.; Luo, Y.M. Chemical constituents from the roots of Ranunculus ternatus and their inhibitory effects on Mycobacterium tuberculosis. Molecules 2013, 18, 11859–11865. [Google Scholar] [CrossRef]
- Zhang, L.; Yang, Z.; Tian, J.K. Two new indolopyridoquinazoline alkaloidal glycosides from Ranunculus ternatus. Chem. Pharm. Bull. 2007, 55, 1267–1269. [Google Scholar] [CrossRef]
- Kaya, G.I.; Somer, N.U.; Konyalioglu, S.; Yalcin, H.T.; Yavaşoglu, N.U.K.; Sarikaya, B.; Onur, M.A. Antioxidant and antibacterial activities of Ranunculus marginatus var. trachycarpus and R. sprunerianus. Turk. J. Biol. 2010, 34, 139–146. [Google Scholar] [CrossRef]
- Azmir, J.; Zaidul, I.S.M.; Rahman, M.M.; Sharif, K.M.; Mohamed, A.; Sahena, F.; Jahurul, M.H.A.; Ghafoor, K.; Norulaini, N.A.N.; Omar, A.K.M. Techniques for extraction of bioactive compounds from plant materials: A review. J. Food Eng. 2013, 117, 426–436. [Google Scholar] [CrossRef]
- Gobbo-Neto, L.; Lopes, N.P. Medicinal plants: Factors of influence on the content of secondary metabolites. Química Nova 2007, 30, 374–381. [Google Scholar] [CrossRef]
- Hrichi, S.; Chaabane-Banaoues, R.; Giuffrida, D.; Mangraviti, D.; Oulad El Majdoub, Y.; Rigano, F.; Mondello, L.; Babba, H.; Mighri, Z.; Cacciola, F. Effect of seasonal variation on the chemical composition and antioxidant and antifungal activities of Convolvulus althaeoides L. leaf extracts. Arab. J. Chem. 2020, 13, 5651–5668. [Google Scholar] [CrossRef]
- Sun, Y.X.; Liu, J.C.; Liu, D.Y. Phytochemicals and bioactivities of Anemone raddeana Regel: A review. Pharmazie 2011, 66, 813–821. [Google Scholar] [PubMed]
- Pei, C.; Fenge, W.; Lisheng, D. Advances in the studies on the chemical constituents and biologic activities for Anemone species. Nat. Prod. Res. Dev. 2004, 16, 581–584. [Google Scholar]
- Han, L.-T.; Li, J.; Huang, F.; Yu, S.-G.; Fang, N.-B. Triterpenoid saponins from Anemone flaccida induce apoptosis activity in HeLa cells. J. Asian Natl. Prod. Res. 2009, 11, 122–127. [Google Scholar] [CrossRef]
- Han, L.-T.; Fang, Y.; Li, M.M.; Yang, H.B.; Huang, F. The antitumor effects of triterpenoid saponins from the Anemone flaccida and the underlying mechanism. Evid. Based Complement. Altern. Med. 2013, 2013, 517931. [Google Scholar] [CrossRef]
- Luan, X.; Guan, Y.; Wang, C.; Zhao, M.; Lu, Q.; Tang, Y.; Liu, Y.; Yu, D.; Wang, X.; Qi, H.; et al. Determination of Raddeanin A in rat plasma by liquid chromatography–tandem mass spectrometry: Application to a pharmacokinetic study. J. Chromatogr. B 2013, 923–924, 43–47. [Google Scholar] [CrossRef]
- Naz, I.; Ramchandani, S.; Khan, M.R.; Yang, M.H.; Ahn, K.S. Anticancer potential of Raddeanin A, a natural triterpenoid isolated from Anemone raddeana Regel. Molecules 2020, 25, 1035. [Google Scholar] [CrossRef]
- Xue, G.; Zou, X.; Zhou, J.-Y.; Sun, W.; Wu, J.; Xu, J.; Wang, R.-P. Raddeanin A induces human gastric cancer cells apoptosis and inhibits their invasion in vitro. Biochem. Biophys. Res. Comm. 2013, 439, 196–202. [Google Scholar] [CrossRef]
- Guan, Y.Y.; Liu, H.-J.; Luan, X.; Xu, J.-R.; Lu, Q.; Liu, Y.-R.; Gao, Y.-G.; Zhao, M.; Chen, H.-Z.; Fang, C. Raddeanin A, a triterpenoid saponin isolated from Anemone raddeana, suppresses the angiogenesis and growth of human colorectal tumor by inhibiting VEGFR2 signaling. Phytomedicine 2015, 22, 103–110. [Google Scholar] [CrossRef] [PubMed]
- Li, J.N.; Yu, Y.; Zhang, Y.-F.; Li, Z.-M.; Cai, G.-Z.; Gong, J.-Y. Synergy of Raddeanin A and cisplatin induced therapeutic effect enhancement in human hepatocellular carcinoma. Biochem. Biophys. Res. Comm. 2017, 485, 335–341. [Google Scholar] [CrossRef] [PubMed]
- Wang, Q.; Mo, J.; Zhao, C.; Huang, K.; Feng, M.; He, W.; Wang, J.; Chen, S.; Xie, Z.; Ma, J.; et al. Raddeanin A suppresses breast cancer-associated osteolysis through inhibiting osteoclasts and breast cancer cells. Cell Death Dis. 2018, 9, 376. [Google Scholar] [CrossRef] [PubMed]
- Ali, S.; Chouhan, R.; Sultan, P.; Hassan, Q.P.; Gandhi, S.G. A comprehensive review of phytochemistry, pharmacology and toxicology of the genus Aconitum L. Adv. Trad. Med. 2023, 23, 299–320. [Google Scholar] [CrossRef]
- Mi, L.; Li, Y.; Sun, M.; Zhang, P.; Li, Y.; Yang, H. A systematic review of pharmacological activities, toxicological mechanisms and pharmacokinetic studies on Aconitum alkaloids. Chin. J. Nat. Med. 2021, 19, 505–520. [Google Scholar] [CrossRef]
- Chan, Y.-T.; Wang, N.; Feng, Y. The toxicology and detoxification of Aconitum: Traditional and modern views. Chin. Med. 2021, 16, 61. [Google Scholar] [CrossRef]
- WHO. Leishmaniasis. Available online: https://www.who.int/news-room/fact-sheets/detail/leishmaniasis (accessed on 16 September 2024).
- No, J.H. Visceral leishmaniasis: Revisiting current treatments and approaches for future discoveries. Acta Trop. 2016, 155, 113–123. [Google Scholar] [CrossRef]
- Jabbar, E.A.K.; AL-Aboody, B.A.; Jarullah, B.A.; Noori, N. Isolation and molecular diagnosis of Leishmania major and study activity of aqueous extract of plant Nigella sativa against the parasite in vitro. Int. J. Pharm. Qual. Assur. 2019, 10, 47–50. [Google Scholar]
- Al-Turkmani, M.O.; Mokrani, L.; Soukkarieh, C. Antileishmanial apoptotic activity of Nigella sativa L. essential oil and thymoquinone triggers on Leishmania tropica. Indian J. Exp. Biol. 2020, 58, 699–705. [Google Scholar]
- Bafghi, A.F.; Vahidi, A.R.; Anvari, M.H.; Barzegar, K.; Ghafourzadeh, M. The in vivo antileishmanial activity of alcoholic extract from Nigella sativa seeds. Afr. J. Microbiol. Res. 2011, 5, 1504–1510. [Google Scholar]
- Bapela, M.J.; Kaiser, M.; Meyer, J.J.M. Antileishmanial activity of selected South African plant species. S. Afr. J. Bot. 2017, 108, 342–345. [Google Scholar] [CrossRef]
- Ramírez-Macias, I.; Marin, C.; Diaz, J.G.; Rosales, M.J.; Gutierrez-Sanchez, R.; Sanchez-Moreno, M. Leishmanicidal activity of nine novel flavonoids from Delphinium staphisagria. Sci. World J. 2012, 2012, 203646. [Google Scholar] [CrossRef] [PubMed]
- Shyaula, S.L.; Tamang, T.; Ghouri, N.; Adhikari, A.; Marasini, S.; Bajracharya, G.B.; Manandhar, M.D.; Choudhary, M.I. Antileishmanial diterpenoid alkaloids from Aconitum spicatum (Bruhl) Stapf. Nat. Prod. Res. 2016, 30, 2590–2593. [Google Scholar] [CrossRef] [PubMed]
- Sundar, S.; Singh, J.; Singh, V.K.; Agrawal, N.; Kumar, R. Current and emerging therapies for the treatment of leishmaniasis. Expert Opin. Orphan Drugs 2024, 12, 19–32. [Google Scholar] [CrossRef]
- Wijnant, G.; Dumetz, F.; Dirkx, L.; Bulte, D.; Cuypers, B.; Van Bocxlaer, K.; Hendrickx, S. Tackling drug resistance and other causes of treatment failure in Leishmaniasis. Front. Trop. Dis. 2022, 3, 837460. [Google Scholar] [CrossRef]
- Wei, J.; Wang, B.; Chen, Y.; Wang, Q.; Ahmed, A.F.; Zhang, Y.; Kang, W. The immunomodulatory effects of active ingredients from Nigella sativa in RAW264.7 cells through NF-κB/MAPK signaling pathways. Front. Nutr. 2022, 9, 899797. [Google Scholar] [CrossRef] [PubMed]
- Di Sotto, A.; Vitalone, A.; Di Giacomo, S. Plant-derived nutraceuticals and immune system modulation: An evidence-based overview. Vaccines 2020, 8, 468. [Google Scholar] [CrossRef]
- Costa-da-Silva, A.C.; Nascimento, D.d.O.; Ferreira, J.R.M.; Guimaraes-Pinto, K.; Freire-de-Lima, L.; Morrot, A.; Decote-Ricardo, D.; Filardy, A.A.; Freire-de-Lima, C.G. Immune responses in Leishmaniasis: An overview. Trop. Med. Infect. Dis. 2022, 7, 54. [Google Scholar] [CrossRef]
- Cedillo-Cortezano, M.; Martinez-Cuevas, L.R.; López, J.A.M.; Barrera López, I.L.; Escutia-Perez, S.; Petricevich, V.L. Use of medicinal plants in the process of wound healing: A literature review. Pharmaceuticals 2024, 17, 303. [Google Scholar] [CrossRef]
- Herrmann, F.; Romero, M.R.; Blazquez, A.G.; Kaufmann, D.; Ashour, M.L.; Kahl, S.; Marin, J.J.; Efferth, T.; Wink, M. Diversity of pharmacological properties in Chinese and European medicinal plants: Cytotoxicity, antiviral and antitrypanosomal screening of 82 herbal drugs. Diversity 2011, 3, 547–580. [Google Scholar] [CrossRef]
- Kou, X.; Kirberger, M.; Yang, Y.; Chen, N. Natural products for cancer prevention associated with Nrf2–ARE pathway. Food Sci. Hum. Wellness 2013, 2, 22–28. [Google Scholar] [CrossRef]
- Gerhauser, C.; Klimo, K.; Heiss, E.; Neumann, I.; Gamal-Eldeen, A.; Knauft, J.; Liu, G.Y.; Sitthimonchai, S.; Frank, N. Mechanism-based in vitro screening of potential cancer chemopreventive agents. Mutat. Res. 2003, 523, 163–172. [Google Scholar] [CrossRef] [PubMed]
- Hensley, K.; Robinson, K.A.; Gabbita, S.P.; Salsman, S.; Floyd, R.A. Reactive oxygen species, cell signaling, and cell injury. Free Radic. Biol. Med. 2000, 28, 1456–1462. [Google Scholar] [CrossRef]
- Block, K.I.; Koch, A.C.; Mead, M.N.; Tothy, P.K.; Newman, R.A.; Gyllenhaal, C. Impact of antioxidant supplementation on chemotherapeutic toxicity: A systematic review of the evidence from randomized controlled trials. Int. J. Cancer 2008, 123, 1227–1239. [Google Scholar] [CrossRef] [PubMed]
- Fuchs-Tarlovsky, V. Role of antioxidants in cancer therapy. Nutrition 2013, 29, 15–21. [Google Scholar] [CrossRef]
- Das, L.; Vinayak, M. Long term effect of curcumin in restoration of tumour suppressor p53 and phase-II antioxidant enzymes via activation of Nrf2 signaling and modulation of inflammation in prevention of cancer. PLoS ONE 2015, 10, e0124000. [Google Scholar] [CrossRef]
- Ji, C.C.; Tang, H.F.; Hu, Y.Y.; Zhang, Y.; Zheng, M.H.; Qin, H.Y.; Li, S.Z.; Wang, X.Y.; Fei, Z.; Cheng, G. Saponin 6 derived from Anemone taipaiensis induces U87 human malignant glioblastoma cell apoptosis via regulation of Fas and Bcl 2 family proteins. Mol. Med. Rep. 2016, 14, 380–386. [Google Scholar] [CrossRef]
- Liu, Q.; Chen, W.; Jiao, Y.; Hou, J.; Wu, Q.; Lu, Y.; Qi, X. Pulsatilla saponin A, an active molecule from Pulsatilla chinensis, induces cancer cell death and inhibits tumor growth in mouse xenograft models. J. Surg. Res. 2014, 188, 387–395. [Google Scholar] [CrossRef]
- Borcsa, B.; Fodor, L.; Csupor, D.; Forgo, P.; Molnar, A.; Hohmann, J. Diterpene alkaloids from the roots of Aconitum moldavicum and assessment of Nav 1.2 sodium channel activity of aconitum alkaloids. Planta Medica 2014, 80, 231–236. [Google Scholar] [CrossRef]
- Mubashir, S.; Dar, M.Y.; Lone, B.A.; Zargar, M.I.; Shah, W.A. Anthelmintic, antimicrobial, antioxidant and cytotoxic activity of Caltha palustris var. alba Kashmir, India. Chin. J. Nat. Med. 2014, 12, 567–572. [Google Scholar] [CrossRef]
- Sanchez-Villamil, J.P.; Bautista-Nino, P.K.; Serrano, N.C.; Rincon, M.Y.; Garg, N.J. Potential role of antioxidants as adjunctive therapy in Chagas disease. Oxid. Med. Cell. Longev. 2020, 2020, 9081813. [Google Scholar] [CrossRef] [PubMed]
- Hall, B.S.; Wilkinson, S.R. Activation of benznidazole by trypanosomal type I nitroreductases results in glyoxal formation. Antimicrob. Agents Chemother. 2012, 56, 115–123. [Google Scholar] [CrossRef] [PubMed]
- Wyllie, S.; Foth, B.J.; Kelner, A.; Sokolova, A.Y.; Berriman, M.; Fairlamb, A.H. Nitroheterocyclic drug resistance mechanisms in Trypanosoma brucei. J. Antimicrob. Chemother. 2016, 71, 625–634. [Google Scholar] [CrossRef]
- Wyllie, S.; Roberts, A.J.; Norval, S.; Patterson, S.; Foth, B.J.; Berriman, M.; Read, K.D.; Fairlamb, A.H. Activation of bicyclic nitro-drugs by a novel nitroreductase (NTR2) in Leishmania. PLoS Pathog. 2016, 12, e1005971. [Google Scholar] [CrossRef] [PubMed]
- Leitsch, D.; Kolarich, D.; Binder, M.; Stadlmann, J.; Altmann, F.; Duchene, M. Trichomonas vaginalis: Metronidazole and other nitroimidazole drugs are reduced by the flavin enzyme thioredoxin reductase and disrupt the cellular redox system: Implications for nitroimidazole toxicity and resistance. Mol. Microbiol. 2009, 72, 518–536. [Google Scholar] [CrossRef]
- Howard, H.K.; Pharoah, M.M.; Ashall, F.; Miles, M.A. Human urine stimulates growth of Leishmania in vitro. Trans. R. Soc. Trop. Med. Hyg. 1991, 85, 477–479. [Google Scholar] [CrossRef]
- Allahverdiyev, A.M.; Bagirova, M.; Elcicek, S.; Koc, R.C.; Oztel, O.N. Effect of human urine on cell cycle and infectivity of Leismania species promastigotes in vitro. Am. J. Trop. Med. Hyg. 2011, 85, 639–643. [Google Scholar] [CrossRef]
- Hirumi, H.; Hirumi, K. Axenic culture of African trypanosome bloodstream forms. Parasitol. Today 1994, 10, 80–84. [Google Scholar] [CrossRef]
- Ou, B.; Hampsch-Woodill, M.; Prior, R.L. Development and validation of an improved oxygen radical absorbance capacity assay using fluorescein as the fluorescent probe. J. Agr. Food Chem. 2001, 49, 4619–4626. [Google Scholar] [CrossRef]
- Tauchen, J.; Huml, L.; Bortl, L.; Doskocil, I.; Jarosova, V.; Marsik, P.; Frankova, A.; Clavo Peralta, Z.M.; Chuspe Zans, M.E.; Havlik, J.; et al. Screening of medicinal plants traditionally used in Peruvian Amazon for in vitro antioxidant and anticancer potential. Nat. Prod. Res. 2019, 33, 2718–2721. [Google Scholar] [CrossRef]
- Rondevaldova, J.; Novy, P.; Tauchen, J.; Drabek, O.; Kotikova, Z.; Dajcl, J.; Mascellani, A.; Chrun, R.; Nguon, S.; Kokoska, L. Determination of antioxidants, minerals and vitamins in Cambodian underutilized fruits and vegetables. J. Food Meas. Charact. 2023, 17, 716–731. [Google Scholar] [CrossRef]
- Sharma, O.P.; Bhat, T.K. DPPH antioxidant assay revisited. Food Chem. 2009, 113, 1202–1205. [Google Scholar] [CrossRef]
- Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods 1983, 65, 55–63. [Google Scholar] [CrossRef] [PubMed]
- Zhang, N.; Zoltner, M.; Leung, K.F.; Scullion, P.; Hutchinson, S.; Del Pino, R.C.; Vincent, I.M.; Zhang, Y.K.; Freund, Y.R.; Alley, M.R.; et al. Host-parasite co-metabolic activation of antitrypanosomal aminomethyl-benzoxaboroles. PLoS Pathog. 2018, 14, e1006850. [Google Scholar] [CrossRef] [PubMed]
- Zahedifard, F.; Bansal, M.; Sharma, N.; Kumar, S.; Shen, S.; Singh, P.; Rathi, B.; Zoltner, M. Phenotypic screening reveals a highly selective phthalimide-based compound with antileishmanial activity. PLoS Negl. Trop. Dis. 2024, 18, e0012050. [Google Scholar] [CrossRef]
- Jain, S.K.; Sahu, R.; Walker, L.A.; Tekwani, B.L. A parasite rescue and transformation assay for antileishmanial screening against intracellular Leishmania donovani amastigotes in THP1 human acute monocytic leukemia cell line. J. Vis. Exp. 2012, 70, e4054. [Google Scholar]
Plant Species | Date of Collection | VSN | Plant Origin | Collected Site | Ethnomedicinal Uses * |
---|---|---|---|---|---|
Aconitum moldavicum Hacq. | June 2016 | CLA30049 | Mt. Stamba | 46°12’50.8″ N, 22°51′35.4″ E | Treatment of arthritis, gout, and rheumatism (herb and root) [5,6,7] |
Aconitum toxicum Rchb. | August 2017 | CLA30063 | Mt. Piatra Craiului | 45°33′12.6″ N, 25°25′27.0″ E | Treatment of skin tumors (herb and root) [5,6,7] |
Aconitum variegatum L. | June 2016 | CLA30048 | Mt. Stamba | 46°12′50.8″ N, 22°51′35.4″ E | Analgesic and antirheumatic properties (herb) [5,6,7] |
Aconitum vulparia Rchb. | July 2016 | CLA30046 | Mt. Postavaru | 45°34′56.1″ N, 25°33′21.7″ E | Treatment of chronic skin disorders and rheumatism (herb) [5,6,7] |
Anemone transsilvanica Fuss. | July 2016 | CLA30047 | Mt. Postavaru | 45°34′56.1″ N, 25°33′21.7″ E | Treatment of bronchiti,. cataract, and rheumatic gout (root) [5,6,7] |
Caltha palustris L. | May 2017 | CLA30064 | Mt. Intorsurii | 45°37′53.4″ N, 26°08′36.7″ E | Treatment of arthritis, gout, rheumatism, anemia, and parasitic diseases (herb) [5,6,7] |
Hepatica nobilis Mill. | May 2017 | CLA30065 | Mt. Almajului | 44°40′46.1″ N, 21°42′28.4″ E | Treatment of various inflammation, rheumatism, and microbial infections (herb and root) [5,6,7] |
Ranunculus acris L. | June 2016 | CLA30042 | Mt. Stamba | 46°12′50.8″ N, 22°51′35.4″ E | Treatment of asthma, bronchitis, malaria, and rheumatism (herb) [5,6,7] |
Ranunculus bulbosus L. | June 2016 | CLA30050 | Mt. Stamba | 46°12′50.8″ N, 22°51′35.4″ E | Treatment for arthritis, gout, and neuralgia pains (herb) [5,6,7] |
Ranunculus carpaticus Herbich | June 2017 | CLA30044 | Mt. Postavaru | 45°34′56.1″ N, 25°33′21.7″ E | Treatment of various inflammation and skin infections (herb) [5,6,7] |
Ranunculus platanifolius L. | June 2017 | CLA30040 | Mt. Postavaru | 45°34′56.1″ N, 25°33′21.7″ E | Treatment of rheumatism (herb) [5,6,7] |
Ranunculus polyanthemos L. | June 2016 | CLA30051 | Mt. Stamba | 46°12′50.8″ N, 22°51′35.4″ E | Treatment of rheumatism, gastric, and duodenal ulcers (herb) [5,6,7] |
Ranunculus repens L. | June 2016 | CLA30045 | Mt. Stamba | 46°12′50.8″ N, 22°51′35.4″ E | Treatment of malaria and rheumatism (herb) [5,6,7] |
Ranunculus sardous Crantz | July 2016 | CLA30067 | Cluj-Napoca | 46°46′26.1″ N, 23°34′55.2″ E | Treatment of various inflammation (herb) [5,6,7] |
Ranunculus serpens subsp. nemorosus L. | June 2017 | CLA30043 | Mt. Postavaru | 45°34′56.1″ N, 25°33′21.7″ E | Treatment of various inflammation and rheumatism (herb) [5,6,7] |
Trollius europaeus L. | June 2017 | CLA30066 | Mt. Postavaru | 45°34′56.1″ N, 25°33′21.7″ E | Treatment of various types of inflammation and bacterial infections (herb) [5,6,7] |
Species | PPT | EY (%) | Assay/Cell Line/Parasite/IC50 (µg/mL) 1 | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
DPPH | ORAC | MTT | Resazurin Assay | ||||||||||
Caco-2 2 | SI | HT29 2 | SI | FHs 74Int 3 | L. infantum (Promastigote) | SI | T. brucei | SI | |||||
A. moldavicum | H | 5.6 | 104.0 ± 2.6 | 23.1 ± 4.6 | 160.7 ± 7.5 | 1.8 | 77.5 ± 10.4 | 3.8 | 291.2 ± 7.2 | 115.5 ± 7.2 | 2.5 | 89.9 ± 1.6 | 3.2 |
A. toxicum | H | 5.8 | 92.6 ± 16.6 | 18.7 ± 6.6 | 292.9 ± 16.6 | 0.9 | 228.2 ± 15.7 | 1.2 | 274.9 ± 26.2 | 34.7 ± 20.7 | 7.9 | 88.8 ± 25 | 3.1 |
R | 10.7 | 192.2 ± 18.2 | 45.7 ± 11 | 245.2 ± 10.3 | 2.1 | >512 | 1.0 | >512 | 230.0 ± 87.4 | 2.2 | 119.8 ± 11 | 4.3 | |
A. variegatum | H | 4.2 | 119.8 ± 15.0 | 26.4 ± 7.7 | 144.3 ± 7.5 | 3.5 | 330.7 ± 17.9 | 1.5 | >512 | 310.0 ± 12.2 | 1.7 | 106.1 ± 21 | 4.8 |
A. vulparia | H | 5.5 | 137 ± 6.6 | 56.4 ± 2.5 | 249.9 ± 0.8 | 2.0 | 184.5 ± 2.1 | 2.8 | >512 | 221.3 ± 14.1 | 2.3 | 113.4 ± 36 | 4.5 |
A. transsilvanica | L | 11.5 | 179.6 ± 12.9 | 35.7 ± 14.7 | 46.9 ± 5.9 | 3.3 | 86.5 ± 4.5 | 1.8 | 154.8 ± 17.2 | 18.6 ± 6.5 | 8.3 | 102.6 ± 14 | 1.5 |
R | 7.4 | >256 | 212.0 ± 22.9 | 65.8 ± 2.6 | 3.9 | 70.2 ± 9.4 | 3.7 | 259.6 ± 19.1 | 41.0 ± 24.0 | 6.3 | 110.9 ± 1.2 | 2.3 | |
C. palustris | H | 7.3 | 98.5 ± 14.7 | 35.9 ± 1.6 | 85.8 ± 7.3 | 3.2 | 148.8 ± 0.5 | 1.9 | 277.4 ± 16.9 | 30.7 ± 1.8 | 9.0 | 83.0 ± 0.0 | 3.3 |
H. nobilis | H | 6.4 | 116.5 ± 21.5 | 46.2 ± 10.1 | 124.1 ± 1.1 | 3.7 | 335.8 ± 19.3 | 1.4 | 463.6 ± 12.0 | 19.5 ± 6.4 | 23.8 | 122.4 ± 24 | 3.8 |
R | 6.9 | >256 | 238.6 ± 14.1 | 46.9 ± 4.4 | 7.1 | 133.0 ± 11.1 | 2.5 | 335.3 ± 10.6 | 22.1 ± 5.8 | 15.2 | 161.7 ± 1.9 | 2.1 | |
R. acris | H | 5.7 | 161.7 ± 24.4 | 36.7 ± 8.8 | >512 | 0.9 | 205.2 ± 15.4 | 2.2 | 450.3 ± 12.1 | 55.3 ± 1.9 | 8.2 | 91.4 ± 3.7 | 4.9 |
R. bulbosus | H | 7.2 | 166.9 ± 10.1 | 62.9 ± 11.1 | 152.3 ± 6.3 | 1.9 | 221.9 ± 5.6 | 1.3 | 285.1 ± 6.3 | 139 ± 25.4 | 2.1 | 170.0 ± 9.9 | 1.7 |
R. carpaticus | H | 6.9 | 207.9 ± 2.0 | 69.3 ± 9.1 | 277.6 ± 9.6 | 1.1 | 387.7 ± 0.5 | 0.8 | 318.9 ± 19.8 | 93.6 ± 11.2 | 3.4 | 171.6 ± 13 | 1.9 |
R. platanifolius | H | 9.5 | >256 | 41.5 ± 6.9 | 242.5 ± 6.8 | 2.1 | 253.2 ± 0.4 | 2.0 | >512 | 41.4 ± 11.1 | 12.5 | 98.3 ± 0.4 | 5.2 |
R. polyanthemos | H | 6.0 | 157.8 ± 17.3 | 99.1 ± 6.9 | 318.2 ± 5.8 | 1.6 | 230.7 ± 9.3 | 2.2 | >512 | 84.0 ± 12.1 | 6.1 | 158.6 ± 22 | 3.2 |
R. repens | H | 8.2 | 190.1 ± 17.9 | 41.6 ± 6.4 | 227.6 ± 5.9 | 2.2 | 295.2 ± 18.0 | 1.7 | >512 | 47.9 ± 11.1 | 10.7 | 128.7 ± 60.3 | 4.0 |
R. sardous | H | 3.1 | 182.7 ± 25.5 | 62.0 ± 6.5 | 94.1 ± 4.4 | 3.8 | 347.9 ± 7.3 | 1.0 | 353.5 ± 21.9 | 131.0 ± 23.7 | 2.7 | 132.0 ± 55 | 2.7 |
R. serpens subsp. nemorosus | H | 4.6 | 240.5 ± 12.8 | 47.7 ± 8.5 | 83.3 ± 4.6 | 1.8 | 67.4 ± 1.8 | 2.3 | 152.9 ± 4.6 | 87.4 ± 13.0 | 1.8 | 138.2 ± 51.1 | 1.1 |
T. europaeus | H | 5.2 | 174.6 ± 40.0 | 38.9 ± 8.9 | 213.9 ± 32.7 | 2.4 | >512 | - | >512 | 108.2 ± 1.1 | 4.7 | 269.3 ± 74.0 | 1.9 |
DMSO | - | - | - | - | >1024 | - | >1024 | - | >1024 | >512 | - | 830.2 ± 42.2 | - |
Trolox 4 | - | - | 14.7 ± 3.5 | 22.4 ± 7.3 | - | - | - | - | - | - | - | - | - |
Vinorelbine 4 | - | - | - | - | 0.03 ± 0.02 | - | - | - | 0.45 ± 0.12 | - | - | - | - |
Amphotericin 4 | - | - | - | - | - | - | - | - | - | 0.184 ± 0.1 | - | - | - |
AN-3057 4 | - | - | - | - | - | - | - | - | - | - | - | 0.019 | - |
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Heller, C.D.; Zahedifard, F.; Doskocil, I.; Pamfil, D.; Zoltner, M.; Kokoska, L.; Rondevaldova, J. Traditional Medicinal Ranunculaceae Species from Romania and Their In Vitro Antioxidant, Antiproliferative, and Antiparasitic Potential. Int. J. Mol. Sci. 2024, 25, 10987. https://doi.org/10.3390/ijms252010987
Heller CD, Zahedifard F, Doskocil I, Pamfil D, Zoltner M, Kokoska L, Rondevaldova J. Traditional Medicinal Ranunculaceae Species from Romania and Their In Vitro Antioxidant, Antiproliferative, and Antiparasitic Potential. International Journal of Molecular Sciences. 2024; 25(20):10987. https://doi.org/10.3390/ijms252010987
Chicago/Turabian StyleHeller, Cristina D., Farnaz Zahedifard, Ivo Doskocil, Doru Pamfil, Martin Zoltner, Ladislav Kokoska, and Johana Rondevaldova. 2024. "Traditional Medicinal Ranunculaceae Species from Romania and Their In Vitro Antioxidant, Antiproliferative, and Antiparasitic Potential" International Journal of Molecular Sciences 25, no. 20: 10987. https://doi.org/10.3390/ijms252010987
APA StyleHeller, C. D., Zahedifard, F., Doskocil, I., Pamfil, D., Zoltner, M., Kokoska, L., & Rondevaldova, J. (2024). Traditional Medicinal Ranunculaceae Species from Romania and Their In Vitro Antioxidant, Antiproliferative, and Antiparasitic Potential. International Journal of Molecular Sciences, 25(20), 10987. https://doi.org/10.3390/ijms252010987