Evaluation of antiproliferative and protective effects of Eupatorium cannabinum L. extracts

Eupatorium cannabinum L. (Asteraceae) has been used for a long time for medicinal purposes due to its various pharmacological effects and richness in active compounds such as phenolics, sesquiterpenes, pyrrolizidine alkaloids, and polysaccharides. Despite the high content of compounds that have important roles in medicinal plants, there are still limited literature data regarding this valuable species. The plant was fractioned using chloroform (EC) and distilled water (EA) and HPLC analysis revealed the presence of eupatorin, eupatilin, and quercetin in EC and caffeic acid and rutin in EA. The antiproliferative potential on BT-20, HepG2, Caco-2, and Jurkat cancer cell lines was assessed by MTS test. Jurkat cells were more sensitive to both extracts (IC50 of 7.35 ± 0.35 for EC and 13.77 ± 2.16 ?g/mL for EA), while the other lines were susceptible only to EC (IC50 88.27 ± 1.34 on Caco-2 cells and over 100 ?g/mL on BT- 20 and HepG2 cells) after 24 h of exposure. In an LPS-induced damage mouse model of endotoxemia, we showed that preventive administration increases the survival times of mice and leads to inhibition of proinflammatory cytokines. Both polar and nonpolar compounds are involved in exerting these effects, but further analytical studies are needed to identify the key responsible compounds and their biochemical pathways.

___

  • Burkovskiy I, Zhou J, Lehmann C (2013). Use of Escherichia coli toxins in sepsis models. Adv Biosci Biotech 4: 424-429.
  • Castillo Q, Triana J, Eiroa J, Padrón J, Plata G, Abel-Santos E, Báez L, Rodríguez D, Jiménez M, Pérez-Pujols M (2015). Flavonoids from Eupatorium illitum and their antiproliferative activities. Pharmacognosy J 7: 178-181.
  • Chen J , Ts a i Y, Hwang T , Wa n g T (2011). Thymol, benzofuranoid, and phenylpropanoid derivatives: anti-inflammatory constituents from Eupatorium cannabinum . J Nat Prod 74: 1021-1027.
  • Chen L, Lee T , Sung P , Shu C , Lim Y , Cheng M, Kuo W , Chen J (2014). New thymol derivatives and cytotoxic constituents from the root of Eupatorium cannabinum ssp. asiaticum . Chem Biodivers 11: 1374-1380.
  • Choi EJ, Lee S, Chae JR, Lee HS, Jun CD, Kim SH (2011). Eupatilin inhibits lipopolysaccharide-induced expression of inflammatory mediators in macrophages. Life Sciences 88: 1121-1126.
  • Chu C, Ren H, Xu N, Xia L, Chen D, Zhang J (2016). Eupatorium lindleyanum DC. sesquiterpenes fraction attenuates lipopolysaccharide-induced acute lung injury in mice. J Ethnopharmacol 185: 263-271.
  • Clavin M, Gorzalczany S, Machoc A, Munoz A, Ferraro G, Acevedo C, Martino V (2007). Anti-inflammatory activity of flavonoids from Eupatorium arnottianum . J Ethnopharmacol 112: 585- 589.
  • Dolečková I, Rárová L, Grúz J, Vondrusová M, Strnad M, Kryštof V (2012). Antiproliferative and antiangiogenic effects of flavone eupatorin, an active constituent of chloroform extract of Orthosiphon stamineus leaves. Fitoterapia 83: 1000-1007.
  • Du L, Chen J, Xing Y (2017). Eupatilin prevents H 2 O 2 -induced oxidative stress and apoptosis in human retinal pigment epithelial cells. Biomed Pharmacother 85: 136-140.
  • Elema E, Schripsema J, Malingre T (1989). Flavones and flavonol glycosides from Eupatorium cannabinum L. Pharmaceutisch Weekblad Scientific Ed 11: 161-164.
  • Fraisse D, Felgines C, Texier O, Lamaison J (2011). Caffeoyl derivatives: Major antioxidant compounds of some wild herbs of the Asteraceae family. Food Nutr Sci 2: 181-192.
  • Habtemariam S, Macpherson A (2000). Cytotoxicity and antibacterial activity of ethanol extract from leaves of a herbal drug, boneset ( Eupatorium perfoliatum ). Phytother Res 14: 575-577.
  • Hendriks H, Balraadjsing W, Huizing HJ, Bruins AP (1987). Investigation into the presence of pyrrolizidine alkaloids in Eupatorium cannabinum by means of positive and negative ion chemical ionization GC-MS. Planta Med 53: 456-461.
  • Hendriks H, Malingré TM, Elema ET (1983). Pyrrolizidine alkaloids, flavonoids and volatile compounds in the genus Eupatorium . Eupatorium cannabinum L., an ancient drug with new perspectives. Pharm Weekbl Sci 5: 281-286.
  • Ionita L, Grigore A, Pirvu L, Draghici E, Bubueanu C, Ionita C, Panteli M, Dobre N (2013). Pharmacological activity of an Eupatorium cannabinum L. extract. Rom Biotech Lett 18: 8779-8786.
  • Judzentiene A, Garjonyte R, Budiene J (2016). Variability, toxicity, and antioxidant activity of Eupatorium cannabinum (hemp agrimony) essential oils. Pharm Biol 54: 945-953.
  • Ke Z, Li M, Liu X, Tan S, Zhou Z, Huang C (2017). 2-Hydroxyeupatolide attenuates inflammatory responses via the inhibiting of NF-κB signaling pathways. RSC Adv 7: 37830-37838.
  • Kim M, Kim D, Na H, Oh T, Shin C, Surh Y (2005). Eupatilin, a pharmacologically active flavone derived from Artemisia plants, induces apoptosis in human gastric cancer (AGS) cells. J Environ Pathol Toxicol Oncol 24: 261-269.
  • Lexa A, Fleurentin J, Lehr P, Mortier F, Pruvost M, Pelt J (1989). Choleretic and hepatoprotective properties of Eupatorium cannabinum in the rat. Planta Med 55: 127-132.
  • Liu P, Liu D, Li W, Zhao T, Sauriol F, Gu Y, Shi Q, Zhang M (2015). Chemical Constituents of Plants from the Genus Eupatorium (1904-2014). Chem Biodivers 12: 1481-1515.
  • Maas M, Deters A, Hensel A (2011). Anti-inflammatory activity of Eupatorium perfoliatum L. extracts, eupafolin, and dimeric guaianolide via iNOS inhibitory activity and modulation of inflammation-related cytokines and chemokines. J Ethnopharmacol 137: 371-381.
  • Michalak B, Granica S, Piwowarski J, Waltenberger B, Stuppner H, Kiss A (2017). Searching for extracts with a potential anti- inflammatory activity conducted using in vitro models. In: Proceedings of the 65th International Congress and Annual Meeting. Basel, Switzerland: Society for Medicinal Plant and Natural Product Research, p. S1-S202.
  • Mirza M, Navaei MN, Dini M (2006). Volatile constituents of essential oils isolated from flowers and leaves of Eupatorium cannabinum L. from Iran. Iran J Pharm Res 2: 149-152.
  • Paolini J, Costa J, Bernardini AF (2005). Analysis of the essential oil from aerial parts of Eupatorium cannabinum subsp. corsicum (L.) by gas chromatography with electron impact and chemical ionization mass spectrometry. J Chromatogr A 1076: 170-178.
  • Ribeiro-Varandas E, Ressurreição F, Viegas W, Delgado M (2014). Cytotoxicity of Eupatorium cannabinum L. ethanolic extract against colon cancer cells and interactions with Bisphenol A and Doxorubicin. BMC Complement Altern Med 14: 264.
  • Salmela A, Pouwels J, Kukkonen-Macchi A, Waris S, Toivonen P, Jaakkola K, Mäki-Jouppila J, Kallio L, Kallio M (2012). The flavonoid eupatorin inactivates the mitotic checkpoint leading to polyploidy and apoptosis. Exp Cell Res 318: 578-592.
  • Senatore F, De Fusco R, Nappolitano F (2001). Eupatorium cannabinum L. ssp. cannabinum (Asteraceae) essential oils. Chemical composition and antibacterial activity. J Essent Oil Res 13: 463-466.
  • Seo H, Surh Y (2001). Eupatilin, a pharmacologically active flavone derived from Artemisia plants, induces apoptosis in human promyelocytic leukemia cells. Mutat Res 496: 191-198.
  • Tanaka T, Narazaki M, Kishimoto T (2014). IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol 6: a016295.
  • Vollmar A, Schäfera W, Wagner H (1986). Immunologically active polysaccharides of E upatorium cannabinum and Eupatorium perfoliatum. Phytochem 25: 377-381.