All Title Author
Keywords Abstract

Analysis of Flavonoids from Eugenia uniflora Leaves and Its Protective Effect against Murine Sepsis

DOI: 10.1155/2012/623940

Full-Text   Cite this paper   Add to My Lib


Eugenia uniflora, referred to as Pitanga cherry shrub, is largely distributed in tropical and subtropical America. This plant is cultivated in many countries and it is suitable for the production of juice, frozen pulp, and tea. Besides, it can be used as treatment for inflammatory diseases. We reported that a flavonoid-rich fraction (HE-Bu) obtained from leaves decreased the lethality induced by cecal ligation and puncture (CLP), a clinically relevant model of sepsis. The oral administration of HE-Bu reduced the late mortality rate by 30%, prevented neutrophil accumulation in lungs, decreased TNF-α and IL-1β serum levels, and markedly decreased iNOS and COX-2 protein expression by ileum cells. Chemical investigation showed myricetin and quercetin rhamnosides as the major components of this fraction. The results showed that HE-Bu protected mice from sepsis and indicated that this edible plant produces compounds that could be considered as potential adjuvants for sepsis treatment. 1. Introduction Eugenia uniflora L. (Myrtaceae) is a tropical and subtropical shrub widely distributed in American countries [1]. It is commonly referred to as Pitanga cherry or Brazilian cherry. Regarding their effects on human health, both fruit and leaves are used as folk medicine to treat similar diseases, although the leaves show the advantage of being perennial and continuously available, while the fruit are available during a short period of the year [2]. The fresh or dried leaves have been used empirically as medicine, since the 15th century [3], for treating inflammatory and stomach diseases, rheumatism, fever, and hypertension [4, 5]. Some studies have confirmed that Eugenia uniflora possesses anti-inflammatory, antimicrobial, and antifungal properties [4, 6–8]. These benefits are usually attributed to the presence of many secondary metabolites present in the leaves, which includes many volatile terpenoid oils, flavonoids, and condensed and hydrolysable tannins, leucoanthocyanidins, and steroids and/or triterpenoids [9]. Flavonoids are presented in many plant extracts, being constantly the focus of pharmacological studies. Despite of their well-described antioxidant activity [10–12], they have shown many other properties, such as anti-inflammatory, antimicrobial, antiaging, anticancer, and antiallergic, hypocholesterolemic and vasodilatation, [10–15]. Together, the anti-inflammatory and antioxidant properties of flavonoids can explain the efficacy of plant extracts against various diseases, such as osteoporosis and rheumatism [15]. Therapeutic properties attributed to


[1]  A. D Rotman, “Las especies argentinas del genero Eugenia L. (Myrtaceae),” Boletin de la Sociedad Argentina de Botanica, vol. 30, pp. 63–93, 1995.
[2]  A. Kanazawa, A. Patin, and A. E. Greene, “Efficient, highly enantioselective synthesis of selina-1,3,7(11)-trien-8-one, a major component of the essential oil of Eugenia uniflora,” Journal of Natural Products, vol. 63, no. 9, pp. 1292–1294, 2000.
[3]  J. R. Alonso, Tratado de Fitomedicina, Isis Ediciones S.R.L, Buenos Aires, Argentina, 1998.
[4]  A. C. Adebajo, K. J. Oloke, and A. J. Aladesanmi, “Antimicrobial activities and microbial transformation of volatile oils of Eugenia uniflora,” Fitoterapia, vol. 60, no. 5, pp. 451–455, 1989.
[5]  A. E. Consolini and M. G. Sarubbio, “Pharmacological effects of Eugenia uniflora (Myrtaceae) aqueous crude extract on rat's heart,” Journal of Ethnopharmacology, vol. 81, no. 1, pp. 57–63, 2002.
[6]  E. E. S. Schapoval, S. M. Silveira, M. L. Miranda, C. B. Alice, and A. T. Henriques, “Evaluation of some pharmacological activities of Eugenia uniflora L,” Journal of Ethnopharmacology, vol. 44, no. 3, pp. 137–142, 1994.
[7]  F. B. Holetz, G. L. Pessini, N. R. Sanches, D. A. G. Cortez, C. V. Nakamura, and B. P. Dias Filho, “Screening of some plants used in the Brazilian folk medicine for the treatment of infectious diseases,” Memorias do Instituto Oswaldo Cruz, vol. 97, no. 7, pp. 1027–1031, 2002.
[8]  E. O. Lima, O. F. Gompertz, A. M. Giesbrecht, and M. Q. Paulo, “In vitro antifungal activity of essential oils obtained from officinal plants against dermatophytes,” Mycoses, vol. 36, no. 9-10, pp. 333–336, 1993.
[9]  A. C. L. Amorim, C. K. F. Lima, A. M. C. Hovell, A. L. P. Miranda, and C. M. Rezende, “Antinociceptive and hypothermic evaluation of the leaf essential oil and isolated terpenoids from Eugenia uniflora L. (Brazilian Pitanga),” Phytomedicine, vol. 16, no. 10, pp. 923–928, 2009.
[10]  F. Cacciola, P. Jandera, Z. Hajdú, P. ?esla, and L. Mondello, “Comprehensive two-dimensional liquid chromatography with parallel gradients for separation of phenolic and flavone antioxidants,” Journal of Chromatography A, vol. 1149, no. 1, pp. 73–87, 2007.
[11]  A. Gugliucci, “Antioxidant effects of Ilex paraguariensis: induction of decreased oxidability of human LDL in vivo,” Biochemical and Biophysical Research Communications, vol. 224, no. 2, pp. 338–344, 1996.
[12]  N. Dartora, L. M. De Souza, A. P. Santana-Filho, M. Iacomini, P. A. J. Gorin, and G. L. Sassaki, “UPLC-PDA-MS evaluation of bioactive compounds from leaves of Ilex paraguariensis with different growth conditions, treatments and ageing,” Food Chemistry, vol. 129, no. 4, pp. 1453–1461, 2011.
[13]  M. Sumino, Y. Saito, F. Ikegami, Y. Hirasaki, and T. Namiki, “Extraction efficiency of shosaikoto (Xiaochaihu Tang) and investigation of the major constituents in the residual crude drugs,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 890524, 2012.
[14]  A.-R. Im, Y.-H. Kim, M. R. Uddin et al., “Scutellaria baicalensis extracts and flavonoids protect rat l6 cells from antimycin a-induced mitochondrial dysfunction,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 517965, 2012.
[15]  M. A. Abd Jalil, A. N. Shuid, and N. Muhammad, “Role of medicinal plants and natural products on osteoporotic fracture healing,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 714512, 2012.
[16]  E. Christaki and S. M. Opal, “Immunomodulatory therapy for sepsis: an update,” Expert Review of Anti-Infective Therapy, vol. 9, no. 11, pp. 1013–1033, 2011.
[17]  J. Cohen, “The immunopathogenesis of sepsis,” Nature, vol. 420, no. 6917, pp. 885–891, 2002.
[18]  C. Thiemermann, “Nitric oxide and septic shock,” General Pharmacology, vol. 29, no. 2, pp. 159–166, 1997.
[19]  L. M. De Souza, N. Dartora, C. T. Scoparo et al., “Comprehensive analysis of maté (Ilex paraguariensis) compounds: development of chemical strategies for matesaponin analysis by mass spectrometry,” Journal of Chromatography A, vol. 1218, no. 41, pp. 7307–7315, 2011.
[20]  D. Rittirsch, M. S. Huber-Lang, M. A. Flierl, and P. A. Ward, “Immunodesign of experimental sepsis by cecal ligation and puncture,” Nature Protocols, vol. 4, no. 1, pp. 31–36, 2009.
[21]  P. P. Bradley, D. A. Priebat, R. D. Christensen, and G. Rothstein, “Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker,” Journal of Investigative Dermatology, vol. 78, no. 3, pp. 206–209, 1982.
[22]  D. W. Landry and J. A. Oliver, “Mechanisms of disease: the pathogenesis of vasodilatory shock,” New England Journal of Medicine, vol. 345, no. 8, pp. 588–595, 2001.
[23]  S. M. Pastores, D. P. Katz, and V. Kvetan, “Splanchnic ischemia and gut mucosal injury in sepsis and the multiple organ dysfunction syndrome,” American Journal of Gastroenterology, vol. 91, no. 9, pp. 1697–1710, 1996.
[24]  A. C. Tinker and A. V. Wallace, “Selective inhibitors of inducible nitric oxide synthase: potential agents for the treatment of inflammatory diseases?” Current Topics in Medicinal Chemistry, vol. 6, no. 2, pp. 77–92, 2006.
[25]  K. Ejima, M. D. Layne, I. M. Carvajal et al., “Cyclooxygenase-2-deficient mice are resistant to endotoxin-induced inflammation and death,” The FASEB Journal, vol. 17, no. 10, pp. 1325–1327, 2003.
[26]  G. B. Celli, A. B. Pereira-Netto, and T. Beta, “Comparative analysis of total phenolic content, antioxidant activity, and flavonoids profile of fruits from two varieties of Brazilian cherry (Eugenia uniflora L.) throughout the fruit developmental stages,” Food Research International, vol. 44, no. 8, pp. 2442–2451, 2011.
[27]  L. M. de Souza, T. R. Cipriani, C. F. Sant'Ana, M. Iacomini, P. A. J. Gorin, and G. L. Sassaki, “Heart-cutting two-dimensional (size exclusion × reversed phase) liquid chromatography-mass spectrometry analysis of flavonol glycosides from leaves of Maytenus ilicifolia,” Journal of Chromatography A, vol. 1216, no. 1, pp. 99–105, 2009.
[28]  E. Hvattum and D. Ekeberg, “Study of the collision-induced radical cleavage of flavonoid glycosides using negative electrospray ionization tandem quadrupole mass spectrometry,” Journal of Mass Spectrometry, vol. 38, no. 1, pp. 43–49, 2003.
[29]  F. Cuyckens and M. Claeys, “Determination of the glycosylation site in flavonoid mono-O-glycosides by collision-induced dissociation of electrospray-generated deprotonated and sodiated molecules,” Journal of Mass Spectrometry, vol. 40, no. 3, pp. 364–372, 2005.
[30]  L. M. de Souza, T. R. Cipriani, R. V. Serrato et al., “Analysis of flavonol glycoside isomers from leaves of Maytenus ilicifolia by offline and online high performance liquid chromatography-electrospray mass spectrometry,” Journal of Chromatography A, vol. 1207, no. 1-2, pp. 101–109, 2008.
[31]  Z. F. Peng, D. Strack, A. Baumert et al., “Antioxidant flavonoids from leaves of Polygonum hydropiper L,” Phytochemistry, vol. 62, no. 2, pp. 219–228, 2003.
[32]  J. H. Collins and M. Elzinga, “The primary structure of actin from rabbit skeletal muscle. Completion and analysis of the amino acid sequence,” Journal of Biological Chemistry, vol. 250, no. 15, pp. 5915–5920, 1975.
[33]  C. T. Scoparo, L. M. de Souza, N. Dartora, G. L. Sassaki, P. A. J. Gorin, and M. Iacomini, “Analysis of Camellia sinensis green and black teas via ultra high performance liquid chromatography assisted by liquid-liquid partition and two-dimensional liquid chromatography (size exclusion×reversed phase),” Journal of Chromatography A, vol. 1222, pp. 29–37, 2012.
[34]  Y. C. Chen, S. C. Shen, W. R. Lee, W. C. Hou, L. L. Yang, and T. J. F. Lee, “Inhibition of nitric oxide synthase inhibitors and lipopolysaccharide induced inducible NOS and cyclooxygenase-2 gene expressions by rutin, quercetin, and quercetin pentaacetate in RAW 264.7 macrophages,” Journal of Cellular Biochemistry, vol. 82, no. 4, pp. 537–548, 2001.
[35]  A. Hiermann, H. W. Schramm, and S. Laufer, “Anti-inflammatory activity of myricetin-3-O-β-D-glucuronide and related compounds,” Inflammation Research, vol. 47, no. 11, pp. 421–427, 1998.
[36]  Y. S. Lee and E. M. Choi, “Myricetin inhibits IL-1β-induced inflammatory mediators in SW982 human synovial sarcoma cells,” International Immunopharmacology, vol. 10, no. 7, pp. 812–814, 2010.
[37]  Y. Li, C. M. Frenz, Z. Li, and M. Chen, “Virtual and In vitro bioassay screening of phytochemical inhibitors from flavonoids and isoflavones against Xanthine oxidase and Cyclooxygenase-2 for gout treatment,” Chemical Biology and Drug Design. In press.


comments powered by Disqus