Plant from Brazil contains a compound with an anti-inflammatory action | AGÊNCIA FAPESP

Plant from Brazil contains a compound with an anti-inflammatory action A substance found in Baccharis retusa DC. has a similar effect to dexamethasone, the drug that is most widely used to treat asthma, a study shows (photo: João Henrique Ghilardi Lago)

Plant from Brazil contains a compound with an anti-inflammatory action

February 25, 2015

By Elton Alisson

Agência FAPESP – Researchers at the Institute of Environmental, Chemical & Pharmaceutical Sciences of the Federal University of São Paulo (UNIFESP) in Brazil have isolated and characterized a bioactive compound with anti-inflammatory, antimicrobial and antiparasitic properties from a plant found in Serra da Mantiqueira, a mountain range in the states of São Paulo, Minas Gerais and Rio de Janeiro.

The compound, called sakuranetin, was identified during a project conducted with support from FAPESP under its Young Investigators Grants program.

“We observed that the anti-inflammatory activity of sakuranetin is very similar to that of dexamethasone, the main corticoid used today in the treatment of severe allergic and inflammatory processes,” said João Henrique Ghilardi Lago, a professor at UNIFESP and the lead investigator for the project.

Sakuranetin was isolated from Baccharis retusa DC., a plant in the Asteraceae family, to which the sunflower (Helianthus annuus) and several other medicinal plants also belong.

According to Lago, the genus Baccharis – one of the most important in the Asteraceae family, which comprises some 500 plant species, including carqueja (Baccharis trimera) – is very common in South and Central America in high-altitude regions such as Serra da Mantiqueira.

When the researchers searched for plant species with bioactive compounds of pharmacological interest in the hills around Campos do Jordão, São Paulo State, they found a large variety of species of Baccharis in the area, the highest in Serra da Mantiqueira at an altitude of 1,628 meters.

“We were surprised by the variety of Baccharis species in the Mantiqueira hills,” Lago told Agência FAPESP. “We collected some ten different species in the area of Campos do Jordão, including Baccharis retusa DC.

To select potentially bioactive species, the researchers prepared extracts from the plants that they had collected and then submitted the extracts to a series of laboratory tests.

The extract from Baccharis retusa DC. showed more anti-inflammatory, antimicrobial and antiparasitic activity compared with the extracts from the other species collected.

Building on this finding, the researchers analyzed the extract from Baccharis retusa DC. by high-performance liquid chromatography and nuclear magnetic resonance spectroscopy to determine the plant’s chemical composition.

Chemical analysis showed that when the raw plant extract was diluted in ethanol about 50% consisted of a single substance: sakuranetin. “This is very rare in plants, which almost always contain a wide variety of compounds,” Lago said.

Next, the researchers fractionated the raw extract and found that the plant’s active substance was sakuranetin.

“The fact that some 50% of the raw extract from Baccharis retusa DC. consisted of sakuranetin facilitated isolation of this compound, which is a flavonoid,” Lago said. Flavonoids are widely distributed plant polyphenols with beneficial effects on human health.

“It’s very rare in natural plant chemistry to obtain such a large amount of a substance, in the order of grams, as for sakuranetin from Baccharis retusa DC.

Antiparasitic activity

To assess the antiparasitic activity of sakuranetin, the researchers at UNIFESP, in partnership with André Tempone at Instituto Adolfo Lutz, Rodrigo Cunha at Universidade Federal do ABC (UFABC) and Paulette Romoff at Universidade Presbiteriana Mackenzie, isolated the compound and tested it with two semi-synthetic derivatives against Leishmania spp. and Trypanosoma cruzi, the parasites that cause leishmaniasis and Chagas disease, respectively.

The tests showed that sakuranetin exhibited antiparasitic activity against Leishmania (L.) amazonensis, Leishmania (V.) braziliensis, Leishmania (L.) major and Leishmania (L.) chagasi at concentrations of 43-52 micrograms per milliliter (μg/ml) and against Trypanosoma cruzi at a lower concentration (20.17 μg/ml).

The two semi-synthetic derivatives of sakuranetin displayed no antiparasitic activity.

Some of the main results of the study, performed as part of the project “Leishmanicidal principles of vegetable species from Atlantic Forest: evaluation, isolation and molecular characterization”, which Lago developed in collaboration with Patricia Sartorelli, another researcher at UNIFESP, were published in the journal Experimental Parasitology. The project was supported by FAPESP.

“Sakuranetin was found to be the only active substance among flavonoids in Baccharis retusa DC. against the parasites that cause leishmaniasis and Chagas disease,” Lago said.

Anti-inflammatory action

In another study, Lago and Carla Prado, also a researcher at UNIFESP, in collaboration with colleagues at the University of São Paulo’s School of Medicine (FMUSP), evaluated the anti-inflammatory activity of sakuranetin in an experimental mouse model of asthma.

Several animals were treated with sakuranetin for five days. A control group received dexamethasone.

The findings, published in the British Journal of Pharmacology, showed that treatment with sakuranetin attenuated various aspects of airway allergic inflammation by reducing pro-inflammatory cytokines and chemokines and controlling oxidative stress.

According to the authors of the study, the effects of sakuranetin were similar to those observed in animals treated with dexamethasone for most of the parameters evaluated.

“Sakuranetin is a potential candidate for the development of a molecular prototype to obtain a new asthma drug,” Lago said.

Antimicrobial action

In collaboration with Marcelo Vallim and Renata Pascon at UNIFESP, and Antonio Doriguetto and Marisi Soares at the Federal University of Alfenas (Minas Gerais), the researchers characterized the crystal structure of sakuranetin and evaluated the antimicrobial action of the bioactive compound against yeasts belonging to the genera Candida and Cryptococcus as well as against the BY 4742 strain of Saccharomyces cerevisiae.

As the authors explain in a paper published in the journal Molecules, sakuranetin displayed strong antifungal activity against these pathogens and may be considered by the pharmaceutical industry as a prototype for the development of more effective antifungal agents.

“We’re now at the crucial point of evaluating the toxicity of sakuranetin,” Lago said. “It’s useless to have a substance with as powerful an anti-inflammatory action as the standard asthma drug if we don’t know the concentration at which it can be administered to animals and humans.”

In addition to sakuranetin, the researchers at UNIFESP studied other bioactive compounds during the project “Sustainable use of biodiversity in remaining areas of Atlantic Forest of São Paulo: evaluation, isolation and molecular characterization of bioactive secondary metabolites in plant species”, supported by FAPESP’s BIOTA Program.

The paper “In vitro antileishmanial and antitrypanosomal activities of flavanones from Baccharis retusa DC. (Asteraceae)” (doi: 10.1016/j.exppara.2011.11.002), by Lago et al., can be read in Experimental Parasitology at www.sciencedirect.com/science/article/pii/S0014489411003298.

The paper “Flavonone treatment reverses airway inflammation and remodeling in an asthma murine model” (doi: 10.1111/bph.12062), by Toledo et al., can be read in the British Journal of Pharmacology at http://onlinelibrary.wiley.com/doi/10.1111/bph.12062/full.

The paper “Structural crystalline characterization of sakuranetin – an antimicrobial flavanone from twigs of Baccharis retusa (Asteraceae)” (doi: 10.3390/molecules19067528), by Lago et al., can be read in Molecules at www.mdpi.com/1420-3049/19/6/7528.

 

  Republish
 

Republish

Agência FAPESP licenses news reports under Creative Commons license CC-BY-NC-ND so that they can be republished free of charge and in a straightforward manner by other digital media or by print media. The name of the author or reporter (when applied) must be cited, as must the source (Agência FAPESP). Using the button HTML below ensures compliance with the rules described in Agência FAPESP’s Digital Content Republication Policy.


Topics most popular