Byrsonima fagifolia: An integrative study to validate the gastroprotective, healing, antidiarrheal, antimicrobial and mutagenic action

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Ethnopharmacological relevance: Ethnopharmacological survey indicated leaves of Byrsonima fagifolia Nied. (Malpighiaceae) against gastrointestinal disorders. Aim of the study:The methanolic extract from the leaves of Byrsonima fagifolia (denominated BF)was evaluated for toxic, mutagenic, gastroprotective, antidiarrheal, antibacterial and immunomodulatory activities. Materials and methods: The preventive and healing action of BF against gastric ulcer was evaluated in experimental models in rodents. We evaluated immunomodulatory (by murine peritoneal macrophages), antidiarrheal (by induced diarrhea with castor oil and intestinal motility) and antibacterial action of BF against standard strain of Escherichia coli, Staphylococcus aureus and Helicobacter pylori. The safety of use of BF was also evaluated by mutagenic (Ames assay) and by analyses of toxicity parameters. Results: Phytochemical BF profile indicated the presence of phenolic compounds with antioxidant and radical-scavenging properties. BF significantly inhibited gastric lesions induced by ethanol and HCl/ethanol and endogenous mucosal sulphydryl groups (SHs) participated efficaciously in BF gastroprotection. OF blocked development of inflammation process and also has antidiarrheal actions. This extract accelerated the healing of the gastric ulcerated mucosa by stimulating proliferative factors and by increasing production of gastric mucus with no toxic action. The substances responsible for the protective action are concentrated in the ethyl acetate fraction that demonstrated no mutagenic action in vitro. Conclusions: Byrsonima fagifolia presents gastroprotective, healing and antidiarrheal activities supporting previous claims that its traditional use by Brazilians can treat these gastrointestinal ailments. Published by Elsevier Ireland Ltd1202149160Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Mutagenicity and antimutagenicity of (−)-hinokinin a trypanosomicidal compound measured by <it>Salmonella</it> microsome and comet assays

<p>Abstract</p> <p>Background</p> <p>The dibenzylbutyrolactone lignan (−)-hinokinin (HK) was derived by partial synthesis from (−)-cubebin, isolated from the dry seeds of the pepper, <it>Piper cubeba</it>. Considering the good trypanosomicidal activity of HK and recalling that natural products are promising starting points for the discovery of novel potentially therapeutic agents, the aim of the present study was to investigate the (anti) mutagenic∕ genotoxic activities of HK.</p> <p>Methods</p> <p>The mutagenic∕ genotoxic activities were evaluated by the Ames test on <it>Salmonella typhimurium</it> strains TA98, TA97a, TA100 and TA102, and the comet assay, so as to assess the safe use of HK in the treatment of Chagas’ disease. The antimutagenic ∕antigenotoxic potential of HK were also tested against the mutagenicity of a variety of direct and indirect acting mutagens, such as 4- nitro-<it>o</it>-phenylenediamine (NOPD), sodium azide (SA), mitomycin C (MMC), benzo[<it>a</it>]pyrene (B[<it>a</it>]P), aflatoxin B₁ (AFB₁), 2-aminoanthracene (2-AA) and 2-aminofluorene (2-AF), by the Ames test, and doxorubicin (DXR) by the comet assay.</p> <p>Results</p> <p>The mutagenicity∕genotoxicity tests showed that HK did not induce any increase in the number of revertants or extent of DNA damage, demonstrating the absence of mutagenic and genotoxic activities. On the other hand, the results on the antimutagenic potential of HK showed a strong inhibitory effect against some direct and indirect-acting mutagens.</p> <p>Conclusions</p> <p>Regarding the use of HK as an antichagasic drug, the absence of mutagenic effects in animal cell and bacterial systems is encouraging. In addition, HK may be a new potential antigenotoxic ∕ antimutagenic agent from natural sources. However, the protective activity of HK is not general and varies with the type of DNA damage-inducing agent used.</p