Evidence for the efficacy of anti-inflammatory plants used in Brazilian traditional medicine with ethnopharmacological relevance.

ETHNOPHARMACOLOGICAL RELEVANCE: When exacerbated, inflammatory processes can culminate in physical and emotional disorders and, if not stopped, can be lethal. The high prevalence of inflammation has become a public health problem, and the need for new drugs to treat this pathology is imminent. The use of medicinal plants has emerged as an alternative, and a survey of data that corroborates its application in inflammatory diseases is the starting point. Furthermore, Brazil harbors a megadiversity, and the traditional use of plants is relevant and needs to be preserved and carefully explored for the discovery of new medicines. AIM OF THE STUDY: This review sought to survey the medicinal plants traditionally used in Brazil for the treatment of inflammatory processes and to perform, in an integrative way, a data survey of these species and analysis of their phytochemical, pharmacological, and molecular approaches. MATERIALS AND METHODS: Brazilian plants that are traditionally used for inflammation (ophthalmia, throat inflammation, orchitis, urinary tract inflammation, ear inflammation, and inflammation in general) are listed in the DATAPLAMT database. This database contains information on approximately 3400 native plants used by Brazilians, which were registered in specific documents produced until 1950. These inflammatory disorders were searched in scientific databases (PubMed/Medline, Scopus, Web of Science, Lilacs, Scielo, Virtual Health Library), with standardization of DECS/MESH descriptors for inflammation in English, Spanish, French, and Portuguese, without chronological limitations. For the inclusion criteria, all articles had to be of the evaluated plant species, without association of synthesized substances, and full articles free available in any of the four languages searched. Duplicated articles and those that were not freely available were excluded. RESULTS: A total of 126 species were identified, culminating in 6181 articles in the search. After evaluation of the inclusion criteria, 172 articles representing 40 different species and 38 families were included in the study. Comparison of reproducibility in intra-species results became difficult because of the large number of extraction solvents tested and the wide diversity of evaluation models used. Although the number of in vitro and in vivo evaluations was high, only one clinical study was found (Abrus precatorius). In the phytochemical analyses, more than 225 compounds, mostly phenolic compounds, were identified. CONCLUSION: This review allowed the grouping of preclinical and clinical studies of several Brazilian species traditionally used for the treatment of many types of inflammation, corroborating new searches for their pharmacological properties as a way to aid public health. Furthermore, the large number of plants that have not yet been studied has encouraged new research to revive traditional knowledge.

Metformin inhibits paclitaxel-induced mechanical allodynia by activating opioidergic pathways and reducing cytokines production in the dorsal root ganglia and thalamus.

It has been shown that AMP-activated protein kinase (AMPK) is involved in the nociceptive processing. This observation has prompted us to investigate the effects of the AMPK activator metformin on the paclitaxel-induced mechanical allodynia, a well-established model of neuropathic pain. Mechanical allodynia was induced by four intraperitoneal (i.p) injections of paclitaxel (2 mg/kg.day) in mice. Metformin was administered per os (p.o.). Naltrexoneandglibenclamide were used to investigate mechanisms mediating metformin activity. Concentrations of cytokines in the dorsal root ganglia (DRG) and thalamus were determined. After a single p.o. administration, the two highest doses of metformin (500 and 1000 mg/kg) attenuated the mechanical allodynia. This response was attenuated by all doses of metformin (250, 500 and 1000 mg/kg) when two administrations, 2 h apart, were carried out. Naltrexone (5 and 10 mg/kg, i.p.), but not glibenclamide (20 and 40 mg/kg, p.o.), attenuated metformin activity. Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and CXCL-1 in the DRG were increased after administration of paclitaxel. Metformin (1000 mg/kg) reduced concentrations of TNF-α, IL-1ß and CXCL-1 in the DRG. Concentration of IL-6, but not TNF-α, in the thalamus was increased after administration of paclitaxel. Metformin (1000 mg/kg) reduced concentration of IL-6 in the thalamus. In summary, metformin exhibits activity in the model of neuropathic pain induced by paclitaxel. This activity may be mediated by activation of opioidergic pathways and reduced production of TNF-α, IL-1ß and CXCL-1 in the DRG and IL-6 in the thalamus.