Case-control association study of polymorphisms in the angiotensinogen and angiotensin-converting enzyme genes and coronary artery disease and systemic artery hypertension in African-Brazilians and Caucasian-Brazilians.

The rennin-angiotensin-aldosterone system (RAAS) is a critical pathway in regulating blood pressure and salt/water homeostasis, possessing an intimate relationship with the development of systemic artery hypertension (SAH). Once hypertension is considered a risk factor for coronary artery disease (CAD), the RAAS is also related to this pathology. This investigation aimed to analyse if the frequencies of AGT M235T (rs699) and ACE I/D (rs4646994) polymorphisms are associated with CAD and SAH in African-Brazilians and Caucasian-Brazilians. In this study we analysed 714 subjects who underwent coronary angiography to detect obstructive lesions and CAD, as well as blood pressure measurement and SAH, grouped according to ethnicity: 266 African-Brazilians and 448 Caucasian-Brazilians. Among CAD and SAH cases and controls, the genotype and allele frequencies of ACE I/D polymorphism were similar in both ethnic groups. The AGT 235TT genotype and 235T allele frequencies were higher in SAH cases (32%, 54.7%) versus controls in Caucasian-Brazilians (19.8%, 46.4%; P = 0.038, P = 0.031, respectively). The AGT 235TT (OR = 1.8; P = 0.028) demonstrated to be an independent factor risk in a multivariate logistic regression increasing SAH risk in Caucasians but not in African-Brazilians. In summary, AGT M235T polymorphism was associated with SAH risk in Caucasian-Brazilians, and no association was detected with CAD. No association was also observed in ACE I/D polymorphism either in CAD or SAH in African-Brazilians and Caucasian-Brazilians.

Antinociceptive and anti-inflammatory effects of Brazilian red propolis extract and formononetin in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Propolis has been used as a folk medicine for centuries around the world due to its wide spectrum of biological activities. The red propolis, a new Brazilian variety of this apimaterial, has presented an unusual chemical composition, including isoflavones such as formononetin and biochanin A. Since both the green and red varieties of propolis are traditionally used as medicine and commercialized with no label differentiation, the study of the activities of red propolis extract has become important in order to clarify whether this product has the same activities as commercial ones. In this work, we demonstrated the potential action of the hydroalcoholic extract of red propolis (HERP) and its biomarker, formononetin, as antinociceptive and anti-inflammatory drugs on experimental models. MATERIALS AND METHODS: The HERP was chemically characterised by HPLC/DAD analyses. The biological activities of the HERP (3, 10, and 30mg/kg) and formononetin (10mg/kg) were evaluated using the antinociceptive (acetic acid, formalin, and glutamate injections) and anti-inflammatory (carrageenan-induced hindpaw oedema and peritonitis) models in mice after oral administration. The open field test was also performed. RESULTS: Formononetin, one of the main biomarker of red propolis, was identified in the HERP (21.62mg/g). Pretreatment with the HERP (10 and 30mg/kg) and formononetin (10mg/kg) produced reduction (P<0.001) in the number of abdominal writhes, but the HERP was more effective (P<0.001) than formononetin. In the formalin test, all HERP doses (3, 10, and 30mg/kg, P<0.001) inhibited the late phase (inflammatory pain) of formalin-induced licking, but the inhibition of neurogenic pain was observed only when the higher doses (10 and 30mg/kg; P<0.05) were used. Formononetin caused inhibition (P<0.001) only in the second phase of formalin-induced nociception similarly at all HERP doses in the same phase of the test. The responses in glutamate-induced model presented crescent inhibition (P<0.05) with 10 and 30mg/kg of HERP. Also, formononetin inhibited (P<0.001) the nociception induced by glutamate similarly to 30mg/kg of HERP. There were no significant differences in the open field test after HERP administration, but formononetin decrease the spontaneous motor behaviour. Regarding the anti-inflammatory assessment, the HERP (10 and 30mg/kg, P<0.05) and formononetin (P<0.001) treatments caused a significant inhibition of the oedema response. All doses of HERP (3, 10, and 30mg/kg, P<0.05) and formononetin (P<0.001) also inhibited the carrageenan-induced leukocyte migration. In both cases, the results for the HERP at 30mg/kg and formononetin were similar. CONCLUSIONS: The HERP and formononetin presented significant anti-inflammatory activity. Moreover, the HERP presented antinociceptive action on inflammatory and neurogenic pain without motor side effects, possibly due to the action of other constituents present in the extract. These results, together, support the popular usage of this natural product.