Multiple Risk Factors for Heart Disease: A Challenge to the Ethnopharmacological Use of Croton urucurana Baill.

Croton urucurana Baill. is a native Brazilian tree, popularly known as "sangra-d'água" or "sangue-de-dragão," based on the red resinous sap of the trunk. Its use has been transmitted through generations based on popular tradition that attributes analgesic, anti-inflammatory, and cardioprotective properties to the tree. However, its cardioprotective effects have not yet been scientifically investigated. Thus, the present study investigated the pharmacological response to an ethanol-soluble fraction from the leaves of C. urucurana in Wistar rats exposed to smoking and dyslipidemia, two important cardiovascular risk factors. The extract was evaluated by high-performance liquid chromatography. Wistar rats received a 0.5% cholesterol-enriched diet and were exposed to cigarette smoke (9 cigarettes/day for 10 weeks). During the last 5 weeks, the animals were orally treated with vehicle (negative control group), C. urucurana extract (30, 100, and 300 mg/kg), or simvastatin (2.5 mg/kg) + enalapril (15 mg/kg). One group of rats that was not exposed to these risk factors was also evaluated (basal group). Electrocardiograms and systolic, diastolic, and mean blood pressure were measured. Blood was collected to measure total cholesterol, triglycerides, urea, and creatinine. The heart and kidneys were collected and processed for oxidative status and histopathological evaluation. The phytochemical analysis revealed different classes of flavonoids and condensed tannins. The model induced dyslipidemia and cardiac and renal oxidative stress and increased levels of urea and creatinine in the negative control group. Treatment with the C. urucurana extract (300 mg/kg) and simvastatin + enalapril decreased cholesterol and triglyceride levels. In contrast to simvastatin + enalapril treatment, the C. urucurana extract exerted cardiac and renal antioxidant effects. No alterations of electrocardiograms, blood pressure, or histopathology were observed between groups. These findings indicate that C. urucurana exerts lipid-lowering, renal, and cardioprotective effects against oxidative stress in a preclinical model of multiple risk factors for heart disease.

Cardioprotective effects of Talinum paniculatum (Jacq.) Gaertn. in doxorubicin-induced cardiotoxicity in hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Talinum paniculatum (Jacq.) Gaertn. (Talinaceae) is a medicinal species that is widely distributed throughout Brazil. Popularly known as "major-gomes," the species is used in folk medicine for the treatment of cardiovascular disorders. AIM OF THE STUDY: To evaluate the effect of an ethanolic extract of T. paniculatum (EETP) in rats with renovascular hypertension and heart failure and determine its chemical composition. MATERIALS AND METHODS: First, EETP was obtained, and its chemical profile was analyzed by LC-DAD-MS. The acute toxicity was evaluated in female Wistar rats. The model of renovascular hypertension was established in male Wistar rats by combining the Goldblatt 2K1C method and intraperitoneal doxorubicin administration for 6 weeks. The animals were then treated daily with EETP (30, 100, and 300 mg/kg) or metoprolol (25 mg/kg) by gavage for 28 days. The negative control group was treated with vehicle (filtered water). The sham group consisted of animals that were not subjected to 2K1C or cardiotoxicity and were treated with vehicle. Renal function was evaluated on days 1, 14, and 28. At the end of treatment, the electrocardiographic profile, blood pressure, and mesenteric vascular reactivity were investigated. Serum urea, creatinine, angiotensin converting enzyme, nitrotyrosine, malondialdehyde, nitrite, aldosterone, and sodium and potassium levels were measured. The heart, aorta artery, liver, and right kidney were collected, weighed, and processed for histopathological analysis. Cardiac chambers also underwent morphometric analysis. RESULTS: No signs of toxicity were observed in female Wistar rats. Thirty-two compounds were annotated from EETP, including flavonoids, chlorogenic acids, and saponins. EETP treatment resulted in a significant cardiorenal-protective response, normalizing electrocardiographic and hemodynamic alterations, and preventing ventricle remodeling. These effects were associated with serum antioxidant activity and angiotensin-converting enzyme (ACE) inhibition. CONCLUSION: The present study demonstrated that EETP may exert cardioprotective effects through serum antioxidant activity and ACE inhibition, preventing alterations of hemodynamic and endothelial function, and reducing damage to cardiac structure. Thus, EETP, especially at the 100 and 300 mg/kg doses, may be useful for preventing doxorubicin-induced cardiotoxicity in hypertensive patients.

Autologous Infusion of Bone Marrow and Mesenchymal Stromal Cells in Patients with Chronic Obstructive Pulmonary Disease: Phase I Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is characterized by the destruction of alveolar walls, chronic inflammation and persistent respiratory symptoms. There is no curative clinical treatment for COPD. In this context, cell-based therapy is a promising therapeutic alternative for COPD. Thus, in this open, controlled and randomized Phase I Clinical Trial, we aimed to assess the safety of the infusion of autologous bone marrow mononuclear cells (BMMC), adipose-derived mesenchymal stromal cells (ADSC) and, especially, the safety of concomitant infusion (co-infusion) of BMMC and ADSC as a new therapeutic alternative for COPD. The rationale for co-infusion of BMMC and ADSC is based on the hypothesis of an additive or synergistic therapeutic effect resulting from this association. METHODS: To achieve the proposed objectives, twenty patients with moderate-to-severe COPD were randomly divided into four groups: control group - patients receiving conventional treatment; BMMC group - patients receiving only BMMC; ADSC group - patients receiving only ADSC, and co-infusion group - patients receiving the concomitant infusion of BMMC and ADSC. Patients were assessed for pulmonary function, biochemical profile, and quality of life over a 12 months follow-up. RESULTS: No adverse events were detected immediately after the infusion of BMMC, ADSC or co-infusion. In the 12-month follow-up, no causal relationship was established between adverse events and cell therapy procedures. Regarding the efficacy, the BMMC group showed an increase in forced expiratory volume (FEV1) and diffusing capacity for carbon monoxide (DLCO). Co-infusion group showed a DLCO, and gas exchange improvement and a better quality of life. CONCLUSION: The results obtained allow us to conclude that cell-based therapy with co-infusion of BMMC and ADSC is a safe procedure and a promising therapeutic for COPD. However, additional studies with a greater number of patients are needed before randomized and controlled Phase III clinical trials can be implemented.