Pharmacological safety of Plinia cauliflora (Mart.) Kausel in rabbits

Abstract

Fruit peels of Plinia cauliflora (Mart.) Kausel are widely used in Brazilian traditional medicine, but no studies have proved the safety of its pharmacological effects on the respiratory, cardiovascular, and central nervous systems. The present study assessed the safety pharmacology of P. cauliflora in New Zealand rabbits. First, an ethanol extract (EEPC) was selected for the pharmacological experiments and chemical characterization. Then, different groups of rabbits were orally treated with EEPC (200 and 2000 mg/kg) or vehicle. Acute behavioral and physiological alterations in the modified Irwin test, respiratory rate, arterial blood gas, and various cardiovascular parameters (i.e., heart rate, blood pressure, and electrocardiography) were evaluated. The main secondary metabolites that were identified in EEPC were ellagic acid, gallic acid, O-deoxyhexosyl quercetin, and the anthocyanin O-hexosyl cyanidin. No significant behavioral or physiological changes were observed in any of the groups. None of the doses of EEPC affected respiratory rate or arterial blood gas, with no changes on blood pressure or electrocardiographic parameters. The present study showed that EEPC did not cause any significant changes in respiratory, cardiovascular, or central nervous system function. These data provide scientific evidence of the effects of this species and important safety data for its clinical use.

Keywords: ABG, Arterial blood gas; ANOVA, One-way analysis of variance; ASE, Accelerated solvent extraction; BB, Buffer Base; BE, Base Excess; BEecf, Base excess in the extracellular fluid compartment; CNS, Central nervous system; Ca++, Calcium; Cardiovascular; Cl, Chloride; DBP, Diastolic blood pressure; ECG, Electrocardiography; EEPC, Ethanol extract of Plinia cauliflora; GAE, Gallic acid equivalent; H+, Hydrogen ion dissociated; HHb, Deoxyhemoglobin; Hct, Hematocrit; Irwin test; K+, Potassium; LA, Left arm; LC-DAD-MS, Liquid chromatography coupled to a diode array detector and mass spectrometer; LL, Left leg; MAP, Mean arterial pressure; Myrtaceae; Na+, Sodium; Na₂CO₃, Sodium carbonate; O2Hb, Oxyhemoglobin; P50, Half of the maximum hemoglobin saturation; PCO2, Partial pressure of carbon dioxide; PO2, Partial pressure of oxygen; RA, Right arm; RL, Right leg; Respiratory; S.E.M, Standard error of the mean; SBP, Systolic blood pressure; SO2, Level of hemoglobin-saturation by oxygen; Toxicology; UFLC, Ultra fast liquid chromatograph; cHCO3, Bicarbonate concentration; ctCO2 (B), Concentration of total carbon dioxide of whole blood; ctCO2 (P), Concentration of total carbon dioxide in plasma; ctO2, Concentration of total oxygen; pH, Potential of hydrogen; tHb, Hemoglobin.

Graphical abstract

Fig. 1

Base peak chromatograms (negative ion mode) from the extracts of peels obtained by ASE with the extractor solvents acetone:water (1:1 v/v), ethanol and ethanol:water (7:3 v/v) and water.

Fig. 2

Base peak chromatograms obtained by negative (A) and positive ion modes (B) from ethanol:water (7:3) extract (EEPC). (*chromatographic peaks are not of the analyzed sample).

Fig. 3

Electrocardiographic quantitative data of rabbits treated with EEPC or vehicle in the PR (A), QRS (B), and QT-segments (C) and P (D), R (E) and T-waves (F) amplitude. Representative electrocardiographic records carried out in limb lead I also are shown (G). Statistical analyses were performed using one-way ANOVA followed by Dunnett post hoc test. The results are expressed as mean ± standard error of the mean (S.E.M.) and p-value of less than 0.05 was considered statistically significant. C: control (vehicle); EEPC: ethanol extract from Plinia cauliflora.

Fig. 4

Acute oral administration of EEPC obtained from P. cauliflora does not affect SBP, DBP, MAP, and HR in New Zealand rabbits. Statistical analyses were performed using one-way ANOVA followed by Dunnett post hoc test. The results are expressed as mean ± standard error of the mean (S.E.M.) and p-value of less than 0.05 was considered statistically significant. C: control (vehicle); DBP: diastolic blood pressure; EEPC: ethanol extract from Plinia cauliflora; HR: heart rate; MAP: mean arterial pressure; SBP: systolic blood pressure.