Polyphenol-rich extract and fractions of Terminalia phaeocarpa Eichler possess hypoglycemic effect, reduce the release of cytokines, and inhibit lipase, α-glucosidase, and α-amilase enzymes.

ETHNOPHARMACOLOGICAL RELEVANCE: species of Terminalia (Combretaceae) are used to treat diabetes and metabolic disorders in Asia, Africa, and America. Terminalia phaeocarpa Eichler is an endemic tree from Brazil, popularly known as capitão. This species is closely related to Terminalia argentea Mart., also vulgarly known as capitão, a native but not endemic tree. Due to their phenotype similarity, these species might eventually prove inseparable and they are indistinctly used by locals to treat diabetes, among other diseases. The potential antidiabetic effect of T. argentea has been previously reported, whereas the biological effects and chemical composition of T. phaeocarpa have never been addressed so far. AIM OF THE STUDY: investigate the hypoglycaemic effect of an ethanol extract (EE) of T. phaeocarpa leaves and its ethyl acetate (FrEtOAc) and hydromethanolic (FrMEOH) fractions, in addition to their activity on the release of pro-inflammatory mediators and inhibition of lipase, α-amylase, and α-glucosidase enzymes. Additionally, it aimed to characterize the chemical composition of the extract and fractions, seeking to identify the compounds related to the biological activities. MATERIALS AND METHODS: The effect on the release of TNF-α, IL-1ß, and CCL-2 was evaluated in LPS-stimulated THP-1 cells (ATCC TIB-202). The inhibition of lipase, α-amylase, and α-glucosidase was tested in vitro, whereas the hypoglycemic effect was assayed in the oral starch tolerance test. The chemical composition was investigated by extensive UHPLC-DAD-ESI-MS/MS analyses. RESULTS: The extract and derived fractions reduced TNF-α (EE pIC50 = 4.58 ± 0.01; FrEtOAc pIC50 = 4.69 ± 0.01; FrMeOH pIC50 = 4.54 ± 0.02) and IL-1ß (EE pIC50 = 4.86 ± 0.02; FrEtOAc pIC50 = 4.86 ± 0.02; FrMeOH pIC50 = 4.75 ± 0.01) release by LPS-stimulated THP-1 cells in a concentration-dependent manner, whereas the inhibitory effect on CCL-2 release did not reach a clear linear relationship for the tested concentrations. The extract and fractions also inhibited in vitro the activity of lipase (EE pIC50 = 3.97 ± 0.12; FrEtOAc pIC50 = 3.87 ± 0.04; FrMeOH pIC50 = 3.67 ± 0.14), α-amylase (EE pIC50 = 4.46 ± 0.27; FrEtOAc pIC50 = 5.47 ± 0.27; FrMeOH pIC50 = 4.26 ± 0.22), and α-glucosidase (EE pIC50 = 5.46 ± 0.05; FrEtOAc pIC50 = 5.79 ± 0.11; FrMeOH pIC50 = 5.74 ± 0.05). The pIC50 values of the test samples were lower than those obtained with orlistat (7.59 ± 0.08) and acarbose (6.04 ± 0.37 and 7.63 ± 0.04) employed as the positive controls respectively in the lipase, α-amylase, and α-glucosidase assays. When assayed in the oral starch tolerance test, the extract and fractions also reduced animal glycaemia. UHPLC-DAD-ESI-MS/MS analyses of the extract and fractions led to the identification of 38 phenolic compounds, mainly phenolic acids, ellagitannins and flavonoids, among others, all of them first-time described for the species. CONCLUSION: Based on our findings, T. phaeocarpa has hypoglycaemic activity and polyphenols are the probable bioactive compounds, which support the ethnomedical use of the species.

Delay of ejaculation induced by Bersama engleriana in nicotinamide/streptozotocin-induced type 2 diabetic rats.

OBJECTIVE: To evaluate the effects of aqueous and methanolic extracts of Bersama engleriana (B. engleriana) leaves on the expulsion phase of fictive ejaculation in nicotinamide/streptozotocin-induced type 2 diabetic male rats. METHODS: The electromyographic activity of the bulbospongiosus muscles was recorded in urethane anaesthetized, spinal cord transected rats receiving dopamine (0.1 µmol/L/kg) intravenously, in the absence or presence of aqueous and methanolic extracts of B. engleriana (2.5, 10, 50, 60, 75 mg/kg). In another experiment, the pro-ejaculatory effect of dopamine (0.1 µmol/L/kg, i.v.) was monitored in rats orally pre-treated with the aqueous and methanolic extracts (60 mg/kg) of B. engleriana for 1 or 4 weeks. RESULTS: Results of the study showed that the intravenous administration of B. engleriana did not provoke any contraction of the ejaculatory muscles whilst rhythmic and rapid contractions of the bulbospongiosus muscles accompanied sometimes by penis movement and expulsion of the urethral contents were recorded after dopamine application. The sequential treatment of animals with B. engleriana extracts (2.5-75.0 mg/kg) followed by dopamine (0.1 µmol/L/kg) resulted in a dose-dependent abolishment of the pro-ejaculatory response due to dopamine. However, in animals orally submitted to a daily gavage with B. engleriana extracts (60 mg/kg) for 1 or 4 weeks, the ejaculation stimulating effect of dopamine (0.1 µmol/L/kg) was significantly delayed (P<0.01) but not completely suppressed. CONCLUSIONS: Present findings suggest the involvement of dopaminergic system in the activity of B. engleriana and further support its aphrodisiac potentials due to sterols and saponins revealed in this plant.