Agrimonia eupatoria L.: An integrative perspective on ethnomedicinal use, phenolic composition and pharmacological activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Agrimonia eupatoria L., a plant which belongs to the Rosaceae family, is widespread in temperate regions, particularly throughout the northern hemisphere. In folk medicine, this plant species has been used for its astringent, anti-inflammatory, analgesic and hypotensive properties as well as in gastrointestinal disorders. As these biological properties have been linked to its phenolic composition, this plant species could be an interesting source of bioactive compounds with therapeutic potential. AIM OF THE STUDY: The aim of the present review is to provide a comprehensive overview of the scientific literature on A. eupatoria, particularly in regard to its ethnobotanics and ethnomedicinal uses, phenolic composition and biological and pharmacological activities. MATERIAL AND METHODS: Literature was retrieved from several bibliographic sources, namely PubMed, ScienceDirect and Google Scholar, since the first report on A. eupatoria in 1993. RESULTS: Regarding the phytochemical composition, A. eupatoria is rich in phenolic acids, flavonoids and tannins. The most commonly reported compounds are astragalin, cynaroside, hyperoside, isoquercitrin, isovitexin, rutin, catechin, procyanidin B3 and agrimoniin. In terms of bioactivity, extracts or fractions obtained from this plant species have shown antioxidant, antimicrobial, antidiabetic, antinociceptive and anti-inflammatory properties, among others. So far, two clinical studies with the infusion of A. eupatoria have shown hepatoprotective properties as well as a protective role in cardiovascular disease, metabolic disorders and diabetes. CONCLUSIONS: In this review, an integrative perspective on ethnomedicinal use, phenolic composition and pharmacological activity of A. eupatoria has been provided. As can be seen, this plant species exhibits several potential applications, including those beyond its traditional ethnomedicinal uses, as the safety of its consumption has been shown clinically. There still is limited pharmacological evidence that corroborates the ethnomedicinal uses of this plant species as well as regarding the specific bioactive compounds.

Vascular activity of infusion and fractions of Cymbopogon citratus (DC) Stapf. in human arteries.

ETHNOPHARMACOLOGICAL RELEVANCE: Cymbopogon citratus (DC.) Stapf has been traditionally used mainly for inflammatory diseases and hypertension. However, the mechanisms underlying its vascular activity remain to be fully characterized and the fractions responsible for its cardiovascular activity are still unknown. AIM OF THE STUDY: In this study, we aimed to assess the vascular activity of Cymbopogon citratus in human arteries and to study the role of cyclooxygenase in its vasorelaxant effects. MATERIALS AND METHODS: Vascular effects of leaves infusion and three fractions (phenolic acids, flavonoids and tannins) were studied using distal segments of human internal thoracic arteries harvested from patients undergoing coronary revascularization, which were mounted as rings in tissue organ baths and maintained at 37 °C in Krebs Henseleit buffer. The effect on basal vascular tone, the effect on the noradrenaline-induced contraction and the vasorelaxant effects were assessed. The role of cyclooxygenase was evaluated with indomethacin. RESULTS: Our results showed a mild effect on the basal vessel tone of the infusion. A significant inhibition on the adrenergic-mediated vasoconstriction was observed for the infusion (0.0002 mg/mL) and the flavonoid fraction (0.2 mg/mL), despite a potentiation was observed in some conditions. A vasorelaxant effect was observed for both the infusion (6.46% of maximal relaxation) and the tannin fraction (26.91% of maximal relaxation, P < 0.05 vs. infusion). Incubation with indomethacin (10 µM) elicited a decrease in the vasorelaxation to the infusion (P < 0.05). CONCLUSIONS: These results suggest that cyclooxygenase may be involved in the vasorelaxation to the infusion of Cymbopogon citratus and that tannins are the compound fraction mainly responsible for this vasorelaxation.

Vascular effects of a polyphenolic fraction from Oxalis pes-caprae L.: role of α-adrenergic receptors Sub-types.

Oxalis pes-caprae L. is a plant of the Oxalidaceae family, from which several compounds have been previously identified. Recently, we showed that an Oxalis pes-caprae L. extract inhibits the vasopressor effect of noradrenaline. In this work we aimed to explore the mechanisms involved in this effect. The results confirmed that the flavonoid fraction present in the extract inhibits noradrenaline-induced contractions and that this effect is concentration-dependent. Also, a parallel shift to the right in the noradrenaline concentration-response curve was observed, suggesting a decrease in efficacy and also in potency. Together these results support the assumption that the extract could exert a non-competitive antagonism on the α-adrenergic receptors. However, experiments in the presence of competitive antagonists for α-adrenergic receptor sub-types (i.e. prazosin, yohimbine and phentolamine) showed that the effect may not be directly mediated by α-adrenergic receptors. Thus, the interaction of this extract with the adrenergic system remains to be confirmed.

Chemistry and Pharmacology of the Kazakh Crataegus Almaatensis Pojark: An Asian Herbal Medicine.

Crataegus almaatensis, an endemic ornamental plant in Kazakhstan is used in popular medicine due to its cardiotonic properties. The most studied species of the same genus are commonly found in Europe, which shows the importance of having the Kazakh species validated via its chemical and pharmacological studies. High-speed countercurrent chromatography (HSCCC) operated under optimized conditions enabled an isolation of the three main compounds from the aqueous phase of the leaves ethanol extract, further identified by nuclear magnetic resonance (NMR), as quercetin 3-O-rhamnoside (quercitrin) (4.02% of the crude extract-CECa); quercetin 3-O-ß-galactoside (hyperoside) (1.82% of CECa); kaempferol 3-O-α-L-rhamnoside (afzelin) (0.94% of CECa). The CECa, the aqueous phase of the crude extract (APCa) together with the isolates were evaluated for their vascular (vascular reactivity in human internal mammary artery-HIMA), anti-nociceptive (formalin-induced liking response and hot plate) and anti-inflammatory (subcutaneous air-pouch model-SAP) activities. CECa at the concentrations of 0.014 and 0.14 mg/mL significantly increased the maximum contractility response of HIMA to noradrenaline. The APCa CR curve (0.007-0.7 mg/mL) showed an intrinsic relaxation effect of the HIMA. APCa at the dose of 100 mg/kg i.p. significantly decreased the total leukocyte count and the IL-1ß release in the SAP wash.

Assessment of luteolin (3',4',5,7-tetrahydroxyflavone) neuropharmacological activity.

Since the discovery that certain flavonoids (namely flavones) specifically recognise the central BDZ receptors, several efforts have been made to identify naturally occurring GABA(A) receptor benzodiazepine binding site ligands. Flavonoid derivatives with a flavone-like structure such as apigenin, chrysin and wogonin have been reported for their anxiolytic-like activity in different animal models of anxiety. Luteolin (3',4',5,7-tetrahydroxyflavone) is a widespread flavonoid aglycon that was reported as devoid of specific affinity for benzodiazepine receptor (BDZ-R) binding site, but its psychopharmacological activity is presently unknown. Considering (1) the close structural similarity with other active flavones, (2) the activity of some of its glycosilated derivatives and (3) the complexity of flavonoid effects in the central nervous system, luteolin was submitted to a battery of tests designed to evaluate its possible activity upon the CNS and its ability to interact with the BDZ-receptor binding sites was also analysed. Luteolin apparently has CNS activity with anxiolytic-like effects despite the low affinity for the BDZ-R shown in vitro. Our findings suggest a possible interaction with other neurotransmitter systems but we cannot rule out the possibility that luteolin's metabolites might show a higher affinity for the BDZ-R in vivo, thus eliciting the evident anxiolytic-like effects through a GABAergic mechanism.

Neuropharmacological evaluation of the putative anxiolytic effects of Passiflora edulis Sims, its sub-fractions and flavonoid constituents.

Passiflora edulis Sims together with several other plants of the genus Passiflora have been reported to possess anxiolytic properties. It has been suggested recently that flavonoids may be partly responsible for the neuropharmacological activity of these plants but there are still few data reporting the relation between the constituents of these plants and their activity. This work evaluated the anxiolytic/sedative activity of an aqueous extract of Passiflora edulis Sims and bioguided its fractionation using the elevated plus-maze model of anxiety and other complementary pharmacological tests. The aqueous extract presented an anxiolytic-like activity without any significant effect upon the motor activity whilst the total flavonoid fraction (TFF) presented an anxiolytic-like activity but compromised motor activity. Through fractionation of TFF it was possible to isolate and characterize luteolin-7-O-[2-rhamnosylglucoside] which showed an anxiolytic-like activity without compromising motor activity.