Neuropharmacological and acute toxicological evaluation of ethanolic extract of Allamanda cathartica L. flowers and plumieride.

Psychiatric diseases affect more than 350 million people all over the world, and medicinal plants have been considered the basis for pharmacological research. The study investigates the anticonvulsant and antidepressant-like activities and acute toxicological effects of ethanolic extract of Allamanda cathartica flowers, and plumieride. The extract was analyzed by HPLC and plumieride was isolated. Toxicity studies were carried out on females Wistar rats (2000 mg/kg). Toxicity was evaluated by measuring biochemical parameters and conducting histopathological analysis. For pharmacological evaluation different doses of the extract (100, 150 and 300 mg/kg, p.o.) and plumieride (0.5, 1 and 2 µg/kg, i.p.) were administered before the Forced-Swimming Test (FST), pentylenetetrazole seizure test (PTZT) or Tail-Suspension Test (TST) in mice. Furthermore, hemolytic activity, cytotoxicity and micronucleus test were performed. In addition, mutagenicity and reproductive/developmental toxicity were estimated by TEST-software analysis. Data show that both treatments induce significant antidepressive-like effect in FST and TST, but not anticonvulsant effect. The effect of plumieride last up to 4 h after treatment. No signs of toxicity, mutagenicity, cytotoxicity or hemolytic activity were observed. The TEST-software demonstrated that plumieride present reproductive/developmental toxicity. Together, the data obtained show that the flowers extract and plumieride present antidepressant-like effect and did not present signals of acute toxicity.

Taxifolin stability: In silico prediction and in vitro degradation with HPLC-UV/UPLC-ESI-MS monitoring.

Taxifolin has a plethora of therapeutic activities and is currently isolated from the stem bark of the tree Larix gmelinni (Dahurian larch). It is a flavonoid of high commercial interest for its use in supplements or in antioxidant-rich functional foods. However, its poor stability and low bioavailability hinder the use of flavonoid in nutritional or pharmaceutical formulations. In this work, taxifolin isolated from the seeds of Mimusops balata, was evaluated by in silico stability prediction studies and in vitro forced degradation studies (acid and alkaline hydrolysis, oxidation, visible/UV radiation, dry/humid heating) monitored by high performance liquid chromatography with ultraviolet detection (HPLC-UV) and ultrahigh performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS). The in silico stability prediction studies indicated the most susceptible regions in the molecule to nucleophilic and electrophilic attacks, as well as the sites susceptible to oxidation. The in vitro forced degradation tests were in agreement with the in silico stability prediction, indicating that taxifolin is extremely unstable (class 1) under alkaline hydrolysis. In addition, taxifolin thermal degradation was increased by humidity. On the other hand, with respect to photosensitivity, taxifolin can be classified as class 4 (stable). Moreover, the alkaline degradation products were characterized by UPLC-ESI-MS/MS as dimers of taxifolin. These results enabled an understanding of the intrinsic lability of taxifolin, contributing to the development of stability-indicating methods, and of appropriate drug release systems, with the aims of preserving its stability and improving its bioavailability.

Biomonitored UHPLC-ESI-QTOF-MS2 and HPLC-UV thermostability study of the aerial parts of Sphagneticola trilobata (L.) Pruski, Asteraceae.

As the temperature of extraction and processing could impact the biological effects of herbal extracts, which have wide chemical diversity, the aim of this work were to investigate the thermostability of herbal derivatives of the aerial parts of Sphagneticola trilobata, a reputed medicinal plant; to biomonitor its oral anti-hyperalgesic effect; and to elucidate the degradation pathways of the major components by UHPLC-ESI-QTOF-MS. The lipophilic markers (kaurenoic acid-KA) and hydrophilic markers [chlorogenic acids; measured as total phenolic compounds (PC), expressed in caffeic acid] were also monitored through a validated HPLC-UV methodology, suitable for quality control and stability studies. The soft extract (drug:solvent ratio of 1:10, ethanol 60% v/v) was exposed to high temperatures (50-180°C). PC showed high thermolability (27.4% of degradation at 150°C), compared to KA (16.5%, at 180°C). These results suggest that the loss of oral anti-hyperalgesic activity observed in the spray-dried extracts (dried at 170°C), compared with the soft and the lyophilized extract may be related to degradation of the active components, especially the polar compounds, i.e. chlorogenic acid derivatives and the four oleanane type triterpenoid saponins. These latter degraded at temperatures above 150°C and vanished at 180°C, as demonstrated in the UHPLC-ESI-QTOF-MS analyses. These results provide a relevant guide for the extraction process of S. trilobata, aimed at preserving the antinociceptive effect.

A Highly Polar Phytocomplex Involving Rutin is Responsible for the Neuromuscular Facilitation Caused by Casearia sylvestris (guaçatonga).

BACKGROUND: Of the various biological activities ascribed to extracts from Casearia sylvestris (guaçatonga), its facilitatory activity, i.e., ability to increase skeletal muscle contractile amplitude, has promising therapeutic applications. In this work, we investigated the components responsible for the previously described neurofacilitation caused by C. sylvestris leaves. METHODS: The methanolic fraction of C. sylvestris leaves was initially fractionated by column chromatography and partitioned in a MeOH:H2O gradient. The resulting fractions were analyzed by analytical HPLC and yielded fraction 5:5 (F55) that was subjected to solid phase extraction and preparative HPLC. Of the seven resulting subfractions, only F55-6 caused muscle facilitation. Subfractions F55-6 and F55-7 (similar in composition to F55-6 by TLC analysis, but inactive) were analyzed by 1H-NMR to identify their constituents. RESULTS: This analysis identified a rutin-glycoside phytocomplex that caused neurofacilitation, a property that commercial rutin alone did not exhibit. CONCLUSION: F55-6 apparently caused neurofacilitation by the same mechanism (presynaptic action) as the methanolic fraction since its activity was also inhibited in tetrodotoxin-pretreated preparations.