RESUMO
Although traditional use of elderberry flowers is recognized by Medical Agencies, there are not suitable products on the Brazilian market. To overcome poor stability of tinctures of Sambucus nigra flowers, we aimed to develop spray dried microparticles. Statistical experimental design was applied taking inlet temperature and maltodextrin% at five different levels. Next, we applied a stability study for 60 days under accelerated conditions (40 °C/75% RH) and 180 days at room temperature (15-30 °C). We monitored flavonoid content as markers. The best drying condition was 188 °C and 65% of carrier and enabled microparticles with more than 90% of markers recovery. After 180 days, the dried extract remained with 90.8% at room temperature. The markers were released from microparticles in two minutes. In conclusion, the spray drying process and formulation enabled elderberry flowers to be easier to apply in solid pharmaceutical forms.
Assuntos
Plantas Medicinais , Sambucus nigra , Sambucus , Água , Medicina Herbária , PósRESUMO
Herbal medicines are important options for the treatment of several illnesses. Although their therapeutic applicability has been demonstrated throughout history, several concerns about their safety and efficacy are raised regularly. Quality control of articles of botanical origin, including plant materials, plant extracts, and herbal medicines, remains a challenge. Traditionally, qualitative (e.g., identification and chromatographic profile) and quantitative (e.g., content analyses) markers are applied for this purpose. The compound-oriented approach may stand alone in some cases (e.g., atropine in Atropa belladonna). However, for most plant materials, plant extracts, and herbal medicines, it is not possible to assure quality based only on the content or presence/absence of one (sometimes randomly selected) compound. In this sense, pattern-oriented approaches have been extensively studied, introducing the use of multivariate data analysis on chromatographic/spectroscopic fingerprints. The use of genetic methods for plant material/plant extract authentication has also been proposed. In this study, traditional approaches are reviewed, although the focus is on the applicability of fingerprints for quality control, highlighting the most used approaches, as well as demonstrating their usefulness. The literature review shows that a pattern-oriented approach may be successfully applied to the quality assessment of articles of botanical origin, while also providing directions for a compound-oriented approach and a rational marker selection. These observations indicate that it may be worth considering to include fingerprints and their data analysis in the regulatory framework for herbal medicines concerning quality control since this is the foundation of the holistic view that these complex products demand.
Assuntos
Plantas Medicinais , Cromatografia , Análise Multivariada , Extratos Vegetais , Controle de QualidadeRESUMO
ABSTRACT The fruits of Litchi chinensis Sonn., Sapindaceae, are renowned for their biological activities. However, their leaves are poorly explored, although they represent an important source of vegetable raw material with biological properties as antioxidant, anti-inflammatory and antinociceptive. An HPLC method was developed and validated for the simultaneous quantification of epicatechin and procyanidin A2 in the leaf hydroethanolic extract of L. chinensis. The markers and other unidentified components were separated on a Luna Phenomenex C18 column (250 mm × 4.6 mm, 5 µm) with mobile phase composed of acetonitrile: water pH 3.0 (with sulfuric acid), in a gradient run; at 1.0 ml min-1, 30 ºC and 278 nm for detection. The method was linear over an epicatechin and procyanidin A2 concentration range of 10–100 µg ml-1. The Limit of Quantification for epicatechin and procyanidin A2 were 1.7 and 2 µg ml-1, respectively. The Relative Standard Deviation (%) values for markers (intra- and inter-day precision studies) were <4.0% and the accuracy was 100 ± 5%. The method was applied to ten samples collected in the state of Santa Catarina (Brazil), which showed 14.8–44.5 and 44.8–69.6 mg g-1 of epicatechin and procyanidin A2, respectively. The proposed method could be a valuable tool for quality assessment of L. chinenis leaves as well as their herbal derivatives.
RESUMO
Ipomoea pes-caprae (L.) R. Br., Convolvulaceae, is a medicinal plant that grows abundantly as a pan-tropical stand plant. The 3² (two factors and three levels) factorial design, was applied to determine the best time and drug/solvent proportion to maximize the flavonoid content in the hydroethanolic extract by maceration process. The antinociceptive and anti-inflammatory effects were studied at 5-20 mg/kg, i.p., using the writhing test and carrageenan-induced pleurisy models in mice. The optimized extract was able to inhibit more than 50% of abdominal writhing at 20 mg/kg, with 55.88%±2.4 of maximum inhibition. Indomethacin, used as positive control, inhibited 64.86% at 10 mg/kg. In the pleurisy model, the extract produced dose-dependent inhibition of the first phase of inflammation (4 h) in the pleural cavity induced by injection of carrageenan (1%) in mice. It inhibited 50%±0.82 (p<0.01) of exudation induced by carrageenan, and 60.88%±0.14 (p<0.01) of leukocyte migration to the pleural cavity. In conclusion, the results validate the technological conditions of the maceration process to produce an optimized bioactive herb extract for the development of analgesic and anti-inflammatory phytopharmaceuticals using 70 ºGL ethanol, a plant to solvent ratio of 12.5% (w/v), and ten days of maceration.
RESUMO
This study investigated the antinociceptive effect of Aleurites moluccana dried extract (DE; 125 to 500 mg/kg, p.o.) and the isolated flavonoid 2â³-O-rhamnosylswertisin (5 to 50.6 µmol/kg, p.o.) using different models of long-lasting inflammatory and neuropathic pain in mice. Attempts were made to analyse the mechanisms through which A. moluccana exerted its effects. A. moluccana DE inhibited complete Freund's adjuvant (CFA)-induced mechanical nociception. It was also evidenced by a reduction of sensitization in the contralateral hindpaw. The extract reversed the mechanical hypersensitivity of partial ligation of sciatic nerve (PLSN)-treated animals, similar to gabapentin. In PLSN model, the opioid, dopaminergic and oxidonitrergic pathways were involved in the A. moluccana DE antinociceptive effects. A single dose of 2â³-O-rhamnosylswertisin inhibited the carrageenan- and CFA-induced mechanical nociception. Furthermore, the compound caused expressive antinociception in PLSN-mice, with inhibition value greater than obtained with gabapentin. Oral treatment with the extract or the isolated compound attenuated the neutrophil migration and IL-1ß levels following carrageenan injection. Of note, A. moluccana DE did not interfere with thermal sensitivity in healthy mice. The absence of side effects, including interference in locomotor activity, motor performance in animals treated with the extract, showed excellent potential for the therapeutic use of this medicinal plant in treating persistent pain in humans.
Assuntos
Aleurites/química , Analgésicos/farmacologia , Flavonas/farmacologia , Dor/tratamento farmacológico , Ramnose/análogos & derivados , Analgésicos/uso terapêutico , Animais , Feminino , Flavonas/uso terapêutico , Interleucina-1beta/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Peroxidase/metabolismo , Ramnose/farmacologia , Ramnose/uso terapêuticoRESUMO
Polygala cyparissias, used in folk medicine as an anaesthetic, has already demonstrated antinociceptive activity against acute pain. In this study, we investigated the antihyperalgesic activity of the P. cyparissias methanol extract (PCME) from which the following compounds were isolated: α-spinasterol (PC1), 1,3-dihydroxy-7-methoxyxanthone (PC2), 1,7-dihydroxy-2,3-methylenedioxyxanthone (PC3) and 1,3,6,8-tetrahydroxy-2,7-dimethoxyxanthone (PC4). The antihyperalgesic effect was evaluated using experimental models of persistent pain induced by carrageenan, lipopolysaccharide (LPS), Freund's Complete Adjuvant (CFA), PGE(2) or epinephrine. The partial ligation of the sciatic nerve (PLSN) model was also used. In inflammatory hyperalgesia induced by carrageenan, LPS, CFA or PGE(2), the inhibition values obtained with the PCME treatment were 68 ± 3%, 89 ± 5%, 43 ± 3% and 40 ± 4%, respectively. In epinephrine-induced hyperalgesia, the extract was effective, reducing 99 ± 11% of response frequency, while in PLSN, 54 ± 4% of inhibition was obtained. These results allow to suggest that the antihyperalgesic activity of PCME is, at least in part, related to its capability to inhibit the hypersensitization induced by pro-inflammatory mediators, such as LPS, carrageenan and CFA, without interfering with locomotor activity or motor performance. Furthermore, compounds PC1, PC3 and PC4 inhibited the carrageenan-induced hyperalgesia with inhibition of 42 ± 6%, 48 ± 5% and 64 ± 4%, respectively. In summary, our data demonstrate that PCME has relevant antihyperalgesic activity and that the isolated PC1, PC3 and PC4 seem to be responsible, at least in part, for this important effect.
Assuntos
Analgésicos/farmacologia , Hiperalgesia/tratamento farmacológico , Extratos Vegetais/farmacologia , Polygala/química , Analgésicos/isolamento & purificação , Animais , Carragenina/efeitos adversos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Epinefrina/efeitos adversos , Feminino , Adjuvante de Freund/efeitos adversos , Hiperalgesia/induzido quimicamente , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Lipopolissacarídeos/efeitos adversos , Medicina Tradicional , Metanol , Camundongos , Neuralgia/tratamento farmacológico , Dor/tratamento farmacológico , Nervo Isquiático/efeitos dos fármacos , Estigmasterol/análogos & derivados , Estigmasterol/isolamento & purificação , Estigmasterol/farmacologia , Xantonas/isolamento & purificação , Xantonas/farmacologiaRESUMO
New, simple, rapid and precise HPLC-PDA method has been developed and validated for quantification of biomarker myrsinoic acid B in stem bark extracts of Rapanea ferruginea Mez. The method employs a Phenomenex C18 column (250 mm × 4.6mm I.D., 5 µm) with acetonitrile:methanol:water (pH 2.6 with phosphoric acid) at 48:30:22 as mobile phase, at a flow rate of 0.7 mL min(-1) and photo diode array (PDA) detection at 270 nm. The validation data show that the method is specific, accurate, precise and robust. The method was linear, over a range of 5-100.0 µg mL(-1), with a limit of detection of 0.369 µg mL(-1) and limit of quantification of 1.233 µg mL(-1). The method has also shown consistent recoveries (average of 101.3% and 0.12% RSD) of the biomarker, with low intra and inter-day relative standard deviation (1.26% and 1.62%, respectively). The evaluated hydroethanolic extract and dry extract presented MAB values of 63.53 and 36.07 mg g(-1), respectively.
Assuntos
Alcenos/análise , Benzofuranos/análise , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/química , Primulaceae/química , Analgésicos/química , Analgésicos/normas , Dessecação , Descoberta de Drogas , Casca de Planta/química , Extratos Vegetais/normas , Controle de Qualidade , Fatores de TempoRESUMO
In this work, didecyldimethylammonium bromide (DDAB) and 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE) (2.5:1) were used to prepare liposomes coated with polyacrylic acid (PAA) using "in situ" polymerization with 2.5, 5 and 25 mM of acrylic acid (AA). The PAA concentrations were chosen to achieve partially to fully covered capsules, and the polymerization reaction was observed with real-time monitoring using dynamic light scattering (NanoDLS). The DDAB:DOPE liposomes showed stability in the tested temperature range (25-70°C), whereas the results confirmed the success of the polymerization according to superficial charge (zeta potential of +66.7±1.2 mV) results and AFM images. For the liposomes that were fully coated with PAA (zeta potential of +0.3±3.9 mV), cytotoxicity was independent of the concentration of albumin. Cationic liposomes and nanocapsules of the stable liposomes coated with PAA were obtained by controlling the surface charge, which was the most important factor related to cytotoxicity. Thus, a potential, safe drug nanocarrier was successfully developed in this work.
Assuntos
Sobrevivência Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/síntese química , Portadores de Fármacos/síntese química , Lipossomos/química , Nanocápsulas/química , Células 3T3 , Resinas Acrílicas/química , Animais , Cátions/química , Materiais Revestidos Biocompatíveis/metabolismo , Materiais Revestidos Biocompatíveis/farmacologia , Portadores de Fármacos/metabolismo , Portadores de Fármacos/farmacologia , Luz , Lipossomos/metabolismo , Lipossomos/farmacologia , Lipossomos/ultraestrutura , Camundongos , Microscopia de Força Atômica , Nanocápsulas/ultraestrutura , Fosfatidiletanolaminas/química , Polimerização , Compostos de Amônio Quaternário/química , Reologia/efeitos dos fármacos , Espalhamento de Radiação , Eletricidade EstáticaRESUMO
Seeking to develop a new analgesic phytomedicine, a spray-dried extract (SDE) of Aleurites moluccana (L.) Willd. leaves was developed in scale up (5 kg). The SDE was standardized at 3% w/w in relation to the flavonoid 2''-O-rhamnosylswertisin. The SDE batches were evaluated in relation to their physical, physiochemical, and pharmacological characteristics. The results demonstrated the reproducibility of the scale up SDE process which, when dosed orally, reduced carrageenan-induced mechanical hypernociception, with an ID(50)% of 443 mg/kg. Similar results were obtained with animals injected with complete Freund's adjuvant (CFA), in which SDE caused inhibition of 48 ± 4%. SDE was effective in preventing prostaglandin E2 (PGE2)-induced mechanical hypernociception (inhibition of 26 ± 10% and 33 ± 3%, at 250 and 500 mg/kg, respectively). Swertisin and 2''-O-rhamnosylswertisin isolated from the own extract were effective in inhibiting the hypernociceptive response induced by carrageenan (70 ± 2% and 50 ± 5%, resp.). Furthermore, 2''-O-rhamnosylswertisin was capable of significantly inhibiting the mechanical sensitization induced by CFA or PGE2, with inhibitions of 25 ± 3% and 94 ± 6%, respectively. These results suggest that the effects of SDE are related, at least in part, to the presence of these flavonoids.