RESUMEN
Prenylated cinnamic acid derivatives are the bioactive components of Brazilian green propolis (BGP). The effect of other botanical components on the pharmacokinetic profiles of these derivatives remains relatively unexplored. In the present study, we investigated the influence of several herbal extracts (turmeric, ginkgo leaf, coffee fruit, soybean, and gotu kola) on the plasma concentrations of cinnamic acid derivatives after BGP consumption. When the herbal extracts were co-administered with BGP in the clinical study, the area under the curve (AUC) values of artepillin C and drupanin, the major BGP components in plasma, were significantly increased by 1.7- and 1.5-fold, respectively, compared to those after BGP administration alone. Among the herbal extracts administered to rats, turmeric extract increased the AUC. Furthermore, a bidirectional transport assay suggested that artepillin C and drupanin are substrates of breast cancer resistance protein (BCRP), a drug elimination transporter. These results suggest that curcumin-containing turmeric extract may increase the plasma concentrations of artepillin C and drupanin via BCRP. Our findings enabled us to estimate the food-herb and herb-herb interactions in vivo in foods and herbal medicines containing cinnamic acid derivatives and prenylated compounds.
RESUMEN
Cinnamic acid derivatives, which are dietary phenolic compounds, are attracting attention for their health benefits. Artepillin C, drupanin, baccharin, and p-coumaric acid are major cinnamic acid derivatives in Brazilian green propolis (BGP) used as functional food materials. To investigate the metabolism of these cinnamic acid derivatives, each compound was administered to rats, and their metabolic profiles were compared with those administered with BGP. Artepillin C is metabolized to hydroxylated metabolites (capillartemisin A), as well as glucuronide. Drupanin sulfate, glucuronide, and hydroxylated form were detected in plasma both after ingestion of drupanin and its 3-phenylpropionic acid ester (baccharin). p-Coumaric acid underwent sulfation, but not glucuronidation. These results reveal that the metabolic pathways of cinnamic acid derivatives in rats comprise ester hydrolysis and hydroxylation, as well as phase-II conjugation. Our findings may provide significant information for estimating the potential activity of various cinnamic acid derivatives derived from functional food materials.
Asunto(s)
Própolis , Animales , Brasil , Cinamatos , Ésteres , Glucurónidos , Redes y Vías Metabólicas , RatasRESUMEN
FoxP3+ regulatory T cells (Tregs) are needed to suppress inflammatory diseases and maintain immune homeostasis. The suppressive function of Tregs can be used to control autoimmune or inflammatory diseases; therefore, it is well studied how Tregs can be artificially up- or downregulated in vitro and in vivo, by using antibodies, chemical compounds, foods, and natural resources. Propolis is a famous functional food that has an anti-inflammatory effect. However, the influences of propolis on Treg function have not been fully evaluated so far. Here, we demonstrated that Brazilian green propolis increases TNFR2 expression in Tregs via the IRF4/cMyc axis, and artepillin C was a major effective component of propolis on Tregs. These results indicate that propolis and artepillin C have the potential as Treg activators via TNFR2 expression and may be useful for the prevention and/or therapy of autoimmune or inflammatory diseases.
RESUMEN
Brazilian green propolis (BGP) has chemical compounds from botanical origin that are mainly cinnamic acid derivatives (artepillin C, baccharin, and drupanin) and flavonoids (kaempferide and 6-methoxykaempferide). These compounds are expected to play an important role in the pharmacological activities of BGP. However, there is little known about the pharmacokinetics and metabolism of these compounds after oral administration of BGP. The aim of this study is to investigate the pharmacokinetics and metabolism of BGP components in humans. Twelve volunteers received 3 capsules containing 360 mg of BGP ethanol extract powder. Plasma samples were collected before and up to 24 h after the intake of BGP capsules. The collected plasma samples with or without hydrolysis by the deconjugating enzyme were analyzed by LC/MS/MS. After enzymatic hydrolysis, the Cmax values of artepillin C and drupanin, which were detected mainly in plasma after ingestion of BGP capsules, were 1255 ± 517 and 2893 ± 711 nM, respectively, of which 89.3% and 88.2% were found to be the phenolic glucuronide conjugate. This is the first time that the pharmacokinetics of the BGP components of human metabolites have been reported. Our results could provide useful information for the design and interpretation of studies to investigate the mechanisms and pharmacological effects of BGP.
Asunto(s)
Cinamatos , Flavonoides , Própolis , Administración Oral , Adulto , Cromatografía Liquida , Cinamatos/sangre , Cinamatos/química , Cinamatos/farmacocinética , Femenino , Flavonoides/sangre , Flavonoides/química , Flavonoides/farmacocinética , Humanos , Masculino , Própolis/administración & dosificación , Própolis/metabolismo , Própolis/farmacocinética , Espectrometría de Masas en Tándem , Adulto JovenRESUMEN
A new cinnamic acid derivative, (E)-3-[4-hydroxy-3-((E)-3-formyl-2-butenyl)phenyl]-2- propenoic acid (20) has been isolated from the ethanol extract of Brazilian green propolis along with three known cinnamic acid derivatives, 3,4-dihydroxy-5-prenyl-(E)-cinnamic acid (4), capillartemisin A (6), and 2,2-dimethylchromene-6-(E)-propenoic acid (8), and a flavonoid, dihydrokaempferide (16) by liquid-liquid participation, a series of column chromatography and preparative HPLC. Their structures have been determined by spectroscopic analyses and chemical synthesis of compound 20. The simultaneous quantification of 20 constituents, including 10 cinnamic acid derivatives, 7 flavonoids, and 3 caffeoylquinic acid derivatives, has also been developed and validated using LC-MS/MS. The new compound 20 was shown to activate PPAR α but not PPAR ß or γ.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Cinamatos/química , Própolis/química , Espectrometría de Masas en Tándem/métodos , Animales , Abejas , Brasil , Cinamatos/síntesis química , Cinamatos/aislamiento & purificaciónRESUMEN
The effects of Brazilian green propolis ethanol extract on Cry j1-induced cys-leukotrienes and histamine release from peripheral leukocytes of patients with allergic rhinitis were investigated. One of the key mechanisms for the anti-allergic properties of the extract was revealed to be the suppression of cys-LTs release. Furthermore, a series of propolis components and their phenethyl esters were synthesized and evaluated as inhibitors of cys-LTs release. Artepillin C, baccharin, and kaempferide were the major active components of the ethanol extract. The inhibitory activity of artepillin C phenethyl ester was comparable to that of existing LT synthesis inhibitors.