RESUMO
Aristolochia trilobata L. is an aromatic plant, popularly known as "mil-homens", and its essential oil (EO) is generally used to treat colic, diarrhea and dysentery disorders. We evaluated the antinociceptive effect of A. trilobata stem EO and of its major compound, the (R)-(-)-6-methyl-5-hepten-2-yl acetate (sulcatyl acetate: SA), using acetic acid (0.85%)-induced writhing response and formalin-induced (20 µL of 1%) nociceptive behavior in mice. We also evaluated the EO and SA effect on motor coordination, using the rota-rod apparatus. EO (25, 50 and 100 mg/kg) or SA (25 and 50 mg/kg) reduced nociceptive behavior in the writhing test (p<0.001). EO (100 mg/kg) and SA (25 and 50 mg/kg) decreased the nociception on the first phase of the formalin test (p<0.05). On the second phase, EO (25: p<0.01; 50: p<0.05 and 100 mg/kg: p<0.001) and SA (25 and 50 mg/kg; p<0.001) reduced the nociceptive response induced by formalin. EO and SA were not able to cause changes in the motor coordination of animals. Together, our results suggest that EO has an analgesic profile and SA seems to be one of the active compounds in this effect.
Assuntos
Analgésicos/farmacologia , Aristolochia/química , Heptanol/farmacologia , Óleos Voláteis/isolamento & purificação , Caules de Planta/química , Acetatos/antagonistas & inibidores , Acetatos/farmacologia , Analgésicos/isolamento & purificação , Animais , Heptanol/análogos & derivados , Heptanol/isolamento & purificação , Masculino , Camundongos , Óleos Voláteis/química , Medição da Dor , Extratos Vegetais/química , Desempenho Psicomotor/efeitos dos fármacos , Teste de Desempenho do Rota-RodRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma comosa Roxb. (C. comosa) or Wan Chak Motluk, Zingiberaceae family, has been used in Thai traditional medicine for the treatment of gynecological problems and inflammation. AIM OF THE STUDY: This study aimed to investigate the therapeutic potential of C. comosa by determining the changes in the lipid profiles in the ovariectomized rats, as a model of estrogen-deficiency-induced hyperlipidemia, after treatment with different components of C. comosa using an untargeted lipidomics approach. MATERIALS AND METHODS: Lipids were extracted from the serum of adult female rats subjected to a sham operation (SHAM; control), ovariectomy (OVX), or OVX with 12-week daily doses of estrogen (17ß-estradiol; E2), (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (DPHD; a phytoestrogen from C. comosa), powdered C. comosa rhizomes or its crude ethanol extract. They were then analyzed by liquid chromatography-mass spectrometry, characterized, and subjected to the orthogonal projections to latent structures discriminant analysis statistical model to identify tentative biomarkers. RESULTS: Levels of five classes of lipids (ceramide, ceramide-1-phosphate, sphingomyelin, 1-O-alkenyl-lysophosphatidylethanolamine and lysophosphatidylethanolamine) were elevated in the OVX rats compared to those in the SHAM rats, while the monoacylglycerols and triacylglycerols were decreased. The E2 treatment only reversed the levels of ceramides, whereas treatments with DPHD, C. comosa extract or powder returned the levels of all upregulated lipids back to those in the SHAM control rats. CONCLUSIONS: The findings suggest the potential beneficial effects of C. comosa on preventing the increased ceramide levels in OVX rats, a possible cause of metabolic disturbance under estrogen deficiency. Overall, the results demonstrated the power of untargeted lipidomics in discovering disease-relevant biomarkers, as well as evaluating the effectiveness of treatment by C. comosa components (DPHD, extract or powder) as utilized in Thai traditional medicine, and also providing scientific support for its folklore use.
Assuntos
Curcuma/química , Terapia de Reposição de Estrogênios , Heptanol/análogos & derivados , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , Lipídeos/sangue , Metabolômica , Ovariectomia , Fitoestrógenos/farmacologia , Extratos Vegetais/farmacologia , Animais , Biomarcadores/sangue , Cromatografia Líquida , Diarileptanoides , Análise Discriminante , Modelos Animais de Doenças , Estradiol/farmacologia , Etanol/química , Feminino , Heptanol/isolamento & purificação , Heptanol/farmacologia , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Metabolômica/métodos , Análise Multivariada , Fitoestrógenos/isolamento & purificação , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Pós , Ratos Sprague-Dawley , Rizoma/química , Solventes/química , Espectrometria de Massas em TandemRESUMO
The mechanisms by which the hexane extract of Curcuma comosa increases femoral blood flow (FBF) in ovariectomized rats are not known. Thus, the aim of the present study was to investigate the acute effects and modes of action of the diarylheptanoid (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (D3), a phyto-oestrogen isolated from C. comosa, on FBF in ovariectomized rats. On Day 7 after ovariectomy, rats were injected once intra-arterially with D3 (100, 200, 400 and 800 µg/kg), 17ß-oestradiol (E2; 1, 2, 4 and 8 µg/kg) or vehicle. In some experiments, rats were injected with N(G)-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg) 120 min after 800 µg/kg D3 or 4 µg/kg E2. In other experiments, rats were injected with 10 mg/kg L-NAME, 900 µg/kg 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or 900 µg/kg ICI 182 780 30 min prior to the injection of 800 µg/kg D3 or 4 µg/kg E2. Mean arterial blood pressure (mABP) and FBF were recorded using a pressure transducer and a laser Doppler flow meter, respectively. Both D3 and E2 dose-dependently increased FBF without changing mABP or heart rate. The EC(50) at 120 min for D3 and E2 was 195.8 and 1.8 µg/kg, respectively. In addition, D3 and E2 dose-dependently decreased femoral vascular resistance (FVR). The EC(50) of D3 was about 100-fold greater than that of E2. The effects of D3 and E2 on FBF and FVR were diminished by intravenous injection of 10 mg/kg l-NAME. Furthermore, 30 min pretreatment with L-NAME (10 mg/kg), ODQ (900 µg/kg) or ICI 182 780 (900 µg/kg) blocked the effects of D3 and E2 on FBF and FVR. The results of the present study suggest that the phyto-oestrogen D3 increases FBF in ovariectomized rats via oestrogen receptor and nitric oxide-guanylyl cyclase signalling, which, in turn, relaxes femoral vascular resistance.
Assuntos
Pressão Arterial/efeitos dos fármacos , Curcuma/química , Artéria Femoral/efeitos dos fármacos , Heptanol/análogos & derivados , Óxido Nítrico/biossíntese , Fitoestrógenos/farmacologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Animais , Pressão Arterial/fisiologia , Diarileptanoides , Relação Dose-Resposta a Droga , Feminino , Artéria Femoral/metabolismo , Artéria Femoral/fisiologia , Guanilato Ciclase/biossíntese , Heptanol/isolamento & purificação , Heptanol/farmacologia , Injeções Intra-Arteriais , Estrutura Molecular , Ovariectomia , Fitoestrógenos/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Resistência Vascular/efeitos dos fármacosRESUMO
Bioassay-guided fractionation of the CH2Cl2-MeOH extract of Pinus flexilis using an assay for protein kinase C (PKC) inhibitory activity led to the isolation of the two new bioactive diarylheptanoids (3R)-1,7-bis(3, 4-dihydroxyphenyl)-3-(beta-D-glucopyranosyl)heptan-3-ol (1) and its aglycon (3R)-1,7-bis(3,4-dihydroxyphenyl)heptan-3-ol (2), together with the three known bioactive compounds, hirsutenone (3), oregonin (4), and hirsutanonol (5). The IC50 values of compounds 1-5 in the PKC assay were 1.4, 1.6, 1.4, 8.6, and 4.6 microg/mL, respectively.