RESUMO
A novel approach using metabolomics coupled with a metabolic network was used to investigate the effects of Tao-Hong-Si-Wu decoction (THSWD) on the rat model of acute blood stasis syndrome. Acute blood stasis syndrome was induced by placing the rats in ice-cold water following two injections with epinephrine. The hemorheological indicators [whole blood viscosity (WBV) and plasma viscosity (PV)] and the blood coagulation indicators [thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB)] were detected. The nonparametric univariate method and multivariate statistical analysis were performed for determining the potential biomarkers. A correlation map was structured between biochemical indicators and hub metabolites to explain the effects mechanism of THSWD. After the administration of THSWD, the levels of WBV, PV, TT, APTT and FIB returned to levels observed in the control group. According to metabolomics coupled with metabolic network analysis, the intervention of THSWD in rats with acute blood stasis syndrome induced substantial and characteristic changes in their metabolic profiles. Fifteen metabolites were screened, which mainly involved 10 pathways and five hub metabolites, namely, l-glutamate, l-phenylalanine, N-acylsphingosine, arachidonic acid and phosphatidate. The biochemical indicators and hub metabolites could be adjusted to close to normal levels by THSWD. Therefore, combining metabolomics and metabolic network helped to evaluate the effects of THSWD on acute blood stasis.
Assuntos
Cromatografia Líquida/métodos , Medicamentos de Ervas Chinesas/farmacologia , Doenças Hematológicas/metabolismo , Metaboloma/efeitos dos fármacos , Metabolômica/métodos , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Feminino , Doenças Hematológicas/sangue , Medicina Tradicional Chinesa , Redes e Vias Metabólicas/efeitos dos fármacos , Ratos , Ratos Wistar , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Roots of Angelica sinensis (Oliv.) Diels (AS) a commonly used herbal, always act as an anti-inflammatory drug in Chinese traditional therapy. In clinical use, AS is always processed before being used for the reason that processing can increase its therapeutic effect. Recent studies have shown that volatile oil of AS (VOAS), an important component in AS, has evident anti-inflammatory activities. AIM OF THE STUDY: In this study, our aim is to evaluate the anti-inflammatory effects of volatile oils from processed products of AS. MATERIALS AND METHODS: In this paper, volatile oils from stir-fried AS (C-VOAS), parched AS with alcohol (J-VOAS), parched AS with soil (T-VOAS), and parched AS with sesame oil (Y-VOAS) were applied to intervene the carrageenan-induced acute inflammation model rats. GC-MS based metabolomics was utilized to determine different metabolites in the inflammatory exudate and plasma samples. RESULTS: The results showed that VOASs could significantly inhibit the release of PGE2, HIS, 5-HT and TNF-α, among which C-VOAS and J-VOAS expressed better effect. Otherwise, 14 potential biomarkers were identified respectively in inflammatory exudate and plasma, which changed highly significantly (P<0.01) in C-VOAS and J-VOAS groups. CONCLUSIONS: We inferred that the anti-inflammatory effect of C-VOAS and J-VOAS were superior to other VOASs.
Assuntos
Angelica sinensis/química , Anti-Inflamatórios/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Inflamação/prevenção & controle , Metabolômica/métodos , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Biomarcadores/metabolismo , Carragenina , Dinoprostona/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/isolamento & purificação , Histamina/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Análise Multivariada , Óleos Voláteis/isolamento & purificação , Fitoterapia , Óleos de Plantas/isolamento & purificação , Raízes de Plantas/química , Plantas Medicinais , Análise de Componente Principal , Ratos Wistar , Serotonina/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
To evaluate the anti-acute inflammation effects of volatile oils from different processed products of Angelicae Sinensis Radix(AS) in the rat model of acute inflammation established by the metabolomic method. Volatile oil of charred AS (C-VOAS), wine-processed AS (J-VOAS), locally processed AS (T-VOAS) and oil-process AS (Y-VOAS) were applied to intervene the rat acute paw swelling inflammation model induced by Carrageenan. Changes in serum HIS, 5-HT, PGE2 and TNF-α content in rats were detected. Gas chromatography-mass spectrometry was used to detect the metabolites in plasma. Potential biomarkers were investigated according to principal component analysis method and partial least-squares discriminant analysis. According to the results, C-VOAS and J-VOAS could significantly inhibit inflammatory mediators Histamine, 5-hydroxytryptamine, prostaglandin-E2 and cytokine tumor necrosis factor-alpha (P<0.01), and T-VOAS and Y-VOAS also showed a significantly inhibitory effect (P<0.05). Compared with the normal group, 14 endogenous metabolite biomarkers showed metabolic disturbance in plasma (P<0.05 or P<0.01). Compared with acute inflammation model group, C-VOAS and J-VOAS could better recover the levels of the endogenous metabolites (P<0.05 or P<0.01) than T-VOAS and Y-VOAS (P<0.05 or P<0.01). This study suggests that C-VOAS and J-VOAS show a better anti-inflammatory effect than T-VOAS and Y-VOAS. Therefore, the metabolomic method could be used to expound the anti-inflammatory mechanism of volatile oils from different processed products of AS, and provide a theoretical basis for clinical application of VOAS.