Evaluation of the mechanism of Danggui-Shaoyao-San in regulating the metabolome of nephrotic syndrome based on urinary metabonomics and bioinformatics approaches.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui-Shaoyao-San (DSS), a well-known classic Traditional Chinese medicine (TCM) formula for enhancing Qi (vital energy and spirit), invigorating blood circulation and promoting diuresis, has been widely used in the treatment of nephrotic syndrome (NS). Previously, we have reported some protective effects of DSS against NS, but the in-depth mechanisms remain unclear. AIM OF THE STUDY: In this study, an ultra performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q/TOF-MS)-based urinary metabonomics coupled with bioinformatics method was employed to evaluate the mechanisms of DSS in treating NS from the perspective of metabolism. MATERIALS AND METHODS: The rat models of NS were established using adriamycin injection. The regulative effects of DSS on NS in rats were first assessed by non-targeted metabonomics, which was based on UPLC-Q/TOF-MS. A series of target prediction models were used to predict the target of components identified in DSS and potential metabolites in NS, combined with the experimental results of metabonomics, to construct the biological network. RESULTS: A total of 16 potential metabolites were screened in NS, of which 13 were significantly regulated by DSS. Metabolic pathway analysis showed that the therapeutic effect of DSS on NS was mainly involved in regulating the amino acid metabolism and energy metabolism. The component-target-metabolites-pathway network revealed 29 targets associated with metabolites that were linked to 27 components of DSS. Bioinformatics analysis showed that the potential targets have various molecular functions (especially serine-type endopeptidase inhibitor activity) and biological process (such as positive regulation of peptidyl-tyrosine phosphorylation or autophosphorylation). CONCLUSIONS: The regulation of disrupted metabolic pathways and the relative targets may be the mechanism for DSS in the treatment of NS. Notably, metabonomics coupled with bioinformatics would be useful to explore the mechanism of DSS against NS and provide better insights on DSS for clinical use.

Morphoanatomical and phytochemical studies for the quality control of Neurolaena lobata (L.) R.Br. ex Cass. (Asteraceae) / Estudios morfoanatomicos y fitoquimicos para el control de calidad de Neurolaena lobata (L.) R.Br. ex Cass. (Asteraceae)

Neurolaena lobata (L.) R.Br. ex Cass. (Asteraceae)Is a popular folk remedy for in Central America. The plant is of commercial value in Guatemala but so far there is not any monograph to guide regional laboratories on ensuring identity and chemical tests for this species. As identity test we here run macro and micro morphoanatomical studies of the characters of the vegetative organs. We also developed standard chemical tests for quality by both TLC and HPLC for infusions and tinctures of varying alcoholic strength. Their radical scavenging activities in DPPH and NO were also measured. Macro and micro morphoanatomical characters of the vegetative organs present a set of characteristics to facilitate the identification of dry powdered samples of this species. We developed optimal conditions for the TLC and HPLC phytochemical fingerprints of the 4 most common pharmacopoeial liquid herbal preparations from this herbal drug, namely infusion, 70%, 45% and 20% hydroalcoholic tinctures. Our work provides the Latin-American industry with a set of analyses to establish the identity and chemistry of N. lobata samples for quality control purposes.

Neurolaena lobata (L.) R.Br. ex cass. (Asteraceae) es un remedio popular popular en América Central. La planta tiene un valor comercial en Guatemala, pero hasta el momento no existe una monografía que guíe a los laboratorios regionales para garantizar la identidad y las pruebas químicas para esta especie. Como prueba de identidad proponemos estudios macro y micro morfoanatómicos de los caracteres de los órganos vegetativos. También desarrollamos pruebas químicas de calidad mediante CCF y CLAR para infusiones y tinturas de grado alcohólico variable. También se midieron sus actividades de captación de radicales en DPPH y NO. Los caracteres macro y micro morfoanatómicos de los órganos vegetativos presentan un conjunto de características para facilitar la identificación de muestras de polvo seco de esta especie. Desarrollamos condiciones óptimas para las huellas dactilares fitoquímicas de CCF y CLAR de las 4 preparaciones herbales líquidas farmacopéicas más comunes de esta droga herbal, a saber, infusión, 70%, 45% y 20% tinturas hidroalcohólicas. Nuestro trabajo proporciona a la industria latinoamericana un conjunto de análisis base para establecer la identidad y la química de las muestras de N. lobata con fines de control de calidad.

Analysis of Effect of Schisandra in the Treatment of Myocardial Infarction Based on Three-Mode Gene Ontology Network.

Schisandra chinensis is a commonly used traditional Chinese medicine, which has been widely used in the treatment of acute myocardial infarction in China. However, it has been difficult to systematically clarify the major pharmacological effect of Schisandra, due to its multi-component complex mechanism. In order to solve this problem, a comprehensive network analysis method was established based-on "component-gene ontology-effect" interactions. Through the network analysis, reduction of cardiac preload and myocardial contractility was shown to be the major effect of Schisandra components, which was further experimentally validated. In addition, the expression of NCOR2 and NFAT in myocyte were experimentally confirmed to be associated with Schisandra in the treatment of AMI, which may be responsible for the preservation effect of myocardial contractility. In conclusion, the three-mode gene ontology network can be an effective network analysis workflow to evaluate the pharmacological effects of a multi-drug complex system.

Extract of Sheng-Mai-San Ameliorates Myocardial Ischemia-Induced Heart Failure by Modulating Ca2+-Calcineurin-Mediated Drp1 Signaling Pathways.

Sheng-Mai-San (SMS) is a well-known traditional Chinese medicine (TCM) complex prescription used to treat heart failure (HF) and angina in clinic. However, its potential therapeutic mechanisms remain unclear. The present study evaluated the cardioprotection of extract of SMS (ESMS) on myocardial ischemia (MI)-induced HF, and explored the underlying molecular mechanisms. The results demonstrated that ESMS (728.0 mg/kg) significantly attenuated MI injury-induced HF by improving cardiac function and pathological changes, decreasing lactate dehydrogenase (LDH), creatine kinase (CK) activities, and brain natriuretic peptide (BNP) levels; increasing ATPase activity; and reducing intracellular Ca2+ levels in MI-induced HF mice model. It also significantly decreased the apoptotic index. In vitro, ESMS (400 µg/mL) inhibited mitochondrial-dependent myocardial apoptosis by modulating the expression of caspase-3 and the Bcl-2/Bax ratio, and improved mitochondrial function through increasing mitochondrial membrane potential and cellular ATP content. ESMS restored intracellular Ca2+ and downregulated the expression of Calcineurin A (CnA), thus inhibiting phosphorylation of dynamin-related protein 1 (Drp1) at Ser616 and increasing phosphorylation of Drp1 at Ser637 to prevent cardiomyocyte mitochondrial fission. Above-mentioned results demonstrated ESMS suppressed mitochondrial-mediated apoptosis in oxygen glucose deprivation (OGD) injured H9c2 cardiomyocytes. These findings suggested that ESMS attenuated MI-induced HF by regulating Ca2+ homeostasis and suppressing mitochondrial mediated apoptosis through the modulation of Ca2+-calcineurin-mediated Drp1 signaling pathways. Our results provide insight into the mechanism and clinical applications of SMS and suggest a potential therapeutic strategy for HF.

[Study on intervention effect of Danggui Shaoyao San on rats with cirrhotic ascites].

OBJECTIVE: To investigate the intervention effect of Danggui Shaoyao San on rats with cirrhotic ascites, and discuss the effect of arginine vasopressin (AVP) on cirrhotic ascites. METHOD: Male SD rats were randomly divided into the control group, the model group, Danggui Shaoyao San low, middle and high dose groups. The cirrhotic ascites rat model was established by CCl4 combined with phenobarbital. Their urines were collected at 24 h to observe urine excretion of each group. Filter papers were used to determine the amount of ascites. The levels of serum alanine aminotransferasa (ALT) , aspartate aminotransferase (AST) were detected by the automatic biochemistry analyzer. Plasma prothrombin time (PT) was evaluated by the blood coagulation analyzer. The concentration of AVP in plasma was detected by enzyme-linked immunosorbent assay (ELISA). Pathological changes in livers were observed by HE staining. RESULT: Compared with the model group, the Danggui Shaoyao San group showed significant improvement in live indexes, with notable decrease in serum ALT and AST and the time of PT, improvement in liver pathological changes. Simultaneously, the amount of ascites decreased to varying degrees, with notable increase in urine in 24 h and decrease in AVP concentration in plasma. CONCLUSION: Danggui Shaoyao San can notably improve liver functions of rats with cirrhotic ascites, reduce the generation of ascites and delay the progress of liver pathological changes. Its mechanism may be related to AVP.