Study of the Mechanism of Action of Guanxin Shutong Capsules in the Treatment of Coronary Heart Disease Based on Metabolomics.

Background: Guan-Xin-Shu-Tong capsule (GXSTC) is a traditional Chinese medicine (TCM) that has been used to treat coronary heart disease (CHD) for many years in China. However, the holistic mechanism of GXSTC against CHD is still unclear. Therefore, the purpose of this paper was to systematically explore the mechanism of action GXSTC in the treatment of CHD rats using a metabolomics strategy. Methods: A CHD model was induced by ligation of the left anterior descending coronary artery (LAD). In each group, echocardiography was performed; the contents of creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate transaminase (AST) in serum were determined; and the myocardial infarct size was measured. The metabolites in plasma were analyzed by UHPLC-MS/MS-based untargeted metabolomics. Then, multivariate statistical analysis was performed to screen potential biomarkers associated with the GXSTC treatment in the LAD-induced rat CHD model. Finally, the MetaboAnalyst 4.0 platform was used for metabolic pathway enrichment analysis. Results: GXSTC was able to regulate the contents of CK, LDH and AST; restore impaired cardiac function; and significantly reduce the myocardial infarction area in model rats. Twenty-two biomarkers and nine metabolic pathways of GXSTC in the treatment of CHD were identified through UHPLC-MS/MS-based untargeted metabolomics analysis. Conclusion: GXSTC regulates metabolic disorders of endogenous components in LAD-induced CHD rats. The anti-CHD mechanism of GXSTC is mainly related to the regulation of amino acid, lipid and hormonal metabolism. This study provides an overall view of the mechanism underlying the action of GXSTC against CHD.

Network pharmacology-based prediction of the active ingredients and mechanism of Shen Gui capsule for application to coronary heart disease.

BACKGROUND: Shen Gui capsule (SGC) is a new national drug in China that is widely used in clinical practice and has significant therapeutic effects on coronary heart disease (CHD). However, its active ingredients and mechanism of action for treating coronary heart disease remain unknown. Therefore, the purpose of this paper is to systematically explore the mechanism and efficacy of SGC in the "multicomponent-multitarget- multipathway" treatment for CHD using network pharmacology technology. METHODS: The potential active ingredients of SGC were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and screened by pharmacokinetic parameters. Their possible targets were predicted using the TCMSP and DrugBank database. The CHD-related targets were identified from Comparative Toxicogenomics Database (CTD), UniProt, and PharmGKB database. The compound-target-disease network was constructed using Cytoscape for visualization. Additionally, the protein functional annotation and identification of signaling pathways of potential targets were performed by Gene Ontology (GO) and KEGG enrichment analysis using the Metascape platform. RESULTS: The 61 active ingredients of SGC were found to regulate neuroactive ligand-receptor interaction, fluid shear stress and atherosclerosis, estrogen signaling pathway and other pathways through 62 targets. SGC is involved in regulating the circulatory system, nervous system and immune system and other aspects of the body, and thus plays a significant role in the treatment of CHD and its complications, showing the mechanism of SGC's "multicomponent, multitarget, and multipathway" prevention and treatment of CHD. In addition, three predictive components were first found to have potential biological activity by this method. CONCLUSION: The studies we have performed successfully predict the effective components and potential targets of SGC in the prevention and treatment of CHD, which helped to systematically clarify its mechanism of action and provided a direction for future research on the modern mechanism of SGC in the treatment of CHD.

Synthesis of boronate-decorated polyethyleneimine-grafted porous layer open tubular capillaries for enrichment of polyphenols in fruit juices.

A combination between modification with porous layer and grafting of polyethyleneimine (PEI) on the inner face of capillary was for the first time developed for boronate affinity in-tube solid-phase microextraction (SPME) material to enhance the extraction capacity for cis-diol-containing polyphenols. The successful synthesis of boronate-decorated polyethyleneimine-grafted porous layer open tubular (BPPLOT) capillary was confirmed by scanning electron micrograph, Fourier transform-infrared spectra and absorption experiments. The porous layer, PEI and boronate affinity provided high specific surface area, more binding sites for boronate groups and specific selectivity of BPPLOT capillary, respectively. The maximum binding quantity of BPPLOT capillary greatly improved, and ranged from 143 to 170 µg m-1 for cis-diol-containing polyphenols (catechin, chlorogenic acid, caffeic acid and epicatechin). A green method based on boronate affinity in-tube SPME was developed for separation and enrichment polyphenols, and some parameters of in-tube SPME were optimized. After in-tube SPME, HPLC with UV detection was used for quantitative determination of polyphenols. Recoveries of standard spiked cis-diol-containing polyphenols from fruit juice were between 80.9% and 102%, with intra-day and inter-day coefficient of variation ranging from 4.8% to 7.3% and 5.0% to 8.6%, respectively. Conversely, recovery of non-cis-diol-containing ferulic acid was no greater than 3.0%. These results suggested that the BPPLOT capillary could effectively separate and enrich cis-diol-containing polyphenols from real samples.

Hypouricemic effect of allopurinol are improved by Pallidifloside D based on the uric acid metabolism enzymes PRPS, HGPRT and PRPPAT.

Allopurinol is a commonly used medication to treat hyperuricemia and its complications. Pallidifloside D, a saponin glycoside constituent from the total saponins of Smilax riparia, had been proved to enhanced hypouricemic effect of allopurinol based on uric acid metabolism enzyme XOD. In this study, we evaluated whether Pallidifloside D (5mg/kg) enhanced hypouricemic effect of allopurinol (5mg/kg) related to others uric acid metabolism enzymes such as PRPS, HGPRT and PRPPAT. We found that, compared with allopurinol alone, the combination of allopurinol and Pallidifloside D significantly up-regulated HGPRT mRNA expression and down-regulated the mRNA expression of PRPS and PRPPAT in PC12 cells (all P<0.01). These results strongly suggest that hypouricemic effect of allopurinol are improved by Pallidifloside D via numerous mechanisms and our data may have a potential value in clinical practice in the treatment of gout and other hyperuricemic conditions.

Pallidifloside D from Smilax riparia enhanced allopurinol effects in hyperuricemia mice.

Pallidifloside D, a saponin glycoside constituent from the total saponins of Smilax riparia, had been proved to be effective in hyperuricemic control. Allopurinol is a commonly used medication to treat hyperuricemia and its complications. In this study, we evaluated whether Pallidifloside D could enhance allopurinol's effects by decreasing the serum uric acid level in a hyperuricemic mouse model induced by potassium oxonate. We found that, compared with allopurinol alone, the combination of allopurinol and Pallidifloside D significantly decreased the serum uric acid level and increased the urine uric acid level (both P<0.05), leading to the normalized serum and urine uric acid concentrations. Data on serum, urine creatinine and BUN supported these observations. Our results showed that the synergistic effects of allopurinol combined with Pallidifloside D were linked to the inhibition of both serum and hepatic xanthine oxidase (XOD), the down-regulation of renal mURAT1 and mGLUT9, and the up-regulation of mOAT1. Our data may have a potential value in clinical practice in the treatment of gout and other hyperuricemic conditions.

Anti-hyperuricemia effects of allopurinol are improved by Smilax riparia, a traditional Chinese herbal medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: The roots and rhizomes of Smilax riparia are called "Niu-Wei-Cai" in traditional Chinese medicine (TCM). This botanical has been used in treating the symptoms of gout and other hyperuricemic-related conditions in TCM. Allopurinol is a commonly used medication to treat hyperuricemia and its complications. In this study, we evaluated whether Smilax riparia could enhance allopurinol׳s effects by decreasing the serum uric acid level in a hyperuricemic mouse model induced by potassium oxonate. MATERIALS AND METHODS: We examined the effects of allopurinol (5mg/kg) administration alone or in combination with Smilax riparia saponins (SRS, 500 mg/kg) on the serum uric acid (SUA), serum creatinine (SCr) and blood urea nitrogen (BUN) levels in a hyperuricemic mouse model. The effects of allopurinol alone or those of allopurinol plus SRS on the XOD activities were measured. Western blot analysis was used to measure the levels of mURAT1, mGLUT9 and mOTA1 in the mice. RESULTS: Compared with allopurinol alone, the combination of allopurinol and SRS significantly decreased the serum uric acid level and increased the urine uric acid level (both P<0.05), leading to the normalized serum and urine uric acid concentrations. Data on serum and urine creatinine and BUN supported these observations. The attenuation of hyperuricemia-induced renal dysfunction was linked to the inhibition of both serum and hepatic xanthine oxidase (XOD), the down-regulation of renal mURAT1 and mGLUT9, and the up-regulation of mOAT1. CONCLUSION: The anti-hyperuricemia effects of allopurinol are improved by Smilax riparia co-administration. The results were supported by the measurement of uric acid, creatinine, BUN, XOD, mURAT1, mGLUT9 and mOAT1. Our data may have a potential value in clinical practice in the treatment of gout and other hyperuricemic conditions.

Pallidifloside D, a saponin glycoside constituent from Smilax riparia, resist to hyperuricemia based on URAT1 and GLUT9 in hyperuricemic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The roots and rhizomes of Smilax riparia (SR), called "Niu-Wei-Cai" in traditional Chinese medicine (TCM), are believed to be effective in treating hyperuricemia and gout symptoms. This study was designed to isolate a saponin glycoside named pallidifloside D from the total saponins of Smilax riparia and to examine its effect in reducing serum uric acid levels in a hyperuricemic mouse model induced by potassium oxonate. MATERIALS AND METHODS: We examined the effects of pallidifloside D treated with 5, 10 and 20mg/kg on serum uric acid levels (SUA), Serum creatinine (SCr) and blood urea nitrogen (BUN) levels in a hyperuricemic mouse. A colorimetric method was used to evaluate the effects of pallidifloside D on the XOD activities, and Western Blotting analysis were carried out to observe protein levels of mURAT1, mGLUT9 and mOTA1 in hyperuricemic mice after treatment with pallidifloside D. RESULTS: The levels of serum uric acid levels (SUA) were suppressed significantly with dose-dependence by pallidifloside D treated with 5, 10 and 20mg/kg (p<0.05, p<0.01 and p<0.01 respectively). Pallidifloside D could down-regulate the expression levels of renal mURAT1 protein in hyperuricemic mice in a dose-dependent manner (p<0.05, p<0.01, and p<0.001 respectively), and the protein levels of mGLUT9 could be down-regulated with dose-dependence (p<0.05 and p<0.01 respectively) by pallidifloside D at the dose of 10 and 20mg/kg. CONCLUSION: These results suggest that pallidifloside D possesses a potent uricosuric effect in hyperuricemic mice through decreasing renal mURAT1 and GLUT9, which contribute to the enhancement of uric acid excretion and attenuate hyperuricemia-induced renal dysfunction.

Effects of Smilaxchinoside A and Smilaxchinoside C, two steroidal glycosides from Smilax riparia, on hyperuricemia in a mouse model.

The roots and rhizomes of Smilax riparia, called 'Niu-Wei-Cai' in traditional Chinese medicine, are believed to be effective in treating the symptoms of gout. However, the active constituents and their uricosuric mechanisms are unknown. In this study, we isolated two steroidal glycosides, named smilaxchinoside A and smilaxchinoside C, from the total saponins obtained from the ethanol extract of the roots of S. riparia. We then examined if these two compounds were effective in reducing serum uric acid levels in a hyperuricemic mouse model induced by potassium oxonate. We observed that these two steroidal glycosides possess potent uricosuric activities, and the observed effects accompanied the reduction of renal mURAT1 and the inhibition of xanthine oxidase, which contribute to the enhancement of uric acid excretion and the reduction of hyperuricemia-induced renal dysfunction. Smilaxchinoside A and smilaxchinoside C may have a clinical utility in treating gout and other medical conditions caused by hyperuricemia.

Riparoside B and timosaponin J, two steroidal glycosides from Smilax riparia, resist to hyperuricemia based on URAT1 in hyperuricemic mice.

The roots and rhizomes of Smilax riparia (SR), called "Niu-Wei-Cai" in traditional Chinese medicine (TCM), are believed to be effective in treating gout symptoms. However, it is not clear if the active constituents and uricosuric mechanisms of S. riparia support its therapeutic activities. In this study, we isolated two steroidal glycosides named riparoside B and timosaponin J from the total saponins of S. riparia. We then examined if these two compounds were effective in reducing serum uric acid levels in a hyperuricemic mouse model induced by potassium oxonate. We found that the two steroidal glycosides possess potent uricosuric effect in hyperuricemic mice through decreasing renal mURAT1 mainly and inhibiting XOD activity in a certain extent, which contribute to the enhancement of uric acid excretion and attenuate hyperuricemia-induced renal dysfunction. Riparoside B and timosaponin J may have a clinical utility in treating gout and other medical conditions caused by hyperuricemia.

Smilax riparia reduces hyperuricemia in mice as a potential treatment of gout.

The roots and rhizomes of Smilax riparia, called "Niu-Wei-Cai" in traditional Chinese medicine (TCM), are believed to be effective in treating gout symptoms. However, it is not clear if the uricosuric mechanisms of S. riparia support its therapeutic activities. In this study, we examined the efficacy of S. riparia in reducing serum uric acid levels in a potassium oxonate-induced hyperuricemia mouse model. We observed that the total saponins of S. riparia could down-regulate renal mURAT1, resulting in the enhancement of urate excretion in the kidney of hyperuricemic mice. These results suggest that S. riparia could be an active anti-gout herbal medicine, which would contribute to the enhancement of uric acid excretion in the kidney.

Immunosuppressive sesquiterpenes from Buddleja daviddi.

Six new sesquiterpenes, 2,6(12),10-humulatrien-7ß-ol-1-one (1), 2 α-acetoxy-5α-methoxy-enantio-caryophylla-8(15)-en-3-one (2), 2α-acetoxy-5α-hydroxy-enantio-caryophylla-8(15)-en-3-one (3), 2α-acetoxy-4ß,5α-hydroxy-enantio-caryophylla-8(15)-en-3-one ( 4), 2α-acetoxy-4ß,5ß-hydroxy-enantio-caryophylla-8(15)-en-3-one (5), 2ß-acetoxy-4-caryophyllen-8ß-ol-3-one (6), and nineteen known compounds were isolated from the ethanol extract of Buddleja daviddi. The structures were elucidated by spectroscopic methods. Compounds 8-11, 14, 16, 17, and 20 showed significant immunosuppressive activities, and 8-11 and 14 were cytotoxic on HeLa and L929 cell lines.

Six new cycloartane triterpene glycosides from Actaea asiatica.

Six new cycloartane triterpene glycosides, (3',12beta)-O-diacetyl-cimigenol-3-O-beta-D-xylopyranoside (1), (4',25)-O-diacetyl-cimigenol-3-O-beta-D-xylopyranoside (2), 2'-O-acetyl-25-O-methyl-cimigenol-3-O-beta-D-xylopyranoside (3), 2'-O-acetyl-25-O-ethyl-cimigenol-3-O-beta-D-xylopyranoside (4), 3'-O-acetyl-cimicifugoside (5), and 4'-O-acetyl-23-epi-26-deoxycimifugoside (6), were isolated from the rhizomes of Actaea asiatica. Their structures were elucidated on the basis of chemical methods and spectroscopic analysis. Compounds 1, 2, 4-6 exhibited positive cytotoxic activities.

[Studies on chemical constituents from rhizome of Anemone flaccida].

OBJECTIVE: To study the chemical constituents from Anemone flaccida. METHOD: Chemical constituents were isolated by repeated column chromatography (silica gel, Toyopearl HW-40C and preparative HPLC). The structures were elucidated on the basis of spectral data analysis. RESULT: Twelve triterpenes were isolated and their structures were identified as follow: oleanolic acid (1), oleanolic acid 3-O-beta-D-glccopyranosyl-(1-->2)-beta-D-xylopyranoside (2), eleutheroside K (3), oleanolic acid 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranoside (4), oleanolic acid 3-O-beta-D-glccopyranosyl-(1-->2)-alpha-L-arabinofurnoside (5), oleanolic acid 3-O-beta-D-glccuronopyranose (6), oleanolic acid 3-O-beta-D-glccuronopyranose methyl ester (7), oleanolic acid 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glccopyranosyl (1-->6)-beta-D-glccopyranosyl (8), oleanolic acid 3-O-beta-D-glccuronopyranose 28-O-alpha-L-rhamnopyranosyl (1-->4)-beta-D-glccopyranosyl (1-->6)-beta-D-glccopyranoside (9), oleanolic acid 3-O-beta-D-glccopyranosyl methyl ester 28-O-alpha-L-rhamnopyranosyl (1-->4)-beta-D-glccopyranosyl (1-->6)-beta-D-glccopyranoside (10), oleanolic acid 3-O-beta-D-glccopyranosyl-(1-->2)-beta-D-xylopyranosyl-28-O-alpha-L-rhamnopyranosyl (1-->4)-beta-D-glccopyranosyl (1-->6)-beta-D-glccopyranoside (11), oleanolic acid 3-O-alpha-L-rh-amnopyranosyl-(1-->2)-alpha-L-arabinopyrnosyl-28-O-alpha-L-rhamnopyranosyl (1-->4)-beta-D-glccopyranosyl (1-->6)-beta-D-glccopyranoside (12). CONCLUSION: compounds 5-8, 10, 12 were isolated from this plant for the first time. Compounds 2, 5 and 11 showed positive anti-tumor activities.

[Study on anti-diabetes active fraction and constituents from Potentilla chinesis].

OBJECTIVE: To study the active fraction and constituents from Potentilla chinesis. METHOD: Tested fractions were obtained by different solvent-partition from 95% ethanol-extracts of P. chinesis, and tested compound was isolated by repeated chromatography. Anti-diabetes experiment was taken by using alloxan-induced diabetic mice. RESULT: The fraction F and the tested compound revealed obvious difference comparing with the control group (P <0.01). CONCLUSION: Fraction F and potentilla flavone revealed the significant hypoglycemic effect in alloxan-induced diabetic mice.

[Studies on chemical constituents in herb of Centella asiatica].

OBJECTIVE: To study the chemical constituents from Centella asiatica. METHOD: Chemical constituents were isolated by repeated column chromatography (Toyopearl HW-40C and HPLC) and their structures were elucidated on the basis of spectroscopic method. RESULT: Five compounds were identified as: docosyl ferulates (1), bayogenin (2), 3beta-6beta-23-trihydroxyolean-12-en-28-oic acid (3), 3beta-6beta-23-trihydroxyurs-12-en-28-oic acid (4), D-gulonic acid (5). CONCLUSION: All of the Compounds were isolated for the first time from C. asiatica.

[Chemical constituents from rhizome of Phlomis umbrosa].

Phlomis umbrosa is a traditional medicinal plant, distributed in the north of China. In the west of Hubei province, its roots were used in the treatment of the rheumatic diseases in Tujia nationality. To study the chemical constituents from the rhizome of Phlomis umbrosa chemical constituents were isolated from the plant by using repeated silica gel, toyopearl HW-40 and preparative HPLC chromatography. The structures of the compounds were elucidated on the basis of one and two dimensional NMR spectroscopic techniques and HRESI-MS. Ten compounds, 6"-syringyl-sesamoside (1), decaffeoylverbascoside (2), calcelarioside B (3), verbascoside (4), isoverbascoside (5), alyssonoside (6), sesamoside (7), shanzhiside methyl ester (8), 8-acetyl-shanzhiside methyl ester (9), 7-epiphlomiol (10) were isolated from P. umbrosa. Compound 1 is a new compound. Compounds 2-6 are isolated from this plant for the first time.

[Chemical constituents from herb of Alternanthera philoxeroides].

OBJECTIVE: To study the active constituents from Alternanthera philoxeroides. METHOD: The constituents were isolated with silica gel and Toyopearl HW-40C gel column chromatography and purified by HPLC. Their structures were elucidated by spectroscopy. RESULT: Nine compounds were isolated and identified as phaeophytin a (1), pheophytin a' (2), oleanoic acid (3), beta-sitosterol (4), 3beta-hydroxystigmast-5-en-7-one (5), alpha-spinasterol (6), 24-methylenecycloartanol (7), cycloeucalenol (8), phytol (9). CONCLUSION: Compounds 1,2,5,7-9 were isolated from this plant for the first time.

[Triterpenes from herb of Potentilla chinesis].

OBJECTIVE: To study the chemical constituents of Potentilla chinesis and their anticancer activities. METHOD: Chemical constituents were isolated by repeated column chromatography (Toyopearl HW-40C and preparative HPLC). The structures were elucidated on the basis of spectral data analysis. The isolated compounds were screened with two anticancer models. RESULT: Fifteen triterpenes, alpha-amyrin (1) , beta-amyrin (2) , ursolic acid (3) , corosolic acid (4), euscaphic acid (5) , pomolic acid (6) , tormentic acid (7), 2alpha, 3alpha-dihydroxyurs-12-en-28-oic acid (8), 2beta, 3beta, 19alpha-trihydroxyurs-12-en-28-oic acid (9), asiatic acid (10) , 24-hydroxy tormentic acid (11) , myrianthic acid (12), oleanolic acid (13), maslinic acid (14) and 2alpha, 3alpha-dihydroxyolean-12-en-28-oic acid (15) , were isolated from P. chinesis. CONCLUSION: Compounds 1, 2, 4 -15 were isolated from the plant for the first time. Compounds 4, 8 - 10, 12, 14 and 15 show anticancer activities. Compounds 4, 9 show strong activities.