[Review of classical prescriptions in treatment of ulcerative colitis].

Ulcerative colitis(UC) is a continuous inflammatory bowel disease with the main clinical manifestations of abdominal pain, diarrhea, and mucous bloody stools, mainly attacking the colorectal mucosa and submucosa. It is characterized by high recurrence rate, difficult cure, and clustering and regional occurrence. Chinese medicinal prescriptions for the treatment of UC have good therapeutic effect, multi-target regulation, slight toxicity, and no obvious side effects. In particular, the classical prescriptions highlight the characteristics and advantages of traditional Chinese medicine theory and have attracted much attention in recent years. To enable researchers to timely and comprehensively understand the classical prescriptions in the treatment of UC, we reviewed the studies about the pharmacodynamic material basis, quality control, action mechanism, and clinical application of relevant classical prescriptions. We first introduced the latest research progress in the active components such as alkaloids, polysaccharides, saponins, and flavonoids in relevant classical prescriptions. Then, we reviewed the latest research achievements on the quality control of classical prescriptions for the treatment of UC by gas chromatography, liquid chromatography, mass spectrometry, liquid chromatography-mass spectrometry and the like. Further, we summarized the research advances in the mechanisms of relevant prescriptions in the treatment of UC based on network pharmacology, molecular docking, integrated pharmacology platform, and animal experiments. Finally, we generalized the clinical application of the classical prescriptions for clearing heat and removing dampness, mildly regulating cold and heat, soothing liver and regulating spleen, strengthening spleen and invigorating Qi, and tonifying spleen and stomach. By systematic summary of the research progress in relevant classical prescriptions, we hope to promote the application and development of such prescriptions in UC treatment.

Neuroendocrine-Immune Regulatory Network of Eucommia ulmoides Oliver.

Eucommia ulmoides Oliver (E. ulmoides) is a popular medicinal herb and health supplement in China, Japan, and Korea, and has a variety of pharmaceutical properties. The neuroendocrine-immune (NEI) network is crucial in maintaining homeostasis and physical or psychological functions at a holistic level, consistent with the regulatory theory of natural medicine. This review aims to systematically summarize the chemical compositions, biological roles, and pharmacological properties of E. ulmoides to build a bridge between it and NEI-associated diseases and to provide a perspective for the development of its new clinical applications. After a review of the literature, we found that E. ulmoides has effects on NEI-related diseases including cancer, neurodegenerative disease, hyperlipidemia, osteoporosis, insomnia, hypertension, diabetes mellitus, and obesity. However, clinical studies on E. ulmoides were scarce. In addition, E. ulmoides derivatives are diverse in China, and they are mainly used to enhance immunity, improve hepatic damage, strengthen bones, and lower blood pressure. Through network pharmacological analysis, we uncovered the possibility that E. ulmoides is involved in functional interactions with cancer development, insulin resistance, NAFLD, and various inflammatory pathways associated with NEI diseases. Overall, this review suggests that E. ulmoides has a wide range of applications for NEI-related diseases and provides a direction for its future research and development.

Design and fabrication of an integrated 3D dynamic multicellular liver-on-a-chip and its application in hepatotoxicity screening.

Nowadays, major methods of in vitro hepatotoxicity research are still based on traditional static two- or three-dimensional cell culture, although these means could investigate some toxic chemicals induced hepatotoxicity, but most of these toxicities failed to reappear in human, at least not in similar or calculable dose level. These failures may cause by the monoculture of only hepatocytes, ignored the signal communication to other non-parenchymal cells in liver tissue, also other complex microenvironment such as endothelial barrier, shear stress and other factors which were really existed in vivo but absent here, final leading to a low reliability of experimental results. In this study, a three-dimensional dynamic multi-cellular liver-on-a-chip device (3D-DMLoC) was developed to reproduce the microenvironment of in vivo liver tissue, including the simulation of hepatic sinusoid, perisinusoidal space and continuous liquid perfusion, hepatocytes could gather to some 3D cell spheroids in this chip. The perfusion could bring a real-time exchange of chemicals, nutrients, metabolites, supply suitable oxygen and a weak shear stress. The pressure and oxygen distribution inner the chip were simulated and evaluated by COMSOL Multiphysics software. HepaRG were co-cultured with HUVEC for 7 days in this chip, expression of hepatic polarization protein ZO-1 and MRP2, liver function factors ALB, UREA and CYP450s were almost all higher than in traditional static culture. Several drugs and heavy metal ions induced hepatotoxicity were then investigated, LDH released from hepatocyte spheroids in mostly 3D-DMLoC groups were higher than same-dosed 2D group, indicated the spheroids were more sensibility to the toxins. The hepatoxicity might be induced by acute hepatocytes injury according to the ratios of secreted AST/ALT contents. In conclusion, a liver-on-a-chip device was successfully developed and verified for better reproducing the in vivo physiological microenvironment of liver. It could be applied for easily, efficiently, and accurately screening the potential hepatotoxic chemicals in future.

Characterization of alkaloids in radix Sophora tonkinensis by UPLC-Q-TOF-MS/MS and its application in the comparison of two different habitats.

Sophora tonkinensis is widely used as traditional Chinese medicine for treating the swelling of the gums and tongue and mouth sores due to flame stomach fire. It is mainly origin from Guangxi, Sichuan provinces of China. Alkaloids are considered as the major bioactive components. A method was established for identifying alkaloids in S. tonkinensis root by UPLC-Q-TOF-MS/MS and was applied in characterizing alkaloids in S. tonkinensis root of two different habitats. Consequently, twenty-four alkaloids including six new compounds were identified in S. tonkinensis root. Additionally, the difference of alkaloids in S. tonkinensis from Guozhou, Sichuan province was investigated. In the present study, we firstly characterize total alkaloids in S. tonkinensis root by UPLC-Q-TOF-MS/MS and firstly established the characteristic fragmentation pathway of alkaloids with hydroxy in S. tonkinensis root.

Design and fabrication of a liver-on-a-chip platform for convenient, highly efficient, and safe in situ perfusion culture of 3D hepatic spheroids.

Spheroid-based three-dimensional (3D) liver culture models, offering a desirable biomimetic microenvironment, are useful for recapitulating liver functions in vitro. However, a user-friendly, robust and specially optimized method has not been well developed for a convenient, highly efficient, and safe in situ perfusion culture of spheroid-based 3D liver models. Here, we have developed a biomimetic and reversibly assembled liver-on-a-chip (3D-LOC) platform and presented a proof of concept for long-term perfusion culture of 3D human HepG2/C3A spheroids for building a 3D liver spheroid model. On the basis of a fast and reversible seal of concave microwell-based PDMS-membrane-PDMS sandwich multilayer chips, it enables a high-throughput and parallel perfusion culture of 1080 cell spheroids in a high mass transfer and low fluid shear stress biomimetic microenvironment as well as allowing the convenient collection and analysis of the cell spheroids. In terms of reducing spheroid loss and maintaining cell morphology and viability in long-term perfusion culture, the cell spheroids in the 3D-LOC were more safe and efficient. Notably, the polarisation, liver-specific functions, and metabolic activity of the cell spheroids in 3D-LOC were also remarkably improved and exhibited better long-term maintenance over conventional perfusion methods. Additionally, a robust micromilling method that incorporates secondary PDMS coating techniques (SPCs) for fabricating V-shaped concave microwells was also developed. The V-shaped concave microwell arrays exhibited a higher distribution density and aperture ratio, making it easy to form large-scale and uniform-sized cell spheroids with minimum cell loss. In summary, the proposed 3D-LOC could provide a convenient and robust solution for the long-term safe perfusion culture of hepatic spheroids and be beneficial for a variety of potential applications including development of bio-artificial livers, disease modeling, and drug toxicity screening.

Therapeutic Effects of Tangshen Formula on Diabetic Nephropathy in db/db Mice Using Cytokine Antibody Array.

OBJECTIVE: Cytokines are essential promoters in the pathogenesis of diabetic nephropathy (DN) in type 2 diabetes. The following study investigates the adjustment mechanism of Tangshen formula (TSF) on cytokine expressions in db/db mice (DN animal model). MATERIALS AND METHODS: Db/db mice were randomly divided into three groups. The treated groups were orally administered with TSF and losartan for 12 weeks. Biochemical and histological examinations were determined at 8 and 12 weeks posttreatment, while the cytokine antibody array analysis was applied to analyze the expression of 144 cytokines in kidney tissues at the end of the 12th week posttreatment. RESULTS: TSF significantly reduced urinary albumin excretion and the levels of blood glucose, cholesterol, triglyceride, creatinine, and urea nitrogen. Furthermore, a significant decrease in glomerulus and mesangial area, as well as the downregulation of 24 cytokines and upregulated expressions of 5 cytokines, was found in the TSF-treated mice. CONCLUSIONS: The present study reveals that TSF could ameliorate the metabolic anomalies and renal injury in db/db mice. One of the important mechanisms for treatment of DN using the treatment of TSF is the control of the JAK/STAT signaling pathway via regulation of IL-2, IL-6, IL-13, Il-15, and IFN-γ expression.

A new method to evaluate the dose-effect relationship of a TCM formula Gegen Qinlian Decoction: "Focus" mode of integrated biomarkers.

It is difficult to accurately evaluate the efficacy of traditional Chinese medicine (TCM), which leads to the uncertainty and complexity of dose-effect analysis. In this study we established the "Focus" mode of biomarkers to characterize the dose-effect relationship of Gegen Qinlian Decoction (GQD), a TCM formula for treating type 2 diabetes mellitus (2-DM). A rat model of 2-DM was established through high fat diet feeding combined with low-dose STZ injection. Rats with 2-DM were administered high, middle or low doses (6.785, 4.071, 1.357 mg·kg-1·d-1, respectively) of GQD extract for 60 d. Metformin (300 mg·kg-1·d-1) was taken as the positive control. Blood samples were collected to assess serum biochemical indexes and metabolic profiling. After "Focus" analysis, the biochemical index triglycerides (TG) and insulin sensitivity (ISI) were identified as focused integrated biomarkers (FIBs), while arachidonic acid and docosatetraenoic acid were the metabolic FIBs. Dose-effect relationship curves of GQD were built based on these types of FIBs. Furthermore, the two dose-effect relationship curves showed similar trends with the middle dosage displaying the greatest efficacy, suggesting that insulin function and arachidonic acid metabolism played important roles in 2-DM and the responses to GQD. The metabolic FIB docosatetraenoic should be further explored for understanding its involvement in the process of 2-DM occurrence and the treatment. This "Focus" mode provides a novel strategy to evaluate the dose-effect relationship of a TCM. The system and concepts established here may also be applicable for assessing the dose-effect relationships of Western medicines.

Metabolism and pharmacokinetics of major polyphenol components in rat plasma after oral administration of total flavonoid tablet from Anemarrhenae Rhizoma.

Total flavonoid tablet from Anemarrhenae Rhizoma (Zhimu tablet), which was made of total polyphenol components extracted from the dried rhizome of Anemarrhena asphodeloides Bge. (Zhimu in Chinese), is a novel traditional Chinese medicine prescribed for the treatment of diabetes. Mangiferin (MF) and neomangiferin (NMF) are the two main components detected and determined in Zhimu tablet, accounting for 8.9% of the total weight of each tablet. In the present study, high performance liquid chromatography (HPLC) coupled with time-of-flight (TOF) tandem mass spectrometry (MS) was applied to characterize the metabolites of MF and NMF in rat plasmas collected at different time points after oral administration of Zhimu tablet at a dose of 3.63g/kg (corresponding to 270mg/kg MF). Accurate mass measurement was used to determine the elemental composition of metabolites and thus to confirm the proposed structures of identified metabolites. Time points of appearance of some metabolites, such as isomers, were also taken into account during the structure confirmation. A total of 21 potential metabolites were found in rat plasma at different time points, and the metabolic pathways in vivo were involved in hydrolysis, methylation, glucuronide conjugation, glycoside conjugation, sulphation, dehydration and isomerisation. Furthermore, a selective and accurate LC-MS assay method was developed and validated for the quantification of MF in plasma. Semi-quantification of main conjugated metabolites was also performed in order to describe the dynamic metabolism profiles of polyphenol components in Zhimu tablet. MF concentration in plasma reached 1.36±0.47µgmL(-1) about 5.0h after oral administration of Zhimu tablet, which showed a 3.24- and 4.91-fold increase in plasma maximum concentration and area under the concentration-time curve (AUC) from 0 to 24h of MF compared with those for rats administered with free MF, respectively. The results indicated that the pharmacokinetic processes and bioavailability of MF in rats would be affected by other components in Zhimu tablet.

[The mechanism of rosiglitazone compound based on network pharmacology].

Applications of network pharmacology are increasingly widespread and methods abound in the field of drug development and pharmacological research. In this study, we choose rosiglitazone compound as the object to predict the targets and to discuss the mechanism based on three kinds of prediction methods of network pharmacology. Comparison of the prediction result has identified that the three kinds of prediction methods had their own characteristics: targets and pathways predicted were not in accordance with each other. However, the calcium signaling pathway could be predicted in the three kinds of methods, which associated with diabetes and cognitive impairment caused by diabetes by bioinformatics analysis. The above conclusion indicates that the calcium signaling pathway is important in signal pathway regulation of rosiglitazone compound, which provides a clue to further explain the mechanism of the compound and also provides a reference for the selection and application of methods of network pharmacology in the actual research.

[Study on inhibitory effects and mechanism of lipophilic components in Salvia miltiorrhiza on angiogenesis in vitro].

In this study, the human umbilical vein endothelial cell model was used to study the regulating effect of lipophilic components in Salvia miltiorrhiza on angiogenesis, and explore its possible mechanism. The cell model was established to determine the effect of lipophilic components in S. miltiorrhiza on the proliferative activity and migration capacity of endothelial cells. Then the realtime fluorescence quantification PCR technology was applied to detect the changes in the gene expressions of angiogenesis-related cytokines VEGF-A, VEGF-C and MMP-9. The results showed that 5 mg x L(-1) lipophilic components in S. miltiorrhiza could inhibit the proliferation and migration of endothelial cells, and reduce the expression of VEGF-A and MMP-9 genes. It indicated that lipophilic components in S. miltiorrhiza may inhibit the proliferation and migration of endothelial cells by inhibiting the expression of VEGF-A and MMP-9 genes, so as to show the inhibitory effect on angiogenesis.

Integrating qualitative and quantitative characterization of traditional Chinese medicine injection by high-performance liquid chromatography with diode array detection and tandem mass spectrometry.

The present study aims to describe and exemplify an integrated strategy of the combination of qualitative and quantitative characterization of a multicomponent mixture for the quality control of traditional Chinese medicine injections with the example of Danhong injection (DHI). The standardized chemical profile of DHI has been established based on liquid chromatography with diode array detection. High-performance liquid chromatography coupled with time-of-flight mass spectrometry and high-performance liquid chromatography with electrospray multistage tandem ion-trap mass spectrometry have been developed to identify the major constituents in DHI. The structures of 26 compounds including nucleotides, phenolic acids, and flavonoid glycosides were identified or tentatively characterized. Meanwhile, the simultaneous determination of seven marker constituents, including uridine, adenosine, danshensu, protocatechuic aldehyde, p-coumaric acid, rosmarinic acid, and salvianolic acid B, in DHI was performed by multiwavelength detection based on high-performance liquid chromatography with diode array detection. The integrated qualitative and quantitative characterization strategy provided an effective and reliable pattern for the comprehensive and systematic characterization of the complex traditional Chinese medicine system.

[Therapeutic effects of gegen qinlian decoction and its mechanism of action on type 2 diabetic rats].

The objective of this study is to fully investigate the therapeutic effect and mechanisms of action of Gegen Qinlian decoction (GD) on type 2 diabetes mellitus (type 2 DM). A rat model of type 2 DM was established with the combination of high-fat diet and multiple low doses of streptozotocin (STZ). Biochemical indicators related to glucose metabolism disorders, insulin resistance, oxidative stress were observed. The type 2 DM rats were administrated with GD for 80 days, the above-mentioned indexes were detected. The results indicated that the hepatic glycogen synthesis level was promoted, fasting blood glucose level and fasting blood insulin level were significantly reduced, insulin sensitivity index was significantly improved; the level of superoxide dismutase (SOD) was increased and the level of malondialdehyde (MDA) was reduced; pathologic morphology of pancreas and kidney was ameliorated in the GD group. It was indicated that the therapeutic mechanisms of action of GD on type 2 DM might be related to its effect of ameliorating glucose metabolism disorders, relieving insulin resistance, increasing the tissues' sensitivity to insulin, improving the antioxidative ability of living system, GD has therapeutic effect on type 2 DM and protective effects against damaged pancreatic function.

[Parallel PLS algorithm using MapReduce and its aplication in spectral modeling].

Partial least squares (PLS) has been widely used in spectral analysis and modeling, and it is computation-intensive and time-demanding when dealing with massive data To solve this problem effectively, a novel parallel PLS using MapReduce is proposed, which consists of two procedures, the parallelization of data standardizing and the parallelization of principal component computing. Using NIR spectral modeling as an example, experiments were conducted on a Hadoop cluster, which is a collection of ordinary computers. The experimental results demonstrate that the parallel PLS algorithm proposed can handle massive spectra, can significantly cut down the modeling time, and gains a basically linear speedup, and can be easily scaled up.

Steaming-induced chemical transformations and holistic quality assessment of red ginseng derived from Panax ginseng by means of HPLC-ESI-MS/MS(n)-based multicomponent quantification fingerprint.

The purpose of this study is to evaluate the steaming-induced chemical transformation of red ginseng manufactured from fresh ginseng by means of simultaneous quantitative and qualitative analyses with a combinative high-performance liquid chromatography-electrospray tandem mass spectrometry (HPLC-ESI-MS/MS(n)) technique. Thirty-six ginsenosides were identified in red ginseng and white ginseng by comparing the mass spectrum and/or matching the empirical molecular formula with that of known published compounds, and 11 of them were determined to be newly generated during the red ginseng preparatory process. The mechanisms involved were further deduced to be hydrolysis, dehydration, isomerization, and decarboxylation at C-20, and hydrolysis also occurs at C-3 or C-6 of the original ginsenosides through the mimic process of steaming and heating in laboratory. The multicomponent quantification fingerprint of ginseng was also established by HPLC-UV method, and the contents of 12 ginsenosides in red and white ginsengs from different sources were determined simultaneously. The ratio of the total content of determined malonyl ginsenosides to the corresponding neutral ginsenosides (T(m-PPD)/T(PPD)) in white ginseng ranged from 0.46 to 0.62 and from 0 to 0.19 in red ginseng. The validated method is expected to provide an effective approach to standardize the processing procedures of ginseng products and regulate the usage of ginseng in Traditional Chinese Medical prescription.

[A novel online process monitoring method based on near infrared spectroscopy and its application to the column chromatographic separation for traditional Chinese medicine].

Near infrared spectroscopy (NIRS) is a process analysis and monitoring tool with many advantages, while it needs to set up quantitative or discriminative calibration models in advance, and needs to adjust these models when the process conditions are varied, which makes it difficult for ordinary user to take its full advantage of it. To tackle this problem, this paper presented a novel, simple and model-free methodology for online process monitoring based on two reciprocal viewpoints of measuring the variability of spectroscopy-both the similarity and dissimilarity of process spectrum, i.e., the adaptive moving window standard deviation function(AMWSW) and similarity function(S). The methodology was validated by a column chromatography process of traditional Chinese medicine using near infrared spectroscopy. The online trend curves of AMWSW and S obtained by proposed method were validated by a comparison with the content variation curves of multiple indicative components analyzed by high performance liquid chromatography (HPLC), and these trend curves demonstrated their potential for real-time process status monitoring, accurately determining the beginning point, the peak point, the end point of the elution, and the phase change from water solution to ethanol solution. The proposed methodology can also be used to other process analysis techniques, such as ultraviolet/visible, infrared, Raman, fluorescence, chromatograph and mass spectrum.

[Comparative study on chemical quality of main species of epimedium].

This study was to comprehensively evaluate the chemical quality of main species of epimedium planted in China. The contents of 5 marker compounds, epimedin A, epimedin B, epimedin C, icariin and baohuoside I, as well as total flavonoids of 22 samples of 8 officinal species of Epimedium were determined by HPLC and UV, separately. Some physical and chemical tests (H2O, total ash, acid-insoluble ash and EtOH extract) were also carried out to investigate their chemical qualities. There were significant differences in types and contents of prenyl-flavonoid glycosides such as epimedin A, epimedin B, epimedin C, icariin and baohuoside I in different species, meanwhile, the physical and chemical parameters results also showed that there were obvious differences in chemical quality among different species of epimedium herb. The results provide theoretical and experimental basis for the establishment of comprehensive quality assessment system of epimedium in China.

Apolipoprotein A-I mimetic peptide inhibits atherosclerosis by altering plasma metabolites in hypercholesterolemia.

An apolipoprotein A-I mimetic peptide, D-4F, has been shown to improve vasodilation and inhibit atherosclerosis in hypercholesterolemic low-density lipoprotein receptor-null (LDLr(-/-)) mice. To study the metabolic variations of D-4F ininhibiting atherosclerosis, metabonomics, a novel system biological strategy to investigate the pathogenesis, was developed. Female LDLr(-/-) mice were fed a Western diet and injected with or without D-4F intraperitoneally. Atherosclerotic lesion formation was measured, whereas plasma metabolic profiling was obtained on the basis of ultra-high-performance liquid chromatography in tandem with time-of-flight mass spectrometry operating in both positive and negative ion modes. Data were processed by multivariate statistical analysis to graphically demonstrate metabolic changes. The partial least-squares discriminate analysis model was validated with cross-validation and permutation tests to ensure the model's reliability. D-4F significantly inhibited the formation of atherosclerosis in a time-dependent manner. The metabolic profiling was altered dramatically in hypercholesterolemic LDLr(-/-) mice, and a significant metabolic profiling change in response to D-4F treatment was observed in both positive and negative ion modes. Thirty-six significantly changed metabolites were identified as potential biomarkers. A series of phospholipid metabolites, including lysophosphatidylcholine (LysoPC), lysophosphatidylethanolamine (LysoPE), phosphatidylcholine (PC), phatidylethanolamine (PE), sphingomyelin (SM), and diacylglycerol (DG), particularly the long-chain LysoPC, was elevated dramatically in hypercholesterolemic LDLr(-/-) mice but reduced by D-4F in a time-dependent manner. Quantitative analysis of LysoPC, LysoPE, PC, and DG using HPLC was chosen to validate the variation of these potential biomarkers, and the results were consistent with the metabonomics findings. Our findings demonstrated that D-4F may inhibit atherosclerosis by regulating phospholipid metabolites specifically by decreasing plasma long-chain LysoPC.

Effective components screening and anti-myocardial infarction mechanism study of the Chinese medicine NSLF6 based on "system to system" mode.

BACKGROUND: Shuanglong formula (SLF), a Chinese medicine composed of panax ginseng and salvia miltiorrhiza exhibited significant effect in the treatment of myocardial infarction (MI) in clinical. Because of the complex nature and lack of stringent quality control, it's difficult to explain the action mechanism of SLF. METHOD: In this study, we present a "system to system" (S2S) mode. Based on this mode, SLF was simplified successively through bioactivity-guided screening to achieve an optimized minimal phytochemical composition (new formula NSLF6) while maintaining its curative effect for MI. RESULTS: Pharmacological test combining with the study of systems biology show that NSLF6 has activity for treatment MI through synergistic therapeutic efficacies between total ginsenosides and total salvianolic acids via promoting cardiac cell regeneration and myocardial angiogenesis, antagonistic myocardial cell oxidative damage. CONCLUSIONS: The present S2S mode may be an effective way for the discovery of new composite drugs from traditional medicines.

An HPLC-ESI-MS method for simultaneous determination of fourteen metabolites of promethazine and caffeine and its application to pharmacokinetic study of the combination therapy against motion sickness.

The combination therapy, promethazine and caffeine had been proven effective in treating motion sickness and counteracting some possible side effects of using promethazine alone while the mechanism and interaction remained unclear. Therefore, an HPLC-ESI-MS method for simultaneous determination of both drugs, and their metabolites was developed for purpose of pharmacokinetic study. To determine as many metabolites as possible, the influence of parameters such as column, flow rate and pH value of mobile phase, ionization polarity and fragmentation voltage were optimized. Fourteen target analytes were well separated and all of them could be identified and determined in plasma after administration of promethazine and caffeine. The LODs and LOQs were 0.9-6.0 and 2.50-16.0 ng/ml, respectively; the recoveries of three levels of quality control samples were from 86.7% to 102%; the intra-day and inter-day precisions were less than 3% and 9%, separately; and the RSDs of compound stability were all lower than 10% within 24h after sample preparation. As a pharmacokinetic study of the combination therapy in 30 healthy volunteers, concentration-time curves of the drugs and metabolites were studied. The present method for simultaneous measurement of more than ten metabolites is valuable for the study of mechanism and interaction of the combination therapy.

[Effect of tangshen formula on phospholipids metabolism in diabetic nephropathy patients].

This study was to report the effect of Tangshen Formula on phospholipids metabolism in diabetic nephropathy patients. A normal phase-HPLC-TOF/MS method was used in this study for the determination of seven species of phospholipids in human plasma. Then, the concentration changes of potential phospholipids biomarkers were discussed in diabetic nephropathy phase III and phase IV patients among different groups, including before and 3, 6 months after administration of Tangshen Formula. Significant increases of PE750, PI885, PC792, PC826, PC830, PC854 and PC802 levels were observed 6 months after administration of Tangshen Formula and conventional western medicine, as well as a decrease of LPC540 level, when compared with those before medication. Concentrations of all the potential phospholipids biomarkers showed a tendency towards normal levels; however, both the improvement degree and onset time of these compounds were not same. Additionally, Tangshen Formula treatment based on conventional western medicine treatment was more efficient in adjusting the levels of these compounds when compared with western medicine treatment alone, especially for the phase IV patients. These results indicated that Tangshen Formula was capable in regulating and improving phospholipids metabolism in diabetic nephropathy patients, which may be related with the direct or indirect inhibition of protein kinase C pathway and the corresponding reduction of phospholipase A2 activity. Therefore, Tangshen Formula may be used as an effective drug for diabetic nephropathy therapy, at least as an adjunctive therapeutic drug.