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Hypothyroidism is known to be closely associated with lipid metabolism. Although our previous serum and urine metabonomics studies have provided some clues about the molecular mechanism of hypothyroidism at the metabolic level, the precise mechanism underlying the pathogenesis of hypothyroidism remains elusive, especially from the aspect of lipid metabolism. In the present study, we applied an ultra high performance liquid chromatography/time-of-flight mass spectrometry (UHPLC/TOF-MS)-based lipidomics method to analyze the global lipid profiles of hypothyroidism in rat cerebellum. Using unsupervised analysis and multivariate statistical analysis, we separated the Sham and hypothyroid groups clearly and screened out 23 potential lipid biomarkers related to hypothyroidism that were primarily involved in sphingolipid metabolism, glycerophospholipid metabolism and β-oxidation of fatty acid. Subsequently, we conducted computational analysis to build and simulate the lipid network of hypothyroidism, knowing that it would be useful to elucidate the pathological mechanism of hypothyroidism. Based on the selected 23 lipid biomarkers, we systematically evaluated the therapeutic effects of Sini decoction ( SND ) and the positive drug T 4 . The results showed that both SND and T 4 can to some extent convert the pathological status of hypothyroidism through different pathways. Overall, this investigation illustrates that lipidomic profiling approach is powerful in giving a complementary view to the pathophysiology of hypothyroidism and offers a valuable tool for systematic study of the therapeutic effects of SND on hypothyroidism at lipid level. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Herb pair serves as the basic building block of a traditional Chinese medicine (TCM) formula. The rhubarb–gardenia herb pair (RGHP), composed of rhubarb and gardenia, has meaningful clinical effects to cure cholestasis diseases. This study was designed to confirm the expected synergistic effects of RGHP at pharmacodynamic and pharmacokinetic levels. Materials and methods Thirty male Sprague-Dawley rats were divided into control, model and drug-treated groups. After intragastrically administrated with α -naphthylisothiocyanate (ANIT) to induce cholestasis, rats were treated with rhubarb, gardenia or RGHP. For pharmacodynamic study, biochemical and histopathological tests were performed to assess the hepatoprotective effects. While for pharmacokinetic study, a LC–MS method was developed for determination of five main chemical markers, namely genipin, rhein, aloe emodin, emodin and chrysophanol in rat plasma. Results The biochemical and histopathological tests suggested that RGHP exerted enhanced hepatoprotective effects against the ANIT-induced cholestasis compared with single herbs. The pharmacokinetic study indicated RGHP could significantly elevate systemic exposure level and prolong retention time of five markers in comparison with rhubarb or gardenia alone. Conclusions The present study demonstrated the synergistic effects of RGHP in ANIT-induced cholestatic rats at pharmacodynamic and pharmacokinetic levels, and has significant enlightenments for the rational use of the related TCM formulas containing RGHP. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Orthosiphon stamineus (OS), a traditional Chinese herb, is often used for promoting urination and treating nephrolithiasis. Aim of the study Urolithiasis is a major worldwide public health burden due to its high incidence of recurrence and damage to renal function. However, the etiology for urolithiasis is not well understood. Metabonomics, the systematic study of small molecule metabolites present in biological samples, has become a valid and powerful tool for understanding disease phenotypes. In this study, a urinary metabolic profiling analysis was performed in a mouse model of renal calcium oxalate crystal deposition to identify potential biomarkers for crystal-induced renal damage and the anti-crystal mechanism of OS. Materials and methods Thirty six mice were randomly divided into six groups including Saline, Crystal, Cystone and OS at dosages of 0.5 g/kg, 1 g/kg, and 2 g/kg. A metabonomics approach using ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) was developed to perform the urinary metabolic profiling analysis. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were utilized to identify differences between the metabolic profiles of mice in the saline control group and crystal group. Results Using partial least squares-discriminant analysis, 30 metabolites were identified as potential biomarkers of crystal-induced renal damage. Most of them were primarily involved in amino acid metabolism, taurine and hypotaurine metabolism, purine metabolism, and the citrate cycle (TCA). After the treatment with OS, the levels of 20 biomarkers had returned to the levels of the control samples. Conclusions Our results suggest that OS has a protective effect for mice with crystal-induced kidney injury via the regulation of multiple metabolic pathways primarily involving amino acid, energy and choline metabolism. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: To investigate the synergistic property of Platycodonis Radix (PG) in a classic Traditional Chinese Medicine (TCM) prescription Shengxian Decoction (SXT) by combining chemical profile with pharmacokinetic analysis strategy. The synergized prescription consisted of Astragali Radix, Anemarrhenae Rhizoma, Bupleuri Radix, and Cimicifuage Rhizoma. Materials and methods: Ultra-performance liquid chromatography/quadruple time-of-flight mass spectrometry (UPLC–Q-TOF/MS) was employed to investigate the chemical fingerprints of SXT and decreased SXT (SXT that removed Platycodonis Radix, SXT-PG). A reliable LC–MS/MS method was developed to examine the pharmacokinetics of 9 marker compounds (including formononetin, calycosin-7-O-β-d-glucoside, ononin, caffeic acid, isoferulic acid, mangiferin, timosaponin E1, timosaponin B-II and timosaponin B) following oral administration of SXT and SXT-PG in rats. Both in vitro chemical profiles and in vivo pharmacokinetic parameters differences between SXT and SXT-PG were conducted. Results: By using UPLC–Q-TOF/MS method, a total of 25 compounds identified from SXT, including 13 triterpenoids, 5 caffeinic derivatives, 4 isoflavonoids and 3 xanthone glycosides. Comparing the chemical fingerprints between SXT and decreased SXT did not reveal significant difference in the chemical profile of other four TCMs. The improved pharmacokinetic profiles of mangiferin, timosaponin E1, timosaponin B-II and timosaponin B were found in SXT group, suggesting the quicker distribution and more effective absorption, when compared with those in the SXT-PG group. Conclusions: These results indicated that PG did not increase the dissolution of synergized prescription when co-decocting, but guided the synergized prescription to target location, reflecting the courier role of PG, which was in line with the clinical principle of TCM. It also established a useful method for TCM synergistic property research. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: The lateral root of Aconitum has been popularly used in traditional Chinese medicine (TMC) known as Fuzi which is beneficial for the treatment of various diseases, such as rheumatism, painful joints, syncope and bronchial asthma. However, it has a potential carditoxicity with a relatively narrow margin of safety. Aim of the study: This paper was designed to explore the mechanisms of Fuzi's toxicity and find out potential tissue-specific biomarkers of toxic effects. Material and methods: A myocardial lipidomics based on ultraperformance lipid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC/Q-TOF MS) was developed to compare three cardiac lipid extraction methods and investigate the changes of lipids in mice heart of three different dosage groups. In addition, we concurrently inspected the biochemical parameters in plasma, observed the histology of the heart and recorded the electrocardiogram (ECG). Results: The cardiotoxicity of Fuzi was dose-dependent, and the high-dose group obviously manifested the heart damage in histology and a certain degree of arrhythmia. Significant changes of 14 lipid metabolites which primarily involved in phospholipid metabolism, sphingolipid metabolism, saturated fatty acid oxidation and unsaturated fatty acid peroxidation were identified and considered as the potential biomarkers of Fuzi toxicity. Conclusion: The lipidomics approach is helpful to search potential tissue-specific biomarkers and understand the underlying mechanisms of Fuzi toxicity on the heart. [Copyright &y& Elsevier]