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Abstract (+)-usnic acid (UA) is an active natural phenolic acid ingredient originating from Chinese traditional Tibetan herb. Usnea acid is expected to become a new agent for anticancer and remarkable antitumor. To reveal its metabolic profile, metabolites identification of UA in vivo was studied using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) in this present study. The chromatographic separation was performed on a C 18 column with a mobile phase consisted of methanol and water with a flow rate of 0.4 ml/min. The mass spectral analysis conducted in a negative electrospray ionization mode combined with information-dependent acquirement technology (IDA) was used to trace all the potential UA metabolites. Several sensitive and specific multiple data-mining techniques especially key product ions (KPIs) filter were applied to hunt and identify metabolites rapidly. As a result, a total of 36 metabolites were detected after oral administration of UA, including 33, 8 and 16 in rat urine, plasma and bile, respectively. These results showed that the probable metabolite pathways of UA were oxidation, reduction, dihydroxylation, glycine conjugation, glucuronide conjugation, N -acetylcysteine conjugation and methylation. It is the first time to elucidate the profile of UA in vivo. These results not only provided the basis of UA pharmacological properties, but also gave the guidance in clinical medication. Moreover, the analysis strategy and methodology proposed in this paper could be widely used in characterization of other phenolic acids metabolites. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Vinegar-baked Radix Bupleuri (VBRB) is usually used to focus other drugs effect on liver in traditional Chinese medicine (TCM). However, no sufficient scientific data are available to support this concept. In this paper, the liver targeting enhancing effect of VBRB on rhein was investigated. 432 of rats were divided into two large groups according to the dose of rhein, low dose group of rhein (LDGR) and high dose group of rhein (HDGR). In each group, the rats were further divided into four subgroups, rhein control and rhein co-administered with three different doses of VBRB peroral. Concentrations of rhein and its metabolite in different tissues were determined by HPLC. Compared to the control group, VBRB significantly increased the distribution of both rhein and its metabolite in liver and meanwhile decreased their distribution in other tissues, indicating a strong liver targeting enhancing effect. This liver targeting effect of VBRB depended on the dose of VBRB and rhein. Low and high dose of VBRB had a more strong effect than medium dose in HDGR; high dose of rhein was more sensitive than low dose of rhein (P <0.05). Rhein existed in two forms after peroral administration in vivo. It was found that the liver targeting effect of VBRB was more remarkable with the native form of rhein compared to its derivative form. The results of this paper demonstrated that co-administration with VBRB is a simple and efficiencient method for liver targeting therapy, and the meridine guide theory of TCM was credible. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance:: Abelmoschus manihot (L.) Medik. var. manihot is one of the most commonly used Chinese medicines and has played an important role in treating chronic glomerulonephritis and diabetic nephropathy. Aim of the study:: Metabolites identification of traditional Chinese medicine (TCM) is a complex and time-consuming process due to the complicity of TCM and subsequent large number of detected ions. In this paper, UPLC–MS combined with pattern recognition analysis approach were used to simplify and quicken the identification of the metabolites of Abelmoschus Manihot. Materials and methods:: Rat urine samples were collected before (as control sample) and after Abelmoschus Manihot administration. Pattern recognition analysis method was used to differentiate components between Abelmoschus Manihot-treated group and its controlled comparison. These components could be considered as Abelmoschus Manihot-related metabolites in vivo. Results:: LC–MS based metabolomics could be an advanced tool to help us find metabolites with regards to its capacity of processing large datasets, differentiating and classifying of sample groups, as well as its indiscriminative nature of biomarker and metabolite identification. Using this method, seven metabolites were identified, which are flavonoid aglycone glucuronidation, sulfatation, and methylation metabolites. Conclusion:: Our results showed that UPLC–MS based- pattern recognition analysis approach can be used to quickly identify Abelmoschus Manihot related metabolites in biological fluids. Furthermore, this work demonstrates the potential application of combining the UPLC–MS approach with the metabolomics approach in identifying the metabolites of TCM. [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]

Abstract: Arctiin, an important lignan compound in Fructus Arctii, has been reported to possess various kinds of bioactivities. Previous studies on the pharmacokinetic of arctiin after oral administration showed that it had a rapid absorption phase followed by a sharp but lasting disappearance. To gain deep insight into the action mechanism of arctiin, the excretion and metabolism of arctiin in vivo should be further studied. In this paper, three metabolites were isolated and identified in rat feces as (−)-enterolactone (M-1), (−)-arctigenin (M-2) and [(2R,3R)-2-(3′-hydroxybenzyl)-3-(3″,4″-dimethoxybenzyl)-butyrolactone] (M-3). Based on the structures of three metabolites, possible metabolic pathways of arctiin in rats are proposed. At the same time, the cumulative excretion rate of arctiin and its metabolites in rat urine and feces were determined, indicating that arctiin was excreted 19.84% in urine and 1.80% in feces, respectively, enterolactone, the most main metabolite, was excreted 35.80% in feces. These results provide very important information for understanding the metabolism and excretion of arctiin in vivo and speculating its action mechanism, they can provide useful information and reference for further metabolic investigations on arctiin in humans. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Swertia chirayita, a medicinal herb endemic to the Tibetan region, is used as a special remedy for liver disorders. The hepatoprotective activity of its plant extracts has been associated with its antioxidant activity. This paper aims to investigate the in vitro and in vivo antioxidant effects of Swertia chirayita extracts (SCE). Materials and methods: Antioxidant ability of Swertia chirayita was investigated by employing several established in vitro methods. In vivo antioxidant activity was tested against CCl4-induced toxicity in mice. The levels and activities of malondialdehyde (MDA) and antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), were then assayed using standard procedures. Results: SCE exhibited strong antioxidant ability in vitro. The liver and kidney of CCl4-intoxicated animals exhibited a significant (p <0.001) decrease in SOD, CAT, and GSH levels. Additionally, these organs exhibited a significant (p <0.001) increase in MDA level. CCl4 did not exhibit toxicity on mice treated with SCE and Vitamin E. The effects of Swertia chirayita (three dosages) were comparable to those of Vitamin E, except in MDA level in the liver and GSH level in the kidney (p <0.05). Conclusion: This study suggests that the ethanolic extract of Swertia chirayita possesses in vitro and in vivo antioxidant effects. This supports the traditional use of Swertia chirayita in Tibetan medicine to cure liver diseases. [Copyright &y& Elsevier]

Abstract: Phlomis umbrosa Turcz has been used as the traditional medicine for thousands of years in China. In this paper, the acetic acid-induced writhing test, the hot plate test, the carrageenan-induced paw edema test, the xylene-induced ear swelling test, and the acetic acid-induced Evans blue leakage and leukocyte infiltration test were used to investigate the antinociceptive and anti-inflammatory activities of the aqueous extract of this plant (25, 50 and 100mg/kg i.p.). Good dose-dependent effects were obtained in most of these tests, except in the hot plate test and the acetic acid-induced Evans blue leakage test. TLC and HPLC analyses showed iridoid glucosides were the main compositions of this extract. These findings suggested that the aqueous extract of P. umbrosa has significant antinociceptive and anti-inflammatory activities. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Traditional Chinese medicine (TCM) has been used in clinical practice for several thousand years. TCM has played an indispensable role in the prevention and treatment of diseases, especially the complicated and chronic ones. Pharmacokinetic study on active constituents in herbal preparations is a good way for us to explain and predict a variety of events related to the efficacy and toxicity of TCM. Aim of the study: A selective and sensitive HPLC–MS/MS method was first developed and validated for the determination of luteolin, kaempferol, apigenin, quercetol, and isorhamnetin in rat plasma. Materials and methods: The LC system consisted of an Agilent Technologies Series 1200 system (Agilent, USA) equipped with an automatic degasser, a quaternary pump, and an autosampler. Chromatographic separations were performed on a Waters SunFire™ C18 column (150mm×4.6mm, 5μm), and the column temperature was maintained at 25°C and the sample injection volume was 20μL. The current LC–MS/MS assay was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery and stability. Results: The validated method was successfully applied to monitoring the concentrations and pharmacokinetic studies of five flavone compounds in rat plasma after a single oral administration of Verbena officinalis L. extract with a dosage of 8.0mL/kg. The time to reach the maximum plasma concentration (T max1) was 0.48±2.14h for luteolin, 0.25±0.13h for kaempferol, 0.97±1.08h for apigenin, 1.04±4.25h for quercetol and 0.25±0.16h for isorhamnetin, and the maximum plasma concentration (T max2) was 3.97±1.48h, 4.05±0.46h, 4.33±0.58h, 2.99±0.48h and 4.02±0.34h. The elimination half-time (t 1/2) of luteolin, kaempferol, apigenin, quercetol and isorhamnetin was 4.02±0.81, 7.65±0.71, 3.30±0.83, 4.55±0.49 and 5.56±1.32h, respectively. Conclusions: This paper described a simple, sensitive and validated LC–MS/MS method for simultaneous determination of luteolin, kaempferol, apigenin, quercetol and isorhamnetin in rat plasma after oral administration of V. officinalis L. extract, and investigated on their pharmacokinetic studies as well, with a short run time of 5min. [Copyright &y& Elsevier]

Abstract: In this paper, microdialysis combined with ultra performance liquid chromatography/mass spectrometry (UPLC-MS) was applied for the determination of ligustilide in freely moving rats'' brain. The extracellular unbound ligustilide could be detected in rat brain within the first time interval (0–20min) after nasal administration but not after oral administration. This result showed that ligustilide could quickly enter the brain after nasal administration; which implied that ligustilide may have a rapid onset of action. This work demonstrated the potential application of microdialysis combined with UPLC-MS in pharmacokinetic studies. Furthermore, the advantage that fewer animals used in the microdialysis experiment was confirmed. [Copyright &y& Elsevier]

Abstract: Tripterygium Glycosides (TG) is effective in the treatment of patients with a variety of inflammatory and autoimmune diseases, especially rheumatoid arthritis (RA) in clinical. Wilforlide A (T1) serves as a quality control standard of TG that be listed in Drug Standard of Ministry of Public Health of the People''s Republic of China. The pharmacologic actions of T1 remain to be unidentified. In this paper, we studied the anti-inflammatory and immune suppressive effect of T1, and compared it with Triptolide (TP), which believed to be the major active component of TG. Carrageenan-induced rat pedal swelling, tampon-induced rat granulation, and mice ear inhibition rate of swelling trail results show that high-dose T1 has obvious anti-inflammatory effect. Colorimetric detection contents of hemolysin, carbon elimination from plasma of mice, mice delayed hypersensitivity immune, and organ index were measured. The results show that T1 has no significant immune suppressive activity, and there has a significant difference with TP and TG. Therefore, we think the content of TP also should be controlled as a supplement standard in order to ensure safe and effective medication. [Copyright &y& Elsevier]