Comparing positive reappraisal and mindfulness in relation to daily emotions during COVID-19: An experience sampling study.

Research has suggested that daily cognitive reappraisal and mindfulness are differentially associated with emotional experience. Nevertheless, the different relationship between these two emotion regulation strategies and emotional experience remains unexplored amidst the COVID-19 pandemic, when people were facing unprecedented challenges and disruptions in their everyday lives. The current study aimed to examine the potential unidirectional or bidirectional relations between two strategies and daily emotional experience during the COVID-19 pandemic and whether the associations between the two strategies and emotional experience varied. A total of 184 college students participated in this study. Daily positive reappraisal, mindful attention and awareness (MAA), positive and negative affect, and COVID-19-related stress were assessed utilizing experience sampling method (three times a day for 14 consecutive days). Results suggested that the directionality of the link between the two strategies and daily emotional experience differed. The links between positive reappraisal and positive affect, negative affect, and COVID-19-related stress were transactional. However, a unidirectional relation was observed between positive affect and subsequent MAA. The study provided support for the contextual perspective of emotion regulation by demonstrating that the efficacy of regulation strategies is contingent upon the context. The identification of optimal conditions for effective strategies remains a crucial area for future research.

Amino acids-targeted metabolomics reveals novel diagnostic biomarkers for ulcerative colitis and Crohn's disease.

Inflammatory bowel disease (IBD), which mainly comprises ulcerative colitis (UC) and Crohn's disease (CD), is a common chronic intestinal inflammatory disease that affects the ileum, rectum, and colon. Currently, the diagnosis of IBD is based on clinical history, physical examination and complementary diagnostic tests. It is challenging for physicians to make a definitive diagnosis. This study aimed to analyze the variation in amino acid metabolites in IBD serum and to identify potential predictive biomarkers of IBD diagnosis and progression. Serum samples were collected from 158 UC patients, 130 CD patients and 138 healthy controls (HCs). The 37 amino acids in serum were determined by ultra-high-pressure liquid chromatography coupled to a mass spectrometer. A panel of three-amino-acid metabolites (taurine, homocitrulline and kynurenine) was identified as a specific biomarker panel of IBD. Receiver operating characteristic analysis (ROC) showed that the panel had a sensitivity of 88.4% with a specificity of 84.6% for discriminating CD patients from UC patients. The biomarkers identified are increased in CD compared to UC. Our approach demonstrated a strong relationship between serum amino acid levels and IBD. We successfully identified serum amino acid biomarkers associated with CD and UC. The biomarker panel has potential in clinical practice for IBD diagnosis and will provide new insights into IBD pathogenesis.

Baitouweng decoction alleviates dextran sulfate sodium-induced ulcerative colitis by suppressing leucine-related mTORC1 signaling and reducing oxidative stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Baitouweng decoction (BTW) has been used for hundreds of years to treat ulcerative colitis (UC) in China and has produced remarkable clinical results. However, the knowledge in protective mechanism of BTW against UC is still unclear. AIM OF THE STUDY: The present study was designed to investigate the anti-UC effects of BTW and the underlying mechanisms involved. METHODS: 3.5% dextran sulfate sodium (DSS)-induced experimental colitis was used to simulate human UC and the mice were treated with BTW (6.83 g/kg), leucine (200 mg/kg, Leu) or rapamycin (2 mg/kg, RAPA) as a positive control for 7 days. The clinical symptoms, serum myeloperoxidase (MPO) and malondialdehyde (MDA) levels were evaluated. Biological samples were collected to detect the effects of BTW on mechanistic target of rapamycin complex 1 (mTORC1) pathway and Leu metabolism. RESULTS: In our study, BTW notably improved the clinical symptoms and histopathological tissue damage and reduced the release of proinflammatory cytokines, including IL-6, IL-1ß and TNF-α in UC mice. BTW also alleviated oxidative stress by decreasing serum MPO and MDA levels. Additionally, BTW significantly suppressed mTORC1 activity in the colon tissues of UC mice. Serum metabolomics analysis revealed that the mice receiving BTW had lower Leu levels, which was in line with the decreased expression of branched-chain α-keto acid dehydrogenase kinase (BCKDK) in the colon tissues. Furthermore, oral administration of Leu aggravated DSS-induced acute colitis and enhanced mTORC1 activity in the colon. CONCLUSION: These data strongly demonstrated that BTW could ameliorate DSS-induced UC by regulating the Leu-related mTORC1 pathway and reducing oxidative stress.

A central alarm system that gates multi-sensory innate threat cues to the amygdala.

Perception of threats is essential for survival. Previous findings suggest that parallel pathways independently relay innate threat signals from different sensory modalities to multiple brain areas, such as the midbrain and hypothalamus, for immediate avoidance. Yet little is known about whether and how multi-sensory innate threat cues are integrated and conveyed from each sensory modality to the amygdala, a critical brain area for threat perception and learning. Here, we report that neurons expressing calcitonin gene-related peptide (CGRP) in the parvocellular subparafascicular nucleus in the thalamus and external lateral parabrachial nucleus in the brainstem respond to multi-sensory threat cues from various sensory modalities and relay negative valence to the lateral and central amygdala, respectively. Both CGRP populations and their amygdala projections are required for multi-sensory threat perception and aversive memory formation. The identification of unified innate threat pathways may provide insights into developing therapeutic candidates for innate fear-related disorders.

Serum lipidomics reveals distinct metabolic profiles for asymptomatic hyperuricemic and gout patients.

OBJECTIVES: This study aimed to characterize the systemic lipid profile of patients with asymptomatic hyperuricemia (HUA) and gout using lipidomics, and to find potential underlying pathological mechanisms therefrom. METHODS: Sera were collected from Affiliated Hospital of Nanjing University of Chinese Medicine as centre 1 (discovery and internal validation sets) and Suzhou Hospital of Traditional Chinese Medicine as centre 2 (external validation set), including 88 normal subjects, 157 HUA and 183 gout patients. Lipidomics was performed by ultra high performance liquid chromatography plus Q-Exactive mass spectrometry (UHPLC-Q Exactive MS). Differential metabolites were identifed by both variable importance in the projection ≥1 in orthogonal partial least-squares discriminant analysis mode and false discovery rate adjusted P ≤ 0.05. Biomarkers were found by logistic regression and receiver operating characteristic (ROC) analysis. RESULTS: In the discovery set, a total of 245 and 150 metabolites, respectively, were found for normal subjects vs HUA and normal subjects vs gout. The disturbed metabolites included diacylglycerol, triacylglycerol (TAG), phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, etc. We also found 116 differential metabolites for HUA vs gout. Among them, the biomarker panel of TAG 18:1-20:0-22:1 and TAG 14:0-16:0-16:1 could differentiate well between HUA and gout. The area under the receiver operating characteristic ROC curve was 0.8288, the sensitivity was 82% and the specificity was 78%, at a 95% CI 0.747, 0.9106. In the internal validation set, the predictive accuracy of TAG 18:1-20:0-22:1 and TAG 14:0-16:0-16:1 panel for differentiation of HUA and gout reached 74.38%, while it was 84.03% in external validation set. CONCLUSION: We identified serum biomarkers panel that have the potential to predict and diagnose HUA and gout patients.

Aqueous Extract of Lysimachia christinae Hance Prevents Cholesterol Gallstone in Mice by Affecting the Intestinal Microflora.

With changes in human dietary patterns, the proportion of high-fat and high-cholesterol foods in the daily diet has increased. As a result, the incidence rate of cholelithiasis is increasing rapidly. Many studies have reported on the crucial role that the intestinal microflora plays in the progression of gallstones. Although the whole herb of Lysimachia christinae, a traditional Chinese medicine, has long been extensively used as a remedy for cholelithiasis in China, its effects on the intestinal microflora remain unknown. Hence, in this study, we investigated the ability of the aqueous extract of L. christinae (LAE) to prevent cholesterol gallstones (CGSs) in model animals by affecting the intestinal microflora. The effects of LAE on body weight, serum lipid profile, visceral organ indexes, and histomorphology were studied in male C57BL/6J mice, which were induced by a lithogenic diet. After the 8-week study, CGSs formation was greatly reduced after LAE treatment. LAE also reduced body weight gain and hyperlipidemia and restored the histomorphological changes. Moreover, the intestinal microflora exhibited significant variation. In the model group fed the lithogenic diet, the abundances of the genera unclassified Porphyromonadaceae, Lactobacillus and Alloprevotella decreased, but in contrast, Akkermansia dramatically increased compared with the control check group, which was fed a normal diet; the administration of LAE reversed these changes. These results imply that L. christinae can be considered an efficient therapy for eliminating CGSs induced by a high-fat and high-cholesterol diet, which may be achieved by influencing the intestinal microflora.

Ginsenoside Rh2 alleviates ulcerative colitis by regulating the STAT3/miR-214 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng is a valuable medicinal herb used in China for the prevention and treatment of cancer, diabetes, cardiovascular diseases and other diseases. As the main active ingredient of ginseng, ginsenoside has a wide range of pharmacological effects. Ginsenoside Rh2, a protopanaxadiol saponin from ginseng, exhibits anti-inflammatory and anticancer effects. AIM OF THE STUDY: The potential biological mechanism of Rh2 in the treatment of ulcerative colitis (UC) has not been clarified clearly. In our research, we aimed to explore the therapeutic effects of Rh2 on dextran sodium sulfate (DSS)-induced colitis and elucidate the mechanism of Rh2 in treating UC. METHODS: DSS-induced UC mice were established and randomly divided into the following four groups: control group, DSS group, Rh2 (50 mg/kg) group and sulfasalazine (SASP, 200 mg/kg) group. Except for the control group, 3% DSS drinking water was given to each group for 7 days, and the other two groups were intragastrically administered with Rh2 and SASP for 10 days. At the end of the experiment, colon samples were collected, and phenotypic and pathological analyses were performed in UC mice. Then, Western blot, immunohistochemistry and quantitative real-time PCR analyses were performed to determine the expression of signaling pathway-related factors. RESULTS: Rh2 markedly alleviated DSS-induced body weight loss, intestinal damage, colon length shortening and disease activity index (DAI) scores. Furthermore, proinflammatory cytokines, such as TNF-α, IL-6 and IL-1ß, were reduced by Rh2. Additionally, STAT3/miR-214 activation was also suppressed by Rh2 administration. In vitro, we demonstrated that Rh2 effectively inhibited IL-6-induced STAT3 phosphorylation and miR-214 expression in cultured normal colonic epithelial cells. CONCLUSION: Our results suggested that Rh2 exhibits potential application value in the treatment of UC, and its mechanism is related to the downregulation of STAT3/miR-214 levels, which is expected to be applicable in the treatment of clinical UC.

Serum metabolomics reveals metabolic profiling for women with hyperandrogenism and insulin resistance in polycystic ovary syndrome.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder. Hyperandrogenism (HA) and insulin resistance (IR) are two important pathogenic factors. OBJECTIVE: We aimed to investigate the inherent disturbed metabolic profiles for women with HA or IR in PCOS as well as discover diagnostic biomarkers. METHODS: A total of 286 subjects were recruited for the study. They constituted the following groups: healthy women (C), those with HA (B1), those with IR but not obese (B2) and obese women with IR (B3) in PCOS. Nine cross-comparisons with PCOS were performed to characterize metabolic disturbances. Serum metabolomic profiles were determined by gas chromatography-mass spectrometry. RESULTS AND CONCLUSION: We found a total of 59 differential metabolites. 28 metabolites for B1 vs C, 32 for B2 vs C and 25 for B3 vs C were discovered. Among them, palmitic acid, cholesterol, myo-inositol, D-allose, 1,5-anhydro-D-sorbitol, 1-monopalmitin, 1-monostearin, glycerol 1-phosphate, malic acid and citric acid, were the common differential metabolites among B1 vs C, B2 vs C and B3 vs C, which related to biosynthesis of unsaturated fatty acids, citrate cycle etc. Besides, 9-biomarker panel can diagnose well between HA and IR in PCOS. They provided areas under the receiver operating characteristic curve of 0.8511 to 1.000 in the discovery phase, and predictive values of 90% to 92% in the validation set. The result indicated that the differential metabolites can reflect the underlying mechanism of PCOS and serve as biomarkers for complementary diagnosis of HA and IR in PCOS.

Identification of the absorbed components and metabolites of Xiao-Ai-Jie-Du decoction and their distribution in rats using ultra high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry.

Xiao-Ai-Jie-Du decoction (XAJDD), a traditional Chinese medicine formula, has long been used for the treatment of hepatocarcinoma, gastric cancer and colorectal cancer. It is composed of six herbal medicines, including Scutellariae Barbatae Herba, Pseudostellariae Radix, Ophiopogonis Radix, Cremastrae Pseudobulbus, Curcumae Rhizoma and Akebiae Fructus. Despite the in-depth study on its pharmacological effects on cancer prevention and treatment, the comprehensive analysis of the chemical components and the absorbed bioactive constituents are not well studied. Thus, an ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) method was established to detect and identify the chemical constituents in XAJDD. The absorbed components and metabolites after oral administration of XAJDD in rats were also studied. In total, 102 components were identified or tentatively characterized in XAJDD, including 30 flavonoids, 19 triterpenoids, 12 organic acids, 9 steroidal saponins, 9 cyclic peptides, 7 phenanthrenes, 5 amino acids, 3 alkaloids and 8 other compounds. After analysing the metabolites in rat plasma and urine after oral administration of XAJDD, a total of 70 compounds were identified, including 15 primary components and 55 metabolites, and metabolic pathways, including hydrogenation, hydroxylation, methylation, sulfonation, and glucuronidation were evaluated. Among these, methylation and glucuronidation were the main metabolic pathways. In conclusion, the developed UHPLC-Q-TOF-MS method with high sensitivity and resolution is suitable for identifying and characterizing the chemical constituents of XAJDD in vitro and characterizing the primary components and their metabolites in vivo; moreover, the results will provide essential data for further studying the relationship between the chemical components and pharmacological activity of XAJDD.

Earlier Degraded Tapetum1 (EDT1) Encodes an ATP-Citrate Lyase Required for Tapetum Programmed Cell Death.

In flowering plants, the tapetum cells in anthers undergo programmed cell death (PCD) at the late meiotic stage, providing nutrients for further development of microspores, including the formation of the pollen wall. However, the molecular basis of tapetum PCD remains elusive. Here we report a tapetum PCD-related mutant in rice (Oryza sativa), earlier degraded tapetum 1 (edt1), that shows complete pollen abortion associated with earlier-than-programmed tapetum cell death. EDT1 encodes a subunit of ATP-citrate lyase (ACL), and is specifically expressed in the tapetum of anthers. EDT1 localized in both the nucleus and the cytoplasm as observed in rice protoplast transient assays. We demonstrated that the A and B subunits of ACL interacted with each other and might function as a heteromultimer in the cytoplasm. EDT1 catalyzes the critical steps in cytosolic acetyl-CoA synthesis. Our data indicated a decrease in ATP level, energy charge, and fatty acid content in mutant edt1 anthers. In addition, the genes encoding secretory proteases or lipid transporters, and the transcription factors known to regulate PCD, were downregulated. Our results demonstrate that the timing of tapetum PCD must be tightly regulated for successful pollen development, and that EDT1 is involved in the tapetum PCD process. This study furthers our understanding of the molecular basis of pollen fertility and fecundity in rice and may also be relevant to other flowering plants.

Limonin ameliorates ulcerative colitis by regulating STAT3/miR-214 signaling pathway.

Ulcerative colitis (UC) is a major inflammatory bowel disease (IBD) which has become a global public health problem. Limonin is a triterpenoid extracted from citrus which possesses the capacities to against inflammations and cell apoptosis. However, the efficacy and the underlying mechanisms of limonin in the treatment of UC remain unclear. In this study, we first investigated the therapeutic effects of limonin on dextran sodiumsulfate (DSS)-induced UC in vivo by examining the changes of disease activity index (DAI), the colon length, the colon histology, and cyto/chemokine levels. We found that limonin markedly reduced DAI, intestinal damages, and the levels of pro-inflammatory cytokines, such as TNF-α and IL-6. In vitro, limonin significantly repressed the productions of pro-inflammatory cytokines in cultured normal colonic epithelial cells. Mechanistically, we demonstrated that limonin improved the prognosis of UC mainly through downregulating p-STAT3/miR-214 levels. Collectively, our results suggested that limonin was a novel therapeutic agent and it was expected to be translated into the clinic to improve the prognosis of UC.

A selfish genetic element confers non-Mendelian inheritance in rice.

Selfish genetic elements are pervasive in eukaryote genomes, but their role remains controversial. We show that qHMS7, a major quantitative genetic locus for hybrid male sterility between wild rice (Oryza meridionalis) and Asian cultivated rice (O. sativa), contains two tightly linked genes [Open Reading Frame 2 (ORF2) and ORF3]. ORF2 encodes a toxic genetic element that aborts pollen in a sporophytic manner, whereas ORF3 encodes an antidote that protects pollen in a gametophytic manner. Pollens lacking ORF3 are selectively eliminated, leading to segregation distortion in the progeny. Analysis of the genetic sequence suggests that ORF3 arose first, followed by gradual functionalization of ORF2 Furthermore, this toxin-antidote system may have promoted the differentiation and/or maintained the genome stability of wild and cultivated rice.

[Screen astragalosides from Huangqi injections by LC-TOF-MS-based mass defect filtering approach].

The samples of Huangqi injection (HI) were analyzed by liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-TOF-MS), and both positive and negative ion modes were employed to obtain the LC-TOF-MS analysis information of chemical compounds in HI. Then the mass defect filtering (MDF) approach, which was developed based on the previously published articles, was utilized to rapidly screen the astragalosides from the obtained LC-TOF-MS data. Each screened astragaloside was confirmed by the presence of no less than 2 quasi-molecular ions. All the screened astragalosides were then tentatively assigned according to the parent ion and daughter ion information. Finally, a total of 62 astragalosides were screened and characterized from the HI samples, including 15 new detected ones. The identification results indicated that acetylation, hydrogenation, dehydrogenation, methoxylation and hydration might be the major conversion reactions involved in the formation of the astragalosides. The LC-TOF-MS-based MDF approach was proved to be a feasible and efficient tool to screen the chemical constituents in complex matrices such as herbal medicines.

Triptolide inhibits proliferation, differentiation and induces apoptosis of osteoblastic MC3T3­E1 cells.

Ankylosing spondylitis (AS) is characterized by the formation of bony spurs. Treatment of the resulting ankylosis, excessive bone formation and associated functional impairment, remain the primary therapeutic aims in research regarding this condition. Triptolide is the primary active component of the perennial vine Tripterygium wilfordii Hook. f., and has previously been demonstrated to exert anti­tumor activities including inhibition of cell growth and the induction of apoptosis, however, the effect of triptolide on osteoblasts remains to be elucidated. In the present study, the MC3T3­E1 mouse osteoblast cell line was treated with differing concentrations of triptolide for various intervals. Cell proliferation was detected using the bromodeoxyuridine assay, cell cycle and apoptosis were measured by flow cytometry, nuclear apoptosis was observed by Hoechst staining and associated proteins were determined via western blot analysis. The cells were then further incubated with osteogenic induction medium supplemented with triptolide for 7 or 12 days and the differentiation to osteoblasts was examined by picrosirius staining, observation of alkaline phosphatase activity and a calcium deposition assay. It was demonstrated that treatment with triptolide significantly inhibited osteoblast proliferation and induced cell cycle arrest and apoptosis of the osteoblasts. Furthermore, treatment with triptolide reduced collagen formation, alkaline phosphatase activity and calcium deposition. The present study demonstrated an inhibitory effect of triptolide on osteoblast proliferation and differentiation, and therefore suggests a potential therapeutic agent for the treatment of AS in the future.

The Antigastric Cancer Activity of San Leng Powder Extract Induces Apoptosis in Balb/C Bearing-SGC-7901 Mice.

San Leng powder extract has been used as medicinal compound for the prevention and treatment of cancers. The antitumor activity of SLPE was determined by treating BALB/C mice harboring a human gastric cancer xenograft with SPLE for 17 days. Mice were also treated with fluorouracil (5-Fu, 25 mg/kg) or a combination of SLPE and 5-Fu. Our results indicate that the inhibition of tumor growth by SLPE might be due to a block in the cell cycle and the induction of apoptosis. These results suggest that SLPE might be useful in the treatment of gastric cancer.

Urinary metabolomics reveals the therapeutic effect of HuangQi Injections in cisplatin-induced nephrotoxic rats.

The side effects of cisplatin (CDDP), notably nephrotoxicity, greatly limited its use in clinical chemotherapy. HuangQi Injections (HI), a commonly used preparation of the well-known Chinese herbal medicine Astragali radix, appeared to be promising treatment for nephrotoxicity without compromising the anti-tumor activity of CDDP. In this study, the urinary metabolomics approach using liquid chromatography time of flight mass spectrometry (LC-TOF/MS) was developed to assess the toxicity-attenuation effects and corresponding mechanisms of HI on CDDP-exposed rats. As a result, successive administration of HI significantly recovered the decline of body weight and downregulated the abnormal increase of serum creatinine and urea. HI partly restored the CDDP-induced alteration of metabolic profiling back into normal condition. Totally 43 toxicity-attenuation potential biomarkers were screened and tentatively identified, which were involved in important metabolic pathways such as amino acid metabolism, TCA cycle, fatty acid metabolism, vitamin B6 metabolism and purine metabolism. The results clearly revealed that HI could alleviate CDDP-induced nephrotoxicity and improve the disturbed metabolic balance induced by repeated CDDP exposure. The present study provided reliable evidence for the protective effect of HI on CDDP-induced toxicity with the multi-target pharmacological characteristics.

Simultaneous determination of notoginsenoside R1 and ginsenoside Re in rat plasma by ultra high performance liquid chromatography with tandem mass spectrometry and its application to a pharmacokinetic study.

A rapid and high sensitive ultra high performance liquid chromatography with tandem mass spectrometry method for the simultaneous determination of notoginsenoside R1 and ginsenoside Re in rat plasma was developed. The analytes and internal standard, digoxin, were extracted from rat plasma via protein precipitation with methanol and separated on an Phenomenex Gemini C18 column within 2 min. Quantitation was performed on a triple quadrupole mass spectrometer employing electrospray ionization technique, operating in multiple reaction monitoring and positive ion mode. The precursor to product ion transitions monitored for notoginsenoside R1, ginsenoside Re, and internal standard were m/z 955.5→775.5, 969.6→789.1, and 803.6→283.1, respectively. The assay was validated with linear range of 1.9-380 ng/mL for notoginsenoside R1 and 0.5-100 ng/mL for ginsenoside Re. The intra- and interday precisions (RSD%) were within 8.96% for each analyte. The absolute recoveries were greater than 93% for R1 and 96% for Re. Each analyte was stable during all sample storage, preparation, and analytic procedures. The method was successfully applied to a pharmacokinetic study of Xuesaitong dispersible tablets in eight rats.

Systematic screening and characterization of astragalosides in an oral solution of Radix Astragali by liquid chromatography with quadrupole time-of-flight mass spectrometry and Peakview software.

Liquid chromatography with quadrupole time-of-flight mass spectrometry coupled with automated data analysis by Peakview software was employed to systematically screen and characterize the astragalosides in Radix Astragali, a Chinese medical preparation. The separation was performed on a poroshell 120 SB-C18 column equipped in a conventional liquid chromatography system. After being separated using a general gradient elution, the analytes were detected by the triple quadrupole time-of-flight mass spectrometer in both positive- and negative-ion modes. The mass defect filtering function built in the Peakview software was utilized to rapidly screen the potential ions of interest, while some functions of Peakview such as Formula Finder, XIC manager, and IDA Explorer were employed to facilitate the assignment or characterization of the screened astragalosides. A total of 42 astragalosides were screened and tentatively characterized or assigned, and 20 of them were firstly detected in Radix Astragali. According to the screened astragalosides, acetylation, glycosidation, hydrogenation, oxidation, and hydration were considered to be the major secondary metabolic pathways involved in the formation of the astragalosides. The combination of liquid chromatography with quadrupole time-of-flight mass spectrometry and automated Peakview analysis is a feasible and efficient tool to screen and identify the constituents in complex matrices of herbal medicines.

[LC-MS/MS method for determination of tripterine in plasma： pharmacokinetic study in Beagles].

To establish a LC-MS/MS method for determination of tripterine in Beagle plasma and study its pharmacokinetics after oral administration of tripterygium tablet. Plasma samples were extracted with dichloromethane and separated on a Phenomenex Luna C8 (2.0 mm×50 mm, 3 µm) column with methanol-acetonitrile isopropanol(1∶1)-1‰formic acid (15∶55 ∶30) as the mobile phase. Tripterine ([M+H] ⁺, m/z 451.3/201.1) and internal standard prednisolone ([M+H] ⁺, m/z 361.1/147.1) were monitored in multiple reaction monitoring (MRM). The concentration-time curves were simulated by drug and statistic software 1.0 and the pharmacokinetic parameters were calculated. There was a good linear relationship between peak area ratio and concentration of tripterine and internal standard prednisolone within range of 0.680 0-136.0 µg•L⁻¹. The limit of quantitation was 0.680 0 µg•L⁻¹ and the intra- and inter-day precision was within 6.15%. The absolute recovery rate was between 50.42% to 51.65%. The concentration-time curves were consistent with the one-compartment model(w=1/cc). The main pharmacokinetic parameters after a single dose were as follows： Cmax (35.64±9.540) µg •L⁻¹,Tmax(2.62±0.69) h,T1/2(2.93±0.29) h, CL (0.308±0.056) L•kg⁻¹â€¢h⁻¹, AUC0-12 (131.16±31.94) µg•L•h⁻¹, AUC0-∞ (142.83±37.57) µg•L•h⁻¹. The established LC-MS/MS method was proved to be sensitive, accurate and convenient, suitable for the pharmacokinetic study of Tripterygium tablet in Beagle dogs.

[Study on biomarker of Tripterygium wilfordii in treatment of rheumatoid arthritis based on PK/PD].

To observe the serum samples and the anti-inflammatory effect of Tripterygium wilfordii in treating RA by using the pharmacokinetic-pharmacodynamic model, make a correlation analysis on concentration-time and effect-time curves, and explore RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in rats by PCR. Methotrexate, tripterine and high-dose T. wilfordii could down-regulate RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in AA rat lymph nodes. The study on PK-PD model showed correlations between inflammatory factors and blood concentration of T. wilfordii. T. wilfordii and its main active constituent tripterine could show the inflammatory effect and treat RA by inhibiting IL-17 cytokine.