Metabolomics for Clinical Biomarker Discovery and Therapeutic Target Identification.

As links between genotype and phenotype, small-molecule metabolites are attractive biomarkers for disease diagnosis, prognosis, classification, drug screening and treatment, insight into understanding disease pathology and identifying potential targets. Metabolomics technology is crucial for discovering targets of small-molecule metabolites involved in disease phenotype. Mass spectrometry-based metabolomics has implemented in applications in various fields including target discovery, explanation of disease mechanisms and compound screening. It is used to analyze the physiological or pathological states of the organism by investigating the changes in endogenous small-molecule metabolites and associated metabolism from complex metabolic pathways in biological samples. The present review provides a critical update of high-throughput functional metabolomics techniques and diverse applications, and recommends the use of mass spectrometry-based metabolomics for discovering small-molecule metabolite signatures that provide valuable insights into metabolic targets. We also recommend using mass spectrometry-based metabolomics as a powerful tool for identifying and understanding metabolic patterns, metabolic targets and for efficacy evaluation of herbal medicine.

Natural products in traditional Chinese medicine: molecular mechanisms and therapeutic targets of renal fibrosis and state-of-the-art drug delivery systems.

Renal fibrosis (RF) is the end stage of several chronic kidney diseases. Its series of changes include excessive accumulation of extracellular matrix, epithelial-mesenchymal transition (EMT) of renal tubular cells, fibroblast activation, immune cell infiltration, and renal cell apoptosis. RF can eventually lead to renal dysfunction or even renal failure. A large body of evidence suggests that natural products in traditional Chinese medicine (TCM) have great potential for treating RF. In this article, we first describe the recent advances in RF treatment by several natural products and clarify their mechanisms of action. They can ameliorate the RF disease phenotype, which includes apoptosis, endoplasmic reticulum stress, and EMT, by affecting relevant signaling pathways and molecular targets, thereby delaying or reversing fibrosis. We also present the roles of nanodrug delivery systems, which have been explored to address the drawback of low oral bioavailability of natural products. This may provide new ideas for using natural products for RF treatment. Finally, we provide new insights into the clinical prospects of herbal natural products.

Detection, mechanisms, and therapeutic implications of oncometabolites.

Metabolic abnormalities are a hallmark of cancer cells and are essential to tumor progression. Oncometabolites have pleiotropic effects on cancer biology and affect a plethora of processes, from oncogenesis and metabolism to therapeutic resistance. Targeting oncometabolites, therefore, could offer promising therapeutic avenues against tumor growth and resistance to treatments. Recent advances in characterizing the metabolic profiles of cancer cells are shedding light on the underlying mechanisms and associated metabolic networks. This review summarizes the diverse detection methods, molecular mechanisms, and therapeutic targets of oncometabolites, which may lead to targeting oncometabolism for cancer therapy.

Translation Animal Models of Diabetic Kidney Disease: Biochemical and Histological Phenotypes, Advantages and Limitations.

Animal models play a crucial role in studying the pathogenesis of diseases, developing new drugs, identifying disease risk markers, and improving means of prevention and treatment. However, modeling diabetic kidney disease (DKD) has posed a challenge for scientists. Although numerous models have been successfully developed, none of them can encompass all the key characteristics of human DKD. It is essential to choose the appropriate model according to the research needs, as different models develop different phenotypes and have their limitations. This paper provides a comprehensive overview of biochemical and histological phenotypes, modeling mechanisms, advantages and limitations of DKD animal models, in order to update relevant model information and provide insights and references for generating or selecting the appropriate animal models to fit different experimental needs.

Exploring Potential Biomarkers and Molecular Mechanisms of Ischemic Cardiomyopathy and COVID-19 Comorbidity Based on Bioinformatics and Systems Biology.

Cardiovascular complications combined with COVID-19 (SARS-CoV-2) lead to a poor prognosis in patients. The common pathogenesis of ischemic cardiomyopathy (ICM) and COVID-19 is still unclear. Here, we explored potential molecular mechanisms and biomarkers for ICM and COVID-19. Common differentially expressed genes (DEGs) of ICM (GSE5406) and COVID-19 (GSE164805) were identified using GEO2R. We performed enrichment and protein-protein interaction analyses and screened key genes. To confirm the diagnostic performance for these hub genes, we used external datasets (GSE116250 and GSE211979) and plotted ROC curves. Transcription factor and microRNA regulatory networks were constructed for the validated hub genes. Finally, drug prediction and molecular docking validation were performed using cMAP. We identified 81 common DEGs, many of which were enriched in terms of their relation to angiogenesis. Three DEGs were identified as key hub genes (HSP90AA1, HSPA9, and SRSF1) in the protein-protein interaction analysis. These hub genes had high diagnostic performance in the four datasets (AUC > 0.7). Mir-16-5p and KLF9 transcription factor co-regulated these hub genes. The drugs vindesine and ON-01910 showed good binding performance to the hub genes. We identified HSP90AA1, HSPA9, and SRSF1 as markers for the co-pathogenesis of ICM and COVID-19, and showed that co-pathogenesis of ICM and COVID-19 may be related to angiogenesis. Vindesine and ON-01910 were predicted as potential therapeutic agents. Our findings will contribute to a deeper understanding of the comorbidity of ICM with COVID-19.

Mass spectrometry-based metabolomics for discovering active ingredients and exploring action mechanism of herbal medicine.

Natural products derived from herbal medicine are a fruitful source of lead compounds because of their structural diversity and potent bioactivities. However, despite the success of active compounds derived from herbal medicine in drug discovery, some approaches cannot effectively elucidate the overall effect and action mechanism due to their multi-component complexity. Fortunately, mass spectrometry-based metabolomics has been recognized as an effective strategy for revealing the effect and discovering active components, detailed molecular mechanisms, and multiple targets of natural products. Rapid identification of lead compounds and isolation of active components from natural products would facilitate new drug development. In this context, mass spectrometry-based metabolomics has established an integrated pharmacology framework for the discovery of bioactivity-correlated constituents, target identification, and the action mechanism of herbal medicine and natural products. High-throughput functional metabolomics techniques could be used to identify natural product structure, biological activity, efficacy mechanisms, and their mode of action on biological processes, assisting bioactive lead discovery, quality control, and accelerating discovery of novel drugs. These techniques are increasingly being developed in the era of big data and use scientific language to clarify the detailed action mechanism of herbal medicine. In this paper, the analytical characteristics and application fields of several commonly used mass spectrometers are introduced, and the application of mass spectrometry in the metabolomics of traditional Chinese medicines in recent years and its active components as well as mechanism of action are also discussed.

Small molecule metabolites: discovery of biomarkers and therapeutic targets.

Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks of diseases. Metabolite signatures that have close proximity to subject's phenotypic informative dimension, are useful for predicting diagnosis and prognosis of diseases as well as monitoring treatments. The lack of early biomarkers could lead to poor diagnosis and serious outcomes. Therefore, noninvasive diagnosis and monitoring methods with high specificity and selectivity are desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool for metabolic biomarker and pathway analysis, for revealing possible mechanisms of human various diseases and deciphering therapeutic potentials. It could help identify functional biomarkers related to phenotypic variation and delineate biochemical pathways changes as early indicators of pathological dysfunction and damage prior to disease development. Recently, scientists have established a large number of metabolic profiles to reveal the underlying mechanisms and metabolic networks for therapeutic target exploration in biomedicine. This review summarized the metabolic analysis on the potential value of small-molecule candidate metabolites as biomarkers with clinical events, which may lead to better diagnosis, prognosis, drug screening and treatment. We also discuss challenges that need to be addressed to fuel the next wave of breakthroughs.

Innovation in identifying metabolites from complex metabolome-Highlights of recent analytical platforms and protocols.

Metabolites are closely intertwined genotypes that can provide clear information about the final phenotype. The high-throughput analysis platform used to identify candidate metabolites and describe their contributions can help to quickly detect metabolic characteristics from large spectral data, which may lead to peak data preprocessing, statistical analysis and functional interpretation. Developing a comprehensive strategy for discovering and verifying bioactive metabolites can provide a large number of new functional biomarkers, and then more closely reveal their functional changes, which has relevant biological significance for disease diagnosis and prognosis treatment.

Flipped classroom improves student learning outcome in Chinese pharmacy education: A systematic review and meta-analysis.

Background: The application of flipped classroom (FC) pedagogy has recently become increasingly popular in Chinese pharmacy education. However, its effectiveness in improving student learning has not yet been assessed. This study aimed to evaluate the effects of teaching with such pedagogical approach by examining studies that compare the FC approach with the traditional lecture-based learning (LBL) module through a systematic review and meta-analysis. Methods: Seven databases, including the PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Chinese Wanfang database, and China Biomedical Literature Database, were searched from the inception to 30 June 2021, to identify eligible articles of randomized controlled studies. The primary outcomes included the theoretical and experimental test scores, and the secondary outcomes were the results from questionnaires about the number of students who preferred the FC or endorsed its improving effects on their learning enthusiasm, self-learning ability, thinking skills, communication skills, and learning efficiency. The quantitative synthesis was conducted with Revman V.5.3 software following the Cochrane Reviewer's Handbook guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Results: Eleven eligible studies published from 2017 to 2020 enrolling 1,200 students were included in this meta-analysis. The quantitative synthesis demonstrated that the FC module presented an overall more significant effectiveness over traditional LBL approach for Chinese pharmacy education in improving student academic performance as measured by theoretical test scores (SMD = 1.08, 95% CI: 0.60-1.56, p < 0.00001) and experimental test scores (MD = 6.62, 95% CI: 4.42-8.82, p < 0.00001). Further sub-group analysis revealed that the preferable effectiveness of FC was also evident in both theory-oriented (SMD = 0.77, 95% CI: 0.10-1.45, p < 0.00001) and experiments-oriented courses (MD = 6.52, 95% CI: 3.48-9.56, p < 0.00001) for both undergraduate (SMD = 0.84, 95% CI: 0.31-1.37, p < 0.00001) and 3-year junior-college students (MD = 8.17, 95% CI: 6.44-9.89, p < 0.00001). Additionally, analysis on the questionnaire outcomes revealed that more respondents preferred for FC and endorsed its improvement effects on developing students' learning enthusiasm, self-learning ability, thinking skills, communication skills, and learning efficiency. Conclusion: Current evidence suggests that FC pedagogical approach can effectively improve student learning outcomes and is applicable to Chinese pharmacy education.

Mechanism of Citri Reticulatae Pericarpium as an Anticancer Agent from the Perspective of Flavonoids: A Review.

Citri Reticulatae Pericarpium (CRP), also known as "chenpi", is the most common qi-regulating drug in traditional Chinese medicine. It is often used to treat cough and indigestion, but in recent years, it has been found to have multi-faceted anti-cancer effects. This article reviews the pharmacology of CRP and the mechanism of the action of flavonoids, the key components of CRP, against cancers including breast cancer, lung cancer, prostate cancer, hepatic carcinoma, gastric cancer, colorectal cancer, esophageal cancer, cervical cancer, bladder cancer and other cancers with a high diagnosis rate. Finally, the specific roles of CRP in important phenotypes such as cell proliferation, apoptosis, autophagy and migration-invasion in cancer were analyzed, and the possible prospects and deficiencies of CRP as an anticancer agent were evaluated.

Xuefu Zhuyu decoction for nonalcoholic fatty liver disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) includes nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH), which ranks only second to viral hepatitis and poses an increasingly serious challenge to global public health and economy. NAFLD has attracted more and more attention, but there is no drugs with exact curative effects are available. The commonly used drugs for the treatment of NAFLD in clinical practice are statins, such drugs, inevitably increase the burden on the live. Compared to statins, traditional Chinese medicines are believed to be "all natural" with fewer side effects, are associated with strong patient compliance. Accordingly, a great deal of clinical studies have shown that Xuefu Zhuyu decoction (XFZYD) can significantly improve the clinical symptoms and enhance the therapeutic effect. Meanwhile, a system review and meta-analysis are conducted by us to further clarify the effectiveness and safety of XFZYD for NAFLD. METHODS: We will apply to database mainly range from the English literature searches Cochrane Library, PubMed, excerpt medica database, and Web of Science to the Chinese literature China national knowledge infrastructure, Chinese biomedical literature database, VIP, and Wanfang database, randomized controlled trials (RCTs) are enrolled to evaluate the effectiveness and safety of XFZYD in the treatment of NAFLD, the enrollment of RCTs is from the establishment of the database to February 01, 2021. Simultaneously we will retrieval clinical registration tests and grey literatures. The 2 researchers worked independently on literature selection, data extraction, and quality assessment. The dichotomous data is expressed in terms of relative risk, the continuous is represented by mean difference or standard mean difference, whether there is heterogeneity is the factor that determines the synthesis of data in fixed effect model or random effect model. Alanine aminotransferase (ALT) or Aspartic acid aminotransferase (AST) coupled with Glutamyltransferase (GGT) is considered as one of the main indicators of the NAFLD, while the pathology, imaging and diagnosis of metabolic syndrome are also auxiliary results. The last, meta-analysis was conducted by RevMan software version 5.3. RESULTS: This study will provide evidence for treatment of NAFLD with XFZYD in terms of effectiveness and safety. CONCLUSION: This systematic review aims to confirm the efficacy and safety of XFZYD in the treatment of NAFLD. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/7CWRK.

Efficacy and safety of Chinese herbal footbaths for the treatment of dysmenorrhea: Protocol for a systematic review and meta-analysis.

BACKGROUND: Chinese herbal footbaths are an external therapy of traditional Chinese medicine that has been widely used to treat dysmenorrhea. This review aims to systematically evaluate its efficacy and safety for the treatment of dysmenorrhea. METHODS: Databases of PubMed, EMBASE, Cochrane Library, CIHAHL, Web of Science, Chinese National Knowledge Infrastructure(CNKI), Chinese Scientific Journals Database (VIP), Wanfang Database, China Biomedical Literature Database(CBM), and Chinese Biomedical Literature Service System (SinoMed) will be searched from the inception to September 30, 2020. The eligible randomized controlled trials (RCTs) will be identified and included. The primary outcomes include pain intensity measured by validated scales of visual analog scale, numeric rating scale, and response rate of symptom reduction. The secondary outcomes are scores on validated pain questionnaires, quality of life measured by SF-36 or other validated scales, and adverse events. Study selection, data extraction, and assessment of bias risk will be conducted by two reviewers independently. RevMan software (V.5.3.5) will be utilized to perform data synthesis. Subgroup and sensitivity analysis will be performed when necessary. The strength of the evidence will be evaluated with the Grading of Recommendations Assessment, Development and Evaluation System. RESULTS: A high-quality synthesis of current evidence of Chinese herbal footbaths for patients with dysmenorrhea will be provided in this study. CONCLUSION: This systematic review will provide evidence of whether Chinese herbal footbaths are an effective and safe intervention for the treatment of dysmenorrhea. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020188256.

Efficacy and safety of mesenchymal stem cells for the treatment of patients infected with COVID-19: a systematic review and meta-analysis protocol.

INTRODUCTION: To date, no specific antivirus drugs or vaccines have been available to prevent or treat the COVID-19 pandemic. Mesenchymal stem cell (MSC) therapy may be a promising therapeutic approach that reduces the high mortality in critical cases. This protocol is proposed for a systematic review and meta-analysis that aims to evaluate the efficacy and safety of MSC therapy on patients with COVID-19. METHODS AND ANALYSIS: Ten databases including PubMed, EMBASE, Cochrane Library, CINAHL, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wanfang database, China Biomedical Literature Database (CBM) and Chinese Biomedical Literature Service System (SinoMed) will be searched from inception to 1 December 2020. All published randomised controlled trials, clinical controlled trials and case series that meet the prespecified eligibility criteria will be included. The primary outcomes include mortality, incidence and severity of adverse events, respiratory improvement, days from ventilator, duration of fever, progression rate from mild or moderate to severe, improvement of such serious symptoms as difficulty breathing or shortness of breath, chest pain or pressure, and loss of speech or movement, biomarkers of laboratory examination and changes in CT. The secondary outcomes include dexamethasone doses and quality of life. Two reviewers will independently perform study selection, data extraction and assessment of bias risk. Data synthesis will be conducted using RevMan software (V.5.3.5). If necessary, subgroup and sensitivity analysis will be performed. Grading of Recommendations Assessment, Development and Evaluation system will be used to assess the strength of evidence. ETHICS AND DISSEMINATION: Ethical approval is not necessary since no individual patient or privacy data have been collected. The results of this review will be disseminated in a peer-reviewed journal or an academic conference presentation. PROSPERO REGISTRATION NUMBER: CRD42020190079.

Efficacy of integrative Traditional Chinese and Western medicine for the treatment of patients infected with 2019 novel coronavirus (COVID-19): A protocol for systematic review and meta analysis.

BACKGROUND: No specific anti-virus drugs or vaccines have been available for the treatment of COVID-19. Integrative traditional Chinese and western medicine has been proposed as a therapeutic option with substantial applications in China. This protocol is proposed for a systematic review and meta-analysis that aims to evaluate the efficacy of integrative traditional Chinese and western medicine treatment on patients with COVID-19. METHODS: Ten databases including PubMed, EMBASE, Cochrane Library, CIHAHL, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wanfang database, China Biomedical Literature Database (CBM) and Chinese Biomedical Literature Service System (SinoMed) will be searched. All published randomized controlled trials, clinical controlled trials, case-control, and case series that meet the pre-specified eligibility criteria will be included. Primary outcome measures include mortality, clinical recovery rate, duration of fever, progression rate from mild or moderate to severe, improvement of symptoms, biomarkers of laboratory examination and changes in computed tomography. Secondary outcomes include dosage of hormonotherapy, incidence and severity of adverse events and quality of life. Study selection, data extraction and assessment of bias risk will be conducted by 2 reviewers independently. RevMan software (V.5.3.5) will be used to perform data synthesis. Subgroup and sensitivity analysis will be performed when necessary. The strength of evidence will be assessed by the GRADE system. RESULTS: This study will provide a well-reported and high-quality synthesis on the efficacy of integrative traditional Chinese and western medicine treatment on patients with COVID-19. CONCLUSION: This systematic review protocol will be helpful for providing evidence of whether integrative traditional Chinese and western medicine treatment is an effective therapeutic approach for patients with COVID-19. ETHICS AND DISSEMINATION: Ethical approval is unnecessary as no individual patient or privacy data is collected. The results of this study will be disseminated in a peer-reviewed scientific journal and/or conference presentation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020167205.

Clustering Cloud-Like Model-Based Targets Underwater Tracking for AUVs.

Autonomous underwater vehicles (AUVs) rely on a mechanically scanned imaging sonar that is fixedly mounted on AUVs for underwater target barrier-avoiding and tracking. When underwater targets cross or approach each other, AUVs sometimes fail to track, or follow the wrong target because of the incorrect association of the multi-target. Therefore, a tracking method adopting the cloud-like model data association algorithm is presented in order to track underwater multiple targets. The clustering cloud-like model (CCM) not only combines the fuzziness and randomness of the qualitative concept, but also achieves the conversion of the quantitative values. Additionally, the nearest neighbor algorithm is also involved in finding the cluster center paired to each target trajectory, and the hardware architecture of AUVs is proposed. A sea trial adopting a mechanically scanned imaging sonar fixedly mounted on an AUV is carried out in order to verify the effectiveness of the proposed algorithm. Experiment results demonstrate that compared with the joint probabilistic data association (JPDA) and near neighbor data association (NNDA) algorithms, the new algorithm has the characteristic of more accurate clustering.

Fractional Exhaled Nitric Oxide for the Diagnosis of Childhood Asthma: a Systematic Review and Meta-analysis.

The gold standard for diagnosing asthma in children is based on clinical history of respiratory symptoms, physical examination, and respiratory function testing. Recent advances indicate that a non-invasive measure of airway inflammation, fractional exhaled nitric oxide (FeNO), provides objective data for use in asthma diagnosis. However, the diagnostic performance of FeNO in children with asthma has not been clearly defined. This systematic review and meta-analysis aimed to evaluate the diagnostic accuracy of FeNO in the clinical determination of asthma in children. Databases of PubMed, the Cochrane Library, EMBASE, MEDION, and Web of Science were searched for relevant articles through March 31, 2016. A bivariate model was used for pooling estimates of sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary receiver operating curves (SROC) as the main diagnostic measures. In total, eight studies met the inclusion criteria, which included 2933 subjects. The pooled estimates of sensitivity, specificity, and DOR for the detection of asthma in children were 0.79 [95 % confidence interval (CI), 0.64-0.89], 0.81 (95 % CI, 0.66-0.90), and 16.52 (95 % CI, 7.64-35.71). The SROC was 0.87 (95 % CI, 0.84-0.90). In brief, FeNO achieves a moderate diagnostic performance in the detection of asthma in children.

Pien-Tze-Huang protects cerebral ischemic injury by inhibiting neuronal apoptosis in acute ischemic stroke rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Pien-Tze-Huang (PZH) is a famous formula of traditional Chinese medicine used to treating stroke. However, the protective effect of PZH and its mechanisms in acute ischemic stroke remain to be explored. AIM OF THE STUDY: To investigate the protective effect of PZH on neuronal apoptosis in acute cerebral ischemic injury rats and explore its underlying mechanisms. MATERIALS AND METHODS: The effects of PZH were studied in acute ischemic stroke rats induced by transient middle cerebral artery occlusion, and the mitochondria-mediated apoptotic proteins including cytochrome C (Cyt C), Bax, Bcl-xl, P53, caspase-3, and caspase-9 as well as AKT and glycogen synthase kinase-3 beta (GSK-3ß) were assessed. RESULTS: Four days of PZH treatment (180 mg/kg) could significantly reduce cerebral infarct volume, improve neurological deficit, attenuate inflammatory response, and inhibit neuronal apoptosis in acute ischemic stroke rats. Moreover, PZH treatment significantly decreased cytosolic Cyt C, Bax, P53, cleaved caspase-3, and cleaved caspase-9 levels, but elevated mitochondrial Cyt C and Bcl-xl levels. PZH treatment also increased phosphorylation of AKT and GSK-3ß. CONCLUSION: PZH potently protects the brain from cerebral ischemia/reperfusion injury in vivo, and inhibiting mitochondria-mediated neuronal apoptosis as well as attenuating inflammatory responses may be involved in this effect. This study provides experimental basis of PZH in treating acute cerebral ischemic stroke, which would provide some novel insights for its prevention and treatment of ischemic stroke.

IN VIVO EFFECT OF GUIDING-HERB RADIX PLATYCODONIS AND RADIX CYATHULAE ON PAEONIFLORIN PHARMACOKINETICS OF XUEFU ZHUYU TANG IN RATS.

BACKGROUND: Xuefu Zhuyu Tang (XFZYT), first recorded in Correction of Errors in Medical Works by Qing-ren Wang, has been proven reliable and effective for curing various diseases such as atherosclerosis, hypertension, hyperlipidemia, and angina pectoris. It consists of 11 herbs and two of them, Radix platycodonis and Radix cyathulae, have been traditionally considered as guiding herbs and deeply valued by tens of millions of Chinese medicine practitioners. Do Radix platycodonis and Radix cyathulae affect the pharmacokinetics of the effective constituent-paeoniflorin of XFZYT? If yes, in what way? This study aims to answer these questions. MATERIALS AND METHODS: The medicinal solutions of XFZYT, XFZYT without Radix platycodonis (XFZYT-JG), XFZYT without Radix cyathulae (XFZYT-NX), and XFZYT without Radix platycodonis and Radix cyathulae (XFZYT-JG-NX) were prepared and administrated to rats in the normal group and the blood-stasis model group by gavage, respectively. The blood samples of rats in the normal group were obtained 5, 10, 15, 20, 30, 45, 60, 120, and 240 minutes after gavage; whereas the blood samples of rats in the blood-stasis model group were obtained 10, 15, 20, 30, 45, 90, 150, and 240 minutes after gavage. Biological samples were processed; the assays of specificity, precision, linearity, intra-day and inter-day precisions, recovery and stability were conducted; high performance liquid chromatography was performed to detect paeoniflorin content; and DAS software was adopted to generate pharmacokinetic parameters. Mobile phase was composed of acetonitrile and water (16:84), detection wavelength was 230 nm, and riboflavin was set as internal standard substance. RESULTS: The pharmacokinetic parameters of the rats in the normal group after oral gavage of XFZYT, XFZYT-JG, XFZYT-NX, and XFZYT-JG-NX were Cmax = (0.363±0.248, 0.065±0.020, 0.099±0.033, 0.099±0.020) mg/L, Tmax = (0.276±0.084, 0.583±0.342, 0.555±0.228, 0.317±0.033)h, t1/2 = (0.501±0.241, 1.021±0.522, 0.853±0.377, 1.227±0.402) h; and AUC0-∞ = (0.381±0.415, 0.13±0.085, 0.166±0.066, 0.185±0.059) mg/L·h.; whereas the pharmacokinetic parameters for the rats in the blood-stasis model group after oral gavage of XFZYT, XFZYT-JG, XFZYT-NX, and XFZYT-JG-NX were Cmax = (0.315±0.153, 0.215±0.044, 0.228±0.056, 0.248±0.09) mg/L, Tmax = (0.5±0, 0.667±0.129, 0.5±0, 0.542±0.102) h, t1/2 = (0.408±0.146, 0.813±0.135, 0.708±0.383, 0.741±0.173) h, and AUC0-∞ = (0.306±0.157, 0.408±0.136, 0.368±0.159, 0.381±0.246) mg/L·h. CONCLUSION: The guiding herbs, Radix platycodonis and Radix cyathulae, significantly increased the absorption amount and rate of paeoniflorin in XFZYT, and accelerated its elimination from the blood.

An herbal formula attenuates collagen-induced arthritis via inhibition of JAK2-STAT3 signaling and regulation of Th17 cells in mice.

Wenjinghuoluo prescription, a traditional Chinese medicine compound treatment of rheumatoid arthritis characterized by wind-cold-dampness arthralgia, contains five herbs, namely, C. cassia Presl., Cinnamomum cassia Presl., Paeonia lactiflora Pall., Saposhnikovia divaricate (Turcz.) Schischk., and Clematis chinensis Osbeck. We have reported that WJHL could inhibit the production of inflammatory mediators in immune cells. This study explored the effect and mechanism of WJHL on collagen-induced arthritis mice. WJHL could significantly improve clinical arthritic conditions; inhibit bone erosion and osteophyte formation in joints; decrease expression of proinflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-17); reduce protein expression levels of JAK2, p-JAK2, STAT3, p-STAT3 and gene expression levels of JAK2, STAT3, IL-17A, RORγt mRNA; elevate osteoprotegerin and Foxp3 mRNA levels and lower Th17 cell proportions in splenocytes. Results suggest that WJHL, specifically regulating the JAK2/STAT3 pathway and Th17 cells, may be a promising herbal medicine candidate for the treatment of RA.