Integrated pharmacokinetic properties and tissue distribution of multiple active constituents in Qing-Yi Recipe: A comparison between granules and decoction.

BACKGROUND: Qing-Yi Recipe, a classic traditional Chinese medicine (TCM), is widely used for treating acute diseases of the abdomen, especially pancreatitis, the efficacy of which has been demonstrated in more than thirty clinical trials. However, the in-vivo pharmacodynamic material basis for this formula remains unclear. METHODS: A sensitive and accurate method for quantifying twenty-two potential bioactive constituents of Qing-Yi Recipe in biological samples was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and this method was fully validated. Then, the integrated pharmacokinetic properties of Qing-Yi Recipe and its major metabolites in rats were investigated using the post-listed granules at both dosages. Subsequently, tissue distributions of those constituents in nine organs (especially the pancreas) were determined, and the overall parameters between the two formulations were compared. RESULTS: Though the chemical profiles of the formulas varied across formulations, the overall exposure level was very similar, and baicalin, wogonoside, geniposide, rhein, costunolide, and paeoniflorin were the top six bioactive compounds in the circulation. All twenty-two natural products reached their first peak within 2 h, and several of them exhibited bimodal or multimodal patterns under the complicated transformation of metabolic enzymes, and the parameters of these products markedly changed compared with those of monomers. Diverse metabolites of emodin and baicalin/baicalein were detected in circulation and tissues, augmenting the in vivo forms of these compounds. Finally, the enrichment of tetrahydropalmatine and corydaline in the pancreas were observed and most compounds remained in the gastrointestinal system, providing a foundation basis for their potential regulatory effects on the gut microbiota as well as the intestinal functions. CONCLUSION: Herein, the pharmacokinetic properties and tissue distribution of multiple potential active constituents in Qing-Yi Recipe were investigated at two dosages, providing a pharmacodynamic material basis of Qing-Yi Recipe for the first time. This investigation is expected to provide a new perspective and reference for future studies on the physiological disposition and potential pharmacodynamic basis of traditional Chinese medicine to treat acute abdomen diseases.

Hypoglycemic activity of immature persimmon (Diospyros kaki Thunb.) extracts and its inhibition mechanism for α-amylase and α-glucosidase.

Persimmon tannins, particularly in immature persimmons, haven't yet received corresponding attention to research on therapy of diabetes mellitus in spite of high hypoglycemic activity. To accurately screening key hypoglycemic components, immature persimmon extracts were isolated and identified using enzyme affinity ultrafiltration and HRLC-ESI-MS/MS. Among them, Hederagenin (IC50 = 0.077 ± 0.003 mg/mL), Ursolic acid (IC50 = 0.001 ± 0.000 mg/mL) and Quercetin dehydrate (IC50 = 0.081 ± 0.001 mg/mL) exhibited the strongest inhibitory effect on α-amylase (HSA and PPA) and α-glucosidase, respectively. And their inhibition mechanisms were analyzed using multi-spectral analysis, atomic force microscope and molecular docking, indicating the bonding with starch digestion enzymes through hydrogen bonding and hydrophobic interaction, and generating the enzyme aggregation. In vivo starch-tolerance experiment further verified that these inhibitors could improve postprandial hyperglycemia (17.18 % âˆ¼ 40.29 %), far more than acarbose. Suppressing, Hederagenin and Ursolic acid as triterpenoids appeared amazing potentiality to alleviate postprandial hyperglycemia, which suggested that IPE were comprehensive exploration values on prevention and treatment of hyperglycemia.

Oriental traditional herbal Medicine--Puerariae Flos: A systematic review.

ETHNOPHARMACOLOGICAL RELEVANCE: Pueraria Flos (PF), a traditional herbal medicine, is botanically from the dried flowers of Pueraria lobate (Willd.) Ohwi. (Chinese: ) or Pueraria thomsonii Benth. (Chinese: ). It has a long history of thousands of years in China for awakening the spleen, clearing the lungs, relieving alcohol. AIM OF THE REVIEW: This review aims to report the up-to-date research progress in ethnopharmacology, phytochemistry, pharmacology and toxicology, metabolism and therapeutic application of PF, so as to provide a strong basis for future clinical treatment and scientific research. MATERIALS AND METHODS: Relevant information on PF was collected from scientific literature databases including PubMed, CNKI and other literature sources (Ph.D. and M.Sc. dissertations and Chinese herbal classic books) by using the keyword "Puerariae". RESULTS: Briefly, phytochemical research report has isolated 39 flavonoids, 19 saponins and 25 volatile oils from PF. Flavonoids and saponins are the most important bioactive compounds, and most of the quality control studies focus on these two types of compounds. Modern pharmacological studies have revealed their significant biological activities in relieving alcoholism, hepatoprotective, anti-tumor, anti-inflammatory, and anti-oxidation, which provides theoretical support for the traditional use. CONCLUSIONS: Comprehensive analysis showed that pharmacological activity of most purified compounds from PF had not been reported. Kakkalide, tectoridin and their deglycosylated metabolites (irisolidone and tectorigenin) has been focused on excessively due to their higher content and better activities. This leads to low development and resources waste. Interestingly, PF made a breakthrough in the field of food. Many kinds of fat-lowering foods such as PILLBOX Onaka have been popular in Japan market, which received extensive attention. Therefore, we suggest that future research can be paid attention on the development of the plant's function in the field of food and medicine, as well as the transformation from experimental to clinical.

3D Microfluidic System for Evaluating Inhibitory Effect of Chinese Herbal Medicine Oldenlandia diffusa on Human Malignant Glioma Invasion Combined with Network Pharmacology Analysis.

OBJECTIVE: To investigate the anti-invasion efficacy of the ethanol extract of Oldenlandia diffusa Will. (EEOD) on a three-dimensional (3D) human malignant glioma (MG) cell invasion and perfusion model based on microfluidic chip culture and the possible mechanism of action of Oldenlandia diffusa Will. (OD). METHODS: The comprehensive pharmacodynamic analysis method in this study was based on microfluidic chip 3D cell perfusion culture technology, and the action mechanism of Chinese medicine (CM) on human MG cells was investigated through network pharmacology analysis. First, the components of EEOD were analyzed by ultraperformance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Then, cell viability and apoptosis were assessed to determine the optimum concentration of EEOD for invasion experiments, and two-dimensional (2D) migration and invasion abilities of U87 and U251 MG cells were evaluated using scratch wound and Transwell assays. The possible mechanism underlying the effects of EEOD on glioma was analyzed through a network pharmacology approach. RESULTS: Thirty-five compounds of EEOD were detected by UPLC-Q-TOF/MS. EEOD suppressed the viability of MG cells, promoted their apoptosis, and inhibited their migratory and invasive potentials (all P<0.05). Network pharmacology analysis showed that OD inhibited the invasion of MG cells by directly regulating MAPK and Wnt pathways through MAPK, EGFR, MYC, GSK3B, and other targets. The anti-invasion effect of OD was also found to be related to the indirect regulation of microtubule cytoskeleton organization. CONCLUSIONS: ]EEOD could inhibit the invasion of human MG cells, and the anti-invasion mechanism of OD might be regulating MAPK and Wnt signaling pathways and microtubule cytoskeleton organization.

Plant polysaccharides with anti-lung injury effects as a potential therapeutic strategy for COVID-19.

When coronavirus disease 2019 (COVID-19) develops into the severe phase, lung injury, acute respiratory distress syndrome, and/or respiratory failure could develop within a few days. As a result of pulmonary tissue injury, pathomorphological changes usually present endothelial dysfunction, inflammatory cell infiltration of the lung interstitium, defective gas exchange, and wall leakage. Consequently, COVID-19 may progress to tremendous lung injury, ongoing lung failure, and death. Exploring the treatment drugs has important implications. Recently, the application of traditional Chinese medicine had better performance in reducing fatalities, relieving symptoms, and curtailing hospitalization. Through constant research and study, plant polysaccharides may emerge as a crucial resource against lung injury with high potency and low side effects. However, the absence of a comprehensive understanding of lung-protective mechanisms impedes further investigation of polysaccharides. In the present article, a comprehensive review of research into plant polysaccharides in the past 5 years was performed. In total, 30 types of polysaccharides from 19 kinds of plants have shown lung-protective effects through the pathological processes of inflammation, oxidative stress, apoptosis, autophagy, epithelial-mesenchymal transition, and immunomodulation by mediating mucin and aquaporins, macrophage, endoplasmic reticulum stress, neutrophil, TGF-ß1 pathways, Nrf2 pathway, and other mechanisms. Moreover, the deficiencies of the current studies and the future research direction are also tentatively discussed. This research provides a comprehensive perspective for better understanding the mechanism and development of polysaccharides against lung injury for the treatment of COVID-19.

Systematic characterization of Puerariae Flos metabolites in vivo and assessment of its protective mechanisms against alcoholic liver injury in a rat model.

Puerariae Flos, a representative homology plant of medicine and food for alcoholism, has a long history of clinical experience and remarkable curative effect in the treatment of alcoholic liver disease (ALD). However, its effective forms and hepatoprotective mechanisms remain unknown. In the present study, a strategy based on UPLC-QTOF MS combined with mass defect filtering technique was established for comprehensive mapping of the metabolic profile of PF in rat plasma, urine, bile, and feces after oral administration. Furthermore, the absorbed constituents into plasma and bile with a relatively high level were subjected to the network analysis, functional enrichment analysis, and molecular docking to clarify the potential mechanism. Finally, the therapeutic effect of PF on ALD and predicted mechanisms were further evaluated using a rat model of alcohol-induced liver injury and Western blot analysis. In total, 25 prototype components and 82 metabolites, including 93 flavonoids, 13 saponins, and one phenolic acid, were identified or tentatively characterized in vivo. In addition, glucuronidation, sulfation, methylation, hydroxylation, and reduction were observed as the major metabolic pathways of PF. The constructed compound-target-pathway network revealed that 11 absorbed constituents associated with the 16 relevant targets could be responsible for the protective activity of PF against ALD by regulating nine pathways attributable to glycolysis/gluconeogenesis, amino acid metabolism, and lipid regulation as well as inflammation and immune regulation. In addition, four active ingredients (6″-O-xylosyltectoridin, genistein-7-glucuronide-4'-sulfate, tectoridin-4'-sulfate, and 6″-O-xylosyltectoridin-4'-sulfate) as well as two target genes (MAO-A and PPAR-α) were screened and validated to play a crucial role with a good molecular docking score. The present results not only increase the understanding on the effective form and molecular mechanisms of PF-mediated protection against ALD but also promote better application of PF as a supplement food and herbal medicine for the treatment of ALD.

Effect of mineral excipients on processing traditional Chinese medicines: an insight into the components, pharmacodynamics and mechanism.

Traditional Chinese medicines are an important class of natural products mainly derives from animals, plants and minerals, most of which need to be improved and processed before clinical use due to their own hard texture, impurities or toxicity. As an important part of solid excipients, mineral excipients that contain some metal elements play indispensable and unique roles in the pretreatment process of traditional Chinese medicine. However, deficiency of holistic understanding of the effect of mineral excipients hinders their application and development. This article reviews several mineral excipients including alumen, talci pulvis, soil, soda lime, halloysitum rubrum and cinnabaris systemically. Their processing significance on traditional Chinese medicines were revealed from components, pharmacodynamics and mechanism aspects. Furthermore, prospect and problems including processing technologies, quality standards of mineral excipients and processing mechanism were put forward. This review supply comprehensive information for better and scientific usage of mineral excipients in processing traditional Chinese medicines.

Hepatoprotective effect of plant polysaccharides from natural resources: A review of the mechanisms and structure-activity relationship.

Liver injury is a common pathological process, which can result in fatty liver, cirrhosis, fibrosis and even cancer. Polysaccharides isolated from plants have been regarded as an important resource of anti-hepatic lesion due to widely distributed in nature and low toxicity. In order to have a better understand of the protective mechanism on liver function, a comprehensive review of research into plant polysaccharides during recent five years was performed. In total, 66 types of polysaccharides from 58 kinds of plant have shown hepatoprotective effect through the pathological process of inflammation, apoptosis and oxidative stress by regulating NF-κB, JAK/STAT, TGF-ß, PI3K/AKT, MAPK, caspase cascade, p53 and Nrf2-Keap1 pathways, lipid metabolism as well as cytochrome P450 enzymes. Moreover, correlations between structure and hepatoprotective activities of plant polysaccharides including primary structure, conformation properties, structural modification and content of uronic acid were also preliminarily explored. This review will provide a comprehensive perspective for better understanding the mechanism and development of polysaccharides against liver injury.

Proteomic analysis of therapeutic effects of Qingyi pellet on rodent severe acute pancreatitis-associated lung injury.

Severe acute pancreatitis (SAP) is a common acute clinical abdomen syndrome which is characterized by pancreatic self-digestion. As one of the major complication of SAP, acute lung injury is the main reason of high mortality. The traditional Chinese medicine Qingyi pellet (QYT) has been widely used for SAP in clinic. In our study, we constructed the severe acute pancreatitis-associated lung injury (SAP-ALI) rat model and treated with QYT, then characterized the protein from the lung tissue by using a mass spectrometry-based proteomic strategy. Our results showed that, in the SAP group, 9 proteins exhibited obvious changes according to the proteomic analysis. Among the 9 proteins, 7 proteins (alpha-2-macroglobulin, Cathepsin S, ras-related protein RAP-1A, integrin beta, protein phosphatase 2A, Intercellular adhesion molecule 1 and p38) were up-regulated, and 2 proteins (adapter molecule Crk and stathmin) were down-regulated. Interestingly, the data of the QYT group showed that adapter molecule Crk and stathmin were up-regulated, but the other 7 proteins were down-regulated. The kyoto encyclopedia of genes shows that the proteins act on PI3K-AKT, chemokine signaling pathways, apoptosis, leukocyte transendothelial migration and focal adhesion. Therefore, the therapeutic effects of QYT on SAP-ALI are potentially through the additive and/or synergistic interactions of numerous components.

Systematically Characterizing Chemical Profile and Potential Mechanisms of Qingre Lidan Decoction Acting on Cholelithiasis by Integrating UHPLC-QTOF-MS and Network Target Analysis.

Qingre Lidan Decoction (QRLDD), a classic precompounded prescription, is widely used as an effective treatment for cholelithiasis clinically. However, its chemical profile and mechanism have not been characterized and elucidated. In the present study, a rapid, sensitive, and reliable ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method was established for comprehensively identifying the major constituents in QRLDD. Furthermore, a network pharmacology strategy based on the chemical profile was applied to clarify the synergetic mechanism. A total of 72 compounds containing flavonoids, terpenes, phenolic acid, anthraquinones, phenethylalchohol glycosides, and other miscellaneous compounds were identified, respectively. 410 disease genes, 432 compound targets, and 71 related pathways based on cholelithiasis-related and compound-related targets databases as well as related pathways predicted by the Kyoto Encyclopedia of Genes and Genomes database were achieved. Among these pathways and genes, pathway in cancer and MAPK signaling pathway may play an important role in the development of cholelithiasis. EGFR may be a crucial target in the conversion of gallstones to gallbladder carcinoma. Regulation of PRKCB/RAF1/MAP2K1/MAPK1 is associated with cell proliferation and differentiation. Thus, the fingerprint coupled with network pharmacology analysis could contribute to simplifying the complex system and providing directions for further research of QRLDD.

Emodin attenuated severe acute pancreatitis via the P2X ligand­gated ion channel 7/NOD­like receptor protein 3 signaling pathway.

Acute pancreatitis (AP) is an aseptic inflammation characterized with an annual incidence rate, and ~20% patients progressing to severe AP (SAP) with a high mortality rate. Although Qingyi decoction has been frequently used for SAP treatment over the past 3 decades in clinic, the actual mechanism of its protective effects remains unknown. As the major active ingredient of Qingyi decoction, emodin was selected in the present study to investigate the effect of emodin against severe acute pancreatitis (SAP) in rats through NOD­like receptor protein 3 (NLRP3) inflammasomes. The rats were randomly divided into a sham operation group, an SAP model group induced by a standard retrograde infusion of 5.0% sodium taurocholate into the biliopancreatic duct, and low­dose (30 mg/kg) and high­dose (60 mg/kg) emodin­treated groups. At 12 h after the event, the plasma amylase, lipase, interleukin (IL)­1ß, IL­18 and myeloperoxidase (MPO) activities were examined. Furthermore, the pathological scores of pancreases were evaluated by hematoxylin and eosin staining. The expression levels of P2X ligand­gated ion channel 7 (P2X7), NLRP3, apoptosis­associated speck­like protein containing a C­terminal caspase recruitment domain and caspase­1 were also analyzed by western blot analysis. The data demonstrated that, compared with the SAP group, emodin could significantly relieve the pancreatic histopathology and acinar cellular structure injury, and notably downregulate the plasma amylase and lipase levels, as well as the MPO activities in pancreatic tissues, in a dose­dependent manner. Furthermore, emodin inhibited the P2X7/NLRP3 signaling pathway followed by the decrease of pro­inflammatory factors, and the latter is beneficial for the recovery of SAP. Collectively, the data indicated that emodin may be an efficient candidate natural product for SAP treatment.

Exploring the Therapeutic Composition and Mechanism of Jiang-Suan-Chu-Bi Recipe on Gouty Arthritis Using an Integrated Approach Based on Chemical Profile, Network Pharmacology and Experimental Support Using Molecular Cell Biology.

BACKGROUND: Gouty arthritis is a common metabolic disease caused by long-term purine metabolic disorder and elevated serum uric acid. Jiang-Suan-Chu-Bi recipe (JSCBR), a traditional Chinese herbal formula prescribed according to utilization frequency and cluster analysis, has been clinically validated remedy for gouty arthritis. However, its therapeutic composition and mechanism remains unclear. METHODS: In the present study, a simple, rapid, and sensitive ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS)-based chemical profiling was firstly established for comprehensively identifying the major constituents in JSCBR. A phytochemistry-based network pharmacology analysis was further performed to explore the potential therapeutic targets and pathways involved in JSCBR bioactivity. Finally, THP-1 cell model was used to verify the prediction results of network pharmacology by western blot analysis. RESULTS: A total of 139 compounds containing phenolic acids, flavonoids, triterpenoid saponins, alkaloids, amino acids, fatty acids, anthraquinones, terpenes, coumarins, and other miscellaneous compounds were identified, respectively. 175 disease genes, 51 potential target nodes, 80 compounds, and 11 related pathways based on network pharmacology analysis were achieved. Among these pathways and genes, NOD-like receptor signaling pathway may play an important role in the curative effect of JSCBR on gouty arthritis by regulation of NRLP3/ASC/CASP1/IL1B. The results of cellular and molecular experiments showed that JSCBR can effectively reduce the protein expression of ASC, caspase-1, IL-1ß, and NRLP3 in monosodium urate-induced THP-1 cells, which indicated that JSCBR mediated inflammation in gouty arthritis by inhibiting the activation of NOD-like receptor signaling pathway. CONCLUSION: Thus, the integrated approaches adopted in the present study could contribute to simplifying the complex system and providing directions for further research of JSCBR.

Evaluating the Efficacy and Adverse Effects of Clearing Heat and Removing Dampness Method of Traditional Chinese Medicine by Comparison with Western Medicine in Patients with Gout.

Objective. In China, the method of clearing heat and removing dampness medicine of Chinese traditional medicine has been widely used on gout. However, the clinical effects are various and not summarized systematically. Methods. In this study, a large number of randomized controlled clinical trials were reviewed and analyzed and the clinical efficacy and adverse reactions of traditional Chinese medicine with clearing heat and removing dampness effects for the treatment of gout were systematically evaluated. A comprehensive search of databases including pubMed, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database, Wanfang Data, and SinoMed was performed. Results. There are 69 randomized controlled trials with 5915 sample sizes meeting the criteria in the study. The results of the meta-analysis indicate that the effects of clearing heat and removing dampness medicine were slightly better than western medicine in the treatment of gout based on the following parameters: serum uric acid (standardized mean difference (SMD):-62.14, 95% confidence interval (CI): -78.12 to-46.15), C reactive protein (SMD: -4.21, 95% CI: -6.19 to -2.23), erythrocyte sedimentation rate (SMD: -6.23, 95% CI: -8.39 to-4.06), and overall clinical response (relative risk (RR): 1.11, 95% CI: 1.08 to 1.15) and, in the profile of adverse drug reactions, the clearing heat and removing dampness medicine showed less adverse reactions than traditional Western medicine (RR: 0.18, 95% CI: 0.10 to 0.32). Conclusions. Through a systemic evaluation of the clinical efficacy of the clearing heat and removing dampness medicine of traditional Chinese medicine and western medicine on gout, the clearing heat and removing dampness medicine and western medicine possessed similar clinical efficacy, but traditional Chinese medicine treatments are superior to western medicine in controlling adverse reactions.

Rapid and Sensitive Determination of 13 Components in a Traditional Chinese Medicine Formula of Da-Huang-Gan-Cao Decoction by High-Performance Liquid Chromatography Coupled with Triple Quadrupole Mass Spectrometry.

Da-Huang-Gan-Cao decoction (DHGCD), which is a classic formula in traditional Chinese medicine, has been clinically used for the treatment of vomiting, constipation, pancreatitis, and cholelithiasis in China and Japan. In this study, a rapid and validated method using HPLC coupled with triple quadrupole MS was developed for the simultaneous determination of 13 components in DHGCD. Separation was performed on an XBridge BEH C18 column (50 × 2.1 mm, 2.5 µm) with a gradient elution of acetonitrile and 0.1% formic acid in water. All calibration curves showed good linear regression (r > 0.9981) within the test range. LODs and LOQs were in the range of 1.0-20 and 2.6-69 ng/mL, respectively. The proposed method was applied for the analysis of the target compounds in 10 batches of DHGCD within a total time of 10 min. This method was conducive for the QC of DHGCD.

Identification of metabolites in human and rat urine after oral administration of Xiao-Qing-Long-Tang granule using ultra high performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry.

Xiao-Qing-Long-Tang is a traditional Chinese formula used for the treatment of cold syndrome, bronchitis, and nasal allergies for thousands of years. However, the in vivo integrated metabolism of its multiple components and the active chemical constituents of Xiao-Qing-Long-Tang remain unknown. In this study, a method using ultra high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was established for the detection and identification of the metabolites in human and rat urine after oral administration of Xiao-Qing-Long-Tang. A total of 19 compounds were detected or tentatively identified in human urine samples, including eight prototypes and 11 metabolites. Also, a total of 50 compounds were detected or tentatively identified in rat urine samples, including 15 prototypes and 35 metabolites detected with either a highly sensitive extracted ion chromatogram method or the MSE determination using Mass Fragment software. Our results indicated that phase Ⅱ reactions (e.g. glucuronidation and sulfation) were the main metabolic pathways of flavones, while phase I reactions (e.g. demethylation and hydroxylation) were the major metabolic reaction for alkaloids, lignans, and ginger essential oil. This investigation provided important structural information on the metabolism of Xiao-Qing-Long-Tang and provided evidence to obtain a more comprehensive metabolic profile.

Chinese Herbal Medicines Attenuate Acute Pancreatitis: Pharmacological Activities and Mechanisms.

Acute pancreatitis (AP) is a commonly occurring gastrointestinal disorder. An increase in the annual incidence of AP has been observed, and it causes acute hospitalization and high mortality. The diagnosis and treatment guidelines for AP recommend conservative medical treatments focused on reducing pancreatic secretion and secondary injury, as a primary therapeutic approach. Unfortunately, the existing treatment options have limited impact on the incidence and severity of AP due to the complex and multifaceted pathological process of this disease. In recent decades, Chinese herbal medicines (CHMs) have been used as efficient therapeutic agents to attenuate AP in Asian countries. Despite early cell culture, animal models, and clinical trials, CHMs are capable of interacting with numerous molecular targets participating in the pathogenesis of AP; however, comprehensive, up-to-date communication in this field is not yet available. This review focuses on the pharmacological activities of CHMs against AP in vitro and in vivo and the underlying mechanisms. A computational prediction of few selected and promising plant-derived molecules (emodin, baicalin, resveratrol, curcumin, ligustrazine, and honokiol) to target numerous proteins or networks involved in AP was initially established based on a network pharmacology simulation. Moreover, we also summarized some potential toxic natural products for pancreas in order to more safe and reasonable medication. These breakthrough findings may have important implications for innovative drug research and the future development of treatments for AP.

Comparative Evaluation of Raw and Ripe Fruits of Forsythia suspensa by HPLC-ESI-MS/MS Analysis and Anti-Microbial Assay.

A multi-component quantification fingerprint based on high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry technique has been established for the comparative analysis of raw and ripe fruits of Forsythia suspensa originated from different provinces. Eighteen bioactive constituents including three phenylethanoid glycosides derivatives, six phenolic acids, three flavonoids, four phenylpropanoids, one fatty acid and one terpenoid were identified and quantified. Total contents of phenylethanoid glycosides, phenylpropanoids and flavonoids from raw samples were found much higher than those from ripe samples, while total content of phenolic acids showed a contrary tendency. Moreover, the anti-microbial activities were comparatively assayed for the first time using five different bacterial strains. Results revealed a positive relationship between contents of total phenolic and anti-microbial activity. The results obtained in the present study may provide useful information for future utilization of F. suspensa.

Two new phenolic acids from the fruits of Forsythia suspense.

Two new phenolic acids forsythiayanoside C (1) and forsythiayanoside D (2), were isolated from the fruits of Forsythia suspense (Thunb.) Vahl. Their structures were elucidated on the basis of chemical and spectral analysis, including 1D, 2D NMR analyses, HRESIMS and CD spectrometry. The cytotoxic and antioxidant activities testing showed that compound 2 exhibited free radical scavenging activity.

Excretion of tectoridin metabolites in rat urine and bile orally administrated at different dosages and their inhibitory activity against aldose reductase.

This study investigated the urinary and biliary excretion of tectoridin, a major active isoflavonoid found in the flowers of Pueraria thomsonii Benth. and the rhizomes of Belamcanda chinensis (L.) DC. Using UHPLC/Q-TOFMS, seven glucuronides and/or sulfated metabolites and four Phase I metabolites were simultaneously quantified in rat urine after oral administration of tectoridin at 100 and 200 mg/kg. Over a 72-h period, 14.2% and 14.7% of the tectoridin were excreted as eleven metabolites in urine, among which, two major metabolites tectorigenin-7-O-ß-D-glucuronide (Te-7G) and tectorigenin accounted for 5.5-5.5% and 4.3-4.4%. Furthermore, the cumulative excretion of four glucuronides and sulfated metabolites in bile accounted for 7.3% and 3.9% of the dose within 60 h, among which, Te-7G and tectorigenin-7-O-glucuronide-4'-O-sulfate (Te-7G-4'S) accounted for 2.3-3.0% and 1.4-3.9%, respectively. The results indicate that the urine was the primary elimination route, and glucuronidation after deglycosylation at C-7 position was the major metabolic pathway of tectoridin in vivo. Moreover, the inhibitory activities of tectoridin and its five metabolites on rat lens aldose reductase were confirmed (IC50: 1.4-15.5 µM), whereas irisolidone-7-O-glucuronide (Ir-7G) and irisolidone showed little activity.