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Abstract In recent years, deep artificial neural networks have attracted much attention and have been applied in various fields because they surpass the parameter fitting effect of traditional methods under the condition of data convergence. On the other hand, limited transmission bandwidth and storage capacity make image compression necessary in communication. Here, a compression algorithm that combines the K‐means clustering algorithm with the neural network algorithm is proposed. First, the pixel points of the image are clustered by K‐means algorithm in order to reduce the amount of data input to the neural network algorithm. Secondly, neural network is used to extract image features which realizes further compression. The experiment results show that the peak signal‐to‐noise ratio (PSNR) is 33.48 dB at most with compression ratio at 32:1. The ablation experiment shows that the run time speeds up 9.5% compared to the algorithm without K‐means clustering. Comprehensive comparison experiment shows that the average PSNR is 30.09 dB, which is larger than other baseline approaches. The proposed algorithm is an efficient solution for image compression.

Abstract Objective Most SARS‐CoV‐2‐infected individuals never require hospitalization. However, some develop prolonged symptoms. We sought to characterize the spectrum of neurologic manifestations in non‐hospitalized Covid‐19 “long haulers”. Methods This is a prospective study of the first 100 consecutive patients (50 SARS‐CoV‐2 laboratory‐positive (SARS‐CoV‐2+) and 50 laboratory‐negative (SARS‐CoV‐2‐) individuals) presenting to our Neuro‐Covid‐19 clinic between May and November 2020. Due to early pandemic testing limitations, patients were included if they met Infectious Diseases Society of America symptoms of Covid‐19, were never hospitalized for pneumonia or hypoxemia, and had neurologic symptoms lasting over 6 weeks. We recorded the frequency of neurologic symptoms and analyzed patient‐reported quality of life measures and standardized cognitive assessments. Results Mean age was 43.2 ± 11.3 years, 70% were female, and 48% were evaluated in televisits. The most frequent comorbidities were depression/anxiety (42%) and autoimmune disease (16%). The main neurologic manifestations were: “brain fog” (81%), headache (68%), numbness/tingling (60%), dysgeusia (59%), anosmia (55%), and myalgias (55%), with only anosmia being more frequent in SARS‐CoV‐2+ than SARS‐CoV‐2‐ patients (37/50 [74%] vs. 18/50 [36%]; p

Introduction: Intraluminal thrombosis after endovascular therapy (EVT) is a peri‐procedural complication that carries a high burden of morbidity and mortality. The use of anti‐thrombotic therapies during EVT remains an evolving field. Recent surveys suggest the glycoprotein IIb/IIIa inhibitor, tirofiban, is often used during EVT. However, the increased intracranial hemorrhage risk and the medication’s long half‐life pose significant challenges to management. Cangrelor, an intravenous and reversible P2Y12 inhibitor, was first approved by FDA in 2015 for use in patients with coronary artery disease undergoing percutaneous intervention. Its rapid onset and offset are beneficial as an anti‐thrombotic during EVT. Our case series aim to characterize the safety and efficacy of cangrelor use in our institution and contribute towards its growing body of data. Methods: Chart review was conducted for patients that required endovascular therapy for acute stroke and received intravenous cangrelor at our center between January 2019 to December 2020. We included patients that underwent both extracranial and intracranial stent placement, as well as patients who suffered from intraluminal thromboses intra‐procedurally. Variables of interest included lesion pathophysiology, peri‐procedural complications including intraluminal re‐occlusion and intracranial hemorrhage, TICI score post‐procedurally, vessel patency and MRS on post‐hospitalization followup. Results: Nine patients received intravenous cangrelor during endovascular therapy. Mean age was 50 (range 41–67 years old), 3/9 patients were male. Seven patients (77.8%) had ischemic stroke, of whom five exhibited tandem intracranial occlusions and three required intraprocedural stent deployment. 3/7 patients received IV TPA prior to EVT. Interestingly, one patient had a previously placed Precise stent for acute internal carotid thrombus, briefly placed on eptifibatide (180mcg/kg), suffered from stent re‐occlusion on POD1 and required repeat thrombectomy with cangrelor intra‐procedurally; stent patency was maintained for the rest of her hospital course. One patient received balloon angioplasty of supraclinoid internal carotid artery. The remaining two patients required cangrelor for visualized intraluminal platelet aggregates during the EVT. Two patients presented with aneurysmal subarachnoid hemorrhage, one treated with flow diversion stent and the other requiring stenting for prolapsed aneurysm coiling. Dosing of cangrelor bolus and infusion varied. Six patients were bolused with 15 mcg/kg, while three patients received 7.5 mcg/kg. Infusion rates range from 0.5 to 4 mcg/kg/minute with all nine patients reaching therapeutic range P2Y12 levels on post‐procedural testing. Cangrelor infusion was transitioned to oral antiplatelet on post‐operative day 4 on average. In all nine patients, vessel and stent patency was maintained intra‐procedurally with cangrelor. Subsequent vascular imaging during hospitalization demonstrated no intraluminal thrombosis. One patient experienced intracranial hemorrhage, however they received intraprocedural eptifibatide (180mcg/kg) and cangrelor infusion (15 mcg/kg bolus, 2 mcg/kg/min) for their extensive clot burden and triple stent placement. Five patients attended three‐month post‐hospitalization followups. Their median MRS was 2 and all followup vessel imaging demonstrated patent vessels. Conclusions: Our case series demonstrate the promising efficacy of cangrelor in patients undergoing emergent endovascular therapy to prevent intraluminal thrombosis. Further studies with larger sample sizes can elucidate the optimal dose of cangrelor, length of treatment before oral transition, and compare its efficacy to eptifibatide.

To realize the continuous compaction control (CCC) of asphalt pavement during construction, continuous detection method was investigated for the compaction degree values. For the trajectory of rollers, a collaborative positioning method was proposed. For the monitoring of rolling process, an embedded-based detection system was designed. For the evaluation of rolling effect, harmonic analysis was introduced and a new index, vibration compaction energy value (VCVe), was proposed. Positioning experiments were conducted, and the accuracy was improved to 0.48 m. Rolling tests were performed, and typical compaction meter values (CMVs), compaction control values (CCVs), and VCVe were obtained. The referenced compaction degree by conventional way was 94.6%, which was used to calibrate the detected values of compaction degree indexes. The results showed that continuous compaction detection can be achieved based on positioning system and vibration analysis. Compared with CMV and CCV, VCVe is less discrete, more stable, and consistent to describe the compaction state. Though, all the CMV, CCV, and VCVe indexes are unable to be used for quality assurance directly or alone, they could be an aid for quality control. Continuous compaction detection system meets the monitoring requirements of pavement construction at a lower cost and could lay a foundation for the intelligent compaction (IC).

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is an excellent analytical technique for rapid analysis of a variety of molecules with straightforward sample pretreatment. The performance of MALDI-TOF MS is largely dependent on matrix type, and the development of novel MALDI matrices has aroused wide interest. Herein, we devoted to seek more robust MALDI matrix for herbal saponins than previous reported, and ginsenoside Rb1, Re, and notoginsenoside R1 were used as model saponins. At the beginning of the present study, 2,5-dihydroxybenzoic acid (DHB) was found to provide the highest intensity for saponins in four conventional MALDI matrices, yet the heterogeneous cocrystallization of DHB with analytes made signal acquisition somewhat "hit and miss." Then, graphene oxide (GO) was proposed as an auxiliary matrix to improve the uniformity of DHB crystallization due to its monolayer structure and good dispersion, which could result in much better shot-to-shot and spot-to-spot reproducibility of saponin analysis. The satisfactory precision further demonstrated that minute quantities of GO (0.1 μg/spot) could greatly reduce the risk of instrument contamination caused by GO detachment from the MALDI target plate under vacuum. More importantly, the sensitivity and linearity of the standard curve for saponins were improved markedly by DHB-GO composite matrix. Finally, the application of detecting the Rb1 in complex biological sample was exploited in rat plasma and proved it applicable for pharmacokinetic study quickly. This work not only opens a new field for applications of DHB-GO in herbal saponin analysis but also offers new ideas for the development of composite matrices to improve MALDI MS performance., (© 2019 John Wiley & Sons, Ltd.)

Lindera aggregata (Sims) Kosterm root has been used in traditional Chinese medicine for the treatment of rheumatism palsy, dyspepsia and frequent urination for a long time. Norisoboldine, the main active constituent of this herb drug, possesses outstanding anti-arthritis activity. However, the in vivo disposition of norisoboldine is known to a limited extent, especially under the pathological condition of rheumatoid arthritis (RA). The aim of this study is to investigate whether and how the absorption of norisoboldine is altered in adjuvant-induced arthritis (AIA) rats. Comparative studies of the intestinal absorption of norisoboldine in normal and AIA rats at different pathological stages of the arthritis were performed using in situ single-pass intestinal perfusion, and the effects of an inhibitor of efflux proteins were also investigated. Norisoboldine was shown to be a substrate of P-glycoprotein (P-gp), as P-gp inhibitor verapamil markedly increased the permeability coefficient (P eff ) of norisoboldine by 88% in the intestine of normal rats. Compared with normal rats, AIA rats displayed increased P eff values of norisoboldine by 84% and 86% on day 5 and day 10 after the appearance of the secondary response of arthritis, respectively. Verapamil could eliminate the difference of intestinal absorption of norisoboldine between normal and AIA rats. Further studies showed that impaired expression and activity of P-gp in AIA rats play a decisive role in the absorption enhancement of norisoboldine. Notably, the impairment of P-gp function positively correlated with the severity of arthritis. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background and Purpose: Madecassoside has potent anti-pulmonary fibrosis (PF) effects when administered p.o., despite having extremely low oral bioavailability. Herein, we explored the mechanism of this anti-PF effect with regard to gut hormones., Experimental Approach: A PF model was established in mice by intratracheal instillation of bleomycin. Haematoxylin and eosin stain and Masson's trichrome stain were used to assess histological changes in the lung. Quantitative-PCR and Western blot detected mRNA and protein levels, respectively, and cytokines were measured by ELISA. Small interfering RNA was used for gene-silencing. EMSA was applied to detect DNA-binding activity., Key Results: Administration of madecassoside, p.o., but not its main metabolite madecassic acid, exhibited a direct anti-PF effect in mice. However, i.p. madecassoside had no anti-PF effect. Madecassoside increased the expression of hepatocyte growth factor (HGF) in colon tissues, and HGF receptor antagonists attenuated its anti-PF effect. Madecassoside facilitated the secretion of HGF from colonic epithelial cells by activating the PPAR-γ pathway, as shown by an up-regulation of PPAR-γ mRNA expression, nuclear translocation and DNA-binding activity both in vitro and in vivo. Also GW9662, a selective PPAR-γ antagonist, almost completely prevented the madecassoside-induced increased expression of HGF and amelioration of PF., Conclusions and Implications: The potent anti-PF effects induced by p.o. madecassoside in mice are not mediated by its metabolites or itself after absorption into blood. Instead, madecassoside increases the activity of PPAR-γ, which subsequently increases HGF expression in colonic epithelial cells. HGF then enters into the circulation and lung tissue to exert an anti-PF effect., (© 2016 The British Pharmacological Society.)

This study investigated the in vitro drug-drug interaction potential of SIPI5357, an arylalkanol-piperazine derivative used in the treatment of depression. Drug-drug interaction occurs via inhibition or induction of enzymes involved in their metabolism. In human liver microsomes, SIPI5357 showed the strongest inhibition of CYP2D6, followed by CYP3A4 (testosterone) and CYP2C8. Inhibition was observed in a concentration-dependent manner, with IC 50 values of 18.45 µM, 36.63 µM (CYP3A4/testosterone), 89.23 µM, respectively. SIPI5357 was predicted not to cause significant metabolic drug-drug interaction via inhibition of CYP1A2, CYP2C9, CYP2C19, CYP2E1 or CYP3A4 (midazolam) because the IC 50 values for these enzymes were both >100 µM (200 times maximum plasma concentration [C max ]). SIPI5357 showed a mixed model inhibition of CYP2D6 (K i = 11.12 µM). The value of [I]/K i for CYP2D6 inhibition by SIPI5357 is below the FDA cut-off value of 0.1; it is therefore reasonable to assume that SIPI5357 will not cause significant CYP2D6 inhibition. However, positive controls (50 µM omeprazole and 25 µM rifampin) caused the anticipated CYP induction, but the highest concentration of SIPI5357 (5 µM; 10 times plasma C max ) had a minimal effect on CYP1A2 and CYP3A4 mRNA levels in freshly isolated human hepatocytes, suggesting that SIPI5357 is not an inducer of these enzymes. However, significant induction of CYP2B6 was observed at 0.5 µM and 5 µM. In conclusion, SIPI5357 might cause drug-drug interaction via induction of CYP2B6. The in vivo drug-drug interaction potential deserves further investigation. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Amyloid β peptide (Aβ) has been thought to be neurotoxic and responsible for the impairment of learning and memory in Alzheimer's disease (AD). Humanin (HN), a 24 amino acid polypeptide first identified from the unaffected occipital lobe of an AD patient, is believed to be neuroprotective against the AD-related neurotoxicity. In this study, we investigated the neuroprotective effects of Colivelin (CLN), a novel HN derivative, against Aβ by using behavioral test, in vivo electrophysiological recording, and intracellular calcium imaging. Our results showed that intrahippocampal injection of CLN (0.2 nmol) effectively prevented Aβ25-35 (4 nmol)-induced deficits in spatial learning and memory of rats in Morris water maze test; the suppression of in vivo hippocampal long term potentiation (LTP) by Aβ25-35 was nearly completely prevented by CLN; in addition, CLN pretreatment also effectively inhibited Aβ25-35-induced calcium overload in primary cultured hippocampal neurons. These results indicate that CLN has significant neuroprotective properties against Aβ, and CLN may holds great promise for the treatment and prevention of AD., (© 2014 Wiley Periodicals, Inc.)

This study aimed to explore the protective effects of madecassoside (Mad), a triterpenoid saponin isolated from Centella asiatica herbs, on experimental pulmonary fibrosis (PF) and underlying mechanisms. PF model was established in mice by endotracheal instillation with bleomycin (5 mg/kg). Mice were orally administered with Mad (10, 20, 40 mg/kg) and prednisone (5 mg/kg) for 7 or 21 days. Mad (20, 40 mg/kg) significantly improved lung pathological changes and reduced collagen deposition. In the aspect of collagen synthesis, Mad (20, 40 mg/kg) reduced the expressions of α-smooth muscle actin and transforming growth factor-β1 (TGF-β1), and inhibited the phosphorylations of Smad2 and Smad3 in the lung tissues. However, in vitro, Mad showed little effect on TGF-β1-induced phosphorylation of either Smad2 or Smad3 in primary mouse lung fibroblasts. Moreover, Mad (20, 40 mg/kg) attenuated oxidative damage and inflammation presented at the early stage of PF, evidenced by reduced total leukocytes in the bronchoalveolar lavage fluid, decreased myeloperoxidase activity and malondialdehyde level, and increased super-oxide dismutase activity and glutathione level in lung tissues. On the other hand, Mad (40 mg/kg) elevated the matrix metalloproteinase 1/tissue inhibitor of metalloproteinase 1 ratio in lung tissues of PF mice mainly by downregulating tissue inhibitor of metalloproteinase 1 expression. The present study demonstrated that Mad can ameliorate PF by preventing the deposition of extracellular matrix, which might be achieved mainly through attenuating inflammation and oxidative stress and consequent TGF-β1 overexpression., (Copyright © 2014 John Wiley & Sons, Ltd.)

Introduction: 'Naoyanghua', composed of the flowers of Rhododendron molle G. Don, is a traditional Chinese medicine that is widely known for its toxicity. Grayanane-type diterpenoids are the main active ingredients in R. molle, as well as possibly their toxicity: they are, however, difficult to isolate and analyse using common chromatographic methods, due to their small amounts and absence of conjugated groups, such as phenyl and α, β-unsaturated ketone., Objective: To establish a highly sensitive, selective and reliable method for the qualitative evaluation of trace diterpenoids in the flowers of R. molle by using tandem solid-phase extraction followed by high-performance liquid chromatography with electrospray ionisation quadrupole-time-of-flight mass spectrometry (HPLC-ESI/QTOF/MS/MS)., Methods: Tandem solid phase extraction (SPE) was undertaken using a polyamide cartridge and a C18E cartridge in succession to enrich the trace diterpenoids. HPLC-ESI/QTOF/MS/MS was used to determine the fragmentation patterns of diterpenoids and to tentatively characterise their fragmentation pathways., Results: HPLC-ESI/QTOF/MS/MS detected a total of 14 diterpenoids, eight of which were identified by comparison with literature sources and six based on fragmentation analysis. Among the latter six, rhodojaponin VI-3-glucoside was tentatively identified as a new diterpenoid glycoside and rhodojaponin VII, rhodojaponin IV and rhodojaponin I were reported from R. molle for the first time., Conclusion: By qualitative research of diterpenoids in this plant by HPLC-ESI/QTOF/MS/MS, a reliable methodology for the analysis of these active constituents of R. molle was established for the first time., (Copyright © 2014 John Wiley & Sons, Ltd.)

Introduction: Homoflavonoids, characterised by one more carbon atom directly added to C6 -C3 -C6 backbone of flavonoids, are rich in the species of genus Ophioglossum. Up to now we have little knowledge about their MS fragmentation patterns. It is therefore necessary to investigate their MS fragmentation pathways so as to distinguish them from other types of flavonoids., Objective: To develop a rapid method for identifying homoflavonoids from Ophioglossum based on their characteristic MS fragmentation., Methods: Mass spectrometry fragmentation pathways and qualitative analysis of homoflavonoids in three ferns of Ophioglosssum were investigated by using high-performance liquid chromatography coupled with diode-array detection and electrospray ionisation tandem mass spectrometry (HPLC-DAD-ESI/MS(n) )., Results: The analyses of the MS(n) spectra of the homoflavonoids allowed us to classify them into two types according to their fragmentation characteristics. The type I homoflavonoids, with an attached additional carbon atom to the C-3 position of the C-ring, presented the initial competing loss of H2 O and CH2 O from their aglycone ions, compared to the initial removal of H2 O or CO in the case of the type II homoflavonoids, which bear the additional carbon atom at the C-2' site of the B-ring and forming ring D. The above characteristic fragmentations of homoflavonoids were quite different from those of other flavonoids, and were successfully applied to identify homoflavonoids in the crude extracts of three Ophioglossum species., Conclusion: The HPLC-DAD-ESI/MS(n) method obtained in the present study provided a powerful tool for identifying homoflavonoids from ferns in the genus Ophioglossum., (Copyright © 2013 John Wiley & Sons, Ltd.)

Introduction: Rheum palmatum is an important traditional Chinese medicine featuring anthraquinones with several activities. Generally, rhein, emodin, aloe-emodin, physcion and chrysophanol are used as chemical markers for the quality control of rhubarb products., Objective: To develop a simple protocol for the quantification of rhein, emodin, aloe-emodin, physcion and chrysophanol in R. palmatum collected at different developmental stages., Methods: (1) H-NMR spectra were measured on samples dissolved in acetone-d6 , quantification was carried out using the signals of H-4 of rhein (δH 8.36), H-7 of emodin (δH 6.68), CH2 OH of aloe-emodin (δH 4.81), OCH3 of physcion (δH 4.02) and CH3 of chrysophanol (δH 2.50), which were well separated from other signals. Quantitative analysis was based on the relative ratio of the intensity of each compound to the known amount of internal standard maleic acid., Results: The quantitative (1) H-NMR (qHNMR) method developed showed good precision, trueness, linearity, repeatability and stability for the quantification of rhein, emodin, aloe-emodin, physcion and chrysophanol. This method was applied successfully to explore the seasonal variations of the five major anthraquinones in R. palmatum, and provided quantitative results in reasonable agreement with those obtained by the HPLC-UV method., Conclusion: Compared with the conventional HPLC-based methods, the qHNMR analysis is rapid, reference-free and convenient with less sample pre-treatment. This technique should be a feasible choice for the quality control of R. palmatum., (Copyright © 2013 John Wiley & Sons, Ltd.)

Cytotoxic assay guided multistep separation on the dichloromethane extract of the roots of Euphorbia kansui resulted in the isolation of 10 ingenol-type diterpenoids (1-4 and 7-12), of which, 5-O-(2'E,4'E-decadienoyl)-20-O-acetylingenol (1) is a new compound, and two are jatrophane-type diterpenoids (13-14). Interconversion of two pairs of positional ester isomers (1-4) in aqueous alcoholic solution was observed, the transesterification mechanism of which was speculated and confirmed by acylation of 3 and 4 to 6 and 5, respectively. All the isolates and the two acyl derivatives (5 and 6) were evaluated in vitro for their cytotoxicities in Bel-7402, Bel-7402/5FU, BGC-823 and SGC-7901 cell lines. The 12 ingenol-type diterpenoids exhibited weak to moderate cytotoxicities, whereas the two jatrophane-type diterpenoids displayed no antiproliferative effects, which, however, may increase the antitumour efficacy of those ingenol-type diterpenoids. The structure--activity relationships were investigated by principal component analysis (PCA) of the pIC₅₀ (-logIC₅₀) values of the compounds tested and their calculated molecular descriptors. The pIC₅₀ values were highly correlated with most descriptors, especially the highest occupied molecular orbital energy (E(HOMO)), absolute hardness (η) and positively charged solvent accessible surface areas (P-ASA). As the values of E(HOMO) increase, η and P-ASA decrease, and the antiproliferative effects of these compounds increase., (Copyright © 2011 John Wiley & Sons, Ltd.)

Introduction: Desmodium styracifolium, with C-flavone glycosides as main pharmacological effective compounds, is a popular Chinese medicinal herb and has been used to treat urination disturbance, urolithiasis, edema and jaundice. However, few systematic methods have been reported on the quality control of this natural herb., Objective: To develop a method for control the quality of D. styracifolium by combining chromatographic fingerprints and major constituent quantification., Method: Separations were performed on an Ultimate XB-C-18 column by gradient elution using acetonitrile and 0.1% aqueous formic acid. Analytes were identified by HPLC coupled with electrospray ionisation mass spectrometry experiments., Results: Twenty common peaks in chromatographic fingerprints were first identified among 15 batches of D. styracifolium from various regions. On basis of this, a HPLC-PAD method was established to simultaneously quantify five major constituents, which was validated for limit of qualification, linearity and interday variation of precision and accuracy., Conclusion: The assay developed could be considered as a suitable quality control method of D. styracifolium., (Copyright © 2011 John Wiley & Sons, Ltd.)

A sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of metacavir and its two metabolites in rat plasma was developed and validated. Tinidazole was used as an internal standard and plasma samples were pretreated with one-step liquid-liquid extraction. In addition, these analytes were separated using an isocratic mobile phase on a reverse-phase C18 column and analyzed by MS in the selected reaction monitoring mode. The monitored precursor to product-ion transitions for metacavir, 2',3'-dideoxyguanosine, O-methylguanine and the internal standard were m/z 266.0 → 166.0, m/z 252.0 → 152.0, m/z 166.0 → 149.0 and m/z 248.0 → 202.0, respectively. The standard curves were found to be linear in the range of 1-1000 ng/mL for metacavir, 5-5000 ng/mL for 2',3'-dideoxyguanosine and 1-1000 ng/mL for O-methylguanine in rat plasma. The precision and accuracy for both within- and between-batch determination of all analytes ranged from 2.83 to 9.19% and from 95.86 to 111.27%, respectively. No significant matrix effect was observed. This developed method was successfully applied to an in vivo pharmacokinetic study after a single intravenous dose of 20 mg/kg metacavir in rats., (Copyright © 2011 John Wiley & Sons, Ltd.)

A high-performance liquid chromatography coupled with photodiode array detection and electrospray ionization tandem mass spectrometry (HPLC-PAD-ESI-MS(n)) method was developed to evaluate the quality of Hypericum japonicum through establishing chromatographic fingerprint and simultaneous determination of seven phenolic compounds. The analysis was achieved on an Ultimate XB-C(18) analytical column (250 mm x 4.6 mm i.d., 5 microm) using an aqueous solution of acetic acid (pH 3.8) and methanol as the mobile phase. Ten samples of H. japonicum from various habitats were investigated and the correlation coefficients of similarity were determined from the HPLC fingerprints. By using an online ESI-MS(n), 20 common peaks in chromatographic fingerprints were identified as phenols, including flavones and their glycosides, flavonones and their glucosides, flavanols, xanthones, phloroglucinols, phenyl propanoids and chromones. Based on the above study, seven phenols which are considered to be major constituents in H. japonicum, including 3,4-dihydroxybenzoic acid (1), taxfolin-7-O-alpha-L-rhamnoside (7), 7-dihydroxy-2-(1-methylpropyl)chromone-8-beta-D-glucoside (8), isoquercitrin (14), quercitrin (16), quercetin-7-O-alpha-L-rhamnoside (18) and quercetin (19) were quantified by the validated HPLC-PAD method. This developed method by combination of chromatographic fingerprint and quantification analysis could be applied to control the quality of H. japonicum., (Copyright (c) 2009 John Wiley & Sons, Ltd.)

Introduction: The leaves of Eriobotrya japonica are used for the treatment of diabetes mellitus, chronic bronchitis, coughs and skin diseases. No method is currently available, however, by which to assess the quality of the crude herb on the basis of the quantitative profile of the main bioactive triterpene acids present., Objective: To develop a simple and accurate HPLC-UV (photodiode array detection) method for the simultaneous quantification of seven triterpene acids in the leaves of E. japonica., Method: Separations were performed on an Ultimate XB-C18 column by gradient elution using methanol:formic acid. Analytes were identified by HPLC coupled with electrospray ionisation mass spectrometry experiments. The quantitative HPLC-UV method was validated for linearity, precision, accuracy, and limits of detection and quantification., Results: Calibration curves presented good linear regression (r > 0.9992) within test ranges. The precision and accuracy of the method were acceptable with overall intra-day and inter-day variations of 1.35-3.30 and 1.98-4.43%, respectively, and overall recoveries of 95.60-102.67% for the seven compounds analysed. The method was successfully applied to the quantification of seven triterpene acids in eleven samples of E. japonica collected from different provinces of China., Conclusion: The developed assay could be considered as a suitable quality control method for E. japonica.

Wogonin, one active ingredient extract from the radix of Scutellaria baicalensis Georgi, is known to possess a broad spectrum of pharmacological, medicinal and therapeutic properties, especially the anticancer activity studied recently. However, no extensive safety studies have been conducted to date. In this paper, the acute and sub-chronic toxicity of the agent were determined using albino mice and Sprague-Dawley rats as animal models. Histopathological examination and viscera parameter investigation were also carried out after autopsy. The LD(50) of wogonin administered by the intravenous injection was 286.15 mg/kg and the 95% confidence limit was 278.27-295.26 mg/kg. A long period of treatment with a high dose of wogonin (120 mg/kg) could induce heart injury in rats. These results provide a foundation for the further clinical investigation of this promising anticancer agent., ((c) 2008 John Wiley & Sons, Ltd.)

5-n-Butyl-4-{4-[2-(1H-tetrazole-5-yl)-1H-pyrrol-1-yl]phenylmethyl}-2,4-dihydro-2-(2,6-dichloridephenyl)-3H-1,2,4-triazol-3-one (1b), a new non-peptide angiotensin type 1 receptor antagonist, has been observed to play a positive role in the treatment of hypertension in preclinical tests. Rats were dosed with the drug, and the major metabolites in the bile were separated by gradient elution high-performance liquid chromatography. HPLC-diode array detection-mass spectrometry, HPLC-electrospray ionization MS/MS methods in negative ion mode and collision-induced dissociation were used to elucidate the structures of the major metabolites of 1b. One dihydroxylated 1b (M1), two monohydoxylated 1b (M2, M3) and one 1b monoglucuronide (M5) were found in male rat bile; however, three monohydoxylated 1b (M2, M3, M4) and one 1b monoglucuronide (M5) were found in female rat bile. These metabolites greatly differ in amount between male and female rat bile., (Copyright (c) 2007 John Wiley & Sons, Ltd.)