Limonoids and alkaloids from Tetradium austrosinense (Hand.-Mazz.) T.G.Hartley.

A pair of new enantiomeric indolopyridoquinazoline-type alkaloids, (+)-1,7S,8R- and (-)-1,7R,8S-trihydroxyrutaecarpine (3a and 3b), and a new limonoid-tyrosamine hybrid, austrosinin (8), along with six known alkaloids and limonoids, were isolated from the stems with leaves of Tetradium austrosinense. Their structures were elucidated on the basis of analysis of MS, NMR, ECD and time-dependent density functional theory-based electronic circular dichroism (TDDFT-ECD) calculations, as well as proposed biosynthetic pathway. An anti-inflammatory bioassay in vitro showed 8 had significant immunosuppressive effect against the production of pro-inflammatory cytokine TNF-α in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.

Self-assembling ferrimagnetic fluorescent micelles for bioimaging guided efficient magnetic hyperthermia therapy.

Multifunctional magnet-fluorescent nanocomposites are widely applied in biomedical applications. Incorporating biocompatible quantum dots with highly ferrimagnetic magnetic nanoparticles into one nanoplatform for achieving efficient magnetic hyperthermia therapy (MHT) is very important. Herein, we reported an amphiphilic block copolymer with a flowable hydrophobic chain to encapsulate highly ferrimagnetic magnetic nanoparticles and ZnS/InP quantum dots via a facile self-assembly method. The obtained ferrimagnetic fluorescent micelle (FMFM) exhibited a uniform diameter of about 180 nm. In stark contrast, larger aggregation (400 nm in diameter) inevitably occurred using common poly(D,L-lactide) (PLA)-based amphiphilic block copolymer with a rigid hydrophobic chain, which was readily cleared by the reticuloendothelial system (RES). The flowable FMFM exhibited long-term colloidal stability within one month and desired fluorescent stability within 84 h. Benefiting from the high ferrimagnetism, the FMFM revealed excellent magnetic heating effect and magnetic resonance imaging capability. With accurate manipulation under an external magnetic field, FMFM realized in vitro enhanced fluorescence imaging sensitivity and accumulation efficiency at the tumor region, achieving in vitro and vivo improved MHT efficacy.

AGI grade-guided chaiqin chengqi decoction treatment for predicted moderately severe and severe acute pancreatitis (CAP trial): study protocol of a randomised, double-blind, placebo-controlled, parallel-group, pragmatic clinical trial.

BACKGROUND: Acute pancreatitis (AP) is a common digestive disease with increased incidence globally but without internationally licenced pharmacological therapy. Moderately severe and severe acute pancreatitis (MSAP/SAP) contributes predominately for its morbidities and mortality and has been managed in West China Hospital for decades using the traditional Chinese medicinal formula chaiqin chengqi decoction (CQCQD). The current study tests whether the early administration of CQCQD will result in improved clinical outcomes in predicted MSAP/SAP patients. METHODS: This is a single-centre, randomised, controlled, double-blind pragmatic clinical trial. AP patients aged 18-75 admitted within 72 h of onset will be assessed at admission for enrolment. We excluded the predicted mild acute pancreatitis (Harmless Acute Pancreatitis Score > 2 at admission) and severe organ failure (Sequential Organ Failure Assessment [SOFA] score of respiratory, cardiovascular, or renal systems > 3) at admission. Eligible patients will be randomly allocated on a 1:1 basis to CQCQD or placebo control administration based on conventional therapy. The administration of CQCQD and placebo is guided by the Acute Gastrointestinal Injury grade-based algorithm. The primary outcome measure will be the duration of respiratory failure (SOFA score of respiratory system ≥ 2) within 28 days after onset. Secondary outcome measures include occurrence of new-onset any organ failure (SOFA score of respiratory, cardiovascular, or renal system ≥ 2) and new-onset persistent organ failure (organ failure lasts > 48 h), dynamic surrogate biochemical markers and clinical severity scores, gut-centred treatment modalities, local complications status, intensive care need and duration, surgical interventions, mortality, and length of hospital stay. Follow-up will be scheduled on 6, 12, and 26 weeks after enrolment to assess AP recurrence, local complications, the requirement for surgical interventions, all-cause mortality, and patient-reported outcomes. DISCUSSION: The results of this study will provide high-quality evidence to appraise the efficacy of CQCQD for the early management of AP patients. TRIAL REGISTRATION: Chictr.org.cn Registry ( ChiCTR2000034325 ). Registered on 2 July, 2020.

Scaling of the strange-metal scattering in unconventional superconductors.

Marked evolution of properties with minute changes in the doping level is a hallmark of the complex chemistry that governs copper oxide superconductivity as manifested in the celebrated superconducting domes and quantum criticality taking place at precise compositions1-4. The strange-metal state, in which the resistivity varies linearly with temperature, has emerged as a central feature in the normal state of copper oxide superconductors5-9. The ubiquity of this behaviour signals an intimate link between the scattering mechanism and superconductivity10-12. However, a clear quantitative picture of the correlation has been lacking. Here we report the observation of precise quantitative scaling laws among the superconducting transition temperature (Tc), the linear-in-T scattering coefficient (A1) and the doping level (x) in electron-doped copper oxide La2-xCexCuO4 (LCCO). High-resolution characterization of epitaxial composition-spread films, which encompass the entire overdoped range of LCCO, has enabled us to systematically map its structural and transport properties with unprecedented accuracy and with increments of Δx = 0.0015. We have uncovered the relations Tc ~ (xc - x)0.5 ~ (A1□)0.5, where xc is the critical doping in which superconductivity disappears and A1□ is the coefficient of the linear resistivity per CuO2 plane. The striking similarity of the Tc versus A1□ relation among copper oxides, iron-based and organic superconductors may be an indication of a common mechanism of the strange-metal behaviour and unconventional superconductivity in these systems.

Long-acting CoAl2O4 spinel catalyst developed on activated alumina pellets by facile synthesis to activate peroxymonosulfate: Controllable cobalt leaching and environmental adaptability.

A novel composite catalyst prepared by fixing cobalt aluminate (CoAl2O4) spinel on formed alumina carrier by impregnation-calcination route is reported, which can be used to efficiently activate peroxymonosulfate (PMS) to degrade p-nitrophenol (PNP). The internal laws of phase composition and preparation conditions are explored in detail, and the results show that the introduction of additional aluminum ions in the preparation process changes the coordination environment and the electronic state of cobalt ions, which leads to the transformation of spinel/inverted spinel in the composition, and further affects the activity and stability of the catalyst. The selected CoAl-Aaps-600 catalyst has high CoAl2O4 content, showing good cycle performance and low cobalt leaching, and has great catalytic degradation performance at different temperatures and a wide pH range. Most notably, a fixed bed reactor packed with 20 g of CoAl-Aaps-600 exhibits excellent capacity to continuously treat 60 L of PNP solution with acceptable PNP removal ratio and low cobalt leaching content. Sulfate radical and singlet oxygen are identified as the main reactive oxygen species produced in CoAl-Aaps-600/PMS system, and the reaction mechanism is reasonably inferred. This work provides a potential application material and process for the treatment of continuous organic wastewater.

Monoterpene indole alkaloids from Melodinus cochinchinensis (Lour.) Merr.

Melodicochinines A - D (1-4), four new monoterpene indole alkaloids (MIAs), along with 21 known ones, were isolated from the stems and twigs of Melodinus cochinchinensis. Their structures were elucidated on the basis of extensive spectroscopic analysis. A ubiquitin-rhodamine 110 assay showed that 11-methyloxytabersonine had potential inhibitory effect against ubiquitin-specific protease 7 (USP7).

Two distinct superconducting states controlled by orientations of local wrinkles in LiFeAs.

For iron-based superconductors, the phase diagrams under pressure or strain exhibit emergent phenomena between unconventional superconductivity and other electronic orders, varying in different systems. As a stoichiometric superconductor, LiFeAs has no structure phase transitions or entangled electronic states, which manifests an ideal platform to explore the pressure or strain effect on unconventional superconductivity. Here, we observe two types of superconducting states controlled by orientations of local wrinkles on the surface of LiFeAs. Using scanning tunneling microscopy/spectroscopy, we find type-I wrinkles enlarge the superconducting gaps and enhance the transition temperature, whereas type-II wrinkles significantly suppress the superconducting gaps. The vortices on wrinkles show a C2 symmetry, indicating the strain effects on the wrinkles. By statistics, we find that the two types of wrinkles are categorized by their orientations. Our results demonstrate that the local strain effect with different directions can tune the superconducting order parameter of LiFeAs very differently, suggesting that the band shifting induced by directional pressure may play an important role in iron-based superconductivity.

Acmoxanthones A-E, New Lavandulated Xanthones from Hypericum acmosepalum N. Robson.

Acmoxanthones A-E (1-5), five new lavandulylated xanthones, were isolated from the aerial parts of Hypericum acmosepalum, together with four known xanthones. Their structures with absolute configurations were elucidated on the basis of analysis of MS, NMR and chiroptical properties. A bioassay against high glucose-induced damage on human umbilical vein endothelial cells (HUVECs) showed ananixanthone (6) and osajaxanthone (7) had potential antioxidative damage activity with EC50 values of 10.5 µg/mL and 7.6 µg/mL, respectively, while 3-hydroxy-2,4-dimethoxyxanthone (8) exhibited cytotoxic effect on the damaged cells with IC50 values of 7.1 µg/mL.

Characteristics of nutrients removal under partial denitrification initiated by different initial nitrate concentration.

The partial denitrification (PD) is a very promising process developed in the last decade, to study the comprehensive influence of influent carbon to nitrogen (C/N) on the activated sludge system under PD, six sequencing batch reactors (SBRs) were operated in parallel at C/N of 2.75, 3.30, 4.13, 5.50, 8.25 and 16.50, the nitrogen removal, phosphorus removal and sludge settleability of PD were investigated. The results showed that PD was observed treating synthetic wastewater in all the six SBRs, and the nitrite accumulation rate (NAR) was highest at C/N of 5.50 (NAR of 82.30%). However, due to the alternate inhibition of NO2--N and free nitrous acid (FNA) produced by a limited carbon source, both the sludge settleability and phosphorus removal deteriorated. The average SVI at C/N of 8.25 was 130% lower than C/N of 3.30, and the average amount of PO43--P released at C/N of 16.5 was 189% higher than C/N of 2.75. Kinetic analysis showed that the denitrification kinetics of PD and complete denitrification were similar, and the nitrite accumulation was caused by the difference between nitrate reduction rate and nitrite reduction rate. Variations of on-line parameters (pH and ORP) revealed that nitrite accumulation could be indicated by judging the nitrate turning point and nitrite turning point on pH and ORP curves, which provided guidance for the setup of PD.

The Relationships between Leptin, Genotype, and Chinese Medicine Body Constitution for Obesity.

METHODS: The adults with body mass index (BMI) more than 27 kg/m2 were enrolled in the study. General personal information, physical condition, TCMBC, biochemical, and SNPs were collected for eligible subjects. The body constitution questionnaire (BCQ) was used to evaluate the relationships between TCMBC tendency, biochemical values, and obesity-related SNPs. RESULTS: Obesity patients tended to have a yin deficiency constitution (YinDC) (n = 33, 66.0%); however, TCMBC in combination is not uncommon (30 subjects with more than two TCMBC in combination). For biochemical profiles, leptin was higher among patients with yang deficiency constitution (YangDC) (YangDC versus non-YangDC: 29.7 ± 24.8 versus 15.9 ± 9.9, P=0.020) and YinDC (YinDC versus non-YinDC: 28.8 ± 23.5 versus 14.4 ± 9.6, P=0.020). The leptin level was highest among YangDC subjects. Higher leptin was found among subjects with three-combined TCMBC than balanced TCMBC subjects who were not inclined to any of three TCMBC. For obesity-related SNPs, the adrenergic receptor beta-3 (ADRB3) gene tended to be high expression among YangDC (YangDC versus non-YangDC: 89.7% versus 71.4%, P=0.091) and uncoupling protein 1 (UCP1) tended to be high expression among phlegm-stasis constitution (PSC) (PSC versus non-PSC: 37.9% versus 9.5%, P=0.052). CONCLUSIONS: The relationships between TCMBC, leptin, and SNPs present alternative viewpoints about TCMBC and could be used as a guide to treat obese patients.

Chaiqin chengqi decoction ameliorates acute pancreatitis in mice via inhibition of neuron activation-mediated acinar cell SP/NK1R signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Chaiqin chengqi decoction (CQCQD) and its derivatives have been widely used in China for the early management of patients with acute pancreatitis (AP). Numerous studies demonstrate the anti-inflammatory and anti-oxidative effects of CQCQD and derivatives, but whether these effects can be attributed to suppressing neurogenic inflammation, has never been studied. AIM OF THE STUDY: To investigate the effects of CQCQD on substance P (SP)-neurokinin 1 receptor (NK1R) based neurogenic inflammation in an experimental AP model. MATERIAL AND METHODS: For AP patients on admission, pain score was accessed by visual analog scale (VAS); the levels of serum SP and expressions of pancreatic SP and NK1R were also determined. For in vivo study, mice received 7 intraperitoneal injections of cerulein (50 µg/kg) at hourly intervals to induce AP, whilst controls received normal saline injections. In the treatment groups, CQCQD (10 g/kg, 200 µl) was intragastrically given at the third, fifth, and seventh of the cerulein injection or the NK1R antagonist CP96345 (5 mg/kg) was intraperitoneally injected 30 min before the first cerulein administration. The von Frey test was performed to evaluate pain behavior. Animals were sacrificed at 12 h from the first cerulein/saline injection for severity assessment. Pharmacology network analysis was used to identify active ingredients of CQCQD for AP and pain. In vitro, freshly isolated pancreatic acinar cells were pre-treated with CQCQD (5 mg/ml), CP96345 (1 µM), or selected active compounds of CQCQD (12.5, 25, and 50 µM) for 30 min, followed by SP incubation for another 30 min. RESULTS: The VAS score as well as the levels of serum SP and expressions of pancreatic SP-NK1R were up-regulated in moderately severe and severe patients compared with those with mild disease. CQCQD, but not CP96345, consistently and significantly ameliorated pain, pancreatic necrosis, and systemic inflammation in cerulein-induced AP as well as inhibited NK1R internalization of pancreatic acinar cells. These effects of CQCQD were associated with reduction of pancreatic SP-NK1R and neuron activity in pancreas, dorsal root ganglia, and spinal cord. Baicalin, emodin, and magnolol, the top 3 active components of CQCQD identified via pharmacology network analysis, suppressed NK1R internalization and NF-κB signal pathway activation in isolated pancreatic acinar cells. CONCLUSIONS: CQCQD ameliorated cerulein-induced AP and its associated pain via inhibiting neuron activation-mediated pancreatic acinar cell SP-NK1R signaling pathways and its active compounds baicalin, emodin, and magnolol contributed to this effect.

Fufang Xueshuantong alleviates diabetic retinopathy by activating the PPAR signalling pathway and complement and coagulation cascades.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Xueshuantong (FXST) is a traditional Chinese patent medicine composed of Panax notoginseng (Burkill) F.H.Chen (Araliaceae), Salvia miltiorrhiza Bunge (Lamiaceae), Astragalus propinquus Schischkin (Leguminosae), and Scrophularia ningpoensis Hemsl. (Scrophulariaceae). It has been widely used for the treatment of diabetic retinopathy (DR) and exerts a positive clinical therapeutic effect. AIM OF THE STUDY: The aim of this study was to observe the effect of FXST on diabetic rat retinas and investigate its pharmacological mechanism for improving DR. METHODS: The diabetic rat model was established by intraperitoneal injection of streptozotocin. The rats were divided into a normal group, diabetic group, and FXST group. The rats in the FXST group were treated with FXST by intragastric administration for 12 weeks while other rats were given the same volume of normal saline. The haemodynamic parameters of the central retinal artery in the rats were measured by ultrasound. Haematoxylin-eosin staining was utilised to observe the pathological structural changes in the retina. The apoptosis of retinal nerve cells was detected by terminal deoxynucleotidyl transferase dUTP nick end labelling. RNA sequencing was used to screen the differentially expressed genes (DEGs), and enrichment analyses were performed. The DEGs were validated through real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: The peak systolic velocity, end diastolic velocity, and mean velocity decreased while the resistance index and pulsatility index increased in the diabetic rat retinas. FXST also improved haemodynamics. In contrast with the diabetic group, FXST allayed the disorder and oedema of the retinal structure in addition to reversing the reductions in retinal thickness and retinal ganglion cell number. It also decreased the apoptosis index of retinal cells. A total of 1134 DEGs were identified by RNA sequencing in the FXST group compared to the diabetic group, including 814 upregulated genes and 320 downregulated genes. These genes were enriched in the complement and coagulation cascades as well as the peroxisome proliferator-activated receptor (PPAR) signalling pathway. Several DEGs, including PPAR gamma, perilipin 4, acyl-CoA dehydrogenase long chain, CD55 molecule, and plasminogen activator urokinase, were identified by qRT-PCR, and the results were consistent with the RNA sequencing data. CONCLUSIONS: FXST alleviates DR by improving the haemodynamics and morphological alterations of diabetic rat retinas, which are mediated by complement and coagulation cascades and the PPAR signalling pathway.

Polycyclic polyprenylated acylphloroglucinols from Hypericum choisianum.

Twenty-one polycyclic polyprenylated acylphloroglucinols, including three new compounds named as hyperichoisins A (3), B (14) and C (21), were isolated from the aerial parts of Hypericum choisianum. The structures of those new compounds were elucidated by analysis of mass, NMR data, and chiroptical properties. A bioassay showed that otogirinin B had significant inhibitory effect on cell proliferation of A549.

HuoXue JieDu formula improves diabetic retinopathy in rats by regulating microRNAs.

ETHNOPHARMACOLOGICAL RELEVANCE: HuoXue JieDu Formula (HXJDF) originates from classical formulas and was formed based on clinical experience. It is composed of Euonymus alatus (Thunb.) Siebold, Panax notoginseng (Burkill) F.H. Chen, the roots of Anguina kirilowii (Maxim.) Kuntze, and Coptis omeiensis (C. Chen) C.Y.Cheng. HXJDF prevents the deterioration of diabetic retinopathy. AIM OF THE STUDY: To evaluate the effects of HXJDF on diabetic retinopathy in rats and investigate the roles of miRNAs in the effects of HXJDF. MATERIALS AND METHODS: A single intraperitoneal injection of streptozotocin (STZ) (65 mg/kg) was used to induce diabetes in rats. Rats were divided into three groups: normal, diabetic, and diabetic + HXJDF. Rats were treated with HXJDF (15.4 g/kg) or water by oral gavage for twelve weeks. At the end of the treatment, rats were anaesthetized, and retinal haemodynamic changes were measured. Then, the retinas were removed and examined by haematoxylin and eosin (HE) staining and TUNEL assays. In addition, miRNA expression profiling was performed using miRNA microarrays and further validated by quantitative real-time PCR (qRT-PCR). RESULTS: Diabetes reduced peak systolic velocity (PSV), end-diastolic velocity (EDV), mean velocity (MV) and central retinal vein velocity (CRV) but increased the resistance index (RI) and pulsatility index (PI). In addition, in the diabetic group, retinal cell arrangement was disordered and loosely arranged, the retinal thickness and retinal ganglion cell (RGC) number decreased, and retinal cell apoptosis increased. In addition, 11 miRNAs were upregulated and 4 miRNAs were downregulated. After treatment, HXJDF improved retinal haemodynamics and morphologic changes, restored retinal thickness and RGC number and decreased retinal cell apoptosis. Furthermore, the changes in miRNA expression were significantly abolished by HXJDF. CONCLUSION: HXJDF may prevent DR by regulating the expression of miRNAs.

High-performance liquid chromatography-based fingerprint analysis with chemical pattern recognition for evaluation of Mahonia bealei (Fort.) Carr.

A simple and efficient high-performance liquid chromatography method combined with chemical pattern recognition was established for quality evaluation of Mahonia bealei (Fort.) Carr. A common pattern of 30 characteristic peaks was applied for similarity analysis, hierarchical cluster analysis, principal component analysis, and partial least squares discriminant analysis in the 37 batches of M. bealei (Fort.) Carr. to discriminate wild M. bealei (Fort.) Carr., cultivated M. bealei (Fort.) Carr., and its substitutes. The results showed that partial least squares discriminant analysis was the most effective method for discrimination. Eight characteristics peaks with higher variable importance in projection values were selected for pattern recognition model. A permutation test and 26 batches of testing set samples were performed to validate the model that was successfully established. All of the training and testing set samples were correctly classified into three clusters (wild M. bealei (Fort.) Carr., cultivated M. bealei (Fort.) Carr., and its substitutes) based on the selected chemical markers. Moreover, 26 batches of unknown samples were used to predict the accuracy of the established model with a discrimination accuracy of 100%. The obtained results indicated that the method showed great potential application for accurate evaluation and prediction of the quality of M. bealei (Fort.) Carr.

Polyprenylated acylphloroglucinols as deubiquitinating protease USP7 inhibitors from Hypericum hookerianum.

Hookerianones A - E (1-5), five new polyprenylated acylphloroglucinols (PPAPs), along with six known ones, were isolated from the aerial parts of Hypericum hookerianum. Their structures were elucidated by analyses of MS, NMR, chiroptical properties, biogenetic pathway, and/or single crystal X-ray diffraction. A ubiquitin-rhodamine 110 assay showed that furohyperforin and hypercalin C, two representative PPAPs in this plant, inhibited more than 90% USP7 at the concentration of 10 µM.

Cereblon harnesses Myc-dependent bioenergetics and activity of CD8+ T lymphocytes.

Immunomodulatory drugs, such as thalidomide and related compounds, potentiate T-cell effector functions. Cereblon (CRBN), a substrate receptor of the DDB1-cullin-RING E3 ubiquitin ligase complex, is the only molecular target for this drug class, where drug-induced, ubiquitin-dependent degradation of known "neosubstrates," such as IKAROS, AIOLOS, and CK1α, accounts for their biological activity. Far less clear is whether these CRBN E3 ligase-modulating compounds disrupt the endogenous functions of CRBN. We report that CRBN functions in a feedback loop that harnesses antigen-specific CD8+ T-cell effector responses. Specifically, Crbn deficiency in murine CD8+ T cells augments their central metabolism manifested as elevated bioenergetics, with supraphysiological levels of polyamines, secondary to enhanced glucose and amino acid transport, and with increased expression of metabolic enzymes, including the polyamine biosynthetic enzyme ornithine decarboxylase. Treatment with CRBN-modulating compounds similarly augments central metabolism of human CD8+ T cells. Notably, the metabolic control of CD8+ T cells by modulating compounds or Crbn deficiency is linked to increased and sustained expression of the master metabolic regulator MYC. Finally, Crbn-deficient T cells have augmented antigen-specific cytolytic activity vs melanoma tumor cells, ex vivo and in vivo, and drive accelerated and highly aggressive graft-versus-host disease. Therefore, CRBN functions to harness the activation of CD8+ T cells, and this phenotype can be exploited by treatment with drugs.

Alopecines A-E, five chloro-containing matrine-type alkaloids with immunosuppressive activities from the seeds of Sophora alopecuroides.

Alopecines A-E (1-5), five unusual matrine-type alkaloids featuring with an additional dichlorocyclopropane (1-3) or a di/tri-chloromethyl (4/5) attached on the D ring, were isolated from the seeds of Sophora alopecuroides. Their structures and absolute configurations were elucidated by extensive spectroscopic techniques, and X-ray diffraction analyses or time-dependent density functional theory-based electronic circular dichroism (TDDFT-ECD) calculations. Alkaloid 4 exhibited potent inhibitory effects on the proliferation of ConA-induced T lymphocytes or LPS-induced B cells with IC50 value of 3.98 or 3.74 µM, respectively.

Aqueous extraction from dachengqi formula granules reduces the severity of mouse acute pancreatitis via inhibition of pancreatic pro-inflammatory signalling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Dachengqi decoction (DCQD) belongs to a family of purgative herbal formulas widely used in China for the treatment of acute pancreatitis (AP). AP is a prevalent digestive disease currently without an effective pharmacological intervention. Formula granules have become the preferred method for delivery of herbal formulation in China given its benefit of potency retention, dosing precision and ease of use. The efficacy of DCQD formula granules (DFGs) in experimental AP models has not been investigated. AIM OF THE STUDY: To analyse and compare the differences in chemical composition of DFGs, with their aqueous extraction (AE) and chloroform extraction (CE) derivatives. To assess their efficacy on severity and targeted pancreatic pro-inflammatory signalling pathways in freshly isolated acinar cells and two models of experimental AP. MATERIAL AND METHODS: UPLC-Q-TOF-MS was used to analyse chemical components of DFGs and their extractions. Freshly isolated mouse pancreatic acinar cells were treated with taurolithocholic acid 3-sulphate disodium salt (TLCS, 500 µM) with or without DFGs, AE and CE. Apoptotic and necrotic cell death pathway activation was measured by caspase 3/7 (10 µl/mL) and propidium iodide (PI, 1 µM), respectively, using a fluorescent plate reader. Necrotic acinar cells were also counted by epifluorescence microscopy. Mice received either 7 intraperitoneal injections of caerulein (50 µg/kg) at hourly intervals or retrograde infusion of TLCS (3 mM, 50 µl) to induce AP (CER-AP and TLCS-AP, respectively). In CER-AP, mice received oral gavage of DFGs (2.1, 4.2 and 5.2 g/kg), AE (0.6, 1.2, and 2.4 g/kg) and CE (4, 9 and 17 mg/kg), or matched DFGs (1.8 g/kg) and AE (1 g/kg) for 3 times at 2-hourly intervals, or a single intraperitoneal injection of DCQD-related monomers rhein (20 mg/kg), narigeinine (25 mg/kg), and honokiol (5 mg/kg) begun at the 3rd injection of caerulein. In TLCS-AP, DFGs (4.2 g/kg) were given orally at 1, 3 and 5 h post-surgery. Disease severity and pancreatic pro-inflammatory markers were determined. RESULTS: The main effective anthraquinones and their glycosides, flavonoids and their glycosides, polyphenols and lignans were found in the DFGs. A higher proportion of polar components including glycosides attached to anthraquinones, phenols and flavonoids was found in AE. Conversely, lower polar components containing methoxy substituted flavonoids and anthraquinones were more abundant in CE. DFGs were given at 4.2 g/kg, a consistent reduction in the pancreatic histopathology score and severity indices was observed in both CER-AP and TLCS-AP. In vitro, AE significantly reduced both apoptotic and necrotic cell death pathway activation, while CE increased TLCS-induced acinar cell necrosis. In vivo, AE at dose of 1.2 g/kg consistently reduced pancreatic histopathological scores and myeloperoxidase in the CER-AP that were associated with suppressed expression of pro-inflammatory meditator mRNAs and proteins. CE increased lung myeloperoxidase and failed to protect against CER-AP in all dosages. AE was demonstrated to be more effective than DFGs in reducing pancreatic histopathological scores and myeloperoxidase. CONCLUSIONS: AE from DFGs alleviated the severity of mouse AP models via an inhibition of pancreatic pro-inflammatory signalling pathways. Efficacy of AE on experimental AP was more potent than its original DFGs and DCQD monomers.

In Vitro and In Vivo Anti-AChE and Antioxidative Effects of Schisandra chinensis Extract: A Potential Candidate for Alzheimer's Disease.

Acetylcholinesterase (AChE) inhibition and antioxidants are two common strategies for the treatment in the early stage of Alzheimer's Disease (AD). In this study, extracts from nine traditional Chinese medical (TCM) herbs were tested for anti-AChE activity by Ellman's microplate assay and cytotoxicity by CCK-8. Based on its excellent AChE inhibition effect and its lowest cytotoxicity, Schisandra chinensis (SC) extract was selected to do the mechanism research. SC extract protected pheochromocytoma (PC12) cells against H2O2-induced toxicity by improving the cell survival rate in a dose-dependent manner. And it also showed significant free radical (DPPH) scavenging activities, ferric reducing antioxidant power (FRAP), and 2,2'-Azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging. To confirm these results, the scopolamine-induced mice models were utilized in this study. Compared with the positive drug (piracetam), SC could also exhibit similar effects to alleviate the mice's cognitive deficits. Moreover, in the mice brain samples, the AChE activity and malondialdehyde (MDA) levels of SC-treatment group both showed a reverse as compared to model group. Taken together, these results all suggested that SC extract may be a potential therapeutic candidate for AD.