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Abstract: A new method of analysis of 11 phenols, including five bibenzyls, three phenanthrenes, and three fluorenones, using high-performance liquid chromatography (HPLC)–diode array detection (DAD) was described. The separation of 11 phenols was effected by RP-HPLC (Beckman Coulter™ ODS column, 5μm, 250mm×4.6mm) using linear gradient elution systems of acetonitrile–1‰ trifluoroacetic acid (TFA). Satisfactory separation of these compounds was obtained in less than 45min. The method was validated for linearity, repeatability, limits of detection (LOD) and limits of quantification (LOQ). Good results were obtained with respect to repeatability (relative standard deviation (RSD)<3.5%) and recovery (85.77–104.92%). The developed method was applied to the simultaneous determination of 11 phenols from totally 31 Dendrobium species (mainly of medicinal plants) as well as other four samples from the similar genera as Pholidota, Flickingeria and Bulbophyllum. The range of the total amounts of bibenzyl, phenanthrene and fluorenone were found to from trace: 4.00, not detected (nd): 0.42 and nd: 0.24μgmg−1, respectively. [Copyright &y& Elsevier]

Gentiana crassicaulis and G. straminea are alpine plants of Gentiana with important medicinal value and complex genetic backgrounds. In this study, the mitochondrial genomes (mtDNAs) of these two species were sequenced. The mtDNAs of G. crassicaulis and G. straminea are 368,808 and 410,086 bp long, respectively, 52 and 49 unique genes are annotated in the two species, and the gene arrangement varies widely. Compared to G. crassicaulis, G. straminea loses three effective genes, namely atp6, trnG-GCC and trnV-GAC. As a pseudogene, the atp6 gene of G. straminea is incomplete, which is rare in higher plants. We detected 1696 and 1858 pairs of long repeats and 213 SSRs and 250 SSs in the mtDNAs of G. crassicaulis and G. straminea, respectively. There are 392 SNPs and 18 InDels between the two genomes, and syntenic sequence and structural variation analysis show low collinearity between the two genomes. Chloroplast DNA transferring to mtDNA is observed in both species, and 46,511 and 55,043 bp transferred segments containing three tRNA genes are identified, respectively. Comparative analysis of mtDNAs of G. crassicaulis, G. straminea and four species of Gentianales determined 18 core genes, and there is no specific gene in G. crassicaulis and G. straminea. The phylogenetic tree based on mtDNAs places Gentianaceae in a branch of Gentianales. This study is the first to analyze the mtDNAs of Gentianaceae, which could provide information for analysis of the structure of mtDNAs of higher plants and phylogenetic research of Gentianaceae and Gentianales. [ABSTRACT FROM AUTHOR]

Background: Quality evaluation of multi-species resourced herb medicine (MSRHM) is a main problem for quality control of herb medicine. Current quality evaluation methodology lost consideration of species discrepancy. New quality evaluation strategy for MSRHM is in urgent need. Qinjiao, a representative MSRHM, originated from Gentiana macrophylla Pall., Gentiana straminea Maxim., Gentiana crassicaulis Duthie ex Burk. or Gentiana dahurica Fisch., has been used as an important herb medicine over 2000 years for expelling wind-dampness and relieving impediment pain. However, quality evaluation among species has never been revealed. The current work proposes an integrated quality evaluation strategy for MSRHM of Qinjiao, which may promote innovation of quality control of MSRHM. Methods: In this work, 58 batches of Qinjiao covering 4 species were collected. Genetic comparative analysis based on ITS2 sequence was conducted. Metabolomics analysis based on TOF–MS and NMR spectrum were carried out. Compounds underlying species differences were identified and their discrepancies among species were investigated by ANOVA analysis and multivariate analysis. Results: Four species of Qinjiao can be authenticated by ITS2 sequence comparation. Metabolomics analysis by TOF/MS and NMR revealed chemical discrepancies among species of Qinjiao. Maximum discrepancy was present between Gentiana crassicaulis Duthie ex Burk. and Gentiana dahurica Fisch. Chemical difference among species were tentative explored. For TOF–MS profiling, 28 constituents were tentative identified, 17 of which were further confirmed by standards. For 1H-NMR profiling, signals from 5 compounds were assigned. Contents discrepancies were investigated by ANOVA analysis. It seems that (seco)iridoids like loganic acid, gentiopicroside or swertiamarin were richer in specie of Gentiana crassicaulis Duthie ex Burk., while flavonoid (morroniside) and triterpenoids (roburic aicd, ursolic acid, oleanolic acid, β-sitosterone) were richer in specie of Gentiana dahurica Fisch. The current research demonstrates that metabolite profiling based on both UPLC/Q-TOF MS and 1H-NMR coupled with ITS2 sequence comparation can be a powerful tool for quality investigation of MSRHM of Qinjiao. Conclusions: A comprehensive quality evaluation strategy for MSRHM was proposed by integrating UPLC-Q-TOF–MS, NMR based metabolic analysis and ITS2 sequence genetic comparation. The proposed quality evaluation strategy shall promote innovation of quality control of traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

Endotoxic shock exhibits a considerably high mortality risk. It is defined as a systemic inflammatory response syndrome caused by a microbial infection. Radix Isatidis has anti-inflammatory, antiviral, and antipyretic effects and is used worldwide. This study investigated the antiendotoxin sepsis effects of an aqueous R. Isatidis extract (RIE) and explored the possible pharmacological molecular mechanisms. Male C57BL/6J mice were intravenously injected with 15 mg/kg lipopolysaccharide (LPS) to induce endotoxic shock. The results demonstrated that the survival rate of mice pretreated with RIE increased, and LPS-induced liver and lung damage were reduced by inhibiting inflammation. For elucidating detailed molecular mechanisms, we focused on LPS-induced transcription factors: nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3). Our results demonstrated that the protective effects of RIE were strongly dependent on IRF3-induced interferon-β, not on NF-κB-induced tumor necrosis factor-α and interleukin-1β. In addition, RIE suppressed the phosphorylation of IRF3, not NF-κB. In conclusion, this study revealed the antiendotoxic properties of RIE on LPS-induced sepsis and provided mechanistic evidence for the beneficial effects of RIE. [ABSTRACT FROM AUTHOR]

Abstract: Picrasma quassioides (D. Don) Benn. is a widely used traditional Chinese medicine for anti‐inflammation and antibiosis. Canthinone and β‐carboline alkaloids are the main characteristic constituents that possess diverse pharmacological effects, such as anti‐inflammatory and anti‐infectious properties. In this study, bioautography in thin‐layer chromatography indicated that the antiradical activity compound may be alkaloids. Then, a simple, fast, and efficient method was established for the separation and purification of two types of alkaloids from P. quassioides by mass‐spectrometry‐directed autopurification system. Eight alkaloids were isolated and purified in this one‐step methodology. Among them, five compounds (3, 95.1%, 58.8 mg; 4, 98.4%, 71.7 mg; 6, 97.8%, 365.4 mg; 7, 97.7%, 172.7 mg; 8, 98.2%, 180.3 mg) were obtained in large amounts with extremely high purities. Then, the antiradical activities of the isolates showed that 4‐methoxy‐5‐hydroxycanthin‐6‐one (6) exhibited obvious 1,1‐diphenyl‐2‐picryl‐hydrazyl free radical scavenging activity with an IC50 value of 84.037 μM. This study offers a new method for the preparation of targeted bioactive alkaloids in P. quassioides. This work also provides a reference for the separation of other targeted chemical components with potential activities from traditional Chinese herbal medicines. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Aerial parts of Peganum harmala Linn (APP) is used as traditional medical herb for treatment of forgetfulness in Uighur medicine in China. But, the active ingredients and underlying mechanisms are unclear. Aim of the study The present study was undertaken to investigate the improvement effects of extract and alkaloid fraction from APP on scopolamine-induced cognitive dysfunction and to elucidate their underlying mechanisms of action, and to support its folk use with scientific evidence, and lay a foundation for its further researches. Materials and methods The acetylcholinesterase (AChE) inhibitory activities of extract (EXT), alkaloid fraction (ALK) and flavonoid fraction (FLA) from APP were evaluated in normal male C57BL/6 mice. The anti-amnesic effects of EXT and ALK from APP were measured in scopolamine-induced memory deficits mice by the Morris water maze (MWM) tasks. The levels of biomarkers, enzyme activity and protein expression of cholinergic system were determined in brain tissues. Results The AChE activity was significantly decreased and the content of neurotransmitter acetylcholine (ACh) was significantly increased in normal mice cortex and hippocampus by treatment with donepezil at dosage of 8 mg/kg, EXT at dosages of 183, 550, 1650 mg/kg and ALK at dosages of 10, 30, 90 mg/kg ( P <0.05), and the AChE activity and the content of ACh were not significantly changed in cortex and hippocampus after treatment with FLA at dosages of 10, 30, 90 mg/kg ( P >0.05). In the MWM task, scopolamine-induced a decrease in both the swimming time within the target zone and the number of crossings where the platform had been placed were significantly reversed by treatment with EXT at dosages of 550, 1650 mg/kg and ALK at dosages of 30, 90 mg/kg ( P <0.05). Moreover, the activity and protein expression of AChE was significantly decreased and the content of neurotransmitter ACh was significantly increased in cerebral cortex of scopolamine-induced mice by treatment with EXT at dosages of 183, 550, 1650 mg/kg and ALK at dosages of 10, 30, 90 mg/kg ( P <0.05), compared with scopolamine-treated group. Conclusions EXT and ALK from APP exert beneficial effect on learning and memory processes in mice with scopolamine-induced memory impairment. APP is an effective traditional folk medicine and the ALK fraction is proved to be the main effective components for the treatment of forgetfulness. The ALK may be valuable source for lead compounds discovery and drug development for treatment of memory impairment such as in Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Borneol (BO) represents a global trade-driven spreading of ethnic medicine traceable to the classical age, and won its name specific to its original habitat "Borneo". BO shows broad spectral pharmacological effects, such as anti-inflammatory, analgesic, antipyretic, inducing resuscitation, and widely applied in the protection and treatment of cardiovascular and cerebrovascular diseases, used singly or mostly in compound formulae. Aim of the study: Three stereoscopic configuration forms of BO, l-borneol (LB), d-borneol (DB), and dl-borneol (synthetic, SB), are formulated in broad spectral application, yet their diverse pharmacodynamic and pharmacokinetic properties caused by configurations, and accurate assay and quality assessment are often overlooked. A systematic review and analysis of lumped studies and applications is necessary to clarify the relationship between configuration and its original plant, analysis method, activity and side effect BO in order to guarantee the efficacy and safety during their application. The public databases including PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure were referenced to summarize a comprehensive research and application data of BO published up to date. This review includes following sections: History and current status, Stereochemistry, Ethnopharmacology, and Quality assessment. In the section of history, the changes of the plant origins of the two isomeric forms of natural BO were described respectively, and the methods for synthetic racemate SB were also included. The section of stereochemistry deals with the stereoscopic structures, physical/chemical property, optical rotation of the three forms of BO, as well as the main related substances like isoborneol, obtained in SB via chemical transformation of camphor and turpentine oil. In the section of Ethnopharmacology, pharmacological activities and pharmacokinetics of different forms of BO were discussed. BO is usually used as an "adjuvant", by enhancing the permeability of the blood-brain barrier and intervene the ADME/T pathways of the other ingredients in the same formulation. In the section of quality assessment, the analytical methods, including chromatography, especially GC, and spectroscopy were addressed on the chiral separation of the coexisting enantiomers. This overview systematically summarized three forms of BO in terms of history, stereochemistry, ethnopharmacology, and quality assessment, which, hopefully, can provide valuable information and strategy for more reasonable application and development of the globally reputed ethnic medicine borneol with characteristics in stereochemistry. [Display omitted] • Borneol (BO) represents an epic ethnodrug denominated from its habitat Borneo. • Natural (d-/l-) and synthetic (dl -) forms of BO are arbitrarily substituted in use. • Diverse biological and transdermal activities are attributed to their chirality. • BO significantly impacts on the PK/PD behaviors of its combined ingredients. • Efficient chiral separation of BO and its related substances needs to be advanced. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Gentiopicroside (GPS), one of iridoid glucoside representatives, is the most potential active component in Gentiana rigescens Franch. ex Hemsl and Gentiana macrophylla Pall. These two herbs have been used to treat jaundice and other hepatic and billiary diseases in traditional Chinese medicine for thousands of years. Aim of the study This study aimed to investigate the protective effects and mechanisms of GPS on α-naphthylisothiocyanate (ANIT) induced cholestatic liver injury in mice. Materials and methods Mice were treated with GPS (130 mg/kg, ig) for 5 consecutive days. On the third day, mice were given a single dose of Alpha-naphthylisothiocyanate (75 mg/kg, ig). Serum biochemical markers and individual bile acids in serum, liver, urine and feces were measured at different time points after ANIT administration. The expression of hepatic bile acid synthesis, uptake and transporter genes as well as ileum bile acid transporter genes were assayed. Results In this study, ANIT exposure resulted in serious cholestasis with liver injury, which was demonstrated by dramatically increased serum levels of ALT, ALP, TBA and TBIL along with TCA CA, MCAs and TMCAs accumulation in both liver and serum. Furthermore, ANIT significantly decreased bile acid synthesis related gene expressions, and increased expression of bile acid transporters in liver. Continuous treatment with GPS attenuated ANIT-induced acute cholestasis as well as liver injury and correct the dyshomeostasis of bile acids induced by ANIT. Our data showed that GPS significantly upregulated the hepatic mRNA levels of synthesis enzymes ( Cyp8b1 and Cyp27a1) and transporters ( Mrp4 Mdr1 and Ost-β ) as well as ileal bile acid circulation mediators ( Asbt and Fgf15) , accompanied by serum and hepatic bile acid levels decrease and further urinary and fecal bile acid levels increase. Conclusion GPS can change bile acids metabolism which highlights its importance in mitigating cholestasis, resulting in the marked decrease of intracellular bile acid pool back toward basal levels. And the protective mechanism was associated with regulation of bile acids-related transporters, but the potential mechanism warrants further investigation. [ABSTRACT FROM AUTHOR]

The methanolic extract and its subfractions from red peony root, the dried roots of Paeonia lactiflora Pallas showed potent antiallergic effects, as inhibition of immunoglobulin E (IgE)-mediated degranulation in rat basophil leukemia (RBL)-2H3 cells. Bioassay-guided fractionation led to the isolation of 16 monoterpene derivatives, including 3 new compounds, paeoniflorol ( 1 ), 4′-hydroxypaeoniflorigenone ( 2 ) and 4- epi -albiflorin ( 3 ), together with 13 known ones ( 4–16 ). The chemical structures of the new compounds were elucidated on the basis of spectroscopic and chemical evidences. Among the isolated monoterpene derivatives, nine compounds showed potent anti-allergic effects and compound 1 was the most effective. A primary structure-activity relationship of monoterpene derivatives was discussed. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Dendrobium aurantiacum var. denneanumis widespread in southern China, locally known as “Shihu”, “Huangcao” or “Fengdou”, has long been used in traditional Chinese medicine for antipyretic, immunomodulatory, anti-aging effects and eye benefiting. Aim of this study To investigate the effects of gigantol extracted from the stem of D. aurantiacum var. denneanum on the formation of galactose-induced cataractogenesis and the potential mechanisms underlying these effects. Materials and methods Cataract lens models were induced by d -galactose both in vitro and in vivo . The transparency of the rat lenses in vitro and in vivo was observed with an anatomical microscope and a slit lamp microscope. The differential protein and action targets of gigantol were determined and compared among the control group, model group, and gigantol group using two-dimensional electrophoresis and mass spectrometry (MS). Enzyme kinetics was used to show the ability of gigantol to respress aldose reductase (AR) and inducible nitric oxide synthase (iNOS). Quantitative real-time PCR (RT-qPCR). was used to detect repression of the expression of AR and iNOS genes. Molecular docking and dynamic simulation were used to predict the interaction points and combination patterns between gigantol, AR, and iNOS. Results Gigantol was found to prevent galactose-induced damage to the rat lenses both in vitro and in vivo , to delay lens turbidity, and to keep the lenses transparent. Differential proteomes, MS, and RT-qPCR showed AR and iNOS to be the target proteins of gigantol. Gigantol reduced the galactose-induced AR and iNOS mRNA expression by 51.2% and 60.9%, respectively. The IC50 of gigantol for inhibition of AR and iNOS activities were 65.67 μg/mL and 8.768 μg/mL, respectively. Gigantol–AR binding sites were Trp111, His110, Tyr48, and Trp20, and gigantol–iNOS binding sites were Ile195 and Gln257. The main forms of interaction were hydrophobic forces, hydrogen bonds, and van der Waals forces. Conclusion Gigantol extracted from D. aurantiacum var. denneanum was found to inhibit galactose-induced formation of cataracts through repression of the gene expression and activity of AR and iNOS. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Eucommiae cortex (EC), the bark of Eucommia ulmoides Oliv., has been traditionally used to treat many diseases in China for more than 2000 years. The pharmacological effects are primarily attributed to the presence of lignans, iridoids and phenolics, which are main active ingredients in EC. Aim of the study First, to investigate the active ingredients that can be absorbed into the rat plasma according to which ingredients exhibit significant correlation of drug concentration–time curve. Second, to establish an efficient ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method for simultaneous determination of ingredients absorbed in rat plasma. Finally, to investigate gender effect on the pharmacokinetics of the ingredients absorbed in male and female rats plasma after oral administration with EC extract. Materials and methods 18 ingredients from EC were detected by UPLC-MS/MS, 9 out of 18 ingredients were absorbed into rat plasma. And 5 ingredients exhibit significant correlation of drug concentration–time curve. They were pinoresinol di-O- β -d-glucopyranoside (PDG), geniposide (GE), geniposidic acid (GA), aucubin (AN) and chlorogenic acid (CA). The analytes were extracted from rat plasma via a simple protein precipitation procedure and osalmid was used as the internal standard. Chromatographic separation was achieved on a Waters ACQUITY HSS T3 column (2.1 mm×100 mm, 1.8 μm) using a gradient elution program with acetonitrile and 0.1% formic acid water as the mobile phase, with a flow rate of 0.3 mL min −1 . The detection was performed on a triple-quadrupole tandem mass spectrometer by multiple reactions monitoring (MRM) mode in a positive ion mode via electrospray ionization (ESI). The transition monitored were / z 683.00[M+H] + →235.10 for PDG, / z 389.00[M+H] + →208.80 for GE, m / z 375.00[M+H] + →194.79 for GA, m / z 364.00[M+NH 4 ] + →148.81 for AN, m / z 355.10[M+H] + →162.84 for CA and m / z 230.03[M+H] + →120.77 for internal standard. Results The developed method showed good linearity over a wide concentration range, the lower limits of quantification and higher accuracy and precision for determination of the 5 analytes. Then the method was applied to study the pharmacokinetics in rats, and the results indicated that there were significant differences in pharmacokinetic parameters of the analytes between the male and female rats, and absorptions of these analytes in male group were all significantly higher than those in female group. Conclusion This study established an efficient, sensitive and selective UPLC-MS/MS method for simultaneous determination of the five ingredients in rat plasma, and it could be successfully applied to the comparative pharmacokinetic studies in male and female rats after oral administration with EC extract. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Seeds of Peganum harmala Linn are traditionally used as folk medical herb in Uighur medicine in China to treat disorders of hemiplegia and amnesia. Previously studies have proved that dominating alkaloids in P. harmala show significant inhibitory activities on the cholinesterase. Aim of the study The aim of the present study is to isolate trace ingredients from seeds of P. harmala and evaluate its inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Materials and methods For sake of screening effective cholinesterase inhibitors, trace compounds were isolated from seeds of P. harmala through a bioassay-guided fractionation and their structures were determined via detailed spectral analysis. The inhibitory activities on AChE and BChE were assessed using an improved Ellman method by UPLC-ESI-MS/MS to determine the common final product choline. Results The activity-guided fractionation led to the isolation of two new alkaloids 2-aldehyde-tetrahydroharmine ( 10 ), 2-carboxyl-3,4-dihydroquinazoline ( 19 ), one syringin structure analog 1-O- β - D -xylopyranose sinapyl alcohol ( 22) , and along with 19 known compounds. Compounds acetylnorharmine ( 6 ), harmic acid methy ester ( 7 ), harmine N -oxide ( 13 ), 6-methoxyindoline ( 14 ), syringin ( 21 ) were first found from genus Peganum and compounds 3-hydroxylated harmine ( 4 ), 1-hydroxy-7-methoxy- β -carboline ( 5 ) were new natural products. The results showed that the 2-aldehyde-tetrahydroharmine ( 10 ) has a potential inbibitive effect on both AChE and BChE with IC 50 values of 12.35±0.24 and 5.51±0.33 µM, respectively. Deoxyvasicine ( 15 ) and vasicine ( 16 ) showed the strongest BChE inhibitory activity with IC 50 values of 0.04±0.01 and 0.1±0.01 µM. The analysis of the structure-activity relationship indicated that the saturation of pyridine ring and the presence of substitution at indole ring, C-1, C-3, C-7 and N-2, for β-carbolines, were essential for effective inhibition of both AChE and BChE and the five-membered ring between C-2 and N-3 as well as the substituent groups sited at C-4 and C-9, for quinazolines, were important to both the AChE/BChE-inhibitory activity. Conclusions Bioassay-guided fractionation has led to the isolation of AChE and BChE inhibitors from the seeds of P. harmala . These results are in agreement with the traditional uses of the seeds of P. harmala . [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Diosbulbin B (DB) is the main hepatotoxic compound distributed in Dioscorea bulbifera L., which is widely used for the treatment of cancer and thyroid disorders in Asia. Scutellarin (SC) is the main compound in medicinal herb Scutellaria barbata D. Don, which is usually combined with Dioscorea bulbifera used for cancer therapy in clinic. Aim of the study This study aims to investigate the protection of SC against the liver injury induced by DB and its engaged mechanism. In addition, the anti-tumor effect of DB and SC is further observed in vivo . Materials and methods The protection of SC against DB-induced liver injury was evaluated by detecting serum alanine/aspartate aminotransferases (ALT/AST) and alkaline phosphatase (ALP) activities, and further liver histological observation. The inflammatory response was assessed by detecting liver myeloperoxidase (MPO) activity, and serum levels of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interferon-γ (IFN-γ). Western-blot analysis was used to detect the protein expression. The oxidative liver injury was evaluated by detecting liver malondialdehyde (MDA) and glutathione (GSH) contents, and glutathione peroxidase (GPx) enzymatic activity. In vivo anti-tumor activity was analyzed in S180 tumor-bearing mice. Results SC significantly decreased the increased serum ALT/AST, and ALP activities induced by DB. Liver histological observation evidenced the protection of SC against DB-induced liver injury. SC obviously reduced the increased liver MPO activity and the number of MPO-positive staining cells induced by DB. SC also reversed the decreased expression of inhibitor of κB (IκB) and the translocation of nuclear factor κB (NF-κB) p65 from cytoplasm to nucleus induced by DB. In addition, SC significantly abrogated the increased serum levels of TNF-α, IL-6, and IFN-γ induced by DB. SC decreased the increased liver MDA content induced by DB significantly, and it also increased liver GSH level. The decreased GPx protein expression and its enzymatic activity induced by DB were both obviously reversed after SC treatment. The results in S180 tumor-bearing mice showed that SC combined with DB significantly inhibited tumor growth in vivo . Conclusions Our results demonstrate that SC prevents DB-induced liver injury by attenuating NF-κB-mediated hepatic inflammation and ameliorating liver oxidative stress injury. Meanwhile, DB plus SC has significant anti-tumor activity in vivo . This study indicates the potential combination of DB with SC for the treatment of cancer in clinic. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Aerial parts of Peganum harmala Linn (APP) is used as traditional medical herb in Uighur medicine in China, and it is traditionally used for treatment of cough and asthma.The aim of the present study is to evaluate the antitussive, expectorant and bronchodilating effects of extract and fractions (alkaloids and flavonoids) from APP, and to support its folk use with scientific evidence, and lay a foundation for its further researches. Materials and methods APP was extracted with 50% ethanol by reflux, extracts were concentrated in vacuum to afford total extract of APP (EXT). EXT was separated to provide alkaloid fraction (ALK) and flavonoid fraction (FLA) by macroporous resin. Antitussive evaluations were carried out with cough models in mice and guinea pigs induced by ammonia liquor, capsaicin, and citric acid. Phenol red secretion experiments in mice were performed to evaluate the expectorant activity. Bronchodilating activities were evaluated with a bronchoconstrictive challenge induced by acetylcholine chloride and histamine in guinea pigs. Results In all the three antitussive tests, the EXT and ALK could significantly inhibit the frequency of cough, and prolong the cough latent period in animals. High dose of EXT (1650 mg/kg) and ALK (90 mg/kg) in mice and in guinea pigs created therapeutic activities as good as that of codeine phosphate (30 mg/kg). EXT could significantly increase phenol red secretion in mice for 0.64, 1.08 and 1.29 fold averagely at dosages of 183, 550, and 1650 mg/kg, ALK for 0.63, 0.96, 1.06 fold averagely at dosages of 10, 30, and 90 mg/kg, and ammonium chloride (1500 mg/kg, standard expectorant drug) for 0.97 fold, comparing with control group. Aminophylline could dramatically prolong the preconvulsive time for 162.28% in guinea pigs, EXT for 67.34%, 101.96% and 138.00% at dosages of 183, 550, and 1650 mg/kg, ALK for 55.47%, 97.74% and 126.77% at dosages of 10, 30, and 90 mg/kg, and FLA for 84.69%, 95.94% and 154.52% at dosages of 10, 30, and 90 mg/kg, comparing with pretreatment. Conclusions APP is an effective traditional folk medicine for the treatment of cough with potent antitussive, expectorant and bronchodilating activities. The alkaloid fraction is proved to be the most effective components of APP. The alkaloids from APP may be valuable lead compounds for drug development of respiratory diseases. [ABSTRACT FROM AUTHOR]

The phytochemical investigation of natural products of Gynura divaricata led to the isolation of eleven caffeoylquinic acid derivatives. They were characterized by spectrometric methods as 5- O -caffeoylquinic acid ( 1 ), 5- O - p -coumaroylquinic acid ( 2 ), 5- O -feruloylquinic acid ( 3 ), methyl 5- O -caffeoylquinate ( 4 ), 3,4-dicaffeoylquinic acid ( 5 ), 3,5-dicaffeoylquinic acid ( 6 ), 4,5-dicaffeoylquinic acid ( 7 ), methyl 3,4-dicaffeoylquinate ( 8 ), methyl 3,5-dicaffeoylquinate ( 9 ), methyl 4,5-dicaffeoylquinate ( 10 ) and ethyl 4,5-dicaffeoylquinate ( 11 ). The individual compounds were screened for the inhibition of yeast α-glucosidase and Protein Tyrosine Phosphatase 1B (PTP1B) using in vitro assays. Among the isolated compounds, 3,4-dicaffeoylquinic acid ( 5 ), 4,5-dicaffeoylquinic acid ( 7 ), methyl 3,4-dicaffeoylquinate ( 8 ) and methyl 4,5-dicaffeoylquinate ( 10 ) exhibited significant inhibitory activities against α-glucosidase. In addition, 5- O - p -coumaroylquinic acid ( 2 ), 3,5-dicaffeoylquinic acid ( 6 ) and 4,5-dicaffeoylquinic acid ( 7 ) had considerable inhibitory effect against PTP1B. Based on these findings, the caffeoylquinic acid derivatives were deduced to be potentially responsible for the anti-diabetic activity of G. divaricata . The preliminary structure–activity relationship study suggests that the number and positioning of caffeoyl groups in the quinic acid derivatives are important for both α-glucosidase and PTP1B inhibitory potency. Moreover, the corresponding methyl esters of some dicaffeoylquinic acids have enhanced inhibitory activity against yeast α-glucosidase. [ABSTRACT FROM AUTHOR]

Dioscorea bulbifera L., a commonly used medicinal plant in China, is reported to induce hepatotoxicity. The present study is undertaken to investigate the hepatotoxicity induced by diosbulbin B (DB), a diterpene lactone isolated from D. bulbifera L., and to further explore its underlying mechanism. DB was administered to mice at the doses of 0, 16, 32, and 64 mg/kg once daily for 12 consecutive days. Liver injury induced by DB was evidenced by the increased activity of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Liver histological evaluation showed that the mice treated with DB exhibited liver damage with the swelling of hepatocytes. Further results showed that the amount of malondialdehyde (MDA) in the liver was increased in mice treated with DB, while the glutathione amount and the enzymatic activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST), copper/zinc–superoxide dismutase (CuZn-SOD), manganese-SOD (Mn-SOD), and catalase (CAT) were all decreased. DB also decreased the gene expression of CuZn-SOD and CAT. Taken together, our results indicate that oral administration of DB for 12 consecutive days can lead to the oxidative stress liver injury in mice. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Erycibe obtusifolia and Erycibe schmidtii, which belong to the same genus as Erycibe, are widely used in traditional medicine for the treatment of joint pain and rheumatoid arthritis (RA). Porana sinensis has become a widely used substitute for Erycibe obtusifolia and Erycibe schmidtii as they have declined in the wild. In the present work, the content of the main active components, the acute toxicity, the anti-nociceptive and anti-inflammatory activities of Porana sinensis, Erycibe obtusifolia and Erycibe schmidtii were compared, and the mechanisms of anti-nociceptive and anti-inflammatory activities were discussed. Materials and methods: A quantitative HPLC (high performance liquid chromatography) method was first developed to compare the content of the main active components (scopoletin, scopolin and chlorogenic acid). The anti-inflammatory and anti-nociceptive activities of 40% ethanolic extracts of the three plants were compared using the models of xylene-induced ear edema, formalin-induced inflammation, carrageenan-induced air pouch inflammation, acetic acid-induced writhing and formalin-induced nociception. The acute toxicity of the 40% ethanolic extracts of the three plants was studied. Results: The assay suggested a large content of scopoletin, scopolin and chlorogenic acid in the three plants. The 40% ethanolic extracts of the three plants were almost non-toxic at the dose of 5g/kg and all of them showed significant anti-inflammatory effects in the tests of xylene-induced ear edema and formalin-induced inflammation. In the carrageenan-induced air pouch inflammation test, the synthesis of PGE2 was significantly inhibited by all the extracts. They significantly inhibited the number of contortions induced by acetic acid and the second phase of the formalin-induced licking response. Naloxone was not able to reverse the analgesic effect of these extracts. Conclusion: The study identifies the similarity of the three plants in their main active components as well as acute toxicity, anti-nociceptive and anti-inflammatory activities. It supports the use of Porana sinensis as a suitable substitute, but further studies are needed to confirm this. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Diosbulbin B (DB) is the main constituent of furano-norditerpenes in Dioscorea bulbifera Linn., which is widely distributed in China and was usually used as a remedy for sore throat, struma and tumor. Owing to its potential antitumor activity, DB has been considered as a promising candidate for drug development. Aim of the study: To study the pharmacokinetic properties and excretion of DB in rats by a sensitive UPLC–MS/MS method. Absolute bioavailability and gender-related pharmacokinetic properties, as well as excretion fractions of DB in urine and feces after oral and intravenous administrations would be addressed for the first time. Materials and methods: Sprague–Dawley rats were administrated orally (32mg/kg) and intravenously (0.5mg/kg) of DB, respectively. The concentrations of DB in rat plasma were determined by a sensitive and well-validated LC–MS/MS method. Main pharmacokinetic parameters including area under the plasma concentration–time curve (AUC), elimination half time (t 1/2), mean residence time (MRT), apparent volume of distribution (V d) and clearance rate (CL) were estimated using a non-compartmental pharmacokinetics data analysis software. Urine and feces of rats were collected within 48h after oral administration (32mg/kg) and detected by UPLC–MS/MS and HPLC, respectively. Results: The standard curves of DB in rat plasma and urine showed good linearity in the concentration range of 1.0–515ng/mL in the method, with acceptable selectivity, precisions, recoveries, and stability. The oral absolute bioavailability of DB in female rats was 2.0%, significantly higher than that of males (0.3%) (p<0.05). Female rats demonstrated longer t 1/2 and MRT (p<0.01), bigger V d and higher CL (p<0.05) than males after intravenous administration of DB. Bigger but no significant difference in excretion fractions of urine and feces in female rats were observed, comparing to those in males. Conclusion: A simple and sensitive UPLC–MS/MS method was developed to determine the pharmacokinetic profiles of DB in rats, as well as the excretion in rat urine. Gender exerted a significant influence on the pharmacokinetics and bioavailability of DB in rats. Female rats showed significantly better absorption of DB than males after oral administration. [Copyright &y& Elsevier]

Abstract: Two new furanoeremophilanes, 1α, 6α-epoxy-9-oxo-10β-hydroxyl-furanoeremophilane (1), and 9-oxo-1α, 6β, 10β-trihydroxy-furanoeremophilane (2) were isolated from Senecio nemorensis. Their structures were elucidated by spectroscopic methods and X-ray crystallography. This is the first report of the isolation of the C1–C6 oxygen bridge of furanoeremophilane. Their cytotoxic effects on BEL7402 and NF-KB cell lines were tested. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: To evaluate the hepatoprotective effect of the root and rhizome of Rhubarb (Rhei Radix et Rhizoma) against α-naphthylisothiocyanate (ANIT)-induced liver injury using metabolic profile of bile acids (BAs) along with biochemical parameters and histological alterations. Materials and methods: Ultra-performance liquid chromatography coupled with quadrupole mass spectrometry (UPLC-MS) was applied to determinate the concentration of BAs, which was followed by multivariate statistical analysis of Principal Component Analysis (PCA) and Partial Least Squares Discriminate Analysis (PLS-DA). Results: Based on PCA results, three groups (Vehicle group, ANIT group and RhO+ANIT group) were clearly distinguished. Tauro-cholic acid (TCA), tauro-hyodesoxycholic acid (THDCA), glyco-cholic acid (GCA), and glyco-chenodeoxycholic acid (GCDCA) were proved to be the most important markers corresponding to ANIT-induced liver injury and protection provided by Rhubarb, which is further confirmed by PLS-DA. A correlation was found between the foregoing BAs and biochemical parameters including serum aspartate aminotransferase (ALT) and aspartate aminotransferase (AST), which confirmed that TCA, THDAC, GCA, and GCDCA could be considered as sensitive biomarkers. Conclusion: The variance of the BAs contents can be used to evaluate ANIT-induced hepatotoxicity caused by ANIT and protective effects of Rhubarb. It also lays the foundation for the further research on the mechanisms of cholestasis as well as the therapeutic effect of Rhubarb. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: The herbal analgesic gel Tong-Luo-San-Jie (TLSJ) and its modifications are used in traditional Chinese medicine to manage cancer pain. However, its mechanisms are still unknown. Aim of the study: To investigate the effects and mechanisms of TLSJ gel on bone cancer pain in a rat model. Materials and methods: A bone cancer pain rat model was established by inoculating Walker 256 rat carcinoma cells directly into the right tibial medullary cavity of Sprague–Dawley rats (150–170g); Phosphate buffered saline (PBS) tibial inoculation was used as control. Cancer-bearing rats were treated twice a day with external TLSJ gel (0.5g/cm2/day) or inert gel control for 21 day (n=10/group). Behavioral tests such as mechanical threshold and paw withdrawal latency (PWL) were carried out. Osteoclastic activities were determined and carboxyterminal pyridinoline cross-linked type I collagen telopeptides (ICTP) and bone-specific alkaline phosphatase (BAP) concentrations were detected with ELISA after treatment. Adverse effects were monitored, and biochemical and histological tests were performed in naïve rats treated with local TLSJ gel for six weeks. Results: TLSJ treatment significantly restored bone cancer-induced decrease of PWL and mechanical threshold compared to inert gel. It also decreased the level of blood serum ICTP and BAP and inhibited osteoclast activities. No adverse effects or abnormal biochemical and histological changes were detected after TLSJ treatment. Conclusion: The present study shows that TLSJ significantly inhibits bone cancer-induced thermal and mechanical sensitization. It suggests that the gel may be useful in managing cancer pain and that it may act by inhibiting osteoclastic activity. [Copyright &y& Elsevier]

Abstract: Harpagide (1) and harpagoside (2) are two iridoid glycosides existing in many medicinal plants. Although they are believed to be the main bioactive compounds related to the anti-inflammatory efficacy of these plants, the mechanisms of their anti-inflammatory activities remain unclear. The results of our present study showed that 1 and 2 had no effects on inhibitions of cyclooxygenase (COX)-1/2 enzyme activity, tumor necrosis factor-α (TNF-α) release, and nitric oxide (NO) production in vitro. However, the hydrolyzed products of 1 and 2 with β-glucosidase treatment showed a significant inhibitory effect on COX-2 activity at 2.5–100μM in a concentration-dependent manner. Our further study revealed that the hydrolyzed 2 product was structurally the same as the hydrolyzed 1 product (H-harpagide (3)). The structure of 3 was 2-(formylmethyl)-2,3,5-trihydroxy-5-methylcyclopentane carbaldehyde, with a backbone similar to prostaglandins and COX-2 inhibitors such as celecoxib. All of them have a pentatomic ring with two adjacent side chains. The result of molecular modeling and docking study showed that 3 could bind to the COX-2 active domain well through hydrophobic and hydrogen-bonding interactions, whereas 1 and 2 could not, implying that the hydrolysis of the glycosidic bond of 1 and 2 is a pre-requisite step for their COX-2 inhibitory activity. [Copyright &y& Elsevier]

Sweroside, an iridoid derived from Traditional Chinese Medicine, is an active component in Swertia pseudochinensis Hara. Swertia pseudochinensis Hara is first recorded in "Inner Mongolia Chinese Herb Medicine"and is considered as a folk medicine for treating hepatitis in northern China. Aim of the study: This study sought to elucidate the role of sweroside in high fat diet induced obesity and fatty liver by using mouse model and investigated the primary molecular mechanism via transcriptomics analysis. C57BL/6 mice were fed high-fat diet (HFD) for 14 weeks to induce obesity, hyperglycemia, and fatty liver. These mice were subsequently treated with HFD alone or mixed with sweroside (at a daily dosage of 60 mg per kg of BW, 120 mg per kg of BW and 240 mg per kg of BW) for 6 weeks. BW and food intake was monitored weekly. Biochemical and pathological analysis were conducted to investigate the effect of sweroside on NAFLD. RNA-sequence and RT-qPCR analysis were performed to analyze the potential mechanism. The mice treated with sweroside were resistant to HFD-induced body weight gain, insulin resistance and hepatic steatosis. Ingenuity pathway analysis (IPA) demonstrated that hepatic gene networks related to lipid metabolism and inflammatory response were down-regulated in the HFD + sweroside group. PPAR-ɑ was located in the center of the hepatic gene network, and the significantly altered genes were CD36 and FGF21, which are related to hepatic inflammation and lipid metabolism. Consistently, upstream-regulators analysis revealed that the main enriched upstream-regulator was PPAR-ɑ. Our results indicate that sweroside may ameliorate obesity with fatty liver via the regulation of lipid metabolism and inflammatory responses. The beneficial effects of sweroside might be closely associated with the regulation of PPAR-α. Image 1 • Sweroside ameliorates the HFD-induce body weight gain, hepatic steatosis and serum lipid levels in DIO mice. • Sweroside improves glucose homeostasis and insulin sensitivity in DIO mice. • Sweroside attenuates HFD-induced hepatic inflammation in DIO mice. • Sweroside improves obesity with fatty liver by regulating the lipid metabolism and inflammatory responses. • The effect of sweroside in regulating inflammatory response and lipid metabolism is closely related with PPAR-α. [ABSTRACT FROM AUTHOR]

Accumulation of hepatic lipid promotes systemic metabolic dysfunction and results in fatty liver. Our previous studies have shown that the alkaloids of Dendrobium nobile Lindl. (DNLA) could regulate the lipid metabolism gene expression in livers of mice. However, the protective effects on hepatic lipid homeostasis and the underlying mechanisms are still unclear. The C57BL/6 male mice were randomly divided into four groups, including control group, model group, DNLA treatment group, and simvastatin positive control group. Mice in the control group and the other three groups were fed with control diet and high fat diet during the full course of this study, respectively. Hepatic lipid accumulation was induced by HFD in mice after 18 weeks of feeding. DNLA (15 mg/kg) and simvastatin (20 mg/kg) were administrated intragastrically in the DNLA treatment group and simvastatin positive control group for another 18 weeks, respectively. HE staining and Oil-Red-O staining of liver tissues were observed. TC and TG levels in liver were assayed. The amount of major bile acids in mice livers were quantified by UPLC-MS. Expression levels of genes were tested by the real-time PCR. The results of HE staining and Oil-Red-O staining showed that DNLA could improve hepatic lipid homeostasis. DNLA significantly decreased liver TC and TG levels in the DNLA group. Moreover, the UPLC-MS analysis showed that DNLA did not only influence the hepatic bile acid quantity but did raise the hydrophilicity. Compared with the model group, DNLA decreased the hepatic levels of several free bile acids, including LCA, DCA, CA, and CDCA, and increased most important taurine-conjugated bile acids levels in liver, including TMCAs, TCDCA, TUDCA, and THDCA. In addition, DNLA also decreased the CA/CDCA ratio. The gene expression levels of Cyp27a1 , Cyp3a11 , Fxr , and Shp were up-regulated in DNLA treatment group. DNLA may improve the hepatic abnormal lipid profile of HFD-fed mice via two pathways: (1) enhancing the taurine-conjugated bile acids which are highly hydrophilic and contribute to the excretion of cholesterol; (2) decreasing the CA/CDCA ratio which is positively related to cholesterol absorption. Image 1 [ABSTRACT FROM AUTHOR]