Preparation and Certification of a New Salvianolic Acid A Reference Material for Food and Drug Research

Salvianolic acid A(Sal A),a water-soluble ingredient in Danshen,has various biological activities.Sal A and its impurities have similar physical and chemical properties,as well as strong reducibility;therefore,they are difficult to prepare and purify.In this study,high-purity Sal A was obtained by purification of sephadex chromatography and preparative chromatography.Furthermore,HPLC-DAD tandem ECD and HPLC-DAD tandem MS methods were used for non-volatile organic impurity analysis,ICP-MS method was used for non-volatile inorganic impurities and mass balance method and quantitative nuclear magnetic resonance were employed to certify the product.The structures of Sal A and its relative impurities were validated by nuclear magnetic resonance spectroscopy and mass spectrometry,and their contents were quantified as well.Following the principles of ISO Guides 34:2009 and 35:2005,a Sal A reference material was certified,covering homogeneity studies,stability studies,characterization,and uncertainty estimations.

Optimized solubility and bioavailability of genistein based on cocrystal engineering

With various potential health-promoting bioactivities,genistein has great prospects in treatment of a series of complex diseases and metabolic syndromes such as cancer,diabetes,cardiovascular diseases,menopausal symptoms and so on.However,poor solubility and unsatisfactory bioavailability seriously limits its clinical application and market development.To optimize the solubility and bioavailability of genistein,the cocrystal of genistein and piperazine was prepared by grinding assisted with solvent based on the concept of cocrystal engineering.Using a series of analytical techniques including single-crystal X-ray diffraction,powder X-ray diffraction,Fourier transform infrared spectroscopy,differential scanning calorimetry and thermogravimetric analysis,the cocrystal was characterized and confirmed.Then,structure analysis on the basis of theoretical calculation and a series of evaluation on the stability,dissolution and bioavailability were carried out.The results indicated that the cocrystal of genistein and piperazine improved the solubility and bioavailability of genistein.Compared with the previous studies on the cocrystal of genistein,this is a systematic and comprehensive investigation from the aspects of preparation,characterization,structural analysis,stability,solubility and bioavailability evaluation.As a simple,efficient and green approach,cocrystal engineering can pave a new path to optimize the pharmaceutical properties of natural products for successful drug formulation and delivery.

Screening, Characterization and Evaluation of Mangiferin Polymorphs

Mangiferin is a compound with many pharmacological activities and exists in many natural products.Anhydrous and hydrate of mangiferin have been reported separately in two literatures,but the polymorphism of this compound has not been realized until this paper.In this study,polymorph screening of mangiferin has been carried out and five forms have been obtained including three new forms never reported.Several solid state characterization methods,such as powder X-ray diffraction,differential scanning calorimetry and thermogravimetry,are used to identify and characterize all of mangiferin forms.The comparison of the crystallographic data and hirshfeld surface analysis were first reported for mangiferin anhydrous and hydrate.Furthermore,the studies on stability,transformation and solubility have been undertaken,the results prompt that form V can be used as the dominant polymorph for the development of innovative pharmaceuticals.

Carbonic anhydrase 2 mediates anti-obesity effects of black tea as thermogenic activator

Obesity is a metabolic disorder due to over-accumulation of adipose tissue and ultimately becomes a“disease”.Brown adipose tissue(BAT)thermogenesis and white adipose tissue(WAT)browning emerge as a potential strategy of anti-obesity by dissipating energy as heat.However,drugs based on adipose tissue thermogenesis have not been successfully approved yet.In current study,we found that black tea extract(BTE)obtained by patentauthorized manufacturing process prevented body weight gain as novel thermogenic activator with reduction of adiposity,improvement of adipose distribution,and glucose metabolism improvement in diet-induced obesity mice.Mechanismly,anti-obesity effect of BTE depends on promoting BAT thermogenesis and WAT browning with upregulation of uncoupling protein 1(UCP1),especially visceral adipose tissue(VAT)with browning resistance.Specifically,utilizing in silico approach of network pharmacology and molecular docking,we identified carbonic anhydrase 2(CA2)in nitrogen metabolism as anti-obesity target of BTE and further elucidated that protein kinase B(AKT)signaling pathway linked CA2 and UCP1.Meanwhile gut microbiota regulation may prompt the CA2-dependent thermogenesis activation.Our findings demonstrated anti-obesity effect of BTE as thermogenic activator through CA2-mediated BAT thermogenesis and WAT browning via CA2-AKT-UCP1 signaling pathway,which could be developed as promising anti-obesity agent with good safety and efficacy.

Up-regulation of Fas Ligand Expression by Sirtuin 1 in both Flow-restricted Vessels and Serum-stimulated Vascular Smooth Muscle Cells

Objective To study the role of sirtuin 1 （SIRT1） in Fas ligand （FasL） expression regulation during vascular lesion formation and to elucidate the potential mechanisms. Methods SIRT1 and FasL protein levels were detected by Western blotting in either mouse arteries extract or the whole rat aortic vascular smooth muscle cell （VSMC） lysate. Smooth muscle cell （SMC）-specific human SIRT1 transgenic （Tg） C57BL/6 mice and their littermate wild-type （WT） controls underwent complete carotid artery ligation （ligation groups） or the ligation-excluded operation （sham groups）. The carotid arteries were collected 1 day after operation. Reverse transcription-polymerase chain reaction was performed to detect the mRNA levels of SIRT1 and FasL. Luciferase reporter assays were performed to detect the effect of WT-SIRT1, a dominant-negative form of SIRT1 （SIRT1H363Y）, and GATA-6 on the promoter activity of FasL. Flow cytometry assay was applied to measure the hypodiploid DNA content of VSMC so as to monitor cellular apoptosis. Results SIRTI was expressed in both rat aortic VSMCs and mouse arteries. Forced SIRT1 expression increased FasL expression both in injured mouse carotid arteries 1 day after ligation （P〈0.001） and VSMCs treated with serum （P〈0.05 at the transcriptional level, P〈0.001 at the protein level）. No notable apoptosis was observed. Furthermore, transcription factor GATA-6 increased the promoter activity of FasL （P〈0.001）. The induction of FasL promoter activity by GATA-6 was enhanced by WT-SIRT1 （P〈0.001）, while SIRT1H363Y significantly relieved the enhancing effect of WT-SIRT1 on GATA-6 （P〈0.001）. Conclusions Overexpression of SIRT1 up-regulates FasL expression in both flow-restricted mouse carotid arteries and serum-stimulated VSMCs. The transcription factor GATA-6 participates in the transcriptional regulation of FasL expression by SIRT 1.

Purity and Uncertainty Study of CRM Betulin by DSC

Betulin(BE)can be obtained from many plants,such as those belonging Betulaceae family,and pharmacological investigations showed its notable biological properties and good potential for food and pharmaceutical development.We investigated the homogeneity,stability,purity,and uncertainty of a newly certified reference material(CRM)of BE.The certified purity value for the CRM of BE was 99.56%with an extended uncertainty of 0.07%(k=2,P=0.95),as determined by differential scanning calorimetry(DSC).In this study,DSC was used for the first time for purity determination of BE.Given its high accuracy,precision,and reproducibility,DSC can be used as an alternative technique for purity determination of CRMs in the pharmaceutical and food industry.

Network pharmacology study of Chinese medicine Xiao-Xu-Ming decoction based on vasoconstrictor related GPCR targets

OBJECTIVE Using bioinformatics methods,to establish Xiao-Xu-Ming decoction(XX.MD) "compound-vasoconstriction G Protein-Coupled Receptors(GPCR) targets" network,and analyze the vasoconstriction regulatory effective components and the potential targets of XXMD.METHODS Ac.cording to the XXMD herb sources,we retrieved the chemical structures from the national scientific da.ta sharing platform for population and health pharmaceutical information center,TCMSP database and the latest research literature.The chemical molecular library was established after class prediction and screening for medicinal and metabolic properties.Five kinds of vasoconstriction GPCR crystal structure including 5-HT receptors(5-HT1 AR,5-HT1 BR),AT1 R,β2-AR,hUTR and ETB were retrieved from Bank Pro.tein Data Bank database or homology modeling using Discovery Studio 4.1 built-in modeling tools.After virtual screening by Libdock molecular docking,the highest rated 50 compounds of each target were col.lected and analyzed.The collected data were further used to construct and analyze the network.RE.SULTS 859 single compound structures information in XXMD were generalized following the screen.ing of obtained 2043 compounds.The complicated compound-vasoconstriction GPCR targets network of XXMD was then constructed and analyzed by molecular docking with the above five kinds of GPCR target receptors.Most of the chemical composition effects were associated with different vasoconstric.tion GPCR targets,while a few effective components can be applied to multiple GPCR targets at the same time,therefore forming synergies.CONCLUSION Vasorelaxant effects of XXMD may not only result from the collaborative interaction between a variety of active ingredients in Chinese medicine and multi.ple targets,but also from the interaction between some effective component and multiple targets.

Research development of Carpesii Fructus

Carpesii Fructus is the fruit of Carpesium abrotanoides L.and is recorded in the Chinese Pharmacopoeia(2015 Edition).Carpesium abrotanoides broadly distribute in China.Traditionally,Carpesii Fructus was used as a parasiticide,especially for ascariasis,pinworms and tapeworm disease.In ancient times,the Carpesium plants were used as traditional Chinese,Korean and Japanese herbal medicines for the treatment of several diseases.Carpesii Fructus was first recorded in the book "Newly Revised Canon of Materia Medica" in the Tang Dynasty of China.The original plant is Compositae Arte.misia santonica(Seriphidium cinum) from middle east Persian.At present,Carpesium abrotanoides issometimes confused with the Lappula family in species classification.In the Song Dynasty of China,"KaiYang Materia Medica" recorded that the best Carpesii Fructus was from Persian.The main compo.nents of Carpesii Fructusare terpenes,phenolic compounds,flavonoids and coumarins.Including telekin,3-epi-isotelekin,11β-13-dihydro-1-epi-inuviscolide,carabrone,carabrol,terpene lactone,gerilin,carpesia,valeric acid,oleic acid,linolenic acid,thirty-one alkane,sterol,etc.The chemical components isolated from whole plants of carpesia are more than 143.In clinical practice,Carpesii Fructus is mainly used as antiparasitic drugs and usually combined with other drugs since the poor efficacy as single drug.Its toxic reaction is closely related to the dose of the drug.Carpesia,asa main component of Carpesii Fructus,might lead to adverse reactions also.At present,Major issuesof Carpesii Fructusare the lack of phar.macological research,as well as lack of in-depth study on the material basis.Therefore,further studies are needed on the drug development and clinical usuage.

Solubility and pharmacokinetics determination of chlorogeninc acid

OBJECTIVE To enhance the quality and efficiency of chlorogeninc acid by investigating the differences among the chlorogeninc acid polymorphs in bioavailability and solubility.METHODS Determinative method was used to analyze the solubility of chlorogeninc acid polymorphs;solid chlorogeninc acid in different forms were orally administered to the rats,and a HPLC method was established to determinate plasma lever of metabolite-acyclovir and the bioavailability was analyzed.RESULTS The indirect pharmacokinetic parameters of Chlorogeninc acid,as the metabolites of the form Ⅰ,Ⅱ,Ⅲ,were as follows:cmaxwas 0.37,0.34 and 0.44mg·L-1,respectively;AUC0→twas 0.71,0.76 and 0.79mg·L-1·h,respectively.CONCLUSION The solubility of form Ⅲ was larger than the other forms′.The solubility of Chlorogeninc acid polymorphs:form Ⅰ,form Ⅱ,form Ⅲ were merely the same,there was no statistically significant difference in pharmacokinetic parameters among these three forms.

Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

Ferroptosis,a unique modality of cell death with mechanistic and morphological differences from other cell death modes,plays a pivotal role in regulating tumorigenesis and offers a new opportunity for modulating anticancer drug resistance.Aberrant epigenetic modifications and posttranslational modifications(PTMs)promote anticancer drug resistance,cancer progression,and metastasis.Accumulating studies indicate that epigenetic modifications can transcriptionally and translationally determine cancer cell vulnerability to ferroptosis and that ferroptosis functions as a driver in nervous system diseases(NSDs),cardiovascular diseases(CVDs),liver diseases,lung diseases,and kidney diseases.In this review,we first summarize the core molecular mechanisms of ferroptosis.Then,the roles of epigenetic processes,including histone PTMs,DNA methylation,and noncoding RNA regulation and PTMs,such as phosphorylation,ubiquitination,SUMOylation,acetylation,methylation,and ADP-ribosylation,are concisely discussed.The roles of epigenetic modifications and PTMs in ferroptosis regulation in the genesis of diseases,including cancers,NSD,CVDs,liver diseases,lung diseases,and kidney diseases,as well as the application of epigenetic and PTM modulators in the therapy of these diseases,are then discussed in detail.Elucidating the mechanisms of ferroptosis regulation mediated by epigenetic modifications and PTMs in cancer and other diseases will facilitate the development of promising combination therapeutic regimens containing epigenetic or PTM-targeting agents and ferroptosis inducers that can be used to overcome chemotherapeutic resistance in cancer and could be used to prevent other diseases.In addition,these mechanisms highlight potential therapeutic approaches to overcome chemoresistance in cancer or halt the genesis of other diseases.

Inhibition of chemokine-like factor 1 improves bloodbrain barrier dysfunction in rats following focal cerebral ischemia

OBJECTIVE To investigate the role of chemokine-like factor 1(CKLF1),a novel C-C chemokine,on brain-blood barrier(BBB)integrity in rat focal cerebral ischemia and reperfusion model.METHODS Antibodies against CKLF1 was applied to the rightcerebral ventricle immediately after transient middle cerebral artery occlusion.Brain water content,Evans blue leakage and the expression of aquaporin-4(AQP-4),matrix metalloproteinase-9(MMP-9),zonula occludens-1(ZO-1)and occludin were measured.RESULTS After treatment with antiCKLF1 antibody,brain water content and Evans blue leakage in ipsilateral hemisphere were decreased in a dose-dependent manner at 24 h after reperfusion,but not changed in contralateral hemisphere.Anti-CKLF1 antibody reduced the expression of AQP-4 and MMP-9,and upregulated the expression of ZO-1 and Occludin.These results suggest that CKLF1 is involved in BBB disruption after reperfusion.CONCLUSION Inhibition of CKLF1 protects against cerebral ischemia by maintaining BBB integrity,possibly via inhibiting the expression of AQP-4 and MMP-9,and increasing the expression of tight junction protein.

Cerebral vasorelaxant material basis of Xiaoxuming decoction study with rat basilar artery

OBJECTIVE To investigate the cerebralvasorelaxant material basis of Xiaoxuming decoction.METHODS According to the Xiaoxuming decoction herb sources,we retrieved the chemical structure from the literatures and the Chinese Natural Product Database(http://pharmdata.ncmi.cn).By using microvessel tension system,we checked the vasorelaxanteffects of Xiaoxuming decoction anti-cerebral ischemia effective components group(XXMDECG)and the available composition compounds on pre-contracted basilar artery ring.RESULTS963 compoundsin the decoction,including 81Fangfeng,77 Mahuang,130 Shengjiang,31 Guizhi,91 Huangqin,127 Renshen,73 Chuanxiong,44 Shaoyao,39 Xingren,42 Fangji,62 Fuzi and 166 Gancao were collected.The five largest number classes of compounds in the decoction are volatile oil(32%),flavone(32%),alkaloid(13%),saponin(7%),polyphenol and organic acid(5%).XXMDECG at concentration from 1 to 400μg·mL-1can dilate the KCl(60 mmol·L-1)and ET-1(0.01μmol·L-1)pre-contracted rat basilar artery rings in a dose-dependent manner.There are 6 compounds with vasorelaxant ratio more than 50%at the concentration of 10μmol·L-1.CONCLUSION Xiaoxuming decoction contains abundant chemical structure.It has the material basis of multiple ingredients and multiple targets.The XXMDECG are able to dilate the rat basilar artery rings in a dose-dependent manner.The network interactions between varies of chemical compounds in Xiaoxuming decoction and the vasoconstriction associated targets result in the comprehensive regulation mechanisms of vascular function.

Analysis of Four Solvatomorphs of Betulin by TG-DTA-EI/PI-MS System Equipped with the Skimmer-Type Interface

Betulin(BE)has exceedingly become a potential natural product,providing multiple pharmacological and biological activi-ties,including anti-cancer,anti-viral,and anti-inflammatory benefits.Previous research indicated that the solvatomorphism of BE can easily occur through crystallization with different organic solvents.This property of BE can directly affect its extraction,isolation,and preparation process.In this study,a system of thermogravimetry(TG)-differential thermal analysis(DTA)coupled with mass spectrometry(MS)with electron ionization(EI)and photoionization(PI)capability,equipped with the skimmer-type interface(i.e.,skimmer-type interfaced TG-DTA-EI/PI-MS system),as a real-time and onsite analysis technique,was employed.Then,four solvatomorphs of BE,namely,with pyridine and water(A),sec-butanol(B),n,n-dimethylformamide(DMF)(C),and isopropanol(V),were analyzed for the first time.Finally,five kinds of the main volatile gaseous species,including H2O,pyridine,sec-butanol,DMF,and isopropanol,were identified clearly.Furthermore,the multi-step desolvation processes of the four solvatomorphs of BE were revealed by this system for the first time.This system showed great potential for the rapid and accurate analysis of various solvatomorphs of natural products.

Author correction to ‘Protective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models’ [Acta Pharmaceutica Sinica B 11 (2021) 1903e1913]

The authors regret that there was a picture error in the Fig.6D1 owing to the image copy mistake of group-CORT when combining the images of different groups.The revision will cause no change with the data value in Fig.6D2,and also do not affect any conclusions of the current work and the description of the whole article.The authors have provided the original data of this figure to Editorial Office,and the corresponding authors or the Editorial Office can be contacted for original data access.

Author correction to‘Protective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models’[Acta Pharmaceutica Sinica B 11(2021)1903-1913]

The authors regret that there was a picture error in Fig.5F owing to the inappropriate data statistics—forgetting gating when data collecting and a picture error in Fig.6F owing to the data copy mistake when drawing the column chart.The revisions cause some changes with the data value.

Antihyperuricemic effect of mangiferin aglycon derivative J99745 by inhibiting xanthine oxidase activity and urate transporter 1 expression in mice

A mangiferin aglycon derivative J99745 has been identified as a potent xanthine oxidase(XOD) inhibitor by previous in vitro study. This study aimed to evaluate the hypouricemic effects of J99745 in experimental hyperuricemia mice, and explore the underlying mechanisms. Mice were orally administered 600 mg/kg xanthine once daily for 7 days and intraperitoneally injected 250 mg/kg oxonic acid on the 7 th day to induce hyperuricemia. Meanwhile, J99745(3, 10, and 30 mg/kg), allopurinol(20 mg/kg) or benzbromarone(20 mg/kg) were orally administered to mice for 7 days. On the 7 th day,uric acid and creatinine in serum and urine, blood urea nitrogen(BUN), malondialdehyde(MDA) content and XOD activities in serum and liver were determined. Morphological changes in kidney were observed using hematoxylin and eosin(H&E) staining. Hepatic XOD, renal urate transporter 1(URAT1), glucose transporter type 9(GLUT9), organic anion transporter 1(OAT1) and ATP-binding cassette transporter G2(ABCG2) were detected by Western blot and real time polymerase chain reaction(PCR). The results showed that J99745 at doses of 10 and 30 mg/kg significantly reduced serum urate, and enhanced fractional excretion of uric acid(FEUA). H&E staining confirmed that J99745 provided greater nephroprotective effects than allopurinol and benzbromarone. Moreover, serum and hepatic XOD activities and renal URAT1 expression declined in J99745-treated hyperuricemia mice. In consistence with the ability to inhibit XOD, J99745 lowered serum MDA content in hyperuricemia mice. Our resultssuggest that J99745 exerts urate-lowering effect by inhibiting XOD activity and URAT1 expression, thus representing a promising candidate as an anti-hyperuricemia agent.

Protective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models

Nicotinicα4β2 receptor antagonists have drawn increasing attention in the development of new antidepressants.In this study,we aimed to investigate the protective effect of VMY-2-95,the new selective antagonist ofα4β2 nicotinic acetylcholine receptor(nAChR)on corticosterone(CORT)injured mice and cellular models.Fluoxetine was applied as a positive control,and the effects of VMY-2-95 were investigated with three different doses or concentrations(1,3,10 mg/kg in mice,and 0.003,0.03,0.1μmol/L in cells).As a result,VMY-2-95 showed significant antidepressant-like effects in the CORT injured mice by improving neuromorphic function,promoting hippocampal nerve proliferation,and regulating the contents of monoamine transmitters.Meanwhile,VMY-2-95 exhibited protective effects on cell viability,cell oxidant,cell apoptosis,and mitochondrial energy metabolism on corticosterone-impaired SH-SY5 Y cells.Also,the PKA-CREB-BDNF signaling pathway was up-regulated by VMY-2-95 both in vitro and in vivo,and pathway blockers were also combined with VMY-2-95 to verify the effects furtherly.Therefore,we preliminarily proved that VMY-2-95 had protective effects in depressed mice and SH-SY5 Y cells against injuries induced by corticosterone.This work indicated that the application of VMY-2-95 is a potential pharmacological solution for depression.This study also supported the development ofα4β2 nAChR antagonists towards neuropsychiatric dysfunctions.

Cocrystal virtual screening based on the XGBoost machine learning model

Co-crystal formation can improve the physicochemical properties of a compound,thus enhancing its druggability.Therefore,artificial intelligence-based co-crystal virtual screening in the early stage of drug development has attracted extensive attention from researchers.However,the complexity of developing and applying algorithms hinders it wide application.This study presents a data-driven co-crystal prediction method based on the XGBoost machine learning model of the scikit-learn package.The simplified molecular input line entry specification(SMILES)information of two compounds is simply inputted to determine whether a co-crystal can be formed.The data set includs the co-crystal records presented in the Cambridge Structural Database(CSD)and the records of no co-crystal formation from extant literature and experiments.RDKit molecular descriptors are adopted as the features of a compound in the data set.The developed model shows excellent performance in the proposed co-crystal training and validation sets with high accuracy,sensitivity,and F1 score.The prediction success rate of the model exceeds 90%.The model therefore provides a simple and feasible scheme for designing and screening co-crystal drugs efficiently and accurately.

Network pharmacology-based analysis of Chinese herbal Naodesheng formula for application to Alzheimer＇s disease

Naodesheng(NDS) formula, which consists of Rhizoma Chuanxiong, Lobed Kudzuvine, Carthamus tinctorius, Radix Notoginseng, and Crataegus pinnatifida, is widely applied for the treatment of cardio/cerebrovascular ischemic diseases, ischemic stroke, and sequelae of cerebral hemorrhage, etc. At present, the studies on NDS formula for Alzheimer's disease(AD) only focus on single component of this prescription, and there is no report about the synergistic mechanism of the constituents in NDS formula for the potential treatment of dementia. Therefore, the present study aimed to predict the potential targets and uncover the mechanisms of NDS formula for the treatment of AD. Firstly, we collected the constituents in NDS formula and key targets toward AD. Then, drug-likeness, oral bioavailability, and blood-brain barrier permeability were evaluated to find drug-like and lead-like constituents for treatment of central nervous system diseases. By combining the advantages of machine learning, molecular docking, and pharmacophore mapping, we attempted to predict the targets of constituents and find potential multi-target compounds from NDS formula. Finally, we built constituent-target network, constituent-target-target network and target-biological pathway network to study the network pharmacology of the constituents in NDS formula. To the best of our knowledge, this represented the first to study the mechanism of NDS formula for potential efficacy for AD treatment by means of the virtual screening and network pharmacology methods.

Pharmacokinetic study of gallocatechin-7-gallate from Pithecellobium clypearia Benth. in rats

The pharmacokinetic profile of gallocatechin-7-gallate (J10688) was studied in rats after intravenous administration. Male and female Sprague-Dawley (SD) rats received 1, 3, and 10 mg/kg (i.v.) of J10688 and plasma drug concentrations were determined by a high performance liquid chromatography-mass spectrometry (LC-MS) method. The pharmacokinetic software Data Analysis System (Version 3.0) was used to calculate the pharmacokinetic parameters. For different i.v. doses of J10688, the mean peak plasma concentration (C-0) values ranged from 11.26 to 50.82 mg/L, and mean area under the concentration -time curve (ALC(0-i)) values ranged from 1.75 to 11.80 (mg ' h/L). J10688 lacked dose dependent pharmacokinetic properties within doses between 1 and 10 mg/kg, based on the power model. The method developed in this study was sensitive, precise, and stable. The pharmacokinetic properties of J10688 in SD rats were shown to have rapid distribution and clearance values. These pharmacokinetic results may contribute to an improved understanding of the pharmacological actions of J10688. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.