The Anticancer Potential of Quassinoids-A Mini-Review

The anticancer potential of quassinoids has attracted a great deal of attention for decades,and scientific data revealing their possible applications in cancer management are continuously increasing in the literature.Aside from the potent cytotoxic and antitumor properties of these degraded triterpenes,several quassinoids have exhibited synergistic effects with anticancer drugs.This article provides an overview of the potential anticancer properties of quassinoids,including their cytotoxic and antitumor activities,mechanisms of action,safety evaluation,and potential benefits in combination with anticancer drugs.

Thoughts and Practice of Design,Fabrication and Application for Traditional Chinese Medicines' Functional Separation of Material Substance

1.The Chemical Composition of Traditional Chinese Medicines'substance Chinese medicine and its compound is essentially a special,macrocosm drug group,which was made of a different chemical composition of the Chemical mother nucleus.Chinese medicine effective components such as alkaloids,flavonoids,glycosides,etc.,which molecular weight is less than

Photothermal probiotics delivery of photodynamic agents for enhanced immunogenic cell death within hypoxia center of solid tumors

Resulting from harsh hypoxic environmental conditions,central cells in the core of solid tumors are usually more aggressive and malignant with a less stable genome.Therefore,therapeutic agents with improved penetration for the activation of immunity in tumor centers exhibit promising potential in immunotherapies.Here,polydopamine-coated Escherichia coli Nissle 1917(EcN)bearing chlorin e6(Ce6)-loaded and polyethyleneimine(PEI)-coated hollow manganese dioxide(shorted as EP-ChP)are applied for enhanced immunotherapy in deep tumors.After accumulation in tumor center through hypoxia targeting,manganese dioxide is degradated under the tumor microenvironment with released Ce6 and thus generates reactive oxygen species(ROS)upon 660 nm laser irradiation,which can further lower thermalresistance of cancer cells via HSP90αdownregulation.Owing to that,heating induced by polydopamine upon 808 nm laser irradiation can achieve effective tumor ablation.Phototherapy upon dual laser induces enhanced immunogenic cell death,while bacterial infections in tumor tissues also trigger innate immunity.This bacteria-based approach provides enhanced antitumor immune responses in deep tumors with great potential in the reshaping of immunosuppression tumor microenvironment.

Comparative analysis of twenty-five compounds in different parts of Astragalus membranaceus var.mongholicus and Astragalus membranaceus by UPLC-MS/MS

As a traditional Chinese medicine,the root of Astragalus membranaceus var.mongholicus(AMM) or A.membranaceus(AM) has been widely used in China and other Asian countries for thousands of years.Till now,the flavonoids,phenolic acids and saponins are considered as the main active components contributing to their therapeutic effect in these plants.In order to clarify the distribution and contents of these compounds in different organs of these plants,a rapid and sensitive analytical method for simultaneous determination of 25 active compounds including seven types(i.e.dihydroflavones,isoflavane,isoflavones,flavones.pterocarpans,phenolic acid and saponins) within 10 min was established using ultra-pressure liquid chromatography coupled with tandem mass spectrometry(UPLC-MS/MS).Then,the established method was fully validated and successfully applied to the determination of the contents of these analytes in different parts(root,rhizome,stem,leaf and flower) of AMM and AM.The results indicated that the contents of the same type of compounds in two different species plants were significantly different.Moreover,the obvious differences were also found for the distribution and contents of different type of compounds in five organs of the same species.The present study could provide necessary information for the rational development and utilization of AMM and AM resource.

Integration of full-length transcriptomics and targeted metabolomics to identify benzylisoquinoline alkaloid biosynthetic genes in Corydalis yanhusuo

Corydalis yanhusuo W.T.Wang is a classic herb that is frequently used in traditional Chinese medicine and is efficacious in promoting blood circulation,enhancing energy,and relieving pain.Benzylisoquinoline alkaloids(BIAs)are the main bioactive ingredients in Corydalis yanhusuo.However,few studies have investigated the BIA biosynthetic pathway in C.yanhusuo,and the biosynthetic pathway of species-specific chemicals such as tetrahydropalmatine remains unclear.We performed full-length transcriptomic and metabolomic analyses to identify candidate genes that might be involved in BIA biosynthesis and identified a total of 101 full-length transcripts and 19 metabolites involved in the BIA biosynthetic pathway.Moreover,the contents of 19 representative BIAs in C.yanhusuo were quantified by classical targeted metabolomic approaches.Their accumulation in the tuber was consistent with the expression patterns of identified BIA biosynthetic genes in tubers and leaves,which reinforces the validity and reliability of the analyses.Full-length genes with similar expression or enrichment patterns were identified,and a complete BIA biosynthesis pathway in C.yanhusuo was constructed according to these findings.Phylogenetic analysis revealed a total of ten enzymes that may possess columbamine-O-methyltransferase activity,which is the final step for tetrahydropalmatine synthesis.Our results span the whole BIA biosynthetic pathway in C.yanhusuo.Our full-length transcriptomic data will enable further molecular cloning of enzymes and activity validation studies.

Characterization of Angiotensin-? Converting Enzyme Inhibiting Peptide from Venerupis philippinarum with Nano-Liquid Chromatography in Combination with Orbitrap Mass Spectrum Detection and Molecular Docking

The complexity and diversity of peptide mixture from protein hydrolysates make their characterization difficult. In this study, a method combining nano LC-MS/MS with molecular docking was applied to identifying and characterizing a peptide with angiotensin-? converting enzyme(ACE-I) inhibiting activity from Venerupis philippinarum hydrolysate. Firstly, ethanol supernatant of V. philippinarum hydrolysate was separated into active fractions with chromatographic methods such as ion-exchange chromatography and high performance liquid chromatography in combination. Then seven peptides from active fraction were identified according to the searching result of the MS/MS spectra against protein databases. Peptides were synthesized and subjected to ACE-Iinhibition assay. The peptide NTLTLIDTGIGMTK showed the highest potency with an IC_(50) of 5.75 μmol L^(-1). The molecular docking analysis showed that the ACE-I inhibiting peptide NTLTLIDTGIGMTK bond with residues Glu123, Glu403, Arg522, Glu376, Gln281 and Asn285 of ACE-I. Therefore, active peptides could be identified with the present method rather than the traditional purification and identification strategies. It may also be feasible to identify other food-derived peptides which target other enzymes and receptors with the method developed in this study.

Overcompensation or limitation to photosynthesis and root hydraulic conductance altered by rehydration in seedlings of sorghum and maize

In view of the prospect of irregular extremes of high and low rainfall due to climate change, the mechanisms underlying plant responses to periods of drought and re-watering need to be understood. Sorghum (Sorghum bicolor L.) and maize (Zea mays L.) were grown in pots of loess soil at three soil moisture levels to examine the effects of different levels of drought over 10 days and plant responses to re-watering (5 days of rehydration). Photosynthesis-related traits recovered rapidly both in sorghum and maize on re-watering, suggesting that photosynthetic function was not severely damaged after a short drought period, although the values of these traits were dramatically reduced during drought per se. However, the two species differed in the extent to which they recovered from severe stress. In sorghum, net photosynthetic rate (P_n), stomatal conductance (G_s), and maximum photochemical efficiency of PSII (F_v/F_m) returned to control levels after re-watering. However, in maize, these parameters exceeded control levels after re-watering. Both overcompensation and pre-drought limitation were observed. Over a range of growth conditions, close relationships between G_s and root hydraulic conductance (K_r) were observed in pooled data sets. P_n, K_r, and their related characteristics were compared among species and treatments. Our results showed that the recovery of K_r is similar between sorghum and maize, at least after a short time of re-watering, although the two species differ in drought-tolerance capacity. Our results also suggest that sorghum can endure moderate drought by adjusting certain traits, but is still as vulnerable as maize under severe drought stress.

Elucidating the interaction of kansui and licorice by comparative plasma/tissue metabolomics and a heatmap with relative fold change

Although compatibility is highly advocated in traditional Chinese medicine (TCM), inappropriate combination of some herbs may reduce the therapeutic action and even produce toxic effects. Kansui and licorice, one of TCM “Eighteen Incompatible Medicaments”, are the most representative cases of improper herbal combination, which may still be applied simultaneously under given conditions. However, the potential mechanism of their compatibility and incompatibility is unclear. In the present study, two different ratios of kansui and licorice, representing their compatibility and incompatibility respectively, were designed to elucidate their interaction by comparative plasma/tissue metabolomics and a heatmap with relative fold change. As a result, glycocholic acid, prostaglandin F2a, dihydroceramide and sphinganine were screened out as the principal alternative biomarkers of compatibility group;sphinganine, dihydroceramide, arachidonic acid, leukotriene B4, acetoacetic acid and linoleic acid were those of incompatibility group. Based on the values of biomarkers in each tissue, the liver was identified as the compatible target organ, while the heart, liver, and kidney were the incompatible target organs. Furthermore, important pathways for compatibility and incompatibility were also constructed. These results help us to better understand and utilize the two herbs, and the study was the first to reveal some innate characters of herbs related to TCM “Eighteen Incompatible Medicaments”.

A convenient method for the determination of molecular weight cut-off of ultrafiltration membranes

With the rapid increase of water contamination,membrane separation technology and their corresponding molecular weight cut-off(MWCO) evaluation method become more necessary.In this study,Panax notoginseng saponins was used as a new standard marker to determinate ultrafiltration(UF) membrane MWCOs,series of Millipore membranes were selected as control group to analyze and calculate the relationship between retention rate and MWCOs with exponential or logarithmic equation.A new and convenient method was provided for determining the membrane MWCO by modeling analysis retention rate with MWCOs,and the regression coefficients >0.990.The feasibility and practicability of established method was verified by different manufactures' membrane and dextrans.In the detection progress,as the main ingredient of Panax notoginseng saponins,Notoginsenoside R_1,Ginsenoside Rg_1,Ginsenoside Rb_1 and Ginsenoside Rd with different surface activity,the MWCO range of UF membranes can be divided into two zones mainly due to the retention rate difference among Notoginsenoside R_1,Ginsenoside Rg_1,Ginsenoside Rb_1 and Ginsenoside Rd.Zone 1,1000-10000;and Zone II,10000-100000.Thus,the new method would be helpful to improve the applicability of UF membrane in separation technology.

Allergenicity studies of Naoluotai injection and H3 injection before and after ultrafiltration

OBJECTIVE To explore the influence of ultrafiltration on the allergenicity of Naoluotai injection and H3 injectable powder in guinea pig.METHODS The ultra filtrated and non-ultra filtrated Naoluotai injection was utilized to do the sensitization test of guinea pig.The guinea pig was sensitized three times by subcutaneous injection of test solution every other day.After 16 dof the first sensitization.All guinea pigs were challenged.The serotonin level in guinea pig plasma before and after the challenge was recognized as the evaluation criteria of allergenicity.RESULTS The increasing rate of serotonin in guinea pigs sensitized by ultra filtrated Naoluotai injection was 5.80% while by non-ultra filtrated Naoluotai injection was 37.03%.The increasing rate in ultra filtrated and non-ultra filtrated H3 injection was 23.59% and 61.94%,respectively.CONCLUSION The animal protein in tradition Chinese medicine injection was thought to be allergized.The ultrafiltration technology could reduce the allergenicity of tradition Chinese medicine injection and improve its safety.

Cytotoxicity and penetration enhancement activity of essential oils from warming the interior medicinals with hot or warm property in terms of Traditional Chinese Medicine

OBJECTIVE: To investigate on the cytotoxicity and penetration enhancement effect of essential oils(EOs) from warming the interior medicinals(WIM)from Traditional Chinese Medicine(TCM).METHODS: EOs were extracted from WIM of Bichengqie(Litseae Fructus), Dingxiang(Flos Syzygii Aromatici), Huajiao(Pericorpium Zanthoxyli Bungeani), and Xiaohuixiang(Fructus Foeniculi) with warm nature, and Ganjiang(Rhizoma Zingiberis),Gaoliangjiang(Rhizoma Alpinioe Officinari), Rougui(Cortex Cinnamomi Cassioe), and Wuzhuyu(Fructus Evodiae Rutoecorpae) with hot nature; respectively.Their chemical compositions were analyzed by gas chromatography-mass spectrometry(GC-MS). The cytotoxicity of the extracted eight EOs on HaCaT cells was measured and compared. Moreover, analyses of cell cycle and cell apoptosis were performed to investigate the cytotoxic mechanism.The transdermal penetration enhancement effects of the extracted eight EOs on ibuprofen were further compared by the modified Franz diffusion cell method.RESULTS: The most abundant constituents in the extracted eight EOs were determined to be monoterpenes, especially oxygen containing monoterpenes.The HaCaT cell cytotoxicity of EOs from WIM with hot nature were significantly(P = 0.020) higher than that with warm nature. Both ginger oil and zanthoxylum oil significantly induced G0/G1 phase arrestment in HaCaT cell cycle. For ginger oil from WIM with hot nature and zanthoxylum oil from WIM with warm nature, the main mechanisms of the cytotoxicity were found to be the induction of cellular necrosis and the cellular apoptosis, respectively. Furthermore, most of the tested EOs showed remarkable penetration enhancement activity on ibuprofen. However, no statistical significance(P =0.18) was found between penetration enhancement activity of EOs from WIM with warm nature and EOs from WIM with hot nature.CONCLUSION: With the enhanced penetration activity, the extracted EOs from the WIM demonstrated their significant effect of the cytotoxicity on the skin cells.

Tomato SlAN11 regulates flavonoid biosynthesis and seed dormancy by interaction with bHLH proteins but not with MYB proteins

The flavonoid compounds are important secondary metabolites with versatile human nutritive benefits and fulfill a multitude of functions during plant growth and development.The abundance of different flavonoid compounds are finely tuned with species-specific pattern by a ternary MBW complex,which consists of a MYB,a bHLH,and a WD40 protein,but the essential role of SlAN11,which is a WD40 protein,is not fully understood in tomato until now.In this study,a tomato WD40 protein named as SlAN11 was characterized as an effective transcription regulator to promote plant anthocyanin and seed proanthocyanidin(PA)contents,with late flavonoid biosynthetic genes activated in 35S::SlAN11 transgenic lines,while the dihydroflavonol flow to the accumulation of flavonols or their glycosylated derivatives was reduced by repressing the expression of SlFLS in this SlAN11-overexpressed lines.The above changes were reversed in 35S::SlAN11-RNAi transgenic lines except remained levels of flavonol compounds and SlFLS expression.Interestingly,our data revealed that SlAN11 gene could affect seed dormancy by regulating the expressions of abscisic acid(ABA)signaling-related genes SlABI3 and SlABI5,and the sensitivity to ABA treatment in seed germination is conversely changed by SlAN11-overexpressed or-downregulated lines.Yeast two-hybrid assays demonstrated that SlAN11 interacted with bHLH but not with MYB proteins in the ternary MBW complex,whereas bHLH interacted with MYB in tomato.Our results indicated that low level of anthocyanins in tomato fruits,with low expression of bHLH(SlTT8)and MYB(SlANT1 and SlAN2)genes,remain unchanged upon modification of SlAN11 gene alone in the transgenic lines.These results suggest that the tomato WD40 protein SlAN11,coordinating with bHLH and MYB proteins,plays a crucial role in the fine adjustment of the flavonoid biosynthesis and seed dormancy in tomato.

A review of Behcet's disease from the perspectives of both Western and Chinese Medicine

Behcet's disease is a condition with a complicated and unclear etiology that comprises multi-systemic, chronic, inflammatory vasculitis. Behcet's disease can affect every tissue and organ in the body,and is characterized by recurrent oral and genital ulcers, ocular inflammation, skin lesions, and other manifestations. The incidence of Behcet's disease has a distinct regional specificity, and is most prevalent along the Silk Road, a route that stretched between the Mediterranean, Middle East and Far East.This article reviews the recent literature to evaluate the prevalence, clinical manifestations, pathogenesis and mechanism, and current treatments of Behcet's disease. Furthermore, the etiology of Behcet's disease will be evaluated from the aspect of Traditional Chinese Medicine(TCM) syndrome differentiation. As Behcet's disease is complex and intractable, its treatment warrants further research.Traditionally, Behcet's disease is treated with Western Medicine(WM) via medications that act locally and systemically; this WM treatment protocol usually has a good effect, but relapse can occur after reducing the dosage. Thus, it may be ideal to treat Behcet's disease via a combination of WM and TCM.Recent studies have indicated that such a combination of Chinese and Western treatments has a better effect than either treatment alone. The aim of the present review is to describe the clinical features of Behcet's disease, and to outline its possible pathogenesis in terms of both TCM and WM. Based on these findings, the present review proposes a Behcet's disease treatment protocol composed of a combination of Chinese and WM that can effectively improve the occurrence of relapse caused by the reduction of the dosage of Western medication.

Bioorthogonal Engineered Virus‑Like Nanoparticles for Efficient Gene Therapy

Gene therapy offers potentially transformative strategies for major human diseases.However,one of the key challenges in gene therapy is developing an effective strategy that could deliver genes into the specific tissue.Here,we report a novel virus-like nanoparticle,the bioorthgonal engineered viruslike recombinant biosome(reBiosome),for efficient gene therapies of cancer and inflammatory diseases.The mutant virus-like biosome(mBiosome)is first prepared by site-specific codon mutation for displaying 4-azido-L-phenylalanine on vesicular stomatitis virus glycoprotein of eBiosome at a rational site,and the reBiosome is then prepared by clicking weak acid-responsive hydrophilic polymer onto the mBiosome via bioorthogonal chemistry.The results show that the reBiosome exhibits reduced virus-like immunogenicity,prolonged blood circulation time and enhanced gene delivery efficiency to weakly acidic foci(like tumor and arthritic tissue).Furthermore,reBiosome demonstrates robust therapeutic efficacy in breast cancer and arthritis by delivering gene editing and silencing systems,respectively.In conclusion,this study develops a universal,safe and efficient platform for gene therapies for cancer and inflammatory diseases.

Logic-gated tumor-microenvironment nanoamplifier enables targeted delivery of CRISPR/Cas9 for multimodal cancer therapy

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies.However,the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression.Here,we propose a self-amplifying logic-gated gene editing strategy for gene/H_(2)O_(2)-mediated/starvation multimodal cancer therapy.In this approach,a hypoxia-degradable covalent-organic framework(COF) is synthesized to coat a-ZIF-8 in which glucose oxidase(GOx) and CRISPR system are packaged.To intensify intracellular redox dyshomeostasis,DNAzymes which can cleave catalase mRNA are loaded as well.When the nano system gets into the tumor,the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx,which amplifies intracellular H^(+)and hypoxia,accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells.These tandem reactions deplete glucose and oxygen,leading to logic-gated-triggered gene editing as well as synergistic gene/H_(2)O_(2)-mediated/starvation therapy.Overall,this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

Methodology of network pharmacology for research on Chinese herbal medicine against COVID-19:A review

Traditional Chinese medicine,as a complementary and alternative medicine,has been practiced for thousands of years in China and possesses remarkable clinical efficacy.Thus,systematic analysis and examination of the mechanistic links between Chinese herbal medicine(CHM)and the complex human body can benefit contemporary understandings by carrying out qualitative and quantitative analysis.With increasing attention,the approach of network pharmacology has begun to unveil the mystery of CHM by constructing the heterogeneous network relationship of“herb-compound-target-pathway,”which corresponds to the holistic mechanisms of CHM.By integrating computational techniques into network pharmacology,the efficiency and accuracy of active compound screening and target fishing have been improved at an unprecedented pace.This review dissects the core innovations to the network pharmacology approach that were developed in the years since 2015 and highlights how this tool has been applied to understanding the coronavirus disease 2019 and refining the clinical use of CHM to combat it.

Oral pyroptosis nanoinhibitor for the treatment of inflammatory bowel disease

Inflammatory bowel disease(IBD)is an autoimmune gastrointestinal disease characterized by chronic relapsing inflammation of the intestine.Excessive pyroptosis that exists in the inflamed intestine can activate damage signals and aggravate local inflammation in IBD.Here,we designed an oral pyroptosis nanoinhibitor,DXMS@CuM@PPADT@PSS(DCMP),which can target intestinal lesions,and respond to reactive oxygen species(ROS)to release active sites and drugs at the lesion.DCMP can inhibit the activation of the nucleotide-binding domain and leucine-rich repeat family pyrin domain containing 3(NLRP3)inflammasomes by scavenging ROS,resulting in the down-regulation of gasdermin D(GSDMD)cleavage thus inhibiting pyroptosis.It also improved intestinal barrier function,decreased inflammatory cytokine levels,and increased the diversity of gut microbiota in mice with colitis.This work is believed to expand the biomedical application of nanomaterials for innate immunity modulation.

Antipyretic and anti-inflammatory activities of Thais luteostoma extracts and underlying mechanisms

Thais luteostoma has been utilized as a crude drug whose shell and soft tissue have been widely used for the treatment of heat syndrome in China for thousands of years. The present study was designed to investigate the antipyretic and anti-inflammatory activities of T. luteostoma. T. luteostoma was divided into shell （TLSH） and soft tissue （TLST） samples in the present study. The rat model of yeast-induced fever was used to investigate their antipyretic effects; and the rat model of hind paw edema induced by carrageenan was utilized to study their anti-inflammatory activities, and at the same time, the concentration variations of the central neurotransmitter [prostaglandin E2 （PGE2） and cyclic adenosine monophosphate （cAMP）], inflammatory mediators [tumor necrosis factor （TNFα）, interleukin-1β （IL-1）, interleukin-2 （IL-2） and interleukin-6 （IL-6）] and ion （Na^＋ and Ca^2＋） were also tested. The results showed that TLSH and TLST extracts significantly inhibited yeast-induced pyrexia in rats （P 〈 0.05）, and exhibited more lasting effects as compared to aspirin, and TLSH had the better antipyretic activity than TLST, and that TLSH and TLST could significantly prevent against carrageenan induced paw edema in rats （P 〈 0.05）; and markedly reduced levels of PGE2, cAMP, TNFα, IL-1β, IL-2, IL-6, and Na^＋/Ca^2＋. In fever model, TLST could significantly reduce the levels of PGE2 （P 〈 0.01） in rats＇ homogenate and TNF a （P 〈 0.05）, IL-113 （P 〈 0.01） in the plasma than TLSH, whereas TLSH could reduce the content of IL-2 （P 〈 0.01） and IL-6 （P 〈 0.01） in plasma and increase the content of Ca2＋ （P 〈 0.01） in plasma and homogenate more significantly than TLST. In conclusion, T. luteostoma extract has antipyretie and anti-inflammatory activities, which may be mediated through the suppression of production of PGE2, cAMP, Na^＋/Ca^2＋ , TNF a, IL-1β, IL-2, and IL-6.

Effects of ferulic acid on antioxidant activity in Angelicae Sinensis Radix, Chuanxiong Rhizoma, and their combination

The present study aimed at exploring different roles of the same compound in different environment, using preparative HPLC, and the significance to investigating bio-active constituents in traditional Chinese medicine （TCM） on the basis of holism. In this study, the depletion of target component ferulic acid （FA） by using preparative HPLC followed by antioxidant activity testing was applied to investigate the roles of FA in Angelicae Sinansis Radix （DG）, Chuanxiong Rhizoma （CX） and their combination （GX）. The antioxidant activity was performed by 1, 1-diphenyl-2-picrylhydrazyl （DPPH） radical-scavenging activity testing. FA was successfully and exclusively depleted from DG, CX, and GX, respectively. By comparing the effects of the samples, it was found that FA was one of the main antioxidant constituents in DG, CX and GX, and the roles of FA were DG 〉 CX 〉 GX. Furthermore, the effects of FA varied at different doses in these herbs. This study provided a reliable and effective approach to clarifying the contribution of same compound in different TCMs to their bio-activities. The role of a constituent in different TCMs might be different, and a component with the same content might have different effects in different chemical environments. Furthermore, this study also suggested the potential utilization of preparative HPLC in the characterization of the roles of multi-ingredients in TCM.

Comparative pharmacodynamic, pharmacokinetic and tissue distribution of Dahuang-Gancao decoction in normal and experimental constipation mice

Dahuang-Gancao decoction(DGD)is a classical formula,which is commonly used for reliving constipation in Chinese clinic.The aim of this study was to investigate the pharmacodynamic,pharmacokinetic and tissue distribution alternations of DGD in normal and constipation mice.DGD exhibited stronger purgative effect in constipation mice by the increased fecal excretion and reduced first defection time compared with normal mice.The Cmax,AUC0-t and MRT0-t of rhein,aloe-emodin,rhein-8-O-β-D-glucoside,sennoside A,and glycyrrhizic acid as main bio-active components in DGD were markedly increased in constipation mice.The tissue distribution of the analytes in constipation mice were higher than those in normal mice with rhein>rhein-8-O-β-D-glucoside>aloe-emodin>glycyrrhizic acid>emodin in liver,and glycyrrhizic acid>rhein-8-O-β-D-glucoside>liquitin>sennoside A>rhein>aloe-emodin>emodin in colon.The kidney concentrations of the analytes showed a descending order of rhein>rhein-8-O-β-D-glucoside>sennoside A>glycyrrhizic acid>aloe-emodin>emodin,most of them were higher while rhein was lower in constipation mice than normal mice.The higher exposure of the anthraquinones in plasma,liver and colon may result in the stronger purgative effect in the constipation mice than normal mice.Rhein is mainly excreted through the kidney,the decreased level of rhein in constipation mice may explain the alleviated side effects.Accumulation of glycyrrhizic acid in colon may related with the moderate property of licorice.These results provided the experimental basis for understanding the therapeutic effects and metabolite profile of DGD.