Background:Triple-negative breast cancer(TNBC)has long been a difficult therapeutic target to overcome because of its extreme aggressiveness,poor efficacy and rarity of available treatment regimens.To explore the anti...Background:Triple-negative breast cancer(TNBC)has long been a difficult therapeutic target to overcome because of its extreme aggressiveness,poor efficacy and rarity of available treatment regimens.To explore the anti-TNBC potential of Caulis Polygoni Multiflori(CPM),this investigation applied an integrated computational and experimental approach.Methods:Bioactive CPM compounds were investigated via screening of three TCM databases(TCMSP,TCMID,and HERB)using Bioavailability(OB≥30%)as inclusion criteria.TNBC targets were obtained from the online resources GeneCards,CTD,and OMIM network pharmacology analysis was used to determine common target(s),utilizing two PPI analysis tools–STRING and Cytoscape.Molecular docking assessed target-compound interactions by means of AutoDock Vina.In vitro studies conducted on MDA-MB-231 cells involved evaluating inhibitory effects via MTT,wound-healing assay,transwell,and qPCR techniques.Results:Six bioactive compounds were identified,with emodin(IC_(50) approximately 15μM)and chrysophanol(IC50 approximately 25μM)showing strong binding to TNBC targets(emodin-HSP90AB1:−9.42 kcal/mol;chrysophanol-SRC:−8.32 kcal/mol).Network analysis revealed 143 shared targets,with BCL2,EGFR and ESR1 as key nodes.Pathway analysis implicated PI3K-AKT signaling and apoptosis.In vitro,emodin and chrysophanol synergistically inhibited proliferation,migration and invasion,while downregulating BCL2,EGFR and ESR1 expression.Conclusion:To the best of our knowledge,this is the first report that describes the synergistic mechanisms of multiple compounds from the extract of CPM in TNBC with chrysophanol and emodin working as the main components by mediating oncogenic pathways.展开更多
Recently, adverse effects of Polygoni Multiflori Radix（PMR） and Polygoni Multiflori Radix Praeparata（PMRP） have attracted intensive attention worldwide. These adverse effects most occurred in cases with high dose ...Recently, adverse effects of Polygoni Multiflori Radix（PMR） and Polygoni Multiflori Radix Praeparata（PMRP） have attracted intensive attention worldwide. These adverse effects most occurred in cases with high dose of prolonged medication course. Liver is usually the target organ of these adverse effects. In the present research, we performed in vivo chronic toxicity study and aimed to evaluate relationships between major constituents of water extractions and total anthraquinone of PMR and PMRP and chronic toxicity. SD rats of both sexes were given water extractions as well as total anthraquinone of PMR and PMRP for 12 weeks. We evaluated basic biochemical indexes, conducted microscopic observations of main organs and assessed early indicators of liver and renal fibrosis. Simvastatin, with hypertriglyceridemia and hypercholesterolemia as its main therapeutic areas, was investigated in our study. Component-toxicity relationships were also discussed. Five male rats died in our study, while all female rats survived, suggesting that some gender differences might be involved. Body weight was significantly changed, and basic biochemical indexes were sporadically occurred during the research. Pathological examinations on liver and kidney showed slight alternations after 12 weeks without dose-dependent relationship. Increase in serum laminin（LN） was observed in almost all male rats, indicating that the risks of liver or kidney fibrosis still existed, especially for males, although no fibrosis was found in the pathological examination of liver and kidney. No major and severe adverse effects were observed after 12 weeks of administration of PMR and PMRP. Regular safety monitoring is still necessary during medication in order to prevent possible risks.展开更多
Polygoni Multiflori Radix(PMR) has been commonly used as a tonic in China for centuries. However, PMR-associated hepatotoxicity is becoming a safety issue. In our previous in vivo study, an interaction between stilben...Polygoni Multiflori Radix(PMR) has been commonly used as a tonic in China for centuries. However, PMR-associated hepatotoxicity is becoming a safety issue. In our previous in vivo study, an interaction between stilbenes and anthraquinones has been discovered and a hypothesis is proposed that the interaction between stilbene glucoside-enriching fraction and emodin may contribute to the side effects of PMR. To further support our previous in vivo results in rats, the present in vitro study was designed to evaluate the effects of 2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-D-glucopyranoside(TSG) on the cellular absorption and human liver microsome metabolism of emodin. The obtained results indicated that the absorption of emodin in Caco-2 cells was enhanced and the metabolism of emodin in human liver microsomes was inhibited after TSG treatment. The effects of the transport inhibitors on the cellular emodin accumulation were also examined. Western blot assay suggested that the depressed metabolism of emodin could be attributed to the down-regulation of UDP-glucuronosyltransferases(UGTs) 1A8, 1A10, and 2B7. These findings definitively demonstrated the existence of interaction between TSG and emodin, which provide a basis for a better understanding of the underlying mechanism for PMR-induced liver injury.展开更多
The raw and processed roots of Plygonum multiflorum Thunb(PM) are used to treat different diseases in clinical practice. In order to clarify the influence of processing, a comparative study of chemical substance analy...The raw and processed roots of Plygonum multiflorum Thunb(PM) are used to treat different diseases in clinical practice. In order to clarify the influence of processing, a comparative study of chemical substance analysis was carried out. As the xenobiotics with a high enough exposure in target organs being considered as the potential effective or toxicity components, an in vivo study was also implemented to characterize the constitutes and metabolites, and meanwhile, the factor of compatibility with black bean were also considered. As a result, a total of 148 compounds were detected in PM extracts and more than 40 compounds were only detected in the processed products, which were probably new components produced during the steaming process. In in vivo study, 7 prototype components and 66 metabolites were detected or tentatively identified, 24 of which were reported for the first time. Our results indicated that processing greatly changed the chemical composition of PM and influenced the disposition of the compounds in vivo. To the best of our knowledge, this was the first global comparative study of raw and processed PM. These results expanded our knowledge about the influence of processing of PM and provided the essential data for further efficacy or toxicity studies.展开更多
The aim of this study is to investigate the protective effects of a small molecular fraction(SMF) of Polygoni multiflori Radix Praeparata(PMRP) in a cyclophosphamide(CTX) induced anemia mouse model. Small molecular fr...The aim of this study is to investigate the protective effects of a small molecular fraction(SMF) of Polygoni multiflori Radix Praeparata(PMRP) in a cyclophosphamide(CTX) induced anemia mouse model. Small molecular fraction of PMRP was prepared and identified by high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(HPLC-Q-TOF-MS). In pharmacology, we examined the peripheral hemogram and thymus and spleen index. The content of granulocyte-macrophage colony-stimulating factor(GM-CSF) in serum was mensurated by enzyme-linked immunosorbent assay(ELISA);The level of superoxide dismutase(SOD), catalase(CAT), total antioxidant capacity(T-AOC), and malondialdehyde(MDA) in serum and spleen tissue homogenate were detected, and glutathione peroxidase(GSH-PX) was assayed in spleen. The results show that SMF can significantly accelerate the recovery of peripheral hemogram, increase the activity of antioxidant enzymes and GM-CSF in serum and spleen. SMF also increases the number of spleen cells, improves bone marrow pathology. In conclusion, the SMF of PMRP promoted the recovery of hematopoietic function in a CTX-induced anemia mouse, which can support SMF to be used as an adjunct to chemotherapy to counteract its side effects.展开更多
2,3,5,4'-tetrahydroxystilbene-2-O-(2'-O-feruloyl)-beta -D-glucopyranoside, 2,3,5,4'-tetra hydroxystilbene-2-O-(2'-O-p-coumaroyl)-beta -D-glucopyranoside were isolated from Radix Polygoni multiflori Pre...2,3,5,4'-tetrahydroxystilbene-2-O-(2'-O-feruloyl)-beta -D-glucopyranoside, 2,3,5,4'-tetra hydroxystilbene-2-O-(2'-O-p-coumaroyl)-beta -D-glucopyranoside were isolated from Radix Polygoni multiflori Preparata. Structures were elucidated by chemical and spectral evidences.展开更多
Matrix metalloproteinases（MMPs） play an essential role in development and tissue remodeling of living organisms. However, the overexpression of MMPs has lead to a series of diseases, such as cancer, arthritis, and a...Matrix metalloproteinases（MMPs） play an essential role in development and tissue remodeling of living organisms. However, the overexpression of MMPs has lead to a series of diseases, such as cancer, arthritis, and atherosclerosis; and inhibition of MMPs may have therapeutic benefits. The discovery of MMP inhibitors from herbal has become a prospective event. We showed that the extract of Polygoni multiflori caulis from ethyl acetate or water（ethyl acetate extract and water extract） can inhibit the activities of MMPs 9, 14, and 16 in a dose-dependent manner and n-butyl alcohol extract of it can also inhibit these MMPs. Furthermore, we found that n-butyl alcohol extract and water extract of it influence the cell viability. These discoveries may contribute to the development of MMP in- hibitors for the therapy of a variety of pathological conditions.展开更多
OBJECTIVE:To learn the mechanisms between gut microbiome and the autoimmunity benefits on Traditional Chinese Medicine(TCM)in central nervous system(CNS),we investigated the neuro-protection effects and gut mircobiota...OBJECTIVE:To learn the mechanisms between gut microbiome and the autoimmunity benefits on Traditional Chinese Medicine(TCM)in central nervous system(CNS),we investigated the neuro-protection effects and gut mircobiota changes of Heshouwu(Radix Polygoni Multiflori)on experimental autoimmune encephalomyelitis(EAE),an animal model of multiple sclerosis(MS).METHODS:Mice were randomly divided into four groups:EAE mice(control phosphate-buffered saline group),50 mg·kg^(-1)·d^(-1)Heshouwu(Radix Polygoni Multiflori)-treated EAE mice,100 mg·kg^(-1)·d^(-1)Heshouwu(Radix Polygoni Multiflori)-treated EAE mice,and 200 mg·kg^(-1)·d^(-1)Heshouwu(Radix Polygoni Multiflori)-treated EAE mice.The spinal cords were stained with hematoxylin and eosin(HE)and luxol fast blue for evaluating inflammatory infiltration and demyelination.The percentages of granulocyte macrophage-colony stimulating factor(GM-CSF)+CD4+,interleukin 17(IL-17)+CD4+,Foxp3 CD4+,and interferon-γ(IFN-γ)+CD4+T cells in the inguinal lymph nodes(LNs)and brain were determined by flow cytometry analysis.16S rRNA gene sequencing was employed to analyze the changes in gut microbiota.RESULTS:We found that Heshouwu(Radix Polygoni Multiflori)alleviated the disease severity and neuropathology of EAE as evaluated by clinical and histopathologyical scores.Heshouwu(Radix Polygoni Multiflori)increased the diversity and abundance of the gut microbiota,and decreased Firmicutes/Bacteroidetes ratio(F/B ratio).Heshouwu(Radix Polygoni Multiflori)also decreased the concentrations of IL-10,and IL-21 and increase the levels of GM-CSF,IL-17A,IL-17F and IL-22 in serum of EAE mice.Moreover,Heshouwu(Radix Polygoni Multiflori)modulated the T cell responses by inhibiting Th17 cells and restoring Treg cells in the small intestine lymphoid tissues and inguinal lymph nodes.Microbiota-depleted mice receiving Heshouwu(Radix Polygoni Multiflori)-treated fecal microbiota transplantation had lower disease severity,neuropathology scores and alleviation of Th17/Treg imbalance compared to ad libitum group.CONCLUSIONS:Our findings suggested that the vital neuro-protection role of Heshouwu(Radix Polygoni Multiflori)(TCM)in immunomodulation effects partly by regulations of gut microbiome.展开更多
[Objectives]To study the protective effects and mechanism of POLYGONI PERFOLIATI HERBA on rats with nonalcoholic steatohepatitis( NASH). [Methods] Sixty rats were randomly divided into normal group,model group,metform...[Objectives]To study the protective effects and mechanism of POLYGONI PERFOLIATI HERBA on rats with nonalcoholic steatohepatitis( NASH). [Methods] Sixty rats were randomly divided into normal group,model group,metformin group( 0. 5 mg/kg),and high dose,medium dose,and low dose groups of total flavonoids of POLYGONI PERFOLIATI HERBA( 600,300,150 mg/kg). The standard feed was given to the normal group,and the model group and the total flavonoids groups were fed with high-fat diet for 13 weeks to establish the NASH rat model. At the 8 th week,the metformin group and the POLYGONI PERFOLIATI HERBA total flavonoids groups were given with the corresponding drug treatment for 6 weeks,blood was taken from the eyeball to collect liver tissue. Biochemical method was used to determine ALT,AST,TC,TG,HDL-c,LDL-c,SOD,MDA,GSH-Px activity or content in serum and HOMA-IR,and ELISA was used to measure the TNF-α,IL-1β and IL-6 content in liver tissue; Western blotting was used to detect the expression levels of AMPK,p-AMPK and ACC in liver tissue. [Results] Total flavonoids of POLYGONI PERFOLIATI HERBA could significantly decrease the activity or content of ALT,AST and MDA in serum of NASH rats( P < 0. 05,P < 0. 01),and enhance the activity of SOD and GSH-Px( P < 0. 05,P < 0. 01),reduce serum TC,TG,LDL-c levels and insulin resistance index,increase HDL-c levels( P < 0. 05,P < 0. 01); down-regulate liver IL-1β,IL-6,TNF-α,ACC levels and up-regulate p-AMPK expression( P < 0. 05,P < 0. 01). [Conclusions]The total flavonoids of POLYGONI PERFOLIATI HERBA have a good protective effect on NASH rats,and its mechanism may be related to the functions of regulating the lipid metabolism,alleviating insulin resistance,inhibiting oxidative stress,inhibiting inflammatory reaction and regulating AMPK and ACC protein expression.展开更多
Objectives: Radix Polygoni Multiflori Praeparata (RPMP) and Dioscorea Bulbifera Rhizomes (DBR) are used in Chinese herbal medicine and have been frequently reported for adverse reactions on liver. In this research, we...Objectives: Radix Polygoni Multiflori Praeparata (RPMP) and Dioscorea Bulbifera Rhizomes (DBR) are used in Chinese herbal medicine and have been frequently reported for adverse reactions on liver. In this research, we aimed to evaluate in vivo effects of RPMP and DBR on rat cytochrome P450 enzymes (CYP1A2, CYP2E1 and CYP3A2) with their respective substrates as probes. Methods: Rats were orally administered RPMP, DBR and RPMP/DBR combination at 12, 10 and (12 + 10) g/kg, respectively, or saline as a control, once daily for 7 days. Thereafter, a cocktail containing 10 mg/kg caffeine, 20 mg/kg chlorzoxazone and 10 mg/kg dapsone was tail vein injected to rats. At defined time points, plasma drug concentrations were simultaneously evaluated by HPLC. Pharmacokinetic parameters simulated by DAS software were used to assess RPMP and/or DBR effects on cytochrome P450 enzymes activity. ANOVA and Dunnett’s test were used for data analysis. Results: Caffeine metabolism was enhanced in RPMP animals and reduced after pretreatment with DBR, but no effect was observed in RPMP/DBR combination group. Chlorzoxazone and dapsone metabolism was enhanced in both RPMP and DBR groups and consequently in combination group. The data suggested that RPMP independently induces rat CYP1A2, CYP2E1 and CYP3A2 activity, while DBR independently inhibits activity of rat CYP1A2 and induces that of CYP2E1 and CYP3A2. RPMP/DBR combination showed no significant benefit compared with the two drugs alone and even showed a neutralized effect in CYP1A2 activity. Conclusions: Caution is needed when RPMP and/or DBR are co-administered with drugs metabolized by human CYP1A2, CYP2E1 and CYP3A4.展开更多
[Objectives]The differences in secondary metabolites of Herba Polygoni Chinensis from Guangxi were analyzed,in order to find flavonoids which can antagonize liver injury and provide a basis for the quality evaluation ...[Objectives]The differences in secondary metabolites of Herba Polygoni Chinensis from Guangxi were analyzed,in order to find flavonoids which can antagonize liver injury and provide a basis for the quality evaluation of Herba Polygoni Chinensis.[Methods]UPLC-MS was used to analyze the secondary metabolites of Herba Polygoni Chinensis,and emphasis was placed on flavonoids.[Results]Flavonoids were abundant in the secondary metabolites of Herba Polygoni Chinensis.Quercitrin,catechin gallate,epicatechin gallate,hyperoside and so on were screened as the components with high content and antagonistic effect on liver injury.[Conclusions]Quercitrin was the flavonoid compound with the highest content among the three origins.It is stable and has a good protective effect on liver,which is representative.Quercitrin can be considered as the target component to be used as an important index for quality evaluation of Herba Polygoni Chinensis.展开更多
[Objectives]This study was conducted to determine the contents of such five heavy metals as lead(Pb),cadmium(Cd),arsenic(As),mercury(Hg)and copper(Cu)and the contents of nine kinds of organochlorine pesticide residues...[Objectives]This study was conducted to determine the contents of such five heavy metals as lead(Pb),cadmium(Cd),arsenic(As),mercury(Hg)and copper(Cu)and the contents of nine kinds of organochlorine pesticide residues including total BHC(α-BHC,β-BHC,γ-BHC,δ-BHC)and total DDT(pp-DDE,pp-DDD,op-DDT,pp-DDT)and pentachloronitrobenzene in the Zhuang medicine Herba Polygoni Chinensis from 13 producing areas.[Methods]The five heavy metals were determined in accordance with the second method of general rule 2341,the inductively coupled plasma mass spectrometry method,in part 4 of the 2020 edition of Chinese Pharmacopoeia;and the nine organochlorines were determined in accordance with the first method of general rule 2341,organochlorine pesticide residue determination method(chromatography),in part 4 of the 2020 edition of Chinese Pharmacopoeia.[Results]In the Herba Polygoni Chinensis from 13 origins,the lead contents were in the range of 0.50-3.28 mg/kg;the cadmium contents were in the range of 0.06-4.21 mg/kg;the arsenic contents were in the range of 0.16-6.9 mg/kg;the copper contents were in the range of 10.5-45.1 mg/kg;the mercury contents were in the range of 0.00-0.003 mg/kg;and the nine organochlorines including the total benzene hexachloride(α-BHC,β-BHC,γ-BHC,δ-BHC),total DDT(pp-DDE,pp-DDD,op-DDT,pp-DDT)and pentachloronitrobenzene were all not detected.Referring to part 4 of the 2020 edition of Chinese Pharmacopoeia,the Cu and As of the Herba Polygoni Chinensis produced in Hezhou exceeded the standards,the Cu of the Herba Polygoni Chinensis produced in Wuzhou exceeded the standard,and the As of the Herba Polygoni Chinensis produced in Yulin City and Guilin City exceeded the standard.[Conclusions]This study provides safety limit test data for the development and utilization of Herba Polygoni Chinensis of the Zhuang medicine.展开更多
Background:The incidence and prevalence of atherosclerosis(AS)is increasing every year and has becoming a major health issue of global concern.Polygoni Cuspidati Rhizoma(PCR)is a Chinese herb that is widely used clini...Background:The incidence and prevalence of atherosclerosis(AS)is increasing every year and has becoming a major health issue of global concern.Polygoni Cuspidati Rhizoma(PCR)is a Chinese herb that is widely used clinically for the treating of AS.However,its pertinent targets and probable mechanisms,still need to be completely explored.Methods:Active compounds and targets for PCR and AS targets were screened using public databases.A“drug-component-disease target”network map was created and analyzed after using the Venn online tool to identify common targets and Cytoscape software to screen drug-disease core targets.Critical targets pathway enrichment analyses are conducted using the Metascape database.Using AutoDock Vina and Pymol software,docking validation and visualization of active components and core targets were carried out.Results:PCR was obtained for ten compounds with 105 AS-related targets.Rhein,quercetin,beta-sitosterol,and luteolin may be drug candidates,and the genes for AKT1,TNF,IL-6,EGFR,TP53,IL-1,RELA,and VEGFA are potential therapeutic targets,according to network analysis.PCR might modulate the AGE/RAGE,PI3K/Akt,IL-17 and NF-ᴋB signaling pathways against the development of AS.Molecular docking indicated that quercetin has high affinity for AKT1 and TNF gene targets.Conclusion:This study provides rare information and scientific basis for further exploration of PC in the treatment of AS.展开更多
To enhance the antifungal response of blackgram (Vigna mungo L.), transgenic plants were generated by transferring bacterial chitinase gene with a CaMV 35S promoter. The chopped multiple shoot cells developed on the c...To enhance the antifungal response of blackgram (Vigna mungo L.), transgenic plants were generated by transferring bacterial chitinase gene with a CaMV 35S promoter. The chopped multiple shoot cells developed on the cotyledonary node were transformed by Particle gun method. Thecalli were raised on the Murashige and Skoog (MS) modified media supplemented with 50 m·gl-1 kanamycin. The transformation efficiency was 13% approximately. The resultant shoot buds were selected and the antibiotic resistant transgenic plantlets were regenerated. The development of the transgenic plants from the shoot buds took about four to six months. The integration of the transgene was confirmed by PCR, RT-PCR, Southern and western blot analyses. The transgenic plants exhibited higher chitinase activity than the non-transformed ones. The chitinase activity was examined by native polyacrylamide in-gel assay. The transgenic plants showed fungal tolerance as evidenced by the delayed onset of the disease and smaller lesions following an in vitro inoculation of the powdery mildew pathogen (Erysiphae polygoni DC). The transgenic plants adapted well to the greenhouse and did not show any phenotypic alterations.展开更多
The epidermal growth factor receptors(EGFRs)in some tumor cells are significant targets for drug discovery.In this work,we have developed an EGFR cell membrane chromatography and online high performance liquid chromat...The epidermal growth factor receptors(EGFRs)in some tumor cells are significant targets for drug discovery.In this work,we have developed an EGFR cell membrane chromatography and online high performance liquid chromatography/mass spectrometry system for screening active component from Rhizoma Polygoni Cuspidati.As a result,resveratrol from Rhizoma Polygoni Cuspidati was found to be the active component acting on EGFR like gefitinib.There was a good relationship between their inhibiting effects on EGFR secretion and HEK293 EGFR cell growth in vitro.The EGFR/CMC-online-HPLC/MS system demonstrated fast and effective characteristics for screening leading compounds from traditional Chinese medicine.展开更多
Objective To investigate the effects of Polygoni Cuspidati Rhizoma et Radix （PCRR） and its ingredient resveratrol （Res） on experimental autoimmune myasthenia gravis （EAMG）. Methods EAMG was induced in Lewis rats...Objective To investigate the effects of Polygoni Cuspidati Rhizoma et Radix （PCRR） and its ingredient resveratrol （Res） on experimental autoimmune myasthenia gravis （EAMG）. Methods EAMG was induced in Lewis rats by the immunization of a synthetic peptide corresponding to region 97-116 of the rat acetylcholine receptor （AChR） α subunit （R97-116）. EAMG rats were randomly divided into PCRR group, Res group, and control （C） group, and were ig administered respectively with PCRR （2 g/kg）, Res （20 mg/kg）, and DMSO （0.4 mL/kg） every day from day 5 after immunization to day 42. Clinical evaluation, lymphocyte proliferation, cytokines, and anti-97-116 antibodies were performed for examination of their therapeutic effects. Results Treatments with PCRR and Res significantly ameliorated clinical symptoms, down-regulated TNF-α and up-regulated IL-10 in serum and culture supernatants of lymphocytes stimulated with R97-116, and decreased levels of anti-R97-116 IgG1 and IgG2a in serum compared with C group. Unexpectedly, PCRR but not Res inhibited lymphocyte proliferation compared with C group. Conclusion PCRR and Res ameliorating EAMG is associated with suppressing immune response, and indicates a therapeutic potential for EAMG and even human myasthenia gravis （MG）. Res may be the main effective ingredient from PCRR ameliorating EAMG, but further experiments are necessary.展开更多
基金supported by 2022 Anhui University Research Project(grant numbers No.2022AH051162)2023 Anhui University Collaborative innovation project(grant numbers No.GXXT-2023-074)National Key Clinical Collaboration Project for Difficult and Complex Diseases(Ovarian Malignancies)Integrating Traditional Chinese and Western Medicine(grant numbers National Traditional Chinese Medicine Comprehensive Development Document(2024)No.3).
文摘Background:Triple-negative breast cancer(TNBC)has long been a difficult therapeutic target to overcome because of its extreme aggressiveness,poor efficacy and rarity of available treatment regimens.To explore the anti-TNBC potential of Caulis Polygoni Multiflori(CPM),this investigation applied an integrated computational and experimental approach.Methods:Bioactive CPM compounds were investigated via screening of three TCM databases(TCMSP,TCMID,and HERB)using Bioavailability(OB≥30%)as inclusion criteria.TNBC targets were obtained from the online resources GeneCards,CTD,and OMIM network pharmacology analysis was used to determine common target(s),utilizing two PPI analysis tools–STRING and Cytoscape.Molecular docking assessed target-compound interactions by means of AutoDock Vina.In vitro studies conducted on MDA-MB-231 cells involved evaluating inhibitory effects via MTT,wound-healing assay,transwell,and qPCR techniques.Results:Six bioactive compounds were identified,with emodin(IC_(50) approximately 15μM)and chrysophanol(IC50 approximately 25μM)showing strong binding to TNBC targets(emodin-HSP90AB1:−9.42 kcal/mol;chrysophanol-SRC:−8.32 kcal/mol).Network analysis revealed 143 shared targets,with BCL2,EGFR and ESR1 as key nodes.Pathway analysis implicated PI3K-AKT signaling and apoptosis.In vitro,emodin and chrysophanol synergistically inhibited proliferation,migration and invasion,while downregulating BCL2,EGFR and ESR1 expression.Conclusion:To the best of our knowledge,this is the first report that describes the synergistic mechanisms of multiple compounds from the extract of CPM in TNBC with chrysophanol and emodin working as the main components by mediating oncogenic pathways.
基金National Natural Science Foundation of China(Grant No.8106033781260553+2 种基金81460623)Natural Science Foundation of Yunnan Province(Grant No.2014FA0352012FD043)
文摘Recently, adverse effects of Polygoni Multiflori Radix（PMR） and Polygoni Multiflori Radix Praeparata（PMRP） have attracted intensive attention worldwide. These adverse effects most occurred in cases with high dose of prolonged medication course. Liver is usually the target organ of these adverse effects. In the present research, we performed in vivo chronic toxicity study and aimed to evaluate relationships between major constituents of water extractions and total anthraquinone of PMR and PMRP and chronic toxicity. SD rats of both sexes were given water extractions as well as total anthraquinone of PMR and PMRP for 12 weeks. We evaluated basic biochemical indexes, conducted microscopic observations of main organs and assessed early indicators of liver and renal fibrosis. Simvastatin, with hypertriglyceridemia and hypercholesterolemia as its main therapeutic areas, was investigated in our study. Component-toxicity relationships were also discussed. Five male rats died in our study, while all female rats survived, suggesting that some gender differences might be involved. Body weight was significantly changed, and basic biochemical indexes were sporadically occurred during the research. Pathological examinations on liver and kidney showed slight alternations after 12 weeks without dose-dependent relationship. Increase in serum laminin（LN） was observed in almost all male rats, indicating that the risks of liver or kidney fibrosis still existed, especially for males, although no fibrosis was found in the pathological examination of liver and kidney. No major and severe adverse effects were observed after 12 weeks of administration of PMR and PMRP. Regular safety monitoring is still necessary during medication in order to prevent possible risks.
基金supported by the National Natural Science Foundation of China(Nos.81573562,81322051,and 81073007)the Natural Science Foundation of Jiangsu Province(No.BK20151442)
文摘Polygoni Multiflori Radix(PMR) has been commonly used as a tonic in China for centuries. However, PMR-associated hepatotoxicity is becoming a safety issue. In our previous in vivo study, an interaction between stilbenes and anthraquinones has been discovered and a hypothesis is proposed that the interaction between stilbene glucoside-enriching fraction and emodin may contribute to the side effects of PMR. To further support our previous in vivo results in rats, the present in vitro study was designed to evaluate the effects of 2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-D-glucopyranoside(TSG) on the cellular absorption and human liver microsome metabolism of emodin. The obtained results indicated that the absorption of emodin in Caco-2 cells was enhanced and the metabolism of emodin in human liver microsomes was inhibited after TSG treatment. The effects of the transport inhibitors on the cellular emodin accumulation were also examined. Western blot assay suggested that the depressed metabolism of emodin could be attributed to the down-regulation of UDP-glucuronosyltransferases(UGTs) 1A8, 1A10, and 2B7. These findings definitively demonstrated the existence of interaction between TSG and emodin, which provide a basis for a better understanding of the underlying mechanism for PMR-induced liver injury.
基金supported by National Natural Science Foundation of China(Nos.81373967 and 81402887)Traditional Chinese Medicine Administration Bureau of Traditional Chinese Medicine Standardization project(No.ZYBZH-Y-SH-38)
文摘The raw and processed roots of Plygonum multiflorum Thunb(PM) are used to treat different diseases in clinical practice. In order to clarify the influence of processing, a comparative study of chemical substance analysis was carried out. As the xenobiotics with a high enough exposure in target organs being considered as the potential effective or toxicity components, an in vivo study was also implemented to characterize the constitutes and metabolites, and meanwhile, the factor of compatibility with black bean were also considered. As a result, a total of 148 compounds were detected in PM extracts and more than 40 compounds were only detected in the processed products, which were probably new components produced during the steaming process. In in vivo study, 7 prototype components and 66 metabolites were detected or tentatively identified, 24 of which were reported for the first time. Our results indicated that processing greatly changed the chemical composition of PM and influenced the disposition of the compounds in vivo. To the best of our knowledge, this was the first global comparative study of raw and processed PM. These results expanded our knowledge about the influence of processing of PM and provided the essential data for further efficacy or toxicity studies.
文摘The aim of this study is to investigate the protective effects of a small molecular fraction(SMF) of Polygoni multiflori Radix Praeparata(PMRP) in a cyclophosphamide(CTX) induced anemia mouse model. Small molecular fraction of PMRP was prepared and identified by high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(HPLC-Q-TOF-MS). In pharmacology, we examined the peripheral hemogram and thymus and spleen index. The content of granulocyte-macrophage colony-stimulating factor(GM-CSF) in serum was mensurated by enzyme-linked immunosorbent assay(ELISA);The level of superoxide dismutase(SOD), catalase(CAT), total antioxidant capacity(T-AOC), and malondialdehyde(MDA) in serum and spleen tissue homogenate were detected, and glutathione peroxidase(GSH-PX) was assayed in spleen. The results show that SMF can significantly accelerate the recovery of peripheral hemogram, increase the activity of antioxidant enzymes and GM-CSF in serum and spleen. SMF also increases the number of spleen cells, improves bone marrow pathology. In conclusion, the SMF of PMRP promoted the recovery of hematopoietic function in a CTX-induced anemia mouse, which can support SMF to be used as an adjunct to chemotherapy to counteract its side effects.
基金the National Natural Science Foundation of China (29872057), Science and Technology Foundation of Shanghai.
文摘2,3,5,4'-tetrahydroxystilbene-2-O-(2'-O-feruloyl)-beta -D-glucopyranoside, 2,3,5,4'-tetra hydroxystilbene-2-O-(2'-O-p-coumaroyl)-beta -D-glucopyranoside were isolated from Radix Polygoni multiflori Preparata. Structures were elucidated by chemical and spectral evidences.
基金Supported by the National Natural Science Foundation of China(No.30571656).
文摘Matrix metalloproteinases（MMPs） play an essential role in development and tissue remodeling of living organisms. However, the overexpression of MMPs has lead to a series of diseases, such as cancer, arthritis, and atherosclerosis; and inhibition of MMPs may have therapeutic benefits. The discovery of MMP inhibitors from herbal has become a prospective event. We showed that the extract of Polygoni multiflori caulis from ethyl acetate or water（ethyl acetate extract and water extract） can inhibit the activities of MMPs 9, 14, and 16 in a dose-dependent manner and n-butyl alcohol extract of it can also inhibit these MMPs. Furthermore, we found that n-butyl alcohol extract and water extract of it influence the cell viability. These discoveries may contribute to the development of MMP in- hibitors for the therapy of a variety of pathological conditions.
基金National Natural Science Foundation of China:Role and Mechanism of Akkermansia-Mediated Activation of Microglia NLRP3 Inflammasome in Multiple Sclerosis(No.82101419)Jiangxi Provincial Natural Science Foundation:the Role and Mechanism of p38 MAPK Signaling Pathway Induced by Intestinal Flora Change in EAE Mice(No.20212BAB216024)+3 种基金Jiangxi Science and Technology Project of Chinese Medicine:Study on the Role and Mechanism of CGAS-STING Signaling Pathway in Microglia Mediated by Rhodiola Sachalinensis in Multiple Sclerosis(No.2021B660,No.2022B1007)Jiangxi Science and Technology Program of Health Commission:the Role and Mechanism of Intestinal Flora Changes in Mediating the Activation of NLRP3 Inflammasome in Microglia in Multiple Sclerosis(No.202210392)Science and Technology Research Project of Jiangxi Education:Study on the Role and Mechanism of p38 MAPK Signaling Pathway Induced by Intestinal Flora Changes in EAE Mice(No.GJJ200215)Scientific Research and Development Project of the First Affiliated Hospital of Nanchang University:Effects of Exercise Training on Intestinal Flora of Multiple Sclerosis Model Rats and Its Mechanism(No.YFYPY202021)。
文摘OBJECTIVE:To learn the mechanisms between gut microbiome and the autoimmunity benefits on Traditional Chinese Medicine(TCM)in central nervous system(CNS),we investigated the neuro-protection effects and gut mircobiota changes of Heshouwu(Radix Polygoni Multiflori)on experimental autoimmune encephalomyelitis(EAE),an animal model of multiple sclerosis(MS).METHODS:Mice were randomly divided into four groups:EAE mice(control phosphate-buffered saline group),50 mg·kg^(-1)·d^(-1)Heshouwu(Radix Polygoni Multiflori)-treated EAE mice,100 mg·kg^(-1)·d^(-1)Heshouwu(Radix Polygoni Multiflori)-treated EAE mice,and 200 mg·kg^(-1)·d^(-1)Heshouwu(Radix Polygoni Multiflori)-treated EAE mice.The spinal cords were stained with hematoxylin and eosin(HE)and luxol fast blue for evaluating inflammatory infiltration and demyelination.The percentages of granulocyte macrophage-colony stimulating factor(GM-CSF)+CD4+,interleukin 17(IL-17)+CD4+,Foxp3 CD4+,and interferon-γ(IFN-γ)+CD4+T cells in the inguinal lymph nodes(LNs)and brain were determined by flow cytometry analysis.16S rRNA gene sequencing was employed to analyze the changes in gut microbiota.RESULTS:We found that Heshouwu(Radix Polygoni Multiflori)alleviated the disease severity and neuropathology of EAE as evaluated by clinical and histopathologyical scores.Heshouwu(Radix Polygoni Multiflori)increased the diversity and abundance of the gut microbiota,and decreased Firmicutes/Bacteroidetes ratio(F/B ratio).Heshouwu(Radix Polygoni Multiflori)also decreased the concentrations of IL-10,and IL-21 and increase the levels of GM-CSF,IL-17A,IL-17F and IL-22 in serum of EAE mice.Moreover,Heshouwu(Radix Polygoni Multiflori)modulated the T cell responses by inhibiting Th17 cells and restoring Treg cells in the small intestine lymphoid tissues and inguinal lymph nodes.Microbiota-depleted mice receiving Heshouwu(Radix Polygoni Multiflori)-treated fecal microbiota transplantation had lower disease severity,neuropathology scores and alleviation of Th17/Treg imbalance compared to ad libitum group.CONCLUSIONS:Our findings suggested that the vital neuro-protection role of Heshouwu(Radix Polygoni Multiflori)(TCM)in immunomodulation effects partly by regulations of gut microbiome.
基金Supported by Project of National Natural Science Foundation(81460602)Natural Science Foundation Project of Guangxi(2017GXNSFAA198326)
文摘[Objectives]To study the protective effects and mechanism of POLYGONI PERFOLIATI HERBA on rats with nonalcoholic steatohepatitis( NASH). [Methods] Sixty rats were randomly divided into normal group,model group,metformin group( 0. 5 mg/kg),and high dose,medium dose,and low dose groups of total flavonoids of POLYGONI PERFOLIATI HERBA( 600,300,150 mg/kg). The standard feed was given to the normal group,and the model group and the total flavonoids groups were fed with high-fat diet for 13 weeks to establish the NASH rat model. At the 8 th week,the metformin group and the POLYGONI PERFOLIATI HERBA total flavonoids groups were given with the corresponding drug treatment for 6 weeks,blood was taken from the eyeball to collect liver tissue. Biochemical method was used to determine ALT,AST,TC,TG,HDL-c,LDL-c,SOD,MDA,GSH-Px activity or content in serum and HOMA-IR,and ELISA was used to measure the TNF-α,IL-1β and IL-6 content in liver tissue; Western blotting was used to detect the expression levels of AMPK,p-AMPK and ACC in liver tissue. [Results] Total flavonoids of POLYGONI PERFOLIATI HERBA could significantly decrease the activity or content of ALT,AST and MDA in serum of NASH rats( P < 0. 05,P < 0. 01),and enhance the activity of SOD and GSH-Px( P < 0. 05,P < 0. 01),reduce serum TC,TG,LDL-c levels and insulin resistance index,increase HDL-c levels( P < 0. 05,P < 0. 01); down-regulate liver IL-1β,IL-6,TNF-α,ACC levels and up-regulate p-AMPK expression( P < 0. 05,P < 0. 01). [Conclusions]The total flavonoids of POLYGONI PERFOLIATI HERBA have a good protective effect on NASH rats,and its mechanism may be related to the functions of regulating the lipid metabolism,alleviating insulin resistance,inhibiting oxidative stress,inhibiting inflammatory reaction and regulating AMPK and ACC protein expression.
文摘Objectives: Radix Polygoni Multiflori Praeparata (RPMP) and Dioscorea Bulbifera Rhizomes (DBR) are used in Chinese herbal medicine and have been frequently reported for adverse reactions on liver. In this research, we aimed to evaluate in vivo effects of RPMP and DBR on rat cytochrome P450 enzymes (CYP1A2, CYP2E1 and CYP3A2) with their respective substrates as probes. Methods: Rats were orally administered RPMP, DBR and RPMP/DBR combination at 12, 10 and (12 + 10) g/kg, respectively, or saline as a control, once daily for 7 days. Thereafter, a cocktail containing 10 mg/kg caffeine, 20 mg/kg chlorzoxazone and 10 mg/kg dapsone was tail vein injected to rats. At defined time points, plasma drug concentrations were simultaneously evaluated by HPLC. Pharmacokinetic parameters simulated by DAS software were used to assess RPMP and/or DBR effects on cytochrome P450 enzymes activity. ANOVA and Dunnett’s test were used for data analysis. Results: Caffeine metabolism was enhanced in RPMP animals and reduced after pretreatment with DBR, but no effect was observed in RPMP/DBR combination group. Chlorzoxazone and dapsone metabolism was enhanced in both RPMP and DBR groups and consequently in combination group. The data suggested that RPMP independently induces rat CYP1A2, CYP2E1 and CYP3A2 activity, while DBR independently inhibits activity of rat CYP1A2 and induces that of CYP2E1 and CYP3A2. RPMP/DBR combination showed no significant benefit compared with the two drugs alone and even showed a neutralized effect in CYP1A2 activity. Conclusions: Caution is needed when RPMP and/or DBR are co-administered with drugs metabolized by human CYP1A2, CYP2E1 and CYP3A4.
基金Development of Huotanmu Capsules,a New Zhuang Drug for Hepatitis B(20183046-1)Collaborative Innovation Center of Zhuang and Yao Ethnic Medicine(Gui Jiao Ke Yan[2013]20)+2 种基金Guangxi Key Laboratory of Zhuang and Yao Ethnic Medicine(Gui Ke Ji Zi[2014]32)Key Discipline of Guangxi:Science of Zhuang Medicine(Gui Jiao Ke Yan[2013]16)First-class Discipline of Guangxi:Ethnopharmacology(Gui Jiao Ke Yan[2018]12).
文摘[Objectives]The differences in secondary metabolites of Herba Polygoni Chinensis from Guangxi were analyzed,in order to find flavonoids which can antagonize liver injury and provide a basis for the quality evaluation of Herba Polygoni Chinensis.[Methods]UPLC-MS was used to analyze the secondary metabolites of Herba Polygoni Chinensis,and emphasis was placed on flavonoids.[Results]Flavonoids were abundant in the secondary metabolites of Herba Polygoni Chinensis.Quercitrin,catechin gallate,epicatechin gallate,hyperoside and so on were screened as the components with high content and antagonistic effect on liver injury.[Conclusions]Quercitrin was the flavonoid compound with the highest content among the three origins.It is stable and has a good protective effect on liver,which is representative.Quercitrin can be considered as the target component to be used as an important index for quality evaluation of Herba Polygoni Chinensis.
基金Development of Huotanmu Capsules,a New Zhuang Ethnic Medicine for the Treatment of Hepatitis B(20183046-1)Collaborative Innovation Center of Zhuang and Yao Ethnic Medicine(GJKY[2013]20)+2 种基金Guangxi Key Laboratory of Zhuang and Yao Ethnic Medicines(GKJZ[2014]32)Guangxi Key Discipline:Zhuang Pharmacology(GJKY[2013]16)First-class Discipline in Guangxi of Traditional Chinese Pharmacology(Direction of Ethnic Medicine)(GJKY[2018]12).
文摘[Objectives]This study was conducted to determine the contents of such five heavy metals as lead(Pb),cadmium(Cd),arsenic(As),mercury(Hg)and copper(Cu)and the contents of nine kinds of organochlorine pesticide residues including total BHC(α-BHC,β-BHC,γ-BHC,δ-BHC)and total DDT(pp-DDE,pp-DDD,op-DDT,pp-DDT)and pentachloronitrobenzene in the Zhuang medicine Herba Polygoni Chinensis from 13 producing areas.[Methods]The five heavy metals were determined in accordance with the second method of general rule 2341,the inductively coupled plasma mass spectrometry method,in part 4 of the 2020 edition of Chinese Pharmacopoeia;and the nine organochlorines were determined in accordance with the first method of general rule 2341,organochlorine pesticide residue determination method(chromatography),in part 4 of the 2020 edition of Chinese Pharmacopoeia.[Results]In the Herba Polygoni Chinensis from 13 origins,the lead contents were in the range of 0.50-3.28 mg/kg;the cadmium contents were in the range of 0.06-4.21 mg/kg;the arsenic contents were in the range of 0.16-6.9 mg/kg;the copper contents were in the range of 10.5-45.1 mg/kg;the mercury contents were in the range of 0.00-0.003 mg/kg;and the nine organochlorines including the total benzene hexachloride(α-BHC,β-BHC,γ-BHC,δ-BHC),total DDT(pp-DDE,pp-DDD,op-DDT,pp-DDT)and pentachloronitrobenzene were all not detected.Referring to part 4 of the 2020 edition of Chinese Pharmacopoeia,the Cu and As of the Herba Polygoni Chinensis produced in Hezhou exceeded the standards,the Cu of the Herba Polygoni Chinensis produced in Wuzhou exceeded the standard,and the As of the Herba Polygoni Chinensis produced in Yulin City and Guilin City exceeded the standard.[Conclusions]This study provides safety limit test data for the development and utilization of Herba Polygoni Chinensis of the Zhuang medicine.
基金supported by Project of first-class discipline construction in Yunnan Province(2022YS13).
文摘Background:The incidence and prevalence of atherosclerosis(AS)is increasing every year and has becoming a major health issue of global concern.Polygoni Cuspidati Rhizoma(PCR)is a Chinese herb that is widely used clinically for the treating of AS.However,its pertinent targets and probable mechanisms,still need to be completely explored.Methods:Active compounds and targets for PCR and AS targets were screened using public databases.A“drug-component-disease target”network map was created and analyzed after using the Venn online tool to identify common targets and Cytoscape software to screen drug-disease core targets.Critical targets pathway enrichment analyses are conducted using the Metascape database.Using AutoDock Vina and Pymol software,docking validation and visualization of active components and core targets were carried out.Results:PCR was obtained for ten compounds with 105 AS-related targets.Rhein,quercetin,beta-sitosterol,and luteolin may be drug candidates,and the genes for AKT1,TNF,IL-6,EGFR,TP53,IL-1,RELA,and VEGFA are potential therapeutic targets,according to network analysis.PCR might modulate the AGE/RAGE,PI3K/Akt,IL-17 and NF-ᴋB signaling pathways against the development of AS.Molecular docking indicated that quercetin has high affinity for AKT1 and TNF gene targets.Conclusion:This study provides rare information and scientific basis for further exploration of PC in the treatment of AS.
文摘To enhance the antifungal response of blackgram (Vigna mungo L.), transgenic plants were generated by transferring bacterial chitinase gene with a CaMV 35S promoter. The chopped multiple shoot cells developed on the cotyledonary node were transformed by Particle gun method. Thecalli were raised on the Murashige and Skoog (MS) modified media supplemented with 50 m·gl-1 kanamycin. The transformation efficiency was 13% approximately. The resultant shoot buds were selected and the antibiotic resistant transgenic plantlets were regenerated. The development of the transgenic plants from the shoot buds took about four to six months. The integration of the transgene was confirmed by PCR, RT-PCR, Southern and western blot analyses. The transgenic plants exhibited higher chitinase activity than the non-transformed ones. The chitinase activity was examined by native polyacrylamide in-gel assay. The transgenic plants showed fungal tolerance as evidenced by the delayed onset of the disease and smaller lesions following an in vitro inoculation of the powdery mildew pathogen (Erysiphae polygoni DC). The transgenic plants adapted well to the greenhouse and did not show any phenotypic alterations.
基金This work was supported by the National Natural Science Foundation of China(Grant number 30730110).
文摘The epidermal growth factor receptors(EGFRs)in some tumor cells are significant targets for drug discovery.In this work,we have developed an EGFR cell membrane chromatography and online high performance liquid chromatography/mass spectrometry system for screening active component from Rhizoma Polygoni Cuspidati.As a result,resveratrol from Rhizoma Polygoni Cuspidati was found to be the active component acting on EGFR like gefitinib.There was a good relationship between their inhibiting effects on EGFR secretion and HEK293 EGFR cell growth in vitro.The EGFR/CMC-online-HPLC/MS system demonstrated fast and effective characteristics for screening leading compounds from traditional Chinese medicine.
文摘Objective To investigate the effects of Polygoni Cuspidati Rhizoma et Radix （PCRR） and its ingredient resveratrol （Res） on experimental autoimmune myasthenia gravis （EAMG）. Methods EAMG was induced in Lewis rats by the immunization of a synthetic peptide corresponding to region 97-116 of the rat acetylcholine receptor （AChR） α subunit （R97-116）. EAMG rats were randomly divided into PCRR group, Res group, and control （C） group, and were ig administered respectively with PCRR （2 g/kg）, Res （20 mg/kg）, and DMSO （0.4 mL/kg） every day from day 5 after immunization to day 42. Clinical evaluation, lymphocyte proliferation, cytokines, and anti-97-116 antibodies were performed for examination of their therapeutic effects. Results Treatments with PCRR and Res significantly ameliorated clinical symptoms, down-regulated TNF-α and up-regulated IL-10 in serum and culture supernatants of lymphocytes stimulated with R97-116, and decreased levels of anti-R97-116 IgG1 and IgG2a in serum compared with C group. Unexpectedly, PCRR but not Res inhibited lymphocyte proliferation compared with C group. Conclusion PCRR and Res ameliorating EAMG is associated with suppressing immune response, and indicates a therapeutic potential for EAMG and even human myasthenia gravis （MG）. Res may be the main effective ingredient from PCRR ameliorating EAMG, but further experiments are necessary.
