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(IC50 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
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: 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
Objective:Polygoni Multiflori Radix(PM)is a traditional herbal medicine with repeated reports of liver injury events in recent years.We wondered whether the classical processing method,namely,nine-time steaming and su...Objective:Polygoni Multiflori Radix(PM)is a traditional herbal medicine with repeated reports of liver injury events in recent years.We wondered whether the classical processing method,namely,nine-time steaming and sun drying(NSSD),had toxicity-attenuating effects on PM and the relationships between toxicity and times of processing,as well as with the alteration trends of its compounds.Materials and Methods:The chemical fingerprints of different PM extracts were developed using ultra-high-performance liquid chromatography.The spectrum-toxicity correlation between the chemical fingerprints and hepatocellular toxicity was analyzed with multiple correlation analysis.Results:The results suggested that the hepatotoxicity of NSSD processing products markedly decreased with the repeated steaming and sun drying,which was obviously superior to the product processed by the modern method.Comprehensive analysis revealed that the contents of cis-stilbene glycoside and emodin-8-O-β-D-glucoside related to liver injury susceptibility were reduced with the times of NSSD processing,which was consistent with the decreased trend of hepatocellular toxicity.After the five times of NSSD,the contents of them as well as the hepatotoxicity of PM were steady.Moreover,we found that the contents of catechin and physcion declined rapidly after the one time of NSSD and then remained stable until the nine times of NSSD.Based on the fact,they could be utilized to indicate whether PM products were processed by steaming and sun drying.Conclusions:This paper confirmed that the NSSD had a good influence on the toxicity attenuating to PM and found four compounds which could apply for the quality control of PM.展开更多
Objective: In this study, the hepatotoxic components of Polygoni multiflori Radix and Polygoni multiflori Radix Praeparata(known as Heshouwu [HSW] and Zhiheshouwu [ZHSW] in China, respectively) were screened, isolated...Objective: In this study, the hepatotoxic components of Polygoni multiflori Radix and Polygoni multiflori Radix Praeparata(known as Heshouwu [HSW] and Zhiheshouwu [ZHSW] in China, respectively) were screened, isolated, and identified. Materials and Methods: The ethanol extracts of HSW and ZHSW were separated into 80 fractions according to their polarity in the preparation liquid phase. Chang liver cell line was used to screen the toxic components of HSW and ZHSW in vitro. The obtained toxic mixture was further collected, isolated, and identified to confirm the hepatotoxic compounds of HSW and ZHSW. Results: The identifid hepatotoxic compounds include 2,3,5,4’-tetrah ydroxystilbene-2-O-β-D-glucoside, emodin, physcion-8-O-β-d-glucoside, physcion, and citreorosein, the fist two among them were the main components of HSW and ZHSW. After processing of HSW, the contents of 2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glucoside and emodin in ZHSW were signifiantly decreased. Conclusions: The traditional processing with herb has signifiant effects on the components, especially the toxic components, in the extract of HSW and is an effective method to reduce its toxicity.展开更多
Objective: To establish a rapid, accurate and reliable analytical method for the simultaneous determination of four major anthraquinones in Polygoni Multiflori Radix(PMR) using single reference standard.Methods: The f...Objective: To establish a rapid, accurate and reliable analytical method for the simultaneous determination of four major anthraquinones in Polygoni Multiflori Radix(PMR) using single reference standard.Methods: The four components including emodin-8-O-β-D-(EMG), physcion-8-O-β-D-glucoside, emodin and physcion were separated on an ODS C18 column within 13 min and detected at 280 nm. Emodin was selected as the reference standard, and the response factor for each analyte with respect to emodin were calculated. Robustness were also tested including different columns, equipments, temperatures, detection wavelengths, and other chromatographic conditions which might influence stability of response factors.Results: The method was validated in terms of linearity(r^2> 0.9995), LOQs(0.820–3.05 ng/m L), LODs(0.180–0.920 ng/m L), precision,accuracy(95.8–103.6%, RSD < 2.80%) and stability. A total of 40 batches of PMR were analyzed and the results were found to have no statistically significant differences compared with those obtained using the external standard method.Conclusion: This work provided a single standard to determine multi-components method for quantitation of four anthraquinones in PMR,which could be applied in the quality control of this herbal drug.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(IC50 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.
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funded by the National Natural Science Foundation of China(Grant No.81630100)the National Industry Program of China(Grant No.201507002)
文摘Objective:Polygoni Multiflori Radix(PM)is a traditional herbal medicine with repeated reports of liver injury events in recent years.We wondered whether the classical processing method,namely,nine-time steaming and sun drying(NSSD),had toxicity-attenuating effects on PM and the relationships between toxicity and times of processing,as well as with the alteration trends of its compounds.Materials and Methods:The chemical fingerprints of different PM extracts were developed using ultra-high-performance liquid chromatography.The spectrum-toxicity correlation between the chemical fingerprints and hepatocellular toxicity was analyzed with multiple correlation analysis.Results:The results suggested that the hepatotoxicity of NSSD processing products markedly decreased with the repeated steaming and sun drying,which was obviously superior to the product processed by the modern method.Comprehensive analysis revealed that the contents of cis-stilbene glycoside and emodin-8-O-β-D-glucoside related to liver injury susceptibility were reduced with the times of NSSD processing,which was consistent with the decreased trend of hepatocellular toxicity.After the five times of NSSD,the contents of them as well as the hepatotoxicity of PM were steady.Moreover,we found that the contents of catechin and physcion declined rapidly after the one time of NSSD and then remained stable until the nine times of NSSD.Based on the fact,they could be utilized to indicate whether PM products were processed by steaming and sun drying.Conclusions:This paper confirmed that the NSSD had a good influence on the toxicity attenuating to PM and found four compounds which could apply for the quality control of PM.
文摘Objective: In this study, the hepatotoxic components of Polygoni multiflori Radix and Polygoni multiflori Radix Praeparata(known as Heshouwu [HSW] and Zhiheshouwu [ZHSW] in China, respectively) were screened, isolated, and identified. Materials and Methods: The ethanol extracts of HSW and ZHSW were separated into 80 fractions according to their polarity in the preparation liquid phase. Chang liver cell line was used to screen the toxic components of HSW and ZHSW in vitro. The obtained toxic mixture was further collected, isolated, and identified to confirm the hepatotoxic compounds of HSW and ZHSW. Results: The identifid hepatotoxic compounds include 2,3,5,4’-tetrah ydroxystilbene-2-O-β-D-glucoside, emodin, physcion-8-O-β-d-glucoside, physcion, and citreorosein, the fist two among them were the main components of HSW and ZHSW. After processing of HSW, the contents of 2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glucoside and emodin in ZHSW were signifiantly decreased. Conclusions: The traditional processing with herb has signifiant effects on the components, especially the toxic components, in the extract of HSW and is an effective method to reduce its toxicity.
基金supported by the traditional Chinese Medicine Industry Special Scientific Research (No.201307002)the National New Drug Innovation Major Project of China (No.2012ZX09304005002)A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
文摘Objective: To establish a rapid, accurate and reliable analytical method for the simultaneous determination of four major anthraquinones in Polygoni Multiflori Radix(PMR) using single reference standard.Methods: The four components including emodin-8-O-β-D-(EMG), physcion-8-O-β-D-glucoside, emodin and physcion were separated on an ODS C18 column within 13 min and detected at 280 nm. Emodin was selected as the reference standard, and the response factor for each analyte with respect to emodin were calculated. Robustness were also tested including different columns, equipments, temperatures, detection wavelengths, and other chromatographic conditions which might influence stability of response factors.Results: The method was validated in terms of linearity(r^2> 0.9995), LOQs(0.820–3.05 ng/m L), LODs(0.180–0.920 ng/m L), precision,accuracy(95.8–103.6%, RSD < 2.80%) and stability. A total of 40 batches of PMR were analyzed and the results were found to have no statistically significant differences compared with those obtained using the external standard method.Conclusion: This work provided a single standard to determine multi-components method for quantitation of four anthraquinones in PMR,which could be applied in the quality control of this herbal drug.
