Using 9200 laser particle size analyzer and KYKY-2800 scanning electron microscope, particle sizes and cellular morphology of Radix Astragalus and Radix Isatidis ultrafine powders were observed. According to the resu...Using 9200 laser particle size analyzer and KYKY-2800 scanning electron microscope, particle sizes and cellular morphology of Radix Astragalus and Radix Isatidis ultrafine powders were observed. According to the results, the particle size of 89. 1 % of Radix Astragalus ultrafine powders ranged from 1.729 [xm to 44.938 |xm, Z )50 =4.368 |xm; the particle size of 93.411% of Radix Isatidis ultrafine powders ranged from 1.510 [xm to 44.938 |xm, Z )50 = 8 .7 2 6 [xm. Radix As-tragalus and Radix Isatidis ultrafine powders were pulverized completely without intact cellular morphology. The antibacterial activity of Radix Astragalus and Radix Isatidis ultrafine powders against chicken-derived E. coli (078) was investigated. The results indicated that Radix Astragalus and Radix Isatidis ultrafine powders exhibited higher antibacterial activity against chicken-derived E. coli (078 ) compared with the corresponding coarse powders. This study laid a solid foundation for the development and application of Chinese medicine ultrafine powder preparations.展开更多
Objective: To investigate the effect of Astragalus Injection on the Skin Lesion Degree and Caspase-14, SOCS1 and STAT3 Levels of Psoriasis Model in Balb/c Nude Mice. Methods:Sixty Balb/c nude mice were randomly divide...Objective: To investigate the effect of Astragalus Injection on the Skin Lesion Degree and Caspase-14, SOCS1 and STAT3 Levels of Psoriasis Model in Balb/c Nude Mice. Methods:Sixty Balb/c nude mice were randomly divided into groups A, B and C with 20 mice in each group. Group A mice were used as blank control, group B mice as model group and group C mice as treatment group. The PASI score of psoriasis, skin thickness, inflammatory factors, serum levels of Caspase-14, SOCS1 and STAT3 in three groups of mice were analyzed after 2 weeks of treatment. Result: After treatment, the P ASI score of group B was significantly higher than that of group C, with statistical significance (P < 0.05);there was statistical significance in the measurements of lesion skin of three groups of mice after treatment (P <0.05). Compared with the blank control group, the thickness of lesion skin in group B and C was significantly higher, and the thickness of lesion skin in treatment group was significantly lower than that in control group (P < 0.05). Compared with the blank control group, the inflammatory factors IL-17, IL-22 and IL-23 in the B and C groups were significantly increased, and the inflammatory factors IL-17, IL-22 and IL-23 in the treatment group were significantly lower than those in the model group. The levels of serum C aspase-14, SOCS1 and STAT3 in three groups of mice were significantly different after treatment (P < 0.05). Compared with the blank control group, the levels of serum C aspase-14 and SOCS1 in B and C groups were significantly lower and the levels of STAT3 were significantly higher, and the levels of inflammatory factors aspase-14 and SO in treatment group were significantly higher than those in control group. The level of CS1 was significantly lower than that of model group, and the level of STAT3 was significantly higher than that of model group (P <0.05). Conclusion: Astragalus membranaceus injection can effectively improve the degree of psoriasis in Balb/c nude mice. Its possible mechanism is that it can decrease the expression of Caspase-14 and SOCS1, reduce the degree of keratosis in the lesion site of mice, improve the local surface hyperplasia, increase the level of STAT3 and enhance the level of local cell proliferation, which is of positive significance for the rehabilitation of psoriasis.展开更多
Objective:To explore and validate the potential targets of Paeoniae Radix Alba(P.Radix,Bai Shao)in protecting against chemical liver injury through network pharmacology,molecular docking technology,and in vitro cell e...Objective:To explore and validate the potential targets of Paeoniae Radix Alba(P.Radix,Bai Shao)in protecting against chemical liver injury through network pharmacology,molecular docking technology,and in vitro cell experiments.Methods:Network pharmacology was used to identify the common potential targets of P.Radix and chemical liver injury.Molecular docking was used to fit the components,which were subsequently verified in vitro.A cell model of hepatic fibrosis was established by activating hepatic stellate cell(HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1.The cells were exposed to different concentrations of total glucosides of paeony(TGP),the active substance of P.Radix,and then evaluated using the cell counting kit-8 assay,enzyme-linked immunosorbent assay,and western blot.Results:Analysis through network pharmacology revealed 13 key compounds of P.Radix,and the potential targets for preventing chemical liver injury were IL-6,AKT serine/threonine kinase 1,jun protooncogene,heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator activated receptor gamma(PPARG),PTGS2,and CASP3.Gene Ontology(GO)enrichment analysis indicated the involvement of response to drugs,membrane rafts,and peptide binding.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation.Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1,PTGS2,PPARG,and CASP3.Different concentrations of TGP can inhibit the expression of COL-I,COL-III,IL-6,TNF-a,IL-1β,HSP-90a,and PTGS2 while increasing the expression of PPAR-γand CASP3 in activated HSC-LX2 cells.Conclusion:P.Radix primarily can regulate targets such as HSP90AA1,PTGS2,PPARG,CASP3.TGP,the main active compound of P.Radix,protects against chemical liver injury by reducing the inflammatory response,activating apoptotic proteins,and promoting the apoptosis of activated HSCs.展开更多
[Objectives]To explore the effects of the compatibility of Radix Puerariae and Radix Rehmanniae on blood glucose and blood lipids in diabetic mouses.[Methods]Diabetic mouse model was established.The body weight and fa...[Objectives]To explore the effects of the compatibility of Radix Puerariae and Radix Rehmanniae on blood glucose and blood lipids in diabetic mouses.[Methods]Diabetic mouse model was established.The body weight and fasting blood glucose of mice were measured after 7 and 14 d of administration,and the biochemical indicators of blood lipids(TC,HDL-C,and LDL-C)were detected after 14 d of administration.[Results]Compared with the Radix Puerariae group and Radix Rehmanniae group,the compatibility group(1:2)had the best hypoglycemic effect(P<0.05),and TC and LDL-C in the compatibility group(2:1)significantly decreased(P<0.05),while HDL-C in the compatibility group(1:1)significantly increased(P<0.05).[Conclusions]Radix Puerariae,Radix Rehmanniae and their combination can reduce the blood glucose of diabetic mice.The compatibility group(1:2)had a significant hypoglycemic effect(P<0.05),and LDL-C in the compatibility group(2:1)significantly declined,while HDL-C in the compatibility group(1:1)rose significantly.展开更多
Ulcerative colitis(UC)is a common inflammatory disease of the gastrointestinal tract.Traditional Chinese medicine(TCM)has long been used in Asia as a treatment for UC and Puerariae Radix(PR)is a reliable anti-diarrhea...Ulcerative colitis(UC)is a common inflammatory disease of the gastrointestinal tract.Traditional Chinese medicine(TCM)has long been used in Asia as a treatment for UC and Puerariae Radix(PR)is a reliable anti-diarrheal therapy.The aims of this study were to investigate the protective effect of PR using the dextran sulfate sodium salt(DSS)-induced UC model in mice and identify molecular mechanisms of PR action.The chemical constituents of PR via ultra-performance liquid chromatography/tandem mass spectrometry and identified potential PR and UC targets using a network pharmacology(NP)approach were obtained to guide mouse experiments.A total of 180 peaks were identified from PR including 48 flavonoids,46 organic acids,14 amino acids,8 phenols,8 carbohydrates,7 alkaloids,6 coumarins and 43 other constituents.NP results showed that caspase-1 was the most dysregulated of the core genes associated with UC.A PR dose of 0.136 mg/g administered to DSS treated mice reversed weight loss and decreased colon lengths found in UC mice.PR also alleviated intestinal mucosal shedding,inflammatory cell infiltration and mucin loss.PR treatment suppressed upregulation of NOD-like receptor protein 3(NLRP3),cysteinyl aspartate-specific proteases-1(caspase-1),apoptosis-associated speck-like(ASC)and gasdermin D(GSDMD)at both the protein and m RNA expression levels.The addition of a small molecule dual-specificity phosphatase inhibitor NSC 95397 inhibited the positive effects of PR.These results indicated that PR exerts a protective effect on DSS-induced colitis by inhibiting NLRP3 inflammasome activation in mice.展开更多
BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated...BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application.However,the specific mechanism by which it works is still unclear.Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair(NRDP)for the treatment of DKD will provide a new way of thinking for the research and development of new drugs.AIM To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking,and then verify the initial findings by in vitro experiments.METHODS The Traditional Chinese Medicine Systems Pharmacology(TCMSP)database was used to screen active ingredient targets of NRDP.Targets for DKD were obtained based on the Genecards,OMIM,and TTD databases.The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram,and Cytoscape 3.9.0 was used to build a"drug-component-target-disease"network.The String database was used to construct protein interaction networks.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology analysis were performed based on the DAVID database.After selecting the targets and the active ingredients,Autodock software was used to perform molecular docking.In experimental validation using renal tubular epithelial cells(TCMK-1),we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability,with glucose solution used to mimic a hyperglycemic environment.Flow cytometry was used to detect the cell cycle progression and apoptosis.Western blot was used to detect the protein expression of STAT3,p-STAT3,BAX,BCL-2,Caspase9,and Caspase3.RESULTS A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP.Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products(AGEs)-receptor for AGEs(RAGE)signaling as the core pathway.Molecular docking showed good binding between each active ingredient and its core targets.In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells,blocked cell cycle progression in the G0/G1 phase,and reduced apoptosis in a concentrationdependent manner.Based on the results of Western blot analysis,NRDP differentially downregulated p-STAT3,BAX,Caspase3,and Caspase9 protein levels(P<0.01 or P<0.05).In addition,BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced,while BCL-2 and STAT3 protein expression was upregulated(P<0.01).CONCLUSION NRDP may upregulate BCL-2 and STAT3 protein expression,and downregulate BAX,Caspase3,and Caspase9 protein expression,thus activating the AGE-RAGE signaling pathway,inhibiting the vitality of TCMK-1 cells,reducing their apoptosis.and arresting them in the G0/G1 phase to protect them from damage by high glucose.展开更多
The traditional Chinese medicine of Radix Hedysari plays an important role in invigorating gas for ascending, benefiting blood for promoting production of fluid, and promoting circulation for removing obstruction in c...The traditional Chinese medicine of Radix Hedysari plays an important role in invigorating gas for ascending, benefiting blood for promoting production of fluid, and promoting circulation for removing obstruction in collaterals, which is consistent with the principle of treatment for osteoporosis. This study is designed to investigate the bioactive components on increasing peak bone mass (PBM) by exploring the spectrum-effect relationship between chromatography fingerprints and effect. Multiple indicators are selected to evaluate the pharmacological activity. In fingerprints, 21 common peaks are obtained, five of which are identified. Furthermore, gray relational analysis (GRA) is a quantitative method of gray system theory and is used to describe the correlation degree of common peaks and pharmacological activities with relational value. 21 components are then divided into three different regions, of which ononin and calycosin play an extremely significant role in increasing PBM. In addition, factor analysis and hierarchical cluster analysis (HCA) are used to screen the optimal producing area for Radix Hedysari. This provides a comprehensive and efficient method to improve the quality evaluation of Radix Hedysari, confirming the bioactive components for PBM-enhancement and further develop its medicinal value.展开更多
Parkinson’s disease(PD)is a common neurodegenerative disorder with no cure.Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity.The present study aimed to explore the neuroprotect...Parkinson’s disease(PD)is a common neurodegenerative disorder with no cure.Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity.The present study aimed to explore the neuroprotective effects of total flavonoids extracted from A.membranaceus(TFA)and their protective mechanisms.TFA offered neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)in the mouse model of Parkinsonism,by improving behavior performance in the gait analysis and pole test,and inhibiting the decline of tyrosine hydroxylase(TH)positive neurons and TH protein expression in substantia nigra of mice.TFA also prevented 1-methyl-4-phenylpyridinium(MPP+)induced neurotoxicity in SHSY5Y cells,by increasing GSH and GSH/GSSG ratio,and reducing reactive oxygen species.In addition,the neuroprotective effects of TFA were associated with its ability to restore MPTP/MPP+induced downregulation of SLC7A11 and glutathione peroxidase 4(GPX-4).In conclusion,we demonstrated that TFA exerted significant neuroprotection against MPTP/MPP+induced neurodegeneration by inhibiting ferroptosis through the regulation of SLC7A11/GPX-4 axis,suggesting the use of TFA as a possible food supplement in the prevention of PD.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
基金Oupported by Spark Program of the Ministry of Science and Technology of China(2015GA620002)Science and Technology Support Program of Science and Technology Department of Hebei Province(12220408D,14966610D)+2 种基金Post-award Grant Program from the Department of Science and Technology of Hebei Province(15926620H)Project of Shijiazhuang Municipal Science and Technology Bureau(141200603A)Project of Chengde Municipal Science and Technology Bureau(2015N0001)
文摘Using 9200 laser particle size analyzer and KYKY-2800 scanning electron microscope, particle sizes and cellular morphology of Radix Astragalus and Radix Isatidis ultrafine powders were observed. According to the results, the particle size of 89. 1 % of Radix Astragalus ultrafine powders ranged from 1.729 [xm to 44.938 |xm, Z )50 =4.368 |xm; the particle size of 93.411% of Radix Isatidis ultrafine powders ranged from 1.510 [xm to 44.938 |xm, Z )50 = 8 .7 2 6 [xm. Radix As-tragalus and Radix Isatidis ultrafine powders were pulverized completely without intact cellular morphology. The antibacterial activity of Radix Astragalus and Radix Isatidis ultrafine powders against chicken-derived E. coli (078) was investigated. The results indicated that Radix Astragalus and Radix Isatidis ultrafine powders exhibited higher antibacterial activity against chicken-derived E. coli (078 ) compared with the corresponding coarse powders. This study laid a solid foundation for the development and application of Chinese medicine ultrafine powder preparations.
文摘Objective: To investigate the effect of Astragalus Injection on the Skin Lesion Degree and Caspase-14, SOCS1 and STAT3 Levels of Psoriasis Model in Balb/c Nude Mice. Methods:Sixty Balb/c nude mice were randomly divided into groups A, B and C with 20 mice in each group. Group A mice were used as blank control, group B mice as model group and group C mice as treatment group. The PASI score of psoriasis, skin thickness, inflammatory factors, serum levels of Caspase-14, SOCS1 and STAT3 in three groups of mice were analyzed after 2 weeks of treatment. Result: After treatment, the P ASI score of group B was significantly higher than that of group C, with statistical significance (P < 0.05);there was statistical significance in the measurements of lesion skin of three groups of mice after treatment (P <0.05). Compared with the blank control group, the thickness of lesion skin in group B and C was significantly higher, and the thickness of lesion skin in treatment group was significantly lower than that in control group (P < 0.05). Compared with the blank control group, the inflammatory factors IL-17, IL-22 and IL-23 in the B and C groups were significantly increased, and the inflammatory factors IL-17, IL-22 and IL-23 in the treatment group were significantly lower than those in the model group. The levels of serum C aspase-14, SOCS1 and STAT3 in three groups of mice were significantly different after treatment (P < 0.05). Compared with the blank control group, the levels of serum C aspase-14 and SOCS1 in B and C groups were significantly lower and the levels of STAT3 were significantly higher, and the levels of inflammatory factors aspase-14 and SO in treatment group were significantly higher than those in control group. The level of CS1 was significantly lower than that of model group, and the level of STAT3 was significantly higher than that of model group (P <0.05). Conclusion: Astragalus membranaceus injection can effectively improve the degree of psoriasis in Balb/c nude mice. Its possible mechanism is that it can decrease the expression of Caspase-14 and SOCS1, reduce the degree of keratosis in the lesion site of mice, improve the local surface hyperplasia, increase the level of STAT3 and enhance the level of local cell proliferation, which is of positive significance for the rehabilitation of psoriasis.
基金supported by the National Natural Science Foundation of China(82074036).
文摘Objective:To explore and validate the potential targets of Paeoniae Radix Alba(P.Radix,Bai Shao)in protecting against chemical liver injury through network pharmacology,molecular docking technology,and in vitro cell experiments.Methods:Network pharmacology was used to identify the common potential targets of P.Radix and chemical liver injury.Molecular docking was used to fit the components,which were subsequently verified in vitro.A cell model of hepatic fibrosis was established by activating hepatic stellate cell(HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1.The cells were exposed to different concentrations of total glucosides of paeony(TGP),the active substance of P.Radix,and then evaluated using the cell counting kit-8 assay,enzyme-linked immunosorbent assay,and western blot.Results:Analysis through network pharmacology revealed 13 key compounds of P.Radix,and the potential targets for preventing chemical liver injury were IL-6,AKT serine/threonine kinase 1,jun protooncogene,heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator activated receptor gamma(PPARG),PTGS2,and CASP3.Gene Ontology(GO)enrichment analysis indicated the involvement of response to drugs,membrane rafts,and peptide binding.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation.Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1,PTGS2,PPARG,and CASP3.Different concentrations of TGP can inhibit the expression of COL-I,COL-III,IL-6,TNF-a,IL-1β,HSP-90a,and PTGS2 while increasing the expression of PPAR-γand CASP3 in activated HSC-LX2 cells.Conclusion:P.Radix primarily can regulate targets such as HSP90AA1,PTGS2,PPARG,CASP3.TGP,the main active compound of P.Radix,protects against chemical liver injury by reducing the inflammatory response,activating apoptotic proteins,and promoting the apoptosis of activated HSCs.
基金Supported by the National Innovation Planning Project for University Students in 2022 in Guangxi(S202210599012).
文摘[Objectives]To explore the effects of the compatibility of Radix Puerariae and Radix Rehmanniae on blood glucose and blood lipids in diabetic mouses.[Methods]Diabetic mouse model was established.The body weight and fasting blood glucose of mice were measured after 7 and 14 d of administration,and the biochemical indicators of blood lipids(TC,HDL-C,and LDL-C)were detected after 14 d of administration.[Results]Compared with the Radix Puerariae group and Radix Rehmanniae group,the compatibility group(1:2)had the best hypoglycemic effect(P<0.05),and TC and LDL-C in the compatibility group(2:1)significantly decreased(P<0.05),while HDL-C in the compatibility group(1:1)significantly increased(P<0.05).[Conclusions]Radix Puerariae,Radix Rehmanniae and their combination can reduce the blood glucose of diabetic mice.The compatibility group(1:2)had a significant hypoglycemic effect(P<0.05),and LDL-C in the compatibility group(2:1)significantly declined,while HDL-C in the compatibility group(1:1)rose significantly.
基金financially supported by the National Natural Science Foundation of China(32172897)Central Significant Changes in the Project at the Corresponding Level(Valuable Resources Capacity-Building for Sustainable Utilization of Traditional Chinese Medicine Program)(2060302)Chinese Herbal Medicine Industry Innovation Team of Shandong Province Agricultural Technology System(SDAIT-20-06)。
文摘Ulcerative colitis(UC)is a common inflammatory disease of the gastrointestinal tract.Traditional Chinese medicine(TCM)has long been used in Asia as a treatment for UC and Puerariae Radix(PR)is a reliable anti-diarrheal therapy.The aims of this study were to investigate the protective effect of PR using the dextran sulfate sodium salt(DSS)-induced UC model in mice and identify molecular mechanisms of PR action.The chemical constituents of PR via ultra-performance liquid chromatography/tandem mass spectrometry and identified potential PR and UC targets using a network pharmacology(NP)approach were obtained to guide mouse experiments.A total of 180 peaks were identified from PR including 48 flavonoids,46 organic acids,14 amino acids,8 phenols,8 carbohydrates,7 alkaloids,6 coumarins and 43 other constituents.NP results showed that caspase-1 was the most dysregulated of the core genes associated with UC.A PR dose of 0.136 mg/g administered to DSS treated mice reversed weight loss and decreased colon lengths found in UC mice.PR also alleviated intestinal mucosal shedding,inflammatory cell infiltration and mucin loss.PR treatment suppressed upregulation of NOD-like receptor protein 3(NLRP3),cysteinyl aspartate-specific proteases-1(caspase-1),apoptosis-associated speck-like(ASC)and gasdermin D(GSDMD)at both the protein and m RNA expression levels.The addition of a small molecule dual-specificity phosphatase inhibitor NSC 95397 inhibited the positive effects of PR.These results indicated that PR exerts a protective effect on DSS-induced colitis by inhibiting NLRP3 inflammasome activation in mice.
基金Supported by National Natural Science Foundation of China,No.81573695,No.81860894,and No.81674096Ningxia Key Research and Development Plan Project,No.2021BEG03106.
文摘BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application.However,the specific mechanism by which it works is still unclear.Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair(NRDP)for the treatment of DKD will provide a new way of thinking for the research and development of new drugs.AIM To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking,and then verify the initial findings by in vitro experiments.METHODS The Traditional Chinese Medicine Systems Pharmacology(TCMSP)database was used to screen active ingredient targets of NRDP.Targets for DKD were obtained based on the Genecards,OMIM,and TTD databases.The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram,and Cytoscape 3.9.0 was used to build a"drug-component-target-disease"network.The String database was used to construct protein interaction networks.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology analysis were performed based on the DAVID database.After selecting the targets and the active ingredients,Autodock software was used to perform molecular docking.In experimental validation using renal tubular epithelial cells(TCMK-1),we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability,with glucose solution used to mimic a hyperglycemic environment.Flow cytometry was used to detect the cell cycle progression and apoptosis.Western blot was used to detect the protein expression of STAT3,p-STAT3,BAX,BCL-2,Caspase9,and Caspase3.RESULTS A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP.Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products(AGEs)-receptor for AGEs(RAGE)signaling as the core pathway.Molecular docking showed good binding between each active ingredient and its core targets.In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells,blocked cell cycle progression in the G0/G1 phase,and reduced apoptosis in a concentrationdependent manner.Based on the results of Western blot analysis,NRDP differentially downregulated p-STAT3,BAX,Caspase3,and Caspase9 protein levels(P<0.01 or P<0.05).In addition,BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced,while BCL-2 and STAT3 protein expression was upregulated(P<0.01).CONCLUSION NRDP may upregulate BCL-2 and STAT3 protein expression,and downregulate BAX,Caspase3,and Caspase9 protein expression,thus activating the AGE-RAGE signaling pathway,inhibiting the vitality of TCMK-1 cells,reducing their apoptosis.and arresting them in the G0/G1 phase to protect them from damage by high glucose.
基金supported by the National Natural Science Funds of China(Grant No.81703664)Science and Technology Funds of Lanzhou,China(Grant No.201603111)
文摘The traditional Chinese medicine of Radix Hedysari plays an important role in invigorating gas for ascending, benefiting blood for promoting production of fluid, and promoting circulation for removing obstruction in collaterals, which is consistent with the principle of treatment for osteoporosis. This study is designed to investigate the bioactive components on increasing peak bone mass (PBM) by exploring the spectrum-effect relationship between chromatography fingerprints and effect. Multiple indicators are selected to evaluate the pharmacological activity. In fingerprints, 21 common peaks are obtained, five of which are identified. Furthermore, gray relational analysis (GRA) is a quantitative method of gray system theory and is used to describe the correlation degree of common peaks and pharmacological activities with relational value. 21 components are then divided into three different regions, of which ononin and calycosin play an extremely significant role in increasing PBM. In addition, factor analysis and hierarchical cluster analysis (HCA) are used to screen the optimal producing area for Radix Hedysari. This provides a comprehensive and efficient method to improve the quality evaluation of Radix Hedysari, confirming the bioactive components for PBM-enhancement and further develop its medicinal value.
文摘Parkinson’s disease(PD)is a common neurodegenerative disorder with no cure.Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity.The present study aimed to explore the neuroprotective effects of total flavonoids extracted from A.membranaceus(TFA)and their protective mechanisms.TFA offered neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)in the mouse model of Parkinsonism,by improving behavior performance in the gait analysis and pole test,and inhibiting the decline of tyrosine hydroxylase(TH)positive neurons and TH protein expression in substantia nigra of mice.TFA also prevented 1-methyl-4-phenylpyridinium(MPP+)induced neurotoxicity in SHSY5Y cells,by increasing GSH and GSH/GSSG ratio,and reducing reactive oxygen species.In addition,the neuroprotective effects of TFA were associated with its ability to restore MPTP/MPP+induced downregulation of SLC7A11 and glutathione peroxidase 4(GPX-4).In conclusion,we demonstrated that TFA exerted significant neuroprotection against MPTP/MPP+induced neurodegeneration by inhibiting ferroptosis through the regulation of SLC7A11/GPX-4 axis,suggesting the use of TFA as a possible food supplement in the prevention of PD.
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.