Thrombosis is a leading cause of mortality and morbidity in patients suffering from polycythemia vera(PV).Drug pair Salviae Miltiorrhizae Radix et Rhizoma(Danshen,DS)and Notoginseng Radix et Rhizoma(Sanqi,SQ)is common...Thrombosis is a leading cause of mortality and morbidity in patients suffering from polycythemia vera(PV).Drug pair Salviae Miltiorrhizae Radix et Rhizoma(Danshen,DS)and Notoginseng Radix et Rhizoma(Sanqi,SQ)is common traditional Chinese medicine(TCM)used in clinical practice to promote blood circulation and eliminate blood stasis.In this study,network pharmacology and molecular docking were used to analyze the potentially active ingredients and underlying mechanisms of drug pair DS-SQ against thrombosis after PV.These results show that 54 targets are related to both disease and the drug pair.Nineteen core targets,including IL-6 and AKT1,were screened.Luteolin and tanshinone IIa from DS as well as quercetin from SQ might be the major substances in the treatment of thrombosis after PV.KEGG enrichment analysis demonstrated that the lipid and atherosclerosis signaling pathway might play a significant role.These results provide valuable insights and a reference for the use of drug pair DS-SQ in management of thrombosis after PV and lay a foundation for further exploration of pharmacological effects.展开更多
Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various phy...Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various physiological functions)and“Yin”(it represents the material foundation of the human body.It plays a role in nourishing,moistening,and cooling the body).Notoginseng Radix et Rhizoma(NRR)is recognized for its properties of resolving blood stasis(it refers to a pathological condition characterized by impaired or stagnant blood circulation within the body).Changes in the compatibility ratio of these herbs often lead to variations in their chemical composition and efficacy.However,the specific alterations in chemical composition and efficacy resulting from compatibility adjustments remain unclear.We aimed to compare the material basis and their effects of different compatibility ratios of PQR and NRR on“Qi”deficiency and blood stasis syndrome(QBS).Methods:This study employed UPLC-Q/TOF-MS to identify effective compounds in the compatibility of PQR and NRR and utilized UPLC-TQ-MS/MS to analyze the dissolution of 16 saponins in PQR and NRR at 9 different ratios.A rat model of QBS was established,and the efficacy of PQR and NRR in treating this syndrome was assessed using hemorheology and coagulation analyses.Results:The study results show that PQR and NRR exhibit significant efficacy,effectively reducing blood viscosity induced by platelet aggregation and lowering inflammatory markers such as IL-6,IL-10,TXB2 and ET associated with vascular injury.Moreover,this combination regulates ATP and ADP levels,enhances energy metabolism,and promotes overall health.A total of 104 compounds in the compatibility of PQR and NRR were identified.The ratios of 1:2 and 1:3 showed the highest total saponin content,but the ratio of 1:1 demonstrated a superior pharmacological effect for the treatment of QBS.Conclusion:In summary,the compatibility of PQR and NRR not only shows the complex interactions between traditional Chinese medicinal materials,but also provides a new idea and method for the treatment of QBS.展开更多
Background:In a previous study,we found that Atractylodes macrocephala and Paeoniae radix(AM-PR)was useful for the alleviation of functional constipation(FC).However,the precise mechanism underlying the compatibility ...Background:In a previous study,we found that Atractylodes macrocephala and Paeoniae radix(AM-PR)was useful for the alleviation of functional constipation(FC).However,the precise mechanism underlying the compatibility between AM and PR in the treatment of FC remains uncertain.This study aims to analyze the pharmacokinetic differences in the active ingredients in the blood of rat models with FC when applied individually and in combination with AM-PR.It also seeks to compare the changes in the content of the active ingredient when applied individually and in combination with in vitro AM-PR,further in-depth investigation into its material foundation in terms of pharmacokinetics,as well as the composition of the substance.Methods:Blood microdialysis samples were collected using microdialysis technology.These samples from rats with FC were compared after administration of AM,PR,and AM-PR.The concentration of the main active ingredients was determined using the Ultra Performance Liquid Chromatography-Tunable Ultraviolet(UPLC-TUV)method.The concentration of the main active ingredients of the decoction compatibility before and after combining AM-PR was also determined using the UPLC-TUV method.Results:Our findings reveal that upon combination,the time to maximum concentration(T_(max))of isochlorogenic acid A(ICA-A)and ataridolide Ⅱ(ATR-Ⅱ)T_(max)was prolonged,terminal elimination half-life(T_(1/2))was reduced,and maximum plasma concentrations(C_(max))increased.The T_(max)of ataridolide Ⅲ(ATR-Ⅲ)remained consistent,whereas its T_(1/2)and C_(max)were significantly reduced.Conversely,for peoniflorin(PAE),T_(max)occurred sooner,T_(1/2)was shortened,and C_(max)increased.The T_(max)for albiflorin(ALB)remained consistent,whereas T_(1/2)and C_(max)witnessed significant increases.The area under the moment curve(AUMC)(0-t)and AUMC(0-∞)of PAE,ALB,ICA-A,ATR-Ⅱ experienced an increase after AM-PR administration in rats,attributable to the heightened C_(max).In comparison to individual herb administration,the T_(max)of ALB was advanced in combination,the T_(max)of PAE remained unchanged,and the T_(max)of ICA-A and ART-Ⅱ was delayed,with an increased area under the concentration-time curve(AUC)(0-t),indicating enhanced C_(max)and bioavailability.Furthermore,the dissolution rates of PAE,ICA-A,and ATR-Ⅱ significantly improved after compatibility.Conclusions:This study partially clarifies the rationale and compatibility of AM-PR in treating FC and offers a new perspective on the pharmacokinetic interactions of AM-PR in FC treatment.展开更多
OBJECTIVE:To investigate the effect and mechanism of Sanqi(Radix Notoginseng)in treating periodontitis.METHODS:The active components and periodontitis targets were analyzed through network pharmacology and molecular d...OBJECTIVE:To investigate the effect and mechanism of Sanqi(Radix Notoginseng)in treating periodontitis.METHODS:The active components and periodontitis targets were analyzed through network pharmacology and molecular docking.A rat model of periodontitis was established and rats were treated by continuous intragastric administration of Sanqi(Radix Notoginseng)at different doses for 30 d.The alveolar bone structure was observed by micro-CT,the periodontal tissue structure was observed by hematoxylin-eosin staining,and the related proteins changes was detected by immunohistochemical staining.RESULTS:Sanqi(Radix Notoginseng)and periodontitis had a total of 96 coincident targets that were significantly enriched in the interleukin 17(IL-17),tumor necrosis factor(TNF),and advanced glycation endproducts and the receptor of advanced glycation endproducts signaling pathways.The active compound quercetin had good binding activity with interleukin 6(IL-6),vascular endothelial growth factor A(VEGFA),matrix metallopeptidase 9(MMP9),tumor necrosis factorα(TNF-α),Jun proto-oncogene(JUN),and C-X-C motif chemokine ligand 8(CXCL8)in periodontitis.Compared with normal group,the distance from the cementoenamel junction(CEJ)to the alveolar bone(AB)was increased,alveolar bone absorption was obvious,the periodontal tissue structure was disorganized,and IL-6 and TNF-αwere upregulated in periodontitis group;meanwhile,the distance from CEJ to AB was significantly decreased,alveolar bone resorption was reduced,periodontal tissue structure was improved,the expression of IL-6,TNF-α,IL-17 and retinoid-ralated orphan receptorγt(RORγt)were decreased,Forkhead Box P3(FOXP3)and IL-10 were increased after Sanqi(Radix Notoginseng)treatment.CONCLUSIONS:Sanqi(Radix Notoginseng)improves the structure of alveolar bone and gum,and reduces inflammation;the mechanism involve in inhibiting IL-17 signaling pathway to suppress Th17 and promote Treg cells differentiation.展开更多
Ultra-performance liquid chromatography-mass spectrometry(UPLC-MS)technology was employed to analyze the chemical composition of three Clematidis Radix et Rhizoma sourced from different origins.Common characteristic c...Ultra-performance liquid chromatography-mass spectrometry(UPLC-MS)technology was employed to analyze the chemical composition of three Clematidis Radix et Rhizoma sourced from different origins.Common characteristic components were identified through comprehensive literature review and the integration of fragment ion data.A rheumatoid arthritis(AA)model was induced in Sprague-Dawley(SD)rats using Freund’s complete adjuvant,and simultaneous administration of extracts from the three original plants of Clematidis Radix et Rhizoma,along with different doses of magnoflorine,was conducted to evaluate differences in therapeutic efficacy.A common characteristic component was identified,magnoflorine,present in Clematis chinensis Osbeck.Clematis hexapetala Pall.,and Clematis manshurica Rupr.Extracts from all three original plants,as well as each dose group of the Rhizomas of Clematis chinensis Osbeck.Clematis hexapetala Pall.,Clematis manshurica Rupr.,and magnoflorine,demonstrated efficacy in alleviating rheumatoid arthritis symptoms by enhancing cellular infiltration,reducing vascular opacification,and lowering serum levels of inflammatory factors.Magnoflorine has the potential to be used as a quality marker for the three original plants of Clematidis Radix et Rhizoma.Additionally,both the three original plants and magnoflorine exhibit therapeutic potential for rheumatoid arthritis,which provides a solid theoretical and experimental basis for the establishment of more scientifically grounded quality standards of Clematidis Radix et Rhizoma and promotes the rational utilization of medicinal resources.展开更多
The potential application of Huangqi(Astragali Radix)in the treatment of diabetes mellitus(DM)has garnered increasing attention.β-cell dysfunction is one of the core mechanisms in the pathogenesis of DM and effective...The potential application of Huangqi(Astragali Radix)in the treatment of diabetes mellitus(DM)has garnered increasing attention.β-cell dysfunction is one of the core mechanisms in the pathogenesis of DM and effectively protecting and restoring pancreaticβ-cell function remains a key challenge in DM prevention and treatment.Studies have shown that the active components of Huangqi(Astragali Radix)can alleviate glucolipotoxicity-inducedβ-cell damage by promoting glucose uptake mediated by glucose transporter 4(GLUT-4),inhibiting the Wnt1/β-catenin signaling pathway to reduce lipid deposition in liver and pancreatic tissues and upregulating peroxisome proliferator-activated receptorα(PPARα)gene expression.Additionally,Huangqi(Astragali Radix)can reduce cell apoptosis by mitigating endoplasmic reticulum stress,suppress pyroptosis via the NF-κB/NLRP3/TXNIP signaling pathway,and inhibit ferroptosis and autophagy to decreaseβ-cell death.Furthermore,Huangqi(Astragali Radix)can promoteβ-cell proliferation by modulating dedifferentiation and transdifferentiation,improve the islet microenvironment by regulating immune function and reducing M1 macrophage polarization,and may delayβ-cell senescence.This review summarizes the research progress of active ingredients in Huangqi(Astragali Radix)in protecting pancreaticβ-cell,which provides new insights and a scientific basis for its future application in DM prevention and treatment.展开更多
Aconiti Lateralis Radix Praeparata(Fuzi)represents a significant traditional Chinese medicine(TCM)that exhibits both notable pharmacological effects and toxicity.Various processing methods are implemented to reduce th...Aconiti Lateralis Radix Praeparata(Fuzi)represents a significant traditional Chinese medicine(TCM)that exhibits both notable pharmacological effects and toxicity.Various processing methods are implemented to reduce the toxicity of raw Fuzi by modifying its toxic and effective components,primarily diterpenoid alkaloids.To comprehensively analyze the chemical variations between different Fuzi products,ultra-high performance liquid chromatography-linear ion trap quadrupole Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS)was employed to systematically characterize Shengfuzi,Heishunpian and Baifupian.A total of 249 diterpenoid alkaloids present in Shengfuzi were identified,while only 111 and 61 in Heishunpian and Baifupian were detected respectively,indicating substantial differences among these products.An untargeted metabolomics approach combined with multivariate statistical analysis revealed 42 potential chemical markers.Through subsequent validation using 52 batches of commercial Heishunpian and Baifupian samples,8 robust markers distinguishing these products were identified,including AC1-propanoic acid-3OH,HE-glucoside,HE-hydroxyvaleric acid-2OH,dihydrosphingosine,N-dodecoxycarbonylvaline and three unknown compounds.Additionally,the MS imaging(MSI)technique was utilized to visualize the spatial distribution of chemical constituents in raw Fuzi,revealing how different processing procedures affect the chemical variations between Heishunpian and Baifupian.The distribution patterns of different diterpenoid alkaloid subtypes partially explained the chemical differences among products.This research provides valuable insights into the material basis for future investigations of different Fuzi products.展开更多
BACKGROUND Restless legs syndrome(RLS)is a neurological disorder characterized by an uncontrollable urge to move the legs during rest.Standard treatments may provide short-term relief but are limited by long-term adve...BACKGROUND Restless legs syndrome(RLS)is a neurological disorder characterized by an uncontrollable urge to move the legs during rest.Standard treatments may provide short-term relief but are limited by long-term adverse effects.Herbal medicine containing Paeoniae Radix(HCP)has traditionally been used in Korean medicine to treat RLS symptoms.AIM To investigate the clinical effectiveness and safety of HCP in treating RLS.METHODS This retrospective chart review study included 15 patients with RLS who were treated with HCP between September 2017 and August 2022 at the Kyung Hee University Korean Medicine Hospital.The demographic,disease-related,and treatment-related characteristics,as well as the impressions of each patient,were analyzed.The study also evaluated the changes in the subjective complaints of RLS symptoms,the Korean version of the International Restless Legs Scale(KIRLS)scores before and after treatment,and the adverse events after HCP administration.RESULTS Following HCP administration,14 patients(93.3%)experienced a decrease in the degree of discomfort associated with their symptoms,with an average reduction to 44.7±35.1%compared to their discomfort levels before taking the drug.After treatment,the mean total K-IRLS score decreased significantly from 23.00±9.75 to 13.93±10.9(P=0.005).Among the HCP,a significant reduction in the K-IRLS score was observed in the Gyejibokryeonghwan(26.0±9.7 to 10.0±9.4,P=0.028)and Jakyakgamchotang(23.2±12.6 to 6.6±4.2,P=0.042)groups.Additionally,no adverse events were reported.CONCLUSION HCP improved symptoms in RLS patients.These results suggest that HCP may be an effective and safe alternative for RLS.A randomized controlled trial is required to confirm these findings.展开更多
[Objectives]To explore the effects of Radix Salviae Miltiorrhizae water extract and Semen Ziziphi Spinosae compound on theβ-secretase activity in mice exposed to aluminum maltolate.[Methods]A total of 60 healthy,clea...[Objectives]To explore the effects of Radix Salviae Miltiorrhizae water extract and Semen Ziziphi Spinosae compound on theβ-secretase activity in mice exposed to aluminum maltolate.[Methods]A total of 60 healthy,clean-grade SPF mice were randomly assigned to four groups based on their body weight,with each group consisting of 15 mice.The groups included a control group,a model group,treatment group 1,and treatment group 2.The control group received an equivalent dose of normal saline,while the model group and treatment groups 1 and 2 were intraperitoneally injected with 0.3 mg/kg of aluminum maltolate solution for 60 d.Additionally,treatment groups 1 and 2 were injected with 0.3 mg/kg of Radix Salviae Miltiorrhizae water extract and 0.3 mg/kg of Semen Ziziphi Spinosae compound,respectively,starting from the 31 st day for a total of 30 d.The cognitive functions of mice,specifically their learning and memory capabilities,were assessed using the Y-shaped water maze test at three distinct time points:prior to,during,and following the experimental procedure.Serum samples were collected for the analysis of various biochemical markers,including hemoglobin(Hb),total cholesterol(TC),triglycerides(TG),total protein(TP),alanine aminotransferase(ALT),and blood urea nitrogen(BUN).Additionally,brain tissues were harvested to evaluate the levels of glutathione peroxidase(GSH-PX)and acetylcholinesterase(AChE)in both serum and brain samples.The expression levels ofα-secretase,β-secretase,andγ-secretase in mouse serum were quantified using enzyme-linked immunosorbent assay(ELISA).[Results]According to the final results of the Y-shaped water maze test,the administration of therapeutic drugs to mice resulted in a gradual reduction in both the swimming time and the distance traveled to reach the platform in treatment groups 1 and 2.Additionally,the number of errors made by these treatment groups was significantly greater than that observed in the control group,with statistically significant differences(P<0.01).Among the three groups subjected to subchronic aluminum exposure,statistically significant differences were observed in the levels of Hb,TC,TG,TP,ALT,BUN,brain GSH-PX,and brain AChE(P<0.05).Furthermore,with the increasing duration of therapeutic drug administration,the levels ofβ-secretase in the brains of mice in both the treatment groups and the model group exhibited a significant decrease,while the levels ofα-secretase showed a significant increase.Additionally,the differences were statistically significant when compared to the control group(P<0.05).[Conclusions]Radix Salviae Miltiorrhizae water extract and Semen Ziziphi Spinosae compound will decrease the expression level ofβ-secretase activity in mice exposed to aluminum maltolate.展开更多
Background:This research aims to investigate potential gene targets and mechanisms through which the traditional Chinese medicine(TCM)Bupleuri Radix(Chaihu)may impact on clear cell renal cell carcinoma(ccRCC)treatment...Background:This research aims to investigate potential gene targets and mechanisms through which the traditional Chinese medicine(TCM)Bupleuri Radix(Chaihu)may impact on clear cell renal cell carcinoma(ccRCC)treatment.Methods:Public databases were employed to identify Cedrenol,an active component of Bupleuri Radix,and its associated gene targets.Among these,the gene RORC(also known as RORγ)was selected for detailed analysis due to its high expression correlation.Expression levels of RORC across various cancers were assessed using the TCGA pan-cancer dataset.Further analyses,including differential expression,prognostic relevance,immune infiltration,single-gene,and functional enrichment analyses,were conducted using the TCGA ccRCC dataset.Additionally,potential drug sensitivities and molecular docking interactions with RORC were explored using the GSCALite and CellMiner databases.The effects of RORC on ccRCC were also validated through cellular experiments.Results:RORC exhibited elevated expression in clear cell renal carcinoma tissue in contrast to normal tissues,and lower RORC expression was related to better prognosis.Immune cell infiltration analysis suggested that RORC may influence the penetration of cells that inhibit immune responses,such as regulatory T cells,thereby affecting ccRCC progression.Furthermore,molecular docking studies revealed that several drugs,including Axitinib,Docetaxel,Methotrexate,and Temsirolimus,have a high affinity for RORC and exhibit strong molecular binding.In cellular experiment experiments confirmed that RORC knockdown led to reduced proliferation,metastasis,and ccRCC cell invasion.Conclusion:The study implies that RORC may be a potential gene target for Bupleuri Radix in the management of ccRCC.展开更多
OBJECTIVE:To evaluate the effects of Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)(HQEZ)on colorectal cancer therapies and to elucidate the potential mechanisms of HQEZ,especially in combinatio...OBJECTIVE:To evaluate the effects of Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)(HQEZ)on colorectal cancer therapies and to elucidate the potential mechanisms of HQEZ,especially in combination with 5-Fluorouracil(5-FU).METHODS:The anti-tumor effects of HQEZ were evaluated in colorectal cancer models both in vivo and in vitro.The network pharmacological assay was used to investigate potential mechanisms of HQEZ.Potential target genes were selected by Gene Ontology(GO)enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,protein-protein interaction network(PPI)and molecular docking.Within key targets,potential targets related to drug sensitivity,especially the sensitivity to 5-FU,were evaluated in HCT116 in vitro by immunofluorescence,quantitative real-time polymerase chain reaction(qPCR)and Western-blot.Then,changes in potential targets were assessed in tumors from tumor-bearing mice and the expression of these targets was also evaluated in colorectal cancer(COAD)patients from the Cancer Genome Atlas Program(TCGA)database.RESULTS:HQEZ significantly enhanced the anti-tumor activity of 5-FU in vivo and inhibit the growth of HCT116 in vitro.By network pharmacological analysis,key targets,such as protein kinase B(AKT1),epidermal growth factor receptor(EGFR),adenosine triphosphate(ATP)binding cassette subfamily B member 1(ABCB1,also named multidrug resistance protein 1,MDR1),ATP binding cassette subfamily G member 2(ABCG2),thymidylate synthetase(TYMS,also named TS),prostaglandinendoperoxide synthase 2(PTGS2),matrix metallopeptidase 2(MMP2),MMP9,toll like receptor 4(TLR4),TLR9 and dihydropyrimidine dehydrogenase(DPYD),were identified.Additionally,4 potential core active ingredients(Folate,Curcumin,quercetin and kaempferol)were identified to be important for the treatment of colorectal cancer with HQEZ.In key targets,chemoresistance related targets were validated to be affected by HQEZ.Furthermore,5-FU sensitivity related targets,including MDR1,TS,EGFR,ribonucleotide reductase catalytic subunit M1,Breast and Ovarian Cancer Susceptibility Protein 1(BRCA1)and mutl homolog 1 were also significantly reduced by HQEZ both in vitro and in vivo.Finally,these validated key targets and 5-FU sensitivity related targets were demonstrated to be up-regulated in COAD patients based on TCGA database.CONCLUSION:HQEZ has synergistic effects on the antitumor activity of 5-FU in the treatment of colorectal cancer both in vivo and in vitro.The beneficial effect of HQEZ results from the inhibition of the drug sensitivity targets associated with 5-FU.The combination therapy of HQEZ with 5-FU or other chemotherapeutic drugs will also improve the anti-tumor efficacy of chemotherapy.展开更多
Background:Sophorae Tonkinensis Radix et Rhizoma(ST,also known as ShanDouGen)pertains to the Sophora genus,which is generally distributed in Southwest China.As a celebrated folk medicine,it has heat-clearing and detox...Background:Sophorae Tonkinensis Radix et Rhizoma(ST,also known as ShanDouGen)pertains to the Sophora genus,which is generally distributed in Southwest China.As a celebrated folk medicine,it has heat-clearing and detoxifying,reducing swelling and soothing pharynx.In recent years,there has been a notable rise in adverse events,including hepatotoxicity,associated with the use of ST,however,the mechanism behind ST-induced hepatotoxicity is unclear.Methods:The effects of ST on liver injury were investigated in vivo.Then,serum and liver samples were then analyzed using high-throughput metabolomics techniques.Furthermore,the application of network pharmacology and multivariate statistical analysis has been instrumental in identifying and predicting biomarkers and targets linked to liver toxicity.Results:In this study,we found that ST extract has a certain degree of damage to the rat liver.Using UPLC-MS/MS techniques,463 compounds were identified from ST,of which 73 compounds were absorbed in the blood of the STH group.Metabolomics results showed that amino acid metabolic biomarkers were associated with liver toxicity induced by ST.Notably,we identified 22 core ingredient as toxic effects Q-markers of ST through correlation analysis between biomarkers and absorbed components.On this basis,it is concluded by network pharmacology that ST may cause liver toxicity through PI3K-Akt signaling pathway,NF-kappa B signaling pathway,MAPK signaling pathway,and other pathways.Conclusion:Our findings also demonstrated that the“chemical composition-blood migration component-liver metabolism”stactics has an enormous potential to discern biomarkers and ingredients,and to elaborate the complexity toxicity mechanism of ST.展开更多
Astragali Radix(AR) and Notoginseng Radix et Rhizoma(NR) are frequently employed in cardiovascular disease treatment. However, the efficacy of the AR-NR medicine pair(AN) in improving cardiac remodeling and its underl...Astragali Radix(AR) and Notoginseng Radix et Rhizoma(NR) are frequently employed in cardiovascular disease treatment. However, the efficacy of the AR-NR medicine pair(AN) in improving cardiac remodeling and its underlying mechanism remains unclear. This study aimed to evaluate AN's cardioprotective effect and potential mechanism on cardiac remodeling using transverse aortic constriction(TAC) in mice and angiotensin II(Ang II)-induced neonatal rat cardiomyocytes(NRCMs) and fibroblasts in vitro. High-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS) characterized 23 main components of AN. AN significantly improved cardiac function in the TAC-induced mice. Furthermore, AN considerably reduced the serum levels of N-terminal pro-B-type natriuretic peptide(NT-pro BNP), cardiac troponin T(CTn-T), and interleukin-6(IL-6) and mitigated inflammatory cell infiltration. Post-AN treatment, TAC-induced heart size approached normal. AN decreased cardiomyocyte cross-sectional area and attenuated the upregulation of cardiac hypertrophy marker genes(ANP, BNP, and MYH7) in vivo and in vitro.Concurrently, AN alleviated collagen deposition in TAC-induced mice. AN also reduced the expression of fibrosis-related indicators(COL1A1 and COL3A1) and inhibited the activation of the transforming growth factor-β1(TGF-β1)/mothers against decapentaplegic homolog 3(Smad3) pathway. Thus, AN improved TAC-induced cardiac remodeling. Moreover, AN downregulated p-dynamin-related protein(Drp1)(Ser616) expression and upregulated mitogen 2(MFN-2) and optic atrophy 1(OPA1) expression in vivo and in vitro, thereby restoring mitochondrial fusion and fission balance. In conclusion, AN improves cardiac remodeling by regulating mitochondrial dynamic balance, providing experimental data for the rational application of Chinese medicine prescriptions with AN as the main component in clinical practice.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
Cyathulae Radix,a traditional Chinese medicine and a common vegetable,boasts a history spanning millennia.It enhances bone density,boosts metabolism,and effectively alleviates osteoporosis-induced pain.Despite its his...Cyathulae Radix,a traditional Chinese medicine and a common vegetable,boasts a history spanning millennia.It enhances bone density,boosts metabolism,and effectively alleviates osteoporosis-induced pain.Despite its historical use,the molecular mechanisms behind Cyathulae Radix’s impact on osteoporosis remain unexplored.In this study,we investigated the effects and mechanisms of Cyathulae Radix ethanol extract(CEE)in inhibiting osteoporosis and osteoclastogenesis.Eight-week-old female mice underwent ovariectomy and were treated with CEE for eight weeks.Micro-computed tomography(micro-CT)assessed histomorphometric parameters,bone tissue staining observed distal femur histomorphology,and three-point bending tests evaluated tibia mechanical properties.Enzyme-linked immunosorbent assay(ELISA)measured serum estradiol(E2),receptor activator for nuclear factor B ligand(RANKL),and osteoprotegerin(OPG)levels.Osteoclastogenesis-related markers were analyzed via Western blotting(WB)and quantitative real-time polymerase chain reaction(qRT-PCR).Additionally,CEE effects on RANKL-induced osteoclast formation and bone resorption were investigated in vitro using tartrate-resistant acid phosphatase(TRAP)staining,qRT-PCR,and WB assay.Compared with the ovariectomy(OVX)group,CEE treatment enhanced trabecular bone density,maximal load-bearing capacity,and various histomorphometric parameters.Serum E2 and OPG levels significantly increased,while Receptor activator of nuclear factor-κB(RANK)decreased in the CEE group.CEE downregulated matrix metallopeptidase 9(MMP-9),Cathepsin K(CTSK),and TRAP gene and protein expression.In bone marrow macrophages(BMMs),CEE reduced mature osteoclasts,bone resorption pit areas,and MMP-9,CTSK,and TRAP expression during osteoclast differentiation.Compared with DMSO treatment,CEE markedly inhibited RANK,TNF receptor associated factor 6(TRAF6),Proto-oncogene c-Fos(c-Fos),Nuclear factor of activated T-cells cytoplasmic 1(NFATc1)expressions,and Extracellular regulated protein kinases(ERK),c-Jun N-terminal kinase(JNK),NF-kappa B-p65(p65)phosphorylation in osteoclasts.In conclusion,CEE significantly inhibits OVX-induced osteoporosis and RANKL-induced osteoclastogenesis,potentially through modulating the Estrogen Receptor(ER)/RANK/NFATc1 signaling pathway.展开更多
This study delved into the mechanism by which the principal component of Astragali Radix regulated ferroptosis in the context of hypoxia-induced pulmonary hypertension,employing a combination of network pharmacology a...This study delved into the mechanism by which the principal component of Astragali Radix regulated ferroptosis in the context of hypoxia-induced pulmonary hypertension,employing a combination of network pharmacology and experimental validation techniques.Active constituents of Astragali Radix and their corresponding targets were identified using the TCMSP database,while therapeutic targets associated with hypoxia-induced pulmonary hypertension were sourced from the GeneCards database.The Venn online tool facilitated the identification of overlapping targets between the active constituents of Astragali Radix and hypoxia-induced pulmonary hypertension.Interaction network diagrams depicting the relationship between Astragali Radix’s active constituents and their targets were constructed using Cytoscape software,with core targets and sub-networks identified using the CytoHubba plug-in.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted using the DAVID database.Additionally,the FerrDb database was consulted to analyze genes implicated in regulating ferroptosis.The investigation revealed 18 active constituents selected from Astragali Radix,with quercetin emerging as the key component.A total of 35 potential targets associated with Astragali Radix in regulating ferroptosis and addressing hypoxia-induced pulmonary hypertension were predicted.Experimental validation demonstrated that quercetin could inhibit the MAPK signaling pathway,resulting in reduced Fe2+and lipid peroxide levels,increased GPX4 expression,and the reversal of ferroptosis.In summary,this study elucidated the fundamental constituents and pivotal signaling pathways through which Astragali Radix modulated ferroptosis and mitigated hypoxia-induced pulmonary hypertension.Specifically,quercetin,a core constituent of Astragali Radix,was observed to inhibit ferroptosis in pulmonary arterial smooth muscle cells via the MAPK pathway and alleviate hypoxia-induced pulmonary hypertension.展开更多
Objective To investigate the antidepressant effects of Yuanzhi(Polygalae Radix;PR)aqueous extract on chronic unpredictable mild stress(CUMS)-induced depression rat models and the underlying mechanisms.Methods A total ...Objective To investigate the antidepressant effects of Yuanzhi(Polygalae Radix;PR)aqueous extract on chronic unpredictable mild stress(CUMS)-induced depression rat models and the underlying mechanisms.Methods A total of 40 male Sprague Dawley(SD)rats were randomly divided into control;model;low dose of PR(PR-L;0.5 g/kg);high dose of PR(PR-H;1 g/kg);and fluoxetine(10 mg/kg)groups;with 8 rats in each group.Except for the rats in control group;those in the other four groups underwent CUMS-induced depression modeling.PR and fluoxetine were administered intragastrically once daily;30 min prior to the CUMS procedure;for 14 consecu-tive days until the behavioral tests were performed.After CUMS modeling;the sucrose prefer-ence test(SPT);open field test(OFT);novelty-suppressed feeding test(NSFT);forced swim test(FST);and tail suspension test(TST)were employed to assess the pharmacological ef-fects of PR on the mitigation of depressive-like behaviors in rat models.Additionally;the en-zyme-linked immunosorbent assay(ELISA)was utilized to quantify the serum levels of tumor necrosis factor(TNF)-α;interleukin(IL)-6;and IL-1βin the rats.Western blot analysis was al-so conducted to evaluate the protein expression levels of nuclear factor kappa-B(NF-κB);in-ducible nitric oxide synthase(iNOS);cyclooxygenase-2(COX-2);nucleotide-binding oligomerization domain(NOD)-like receptor family pyrin domain containing 3(NLRP3);apoptosis-associated speck-like protein containing caspase recruitment domain(ASC);and caspase-1 in the hippocampal tissues of the rats.Immunofluorescence staining was per-formed to observe the morphological changes in ionized calcium-binding adapter molecule 1 positive(Iba-1+)cells in the dentate gyrus(DG)of rats with CUMS-induced depression.Results(i)Treatment with PR-H and fluoxetine resulted in significant enhancements in both the total distance and time the rats moved during tests(P<0.01 and P<0.05;respectively).Post-administration of PR-H and fluoxetine also led to statistically significant increase in su-crose preference among rats(P<0.05).Besides;PR-L;PR-H;and fluoxetine treatment markedly decreased the latency of ingestion(P<0.05;P<0.05;and P<0.01;respectively).As observed from the FST;PR-L;PR-H;and fluoxetine presented antidepressant effects on rats with CUMS-induced depression;leading to the reduction in time of their immobility(P<0.05;P<0.01;and P<0.01;respectively).The results of TST indicated reduced immobility time in rats receiving PR-H and fluoxetine treatment as well(P<0.01).(ii)Rats in model group showed an increase in the levels of Iba-1+microglia in their left and right brains in compari-son with control group(P<0.01).However;such increase was negated post PR treatment(P<0.01).Treatment with PR-L;PR-H;and fluoxetine considerably reduced the levels of inflam-matory factors(TNF-α;IL-1β;and IL-6;P<0.01).In addition;treatment of PR-L and PR-H ef-fectively counteracted the elevated levels of NLRP3;ASC;and caspase-1;and markedly down-regulated the expression levels of phosphorylated p65(p-p65);COX-2;and iNOS in rats’hip-pocampus(P<0.01).Conclusion Collectively;these findings indicate that PR exerts an antidepressant effect on rats with CUMS-induced depression partially through the modulation of the NLRP3 and NF-κB signaling pathways.展开更多
基金supported by grant from the Project of the National Natural Science Foundation of China(Grant No.82060028)funded by the Yunnan Blood Disease Clinical Medical Center(Grant No.2023YJZX-XY05)+2 种基金the Yunnan Health Commission(L2019003)to TSthe Yunnan Provincial Key Laboratory of Clinical Virology(Grant No.202205AG070005)the Yunnan Provincial Key Laboratory of Innovative Application of Traditional Chinese Medicine.
文摘Thrombosis is a leading cause of mortality and morbidity in patients suffering from polycythemia vera(PV).Drug pair Salviae Miltiorrhizae Radix et Rhizoma(Danshen,DS)and Notoginseng Radix et Rhizoma(Sanqi,SQ)is common traditional Chinese medicine(TCM)used in clinical practice to promote blood circulation and eliminate blood stasis.In this study,network pharmacology and molecular docking were used to analyze the potentially active ingredients and underlying mechanisms of drug pair DS-SQ against thrombosis after PV.These results show that 54 targets are related to both disease and the drug pair.Nineteen core targets,including IL-6 and AKT1,were screened.Luteolin and tanshinone IIa from DS as well as quercetin from SQ might be the major substances in the treatment of thrombosis after PV.KEGG enrichment analysis demonstrated that the lipid and atherosclerosis signaling pathway might play a significant role.These results provide valuable insights and a reference for the use of drug pair DS-SQ in management of thrombosis after PV and lay a foundation for further exploration of pharmacological effects.
基金funded by the Entrusted service project of Shaanxi Administration of Traditional Chinese Medicine(ZYJXG-L23001)2023 Sanqin Talent Special Support Program Innovation and Entrepreneurship Team Project,and Sci-Tech Innovation Talent System Construction Program of Shaanxi University of Chinese Medicine(2023).
文摘Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various physiological functions)and“Yin”(it represents the material foundation of the human body.It plays a role in nourishing,moistening,and cooling the body).Notoginseng Radix et Rhizoma(NRR)is recognized for its properties of resolving blood stasis(it refers to a pathological condition characterized by impaired or stagnant blood circulation within the body).Changes in the compatibility ratio of these herbs often lead to variations in their chemical composition and efficacy.However,the specific alterations in chemical composition and efficacy resulting from compatibility adjustments remain unclear.We aimed to compare the material basis and their effects of different compatibility ratios of PQR and NRR on“Qi”deficiency and blood stasis syndrome(QBS).Methods:This study employed UPLC-Q/TOF-MS to identify effective compounds in the compatibility of PQR and NRR and utilized UPLC-TQ-MS/MS to analyze the dissolution of 16 saponins in PQR and NRR at 9 different ratios.A rat model of QBS was established,and the efficacy of PQR and NRR in treating this syndrome was assessed using hemorheology and coagulation analyses.Results:The study results show that PQR and NRR exhibit significant efficacy,effectively reducing blood viscosity induced by platelet aggregation and lowering inflammatory markers such as IL-6,IL-10,TXB2 and ET associated with vascular injury.Moreover,this combination regulates ATP and ADP levels,enhances energy metabolism,and promotes overall health.A total of 104 compounds in the compatibility of PQR and NRR were identified.The ratios of 1:2 and 1:3 showed the highest total saponin content,but the ratio of 1:1 demonstrated a superior pharmacological effect for the treatment of QBS.Conclusion:In summary,the compatibility of PQR and NRR not only shows the complex interactions between traditional Chinese medicinal materials,but also provides a new idea and method for the treatment of QBS.
基金Natural Science Foundation of Zhejiang Province,Grant/Award Number:Y19H280022。
文摘Background:In a previous study,we found that Atractylodes macrocephala and Paeoniae radix(AM-PR)was useful for the alleviation of functional constipation(FC).However,the precise mechanism underlying the compatibility between AM and PR in the treatment of FC remains uncertain.This study aims to analyze the pharmacokinetic differences in the active ingredients in the blood of rat models with FC when applied individually and in combination with AM-PR.It also seeks to compare the changes in the content of the active ingredient when applied individually and in combination with in vitro AM-PR,further in-depth investigation into its material foundation in terms of pharmacokinetics,as well as the composition of the substance.Methods:Blood microdialysis samples were collected using microdialysis technology.These samples from rats with FC were compared after administration of AM,PR,and AM-PR.The concentration of the main active ingredients was determined using the Ultra Performance Liquid Chromatography-Tunable Ultraviolet(UPLC-TUV)method.The concentration of the main active ingredients of the decoction compatibility before and after combining AM-PR was also determined using the UPLC-TUV method.Results:Our findings reveal that upon combination,the time to maximum concentration(T_(max))of isochlorogenic acid A(ICA-A)and ataridolide Ⅱ(ATR-Ⅱ)T_(max)was prolonged,terminal elimination half-life(T_(1/2))was reduced,and maximum plasma concentrations(C_(max))increased.The T_(max)of ataridolide Ⅲ(ATR-Ⅲ)remained consistent,whereas its T_(1/2)and C_(max)were significantly reduced.Conversely,for peoniflorin(PAE),T_(max)occurred sooner,T_(1/2)was shortened,and C_(max)increased.The T_(max)for albiflorin(ALB)remained consistent,whereas T_(1/2)and C_(max)witnessed significant increases.The area under the moment curve(AUMC)(0-t)and AUMC(0-∞)of PAE,ALB,ICA-A,ATR-Ⅱ experienced an increase after AM-PR administration in rats,attributable to the heightened C_(max).In comparison to individual herb administration,the T_(max)of ALB was advanced in combination,the T_(max)of PAE remained unchanged,and the T_(max)of ICA-A and ART-Ⅱ was delayed,with an increased area under the concentration-time curve(AUC)(0-t),indicating enhanced C_(max)and bioavailability.Furthermore,the dissolution rates of PAE,ICA-A,and ATR-Ⅱ significantly improved after compatibility.Conclusions:This study partially clarifies the rationale and compatibility of AM-PR in treating FC and offers a new perspective on the pharmacokinetic interactions of AM-PR in FC treatment.
基金Scientific Research Fund of Education Department of Yunnan Province Project:Potential Targets and Molecular Mechanisms of Sanqi(Radix Notoginseng),an Active Component of Yunnan Baiyao,in the Treatment of Periodontitis(No.2022Y204)Special Project for The Selection of High-level Scientific and Technological Talents and Innovation Teams-technical Innovation Talents Training Object Project:Technical Innovation Personnel Training Object Project(202405AD350005)。
文摘OBJECTIVE:To investigate the effect and mechanism of Sanqi(Radix Notoginseng)in treating periodontitis.METHODS:The active components and periodontitis targets were analyzed through network pharmacology and molecular docking.A rat model of periodontitis was established and rats were treated by continuous intragastric administration of Sanqi(Radix Notoginseng)at different doses for 30 d.The alveolar bone structure was observed by micro-CT,the periodontal tissue structure was observed by hematoxylin-eosin staining,and the related proteins changes was detected by immunohistochemical staining.RESULTS:Sanqi(Radix Notoginseng)and periodontitis had a total of 96 coincident targets that were significantly enriched in the interleukin 17(IL-17),tumor necrosis factor(TNF),and advanced glycation endproducts and the receptor of advanced glycation endproducts signaling pathways.The active compound quercetin had good binding activity with interleukin 6(IL-6),vascular endothelial growth factor A(VEGFA),matrix metallopeptidase 9(MMP9),tumor necrosis factorα(TNF-α),Jun proto-oncogene(JUN),and C-X-C motif chemokine ligand 8(CXCL8)in periodontitis.Compared with normal group,the distance from the cementoenamel junction(CEJ)to the alveolar bone(AB)was increased,alveolar bone absorption was obvious,the periodontal tissue structure was disorganized,and IL-6 and TNF-αwere upregulated in periodontitis group;meanwhile,the distance from CEJ to AB was significantly decreased,alveolar bone resorption was reduced,periodontal tissue structure was improved,the expression of IL-6,TNF-α,IL-17 and retinoid-ralated orphan receptorγt(RORγt)were decreased,Forkhead Box P3(FOXP3)and IL-10 were increased after Sanqi(Radix Notoginseng)treatment.CONCLUSIONS:Sanqi(Radix Notoginseng)improves the structure of alveolar bone and gum,and reduces inflammation;the mechanism involve in inhibiting IL-17 signaling pathway to suppress Th17 and promote Treg cells differentiation.
基金support from various sources including 2023 Basic Research Project of Colleges and Universities of Liaoning Provincial Department of Education(JYTZD2023137)Career Development Support Plan for Young and Middle-aged Teachers in Shenyang Pharmaceutical University(ZQN2021014)+2 种基金2024 Basic Scientific Research Funding Project of Liaoning Provincial Department of Education(LJ212410163051)Liaoning Province Science and Technology Plan Joint Plan(2024-MSLH-448)Liaoning Provincial Innovation Capacity Promotion Joint Fund(2022-NLTS-12-01).
文摘Ultra-performance liquid chromatography-mass spectrometry(UPLC-MS)technology was employed to analyze the chemical composition of three Clematidis Radix et Rhizoma sourced from different origins.Common characteristic components were identified through comprehensive literature review and the integration of fragment ion data.A rheumatoid arthritis(AA)model was induced in Sprague-Dawley(SD)rats using Freund’s complete adjuvant,and simultaneous administration of extracts from the three original plants of Clematidis Radix et Rhizoma,along with different doses of magnoflorine,was conducted to evaluate differences in therapeutic efficacy.A common characteristic component was identified,magnoflorine,present in Clematis chinensis Osbeck.Clematis hexapetala Pall.,and Clematis manshurica Rupr.Extracts from all three original plants,as well as each dose group of the Rhizomas of Clematis chinensis Osbeck.Clematis hexapetala Pall.,Clematis manshurica Rupr.,and magnoflorine,demonstrated efficacy in alleviating rheumatoid arthritis symptoms by enhancing cellular infiltration,reducing vascular opacification,and lowering serum levels of inflammatory factors.Magnoflorine has the potential to be used as a quality marker for the three original plants of Clematidis Radix et Rhizoma.Additionally,both the three original plants and magnoflorine exhibit therapeutic potential for rheumatoid arthritis,which provides a solid theoretical and experimental basis for the establishment of more scientifically grounded quality standards of Clematidis Radix et Rhizoma and promotes the rational utilization of medicinal resources.
基金supported by National Natural Science Foundation of China(81774304)Shaanxi Traditional Chinese Medicine Administration Research Project(SZYKJCYC-2025-JC-016)+1 种基金Qinchuangyuan Traditional Chinese Medicine Industrial Innovation Cluster Project(L2024-QCY-ZYYJJQ-X85)Xianyang Science and Technology Bureau Key R&D Program(L2022ZDYFSF003)。
文摘The potential application of Huangqi(Astragali Radix)in the treatment of diabetes mellitus(DM)has garnered increasing attention.β-cell dysfunction is one of the core mechanisms in the pathogenesis of DM and effectively protecting and restoring pancreaticβ-cell function remains a key challenge in DM prevention and treatment.Studies have shown that the active components of Huangqi(Astragali Radix)can alleviate glucolipotoxicity-inducedβ-cell damage by promoting glucose uptake mediated by glucose transporter 4(GLUT-4),inhibiting the Wnt1/β-catenin signaling pathway to reduce lipid deposition in liver and pancreatic tissues and upregulating peroxisome proliferator-activated receptorα(PPARα)gene expression.Additionally,Huangqi(Astragali Radix)can reduce cell apoptosis by mitigating endoplasmic reticulum stress,suppress pyroptosis via the NF-κB/NLRP3/TXNIP signaling pathway,and inhibit ferroptosis and autophagy to decreaseβ-cell death.Furthermore,Huangqi(Astragali Radix)can promoteβ-cell proliferation by modulating dedifferentiation and transdifferentiation,improve the islet microenvironment by regulating immune function and reducing M1 macrophage polarization,and may delayβ-cell senescence.This review summarizes the research progress of active ingredients in Huangqi(Astragali Radix)in protecting pancreaticβ-cell,which provides new insights and a scientific basis for its future application in DM prevention and treatment.
基金supported by the Qi-Huang Chief Scientist Program of the National Administration of Traditional Chinese Medicine(2020)the National Key Research and Development Program of China(No.2022YFC3501705)+1 种基金Shanghai Sailing Program(No.23YF1447500)the China Postdoctoral Science Foundation(No.2023M732335).
文摘Aconiti Lateralis Radix Praeparata(Fuzi)represents a significant traditional Chinese medicine(TCM)that exhibits both notable pharmacological effects and toxicity.Various processing methods are implemented to reduce the toxicity of raw Fuzi by modifying its toxic and effective components,primarily diterpenoid alkaloids.To comprehensively analyze the chemical variations between different Fuzi products,ultra-high performance liquid chromatography-linear ion trap quadrupole Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS)was employed to systematically characterize Shengfuzi,Heishunpian and Baifupian.A total of 249 diterpenoid alkaloids present in Shengfuzi were identified,while only 111 and 61 in Heishunpian and Baifupian were detected respectively,indicating substantial differences among these products.An untargeted metabolomics approach combined with multivariate statistical analysis revealed 42 potential chemical markers.Through subsequent validation using 52 batches of commercial Heishunpian and Baifupian samples,8 robust markers distinguishing these products were identified,including AC1-propanoic acid-3OH,HE-glucoside,HE-hydroxyvaleric acid-2OH,dihydrosphingosine,N-dodecoxycarbonylvaline and three unknown compounds.Additionally,the MS imaging(MSI)technique was utilized to visualize the spatial distribution of chemical constituents in raw Fuzi,revealing how different processing procedures affect the chemical variations between Heishunpian and Baifupian.The distribution patterns of different diterpenoid alkaloid subtypes partially explained the chemical differences among products.This research provides valuable insights into the material basis for future investigations of different Fuzi products.
基金Supported by Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),the Ministry of Health and Welfare,Republic of Korea,No.RS-2023-KH142002.
文摘BACKGROUND Restless legs syndrome(RLS)is a neurological disorder characterized by an uncontrollable urge to move the legs during rest.Standard treatments may provide short-term relief but are limited by long-term adverse effects.Herbal medicine containing Paeoniae Radix(HCP)has traditionally been used in Korean medicine to treat RLS symptoms.AIM To investigate the clinical effectiveness and safety of HCP in treating RLS.METHODS This retrospective chart review study included 15 patients with RLS who were treated with HCP between September 2017 and August 2022 at the Kyung Hee University Korean Medicine Hospital.The demographic,disease-related,and treatment-related characteristics,as well as the impressions of each patient,were analyzed.The study also evaluated the changes in the subjective complaints of RLS symptoms,the Korean version of the International Restless Legs Scale(KIRLS)scores before and after treatment,and the adverse events after HCP administration.RESULTS Following HCP administration,14 patients(93.3%)experienced a decrease in the degree of discomfort associated with their symptoms,with an average reduction to 44.7±35.1%compared to their discomfort levels before taking the drug.After treatment,the mean total K-IRLS score decreased significantly from 23.00±9.75 to 13.93±10.9(P=0.005).Among the HCP,a significant reduction in the K-IRLS score was observed in the Gyejibokryeonghwan(26.0±9.7 to 10.0±9.4,P=0.028)and Jakyakgamchotang(23.2±12.6 to 6.6±4.2,P=0.042)groups.Additionally,no adverse events were reported.CONCLUSION HCP improved symptoms in RLS patients.These results suggest that HCP may be an effective and safe alternative for RLS.A randomized controlled trial is required to confirm these findings.
基金Supported by Undergraduate Innovation and Entrepreneurship Training Program(202410599042).
文摘[Objectives]To explore the effects of Radix Salviae Miltiorrhizae water extract and Semen Ziziphi Spinosae compound on theβ-secretase activity in mice exposed to aluminum maltolate.[Methods]A total of 60 healthy,clean-grade SPF mice were randomly assigned to four groups based on their body weight,with each group consisting of 15 mice.The groups included a control group,a model group,treatment group 1,and treatment group 2.The control group received an equivalent dose of normal saline,while the model group and treatment groups 1 and 2 were intraperitoneally injected with 0.3 mg/kg of aluminum maltolate solution for 60 d.Additionally,treatment groups 1 and 2 were injected with 0.3 mg/kg of Radix Salviae Miltiorrhizae water extract and 0.3 mg/kg of Semen Ziziphi Spinosae compound,respectively,starting from the 31 st day for a total of 30 d.The cognitive functions of mice,specifically their learning and memory capabilities,were assessed using the Y-shaped water maze test at three distinct time points:prior to,during,and following the experimental procedure.Serum samples were collected for the analysis of various biochemical markers,including hemoglobin(Hb),total cholesterol(TC),triglycerides(TG),total protein(TP),alanine aminotransferase(ALT),and blood urea nitrogen(BUN).Additionally,brain tissues were harvested to evaluate the levels of glutathione peroxidase(GSH-PX)and acetylcholinesterase(AChE)in both serum and brain samples.The expression levels ofα-secretase,β-secretase,andγ-secretase in mouse serum were quantified using enzyme-linked immunosorbent assay(ELISA).[Results]According to the final results of the Y-shaped water maze test,the administration of therapeutic drugs to mice resulted in a gradual reduction in both the swimming time and the distance traveled to reach the platform in treatment groups 1 and 2.Additionally,the number of errors made by these treatment groups was significantly greater than that observed in the control group,with statistically significant differences(P<0.01).Among the three groups subjected to subchronic aluminum exposure,statistically significant differences were observed in the levels of Hb,TC,TG,TP,ALT,BUN,brain GSH-PX,and brain AChE(P<0.05).Furthermore,with the increasing duration of therapeutic drug administration,the levels ofβ-secretase in the brains of mice in both the treatment groups and the model group exhibited a significant decrease,while the levels ofα-secretase showed a significant increase.Additionally,the differences were statistically significant when compared to the control group(P<0.05).[Conclusions]Radix Salviae Miltiorrhizae water extract and Semen Ziziphi Spinosae compound will decrease the expression level ofβ-secretase activity in mice exposed to aluminum maltolate.
基金supported by Hubei Provincial Department of Science and Technology,Innovation and Development Joint Fund(No.2022CFD145)Young Talents Project of Hubei Provincial Administration of Traditional Chinese Medicine(No.ZY2023Q002).
文摘Background:This research aims to investigate potential gene targets and mechanisms through which the traditional Chinese medicine(TCM)Bupleuri Radix(Chaihu)may impact on clear cell renal cell carcinoma(ccRCC)treatment.Methods:Public databases were employed to identify Cedrenol,an active component of Bupleuri Radix,and its associated gene targets.Among these,the gene RORC(also known as RORγ)was selected for detailed analysis due to its high expression correlation.Expression levels of RORC across various cancers were assessed using the TCGA pan-cancer dataset.Further analyses,including differential expression,prognostic relevance,immune infiltration,single-gene,and functional enrichment analyses,were conducted using the TCGA ccRCC dataset.Additionally,potential drug sensitivities and molecular docking interactions with RORC were explored using the GSCALite and CellMiner databases.The effects of RORC on ccRCC were also validated through cellular experiments.Results:RORC exhibited elevated expression in clear cell renal carcinoma tissue in contrast to normal tissues,and lower RORC expression was related to better prognosis.Immune cell infiltration analysis suggested that RORC may influence the penetration of cells that inhibit immune responses,such as regulatory T cells,thereby affecting ccRCC progression.Furthermore,molecular docking studies revealed that several drugs,including Axitinib,Docetaxel,Methotrexate,and Temsirolimus,have a high affinity for RORC and exhibit strong molecular binding.In cellular experiment experiments confirmed that RORC knockdown led to reduced proliferation,metastasis,and ccRCC cell invasion.Conclusion:The study implies that RORC may be a potential gene target for Bupleuri Radix in the management of ccRCC.
基金National Natural Science Foundation of China Youth Found Project:Anti-Colorectal Cancer Metastasis Mechanism of Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)According to the Hypoxia-Inducible Factor 2 Alpha/β-Catenin Cross-Talk Which Influence the Colon Tumor Stem Cells in Hypoxia Microenvironment(No.82003961)National Natural Science Foundation of China Youth Found Project:the Mechanism of the Compatibility of Huangqi(Radix Astragali Mongolici)and Ezhu(Rhizoma Curcumae Phaeocaulis)on the Early Metastasis of Hepatocellular Carcinoma Mediated by Cancer Associated Fibroblasts(82104408)+1 种基金Science Foundation of China Project:Involvement of Hypoxia Inducible Factor-1αSignal in Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)Combination Induced Remolding of Tumor Hypoxic Microenvironment(No.82074035)Science and Technology Development Project of Traditional Chinese Medicine in Jiangsu Province:Mechanism of Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)Herb Pair on the Inhibition of Colon Cancer Metastasis Through the Wnt/β-catenin Pathway(No.YB201921)。
文摘OBJECTIVE:To evaluate the effects of Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)(HQEZ)on colorectal cancer therapies and to elucidate the potential mechanisms of HQEZ,especially in combination with 5-Fluorouracil(5-FU).METHODS:The anti-tumor effects of HQEZ were evaluated in colorectal cancer models both in vivo and in vitro.The network pharmacological assay was used to investigate potential mechanisms of HQEZ.Potential target genes were selected by Gene Ontology(GO)enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,protein-protein interaction network(PPI)and molecular docking.Within key targets,potential targets related to drug sensitivity,especially the sensitivity to 5-FU,were evaluated in HCT116 in vitro by immunofluorescence,quantitative real-time polymerase chain reaction(qPCR)and Western-blot.Then,changes in potential targets were assessed in tumors from tumor-bearing mice and the expression of these targets was also evaluated in colorectal cancer(COAD)patients from the Cancer Genome Atlas Program(TCGA)database.RESULTS:HQEZ significantly enhanced the anti-tumor activity of 5-FU in vivo and inhibit the growth of HCT116 in vitro.By network pharmacological analysis,key targets,such as protein kinase B(AKT1),epidermal growth factor receptor(EGFR),adenosine triphosphate(ATP)binding cassette subfamily B member 1(ABCB1,also named multidrug resistance protein 1,MDR1),ATP binding cassette subfamily G member 2(ABCG2),thymidylate synthetase(TYMS,also named TS),prostaglandinendoperoxide synthase 2(PTGS2),matrix metallopeptidase 2(MMP2),MMP9,toll like receptor 4(TLR4),TLR9 and dihydropyrimidine dehydrogenase(DPYD),were identified.Additionally,4 potential core active ingredients(Folate,Curcumin,quercetin and kaempferol)were identified to be important for the treatment of colorectal cancer with HQEZ.In key targets,chemoresistance related targets were validated to be affected by HQEZ.Furthermore,5-FU sensitivity related targets,including MDR1,TS,EGFR,ribonucleotide reductase catalytic subunit M1,Breast and Ovarian Cancer Susceptibility Protein 1(BRCA1)and mutl homolog 1 were also significantly reduced by HQEZ both in vitro and in vivo.Finally,these validated key targets and 5-FU sensitivity related targets were demonstrated to be up-regulated in COAD patients based on TCGA database.CONCLUSION:HQEZ has synergistic effects on the antitumor activity of 5-FU in the treatment of colorectal cancer both in vivo and in vitro.The beneficial effect of HQEZ results from the inhibition of the drug sensitivity targets associated with 5-FU.The combination therapy of HQEZ with 5-FU or other chemotherapeutic drugs will also improve the anti-tumor efficacy of chemotherapy.
基金supported High-level Innovative Talents of Guizhou Province(QianKeHe platform talents-GCC[2023]047)Guizhou Province"14th Five Year Plan"key discipline of traditional Chinese medicine and ethnic medicine(QZYYZDXK(JS)-2021-03)Guizhou Administration of Traditional Chinese Medicine,Traditional Chinese medicine,ethnic medicine science and technology research project(QZYY-2021-098).
文摘Background:Sophorae Tonkinensis Radix et Rhizoma(ST,also known as ShanDouGen)pertains to the Sophora genus,which is generally distributed in Southwest China.As a celebrated folk medicine,it has heat-clearing and detoxifying,reducing swelling and soothing pharynx.In recent years,there has been a notable rise in adverse events,including hepatotoxicity,associated with the use of ST,however,the mechanism behind ST-induced hepatotoxicity is unclear.Methods:The effects of ST on liver injury were investigated in vivo.Then,serum and liver samples were then analyzed using high-throughput metabolomics techniques.Furthermore,the application of network pharmacology and multivariate statistical analysis has been instrumental in identifying and predicting biomarkers and targets linked to liver toxicity.Results:In this study,we found that ST extract has a certain degree of damage to the rat liver.Using UPLC-MS/MS techniques,463 compounds were identified from ST,of which 73 compounds were absorbed in the blood of the STH group.Metabolomics results showed that amino acid metabolic biomarkers were associated with liver toxicity induced by ST.Notably,we identified 22 core ingredient as toxic effects Q-markers of ST through correlation analysis between biomarkers and absorbed components.On this basis,it is concluded by network pharmacology that ST may cause liver toxicity through PI3K-Akt signaling pathway,NF-kappa B signaling pathway,MAPK signaling pathway,and other pathways.Conclusion:Our findings also demonstrated that the“chemical composition-blood migration component-liver metabolism”stactics has an enormous potential to discern biomarkers and ingredients,and to elaborate the complexity toxicity mechanism of ST.
基金supported by the National Natural Science Foundation of China (Nos. 82274231 and 81973506)the State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University, No.CMEMR2023-B12)+2 种基金the Fundamental Research Funds for the Central Universities (No. 2632023TD06)the Young Talent Support Project of Jiangsu Association for Science and Technology(No. TJ-2022-025)the Qinglan Project of Jiangsu Province。
文摘Astragali Radix(AR) and Notoginseng Radix et Rhizoma(NR) are frequently employed in cardiovascular disease treatment. However, the efficacy of the AR-NR medicine pair(AN) in improving cardiac remodeling and its underlying mechanism remains unclear. This study aimed to evaluate AN's cardioprotective effect and potential mechanism on cardiac remodeling using transverse aortic constriction(TAC) in mice and angiotensin II(Ang II)-induced neonatal rat cardiomyocytes(NRCMs) and fibroblasts in vitro. High-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS) characterized 23 main components of AN. AN significantly improved cardiac function in the TAC-induced mice. Furthermore, AN considerably reduced the serum levels of N-terminal pro-B-type natriuretic peptide(NT-pro BNP), cardiac troponin T(CTn-T), and interleukin-6(IL-6) and mitigated inflammatory cell infiltration. Post-AN treatment, TAC-induced heart size approached normal. AN decreased cardiomyocyte cross-sectional area and attenuated the upregulation of cardiac hypertrophy marker genes(ANP, BNP, and MYH7) in vivo and in vitro.Concurrently, AN alleviated collagen deposition in TAC-induced mice. AN also reduced the expression of fibrosis-related indicators(COL1A1 and COL3A1) and inhibited the activation of the transforming growth factor-β1(TGF-β1)/mothers against decapentaplegic homolog 3(Smad3) pathway. Thus, AN improved TAC-induced cardiac remodeling. Moreover, AN downregulated p-dynamin-related protein(Drp1)(Ser616) expression and upregulated mitogen 2(MFN-2) and optic atrophy 1(OPA1) expression in vivo and in vitro, thereby restoring mitochondrial fusion and fission balance. In conclusion, AN improves cardiac remodeling by regulating mitochondrial dynamic balance, providing experimental data for the rational application of Chinese medicine prescriptions with AN as the main component in clinical practice.
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supported by the National Natural Science Foundation of China(Nos.81273816,81774379,and 81370974)the Natural Science Foundation of Hunan Province,China(Nos.2017JJ2338 and 2020JJ4860)+1 种基金the Fundamental Research Funds for the Central Universities of Central South University(No.502211706)the Fund for the Key Laboratory of Hunan Province,China(No.2017TP1004).
文摘Cyathulae Radix,a traditional Chinese medicine and a common vegetable,boasts a history spanning millennia.It enhances bone density,boosts metabolism,and effectively alleviates osteoporosis-induced pain.Despite its historical use,the molecular mechanisms behind Cyathulae Radix’s impact on osteoporosis remain unexplored.In this study,we investigated the effects and mechanisms of Cyathulae Radix ethanol extract(CEE)in inhibiting osteoporosis and osteoclastogenesis.Eight-week-old female mice underwent ovariectomy and were treated with CEE for eight weeks.Micro-computed tomography(micro-CT)assessed histomorphometric parameters,bone tissue staining observed distal femur histomorphology,and three-point bending tests evaluated tibia mechanical properties.Enzyme-linked immunosorbent assay(ELISA)measured serum estradiol(E2),receptor activator for nuclear factor B ligand(RANKL),and osteoprotegerin(OPG)levels.Osteoclastogenesis-related markers were analyzed via Western blotting(WB)and quantitative real-time polymerase chain reaction(qRT-PCR).Additionally,CEE effects on RANKL-induced osteoclast formation and bone resorption were investigated in vitro using tartrate-resistant acid phosphatase(TRAP)staining,qRT-PCR,and WB assay.Compared with the ovariectomy(OVX)group,CEE treatment enhanced trabecular bone density,maximal load-bearing capacity,and various histomorphometric parameters.Serum E2 and OPG levels significantly increased,while Receptor activator of nuclear factor-κB(RANK)decreased in the CEE group.CEE downregulated matrix metallopeptidase 9(MMP-9),Cathepsin K(CTSK),and TRAP gene and protein expression.In bone marrow macrophages(BMMs),CEE reduced mature osteoclasts,bone resorption pit areas,and MMP-9,CTSK,and TRAP expression during osteoclast differentiation.Compared with DMSO treatment,CEE markedly inhibited RANK,TNF receptor associated factor 6(TRAF6),Proto-oncogene c-Fos(c-Fos),Nuclear factor of activated T-cells cytoplasmic 1(NFATc1)expressions,and Extracellular regulated protein kinases(ERK),c-Jun N-terminal kinase(JNK),NF-kappa B-p65(p65)phosphorylation in osteoclasts.In conclusion,CEE significantly inhibits OVX-induced osteoporosis and RANKL-induced osteoclastogenesis,potentially through modulating the Estrogen Receptor(ER)/RANK/NFATc1 signaling pathway.
基金National Natural Science Foundation of China(Grant No.82305214)Hunan Province’s Natural Science Fund(Grant No.2023JJ40401)+2 种基金Hunan Administration of Traditional Chinese Medicine(Grant No.B2023024)Hunan Provincial Department of Education Outstanding Youth Project(Grant No.22B0394)State Key Laboratory Project of Chinese Medicine Powder and Innovative Drugs Project(Grant No.21PTKF1002).
文摘This study delved into the mechanism by which the principal component of Astragali Radix regulated ferroptosis in the context of hypoxia-induced pulmonary hypertension,employing a combination of network pharmacology and experimental validation techniques.Active constituents of Astragali Radix and their corresponding targets were identified using the TCMSP database,while therapeutic targets associated with hypoxia-induced pulmonary hypertension were sourced from the GeneCards database.The Venn online tool facilitated the identification of overlapping targets between the active constituents of Astragali Radix and hypoxia-induced pulmonary hypertension.Interaction network diagrams depicting the relationship between Astragali Radix’s active constituents and their targets were constructed using Cytoscape software,with core targets and sub-networks identified using the CytoHubba plug-in.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted using the DAVID database.Additionally,the FerrDb database was consulted to analyze genes implicated in regulating ferroptosis.The investigation revealed 18 active constituents selected from Astragali Radix,with quercetin emerging as the key component.A total of 35 potential targets associated with Astragali Radix in regulating ferroptosis and addressing hypoxia-induced pulmonary hypertension were predicted.Experimental validation demonstrated that quercetin could inhibit the MAPK signaling pathway,resulting in reduced Fe2+and lipid peroxide levels,increased GPX4 expression,and the reversal of ferroptosis.In summary,this study elucidated the fundamental constituents and pivotal signaling pathways through which Astragali Radix modulated ferroptosis and mitigated hypoxia-induced pulmonary hypertension.Specifically,quercetin,a core constituent of Astragali Radix,was observed to inhibit ferroptosis in pulmonary arterial smooth muscle cells via the MAPK pathway and alleviate hypoxia-induced pulmonary hypertension.
基金International Cooperative Project of Traditional Chinese Medicine(GZYYG2020023)CAMS Innovation Fund for Medical Sciences(CIFMS)Grant(2021-I2M-1-034)Key Research Project of Hunan Province(222SK2018).
文摘Objective To investigate the antidepressant effects of Yuanzhi(Polygalae Radix;PR)aqueous extract on chronic unpredictable mild stress(CUMS)-induced depression rat models and the underlying mechanisms.Methods A total of 40 male Sprague Dawley(SD)rats were randomly divided into control;model;low dose of PR(PR-L;0.5 g/kg);high dose of PR(PR-H;1 g/kg);and fluoxetine(10 mg/kg)groups;with 8 rats in each group.Except for the rats in control group;those in the other four groups underwent CUMS-induced depression modeling.PR and fluoxetine were administered intragastrically once daily;30 min prior to the CUMS procedure;for 14 consecu-tive days until the behavioral tests were performed.After CUMS modeling;the sucrose prefer-ence test(SPT);open field test(OFT);novelty-suppressed feeding test(NSFT);forced swim test(FST);and tail suspension test(TST)were employed to assess the pharmacological ef-fects of PR on the mitigation of depressive-like behaviors in rat models.Additionally;the en-zyme-linked immunosorbent assay(ELISA)was utilized to quantify the serum levels of tumor necrosis factor(TNF)-α;interleukin(IL)-6;and IL-1βin the rats.Western blot analysis was al-so conducted to evaluate the protein expression levels of nuclear factor kappa-B(NF-κB);in-ducible nitric oxide synthase(iNOS);cyclooxygenase-2(COX-2);nucleotide-binding oligomerization domain(NOD)-like receptor family pyrin domain containing 3(NLRP3);apoptosis-associated speck-like protein containing caspase recruitment domain(ASC);and caspase-1 in the hippocampal tissues of the rats.Immunofluorescence staining was per-formed to observe the morphological changes in ionized calcium-binding adapter molecule 1 positive(Iba-1+)cells in the dentate gyrus(DG)of rats with CUMS-induced depression.Results(i)Treatment with PR-H and fluoxetine resulted in significant enhancements in both the total distance and time the rats moved during tests(P<0.01 and P<0.05;respectively).Post-administration of PR-H and fluoxetine also led to statistically significant increase in su-crose preference among rats(P<0.05).Besides;PR-L;PR-H;and fluoxetine treatment markedly decreased the latency of ingestion(P<0.05;P<0.05;and P<0.01;respectively).As observed from the FST;PR-L;PR-H;and fluoxetine presented antidepressant effects on rats with CUMS-induced depression;leading to the reduction in time of their immobility(P<0.05;P<0.01;and P<0.01;respectively).The results of TST indicated reduced immobility time in rats receiving PR-H and fluoxetine treatment as well(P<0.01).(ii)Rats in model group showed an increase in the levels of Iba-1+microglia in their left and right brains in compari-son with control group(P<0.01).However;such increase was negated post PR treatment(P<0.01).Treatment with PR-L;PR-H;and fluoxetine considerably reduced the levels of inflam-matory factors(TNF-α;IL-1β;and IL-6;P<0.01).In addition;treatment of PR-L and PR-H ef-fectively counteracted the elevated levels of NLRP3;ASC;and caspase-1;and markedly down-regulated the expression levels of phosphorylated p65(p-p65);COX-2;and iNOS in rats’hip-pocampus(P<0.01).Conclusion Collectively;these findings indicate that PR exerts an antidepressant effect on rats with CUMS-induced depression partially through the modulation of the NLRP3 and NF-κB signaling pathways.
