Enhanced identification and localization of metabolites in Scutellariae Radix using ion mobility enabled MALDI-Q-TOF/MS imaging

Unraveling the distribution of metabolites in traditional Chinese medicine(TCM)provides direct indications for understanding their regulatory and functional basis,which is of paramount significance for better utilization and quality control of medicinal plants[1].Recently,imaging techniques such as near-infrared spectroscopy,Raman spectroscopy,and mass spectrometry(MS)were explored to reveal the spatial context of component accumulation and localization[2,3].

Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation

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.

Antidepressant effects of Yuanzhi (Polygalae Radix) extract on chronic unpredictable mild stress-induced depression in rats: modulation of the NLRP3 inflammasome and NF-κB pathway

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.

Systematic investigation of Radix Salviae for treating diabetic peripheral neuropathy disease based on network Pharmacology

BACKGROUND Diabetic peripheral neuropathy(DPN)is a debilitating complication of diabetes mellitus with limited available treatment options.Radix Salviae,a traditional Chinese herb,has shown promise in treating DPN,but its therapeutic mech-anisms have not been systematically investigated.AIM Radix Salviae(Danshen in pinin),a traditional Chinese medicine(TCM),is widely used to treat DPN in China.However,the mechanism through which Radix Salviae treats DPN remains unclear.Therefore,we aimed to explore the mechanism of action of Radix Salviae against DPN using network pharmacology.METHODS The active ingredients and target genes of Radix Salviae were screened using the TCM pharmacology database and analysis platform.The genes associated with DPN were obtained from the Gene Cards and OMIM databases,a drug-com-position-target-disease network was constructed,and a protein–protein inter-action network was subsequently constructed to screen the main targets.Gene Ontology(GO)functional annotation and pathway enrichment analysis were performed via the Kyoto Encyclopedia of Genes and Genomes(KEGG)using Bioconductor.RESULTS A total of 56 effective components,108 targets and 4581 DPN-related target genes of Radix Salviae were screened.Intervention with Radix Salviae for DPN mainly involved 81 target genes.The top 30 major targets were selected for enrichment analysis of GO and KEGG pathways.CONCLUSION These results suggested that Radix Salviae could treat DPN by regulating the AGE-RAGE signaling pathway and the PI3K-Akt signaling pathway.Therefore,Danshen may affect DPN by regulating inflammation and apoptosis.

Potential application of Nardostachyos Radix et Rhizoma-Rhubarb for the treatment of diabetic kidney disease based on network pharmacology and cell culture experimental verification

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.

Protective mechanism of Paeoniae Radix Alba against chemical liver injury based on network pharmacology,molecular docking,and in vitro experiments

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.

Effects of Radix Puerariae, Radix Rehmanniae and Their Compatibility on Blood Glucose and Blood Lipids in Mice

[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.

Determination of Benzoylaconitine Compounds in the Decoctions of Aconiti Lateralis Radix Praeparata(Heishun Pieces),Trichosanthis Fructus and Their Combination

[Objectives]This study was conducted to determine the contents of benzoylmesaconine,benzoylaconitine and benzoylhypacoitine in the decoctions of Heishun pieces,Trichosanthis Fructus and their combination.[Methods]Heishun pieces,Trichosanthis Fructus and their combination were extracted for different time periods,and then grouped.HPLC was performed using an Agilent ZORBAX SB-C 18 chromatographic column(4.6 mm×250 mm,5μm)and acetonitrile-0.02 mol/L sodium dihydrogen phosphate as the mobile phase at a flow rate of 1 mL/min and a column temperature of 30℃,and the sample volume was 20μL.The detection wavelength was 230 nm.[Results]The total amounts of benzoylmesaconine,benzoylaconitine and benzoylhypacoitine in the single decoction group of Heishun pieces were all significantly different from those in the combined decoction group at corresponding time.[Conclusions]The total content of the benzoylaconitine type increased significantly after the combined decoction of Heishun pieces and Fructus Trichosanthis,which proves the scientificity of"eighteen incompatible medicaments,19 counteraction"in traditional Chinese medicine to some extent.

Advances in Research of Anti-tumor Effect of Aconiti Radix

In this paper,the anti-tumor effects of Aconiti Radix were reviewed and summarized,and the clinical feasibility of Aconiti Radix as a potential anti-tumor drug was analyzed,in order to provide a useful reference for the future research and development of new anti-cancer drugs of Aconiti Radix.

Effect of Milk Processed Arnebiae Radix on Body Temperature of Fever Rats

[Objectives]To investigate the synergistic effect of Arnebiae Radix after processing.[Methods]The effects of raw Arnebiae Radix and milk processed Arnebiae Radix on hypothermia in yeast-induced febrile rats were compared.[Results]The processed and unprocessed Arnebiae Radix at high,medium and low doses all had a certain effect on inhibiting the rise of body temperature in rats.The high dose unprocessed group,the medium dose processed group and the high dose processed group had the best inhibitory effect on body temperature,the low dose processed group could delay the fever time,and the low dose unprocessed group had poor inhibitory effect on fever.[Conclusions]The prepared Arnebiae Radix has enhanced drug effect,and milk processed Arnebiae Radix can be used to replace common Arnebiae Radix to reduce the dosage of Arnebiae Radix and save Arnebiae Radix resources.

Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase

Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after longterm use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saikosaponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-kB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.Furthermore,the mechanisms by which RPA attenuates RBinduced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to saikogenins in vivo.Different from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity.Based on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NFkB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosaponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.

Action Mechanism of Radix Aucklandiae against Gastric Ulcer Based on Network Pharmacology

[Objectives] To explore the potential targets and action mechanism of radix aucklandiae (RA) in the treatment of gastric ulcer (GU) by network pharmacology. [Methods] Gene targets were obtained through TCMSP, DisGeNet, OMIM, GeneCards databases, which related to GU and the active components of RA. The mutual potential functional targets were selected through Venny to constitute the PPI protein interaction network. The DAVID database was applied for GO and KEGG enrichment analysis of the common targets to construct the "Active component-Target-Pathway" network and analyze the relationship between them. [Results] There are 31 active components, 82 related targets and 16 common targets in the treatment of GU. The active components in Ra may exert anti-ulcer effects through six signaling pathways, including NF-κB, Toll-like receptors, VEGF and HIF-1. In addition, PTGS2, TNF, TLR4, JUN, IL2, SRC, RELA, KDR, NOS2 and PLAU may be the 10 key targets of Ra in the treatment of GU. [Conclusions] Ra controls GU through the synergies of multiple components, targets and pathways. It can provide a theoretical basis for further study on the mechanism of RA in treating GU.

当归不同药用部位的化学成分及药理作用研究进展

当归作为“分根梢”理论的代表药材,其以不同药用部位分别入药起源于唐代,形成于金元,兴盛于明清;经历代医家临床实践总结,逐渐确立了归头止血、归身补血、归尾活血的作用功效。现代研究表明,当归中含有当归多糖、挥发油、有机酸、无机盐等药效部位及阿魏酸、绿原酸、欧前胡素、藁本内酯等药效成分;在当归头、当归身及当归尾等不同药用部位中,上述药效物质基础的种类分布均匀、区别不大,但含量及相关比例差异明显;多数学者认为,含量、比例差异可能是导致当归不同药用部位存在较大药理作用差异的主要原因。通过对相关文献的检索,梳理和总结近年来国内外对当归不同药用部位中药效物质基础分布情况及相关药理作用的研究,从当归不同药用部位中药效物质基础的种类分布和含量差异两个方面综合分析,并结合相关药效物质基础对应的药理作用研究,找寻当归不同药用部位间存在的“成分-效用”关系,以期为历代医家将当归按当归头、当归身、当归尾分别入药提供更强有力的佐证,同时为当归提出进一步研究的主要方向和思路。

Active components of Bupleuri Radix in the treatment of schizophrenia analyzed by network pharmacology and clinical verification

Background:Bupleuri Radix is a common Chinese medicinal material in traditional Chinese medicine.Currently,the therapeutic effect of treating schizophrenia is relatively well understood.However,there are fewer studies examining the underlying mechanisms of its treatment.The objective of the study was to investigate the primary mechanisms of Bupleuri Radix in treating schizophrenia through network pharmacology and clinical validation.Method:Network pharmacology revealed possible molecular mechanisms,followed by clinical verification.Sixty-seven schizophrenia patients undergoing treatment at the Hunan Brain Hospital between October and November 2022 were recruited and randomly divided into the olanzapine group and the olanzapine+Bupleuri Radix group.Additionally,32 healthy people undergoing physical examinations during the same period were included as the control group.The patient’s positive and negative symptom scale scores were compared.qPCR was used to detect the mRNA expression levels of ESR1,mTOR,EIF4E,and SMAD4 in peripheral blood.Results:Through network pharmacological analysis,it was concluded in this study that Bupleuri Radix might regulate the mTOR,PI3K-Akt,and HIF-1 signaling pathways.Clinical experiments indicated that compared with before treatment,the positive and negative symptom scale scores and total scores of the two treatment groups were significantly decreased after treatment(P<0.01).In addition,the positive and negative symptom scale scores and total scores in the olanzapine+Bupleuri Radix group were significantly decreased(P<0.01)compared to the olanzapine group after treatment.Before treatment,ESR1 mRNA expression levels in peripheral blood were significantly higher in the two treatment groups than in the control group,whereas the mRNA expression levels of mTOR,EIF4E,and SMAD4 in peripheral blood were significantly lower(P<0.01).The mRNA expression levels of mTOR,EIF4E,and SMAD4 in peripheral blood were significantly higher after therapy than before treatment,whereas the mRNA expression levels of ESR1 in peripheral blood were significantly lower(P<0.01).After therapy,the olanzapine+Bupleuri Radix group’s mRNA expression levels of mTOR,EIF4E,and SMAD4 were significantly higher than those of the olanzapine group,whereas the mRNA expression levels of ESR1 were significantly lower(P<0.01).Conclusion:The mechanism of Bupleuri Radix’s therapeutic efficacy in schizophrenia may involve the up-regulation of mTOR,EIF4E,and SMAD4 mRNA expression and the down-regulation of ESR1 mRNA expression in peripheral blood.

益智仁-乌药药对调控PI3K/Akt/mTOR通路介导细胞自噬保护肾小球足细胞的作用机制研究

目的研究益智仁-乌药药对通过调控PI3K/Akt/mTOR信号通路促进足细胞自噬治疗糖尿病肾病(Diabetic Nephropathy,DN)的作用。方法60只造模成功的C57BL/KSJ-db/db(以下简称db/db)小鼠随机分为模型组、二甲双胍组、缬沙坦组、益智仁-乌药药对(低、中、高剂量)组,每组10只;另取10只C57BL/KSJ-db/m(以下简称db/m)小鼠为正常组,正常组和模型组给予生理盐水,治疗组小鼠分别给予相应药物,给药8周后检测小鼠肾脏病理学改变,足细胞自噬体数量、结构及相关蛋白表达。结果与模型组相比,益智仁-乌药药对组可显著减轻糖尿病肾病小鼠肾小球基底膜增厚情况,增加足细胞自噬体数量,显著升高自噬相关蛋白表达(P<0.05),降低PI3K/Akt/mTOR信号通路相关蛋白的表达(P<0.05)。其中益智仁-乌药药对高剂量组各指标改善优于益智仁-乌药低、中剂量组。结论益智仁-乌药药对通过抑制PI3K/Akt/mTOR信号通路激活,提高足细胞自噬水平,减轻足细胞损伤,发挥治疗糖尿病肾病的作用。

Network pharmacology and verification experiment-based prediction of active components and potential targets of Alpiniae Oxyphyllae Fructus-Saposhnikoviae Radix(Yizhiren-Fangfeng)for treatment of diabetic kidney disease

Background:In this study,we analyzed the potential active components,related crucial targets and possible signaling pathway mechanisms of Alpiniae Oxyphyllae Fructus and Saposhnikoviae Radix(AOF-SR)herb pairs in the treatment of diabetic kidney disease(DKD)using network pharmacology and verification experiments.Methods:The active compounds and potential targets of AOF-SR were derived from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,The Encyclopedia of Traditional Chinese Medicine,and PubChem databases,and the potential therapeutic targets of DKD were derived from the OMIM,Drugbank,and DisGeNET databases.The“compounds-diseases-targets”network was constructed using Cytoscape 3.6.0.ClusterMaker functionality in Cytoscape is being used to screen important targets for AOF-SR treatment of DKD.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of important targets were performed using DAVID database.In addition,according to the predicted results of network pharmacology,HK-2 cells were used to construct DKD model for verification experiment.HK-2 cells were divided into control group,high glucose(HG)group and AOF-SR(HG+AOF-SR)group to detect survival rate and expression of key proteins in NF-κB and PI3K/Akt signaling pathways.Results:A total of 38 compounds were selected from AOF-SR,of which 23 were Alpiniae Oxyphyllae Fructus and 15 were Saposhnikoviae Radix.Through enrichment analysis of 82 important targets,88 signaling pathways were identified;some of these pathways,such as the NF-κB,PI3K-Akt,IL-17,and JAK/STAT signaling pathways,regulate the pathological process of DKD.In verification experiment,the HK-2 cells survival rate was higher in the HG+AOF-SR group than in the HG group(P<0.05).Moreover,western blotting results showed that the expression levels of NF-κB,p-PI3K,and p-Akt in HG+AOF-SR group were significantly lower than those in HG group(P<0.05).Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of AOF-SR treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by AOF-SR.

Study on the Mechanism of Pseudostellariae Radix in Regulating Angiogenesis Based on Network Pharmacology and a Dual-screening System

[Objectives]This study was conducted to clarify the action mechanism of Pseudostellariae Radix in regulating angiogenesis by using network pharmacology and a dual-screening system,and to provide a basis for its clinical treatment of cardiovascular diseases.[Methods]The TCMSP database was used for preliminary screening to obtain the active compounds of Pseudostellariae Radix and the protein targets of its action.GeneCards and OMIM databases were used to search for targets related to angiogenesis.Cytoscape 3.9.1 was used to construct a drug-target network and protein interaction network of Pseudostellariae Radix in angiogenesis.The GO enrichment analysis and KEGG pathway analysis of the targets of Pseudostellariae Radix in angiogenesis were carried out on Metascape platform.The effects of the screened active compounds were verified using a dual-screening system.[Results]Six active components of Pseudostellariae Radix,luteolin,acetin,beta-sitosterol,linarin,schottenol and 1-monolinolein,were screened by TCMSP database;and the six active components were predicted with 78 common target proteins related to angiogenesis,of which 19 were core targets.Pseudostellariae Radix mainly intervened in angiogenesis through domain specific binding,ubiquitin-like protein ligase binding,kinase binding and other molecular functions to regulate biological processes such as membrane microdomain,plasma membrane raft and caveola.The results of KEGG enrichment indicated that pathways in cancer,lipid and atherosclerosis,hepatitis B,apoptosis,toxoplasmosis and other key pathways might be the mechanism for the intervention of angiogenesis.The results of the dual-screening system showed that luteolin,acacetin,beta-sitosterol and linarin protected HUVECs and promoted zebrafish angiogenesis.[Conclusions]This study preliminarily demonstrated that luteolin,acacetin,beta-sitosterol and linarin could intervene in angiogenesis through multiple targets and multiple pathways,providing ideas and a scientific basis for the treatment of cardiovascular diseases.

Molecular mechanism study of Radix Pueraria for the treatment of glioma based on network pharmacology

Radix Pueraria(RP)has a long history of dual-use in medicine and food,and is well known as“Asian ginseng”.Recently,some studies about the effect of RP against glioma have been reported.However,little is elucidated about the molecular mechanism of interaction.This study used network pharmacology and molecular docking techniques to clarify the molecular mechanism of RP in the treatment of glioma.Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was applied to screen potential active ingredients of RP and their targets.Targets for glioma were obtained from Genecards,OMIM,and Therapeutic Target Database(TTD).The topological analysis of cross-target and core target interaction was conducted using protein-protein interaction analysis(PPI).With the application of bioinformatics,GO and KEGG enrichment analyses were further carried out.Molecular docking was used then to validate the binding affinity between active components and key targets.This study successfully identified 6 potential active ingredients,namely beta-sitosterol,daidzein,formononetin,genistein,ononin,and puerarin.The hub targets were AKT1,TP53,VEGRA,EGFR,and MAPK3.These targets were mainly involved in biological processes,such as RNA polymerase II-specific DNA-binding transcription factor binding,and positive regulation of cell migration in the membrane raft,and were regulated by PI3K-Akt pathway.Further study showed that almost all the compounds had good binding abilities with above-mentioned targets.In short,this study systematically revealed the anti-glioma mechanism of RP to provide reference for the treatment of glioma.

麦冬抗肿瘤作用机制研究进展

麦冬是我国的传统中药,具有养阴生津、润肺清心的功效。越来越多的研究发现,麦冬除了传统功效外还具有对多种肿瘤的抑制作用。麦冬可通过抑制肿瘤细胞增殖、诱导肿瘤细胞凋亡、坏死性凋亡、铁死亡、焦亡、自噬、细胞周期阻滞、抑制肿瘤细胞转移和血管生成以及逆转肿瘤细胞耐药性等多种机制发挥抗肿瘤作用。对近年来麦冬块根提取物及其活性单体的抗肿瘤作用研究进展进行综述,为麦冬抗肿瘤的深入研究和对麦冬的进一步开发利用提供可借鉴的思路和方向。

Advances in toxicological studies of Radix Phytolaccae

Radix Phytolaccae is the dried root of Phytolacca acinosa Roxb or P.ameri-cana L,which is commonly used as a traditional Chinese medicine to treat diseases like cirrhotic ascites,hepatitis B,nephrotic syndrome,psoriasis,etc.However,there is no exact basis for its clinical application safety.In this paper,the toxic effects and mechanism of Saponin A(EsA),the main component of Radix Phytolaccae,were summarized by searching the results and reports of toxicology related to the plant from 1991 to 2023 on CNKI and pubmed,aiming to provide reference for the toxicological research and future research direction of Radix Phytolaccae,so that Radix Phytolaccae can be safely and effectively used in clinical practice.