Atractylodes macrocephala Koidz.(A.macrocephala)is a medicinal and edible plant species belonging to the Compositae family.Its rhizome serves both therapeutic and nutritional purposes in China.This investigation led t...Atractylodes macrocephala Koidz.(A.macrocephala)is a medicinal and edible plant species belonging to the Compositae family.Its rhizome serves both therapeutic and nutritional purposes in China.This investigation led to the isolation of thirteen novel rearranged 9(8→7)-abeo-eudesmane-type sesquiterpenoid dimers(SDs),atramacronins A-M(1-13),three eudesmane-type SDs,atramacronins N-P(14-16),and two previously identified meroterpenoids,atrachinenin G(17)and atrachineninΙ(18),from Atractylodes macrocephala.Structure elucidation was accomplished through comprehensive spectroscopic analysis and single-crystal X-ray diffraction.Compounds 1,4-7,9,and 10 exhibited notable cytotoxicity against Hep3B,HepG2,and Huh7 cell lines,with half maximal inhibitory concentration(IC_(50))values ranging from 3.71 to 13.99μmol·L^(-1).展开更多
Ulcerative colitis (UC) is a persistent,diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide.Atractylodes lancea (Thunb.) DC.and Atractylodis macrocephala Koidz.are tradition...Ulcerative colitis (UC) is a persistent,diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide.Atractylodes lancea (Thunb.) DC.and Atractylodis macrocephala Koidz.are traditional Chinese medicines (TCMs) with a long history of clinical application,particularly for gastrointestinal disorders.Both Atractylodis Rhizoma (AR)and Atractylodis Macrocephala Rhizoma (AM) have shown significant efficacy in managing UC;however,the underlying mechanism by which the AR-AM herbal pair promotes intestinal mucosal healing remains poorly understood.The therapeutic effects of the ethanolic extract of AR-AM (EEAR-AM) were evaluated in a murine UC model induced by dextran sodium sulfate(DSS).A network pharmacology approach was employed to explore the anti-UC properties of EEAR-AM,including identification of active compounds,prediction of potential targets,and construction of a protein-protein interaction (PPI) network.Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently performed to preliminarily elucidate the mechanisms of EEAR-AM in UC treatment.Finally,the proposed molecular mechanisms were validated in both DSS-induced UC mice and Caco-2 cells.In vivo results demonstrated that EEAR-AM significantly attenuated DSS-induced weight loss,reduced colon shortening,lowered the disease activity index (DAI) score,and modulated the spleen coefficient.Moreover,EEAR-AM improved colonic tissue architecture,reduced inflammatory infiltration,restored goblet cell density,enhanced mucin MUC2 expression,and elevated levels of tight junction (TJ) proteins.Additionally,EEAR-AM suppressed the expression of matrix metalloproteinase 2 (MMP-2) and MMP-9.Network pharmacology analyses indicated that EEAR-AM may ameliorate intestinal mucosal dysfunction through modulation of the exchange protein directly activated by cAMP 1 (Epac1)/Ras-associated protein 1 (Rap1) pathway and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathways.These actions potentially enhance cellular barrier integrity and reduce the release of inflammatory mediators.Western blotting results confirmed that EEAR-AM activated the Epac1/Rap1 pathway while downregulating the PI3K/AKT pathway in both DSS-induced UC mice and Caco-2cells,consistent with predictions from network pharmacology.This study represents the first evidence that the EEAR-AM herbal pair improves intestinal mucosal barrier function in UC,with therapeutic effects likely mediated by activation of the Epac1/Rap1 pathway and inhibition of the PI3K/AKT pathway.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
Atractylodimers A-D(1-4),sesquiterpenoid dimers(SDs)featuring a unique cage-like structure,were isolated from the rhizomes of Atractylodes macrocephala.The most distinctive characteristic of these isolates was the hig...Atractylodimers A-D(1-4),sesquiterpenoid dimers(SDs)featuring a unique cage-like structure,were isolated from the rhizomes of Atractylodes macrocephala.The most distinctive characteristic of these isolates was the highly twisted“cap”structure based on highly twisted five-membered oxygen heterocyclic rings.Notably,compound 1 contained a furo[2,3b]furan ring,a caged 3,10-oxa-tricyclo[5.2.1.04,9]decane moiety,and 6/6/5/5/5/5/6/6 octocyclic skeleton.Compounds 2-3 exhibited a spiro-tetrahydrofuran ring,while compound 4 incorporated a caged spiro-2,5,9-oxa-tricyclo[5.2.1.0^(4,10)]decane scaffold for unit linkage.Their structures were definitively established through spectroscopic methods and X-ray diffraction experiments.Plausible biosynthetic pathways of compounds 1-4 were proposed.Compounds 1 and 2 demonstrated significant neuroprotective effects against serum deprivationinduced PC12 cell damage.展开更多
The crude and processed Paeoniae Radix Alba-Atractylodis Macrocephalae Rhizoma herbal pairs, originated from Bai-zhu-shao-yao-san, are used to treat different diseases clinically. In order to evaluate the crude and pr...The crude and processed Paeoniae Radix Alba-Atractylodis Macrocephalae Rhizoma herbal pairs, originated from Bai-zhu-shao-yao-san, are used to treat different diseases clinically. In order to evaluate the crude and processed Paeoniae Radix-Atractylodis Macrocephalae Rhizoma herbal pairs, a simple, easy, and sensitive high-performance liquid chromatography coupled with diode array detectors was developed for simultaneous determination of nine bioactive components in the herbal pairs. The calibration curve exhibited good linearity（r2≥0.9992）. The LODs and LOQs were ≤7.30 and 11.53 μg/m L, respectively. The intra-, inter-day and repeatability RSD values of the nine compounds were less than 3.86%, 2.71%, and 4.29%, respectively. The RSD stability values were less than 3.64%. The recovery of the method was in the range of 96.70%–102.10%, with RSD values less than 3.52%. The developed method can be applied to the intrinsic quality control of crude and processed Paeoniae Radix-Atractylodis Macrocephalae Rhizoma herbal pairs.展开更多
First at all, it introduced the concept and the damages of continuous cropping obstacle. Then, it analyzed the causes of continuous cropping obstacles for Atractylodes macrocephala Koidz. In the end, in order to provi...First at all, it introduced the concept and the damages of continuous cropping obstacle. Then, it analyzed the causes of continuous cropping obstacles for Atractylodes macrocephala Koidz. In the end, in order to provide guidance for pro- moting sustainable development of Atractylodes macrocephala Koidz industry in Pingjiang County, it put forward some control methods for eliminating continuous cropping obstacles of Atractylodes macrocephala Koidz, including breeding varieties with high resistance; applying rotation cropping and intercropping reasonable; rational fertilization and soil disinfection; introducing antagonistic bacterial and eliminating au- tointoxication.展开更多
Astragalus membranaceus(Radix Astragali, RA) and Atractylodes macrocephala(Rhizoma Atractylodis Macrocephalae, RAM) are often used to treat gastrointestinal diseases. In the present study, we determined the effects of...Astragalus membranaceus(Radix Astragali, RA) and Atractylodes macrocephala(Rhizoma Atractylodis Macrocephalae, RAM) are often used to treat gastrointestinal diseases. In the present study, we determined the effects of polysaccharides extracts from these two herbs on IEC-6 cell migration and explored the potential underlying mechanisms. A migration model with IEC-6 cells was induced using a single-edged razor blade along the diameter of cell layers in six-well polystyrene plates. The cells were grown in control--media or media containing spermidine(5 μmol·L^(-1), SPD), alpha-difluoromethylornithine(2.5 mmol·L^(-1), DFMO), 4-Aminopyridine-(40 μ-mol·L^(-1), 4-AP), the polysaccharide extracts of RA or RAM(50, 100, or 200 mg·L^(-1)), DFMO plus SPD, or DFMO plus polysaccharide extracts of RA or RAM for 12 or 24 h. Next, cytosolic free Ca^(2+)([Ca^(2+)]cyt) was measured using laser confocal microscopy, and cellular polyamine content was quantified with HPLC. Kv1.1 mRNA expression was assessed using RT-qPCR and Kv1.1 and RhoA protein expressions were measured with Western blotting analysis. A cell migration assay was carried out using Image-Pro Plus software. In addition, GC-MS was introduced to analyze the monosaccharide composition of both polysaccharide extracts. The resutls showed that treatment with polysaccharide extracts of RA or RAM significantly increased cellular polyamine content, elevated [Ca^(2+)]cyt and accelerated migration of IEC-6 cells, compared with the controls(P < 0.01). Polysaccharide extracts not only reversed the inhibitory effects of DFMO on cellular polyamine content and [Ca^(2+)]cyt, but also restored IEC-6 cell migration to control level(P < 0.01 or < 0.05). Kv1.1 mRNA and protein expressions were increased(P < 0.05) after polysaccharide extract treatment in polyamine-deficient IEC-6 cells and RhoA protein expression was increased. Molar ratios of D-ribose, D-arabinose, L-rhamnose, D-mannose, D-glucose, and D-galactose was 1.0:14.1:0.3:19.9:181.3:6.3 in RA and 1.0:4.3:0.1:5.7:2.8:2.2 in RAM. In conclusion, treatment with RA and RAM polysaccharide extracts stimulated migration of intestinal epithelial cells via a polyamine-Kv1.1 channel activated signaling pathway, which facilitated intestinal injury healing.展开更多
OBJECTIVE:To investigate the antagonistic effect of the extract of Baizhu(Rhizoma Atractylodis Macrocephalae)(RAM)on the intestinal absorption of brucine and strychnine in Strychnos nux-vomica(NUX)and propose the mech...OBJECTIVE:To investigate the antagonistic effect of the extract of Baizhu(Rhizoma Atractylodis Macrocephalae)(RAM)on the intestinal absorption of brucine and strychnine in Strychnos nux-vomica(NUX)and propose the mechanism of these effects.METHODS:The apparent permeability value(Papp)and absorption rate constant(Ka)were chosen as indices.The everted intestinal sac model and in situ single-pass intestinal perfusion model were used to study the effects of the RAM extract on the absorption of brucine and strychnine.To confirm the results,the brucine and strychnine concentrations in hepatic portal venous blood were determined.Western blotting was used to study P-glycoprotein(P-gp)expression in the Caco-2 cell line.RESULTS:Papp and Ka of brucine and strychnine were significantly increased in the presence of a P-gp inhibitor,but no significant increase was noted in the presence of a tight junction regulator.The RAM extract inhibited the absorption of brucine and strychnine and enhanced P-gp expression.CONCLUSION:The primary absorption mechanism for brucine and strychnine is passive transport,which is affected by P-gp.展开更多
Three eudesmanolide sesquiterpene-phenol hybrids,atramacronoids A-C(1-3),featuring an unusual6/6/5/5/6 skeleton furnished by forming an unexpected C-8-C-16 linkage,were obtained from the rhizomes of Atractylodes macro...Three eudesmanolide sesquiterpene-phenol hybrids,atramacronoids A-C(1-3),featuring an unusual6/6/5/5/6 skeleton furnished by forming an unexpected C-8-C-16 linkage,were obtained from the rhizomes of Atractylodes macrocephala.Their structures and absolute configurations were elucidated by spectroscopic data analysis,chemical calculations,combined with X-ray diffractions.The plausible biosynthetic pathways for compounds 1-3 are proposed.Surprisingly,compound 1 exhibited cytotoxicity against SGC-7901 cells by inducing cells apoptosis,which might relate to the promotion of synthesis of neutrophil elastase.展开更多
The study examined the inhibitory effect of Atractylodes macrocephala （AM） on the uterine contraction during premature delivery and explored its electrophysiological mechanism by studying the effects of AM on the C...The study examined the inhibitory effect of Atractylodes macrocephala （AM） on the uterine contraction during premature delivery and explored its electrophysiological mechanism by studying the effects of AM on the Ca^2＋-activated K^＋ currents of pregnant human myometrial smooth muscle cells with or without the treatment with intedeukin-6. Single cells were acutely isolated from pregnant human myometrial smooth muscles. Whole-cell Ca^2＋-activated K^＋ currents were recorded by using an Axopatchl-D amplifier. The cells were divided into three groups： group A in which AM was added into perfusate, group B, in which interleukin-6 was added into perfusate） and group C in which AM was added into perfusate after addition of interleukin-6. IL-6 10 ng/mL inhibited BKca by 36.9%±13.7% as compared with control （P〈0.01）. AM at 2 mg/mL raised BKca by 36.7%±22.6% or 45.2%±13.7% with or without the treatment of IL-6, respectively （P〈0.01）. It is concluded that AM was able to enhance the BKca of pregnant human myometrial smooth muscle cells treated or untreated with interleukin-6 and its effect on the BKca IL-treated cells was stronger that its effect on BKca of untreated cells. Our results suggested that AM can help to maintain the membrane potentials and the resting status of pregnant human myometrial smooth muscle cells.展开更多
Objectives:To provide a theoretical basis for the development of the new products of Poria cocos-Atractylodes macrocephala couplet medicine.Methods:All prescription preparations containing Poria cocos and Atractylodes...Objectives:To provide a theoretical basis for the development of the new products of Poria cocos-Atractylodes macrocephala couplet medicine.Methods:All prescription preparations containing Poria cocos and Atractylodes macrocephala were collected from the Drug Standards of the Ministry of Public Health Drug Standard·Traditional Chinese Medicine Set Prescription Preparation(called Traditional Chinese Medicine Set Prescription Preparation for short).After standardization,the information of each prescription preparation was input into the Chinese Traditional Medicine Inheritance Support Platform(V2.5),and the relevant rules of the software were adopted.Data mining methods were used to analyze the frequency of drugs,main symptoms and diseases in prescriptions,and to analyze the regularity of prescriptions.The prescription rules of top 2 high frequency attending syndromes and diseases were analyzed.Results:There were total of 337 prescription preparations containing couplet medicine of Poria cocos and Atractylodes macrocephala,107 kinds of main symptoms and 66 kinds of diseases.The high frequency syndromes were deficiency of Qi and blood and weakness of spleen and stomach,and the high frequency syndromes were anorexia and irregular menstruation.Conclusion:The couplet medicine of Poria cocos-atractylodes macrocephala prescription is mainly used to treat digestive tract diseases and gynecological diseases;it mostly takes tonifying deficiency efficat.It can treat different diseases being compatible with different medicinal materials.The study can provide theoretical basis for clinical application and new drug development of the couplet medicine of Poria cocos-atractylodes macrocephala.展开更多
Rhizome atractylodes macrocephalae is the dry roots of Atractylodes macrocephala Koidz.It is one of commonly used Chinese medicine.In the "Shennong′s Herbal",it was listed as the top grade.It mainly contain...Rhizome atractylodes macrocephalae is the dry roots of Atractylodes macrocephala Koidz.It is one of commonly used Chinese medicine.In the "Shennong′s Herbal",it was listed as the top grade.It mainly contains volatile oil,atractylenolides,atractylodes polysaccharides,glycosides and amino acids.And it has the medical functions of good for spleen and intestine,diuretic and dehumidification,hidroschesis,miscarriage prevention and soon.In order to provide references for further development and utilization,this paper systematic arranged the Chinese medicine atractylodes chemical composition,pharmacological effects,processing technology and effect of processing technology on chemical composition and pharmacological action.展开更多
[Objective] The paper was to explore the effective agent against seedling blight of Atractylodes macrocephala. [Method] The control effects of 60% validamycin A SP against seeding blight of A. macrocephala were studie...[Objective] The paper was to explore the effective agent against seedling blight of Atractylodes macrocephala. [Method] The control effects of 60% validamycin A SP against seeding blight of A. macrocephala were studied in the field, and compared with that of control agent 20% bismerthiazol WP. [Result] At 14 d post the third spraying, the control effect of 60% validamycin A SP at the dose of 495-540 g/hm;was 76.9%,which was equivalent to that of control agent 20% bismerthiazol WP sprayed at the dose of 270 g/hm;（76.7%）. [Conclusion] 60% Validamycin A SP could be used as the ideal agent against seedling blight of A. macrocephala, with good prospects of application and popularization.展开更多
[Objectives]The paper was to explore the pharmacodynamic substances and mechanism of Atractylodes macrocephala in treating primary dysmenorrhea(PD).[Methods]The components of A.macrocephala were qualitatively identifi...[Objectives]The paper was to explore the pharmacodynamic substances and mechanism of Atractylodes macrocephala in treating primary dysmenorrhea(PD).[Methods]The components of A.macrocephala were qualitatively identified by ultra high performance liquid chromatography quadrupole-time of flight mass spectrometry(UPLC-MS)combined with analyst TF 1.7.1 and peakview 2.2 software with reference to internal databases and literatures.The chemical components of A.macrocephala and the target of PD were collected by using network pharmacological data.The common genes were analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)of genes and genomes with the help of String database and Metascape platform,and the affinity between core molecules and key targets was verified.[Results]A total of 23 chemical components of A.macrocephala were identified,and 301 gene targets of chemical components of A.macrocephala,614 targets of PD,and 25 intersection targets were obtained.GO analysis results obtained 505 biological processes,11 cellular components,and 33 molecular functions.KEGG pathway analysis showed that it mainly involved TNF signaling pathway,IL-17 signaling pathway,estrogen receptor signaling pathway and arachidonic acid metabolism.The top 4 targets of PPI network centrality and the top 5 compounds of A.macrocephala-component-target-disease network centrality were selected for docking.The docking results showed that atractylenolide I,Selinar-4(15),7(11)-dien-8-one,and atractylenolide II had strong binding ability.[Conclusions]A.macrocephala may exert a curative effect on PD by targeting atractylenolide I,Selinar-4(15),7(11)-dien-8-one,and atractylenolide II on key targets such as TNF,IL6,IL1β,PTGS2 to regulate cellular TNF signaling pathway,IL-17 signaling pathway,estrogen receptor signaling pathway,and arachidonic acid metabolism.展开更多
Objective: to study the effect of different conditions on the content change and internal law of Atractylenolide I, II and III. Methods: the samples of Atractylodes macrocephala Koidz were treated with different bakin...Objective: to study the effect of different conditions on the content change and internal law of Atractylenolide I, II and III. Methods: the samples of Atractylodes macrocephala Koidz were treated with different baking temperatures, baking time, humidity, open space time, sample morphology and other conditions. The contents of Atractylodes macrocephala Koidz I, II and III were determined by HPLC, and the change rules were analyzed. Results: for the original medicinal materials and decoction pieces, temperature and heating time had a certain effect on the conversion amount, but the effect was limited. However, under the influence of the appropriate heating temperature and heating time, the content of pulverized sample powder changed significantly. In the case of Atractylodes macrocephala Koidz in the form of powder, with the increase of storage time, the content of Atractylenolide I, II and III changed significantly. Conclusion: comparison of the content change law of Atractylodes macrocephala Koidz lactone I, II, III is conducive to optimizing the processing method of Atractylodes macrocephala Koidz, and provides a reference for the quality control of Atractylodes macrocephala Koidz.展开更多
Background and aims:Metabolic dysfunction-associated fatty liver disease(MAFLD)is a common chronic condition that can lead to cancer due to its complex pathogenesis.Therapeutic agents targeting AMPactivated protein ki...Background and aims:Metabolic dysfunction-associated fatty liver disease(MAFLD)is a common chronic condition that can lead to cancer due to its complex pathogenesis.Therapeutic agents targeting AMPactivated protein kinase(AMPK)activation have been suggested as potential treatments for metabolic disorders such as metabolic dysfunction-associated steatohepatitis(MASH).Rhizoma Atractylodis Macrocephalae(RAM)has been clinically used to treat obesity-related health problems,but its therapeutic effects on MAFLD and the underlying mechanism remain unclear.Therefore,this study was conducted to evaluate the function and underlying mechanism of RAM in the treatment of MAFLD.Methods:The effect of RAM decoction on MAFLD was evaluated using a high-fat diet(HFD)-induced MAFLD mouse model.In vitro studies were conducted using a palmitic acid/oleic acid-induced lipid accumulation model in the alpha mouse liver 12 cells and RAM-containing serum.The underlying mechanisms were elucidated through a combination of network pharmacology analysis,immunohistochemistry,western blotting,and polymerase chain reaction analysis.Results:Administration of RAM decoction significantly reduced body weight gain in MAFLD mice without changing food intake.The weights of the liver and inguinal adipose tissues were also reduced after RAM treatment.Additionally,RAM administration decreased serum levels of alanine aminotransferase,aspartate transaminase,total cholesterol,triglyceride,low-density lipoprotein cholesterol,and glucose,while reducing lipid droplet accumulation in the liver tissues of MAFLD mice.The underlying mechanisms included the activation of the phosphorylation of AMPK and acetyl-CoA carboxylase(ACC),and inhibition of the expression of sterol regulatory element binding protein 1(SREBP1).However,RAM did not alter the protein expression levels of peroxisome proliferator-activated receptor a and carnitine palmitoyltransferase-1a.Furthermore,the RAM-induced upregulation of phosphorylated AMPK,phosphorylated ACC,and SREBP1 expression,as well as the downregulation of fatty acid synthase expression,were reversed by using an AMPK inhibitor.Conclusions:Through a combination of network pharmacology and experimental validation,we demonstrated that RAM may exert therapeutic effects on MAFLD by inhibiting lipid synthesis and activating phosphorylated AMPK pathways.展开更多
基金supported by the National Natural Science Foundation of China(Nos.32470414,32100319,and 82104377)the Fundamental Research Funds for the Central Universities,SWU(No.SWU-KR22052)+1 种基金the Natural Science Foundation of Chongqing,China(No.CSTB2022NSCQMSX0878)Chongqing Municipal Training Program of Innovation and Entrepreneurship for Undergraduates(No.S20241063290).
文摘Atractylodes macrocephala Koidz.(A.macrocephala)is a medicinal and edible plant species belonging to the Compositae family.Its rhizome serves both therapeutic and nutritional purposes in China.This investigation led to the isolation of thirteen novel rearranged 9(8→7)-abeo-eudesmane-type sesquiterpenoid dimers(SDs),atramacronins A-M(1-13),three eudesmane-type SDs,atramacronins N-P(14-16),and two previously identified meroterpenoids,atrachinenin G(17)and atrachineninΙ(18),from Atractylodes macrocephala.Structure elucidation was accomplished through comprehensive spectroscopic analysis and single-crystal X-ray diffraction.Compounds 1,4-7,9,and 10 exhibited notable cytotoxicity against Hep3B,HepG2,and Huh7 cell lines,with half maximal inhibitory concentration(IC_(50))values ranging from 3.71 to 13.99μmol·L^(-1).
基金supported by the Key Scientific Research Project of Hubei Provincial Department of Education (No.D20232001)。
文摘Ulcerative colitis (UC) is a persistent,diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide.Atractylodes lancea (Thunb.) DC.and Atractylodis macrocephala Koidz.are traditional Chinese medicines (TCMs) with a long history of clinical application,particularly for gastrointestinal disorders.Both Atractylodis Rhizoma (AR)and Atractylodis Macrocephala Rhizoma (AM) have shown significant efficacy in managing UC;however,the underlying mechanism by which the AR-AM herbal pair promotes intestinal mucosal healing remains poorly understood.The therapeutic effects of the ethanolic extract of AR-AM (EEAR-AM) were evaluated in a murine UC model induced by dextran sodium sulfate(DSS).A network pharmacology approach was employed to explore the anti-UC properties of EEAR-AM,including identification of active compounds,prediction of potential targets,and construction of a protein-protein interaction (PPI) network.Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently performed to preliminarily elucidate the mechanisms of EEAR-AM in UC treatment.Finally,the proposed molecular mechanisms were validated in both DSS-induced UC mice and Caco-2 cells.In vivo results demonstrated that EEAR-AM significantly attenuated DSS-induced weight loss,reduced colon shortening,lowered the disease activity index (DAI) score,and modulated the spleen coefficient.Moreover,EEAR-AM improved colonic tissue architecture,reduced inflammatory infiltration,restored goblet cell density,enhanced mucin MUC2 expression,and elevated levels of tight junction (TJ) proteins.Additionally,EEAR-AM suppressed the expression of matrix metalloproteinase 2 (MMP-2) and MMP-9.Network pharmacology analyses indicated that EEAR-AM may ameliorate intestinal mucosal dysfunction through modulation of the exchange protein directly activated by cAMP 1 (Epac1)/Ras-associated protein 1 (Rap1) pathway and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathways.These actions potentially enhance cellular barrier integrity and reduce the release of inflammatory mediators.Western blotting results confirmed that EEAR-AM activated the Epac1/Rap1 pathway while downregulating the PI3K/AKT pathway in both DSS-induced UC mice and Caco-2cells,consistent with predictions from network pharmacology.This study represents the first evidence that the EEAR-AM herbal pair improves intestinal mucosal barrier function in UC,with therapeutic effects likely mediated by activation of the Epac1/Rap1 pathway and inhibition of the PI3K/AKT pathway.
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supported by the CAMS Innovation Fund for Medical Science(No.2023-I2M-006)the National Key R&D Program of China(No.2019YFC1711000)。
文摘Atractylodimers A-D(1-4),sesquiterpenoid dimers(SDs)featuring a unique cage-like structure,were isolated from the rhizomes of Atractylodes macrocephala.The most distinctive characteristic of these isolates was the highly twisted“cap”structure based on highly twisted five-membered oxygen heterocyclic rings.Notably,compound 1 contained a furo[2,3b]furan ring,a caged 3,10-oxa-tricyclo[5.2.1.04,9]decane moiety,and 6/6/5/5/5/5/6/6 octocyclic skeleton.Compounds 2-3 exhibited a spiro-tetrahydrofuran ring,while compound 4 incorporated a caged spiro-2,5,9-oxa-tricyclo[5.2.1.0^(4,10)]decane scaffold for unit linkage.Their structures were definitively established through spectroscopic methods and X-ray diffraction experiments.Plausible biosynthetic pathways of compounds 1-4 were proposed.Compounds 1 and 2 demonstrated significant neuroprotective effects against serum deprivationinduced PC12 cell damage.
基金The National Natural Science Foundation of China(Grant No.81202918)the Open Project of National First-Class Key Discipline for Science of Chinese Materia Medica,Nanjing University of Chinese Medicine(Grant No.2011ZYX2-006)+2 种基金the Science and Technology Project of Hangzhou,China(Grant No.20130533B68 and 20131813A23)the Chinese Medicine Research Program of Zhejiang Province,China(Grant No.2014ZQ008 and 2015ZQ011)the Science Foundation of Zhejiang Chinese Medical University(Grant No.2011ZY25 and 2013ZZ12)
文摘The crude and processed Paeoniae Radix Alba-Atractylodis Macrocephalae Rhizoma herbal pairs, originated from Bai-zhu-shao-yao-san, are used to treat different diseases clinically. In order to evaluate the crude and processed Paeoniae Radix-Atractylodis Macrocephalae Rhizoma herbal pairs, a simple, easy, and sensitive high-performance liquid chromatography coupled with diode array detectors was developed for simultaneous determination of nine bioactive components in the herbal pairs. The calibration curve exhibited good linearity（r2≥0.9992）. The LODs and LOQs were ≤7.30 and 11.53 μg/m L, respectively. The intra-, inter-day and repeatability RSD values of the nine compounds were less than 3.86%, 2.71%, and 4.29%, respectively. The RSD stability values were less than 3.64%. The recovery of the method was in the range of 96.70%–102.10%, with RSD values less than 3.52%. The developed method can be applied to the intrinsic quality control of crude and processed Paeoniae Radix-Atractylodis Macrocephalae Rhizoma herbal pairs.
文摘First at all, it introduced the concept and the damages of continuous cropping obstacle. Then, it analyzed the causes of continuous cropping obstacles for Atractylodes macrocephala Koidz. In the end, in order to provide guidance for pro- moting sustainable development of Atractylodes macrocephala Koidz industry in Pingjiang County, it put forward some control methods for eliminating continuous cropping obstacles of Atractylodes macrocephala Koidz, including breeding varieties with high resistance; applying rotation cropping and intercropping reasonable; rational fertilization and soil disinfection; introducing antagonistic bacterial and eliminating au- tointoxication.
基金supported by the National Natural Science Foundation of China(Nos.30772753,81173254,and 81673940)the Science and Technology Program of Guangzhou(No.20160701335)the First-class discipline construction major project of Guangzhou University of Chinese Medicine(Guangzhou University of Chinese Medicine Planning,2018-No.6)
文摘Astragalus membranaceus(Radix Astragali, RA) and Atractylodes macrocephala(Rhizoma Atractylodis Macrocephalae, RAM) are often used to treat gastrointestinal diseases. In the present study, we determined the effects of polysaccharides extracts from these two herbs on IEC-6 cell migration and explored the potential underlying mechanisms. A migration model with IEC-6 cells was induced using a single-edged razor blade along the diameter of cell layers in six-well polystyrene plates. The cells were grown in control--media or media containing spermidine(5 μmol·L^(-1), SPD), alpha-difluoromethylornithine(2.5 mmol·L^(-1), DFMO), 4-Aminopyridine-(40 μ-mol·L^(-1), 4-AP), the polysaccharide extracts of RA or RAM(50, 100, or 200 mg·L^(-1)), DFMO plus SPD, or DFMO plus polysaccharide extracts of RA or RAM for 12 or 24 h. Next, cytosolic free Ca^(2+)([Ca^(2+)]cyt) was measured using laser confocal microscopy, and cellular polyamine content was quantified with HPLC. Kv1.1 mRNA expression was assessed using RT-qPCR and Kv1.1 and RhoA protein expressions were measured with Western blotting analysis. A cell migration assay was carried out using Image-Pro Plus software. In addition, GC-MS was introduced to analyze the monosaccharide composition of both polysaccharide extracts. The resutls showed that treatment with polysaccharide extracts of RA or RAM significantly increased cellular polyamine content, elevated [Ca^(2+)]cyt and accelerated migration of IEC-6 cells, compared with the controls(P < 0.01). Polysaccharide extracts not only reversed the inhibitory effects of DFMO on cellular polyamine content and [Ca^(2+)]cyt, but also restored IEC-6 cell migration to control level(P < 0.01 or < 0.05). Kv1.1 mRNA and protein expressions were increased(P < 0.05) after polysaccharide extract treatment in polyamine-deficient IEC-6 cells and RhoA protein expression was increased. Molar ratios of D-ribose, D-arabinose, L-rhamnose, D-mannose, D-glucose, and D-galactose was 1.0:14.1:0.3:19.9:181.3:6.3 in RA and 1.0:4.3:0.1:5.7:2.8:2.2 in RAM. In conclusion, treatment with RA and RAM polysaccharide extracts stimulated migration of intestinal epithelial cells via a polyamine-Kv1.1 channel activated signaling pathway, which facilitated intestinal injury healing.
基金the National Natural Science Foundation of China(No.81660757 and No.81303237)the Academic and Technological Foregoer Funds of Jiangxi Province,China(No.20162BCB22015)+3 种基金the Project on Cultivation of Medical Elite(Gan Po Ying Cai 555)(2013296)the Youth Science Funds of Jiangxi Province,China(No.20153BCB23019)the National Natural Science Foundation of Jiangxi Province(No.20161ACB21020)the Natural Science Research Project of Huaian(No.HAB201716)。
文摘OBJECTIVE:To investigate the antagonistic effect of the extract of Baizhu(Rhizoma Atractylodis Macrocephalae)(RAM)on the intestinal absorption of brucine and strychnine in Strychnos nux-vomica(NUX)and propose the mechanism of these effects.METHODS:The apparent permeability value(Papp)and absorption rate constant(Ka)were chosen as indices.The everted intestinal sac model and in situ single-pass intestinal perfusion model were used to study the effects of the RAM extract on the absorption of brucine and strychnine.To confirm the results,the brucine and strychnine concentrations in hepatic portal venous blood were determined.Western blotting was used to study P-glycoprotein(P-gp)expression in the Caco-2 cell line.RESULTS:Papp and Ka of brucine and strychnine were significantly increased in the presence of a P-gp inhibitor,but no significant increase was noted in the presence of a tight junction regulator.The RAM extract inhibited the absorption of brucine and strychnine and enhanced P-gp expression.CONCLUSION:The primary absorption mechanism for brucine and strychnine is passive transport,which is affected by P-gp.
基金supported by the National Natural Science Foundation of China(No.82073992)the CAMS Innovation Fund for Medical Sciences(CIFMS,No.2021-I2M-1-071)。
文摘Three eudesmanolide sesquiterpene-phenol hybrids,atramacronoids A-C(1-3),featuring an unusual6/6/5/5/6 skeleton furnished by forming an unexpected C-8-C-16 linkage,were obtained from the rhizomes of Atractylodes macrocephala.Their structures and absolute configurations were elucidated by spectroscopic data analysis,chemical calculations,combined with X-ray diffractions.The plausible biosynthetic pathways for compounds 1-3 are proposed.Surprisingly,compound 1 exhibited cytotoxicity against SGC-7901 cells by inducing cells apoptosis,which might relate to the promotion of synthesis of neutrophil elastase.
文摘The study examined the inhibitory effect of Atractylodes macrocephala （AM） on the uterine contraction during premature delivery and explored its electrophysiological mechanism by studying the effects of AM on the Ca^2＋-activated K^＋ currents of pregnant human myometrial smooth muscle cells with or without the treatment with intedeukin-6. Single cells were acutely isolated from pregnant human myometrial smooth muscles. Whole-cell Ca^2＋-activated K^＋ currents were recorded by using an Axopatchl-D amplifier. The cells were divided into three groups： group A in which AM was added into perfusate, group B, in which interleukin-6 was added into perfusate） and group C in which AM was added into perfusate after addition of interleukin-6. IL-6 10 ng/mL inhibited BKca by 36.9%±13.7% as compared with control （P〈0.01）. AM at 2 mg/mL raised BKca by 36.7%±22.6% or 45.2%±13.7% with or without the treatment of IL-6, respectively （P〈0.01）. It is concluded that AM was able to enhance the BKca of pregnant human myometrial smooth muscle cells treated or untreated with interleukin-6 and its effect on the BKca IL-treated cells was stronger that its effect on BKca of untreated cells. Our results suggested that AM can help to maintain the membrane potentials and the resting status of pregnant human myometrial smooth muscle cells.
文摘Objectives:To provide a theoretical basis for the development of the new products of Poria cocos-Atractylodes macrocephala couplet medicine.Methods:All prescription preparations containing Poria cocos and Atractylodes macrocephala were collected from the Drug Standards of the Ministry of Public Health Drug Standard·Traditional Chinese Medicine Set Prescription Preparation(called Traditional Chinese Medicine Set Prescription Preparation for short).After standardization,the information of each prescription preparation was input into the Chinese Traditional Medicine Inheritance Support Platform(V2.5),and the relevant rules of the software were adopted.Data mining methods were used to analyze the frequency of drugs,main symptoms and diseases in prescriptions,and to analyze the regularity of prescriptions.The prescription rules of top 2 high frequency attending syndromes and diseases were analyzed.Results:There were total of 337 prescription preparations containing couplet medicine of Poria cocos and Atractylodes macrocephala,107 kinds of main symptoms and 66 kinds of diseases.The high frequency syndromes were deficiency of Qi and blood and weakness of spleen and stomach,and the high frequency syndromes were anorexia and irregular menstruation.Conclusion:The couplet medicine of Poria cocos-atractylodes macrocephala prescription is mainly used to treat digestive tract diseases and gynecological diseases;it mostly takes tonifying deficiency efficat.It can treat different diseases being compatible with different medicinal materials.The study can provide theoretical basis for clinical application and new drug development of the couplet medicine of Poria cocos-atractylodes macrocephala.
基金supported by National Natural Science Foundation of China(81473549)National Natural Science Foundation of China Youth Fund Project(31402237)+1 种基金National "Major New Drug Creation" Major Science and Technology Projects(2014ZX09304-306-04)Ministry of Education of the Central University Basic Scientific Research Business Fee(XDJK2015D016)
文摘Rhizome atractylodes macrocephalae is the dry roots of Atractylodes macrocephala Koidz.It is one of commonly used Chinese medicine.In the "Shennong′s Herbal",it was listed as the top grade.It mainly contains volatile oil,atractylenolides,atractylodes polysaccharides,glycosides and amino acids.And it has the medical functions of good for spleen and intestine,diuretic and dehumidification,hidroschesis,miscarriage prevention and soon.In order to provide references for further development and utilization,this paper systematic arranged the Chinese medicine atractylodes chemical composition,pharmacological effects,processing technology and effect of processing technology on chemical composition and pharmacological action.
文摘[Objective] The paper was to explore the effective agent against seedling blight of Atractylodes macrocephala. [Method] The control effects of 60% validamycin A SP against seeding blight of A. macrocephala were studied in the field, and compared with that of control agent 20% bismerthiazol WP. [Result] At 14 d post the third spraying, the control effect of 60% validamycin A SP at the dose of 495-540 g/hm;was 76.9%,which was equivalent to that of control agent 20% bismerthiazol WP sprayed at the dose of 270 g/hm;（76.7%）. [Conclusion] 60% Validamycin A SP could be used as the ideal agent against seedling blight of A. macrocephala, with good prospects of application and popularization.
基金Youth Science Foundation Project of National Natural Science Foundation of China(82104384)Science and Technology Research Project of Colleges and Universities in Hebei Province(QN2021008)+3 种基金Research Start-up Fund for High-level Talents of Chengde Medical University(202103)Key Discipline Construction Project of Colleges and Universities in Hebei Province(JJG[2013]4)"Technology Innovation Guidance Special-Science and Technology Work Consultation"Project of Hebei Provincial Department of Science and TechnologyYouth PI Science and Technology Innovation Team of TCM Pharmacodynamic Substance Foundation of Chengde Medical University.
文摘[Objectives]The paper was to explore the pharmacodynamic substances and mechanism of Atractylodes macrocephala in treating primary dysmenorrhea(PD).[Methods]The components of A.macrocephala were qualitatively identified by ultra high performance liquid chromatography quadrupole-time of flight mass spectrometry(UPLC-MS)combined with analyst TF 1.7.1 and peakview 2.2 software with reference to internal databases and literatures.The chemical components of A.macrocephala and the target of PD were collected by using network pharmacological data.The common genes were analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)of genes and genomes with the help of String database and Metascape platform,and the affinity between core molecules and key targets was verified.[Results]A total of 23 chemical components of A.macrocephala were identified,and 301 gene targets of chemical components of A.macrocephala,614 targets of PD,and 25 intersection targets were obtained.GO analysis results obtained 505 biological processes,11 cellular components,and 33 molecular functions.KEGG pathway analysis showed that it mainly involved TNF signaling pathway,IL-17 signaling pathway,estrogen receptor signaling pathway and arachidonic acid metabolism.The top 4 targets of PPI network centrality and the top 5 compounds of A.macrocephala-component-target-disease network centrality were selected for docking.The docking results showed that atractylenolide I,Selinar-4(15),7(11)-dien-8-one,and atractylenolide II had strong binding ability.[Conclusions]A.macrocephala may exert a curative effect on PD by targeting atractylenolide I,Selinar-4(15),7(11)-dien-8-one,and atractylenolide II on key targets such as TNF,IL6,IL1β,PTGS2 to regulate cellular TNF signaling pathway,IL-17 signaling pathway,estrogen receptor signaling pathway,and arachidonic acid metabolism.
文摘Objective: to study the effect of different conditions on the content change and internal law of Atractylenolide I, II and III. Methods: the samples of Atractylodes macrocephala Koidz were treated with different baking temperatures, baking time, humidity, open space time, sample morphology and other conditions. The contents of Atractylodes macrocephala Koidz I, II and III were determined by HPLC, and the change rules were analyzed. Results: for the original medicinal materials and decoction pieces, temperature and heating time had a certain effect on the conversion amount, but the effect was limited. However, under the influence of the appropriate heating temperature and heating time, the content of pulverized sample powder changed significantly. In the case of Atractylodes macrocephala Koidz in the form of powder, with the increase of storage time, the content of Atractylenolide I, II and III changed significantly. Conclusion: comparison of the content change law of Atractylodes macrocephala Koidz lactone I, II, III is conducive to optimizing the processing method of Atractylodes macrocephala Koidz, and provides a reference for the quality control of Atractylodes macrocephala Koidz.
基金supported by the National Natural Science Foundation of China(No.82370582 to Xiaoni Kong)The YangFan project from the Science and Technology Commission of Shanghai Municipality(No.22YF1449600 to Jiacheng Lin)State Administration of Traditional Chinese Medicine High-level Key Disciplines Program(No.ZYYZDXK-2023060)。
文摘Background and aims:Metabolic dysfunction-associated fatty liver disease(MAFLD)is a common chronic condition that can lead to cancer due to its complex pathogenesis.Therapeutic agents targeting AMPactivated protein kinase(AMPK)activation have been suggested as potential treatments for metabolic disorders such as metabolic dysfunction-associated steatohepatitis(MASH).Rhizoma Atractylodis Macrocephalae(RAM)has been clinically used to treat obesity-related health problems,but its therapeutic effects on MAFLD and the underlying mechanism remain unclear.Therefore,this study was conducted to evaluate the function and underlying mechanism of RAM in the treatment of MAFLD.Methods:The effect of RAM decoction on MAFLD was evaluated using a high-fat diet(HFD)-induced MAFLD mouse model.In vitro studies were conducted using a palmitic acid/oleic acid-induced lipid accumulation model in the alpha mouse liver 12 cells and RAM-containing serum.The underlying mechanisms were elucidated through a combination of network pharmacology analysis,immunohistochemistry,western blotting,and polymerase chain reaction analysis.Results:Administration of RAM decoction significantly reduced body weight gain in MAFLD mice without changing food intake.The weights of the liver and inguinal adipose tissues were also reduced after RAM treatment.Additionally,RAM administration decreased serum levels of alanine aminotransferase,aspartate transaminase,total cholesterol,triglyceride,low-density lipoprotein cholesterol,and glucose,while reducing lipid droplet accumulation in the liver tissues of MAFLD mice.The underlying mechanisms included the activation of the phosphorylation of AMPK and acetyl-CoA carboxylase(ACC),and inhibition of the expression of sterol regulatory element binding protein 1(SREBP1).However,RAM did not alter the protein expression levels of peroxisome proliferator-activated receptor a and carnitine palmitoyltransferase-1a.Furthermore,the RAM-induced upregulation of phosphorylated AMPK,phosphorylated ACC,and SREBP1 expression,as well as the downregulation of fatty acid synthase expression,were reversed by using an AMPK inhibitor.Conclusions:Through a combination of network pharmacology and experimental validation,we demonstrated that RAM may exert therapeutic effects on MAFLD by inhibiting lipid synthesis and activating phosphorylated AMPK pathways.
