Chemical composition and pharmacological activities of Atractylodes lancea:A review

Atractylodes lancea(called Cangzhu in China)is a medicinal plant that has long been used as tonic agent in various ethno-medical systems in East Asia,especially in China,for the treatment of gastrointestinal dysfunction,cancer,osteoporosis,obesity and fetal irritability.We used the TCMSP database to search for the main active ingredients and traditional Chinese medicine targets of Atractylodes macrocephala.There are a total of 38 related articles,of which 27 are closely related to chemical composition and activity.This study reviews the chemical components and pharmacological effects of A.lancea,aiming to provide reference for its further research and development.

Chemical components and protective effects of Atractylodes japonica Koidz.ex Kitam against acetic acid-induced gastric ulcer in rats

BACKGROUND Atractylodes japonica Koidz.ex Kitam.(A.japonica,Chinese name:Guan-Cangzhu,Japanese name:Byaku-jutsu),a perennial herb,which is mainly distributed in northeast area of China,it’s often used to treat digestive system diseases such as gastric ulcer(GU).However,the mechanism of its potential protective effects against GU remains unclear.AIM To investigate the protective effects of A.japonica on acetic acid-induced GU rats.METHODS The chemical constituents of A.japonica were determined by ultra performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)analysis.The rat model of GU was simulated by acetic acid method.The pathological changes of gastric tissues were evaluated by hematoxylin-eosin stain,the levels of epidermal growth factor(EGF),EGF receptor(EGFR),nuclear factor kappa-B(NF-κB),interleukin-1β(IL-1β),IL-10,Na^(+)-K^(+)-ATPase(NKA)in serum and gastric tissues were determined by enzyme-linked immunosorbent assay,and the mRNA expressions of EGFR,NF-κBp65,IkappaBalpha(IκBα)and Zonula Occludens-1(ZO-1)in gastric tissues were determined by real-time reverse transcription polymerase chain reaction,and the efficacy was observed.Then,plasma metabolomic analysis was performed by UPLC-MS/MS to screen the specific potential biomarkers,metabolic pathways and to explore the possible mechani-sms.RESULTS 48 chemical constituents were identified.Many of them have strong pharmacological activity,the results also revealed that A.japonica significantly improved the pathological damage of gastric tissues,increased the expression levels of IL-10,IκBαrelated to anti-inflammatory factors,decreased the expression levels of IL-1β,NF-κB,NF-κBp65,related to proinflammatory factors,restored the levels of factors about EGF,EGFR,ZO-1 associated with ulcer healing and the levels of factors about NKA associated with energy metabolism.Metabolomic analysis identified 10 potential differential metabolites and enriched 7 related metabolic pathways.CONCLUSION These findings contribute to the understanding of the potential mechanism of A.japonica to improve acetic acidinduced GU,and will be of great importance for the development and clinical application of natural drugs related to A.japonica.

Effects of Different Initial Processing Methods on Atractylodin Content of Atractylodes chinensis

[Objectives]The paper was to compare the effects of different initial processing methods on atractylodin content of Atractylodes chinensis.[Methods]The atractylodin content of A.chinensis obtained by different initial processing methods was determined by HPLC.The loss rate on drying was determined by weighing.[Results]In the study of drying methods,the atractylodin content varied significantly among different thicknesses of slices,and the overall content of the product with the slice thickness of 5 mm was higher.Among different drying methods,constant temperature vacuum drying and shade drying of 5 mm slice resulted in the highest content of atractylodin.In the experiment of root impacting,root impacting twice received the best effect,and there was no significant difference in the atractylosin content of A.chinensis between drying in the sun and drying in the shade after root impacting twice(P>0.05).[Conclusions]Constant temperature vacuum drying or drying in the shade with the slice thickness of 5 mm,and root impacting twice is the best initial processing method,which leads to high atractylodin content of A.chinensis and good quality of medicinal materials.

Therapeutic potential and pharmacological activities of Atractylodes lancea (Thunb.) DC.

The rhizome of Atractylodes Iancen(A.lancea)(Thunb.) DC.(AL)is extensively used in Chinese,Thai,and Japanese traditional medicines as crude extracts/decoctions or a component in various herbal formulations.Various pharmacological activities of Al.and its major constituents have been demonstrated in ritro.ex ciro.and in animal models.Results from the toxicity studies in animal models suggest safety profile of AL,and its active constituents.Despite extensive use with positive impression in many diseases,there has not been a clinical study that can conclusively support its efficacy and safely profile in human.This review comprehensively summarizes current information on the pharmacological activities of AL and their active constituents including anticancer,anti-inflammatory,antimicrobial and antipyretic activities,as well as activities on central nervous,cardiovascular,and gastrointestinal systems.

A new polyacetylene glycoside from the rhizomes of Atractylodes lancea

A new polyacetylene glycoside,（1,3Z,11E）-tridecatriene-7,9-diyne-5-hydroxyl-6-O-β-D-glucopyranoside,was isolated from the rhizomes of Atractylodes lancea（Thunb.） DC.Its structure was elucidated on the basis of spectral analysis.

Two New Sesquiterpenes from Atractylodes macrocehpala

Two new sesquiterpenes: beishulenolide A 1 and peroxiatractylenolide III 2 wereisolated from Atraclylodes macrocephala Koids (compositae).Their structures were elucidated onthe basis of spectral evidence, especially 2D-NMR methods and chemical conversion.

Effects of Atractylodes Macrocephala on the Cytomembrane Ca^(2+)-activated K^+ Currents in Cells of Human Pregnant Myometrial Smooth Muscles

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.

Immunomodulating Activities of Polysaccharides from ZhuQin Formula and Atractylodes in Hypoimmune Mice

[Objectives] To investigate the infrared identification of ZhuQin Formula and Atractylodes polysaccharides and its effect on immune function in immunocompromised mice. [Methods] In this experiment,the structure of polysaccharides was analyzed by Fourier transform infrared spectroscopy. The experiment was divided into the polysaccharide groups of high,medium and low dose of ZhuQin,the extraction group of ZhuQin,the polysaccharide group of Atractylodes,the positive drug group,the blank group and the model group. The model of immunosuppressed mice was established by intraperitoneal injection of cyclophosphamide. The carbon clearance index,immune organ index,serum hemolysin,spleen T and B lymphocyte transformation rate were determined. [Results]The results show that the polysaccharides have obvious absorption peaks of polysaccharides; Formula extracts and polysaccharides can enhance the immune function of immunosuppressive mice at a certain dose level,and the effect of formula polysaccharide is better than that of extract and single traditional Chinese medicine polysaccharides. [Conclusions] The results suggest that the polysaccharides of ZhuQin Formula and Atractylodes may be acidic polysaccharides containing pyran ring and furan ring. ZhuQin Formula polysaccharide may play an immunomodulatory role mainly by improving the specific immunity of the organism.

Advances in research on chemical constituents,pharmacological actions and processing of atractylodes macrocephala

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.

Control Effect of Validamycin against Seedling Blight of Atractylodes macrocephala

[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.

Study on the Mechanism of Atractylodes lancea in the Treatment of Diabetes Based on Network Pharmacology

[Objectives]To predict the mechanism of Atractylodes lancea in the treatment of diabetes by using the method of network pharmacology.[Methods]The active constituents of A.lancea were mined and their action targets were predicted by using TCMSP database,and the targets of diabetes were screened out by GeneCards,and OMIM databases.The"constituent-target-pathway-disease"network of A.lancea in the treatment of diabetes was constructed by using Cytoscape software.The target protein-related interaction network was constructed by STRING database,and the biological function annotation and pathway analysis of key targets were carried out.[Results]The 4 active constituents of A.lancea could treat diabetes by intervening in 47 targets,95 GO biological processes and 116 main biological pathways.[Conclusions]The wogonin,NSC63551,3β-acetoxy atractylone andβ-carotene in A.lancea may regulate nuclear receptor activity,transcription factor activity(directly bind to the ligand-regulated sequence-specific DNA),steroid receptor,G protein-coupled amine receptor activity,sodium-chloride transporter activity,neurotransmitter receptor activity and other pharmacological effects,by mediating AGE-RAGE pathway,IL-17 pathway,PI3K-Akt pathway,p53 pathway,etc.,so as to treat diabetes.

Pharmacodynamic Substance and Mechanism of Atractylodes macrocephala in Treating PD Based on LC-MS and Network Pharmacology Technology

[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.

Quality Evaluation of Atractylodes chinensis(DC.)Koidz.in Chengde Region Based on Dual Component Analysis

[Objectives]To evaluate the quality of Atractylodes chinensis(DC.)Koidz.in Chengde region.[Methods]35 samples of A.chinensis from different growth years were collected,and a high performance liquid chromatography(HPLC)method was established for the dual components of atractylodin and atractylone,and the quality evaluation was conducted on the cultivated A.chinensis from Chengde region in terms of moisture,ash and volatile oil content.[Results]The moisture content of all samples met the regulations,and the content of volatile oil was relatively high.Among them,seven samples with atractylodin content lower than 0.3%were unqualified products(accounting for 20%),and one sample had excessive ash content(accounting for 3%).[Conclusions]The established method for the determination of the dual components of Atractylodis Rhizoma is stable,simple,fast,precise and reusable.Besides,according to the Pearson correlation analysis among the indicators,it is concluded that the atractylodin and atractylone content are significantly related to the growth period and the volatile oil content.In addition,the quality evaluation indicators of A.chinensis in Chengde region show that there are differences in the quality of Atractylodis Rhizoma,but the overall pass rate is relatively high.It is necessary to further study the reasons for the differences.

Research Progress of Diseases on Atractylodes lancea

According to the current situation of diseases on Atractylodes lancea , the etiology, pathogenesis, symptoms and control methods of root diseases, leaf diseases and other diseases of A. lancea are analyzed, in order to provide a reference for the diagnosis and control of diseases on A. lancea .

Seed Propagation Technique of Atractylodes lancea in Maoshan, Jiangsu

Due to over exploitation, the Atractylodes resources in such five counties and cities as Jurong, Jintan, Lishui, Liyang and Gaochun have been exhausted. This paper summarized the seed propagation technique of Atractylodes lancea in Maoshan, Jiangsu Province, aiming to provide reference for the restoration of A. lancea production in Maoshan, Jiangsu.

Atramacronoids A-C,three eudesmanolide sesquiterpene-phenol hybrids with an unprecedented C-C linkage from the rhizomes of Atractylodes macrocephala

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.

Populational change of CD4^(+)CD25^(+)Treg cells is responsible for the synergistic effect of the combination of RAMP2 with baicalin in treating recurrent spontaneous abortion mouse models

Background: The absence of a safe and effective therapy for recurrent spontaneous abortion due to a maternofetal failure in immunological tolerance remains an intractable clinical obstacle for surgeons. Recently, traditional Chinese medicine has become a feasible alternative for certain diseases, including recurrent spontaneous abortion. However, because of the complex composition of the traditional Chinese medicine formula, its action mechanism remains unclear. Methods: We selected two isolated active ingredients (RAMP and baicalin) from the traditional Chinese medicine formula and used an abortion-prone CBA/J × DBA/2 model to simulate human RSA and compared the changes in fetal resorption rate, Treg cell percentage, and relevant cytokines before and after combination therapy. In addition, The mechanisms were preliminarily discussed using in vitro differentiation models. Results: In CBA/J × DBA/2 abortion-prone mice, the combination therapy resulted in a lower embryo resorption rate compared to that obtained with individual delivery of either RAMP or baicalin, thereby playing an embryo-protective role through the increase in Treg cells for the maintenance of maternal-fetal immune tolerance. In in vitro primary cell differentiation experiments, the concentration of Treg cells significantly increased from 11% to 17.9% after the combination therapy compared to that of the single administration group. Conclusion: the synergistic effects of RAMP and baicalin were responsible for Treg differentiation. The present study provides a solid basis for improving the applicability of traditional Chinese herbs in the treatment of recurrent spontaneous abortion.

Polysaccharide extracts of Astragalus membranaceus and Atractylodes macrocephala promote intestinal epithelial cell migration by activating the polyamine-mediated K^+ channel

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.

Atractylodes lancea rhizome water extract reduces triptolide-induced toxicity and enhances anti-inflammatory effects

The present study was designed to explore the influence of water extracts of Atractylodes lancea rhizomes on the toxicity and anti-inflammatory effects of triptolide(TP). A water extract was prepared from A. lancea rhizomes and co-administered with TP in C57BL/6 mice. The toxicity was assayed by determining serum biochemical parameters and visceral indexes and by liver histopathological analysis. The hepatic CYP3A expression levels were detected using Western blotting and RT-PCR methods. The data showed that the water extract of A. lancea rhizomes reduced triptolide-induced toxicity, probably by inducing the hepatic expression of CYP3A. The anti-inflammatory effects of TP were evaluated in mice using a xylene-induced ear edema test. By comparing ear edema inhibition rates, we found that the water extract could also increase the anti-inflammatory effects of TP. In conclusion, our results suggested that the water extract of A. lancea rhizomes, used in combination with TP, has a potential in reducing TP-induced toxicity and enhancing its anti-inflammatory effects.

Nitric Oxide and Brassinosteroids Mediated Fungal Endophyte-Induced Volatile Oil Production Through Protein Phosphorylation Pathways in Atractylodes lancea Plantlets

Fungal endophytes have been isolated from almost every plant, infecting their hosts without causing visible disease symptoms, and yet have still proved to be involved in plant secondary metabolites accumulation. To decipher the possible physiological mechanisms of the endophytic fungus-host interaction, the role of protein phosphorylation and the relationship between endophytic fungus-induced kinase activity and nitric oxide （NO） and brassinolide （BL） in endophyte-enhanced volatile oil accumulation in Atractylodes lancea plantlets were investigated using pharmacological and biochemical approaches. Inoculation with the endophytic fungus Gilmaniella sp. ALl2 enhanced the activities of total protein phosphorylation, Ca2^-dependent protein kinase, and volatile oil accumulation in A. lancea plantlets. The upregulation of protein kinase activity could be blocked by the BL inhibitor brassinazole. Furthermore, pretreatments with the NO-specific scavenger cPTIO significantly reduced the increased activities of protein kinases in A. lancea plantlets inoculated with endophytic fungus. Pretreatments with different protein kinase inhibitors also reduced fungus-induced NO production and volatile oil accumulation, but had barely no effect on the BL level. These data suggest that protein phosphorylation is required for endophyte- induced volatile oil production in A. lancea plantlets, and that crosstalk between protein phosphorylation and the NO pathway may occur and act as a downstream signaling event of the BL pathway.