This study aims to mine the transcription factors that affect the genuineness of Codonopsis pilosula in Shanxi based on the transcriptome data of C. pilosula samples collected from Shanxi and Gansu, and then analyze the gene expression patterns, which will provide a theoretical basis for the molecular assisted breeding of C. pilosula. Gene ontology(GO) functional annotation, conserved motif prediction, and gene expression pattern analysis were performed for the differential transcription factors predicted based on the transcriptome data of C. pilosula from different habitats. A total of 61 differentially expressed genes(DEGs) were screened out from the transcriptome data. Most of the DEGs belonged to AP2/ERF-ERF family, with the conserved motif of [2X]-[LG]-[3X]-T-[3X]-[AARAYDRAA]-[3X]-[RG]-[2X]-A-[2X]-[NFP]. Forty-three of the DEGs showed significantly higher gene expression in C. pilosula samples from Shanxi than in the samples from Gansu, including 11 genes in the AP2/ERF-ERF family, 5 genes in the NAC fa-mily, 1 gene in the bHLH family, and 2 genes in the RWP-RK family, while 18 transcription factors showed higher expression levels in the samples from Gansu. GO annotation predicted that most of the DEGs were enriched in GO terms related to transcriptional binding activity(103), metabolic process(26), and stress response(23). The expression of transcription factor genes, CpNAC92, CpNAC100, CpbHLH128, and CpRAP2-7 was higher in the samples from Shanxi and in the roots of C. pilosula. CpNAC92, CpbHLH128, and CpRAP2-7 responded to the low temperature, temperature difference, and iron stresses, while CpNAC100 only responded to low temperature and iron stresses. The screening and expression analysis of the specific transcription factors CpNAC92, CpNAC100, CpbHLH128, and CpRAP2-7 in C. pilosula in Shanxi laid a theoretical foundation for further research on the mechanism of genuineness formation of C. pilosula.
Codonopsis/chemistry* ; Transcription Factors/genetics* ; Gene Expression Profiling ; Transcriptome ; Iron

This paper aims to explore the activity of Codonopsis canescens extract against rheumatoid arthritis(RA) based on the Toll-like receptors(TLRs)/mitogen-activated protein kinases(MAPKs)/nuclear factor kappa B(NF-κB) signaling pathways and its mechanism. The ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) was used to identify the components of C. canescens extract. Forty-eight male SD rats were randomly divided into six groups, namely the normal group, the model group, the methotrexate(MTX) tablet group, and the low, medium, and high-dose C. canescens extract(ZDS-L, ZDS-M, and ZDS-H) groups, with 8 rats in each group. The model of collagen-induced arthritis in rats was induced by injection of bovine type Ⅱ collagen emulsion. MTX(2.5 mg·kg~(-1)), ZDS-L, ZDS-M, and ZDS-H(0.3 g·kg~(-1), 0.6 g·kg~(-1), and 1.2 g·kg~(-1)) were administrated by gavage. Rats in the normal group and the model group received distilled water. MTX was given once every three days for 28 days, and the rest medicines were given once daily for 28 days. Body weight, degree of foot swelling, arthritis index, immune organ index, synovial histopathological changes, and serum levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interleukin-6(IL-6) were observed. Protein expressions of TLR2, TLR4, NF-κB p65, p38 MAPK, and p-p38 MAPK in rats were determined by Western blot. Thirty-four main components were identified by UPLC-Q-TOF-MS, including 15 flavonoids, 7 phenylpropanoids, 4 terpenoids, 4 organic acids, 2 esters, and 2 polyalkynes. As compared with the normal group, the body weight of the model group was significantly decreased(P<0.01), and foot swelling(P<0.05, P<0.01), arthritis index(P<0.01), and the immune organ index(P<0.01) were significantly increased. The synovial histopathological injury was obviously observed in the model group. The serum levels of inflammatory factors TNF-α, IL-1β, and IL-6 were significantly increased(P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK in the synovial tissue were significantly increased(P<0.01) in the model group. As compared with the model group, the body weights of the ZDS dose groups were increased(P<0.01), and the degree of foot swelling(P<0.01) and the arthritis index were decreased(P<0.05, P<0.01). The immune organ index was decreased(P<0.01) in the ZDS dose groups, and the synovial tissue hyperplasia and inflammatory cell infiltration were alleviated. The serum levels of TNF-α, IL-1β, and IL-6 were significantly decreased(P<0.05, P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK were decreased(P<0.05, P<0.01) in the ZDS dose groups. C. canescens extract containing apigenin, tricin, chlorogenic acid, aesculin, ferulic acid, caffeic acid, and oleanolic acid has a good anti-RA effect, and the mechanism may be related to the inhibition of TLRs/MAPKs/NF-κB signaling pathways.
Animals ; Cattle ; Male ; Rats ; Arthritis, Experimental/drug therapy* ; Arthritis, Rheumatoid/drug therapy* ; Body Weight ; Codonopsis/chemistry* ; Interleukin-6/blood* ; NF-kappa B/genetics* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Plant Extracts/therapeutic use* ; Rats, Sprague-Dawley ; Signal Transduction ; Toll-Like Receptor 2/metabolism* ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/pharmacology*

With the improvement of living standard,the theory of " medicine and food homology" has developed rapidly in the field of diet,medicine and health preservation. In recent years,many literatures have been reported on the active ingredients and pharmacological effects of medicinal and edible plants,but relatively few reports have been reported on their safety investigation. Therefore,to further evaluate the quality and safety of medicinal and edible plants,Astragali Radix,Codonopsis Radix and Laminariae Thallus were selected as our research objects in this study. Moreover,the pollution level and the potential health risk of heavy metals were deeply assessed in different types of medicinal and edible plants. Especially,the contents of chromium,copper,arsenic,cadmium,mercury and lead in these three herbs were determined by inductively coupled plasma mass spectrometry( ICP-MS),and their health risk level was evaluated by target hazard coefficient method. The results showed that under the international heavy metal limit standard( ISO 18664-2015,GB 2762-2017),the over-standard rates were 25%,77% and 100% in 16 batches of Astragali Radix,26 batches of Codonopsis Radix and 9 batches of Laminariae Thallus,respectively. Besides,the values of target hazard quotients( THQ) for adults and children are 0. 028 244,0. 063 505 and 0. 014 485,0. 032 568 in Astragalus membranaceus and Codonopsis pilosula,respectively,which were higher than the standard values of 0. 02 and 0. 011 25. While,the total heavy metals THQ values for adults and children are 0. 023 734 and 0. 020 287 in Laminariae Thallus,which were much higher than the standard values of 0. 008 0 and 0. 007 5. However,the CR values of As,Cd and Pb in the three herbs were lower than 1×10~(-6). Above results indicated that those six harmful elements have certain health hazards to the exposed population,but there is no potential carcinogenic effect. It can be seen that,there were still presence of the pollution of harmful elements,and it is necessary to establish the reasonable limit standards and quality control methods of medicinal and edible plants in time.
Adult ; Astragalus propinquus ; Child ; Codonopsis/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Humans ; Laminaria/chemistry* ; Metals, Heavy/analysis* ; Plant Preparations/chemistry* ; Plants, Edible/chemistry* ; Plants, Medicinal/chemistry* ; Risk Assessment

In this paper, the RP-HPLC specific chromatography was adopted, with DIKMA-C18 (4.6 mm x 250 mm, 5 µm) as the chromatographic column, with a gradient elution compose of acetonitrile and 0.1% phosphoric acid at flow rate of 0.8 mL · min(-1), the detection wavelength was 220 nm. The difference of the HPLC specific chromatograms between the Lu Dangshen and other different base sources and different producing area of Codonopsis Radix was compared, involved in the similarities and differences of the number and the relative peak area of characteristic peaks in the HPLC specific chromatograms. The HPLC specific chromatograms of Lu Dangshen was established and the relative retention times of seven peaks was determined, and the peaks of codonopyrrolidium B, syringin, lobetyolin, tangshenoside I and atractylenoide III were identified; The HPLC specific chromatograms of Lu Dangshen provided a method for scientific evaluation and effective control the quality of Lu Dangshen from Shanxi famous-region.
Chromatography, High Pressure Liquid ; methods ; Codonopsis ; chemistry ; Drugs, Chinese Herbal ; analysis ; Glucosides ; analysis ; Phenylpropionates ; analysis ; Plant Roots ; chemistry ; Quality Control

Design space approach is applied in this study to enhance the robustness of first ethanol precipitation process of Codonopsis Radix (Dangshen) by optimizing parameters. Total flavonoid recovery, dry matter removal, and pigment removal were defined as the process critical quality attributes (CQAs). Plackett-Burman designed experiments were carried out to find the critical process parameters (CPPs). Dry matter content of concentrated extract (DMCE), mass ratio of ethanol to concentrated extract (E/C ratio) and concentration of ethanol (CEA) were identified as the CPPs. Box-Behnken designed experiments were performed to establish the quantitative models between CPPs and CQAs. Probability based design space was obtained and verified using Monte-Carlo simulation method. According to the verification results, the robustness of first ethanol precipitation process of Dangshen can be guaranteed by operating within the design space parameters. Recommended normal operation space are as follows: dry matter content of concentrated extract of 45.0% - 48.0%, E/C ratio of 2.48-2.80 g x g(-1), and the concentration of ethanol of 92.0% - 92.7%.
Chemical Precipitation ; Chemistry, Pharmaceutical ; methods ; Codonopsis ; chemistry ; Drugs, Chinese Herbal ; chemistry ; isolation & purification

Animals ; Codonopsis ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Myocardial Reperfusion Injury ; drug therapy ; Rats ; Selenium ; pharmacology

Adolescent ; Altitude ; Brain ; drug effects ; Codonopsis ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Tablets

OBJECTIVETo study the effects of the Rich Selenium-Banqiao-Codonopsis Pilosula (BCPA) injecta on the aged rats' immune functions and its underlying mechanism.

METHODSTotally 60 rats, composed of 2, 12 and 22 month age old (half male and half female), were served as a young group, middle-age group and aged group respectively. Each group rats were randomly divided into the control and the BCPA subgroup (n = 10). The BCPA group was injected with BCPA at 7.2 g/kg intraperitoneally every day and the control group was injected the same volume of normal saline. All rats were conventionally fed for 45 days. An immune injection was performed after 15 days of BCPA injection. On the 22nd day, late-onset immune response would be induced. The caudal vein blood was collected and the antigen specific IgG, IgG1 and IgG2a antibody was detected on the 15th, 30th and 45th day. On the 45th day, the major T cell subgroups of splenic cells were analyzed and splenic cells were proliferated.

RESULTSNo significant difference in the delayed-type hypersensivity (DTH) reaction was found between the control and the BCPA subgroups in the young and middle-aged rats while the aged BCPA subgroup had a stronger DTH reaction. There was no significant difference in the blood content of specific IgG, IgG1 and IgG2a antibody between the young and middle-age BCPA group while the aged BCPA group rats had an obvious enhancing reaction to the three antibodies mentioned above (P < 0.05). There was no obvious difference in the number of the CD3+ lymphocytes and the CD4+ T helper lymphocytes between the control and the BCPA subgroup in the young aged rats while a significant increase was spotted between the middle-aged and the aged group (P < 0.05). The splenic cells from young BCPA group rats had a strong proliferation response (P < 0.05).

CONCLUSIONBCPA can enhance DTH reaction, potentiate the production of specific IgG, IgG1 and IgG2a antibody to resist KLH, improve the reaction to antigen, increase the amount of CD4+ cell, promote the immune response and had an important role in anti-immunosenescence and antioxidant capacity improvement in the aged rats.

Aging ; Animals ; CD4-Positive T-Lymphocytes ; immunology ; Codonopsis ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Female ; Immune System ; drug effects ; Immunoglobulin G ; blood ; Male ; Rats ; Selenium ; pharmacology ; Spleen ; immunology

Animals ; Codonopsis ; chemistry ; Diabetes Mellitus, Experimental ; drug therapy ; Female ; Male ; Mice ; Polysaccharides ; therapeutic use

Animals ; Codonopsis ; chemistry ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Fatigue ; drug therapy ; Female ; Hypoxia ; drug therapy ; Male ; Mice ; Selenium ; pharmacology