Dao-di medicinal materials produced in a specific environment always present excellent appearance and high quality. Because of the unique appearance, Ginseng Radix et Rhizoma is regarded as a paradigm in the research on excellent appearance. This paper systematically summarized the research progress in the genetic and environmental factors influencing the formation of the excellent appearance of Ginseng Radix et Rhizoma, aiming to provide reference for the quality improvement of Ginseng Radix et Rhizoma and the scientific connotation of Dao-di Chinese medicinal materials. The Ginseng Radix et Rhizoma with high quality generally has a robust and long rhizome, a large angle between branch roots, and the simultaneous presence of a robust basal part of rhizome, adventitious roots, rhizome bark with circular wrinkles, and fibrous roots with pearl points. The cultivated and wild Ginseng Radix et Rhizoma have significant differences in the appearance and no significant difference in the population genetic diversity. The differences in the appearance are associated with cell wall modification, transcriptional regulation of genes involved in plant hormone transduction, DNA methylation, and miRNA regulation. The rhizosphere soil microorganisms including Fusarium and Alternaria, as well as the endophytes Trichoderma hamatum and Nectria haematococca, may be the key microorganisms affecting the growth and development of Panax ginseng. Cultivation mode, variety, and root exudates may be the main factors influencing the stability of rhizosphere microbial community. Ginsenosides may be involved in the formation of the excellent appearance. However, most of the available studies focus on the partial or single factors in the formation of Dao-di medicinal materials, ignoring the relationship within the complex ecosystems, which limits the research on the formation mechanism of Dao-di medicinal materials. In the future, the experimental models for the research involving genetic and environmental factors should be established and mutant materials should be developed to clarify the internal relationship between factors and provide scientific support for the research on Dao-di medicinal materials.
Alternaria ; Microbiota ; Panax/genetics* ; Rhizome

This study compared the transcriptome of Atractylodes lancea rhizome at different development stages and explored genes encoding the key enzymes of the sesquiterpenoid biosynthesis pathway. Specifically, Illumina NovaSeq 6000 was employed for sequencing the cDNA libraries of A. lancea rhizome samples at the growth stage(SZ), flowering stage(KH), and harvesting stage(CS), respectively. Finally, a total of 388 201 748 clean reads were obtained, and 16 925, 8 616, and 13 702 differentially expressed genes(DEGs) were identified between SZ and KH, KH and CS, and SZ and CS, separately. Among them, 53 genes were involved in the sesquiterpenoid biosynthesis pathways: 9 encoding 6 enzymes of the mevalonic acid(MVA) pathway, 15 encoding 7 enzymes of the 2-C-methyl-D-erythritol-4-phosphate(MEP) pathway, and 29 of sesquiterpenoid and triterpenoid biosynthesis pathway. Weighted gene co-expression network analysis(WGCNA) yielded 12 genes related to sesquiterpenoid biosynthesis for the SZ, 1 gene for the KH, and 1 gene for CS, and several candidate genes for sesquiterpenoid biosynthesis were discovered based on the co-expression network. This study laid a solid foundation for further research on the sesquiterpenoid biosynthesis pathway, analysis of the regulation mechanism, and mechanism for the accumulation of sesquiterpenoids in A. lancea.
Atractylodes/genetics* ; Mevalonic Acid/metabolism* ; Rhizome/genetics* ; Sesquiterpenes/metabolism* ; Transcriptome ; Triterpenes/metabolism*

Cerebral ischemia is one of the most common diseases in China, and the drug pair of Chuanxiong Rhizoma and Paeoniae Radix Rubra can intervene in cerebral ischemia to reduce the inflammatory response of cerebral ischemia and apoptosis. To reveal the intervention mechanism of Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair on cerebral ischemia systematically, computer network pharmacology technology was used in this paper to predict the target and signaling pathway of the drug pair on the intervention of cerebral ischemia, and then the molecular docking technology was used to further analyze the mechanism of the intervention. The target results were then verified by the rat cerebral ischemia model. The target network results showed that the active compounds of Chuanxiong Rhizoma-Paeoniae Radix Rubra for cerebral ischemic disease contained 30 compounds, 38 targets and 9 pathways. The main compounds included phenolic acids in Chuanxiong Rhizoma and monoterpene glycosides in Paeoniae Radix Rubra. The key targets involved mitogen-activated protein kinase 1(MAPK1), steroid receptor coactivator(SRC), epidermal growth factor receptor(EGFR), mitogen-activated protein kinase 14(MAPK14), caspase-3(CASP3), caspase-7(CASP7), estrogen receptor 1(ESR1), and mitogen-activated protein kinase 8(MAPK8), etc. The target gene functions were biased towards protein kinase activity, protein autophosphorylation, peptidyl-serine phosphorylation and protein serine/threonine kinase activity, etc. The important KEGG pathways involved Ras signaling pathway, ErbB signaling pathway and VEGF signaling pathway. Molecular docking results showed that catechin, oxypaeoniflorin, albiflorin, paeoniflorin and benzoylpaeoniflorin had strong binding ability with MAPK1, SRC, EGFR, MAPK14 and CASP7. MCAO rat experimental results showed that Chuanxiong Rhizoma-Paeoniae Radix Rubra significantly improved the cerebral ischemia injury and interstitial edema, and significantly reduced the activation of caspase-7 and the phosphorylation of ERK1/2. The Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair alleviated cerebral ischemia injury through a network model of multi-phenotype intervention by promoting cell proliferation and differentiation, reducing inflammatory factor expression, protecting nerve cells from death and figh-ting against neuronal cell apoptosis, with its action signaling pathway most related to Ras signaling pathway, ErbB signaling pathway and VEGF signaling pathway. This study provides the basis for clinical intervention of Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair on cerebral ischemia, and also provides ideas for the modernization of drug pairs.
Animals ; Brain Ischemia/genetics* ; Cerebral Infarction ; Drugs, Chinese Herbal ; Molecular Docking Simulation ; Paeonia ; Rats ; Rhizome

This study aims to explore the main mechanism of Astragali Radix-Coptis Rhizoma pair(hereinafter referred to as the pair) in the treatment of type 2 diabetes mellitus(T2 DM) based on network pharmacology and animal experiment. The main Chinese medicine compound prescriptions for T2 DM were retrieved from CNKI database and the medicinals with high frequency among these prescriptions were screened. The active components in the above medicinals were searched from TCMSP, TCMID, and previous research, targets of the components from SwissTargetPrediction and SEA, and targets for the treatment of T2 DM from DISGENET, TTD, and DrugBank. Thereby, the medicinal-component-disease-target network was constructed with Cytoscape. The targets were input in String database to yield the related proteins and the protein-protein interaction(PPI) network was constructed by Cytoscape. The biological functions of proteins in the PPI network were analyzed by Cluego. Then, high-fat high-sugar diet and 30 mg·kg~(-1) streptozotocin(STZ, intraperitoneal injection, once) were employed to induce T2 DM in rats and the T2 DM rats were classified into the control group, model group, positive drug(metformin) group, and pair group. After one month of administration, the changes of blood glucose and blood lipids [triglyceride(TG), cholesterol(CHO), low density lipoprotein(LDL), high density lipoprotein(HDL)] were detected with biochemical methods and pathological changes of islet and collagen deposition in pancreatic tissue by HE staining and Masson staining, respectively. The result showed that pair can be used for T2 DM treatment. ras-related C3 botulinum toxin substrate 1(RAC1), paraoxonase 1(PON1), beta-galactoside alpha 2,6-sialyltransferase 1(ST6 GAL1), insulin receptor(INSR), sex hormone-binding globulin(SHBG), ileal sodium/bile acid cotransporter(SLC10 A2), endothelin-1 receptor A(EDNRA), peroxisome proliferator-activated receptor A(PPARA), endothelin receptor B(EDNRB), and 5-hydroxytryptamine receptor 2 A(HTR2 A) were the targets of the pair for the treatment of T2 DM. The main biological functions of the pair were regulating the metabolism of blood glucose and li-pids and protecting the cardiovascular system. The fasting blood glucose, and serum TG, CHO, and LDL were higher(P<0.01) and the HDL was lower(P<0.05) in the model group than in the control group on the 7 th, 14 th, and 28 th days. The fas-ting blood glucose and the serum TG, CHO, and LDL decreased(P<0.05) and the serum HDL increased(P<0.05) in the metformin group and the pair group as compared with those in the model group on the 14 th and 28 th days. There were no significant differences in blood glucose, TG, CHO, LDL, and HDL between the metformin group and the pair group. Rats in the model group demonstrated damaged structures of islets and pancreas, obviously increased deposition of collagen in islets and pancreas, and blurred cell boundaries. Metformin and the pair significantly alleviated the damaged structures and collagen deposition. The pair can effectively regulate the disorders of blood glucose and lipid metabolism in T2 DM and protect the structure and functions of pancreas and islets by controlling cardiovascular system, which is worthy of clinical application and can be used for drug development.
Animals ; Blood Glucose ; Coptis ; Diabetes Mellitus, Type 2/genetics* ; Drugs, Chinese Herbal ; Metformin ; Rats ; Rhizome

The present study explored the mechanism of Fagopyri Dibotryis Rhizoma(FDR) and its main active components in the treatment of acute lung injury(ALI) based on the network pharmacology and the in vitro experiments. The main active components of FDR were obtained from the TCMSP database and screened by oral bioavailability and drug-likeness. The related target proteins of FDR were retrieved from the PubChem database, and the target genes related to ALI were screened out from the GeneCards database. A protein-protein interaction(PPI) network of compound target proteins and ALI target genes was constructed using STRING 11.0. Ingenuity Pathway Analysis(IPA) platform was used to analyze the common pathways of the potential compound target proteins of FDR and ALI target genes, thereby predicting the key targets and potential signaling pathways of FDR for the treatment of ALI. Finally, the potential pathways and key targets were verified by the in vitro experiments of lipopolysaccharide-induced RAW264.7 cells intervened by epicatechin(EC), the active component of FDR. The results of network pharmacology showed that 15 potential active components such as EC, procyanidin B1, and luteolin presumedly functioned in the treatment of ALI through nuclear transcription factor-κB(NF-κB) signaling pathway, transforming growth factor-β(TGF-β) signaling pathway, and adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway through key targets, such as RELA(P65). The results of in vitro experiments showed that 25 μmol·L~(-1) EC had no toxicity to cells and could inhibit the expression of the p65-phosphorylated protein in the NF-κB signaling pathway to down-regulate the expression of downstream inflammatory cytokines, including tumor necrosis factor-α(TNF-α), IL-1β and nitric oxide(NO), and up-regulate the expression of IL-10. These results suggested that the therapeutic efficacy of FDR on ALI was achieved by inhibiting the phosphorylation of p65 protein in the NF-κB signaling pathway and down-regulating the level of proinflammatory cytokines downstream of the signaling pathways.
Acute Lung Injury/genetics* ; Lipopolysaccharides ; NF-kappa B/metabolism* ; Rhizome ; Signal Transduction

This study aimed to elucidate the effective components of Shengxian Decoction and its mechanism of action in treating chronic heart failure. Firstly, UHPLC-Q-TOF-MS was established to identify the main chemical constituents in the rat serum after intragastric administration with Shengxian Decoction. Secondly, the absorbed components in serum were then used for the network pharmacology analysis to infer the mechanism and effective components. Targets for constituents in serum were predicted at TCMSP and Swiss-TargetPrediction database. An association network map was drawn by network visualization software Cytoscape 3.6.1. Finally, GO enrichment analysis and KEGG pathway enrichment analysis were carried out for the core target genes. By UHPLC-Q-TOF-MS, 18 prototype compounds were definitely identified, including five compounds from Astragali Radix, four compounds from Anemarrhenae Rhizoma, four compounds from Bupleuri Radix, four compounds from Cimicifugae Rhizoma, and one compound from Platycodonis Radix. Those components of Shengxian Decoction were closely associated with 13 key protein targets, including inflammatory factors, like IL6, IL1 B, TNF, PTGS2, IL10; redox enzymes CAT, HMOX1, and MPO; cardiovascular targets, like VEGFA, NOS3, and NOS2; and transmememial proteins CAV1 and INS. Network pharmacology analysis showed that the 18 compounds could be responsible for the treatment of chronic heart failure by regulating HIF-1 signaling pathways, PI3 K-Akt signaling pathways, cGMP-PKG signaling pathways, cAMP signaling pathways and TNF signaling pathways. This study provided a scientific basis for mechanism and effective ingredients of Shengxian Decoction.
Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Heart Failure/genetics* ; Rats ; Rhizome ; Signal Transduction

This study aims to explore the mechanism of fresh Phragmitis Rhizoma against chronic bronchitis airway inflammation. The SD rats of SPF grade were divided into control group, model group, Guilongkechuanning group(GLKCN, 1.125 g·kg~(-1)), high-dose fresh Phragmitis Rhizoma group(LG-HD, 15 g·kg~(-1)), and low-dose fresh Phragmitis Rhizoma group(LG-LD, 7.5 g·kg~(-1)). The chronic bronchitis models of rats in other groups except the control group were induced by the modified smoking method. From the 15 th day of modeling, the rats were given corresponding agents by gavage for 20 consecutive days. After the last administration, the rats were sacrificed for sample collection. Enzyme-linked immunosorbent assay(ELISA) was employed to detect serum transforming growth factor-β(TGF-β) and interleukin-6(IL-6) levels. The protein expression of TGF-β, IL-1β and IL-6 in lung tissue was detected by immunohistochemical method. Masson staining was performed to detect collagen fibers and muscle fibers in lung tissue, and HE staining to detect the pathological changes of lung tissue. Human bronchial epithelial(16 HBE) cells were cultured in vitro, and CCK-8(cell counting kit-8) method was used to detect the cytotoxicity of cigarette smoke extract(CSE) and fresh Phragmitis Rhizoma. After the exposure of 16 HBE cells to 3.5% CSE and appropriate concentration(800, 400 μg·mL~(-1)) of fresh Phragmitis Rhizoma for 24 h, quantitative real-time PCR was conducted to determine the mRNA levels of TGF-β and IL-1β, and Western blot was employed to determine the protein levels of TGF-β and IL-6 in the cells. The rat model of chronic bronchitis induced by smoking was successfully established. Fresh Phragmitis Rhizoma reduced serum TGF-β and IL-6 levels, down-regulated the protein levels of TGF-β, IL-1β, and IL-6 in lung tissue, and alleviated pathological changes and fibrotic lesions in lung tissue. Moreover, it down-regulated the CSE-induced protein expression of TGF-β and IL-6 as well as the mRNA level of TGF-β in 16 HBE cells. These results indicated that fresh Phragmitis Rhizoma could prevent airway inflammation from chronic bronchitis and promote cell repair by inhibiting the TGF-β signaling pathway.
Animals ; Bronchitis, Chronic/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Inflammation ; Lung ; Poaceae/chemistry* ; Rats ; Rats, Sprague-Dawley ; Rhizome ; Signal Transduction ; Transforming Growth Factor beta/genetics*

This study investigated the material basis and mechanism of Pinelliae Rhizoma Decoction in the treatment of airway inflammation. The cigarette smoke combined with lipopolysaccharide(LPS) was used to induce an airway inflammation model in mice. The expression levels of IL-6 and IL-8 in the bronchoalveolar lavage fluid(BALF) and the phosphorylation levels of p38 and IκB in the lungs of mice were taken as indexes to screen the effective extracts by system solvent extraction from Pinelliae Rhizoma Decoction(dichloromethane extract, ethyl acetate extract, n-butanol extract, etc.). Meanwhile, the human bronchial epithelial(16-HBE) cell model of cigarette smoke extract(CSE)-induced injury was established, and the mRNA expression levels of IL-6 and IL-8 and the phosphorylation levels of p38 and IκB proteins were also taken as indexes to evaluate the anti-inflammatory effect of different extracts of Pinelliae Rhizoma Decoction. The results showed that Pinelliae Rhizoma Decoction significantly antagonized airway inflammation in mice by down-regulating the expression levels of IL-6 and IL-8 in mice with airway inflammation and 16-HBE cells with CSE-induced injury and inhibiting the phosphorylation levels of p38 and IκB. The dichloromethane and ethyl acetate extracts of Pinelliae Rhizoma Decoction showed significant anti-inflammatory effects, while such effects of other extracts were not prominent. Furthermore, the database of Pinelliae Rhizoma composition was constructed, and the components in effective extracts were analyzed by HPLC-TOF-MS and Nano-LC-MS/MS. As revealed by the results, the compositions of the two effective extracts were similar with 36 common components. They were combined and then divided into Pinelliae Rhizoma alkaloids(PTAs) and Pinelliae Rhizoma non-alkaloids(PTNAs) by 732 cation-exchange resin. Further in vitro investigation confirmed the significant anti-inflammatory effect of PTNAs, while such effect of PTAs was not manifest. The MS analysis showed 172 peptides and 7 organic acids in PTNAs. The peptide content in PTNAs was 63.5% measured by quantitative analysis of BCA assay, and the organic acid content was 9.92% by potentiometric titration method. The findings of this study suggested that Pinelliae Rhizoma Decoction could antagonize airway inflammation in mice by inhibiting phosphorylation of p38 and IκB and blocking the activation of MAPK and NF-κB signaling pathways, and the effective components were related to the peptides and organic acids in PTNAs. The above results lay a foundation for the research on the mechanism and material basis of Pinelliae Rhizoma in antagonizing airway inflammation.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Inflammation/drug therapy* ; Mice ; NF-kappa B/genetics* ; Pinellia/chemistry* ; Respiratory Tract Diseases/drug therapy* ; Rhizome ; Tandem Mass Spectrometry

Rhizome rot disease is one of the main disease of planted Polygonatum kingianum. In this study, six strains of pathogenic fungus was isolated from P. kingianum samples with rhizome rot disease collected from six counties in Yunnan province. Its pathogenicity was confirmed by inoculation to healthy P. kingianum rhizome according to Koch's postulates. The colonies of the isolated fungi on potato dextrose agar(PDA) were orange with abundant crescentic conidia which were eseptate with a mean size of 19. 3-24. 9 μm×5. 2-5. 9 μm and a L/W ratio of 3. 4-4. 5. There was an oil ball in the center of the conidium. It's easy to see setae on PDA colony.The phylogenetic tree based on ITS, GAPDH, CHS-1, HIS3, ACT, and TUB2 sequences by maximum likelihood(ML) method indicated that the pathogenic fungus for P. kingianum rhizome rot disease was clustered into the clade of Colletotrichum spaethianum species complex, and was close to C. spaethianum. However, there were some differences in morphological and genetic characteristics between the pathogenic fungus and C. spaethianum. Therefore, the pathogenic fungus for rhizome rot disease of P. kingianum was identified as a new Colletotrichum species named C. kingianum. The disease spreads primarily due to the plantation of infected seedlings of P. kingianum. It is necessary to choose healthy seedlings and take rigorous disinfection measures for the disease prevention.
China ; Colletotrichum/genetics* ; Phylogeny ; Polygonatum ; Rhizome

Anemone flaccida Fr. Schmidt is a perennial medicinal herb that contains pentacyclic triterpenoid saponins as the major bioactive constituents. In China, the rhizomes are used as treatments for a variety of ailments including arthritis. However, yields of the saponins are low, and little is known about the plant's genetic background or phytohormonal responsiveness. Using one-quarter of the 454 pyrosequencing information from the Roche GS FLX Titanium platform, we performed a transcriptomic analysis to identify 157 genes putatively encoding 26 enzymes involved in the synthesis of the bioactive compounds. It was revealed that there are two biosynthetic pathways of triterpene saponins in A. flaccida. One pathway depends on β-amyrin synthase and is similar to that found in other plants. The second, subsidiary ("backburner") pathway is catalyzed by camelliol C synthase and yields β-amyrin as minor byproduct. Both pathways used cytochrome P450-dependent monooxygenases (CYPs) and family 1 uridine diphosphate glycosyltransferases (UGTs) to modify the triterpenoid backbone. The expression of CYPs and UGTs were quite different in roots treated with the phytohormones methyl jasmonate, salicylic acid and indole-3-acetic acid. This study provides the first large-scale transcriptional dataset for the biosynthetic pathways of triterpene saponins and their phytohormonal responsiveness in the genus Anemone.
Anemone ; drug effects ; genetics ; metabolism ; Biosynthetic Pathways ; drug effects ; genetics ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; drug effects ; Glycosyltransferases ; genetics ; metabolism ; Oleanolic Acid ; analogs & derivatives ; metabolism ; Plant Growth Regulators ; pharmacology ; Plant Proteins ; genetics ; metabolism ; Plants, Medicinal ; Rhizome ; drug effects ; genetics ; metabolism ; Saponins ; metabolism ; Triterpenes ; metabolism