A Comparative Analysis of the Chloroplast Genomes of Four Polygonum Medicinal Plants.

Polygonum is a generalized genus of the Polygonaceae family that includes various herbaceous plants. In order to provide aid in understanding the evolutionary and phylogenetic relationship in Polygonum at the chloroplast (cp) genome-scale level, we sequenced and annotated the complete chloroplast genomes of four Polygonum species using next-generation sequencing technology and CpGAVAS. Then, repeat sequences, IR contractions, and expansion and transformation sites of chloroplast genomes of four Polygonum species were studied, and a phylogenetic tree was built using the chloroplast genomes of Polygonum. The results indicated that the chloroplast genome construction of Polygonum also displayed characteristic four types of results, comparable to the published chloroplast genome of recorded angiosperms. The chloroplast genomes of the four Polygonum plants are highly consistent in genome size (159,015 bp-163,461 bp), number of genes (112 genes, including 78 protein-coding genes, 30 tRNA genes, and 4 rRNA genes), gene types, gene order, codon usage, and repeat sequence distribution, which identifies the high preservation among the Polygonum chloroplast genomes. The Polygonum phylogenetic tree was recreated by a full sequence of the chloroplast genome, which illustrates that the P. bistorta, P. orientale, and P. perfoliatum are divided into the same branch, and P. aviculare belongs to Fallopia. The precise system site of lots base parts requires further verification, but the study would provide a basis for developing the available genetic resources and evolutionary relationships of Polygonum.

Endophytic bacterial and fungal community compositions in different organs of ginseng (Panax ginseng).

Panax ginseng (Panax ginseng C. A. Mey.) is a perennial herb of the genus ginseng, which is used as medicine with dried roots and rhizomes. With the deepening of research on ginseng, the chemical components and pharmacological effects of ginseng have gradually been discovered. Endophytes are beneficial to host plants. However, the composition of endophytes in different organs from ginseng is poorly elucidated. The report of ginsenoside production by endophytic microbes isolated from Panax sp., motivated us to explore the endophytic microbial diversity related to the roots, stems, and leaves. In this study, the V5-V7 variable region of endophytic bacteria 16S rRNA gene and V1 variable region of endophytic fungi ITS gene in different organs were analyzed by high-throughput sequencing. The diversity and abundance of endophytic microbes in the three organs are different and are affected by the organs. For example, the most abundant endophytic bacterial genus in roots was Mycobacterium, while, the stems and leaves were Ochrobactrum. Similarly, the fungal endophytes, Coniothyrium and Cladosporium, were also found in high abundance in stems, in comparison to roots and leaves. The Shannon index shows that the diversity of endophytic bacteria in roots is the highest, and the richness of endophytic bacterial was root > stem (p < 0.05). Principal coordinate analysis showed that there were obvious microbial differences among the three groups, and the endophytic bacterial composition of the leaves was closer to that of the roots. This study provides an important reference for the study of endophytic microorganisms in ginseng.

Global Pharmacopoeia Genome Database is an integrated and mineable genomic database for traditional medicines derived from eight international pharmacopoeias.

Genomic data have demonstrated considerable traction in accelerating contemporary studies in traditional medicine. However, the lack of a uniform format and dispersed storage limits the full potential of herb genomic data. In this study, we developed a Global Pharmacopoeia Genome Database (GPGD). The database contains 34,346 records for 903 herb species from eight global pharmacopoeias (Brazilian, Egyptian, European, Indian, Japanese, Korean, the Pharmacopoeia of the People's Republic of China, and U.S. Pharmacopoeia's Herbal Medicines Compendium). In particular, the GPGD contains 21,872 DNA barcodes from 867 species, 2,203 organelle genomes from 674 species, 55 whole genomes from 49 species, 534 genomic sequencing datasets from 366 species, and 9,682 transcriptome datasets from 350 species. Among the organelle genomes, 534 genomes from 366 species were newly generated in this study. Whole genomes, organelle genomes, genomic fragments, transcriptomes, and DNA barcodes were uniformly formatted and arranged by species. The GPGD is publicly accessible at http://www.gpgenome.com and serves as an essential resource for species identification, decomposition of biosynthetic pathways, and molecular-assisted breeding analysis. Thus, the database is an invaluable resource for future studies on herbal medicine safety, drug discovery, and the protection and rational use of herbal resources.

Hepatoprotective effects of Cassiae Semen on mice with non-alcoholic fatty liver disease based on gut microbiota.

Cassiae Semen (CS), the seeds of Cassia obtusifolia L. and C. tora L, have a long medicinal history in China, with suggestions for it to relieve constipation and exert hepatoprotective effects. However, the underlying mechanisms are still unclear. In this study, mice with high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) were used to study the hepatoprotective effects of CS. The relationship between gut microbiota and hepatoprotective effect mechanisms mediated by CS extracts, the total aglycone extracts of CS, rubrofusarin-6-ß-gentiobioside, and aurantio-obtusin were examined. Our data indicate that CS extracts and components confer a protective effect by ameliorating lipid accumulation, intestinal barrier damage, liver damage, and inflammation on HFD-induced liver injury. Meanwhile, fecal microbe transplantation exerted the pharmacological effect of CS on HFD-fed mice; however, the efficacy of CS was inhibited or eliminated by antibiotic-induced dysbiosis. In conclusion, the therapeutic effects of CS on NAFLD were closely related to the gut microbiota, suggesting a role for TCM in treating disease.

Ginsenosides Improve Nonalcoholic Fatty Liver Disease via Integrated Regulation of Gut Microbiota, Inflammation and Energy Homeostasis.

Ginseng, the root and rhizome of Panax ginseng C. A. Mey., is a famous herbal medicine, and its major ginsenosides exert beneficial effects on nonalcoholic fatty liver disease (NAFLD). Due to the multicomponent and multitarget features of ginsenosides, their detailed mechanisms remain unclear. This study aimed to explore the role of ginsenosides on NAFLD and the potential mechanisms mediated by the gut microbiota and related molecular processes. C57BL/6J mice were fed a high-fat diet (HFD) supplemented or not supplemented with ginsenoside extract (GE) for 12 weeks. A strategy that integrates bacterial gene sequencing, serum pharmacochemistry and network pharmacology was applied. The results showed that GE significantly alleviated HFD-induced NAFLD symptoms in a dose-dependent manner. Furthermore, GE treatment modulated the HFD-induced imbalance in the gut microbiota and alleviated dysbiosis-mediated gut leakage and metabolic endotoxemia. Additionally, 20 components were identified in the mouse plasma after the oral administration of GE, and they interacted with 82 NAFLD-related targets. A network analysis revealed that anti-inflammatory effects and regulation of the metabolic balance might be responsible for the effects of GE on NAFLD. A validation experiment was then conducted, and the results suggested that GE suppressed NF-κB/IκB signaling activation and decreased the release and mRNA levels of proinflammatory factors (TNF-α, IL-1ß and IL-6). Additionally, GE promoted hepatic lipolytic genes (CPT-1a), inhibited lipogenic genes (SREBP-1c, FAS, ACC-1) and improved leptin resistance. These findings imply that the benefits of GE are involved in modulating the gut microbiota, enhancing the gut barrier function, restoring the energy balance, and alleviating metabolic inflammation. Moreover, GE might serve as a potential agent for the prevention of NAFLD through the integration of prebiotic, anti-inflammatory and energy-regulatory effects.

Prediction of the globally ecological suitability of Panax quinquefolius by the geographic information system for global medicinal plants (GMPGIS).

American ginseng (Panax quinquefolius L.) is a well-known Asian traditional herbal medicine with a large market demand. The plant is native to eastern North America, and its main producing areas worldwide are decreasing due to continuous cropping obstacles and environmental changes. Therefore, the identification of maximum similarities of new ecological distribution of P. quinquefolius, and prediction of its response to climate change in the future are necessary for plant introduction and cultivation. In this study, the areas with potential ecological suitability for P. quinquefolius were predicted using the geographic information system for global medicinal plants (GMPGIS) based on 476 occurrence points and 19 bioclimatic variables. The results indicate that the new ecologically suitable areas for P. quinquefolius are East Asia and the mid-eastern Europe, which are mainly distributed in China, Russia, Japan, Ukraine, Belarus, North Korean, South Korea, andRomania. Under global climate change scenarios, the suitable planting areas for P. quinquefolius would be increased by 9.16%-30.97%, and expandingnorth and west over the current ecologically suitable areas by 2070. The potential increased areas that are ecologically suitable include northern Canada, Eastern Europe, and the Lesser Khingan Mountains of China, and reduced regions are mainly in central China, the southern U.S., and southern Europe. Jackknife tests indicate that the precipitation of the warmest quarter was the important climatic factor controlling the distribution of P. quinquefolius. Our findings can be used as auseful guide for P. quinquefolius introduction and cultivation in ecologically suitable areas.

Wuji Wan Formula Ameliorates Diarrhea and Disordered Colonic Motility in Post-inflammation Irritable Bowel Syndrome Rats by Modulating the Gut Microbiota.

Emerging evidence suggests that gut microbiota contribute to the treatment of post-inflammatory irritable bowel syndrome (PI-IBS). Our previous studies have demonstrated that a Chinese formula, Wuji Wan, has the ability to mitigate abdominal pain and diarrhea in PI-IBS rats. However, little is known about the underlying mechanism and whether the gut microbiota mediate the effect of Wuji Wan on PI-IBS. Thus, the aim of this study was to determine whether Wuji Wan mitigated PI-IBS by modifying the gut microbiota. PI-IBS was induced in Sprague-Dawley rats by enema using 4% acetic acid and restraint stress. Rats were fed water, Wuji Wan extract (630 mg/kg) or pinaverium bromide (13.5 mg/kg). Our data showed that Wuji Wan effectively ameliorated abdominal pain, colonic motility abnormality and visceral hypersensitivity. Analysis of the fecal microbiota showed that Wuji Wan could reverse the reduction in richness of the gut microbiota and significantly increase the relative abundances of Akkermansia, Bacteroides, and Parasutterella; however, Lactobacillus and Prevotella were markedly decreased in the PI-IBS rats. Moreover, Wuji Wan promoted goblet cell proliferation in the colonic mucosa by increasing the release of mucin, up-regulating the distribution of tight junction proteins Occludin and ZO-1 and down-regulating the expression of MLCK in colonic epithelial cells. These findings suggest that Wuji Wan may remit IBS by modulating the gut microbiota and stabilizing the gut mucosal barrier, indicating that the use of a classical formula of Traditional Chinese Medicine (TCM) that exhibits a prebiotic effect may be a promising strategy for PI-IBS treatment.

Panax ginseng genome examination for ginsenoside biosynthesis.

Ginseng, which contains ginsenosides as bioactive compounds, has been regarded as an important traditional medicine for several millennia. However, the genetic background of ginseng remains poorly understood, partly because of the plant's large and complex genome composition. We report the entire genome sequence of Panax ginseng using next-generation sequencing. The 3.5-Gb nucleotide sequence contains more than 60% repeats and encodes 42 006 predicted genes. Twenty-two transcriptome datasets and mass spectrometry images of ginseng roots were adopted to precisely quantify the functional genes. Thirty-one genes were identified to be involved in the mevalonic acid pathway. Eight of these genes were annotated as 3-hydroxy-3-methylglutaryl-CoA reductases, which displayed diverse structures and expression characteristics. A total of 225 UDP-glycosyltransferases (UGTs) were identified, and these UGTs accounted for one of the largest gene families of ginseng. Tandem repeats contributed to the duplication and divergence of UGTs. Molecular modeling of UGTs in the 71st, 74th, and 94th families revealed a regiospecific conserved motif located at the N-terminus. Molecular docking predicted that this motif captures ginsenoside precursors. The ginseng genome represents a valuable resource for understanding and improving the breeding, cultivation, and synthesis biology of this key herb.

Complete Chloroplast Genome Sequence and Phylogenetic Analysis of the Medicinal Plant Artemisia annua.

The complete chloroplast genome of Artemisia annua (Asteraceae), the primary source of artemisinin, was sequenced and analyzed. The A. annua cp genome is 150,995 bp, and harbors a pair of inverted repeat regions (IRa and IRb), of 24,850 bp each that separate large (LSC, 82,988 bp) and small (SSC, 18,267 bp) single-copy regions. Our annotation revealed that the A. annua cp genome contains 113 genes and 18 duplicated genes. The gene order in the SSC region of A. annua is inverted; this fact is consistent with the sequences of chloroplast genomes from three other Artemisia species. Fifteen (15) forward and seventeen (17) inverted repeats were detected in the genome. The existence of rich SSR loci in the genome suggests opportunities for future population genetics work on this anti-malarial medicinal plant. In A. annua cpDNA, the rps19 gene was found in the LSC region rather than the IR region, and the rps19 pseudogene was absent in the IR region. Sequence divergence analysis of five Asteraceae species indicated that the most highly divergent regions were found in the intergenic spacers, and that the differences between A. annua and A. fukudo were very slight. A phylogenetic analysis revealed a sister relationship between A. annua and A. fukudo. This study identified the unique characteristics of the A. annua cp genome. These results offer valuable information for future research on Artemisia species identification and for the selective breeding of A. annua with high pharmaceutical efficacy.

Comprehensive Characterization for Ginsenosides Biosynthesis in Ginseng Root by Integration Analysis of Chemical and Transcriptome.

Herbgenomics provides a global platform to explore the genetics and biology of herbs on the genome level. Panax ginseng C.A. Meyer is an important medicinal plant with numerous pharmaceutical effects. Previous reports mainly discussed the transcriptome of ginseng at the organ level. However, based on mass spectrometry imaging analyses, the ginsenosides varied among different tissues. In this work, ginseng root was separated into three tissues-periderm, cortex and stele-each for five duplicates. The chemical analysis and transcriptome analysis were conducted simultaneously. Gene-encoding enzymes involved in ginsenosides biosynthesis and modification were studied based on gene and molecule data. Eight widely-used ginsenosides were distributed unevenly in ginseng roots. A total of 182,881 unigenes were assembled with an N50 contig size of 1374 bp. About 21,000 of these unigenes were positively correlated with the content of ginsenosides. Additionally, we identified 192 transcripts encoding enzymes involved in two triterpenoid biosynthesis pathways and 290 transcripts encoding UDP-glycosyltransferases (UGTs). Of these UGTs, 195 UGTs (67.2%) were more highly expressed in the periderm, and that seven UGTs and one UGT were specifically expressed in the periderm and stele, respectively. This genetic resource will help to improve the interpretation on complex mechanisms of ginsenosides biosynthesis, accumulation, and transportation.

[Genomic research of traditional Chinese medicines in vivo metabolism].

Gene is the base of in vivo metabolism and effectiveness for traditional Chinese medicines (TCM), and the gene expression, regulation and modification are used as the research directions to perform the TCM multi-component, multi-link and multi-target in vivo metabolism studies, which will improve the research on TCM metabolic proecess, effect target and molecular mechanism. Humans are superorganisms with 1% genes inherited from parents and 99% genes from various parts of the human body, mainly coming from the microorganisms in intestinal flora. These indicate that genetically inherited human genome and "second genome" could affect the TCM in vivo metabolism from inheritance and "environmental" aspects respectively. In the present paper, typical case study was used to discuss related TCM in vivo metabolic genomics research, mainly including TCM genomics research and gut metagenomics research, as well as the personalized medicine evoked from the individual difference of above genomics (metagenomics).