The development of new drugs is multidisciplinary and systematic work. High-throughput techniques based on "-omics" have driven the discovery of biomarkers in diseases and therapeutic targets of drugs. A transcriptome is the complete set of all RNAs transcribed by certain tissues or cells at a specific stage of development or physiological condition. Transcriptome research can demonstrate gene functions and structures from the whole level and reveal the molecular mechanism of specific biological processes in diseases. Currently, gene expression microarray and high-throughput RNA-sequencing have been widely used in biological, medical, clinical, and drug research. The former has been applied in drug screening and biomarker detection of drugs due to its high throughput, fast detection speed, simple analysis, and relatively low price. With the further development of detection technology and the improvement of analytical methods, the detection flux of RNAseq is much higher but the price is lower, hence it has powerful advantages in detecting biomarkers and drug discovery. Compared with the traditional RNA-seq, scRNA-seq has higher accuracy and efficiency, especially the single-cell level of gene expression pattern analysis can provide more information for drug and biomarker discovery. Therefore, (sc) RNA-seq has broader application prospects, especially in the field of drug discovery. In this overview, we will review the application of these technologies in drug, especially in natural drug and biomarker discovery and development. Emerging applications of scRNA-seq and the third generation RNA-sequencing tools are also discussed.
Siraitia grosvenorii (Swingle) C. Jeffrey, a member of the family Cucurbitaceae, is a unique economic and medicinal plant grown in China. For more than 300 years, S. grosvenorii has been used as a natural sweetener and as a traditional medicine for the treatment of pharyngitis, pharyngeal pain, as well as an anti-tussive remedy in China. It is one of the first approved medicine food homology species in China. It has been widely studied as a natural product with high development potential. Therefore, the present paper provides a review of the botanical characterization, traditional uses and ethnopharmacology, food and nutritional values, chemical constituents, pharmacological effects, toxicology, and development direction for the future of S. grosvenorii. Phytochemical studies have revealed that the chemical composition of this plant mainly includes iridoid and phenylpropanoid glycosides. Several compounds such as triterpenoids, flavonoids, and amino acids have been isolated from the plant. S. grosvenorii and its active constituents possess broad pharmacological properties, such as antioxidant, hypoglycemic, immunologic, anti-tussive and sputum-reducing, hepatoprotective, and antimicrobial activities, etc. By documenting the comprehensive information of S. grosvenorii, we hope to establishes the groundwork for further research on the mechanism of action of S. grosvenorii and its development as a new health food in the future.
Oleanolic acid glucuronosyltransferase (OAGT) genes synthesizing the direct precursor of oleanane-type ginsenosides were discovered. The four recombinant proteins of OAGT were able to transfer glucuronic acid at C-3 of oleanolic acid that yields oleanolic acid 3-O-β-glucuronide. Ginsenosides are the primary active components in the genus Panax, and great efforts have been made to elucidate the mechanisms underlying dammarane-type ginsenoside biosynthesis. However, there is limited information on oleanane-type ginsenosides. Here, high-performance liquid chromatography analysis demonstrated that oleanane-type ginsenosides (particularly ginsenoside Ro and chikusetsusaponin IV and IVa) are the abundant ginsenosides in Panax zingiberensis, an extremely endangered Panax species in southwest China. These ginsenosides are derived from oleanolic acid 3-O-β-glucuronide, which may be formed from oleanolic acid catalyzed by an unknown oleanolic acid glucuronosyltransferase (OAGT). Transcriptomic analysis of leaves, stems, main roots, and fibrous roots of P. zingiberensis was performed, and a total of 46,098 unigenes were obtained, including all the identified homologous genes involved in ginsenoside biosynthesis. The most upstream genes were highly expressed in the leaves, and the UDP-glucosyltransferase genes were highly expressed in the roots. This finding indicated that the precursors of ginsenosides are mainly synthesized in the leaves and transported to different parts for the formation of particular ginsenosides. For the first time, enzyme activity assay characterized four genes (three from P. zingiberensis and one from P. japonicus var. major, another Panax species with oleanane-type ginsenosides) encoding OAGT, which particularly transfer glucuronic acid at C-3 of oleanolic acid to form oleanolic acid 3-O-β-glucuronide. Taken together, our study provides valuable genetic information for P. zingiberensis and the genes responsible for synthesizing the direct precursor of oleanane-type ginsenosides.
Sophora tonkinensis belongs to genus Sophora of the fabaceae family. it is mainly distributed in the ridge and peak regions of limestone areas in western china and has high medicinal value and important ecological functions. Wild populations of S. tonkinensis are in danger and need urgent conservation. furthermore, wild S. tonkinensis resources are very limited relative to the needs of the market, and many adulterants are present on the market. therefore, a method for authenticating S. tonkinensis and its adulterants at the molecular level is needed. chloroplast genomes are valuable sources of genetic markers for phylogenetic analyses, genetic diversity evaluation, and plant molecular identification. In this study, we report the complete chloroplast genome of S. tonkinensis. The circular complete chloroplast genome was 154,644 bp in length, containing an 85,810 bp long single-copy (LSC) region, an 18,321 bp short single-copy (SSC) region and two inverted repeat (IR) regions of 50,513 bp. The S. tonkinensis chloroplast genome comprised 129 genes, including 83 protein-coding genes, 38 transfer RNA (tRNA) genes, and 8 ribosomal RNA (rRNA) genes. The structure, gene order and guanine and cytosine (Gc) content of the S. tonkinensis chloroplast genome were similar to those of the Sophora alopecuroides and Sophora flavescens chloroplast genomes. A total of 1,760 simple sequence repeats (SSRs) were identified in the chloroplast genome of S. tonkinensis, and most of them (93.1%) were mononucleotides. Moreover, the identified SSRs were mainly distributed in the LSC region, accounting for 60% of the total number of SSRs, while 316 (18%) and 383 (22%) were located in the SSC and IR regions, respectively. Only one complete copy of the rpl2 gene was present at the LSc/iRB boundary, while another copy was absent from the iRA region because of the incomplete structure caused by iR region expansion and contraction. the phylogenetic analysis placed S. tonkinensis in papilionoideae, sister to S. flavescens, and the genera Sophora and Ammopiptanthus were closely related. the complete genome sequencing and chloroplast genome comparative analysis of S. tonkinensis and its closely related species presented in this paper will help formulate effective conservation and management strategies as well as molecular identification approaches for this important medicinal plant.
Spatholobus suberectus Dunn ( S . suberectus ), which belongs to the Leguminosae, is an important medicinal plant in China. Owing to its long growth cycle and increased use in human medicine, wild resources of S . suberectus have decreased rapidly and may be on the verge of extinction. De novo assembly of the whole S . suberectus genome provides us a critical potential resource towards biosynthesis of the main bioactive components and seed development regulation mechanism of this plant. Utilizing several sequencing technologies such as Illumina HiSeq X Ten, single-molecule real-time sequencing, 10x Genomics, as well as new assembly techniques such as FALCON and chromatin interaction mapping (Hi-C), we assembled a chromosome-scale genome about 798 Mb in size. In total, 748 Mb (93.73%) of the contig sequences were anchored onto nine chromosomes with the longest scaffold being 103.57 Mb. Further annotation analyses predicted 31,634 protein-coding genes, of which 93.9% have been functionally annotated. All data generated in this study is available in public databases.
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