Search

Gastrointestinal cancer (GIC), primarily including colorectal cancer, gastric cancer, liver cancer, pancreatic cancer, and esophageal cancer, is one of the most common causes of cancer-related deaths with increasing prevalence and poor prognosis. Medicinal plants have been shown to be a great resource for the treatment of GIC. Due to their complex manifestations of multi-component and multi-target, the underlying mechanisms how they function against GIC remain to be completely deciphered. Cell metabolism is of primary importance in the initialization and development of GIC, which is reported to be a potential target. As an essential supplement to the newest "omics" sciences, metabolomics focuses on the systematic study of the small exogenous and endogenous metabolites involved in extensive biochemical metabolic pathways of living system. In good agreement with the systemic perspective of medicinal plants, metabolomics offers a new insight into the efficacy assessment and action mechanism investigation of medicinal plants as adjuvant therapeutics for GIC therapy. In this review, the metabolomics investigations on metabolism-targeting therapies for GIC in the recent 10 years were systematically reviewed from five aspects of carbohydrate, lipid, amino acid, and nucleotide metabolisms, as well as other altered metabolisms (microbial metabolism, inflammation, and oxidation), with particular attention to the potential of active compounds, extracts, and formulae from medicinal plants. Meanwhile, the current perspectives and future challenges of metabolism-targeting therapies of medicinal plants for GIC were also discussed. In conclusion, the understanding of the action mechanisms of medicinal plants in GIC from the metabolomics perspective will contribute to the clinical application of potential candidates from the resourceful medicinal plants as novel and efficient adjuvant therapeutics for GIC therapy. [ABSTRACT FROM AUTHOR]

Polygonum cuspidatum (Japanese knotweed, also known as Huzhang in Chinese), a plant that produces bioactive components such as stilbenes and quinones, has long been recognized as important in traditional Chinese herbal medicine. To better understand the biological features of this plant and to gain genetic insight into the biosynthesis of its natural products, we assembled a draft genome of P. cuspidatum using Illumina sequencing technology. The draft genome is ca. 2.56 Gb long, with 71.54% of the genome annotated as transposable elements. Integrated gene prediction suggested that the P. cuspidatum genome encodes 55,075 functional genes, including 6,776 gene families that are conserved in the five eudicot species examined and 2,386 that are unique to P. cuspidatum. Among the functional genes identified, 4,753 are predicted to encode transcription factors. We traced the gene duplication history of P. cuspidatum and determined that it has undergone two whole-genome duplication events about 65 and 6.6 million years ago. Roots are considered the primary medicinal tissue, and transcriptome analysis identified 2,173 genes that were expressed at higher levels in roots compared to aboveground tissues. Detailed phylogenetic analysis demonstrated expansion of the gene family encoding stilbene synthase and chalcone synthase enzymes in the phenylpropanoid metabolic pathway, which is associated with the biosynthesis of resveratrol, a pharmacologically important stilbene. Analysis of the draft genome identified 7 abscisic acid and water deficit stress-induced protein-coding genes and 14 cysteine-rich transmembrane module genes predicted to be involved in stress responses. The draft de novo genome assembly produced in this study represents a valuable resource for the molecular characterization of medicinal compounds in P. cuspidatum , the improvement of this important medicinal plant, and the exploration of its abiotic stress resistance. [ABSTRACT FROM AUTHOR]

The study determined the chemical constituents and anti-inflammatory effects of leaf oil from Cinnamomum subavenium (CS-LO) that has been used in folk medicine to treat various symptoms including inflammation. The anti-inflammatory effects of the oil were evaluated by LPS-stimulated RAW264.7 cells and the Carr-induced hind mouse paw edema model, respectively. In vitro, nitric oxide (NO), prostaglandin E2 (PGE2), TNF-α, IL-6, and IL-1β were significantly decreased by CS-LO, and the expression of nuclear factor-κB (NF-κB) protein was blocked as well. In in vivo, the malondialdehyde (MDA) and paw edema levels were decreased by CS-LO, and the same result came up on the NO and tumor necrosis factor (TNF-a) of serum at the 5th h after Carr injection. In addition, iNOS and COX-2 immunoreactive cells of the paw tissue were decreased significantly by CS-LO (200 mg/kg) in histological examination. The present findings indicated that CS-LO have anti-inflammatory properties, and the effects might be caused through inhibiting iNOS, COX-2, TNF-α, IL-1β, and IL-6 expression via affecting NF-κB pathway, which will provide a power scientific basis for CS-LO to be used as the treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]

Anthraquinones are bioactive natural products, some of which are active components in medicinal medicines, especially Chinese medicines. These compounds exert actions including purgation, anti-inflammation, immunoregulation, antihyperlipidemia, and anticancer effects. This study aimed to review the pharmacokinetics (PKs) of anthraquinones, which are importantly associated with their pharmacological and toxicological effects. Anthraquinones are absorbed mainly in intestines. The absorption rates of free anthraquinones are faster than those of their conjugated glycosides because of the higher liposolubility. A fluctuation in blood concentration and two absorption peaks of anthraquinones may result from the hepato-intestinal circulation, reabsorption, and transformation. Anthraquinones are widely distributed throughout the body, mainly in blood-flow rich organs and tissues, such as blood, intestines, stomach, liver, lung, kidney, and fat. The metabolic pathways of anthraquinones are hydrolysis, glycuronidation, sulfation, methylation/demethylation, hydroxylation/dehydroxylation, oxidation/reduction (hydrogenation), acetylation and esterification by intestinal flora and liver metabolic enzymes, among which hydrolysis, glycuronidation and sulfation are dominant. Of note, anthraquinones can be transformed into each other. The main excretion routes for anthraquinones are the kidney, recta, and gallbladder. Conclusion: Some anthraquinones and their glycosides, such as aloe-emodin, chrysophanol, emodin, physcion, rhein and sennosides, have attracted the most PK research interest due to their more biological activities and/or detectability. Anthraquinones are mainly absorbed in the intestines and are mostly distributed in blood flow-rich tissues and organs. Transformation into another anthraquinone may increase the blood concentration of the latter, leading to an increased pharmacological and/or toxicological effect. Drug-drug interactions influencing PK may provide insights into drug compatibility theory to enhance or reduce pharmacological/toxicological effects in Chinese medicine formulae and deserve deep investigation. [ABSTRACT FROM AUTHOR]

[Display omitted] • Global transcriptome analysis revealed key metabolites biosynthetic related genes. • Organ-specific transcription factors may mediate root metabolic processes. • Novel simple sequence repeats were identified. • Root accumulating resveratrol and emodin are correlated to the local activities of their biosynthetic genes. Polygonum cuspidatum is an important medicinal plant, which produces bioactive stilbenes and quinones, has been developed to be an important economic crop and cultivated in the Qinba mountain area, central China for years. Little is understood about its genetic characterization, which has impeded functional genomic studies of P. cuspidatum. In order to tackle genetic insights into the metabolic pathways of natural products, a comprehensive transcriptome analysis was conducted using Illumina sequencing amongst five major organs, namely roots, stems, leaves, flowers, and fruits in P. cuspidatum. As a result, 219,411 non-redundant transcripts and 159,545 functionally annotated unigenes were identified with mean lengths of 662 and 813 nucleotides, respectively. Organ-specific gene analysis unveiled that flowers presents the most abundance of unique transcripts (7,366), whereas the least does in roots (1,052). The gene expression profiles related to the metabolism of resveratrol and anthraquinone were investigated, and the contents of bioactive compounds in the different organs were determined, revealing that resveratrol and emodin were preferentially accumulated in the roots. In addition, our transcription factor analysis suggested that some bHLH- and MYB-TF family genes showed organ-enriched expression patterns and may mediate the metabolic processes. A total number of 25,404 simple sequence repeats were identified, which will benefit germplasm identification and discrimination of P. cuspidatum varieties. This study presents the assembly of a de novo transcriptome that will promote the investigation of the biosynthetic genes of natural products in P. cuspidatum , and enrich the genetic knowledge of this medical plant. [ABSTRACT FROM AUTHOR]

• The correlation between bioactive compounds and rhizosphere microbiome in P. cuspidatum. • The Stenotrophomonas was specifically enriched in the root endosphere. • Bcteroides , and Erysipelatoclostridium might promote resveratrol synthesis. Polygonum cuspidatum (Polygonum cuspidatum Sieb. & Zucc.), a medicinal plant that is abundantly accumulating bioactive compounds in its roots, is the primary source of resveratrol in industry and has long been recognized as raw materials for traditional Chinese medicine. Plant root secondary metabolism is correlated to its surrounding microbial communities. However, the root-associated microbiomes of P. cuspidatum and the potential correlation between the bioactive compounds and microbiomes are poorly understood. To unveil the root-associated bacterial community, the microbiome compositions of P. cuspidatum roots across four cultivation years were analyzed by using 16S rRNA gene sequencing. Furthermore, the relationships among root-associated bacteria, soil properties, and four major bioactive compounds (polydatin, resveratrol, emodin, and physcion) were explored by a multivariate correlation study. The composition of the rhizosphere microbiome significantly differed from that of the endosphere microbiome. The composition of the rhizosphere microbiome significantly varied across different cultivation years and soil properties, contributing to the majority of variance. Regarding different cultivation years and soil properties, the compositions of the root endosphere microbiome remained relatively stable, indicating a strong selection effect in P. cuspidatum roots. Among root endosphere microbes, Stenotrophomonas was specifically enriched from rhizosphere with a 15 times increase of relative abundance, exhibiting no significant variation across different cultivation years. The relative abundance of rhizosphere Stenotrophomonas was positively correlated with the content of emodin. Taken together, this study demonstrated that the stability of the root endosphere microbiome with a dominance of Stenotrophomonas may maintain the growth of P. cuspidatum through the combined effect of emodin. The contents of bioactive compounds in roots exhibited distinct correlations with specific bacteria, suggesting that Bacteroides , Acinetobacter , Erysipelatoclostridium , and Achromobacter may enhance the accumulation of resveratrol. This study provides insights into the interaction networks among P. cuspidatum root-associated bacteria, cultivation years, soil properties, and bioactive compounds, giving us a new opportunity to manipulate the production of bioactive compounds, and thus improve the industrial and medicinal value of P. cuspidatum in future. [ABSTRACT FROM AUTHOR]