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Background Polygonum cuspidatum Sieb. et Zucc. is a well-known medicinal plant whose pharmacological effects derive mainly from its stilbenes, anthraquinones, and flavonoids. These compounds accumulate differentially in the root, stem, and leaf; however, the molecular basis of such tissue-specific accumulation remains poorly understood. Because tissue-specific accumulation of compounds is usually associated with tissue-specific expression of the related biosynthetic enzyme genes and regulators, we aimed to clarify and compare the transcripts expressed in different tissues of P. cuspidatum in this study. Results High-throughput RNA sequencing was performed using three different tissues (the leaf, stem, and root) of P. cuspidatum. In total, 80,981 unigenes were obtained, of which 40,729 were annotated, and 21,235 differentially expressed genes were identified. Fifty-four candidate synthetase genes and 12 transcription factors associated with stilbene, flavonoid, and anthraquinone biosynthetic pathways were identified, and their expression levels in the three different tissues were analyzed. Phylogenetic analysis of polyketide synthase gene families revealed two novel CHS genes in P. cuspidatum. Most phenylpropanoid pathway genes were predominantly expressed in the root and stem, while methylerythritol 4-phosphate and isochorismate pathways for anthraquinone biosynthesis were dominant in the leaf. The expression patterns of synthase genes were almost in accordance with metabolite profiling in different tissues of P. cuspidatum as measured by high-performance liquid chromatography or ultraviolet spectrophotometry. All predicted transcription factors associated with regulation of the phenylpropanoid pathway were expressed at lower levels in the stem than in the leaf and root, but no consistent trend in their expression was observed between the leaf and the root. Conclusions The molecular knowledge of key genes involved in the biosynthesis of P. cuspidatum stilbenes, flavonoids, and anthraquinones is poor. This study offers some novel insights into the biosynthetic regulation of bioactive compounds in different P. cuspidatum tissues and provides valuable resources for the potential metabolic engineering of this important medicinal plant.

Knotweed Polygonum cuspidatum s.l. is a large, suffrutescent, perennial forb native to northeastern Asia that was imported as an ornamental and has become a widespread invasive species in urban and rural environments of North America and Europe. Studies have demonstrated knotweed allelopathy to the germination and growth of many tracheophytes, but we have found no studies of knotweed toxicity to bryophytes. Therefore, the aim of this study was to determine if knotweed extracts affected the growth of the gametophytes of two mosses: Atrichum angustatum and Thuidium delicatulum. Both moss species were exposed to aqueous rhizome extracts of knotweed in concentrations of 0 (control), 10, 25, 50 and 75% for a total of nine days in the laboratory. All non-zero concentrations resulted in significant losses of green biomass, with the greatest losses occurring at the highest concentrations. Samples exposed to the three highest concentrations lost 80% of green mass after nine days. These results help explain the scarcity of moss growth on or near live knotweed crowns.

Poaceae species such as silver grass or reed are commonly used in traditional mulch farming in Japan, where the Nishi-Awa area is a Globally Important Agricultural Heritage Systems (GIAHS) site. Farmers here have traditionally used silver grass for mulch farming; furthermore, local farmers have learned from long-standing experience that Japanese knotweed (Fallopia japonica, Polygonaceae) is better for cultivation of solanaceous crops in this area. However, it is unclear why Japanese knotweed mulching is beneficial for cultivation of solanaceous crops. Thus, in this study, we hypothesized that Japanese knotweed mulching may be effective in avoiding hazards associated with continuous potato cropping, as native potato used to be cultivated twice a year in the past. Therefore, we investigated the effects of Japanese knotweed mulching on continuous potato cropping and after tomato cropping, which is another solanaceous crop species. Field experiments were conducted in 2018. First, we compared Japanese knotweed mulching, silver grass mulching and no grass mulching (control) in a soil under continuous potato cultivation and in an uncultivated soil. As a result, the extent of the potato yield decrease was reduced by Japanese knotweed mulching. Secondly, we compared Japanese knotweed-mulching and no grass mulching in a soil after a tomato crop and in an uncultivated soil. The extent of decrease in potato growth and yield was also reduced by Japanese knotweed mulching. These findings indicate that mulching with Japanese knotweed helped to avoid the risks associated with continuous potato cropping.

We investigated the potential of two terrestrial biomass invasive species in the United-Kingdom as lignocellulosic biofuel feedstocks: Japanese Knotweed (Fallopia japonica) and Rhododendron (Rhododendron ponticum). We demonstrate that a pretreatment technique using a low-cost protic ionic liquid, the ionoSolv process, can be used for such types of plant species considered as waste, to allow their integration into a biorefinery. N,N,N-Dimethylbutylammonium hydrogen sulfate ([DMBA][HSO4]) was able to fractionate the biomass into a cellulose-rich pulp and a lignin stream at high temperatures (150–170 °C) and short reaction times (15–60 minutes). More than 70–80% of the subsequent cellulose was hydrolysed into fermentable sugars, which were fermented into the renewable energy vector bioethanol.

Junjie Bi,1,* Yuhua Lin,1,* Yipeng Sun,1,* Mengzhe Zhang,2,* Qingge Chen,1 Xiayi Miu,1 Lingling Tang,1 Jinjin Liu,1 Linyun Zhu,1 Zhenhua Ni,3 Xiongbiao Wang1 1Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, People’s Republic of China; 2Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, People’s Republic of China; 3Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenhua Ni; Xiongbiao Wang Email zhenhuani@yeah.net; xiongbiao6@yahoo.comBackground: Polygonum cuspidatum is a Chinese medicine commonly used to treat phlegm-heat asthma. However, its anti-asthmatic active ingredients and mechanism are still unknown. The aim of this study was to predict the active ingredients and pathways of Polygonum cuspidatum and to further explore the potential molecular mechanism in asthma by using network pharmacology.Methods: The active ingredients and their targets related to Polygonum cuspidatum were seeked out with the TCM systematic pharmacology analysis platform (TCMSP), and the ingredient-target network was constructed. The GeneCards, DrugBank and OMIM databases were used to collect and screen asthma targets, and then the drug-target-disease interaction network was constructed with Cytoscape software. A target protein-protein interaction (PPI) network was constructed using the STRING database to screen key targets. Finally, GO and KEGG analyses were used to identify biological processes and signaling pathways. The anti-asthmatic effects of Polygonum cuspidatum and its active ingredients were tested in vitro for regulating airway smooth muscle (ASM) cells proliferation and MUC5AC expression, two main symptoms of asthma, by using Real-time PCR, Western blotting, CCK-8 assays and annexin V-FITC staining.Results: Twelve active ingredients in Polygonum cuspidatum and 479 related target proteins were screened in the relevant databases. Among these target proteins, 191 genes had been found to be differentially expressed in asthma. PPI network analysis and KEGG pathway enrichment analysis predicted that the Polygonum cuspidatum could regulate the AKT, MAPK and apoptosis signaling pathways. Consistently, further in vitro experiments demonstrated that Polygonum cuspidatum and resveratrol (one active ingredient of Polygonum cuspidatum) were shown to inhibit ASM cells proliferation and promoted apoptosis of ASM cells. Furthermore, Polygonum cuspidatum and resveratrol inhibited PDGF-induced AKT/mTOR activation in ASM cells. In addition, Polygonum cuspidatum decreased H2O2 induced MUC5AC overexpression in airway epithelial NCI-H292 cells.Conclusion: Polygonum cuspidatum could alleviate the symptoms of asthma including ASM cells proliferation and MUC5AC expression through the mechanisms predicted by network pharmacology, which provides a basis for further understanding of Polygonum cuspidatum in the treatment of asthma.Keywords: Polygonum cuspidatum, asthma, ASM cells, MUC5AC, network pharmacology

A chronic multi-symptom illness of unknown etiology, Gulf War Illness (GWI) affects 175,000 to 250,000 veterans of the Gulf War. Because inflammation has suspected involvement in the pathophysiology of GWI, botanical treatments that target inflammation may be beneficial in reducing symptoms. No FDA-approved treatments currently exist for GWI, and rapid prioritization of agents for future efficacy testing is important. This study is part of a larger project that screened nine different botanical compounds with purported anti-inflammatory properties for potential treatment of GWI. We tested three botanicals (resveratrol [Polygonum cuspidatum], luteolin, and fisetin [Rhus succedanea]) on symptom severity of GWI in this placebo-controlled, pseudo-randomized clinical trial. Twenty-one male veterans with GWI completed the study protocol, which consisted of 1 month (30 days ± 3) of baseline symptom reports, 1 month of placebo, 1 month of lower-dose botanical, and 1 month of higher-dose botanical. Participants completed up to 3 different botanicals, repeating the placebo, lower-dose, and higher-dose cycle for each botanical assigned. Linear mixed models were used for analyses. Resveratrol reduced GWI symptom severity significantly more than placebo at both the lower (p = 0.035) and higher (p = 0.004) dosages. Luteolin did not decrease symptom severity more than placebo at either the lower (p = 0.718) or higher dosages (p = 0.492). Similarly, fisetin did not reduce symptom severity at either the lower (p = 0.504) or higher (p = 0.616) dosages. Preliminary findings from this screening study suggest that resveratrol may be beneficial in reducing symptoms of GWI and should be prioritized for future testing. Larger trials are required to determine efficacy, response rates, durability of effects, safety, and optimal dosage. This trial was registered on ClinicalTrials.gov (NCT02909686) on 13 September 2016.

Human babesiosis is a CDC reportable disease in the United States and is recognized as an emerging health risk in multiple parts of the world. The current treatment for human babesiosis is suboptimal due to treatment failures and unwanted side effects. Although Babesia duncani was first described almost 30 years ago, further research is needed to elucidate its pathogenesis and clarify optimal treatment regimens. Here, we screened a panel of herbal medicines and identified Cryptolepis sanguinolenta, Artemisia annua, Scutellaria baicalensis, Alchornea cordifolia, and Polygonum cuspidatum to have good in vitro inhibitory activity against B. duncani in the hamster erythrocyte model. Furthermore, we found their potential bioactive compounds, cryptolepine, artemisinin, artesunate, artemether, and baicalein, to have good activity against B. duncani, with IC50 values of 3.4 μM, 14 μM, 7.4 μM, 7.8 μM, and 12 μM, respectively, which are comparable or lower than that of the currently used drugs quinine (10 μM) and clindamycin (37 μM). B. duncani treated with cryptolepine and quinine at their respective 1×, 2×, 4× and 8× IC50 values, and by artemether at 8× IC50 for three days could not regrow in subculture. Additionally, Cryptolepis sanguinolenta 90% ethanol extract also exhibited no regrowth after 6 days of subculture at doses of 2×, 4×, and 8× IC50 values. Our results indicate that some botanical medicines and their active constituents have potent activity against B. duncani in vitro and may be further explored for more effective treatment of babesiosis.

Flavan-3-ols and proanthocyanidins of invasive alien plants Japanese knotweed (Fallopia japonica Houtt.), giant knotweed (Fallopia sachalinensis F. Schmidt) and Bohemian knotweed (Fallopia × bohemica (Chrtek &amp, Chrtkova) J.P. Bailey) were investigated using high performance thin-layer chromatography (HPTLC) coupled to densitometry, image analysis and mass spectrometry (HPTLC–MS/MS). (+)-Catechin, (−)-epicatechin, (−)-epicatechin gallate and procyanidin B2 were found in rhizomes of these three species, and for the first time in Bohemian knotweed. (−)-Epicatechin gallate, procyanidin B1, procyanidin B2 and procyanidin C1 were found in giant knotweed rhizomes for the first time. Rhizomes of Bohemian and giant knotweed have the same chemical profiles of proanthocyanidins with respect to the degree of polymerization and with respect to gallates. Japanese and Bohemian knotweed have equal chromatographic fingerprint profiles with the additional peak not present in giant knotweed. Within the individual species giant knotweed rhizomes and leaves have the most similar fingerprints, while the fingerprints of Japanese and Bohemian knotweed rhizomes have additional peaks not found in leaves. Rhizomes of all three species proved to be a rich source of proanthocyanidins, with the highest content in Japanese and the lowest in Bohemian knotweed (based on the total peak areas). The contents of monomers in Japanese, Bohemian and giant knotweed rhizomes were 2.99 kg/t of dry mass (DM), 1.52 kg/t DM, 2.36 kg/t DM, respectively, while the contents of dimers were 2.81 kg/t DM, 1.09 kg/t DM, 2.17 kg/t DM, respectively. All B-type proanthocyanidins from monomers to decamers (monomers—flavan-3-ols, dimers, trimers, tetramers, pentamers, hexamers, heptamers, octamers, nonamers and decamers) and some of their gallates (monomer gallates, dimer gallates, dimer digallates, trimer gallates, tetramer gallates, pentamer gallates and hexamer gallates) were identified in rhizomes of Bohemian knotweed and giant knotweed. Pentamer gallates, hexamers, hexamer gallates, nonamers and decamers were identified for the first time in this study in Bohemian and giant knotweed rhizomes.

Funder: The David and Claudia Harding Foundation, Background: Invasive alien plant species often have negative environmental and social impacts, such as loss of biodiversity and alteration of ecosystem services. As a result, managing the introduction, establishment, and abundance of invasive species is a major priority. To do this effectively, we need evidence on the effect of management interventions (such as using herbicide or cutting to control invasive plants). This evidence should not only include the effects of these management interventions on invasive alien species, but also on native species and other non-target outcomes such as ecosystem services. Such evidence would allow for comparison of the trade-offs between different management interventions. In the planned review we aim to assess how management interventions to control nine priority invasive alien plants species in England and Wales affect environmental outcomes. These species are: Japanese knotweed (Fallopia japonica) Nuttall’s waterweed (Elodea nuttallii), Chilean rhubarb (Gunnera tinctoria), Giant hogweed (Heracleum mantegazzianum), Floating pennywort (Hydrocotyle ranunculoides), Himalayan balsam (Impatiens glandulifera), Curly waterweed (Lagarosiphon major), American skunk cabbage (Lysichiton americanus), Parrot’s feather (Myriophyllum aquaticum). Methods: Searches will be in English and use bibliographic databases (Scopus, Web of Science Core Collection, Open Access Theses and Dissertations, and Conservation Evidence) and internet searches (Google Scholar), as well as specialist databases. Our methodology will only use the names of each species (scientific names and common names, including synonyms) as our search string (we will not use qualifiers, such as “AND invasive”). This will give low specificity but will increase the likelihood of capturing all relevant information. We will use predefined criteria for study inclusion and data extraction. We will screen publications in two stages: (1) using titles and abstracts and (2) using full texts. Consistency of inclusion will be checked by two people screening a random sample of 10% of titles and abstracts. This dual-screening will be subject to kappa analysis and any disagreements resolved through discussion. We will use critical appraisal to assess study validity by identifying studies that are potentially prone to bias.

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Porphyromonas gingivalis triggers a range of innate immune responses in the host that may contribute to the development of periodontitis and dementing diseases including Alzheimer’s disease (AD). This study aimed to assess the mode of action of trans-resveratrol in modulating the P. gingivalis lipopolysaccharide (PgLPS) induced metabolic inflammation in a neuronal cell model. Confluent IMR-32 neuroblastoma cells were treated with trans-resveratrol from Polygonum cuspidatum in the presence or absence of PgLPS. The abundance of messenger ribo-nucleic acid (mRNA) transcripts of a panel of 92 genes was quantitatively assessed through targeted transcriptome profiling technique and the biochemical pathways affected were identified through Ingenuity Pathway Analysis. Gene expression analysis revealed that trans-resveratrol down-regulated the mRNA of multiple gene markers including growth factors, transcription factors, kinases, trans-membrane receptors, cytokines and enzymes that were otherwise activated by PgLPS treatment of IMR-32 neuroblastoma cells. Pathway analysis demonstrated that the cellular oxidative stress caused by the activation of phosphoinositide-3-kinase/Akt1 (PI3K/Akt1) pathway that leads to the production of reactive oxygen species (ROS), chronic inflammatory response induced by the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway and nutrient utilization pathways were favourably modulated by trans-resveratrol in the PgLPS challenged IMR-32 cells. This study demonstrates the potential of trans-resveratrol as a bioactive compound with multiple modes of intracellular action further supporting its therapeutic application in neuroinflammatory diseases.

Detoxifying and blood-activating Chinese medicine granule formula, which includes 15 g of Polygonum cuspidatum Sieb. et Zucc. (Polygonum cuspidatum) and 10 g of Crataegus pinnatifida Bunge (Hawthorn), can relieve the symptoms and serve as supplementary treatment for unstable angina.This study aimed to explore the role of detoxifying and blood-activating formulae in the treatment of unstable angina and the potential mechanism involved.A total of 144 participants with unstable angina were randomly divided into experimental and control groups. Both groups were treated with standardized Western medicine; the experimental group was additionally treated with detoxifying and blood-activating Chinese medicine granules, which included 15 g of P. cuspidatum and 10 g of C. pinnatifida for 4 weeks. The primary endpoint was the frequency of weekly angina pectoris attacks before and after treatment. The secondary endpoints, also observed before and after treatment, included blood glucose, blood lipids, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10, and adiponectin levels, as well as the ratio of pro/anti-inflammatory factors and evaluation scales of symptoms and syndromes in Chinese and Western medicine.In both experimental and control groups, the frequency of weekly angina pectoris attacks was lower after treatment (P 0.01), but with no significant intergroup difference (P = 0.10). After intervention, the hs-CRP, TNF-α, and IL-6 levels decreased, while the IL-10 and adiponectin levels significantly increased in the experimental group (P 0.05 or 0.01). The ratios of the inflammatory factors significantly decreased after treatment, particularly in the experimental group (P 0.01). Symptoms and syndromes were also ameliorated in the experimental group (P 0.01), showing a significant difference from the control group (P 0.01).Detoxifying and blood-activating formulae can reduce the frequency and relieve symptoms of unstable angina, and this mechanism may be related to a regulation of the balance of pro- and anti-inflammatory factors.

This article reviews the research progress of the chemical constituents and biosynthesis mechanisms of Polygonum cuspidatum. The chemistry components isolated from P. cuspidatum are mainly anthraquinones, naphthoquinones, stilbenes, flavonoids, and other compounds. The synthase genes involved in the biosynthesis process were summarized. The biosynthesis mechanism of stilbenes and anthraquinones was discussed. This article hopefully to provide a reference for further research, development and utilization of P. cuspidatum.

This study investigated the effects of the n-BuOH soluble fraction of Polygoni Cuspidati 80% ethanol extract (POCU1b) on high-fat diet (HFD)-induced obesity, non-alcoholic fatty liver (NAFL), and insulin resistance (IR) to find a safe and more effective agent. HPLC profiling of POCU1b identified seven marker compounds. POCU1b increased glycerol release, cyclic adenosine monophosphate (cAMP) level, and inhibited phosphodiesterase (PDE) activity. Seven weeks of POCU1b treatment decreased body weight gain, weight and adipocyte size in fat tissues, serum lipids, and triglyceride and lipid droplets in the livers of HFD-fed rats. POCU1b improved blood glucose, insulin sensitivity, and impaired insulin secretion in the pancreas. Further, POCU1b ameliorated adiponectin, leptin, IL-6 and TNF-&alpha, levels, increased AMPK and p-ACC expression, activated CPT-1 activity, and suppressed FAS mRNA, SOCS-3 protein expression, and NF-&kappa, B DNA-binding activity. When compared with the Xenical&reg, treated group, a positive group, the action of POCU1b on body weight was more effective than that of Xenical. POCU1b did not show side effects, such as oily spotting and loss of appetite. These results suggest that POCU1b possesses therapeutic or preventive potential for obesity, NAFL and IR via inhibitions of pancreatic lipase and cAMP-dependent PDE activity, AMPK activation, and SOCS-3 suppression, without oily spotting and loss of appetite.

Anaerobic co-digestion of animal manure and lignocellulosic biomass is a potent approach for sustainable biomethane production. Co-digestion of dairy manure (DM) and Japanese knotweed (JK), which was collected from a riverbank, was investigated at five different DM-to-JK mixing ratios (100:0, 90:10, 80:20, 60:40, and 0:100; wet weight basis) under thermophilic condition. The results showed that the methane yields obtain from the co-digestion of DM and JK were much higher than that obtained from JK alone (104 ml/gVS), which indicates the synergistic effect and the benefits of co-digesting JK with DM. The highest methane yield (232 ml/gVS) was obtained from the DM-to-JK ratio of 90:10, which was 14.9% and 123.1% higher than that from DM and JK alone, respectively. It also showed the highest synergistic effect (61 ml/gVS). However, further increase in JK ratios led to the decrease in methane yield and synergistic effect. Therefore, applying the co-digestion of DM and JK at a ratio of 90:10 is recommended for biomethane production.

Hyperlipidemia is a major risk factor and pathological basis for cardiovascular diseases. Polygonum cuspidatum (HZ), a famous traditional Chinese medicine, is frequently used to treat hyperlipidemia. However, little is known about its underlying mechanism. Herein, an integrated approach combining multiplatform-based metabonomics and network analysis was adopted to elucidate the ameliorative mechanism of HZ on hyperlipidemia. The global metabolomic characters of HZ on hyperlipidemia were investigated by GC-MS and LC-MS based metabonomics. Significant metabonomic alterations were observed in hyperlipidemic group, which could be restored by HZ supplementation. Furthermore, the drug-ingredients-target-metabolic pathway network was constructed, and the result indicated that HZ exhibited hypolipidemic efficacy through resveratrol, polydatin, torachrysone-8-O-β-D-(6'-oxayl)-glucoside, physciondiglucoside, (+)-catechin, β-sitosterol, quercetin, luteolin and physovenine acting on phospholipase A2, unspecific monooxygenase, arachidonate 15-lipoxygenase, aromatic-L-amino-acid decarboxylase, alcohol dehydrogenase and triacylglycerol lipase. In conclusion, this study explored potential mechanism of HZ on hyperlipidemia with the aid of the integrated approach combining multiplatform-based metabonomics and network analysis, which might provide a theoretical basis for the clinical application of HZ.