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Hepatic steatosis, characterized by excessive lipid accumulation in the liver, can be ameliorated by autophagy activation. Polygoni Cuspidati rhizome et Radix (PCRR), traditionally used to treat atherosclerosis, hepatitis, and gallstones, has recently demonstrated anti-steatotic effects in the liver. However, the active compounds and underlying mechanisms remain unclear. This study investigated whether PCRR water extract improves steatosis by modulating hepatic autophagic flux. We found that PCRR water extract promoted autophagic flux, enhanced lysosomal biogenesis, and alleviated lipid accumulation in the liver cell lines as well as in the livers of rats with steatosis. Mechanistically, PCRR water extract inhibited mechanistic target of rapamycin complex 1 (mTORC1) activity, leading to dephosphorylation and subsequent nuclear translocation of transcription factor EB (TFEB), a key regulator of lipophagy. TFEB knockdown attenuated PCRR-mediated lipophagy promotion in the liver cell lines. Furthermore, chloroquine (CQ)-mediated autophagy blockage abrogated the therapeutic effect of PCRR against hepatic steatosis in high-fat diet (HFD)-fed rats. These findings suggest that PCRR water extract acts as a novel autophagy enhancer and holds therapeutic potential for hepatic steatosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Sporopollenin is a natural biological macromolecule consisting of highly cross-linked carbon, hydrogen, and oxygen atoms, with a highly porous structure and multifunctional groups. In this work, a novel surface molecularly imprinted polymer based on magnetically aminated cattail sporopollenin (MACSp-SMIP) was prepared for the specific and efficient adsorption of resveratrol, with the aim of purifying resveratrol from Polygonum cuspidatum extracts. MACSp-SMIP was found to have a porous structure covered with the multi-layered sponge-like imprinted polymers. MACSp-SMIP had a high adsorption capacity for resveratrol (65.77 mg·g -1 ) and excellent selectivity (imprinting factor 5.64). The adsorption of resveratrol by MACSp-SMIP was a homogeneous diffusion dominated by chemical adsorption with three stages of external diffusion, internal diffusion, and micropore diffusion. MACSp-SMIP was used as an adsorbent in molecularly imprinted solid-phase extraction for the purification of resveratrol from P. cuspidatum extracts, achieving a resveratrol recovery of 94.33 % and a purity of 76.67 % in the final products. MACSp-SMIP maintained a satisfactory recovery of resveratrol (88.18 %) after six cycles. Overall, this work developed a promising biological macromolecule-based adsorbent MACSp-SMIP for the specific and efficient adsorption of resveratrol, and also provided an efficient and simple approach for the selective purification of resveratrol from P. cuspidatum extracts for food/nutraceutical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Polygoni Cuspidati Rhizoma et Radix (Huzhang in Chinese), refers to the root and rhizome of Polygonum cuspidatum Sieb. et Zucc. Huzhang is commonly used in clinical practice for the prevention and treatment of diabetes and its complications, but its active components and regulatory mechanisms have not yet been thoroughly analyzed., Purpose: The network pharmacology combined with multi-omics analysis will be employed to dissect the substance basis and action mechanism of Huzhang in exerting its anti-diabetic activity., Methods: This study employed phenotypic indicators for baseline assessment, followed by integrated analysis using network pharmacology, metabolomics, transcriptomics, and qPCR technology to elucidate the active components and pharmacological mechanisms of Huzhang., Results: The analysis of network pharmacology revealed that polydatin is a potential active component responsible for the anti-T2DM pharmacological effects of Huzhang. In vivo experimental results demonstrated that polydatin significantly regulates blood glucose, lipid levels, liver function, and liver pathological damage in diabetic rats. Analysis results from transcriptomics, metabolomics, and qPCR validation showed that polydatin comprehensively regulates glucose and lipid metabolism in T2DM by modulating bile acid metabolism, fatty acid oxidation, and lipogenesis., Conclusion: Polydatin is a key component of Huzhang in treating T2DM, and its regulatory mechanisms are diverse, indicating significant development potential., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Ethnopharmacological Relevance: The root of Polygonum cuspidatum Sieb. et Zucc (PC), known as 'Huzhang' in the Chinese Pharmacopoeia, has been traditionally employed for its anti-inflammatory, antiviral, antimicrobial, and other biological activities. Polydatin (PD) and its aglycone, resveratrol (RES), are key pharmacologically active components responsible for exerting anti-inflammatory and antioxidant effects. However, its specific targets and action mechanisms remain unclear., Aim of the Study: The equilibrium of the KEAP1-NRF2 system serves as the primary protective response to oxidative and electrophilic stresses within the body, particularly in cases of acute lung injury caused by pathogenic microbial infection. In this study, the precise mechanisms by which RES alleviates oxidative stress damage in conjunction with NRF2 activators are discussed., Materials and Methods: The active components from PC were screened to evaluate their potential to inhibit reactive oxygen species (ROS) and activate antioxidant activity dependent on antioxidant response elements (ARE). RES was evaluated for its potential to alleviate the oxidative stress caused by pathogenic microbial infection. Functional probes were designed to study the RES distribution and identify its targets. A lipopolysaccharide (LPS)-induced oxidative injury model was used to evaluate the effects of RES on the KEAP1-NRF2/ARE pathway in RAW 264.7 cells. The interaction between RES and NRF2 was elucidated using drug-affinity responsive target stability (DARTS), cellular thermal shift assays (CETSA), co-immunoprecipitation (Co-IP), and microscale thermophoresis (MST) techniques. The key binding sites were predicted using molecular docking and validated in NRF2-knockdownand reconstructed cells. Finally, protective effects against pulmonary stress were verified in a mouse model of pathogenic infection., Results: The accumulation of RES in lung macrophages disrupted the binding between KEAP1 and NRF2, thereby preventing the ubiquitination degradation of NRF2 through its interaction with Ile28 on the NRF2-DLG motif. The activation of NRF2 resulted in the upregulation of nuclear transcription, enhances the expression of antioxidant genes dependent on ARE, suppresses ROS generation, and ameliorates oxidative damage both in vivo and in vitro., Conclusion: These findings shed light on the potential of RES to mitigate oxidative stress damage caused by pathogenic microorganism-induced lung infections and facilitate the discovery of novel small molecule modulators targeting the KEAP1-NRF2 DLG motif interaction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Reynoutria japonica Houtt is a medicinal plant renowned for its diverse pharmacological properties, including heat-clearing, toxin-removing, blood circulation promotion, blood stasis removal, diuretic action, and pain relief. The plant is commonly utilized in Traditional Chinese Medicine (TCM), and its major bioactive constituents consist of polydatin (PD) and resveratrol (RES)., Aim of the Study: To summarize the relevant targets of PD in various oxidative stress-related diseases through the activation of Silence information regulator1 (SIRT1). Furthermore, elucidating the pharmacological effects and signaling mechanisms to establish the basis for PD's secure clinical implementation and expanded range of application., Materials and Methods: Literature published before November 2023 on the structural analysis and pharmacological activities of PD was collected using online databases such as Google Scholar, PubMed, and Web of Science. The keywords were "polydatin", "SIRT1" and "oxidative stress". The inclusion criteria were research articles published in English, including in vivo and in vitro experiments and clinical studies. Non-research articles such as reviews, meta-analyses, and letters were excluded., Results: PD has been found to have significantly protective and curative effects on diseases associated with oxidative stress by regulating SIRT1-related targets including peroxisome proliferator-activated receptor γ coactivator 1-alpha (PGC-1α), nuclear factor erythroid2-related factor 2 (Nrf2), high mobility group box 1 protein (HMGB1), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), p38/p53, as well as endothelial nitric oxide synthase (eNOs), among others. Strong evidence suggests that PD is an effective natural product for treating diseases related to oxidative stress., Conclusion: PD holds promise as an effective treatment for a wide range of diseases, with SIRT1-mediated oxidative stress as its potential pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Polygonum cuspidatum Sieb. et Zucc. is mainly distributed in Shanxi, Gansu, and Sichuan province of China. It is also found in Korea and Japan. Its dried roots and rhizomes are used as medicinal herbs and have been used to treat hyperglycemia and various inflammatory disorders., Aim of the Review: This paper aims to provide an up-to-date review of the developments in the studies involving the extraction and purification, structure analysis, pharmacological effects, and potential applications of polysaccharides obtained from Polygonum cuspidatum. Additionally, the possible future research directions of this plant are discussed., Materials and Methods: This article used "Polygonum cuspidatum polysaccharide (PCP)" and "Polygonum cuspidatum" as the keywords and gathered relevant data on Polygonum cuspidatum using electronic databases (Elsevier, PubMed, ACS, CNKI, Google Scholar, Baidu Scholar, Web of Science), relevant books, and classic literature about Chinese herb., Results: Excluding irrelevant and repetitive documents, 278 documents were finally included, of which 88 were in Chinese and 190 were in English. The CiteSpace software was used to visualize the trends and keywords in this research field. We concluded that the main extraction methods for Polygonum cuspidatum polysaccharide are water extraction and alcohol precipitation, microwave-assisted extraction, ultrasound-assisted extraction, and microjet extraction. High-performance liquid chromatography and column chromatography are also commonly used in the separation and purification of PCP. PCP has antitumor, immunomodulatory, hypoglycemic, and antioxidant effects. This paper provides an updated and deeper understanding of PCP, serving as a theoretical foundation for the further optimization of polysaccharide structures and the development of PCP as a novel functional material for clinical application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

This work offered a productive technique for resveratrol extraction from Polygonum Cuspidatum (P. Cuspidatum) using ionic liquids in synergy with ultrasound-enzyme-assisted extraction (UEAE). Firstly, ionic liquids with different carbon chains and anions were evaluated. Subsequently, a comprehensive investigation was carried out to evaluate the effect of seven crucial parameters on the resveratrol yield: pH value, enzyme concentration, extraction temperature, extraction time, ultrasonic power, concentration of ionic liquid (IL concentration) and the liquid-solid ratio. Employing the Plackett-Burman Design (PBD), the critical factors were effectively identified. Building upon this foundation, the process was further optimized through the application of Response Surface Methodology (RSM) and an Artificial Neural Network-Genetic Algorithm (ANN-GA). The following criteria were determined to be the ideal extraction conditions: an enzyme concentration of 2.18%, extraction temperature of 58 °C, a liquid-solid ratio of 29 mL/g, pH value of 5.5, extraction time of 30 min, ultrasonic power of 250 W, and extraction solvent of 0.5 mol/L 1-butyl-3-methylimidazolium bromide. Under these conditions, the resveratrol yield was determined to be 2.90 ± 0.15 mg/g. Comparative analysis revealed that the ANN-GA model provided a better fit to the experimental data of resveratrol yield than the RSM model, suggesting superior predictive capabilities of the ANN-GA approach. The introduction of a novel green solvent system in this experiment not only simplifies the extraction process but also enhances safety and feasibility. This research paves the way for innovative approaches to extracting resveratrol from botanical sources, showcasing its significant potential for a wide range of applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Mas-related G protein-coupled receptor X2 (MrgprX2) is acknowledged as a mast cell-specific receptor, playing a crucial role in orchestrating anaphylactoid responses through mast cell degranulation. It holds promise as a target for regulating allergic and inflammatory diseases mediated by mast cells. Polygonum cuspidatum (PC) has shown notable anti-anaphylactoid effects, while its pharmacologically active components remain unclear. In this study, we successfully utilized MrgprX2 high-expressing cell membrane chromatography (CMC), in conjunction with liquid chromatography-mass spectrometry (LC-MS), to identify active anti-anaphylactoid components in PC. Our study pinpointed polydatin, resveratrol, and emodin-8-O-β-d-glucoside as potential anti-anaphylactoid compounds in PC. Their anti-anaphylactoid activities were evaluated through β-aminohexosidase and histamine release assays, demonstrating a concentration-dependent inhibition for both β-aminohexosidase and histamine release. This approach, integrating MrgprX2 high-expression CMC with LC-MS, proves effective in screening potential anti-anaphylactoid ingredients in natural herbal medicines. The findings from this study illuminated the anti-anaphylactoid properties of specific components in PC and provided an efficient method for the drug development of natural products., (© 2024 Wiley‐VCH GmbH.)

Objective: Traditional Chinese medicine Polygonum cuspidatum (PC) has significant effects on reducing pain. In this study, we investigated the analgesic effects of the alcohol extract of PC on three types of inflammatory pain and explored its mechanism., Methods: Potential targets for the analgesic effects of the main active components of PC alcohol extract were screened by network pharmacology and molecular docking. Three different inflammatory pain mouse models (acetic acid twisting, formalin foot swelling, and xylene ear swelling) were used to study the analgesic effects of PC. The expression of latent signaling pathways in L 4-6 spinal cord tissues in formalin foot swelling mice was evaluated using real-time qPCR (RT-qPCR), Western blot (WB), and immunohistochemistry (IHC) analyses., Results: Network pharmacology analysis shows that PC analgesic mechanism is related to the MAPK/ERK signaling pathway. The five main active components of PC have good docking ability with JNK and p38. PC alcohol extract significantly reduced the pain behavior and alleviated inflammatory reactions in three mouse models, inhibited the mRNA and protein phosphorylation levels of JNK, ERK, p38, and CREB in spinal cord tissues., Conclusion: PC alcohol extract can inhibit inflammation and alleviate pain, which is related to its inhibition of the MAPK/ERK signaling pathway in spinal cord. Thus, PC alcohol extract is a promising candidate for pain treatment., Competing Interests: The authors declare no competing of interest., (© 2023 Lan et al.)

Fallopia japonica (Asian knotweed) is a medicinal herb traditionally used to treat inflammation, among other conditions. However, the effects of F. japonica root extract (FJE) on airway inflammation associated with combined allergic rhinitis and asthma (CARAS) and the related mechanisms have not been investigated. This study examined the effect of FJE against CARAS in an ovalbumin (OVA)-induced CARAS mouse model. Six-week-old male BALB/c mice were randomly segregated into six groups. Mice were sensitized intraperitoneally with OVA on days 1, 8, and 15, and administered saline, Dexamethasone (1.5 mg/kg), or FJE (50, 100, or 200 mg/kg) once a day for 16 days. Nasal symptoms, inflammatory cells, OVA-specific immunoglobulins, cytokine production, mast cell activation, and nasal histopathology were assessed. Administration of FJE down-regulated OVA-specific IgE and up-regulated OVA-specific IgG2a in serum. FJE reduced the production of T helper (Th) type 2 cytokines, and the Th1 cytokine levels were enhanced in nasal and bronchoalveolar lavage fluid. Moreover, FJE positively regulated allergic responses by reducing the accumulation of inflammatory cells, improving nasal and lung histopathological characteristics, and inhibiting inflammation-associated cytokines. FJE positively modulated the IL-33/TSLP/NF-B signaling pathway, which is involved in regulating inflammatory cells, immunoglobulin levels, and pro-inflammatory cytokines at the molecular level.

Phytochemicals are natural compounds found in plants that have potential health benefits such as antioxidants, anti-inflammatory and anti-cancer properties, and immune reinforcement. Polygonum cuspidatum Sieb. et Zucc. is a source rich in resveratrol, traditionally consumed as an infusion. In this study, P. cuspidatum root extraction conditions were optimized to increase antioxidant capacity (DPPH, ABTS+), extraction yield, resveratrol concentration, and total polyphenolic compounds (TPC) via ultrasonic-assisted extraction using a Box-Behnken design (BBD). The biological activities of the optimized extract and the infusion were compared. The optimized extract was obtained using a solvent/root powder ratio of 4, 60% ethanol concentration, and 60% ultrasonic power. The optimized extract showed higher biological activities than the infusion. The optimized extract contained 16.6 mg mL -1 resveratrol, high antioxidant activities (135.1 µg TE mL -1 for DPPH, and 230.4 µg TE mL -1 for ABTS+), TPC (33.2 mg GAE mL -1 ), and extraction yield of 12.4%. The EC 50 value (effective concentration 50) of the optimized extract was 0.194 µg mL -1 , which revealed high cytotoxic activity against the Caco-2 cell line. The optimized extract could be used to develop functional beverages with high antioxidant capacity, antioxidants for edible oils, functional foods, and cosmetics.

Neuraminidase is an important target in the treatment of the influenza A virus. Screening natural neuraminidase inhibitors from medicinal plants is crucial for drug research. This study proposed a rapid strategy for identifying neuraminidase inhibitors from different crude extracts (Polygonum cuspidatum, Cortex Fraxini, and Herba Siegesbeckiae) using ultrafiltration combined with mass spectrometry guided by molecular docking. Firstly, the main component library of the three herbs was established, followed by molecular docking between the components and neuraminidase. Only the crude extracts with numbers of potential neuraminidase inhibitors identified by molecular docking were selected for ultrafiltration. This guided approach reduced experimental blindness and improved efficiency. The results of molecular docking indicated that the compounds in Polygonum cuspidatum demonstrated good binding affinity with neuraminidase. Subsequently, ultrafiltration-mass spectrometry was employed to screen for neuraminidase inhibitors in Polygonum cuspidatum. A total of five compounds were fished out, and they were identified as trans-polydatin, cis-polydatin, emodin-1-O-β-D-glucoside, emodin-8-O-β-D-glucoside, and emodin. The enzyme inhibitory assay showed that they all had neuraminidase inhibitory effects. In addition, the key residues of the interaction between neuraminidase and fished compounds were predicted. In all, this study could provide a strategy for the rapid screening of the potential enzyme inhibitors from medicinal herbs., (© 2023 Wiley-VCH GmbH.)

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a chronic liver disease that currently lacks approved pharmacological treatment options. The mechanisms and active ingredients of Polygonum cuspidatum (PC) that regulate the mitochondria to relieve MAFLD have not been assessed. Thus, this study was designed to explore the bioactive components of PC extract in regulating mitochondria to alleviate high-fat diet-induced MAFLD using mitochondrial pharmacology and pharmacochemistry. Our results demonstrate that PC protected the mitochondrial ultrastructure and inhibited oxidative stress and energy metabolism disorder in the liver mitochondria. Furthermore, PC-derived components in the liver mitochondria attenuated oxidative stress and restored the energy metabolism of fat emulsion-induced steatosis in L02 cell. Sixteen compounds were identified in the liver-mitochondrial extracts of PC-treated rats. The antisteatotic effects of three identified monomers and anti-MAFLD ability of the monomer group were confirmed. Collectively, our data suggest that the extract of PC can alleviate lipid metabolism disorder in MAFLD by protecting the mitochondrial ultrastructure, reducing oxidative stress injury, and promoting energy metabolism. The sixteen identified compounds were potentially the main effective ingredients of PC in treating MAFLD. Thus, PC shows potential in treating MAFLD and related mitochondrial dysfunction. The proposed strategy to identify the ingredients of herbal medicines based on mitochondrial pharmacology and pharmacochemistry presents a new approach in exploring the pharmacodynamic components of herbal medicines that regulate mitochondria in preventing and treating diseases., Competing Interests: Conflict of Interest Statement The authors have no conflicts of interest to declare., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

COVID-19, resulting from infection by the SARS-CoV-2 virus, caused a contagious pandemic. Even with the current vaccines, there is still an urgent need to develop effective pharmacological treatments against this deadly disease. Here, we show that the water and ethanol extracts of the root and rhizome of Polygonum cuspidatum (Polygoni Cuspidati Rhizoma et Radix), a common Chinese herbal medicine, blocked the entry of wild-type and the omicron variant of the SARS-CoV-2 pseudotyped virus into fibroblasts or zebrafish larvae, with IC 50 values ranging from 0.015 to 0.04 mg/mL. The extracts were shown to inhibit various aspects of the pseudovirus entry, including the interaction between the spike protein (S-protein) and the angiotensin-converting enzyme II (ACE2) receptor, and the 3CL protease activity. Out of the chemical compounds tested in this report, gallic acid, a phytochemical in P. cuspidatum , was shown to have a significant anti-viral effect. Therefore, this might be responsible, at least in part, for the anti-viral efficacy of the herbal extract. Together, our data suggest that the extracts of P. cuspidatum inhibit the entry of wild-type and the omicron variant of SARS-CoV-2, and so they could be considered as potent treatments against COVID-19.

Introduction: The quantitative analysis of trace resveratrol and polydatin in plant tissues is suitable for elucidation of the compounds' mechanisms of action., Objectives: The main objective of this work was to develop a feasible and effective sample pretreatment method to measure the concentrations of resveratrol and polydatin in complex samples., Methodology: A polymer sorbent, poly(2-mercaptobenzimidazole), was electrochemically prepared and utilized for selective extraction, while resveratrol and polydatin were used as target analytes. The sorbent was characterized by cyclic voltammetry, scanning electron microscopy and Fourier transform infrared spectroscopy. After extraction and elution, the analytes were analyzed by a Thermo U3000 HPLC system. Several affecting parameters, including the volume of elution solution, sample pH value, sample flow rate and sample volume, were evaluated and optimized., Results: The proposed method showed good linearity with low limits of detection (from 0.5 to 0.8 ng·mL -1 ) and ideal accuracy with spiked recoveries from 81.30% to 99.16%. A good enrichment factor (more than 200-fold) together with good sensitivity was obtained with this method. Analysis of resveratrol and polydatin in Polygonum cuspidatum samples by this method is efficient., Conclusion: The method developed in this work exhibits several significant merits, including easy operation and high extraction efficiency, indicating that electrochemically prepared polymer sorbent is useful for sample pretreatment and analysis of traditional Chinese medicine samples., (© 2022 John Wiley & Sons, Ltd.)

Polygonum cuspidatum (PC) has been reported to exert a potent antihyperlipidemic effect. However, its mechanisms of action and active ingredients remain elusive and require further research. In this study, we first conducted in vivo experiments to validate that Polygonum cuspidatum extract (PCE) could ameliorate the blood lipid level in hyperlipidemia model rats. Then, ultrahigh performance liquid chromatography coupled with Q-Exactive MS/MS (UPLC-QE-MS/MS) was applied to verify its 12 main active ingredients. The pharmacophore matching model was employed to predict the target point of the active ingredient, and 27 overlapping genes were identified via database and literature mining. String online database and Cytoscape software were utilized to construct a Protein-Protein Interaction (PPI) network, followed by function annotation analysis and pathway enrichment analysis. The results showed that the PI3K/AKT signaling pathway and its downstream FOXO3/ER α factors were significantly enriched. Furthermore, in vitro experiments were performed to determine the lipid content and oxidative stress (OS) indicators in OA-induced HepG2 cells, and immunofluorescence and western blotting analysis were carried out to analyze the effects of PCE on related proteins. Our experimental results show that the mechanism of antihyperlipidemic action of PCE is related to the activation of the PI3K/AKT signaling pathway and its downstream FOXO3/ER α factors, and polydatin and resveratrol are the main active ingredients in PCE that exert antihyperlipidemic effects., Competing Interests: There are no conflicts of interest associated with this paper., (Copyright © 2021 Ting Tao et al.)

Ethnopharmacological Relevance: 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., Aim of the Study: This study aimed to explore the role of detoxifying and blood-activating formulae in the treatment of unstable angina and the potential mechanism involved., Materials and Methods: 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., Results: 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)., Conclusions: 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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Epstein-Barr virus (EBV), a human herpesvirus, is several human lymphoid malignancies-associated. Our earlier study found the effect of Polygonum cuspidatum root on promoting EBV-positive apoptosis. Therefore, this study investigated the effects of the Polygonum cuspidatum ethyl acetate subfraction containing emodin on EBV gene expression and anti-EBV tumor cells. Resultantly, the the Polygonum cuspidatum ethyl acetate subfraction containing emodin (F3a) promoted Raji cell death (50% cytotoxic concentration, CC 50 : 12.08 µg/mL); the 12.5 µg/mL F3a effect transcribed BRLF1 and BNLF1 and increased latent membrane protein 1 (LMP1), which may reduce the intracellular phospho-extracellular signal-regulated kinase (ERK) and phospho-inhibitor of Nuclear factor kappa B α (IκBα). Meanwhile, the Raji cells increased the intracellular reactive-oxygen species (ROS), activated the apoptosis-related proteins, cleaved caspase 3 and poly(ADP-ribose)polymerase (PARP), and increased the apoptosis percentage. Therefore, the Polygonum cuspidatum ethyl acetate subfraction containing emodin could be a therapeutic drug for EBV-related tumors.

Background: Japanese knotweed (R. japonica var japonica) is one of the world's 100 worst invasive species, causing crop losses, damage to infrastructure, and erosion of ecosystem services. In the UK, this species is an all-female clone, which spreads by vegetative reproduction. Despite this genetic continuity, Japanese knotweed can colonise a wide variety of environmental habitats. However, little is known about the phenotypic plasticity responsible for the ability of Japanese knotweed to invade and thrive in such diverse habitats. We have used attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy, in which the spectral fingerprint generated allows subtle differences in composition to be clearly visualized, to examine regional differences in clonal Japanese knotweed., Results: We have shown distinct differences in the spectral fingerprint region (1800-900 cm - 1 ) of Japanese knotweed from three different regions in the UK that were sufficient to successfully identify plants from different geographical regions with high accuracy using support vector machine (SVM) chemometrics., Conclusions: These differences were not correlated with environmental variations between regions, raising the possibility that epigenetic modifications may contribute to the phenotypic plasticity responsible for the ability of R. japonica to invade and thrive in such diverse habitats., (© 2021. The Author(s).)

Background : The coronavirus disease 2019 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected more than 210 million individuals globally and resulted in over 4 million deaths since the first report in December 2019. The early use of traditional Chinese medicine (TCM) for light and ordinary patients, can rapidly improve symptoms, shorten hospitalization days and reduce severe cases transformed from light and normal. Many TCM formulas and products have a wide application in treating infectious and non-infectious diseases. Polygonum cuspidatum Sieb. et Zucc. ( P. cuspidatum ), is an important Traditional Chinese Medicine with actions of clearing away heat and eliminating dampness, draining the gallbladder to relieve jaundice, removing blood stasis to alleviate pain, resolving phlegm and arrest cough. In the search for anti-SARS-CoV-2, P. cuspidatum was recommended as as a therapeutic drug of COVID-19 pneumonia.In this study, we aimed to identifies P. cuspidatum is the potential broad-spectrum inhibitor for the treatment of coronaviruses infections. Methods : In the present study , we infected human malignant embryonal rhabdomyoma (RD) cells with the OC43 strain of the coronavirus, which represent an alternative model for SARS-CoV-2 and then employed the cell viability assay kit for the antiviral activity. We combined computer aided virtual screening to predicte the binding site and employed Surface plasmon resonance analysis (SPR) to comfirm the interaction between drugs and coronavirus. We employed fluorescence resonance energy transfer technology to identify drug's inhibition in the proteolytic activity of 3CLpro and Plpro. Results : Based on our results, polydatin and resveratrol derived from P. cuspidatum significantly suppressed HCoV-OC43 replication. 50% inhibitory concentration (IC 50 ) values of polydatin inhibited SARS-CoV-2 Mpro and Plpro, MERS Mpro and Plpro were 18.66, 125, 14.6 and 25.42 μm, respectively. IC 50 values of resveratrol inhibited SARS-CoV-2 Mpro and Plpro, MERS Mpro and Plpro were 29.81 ,60.86, 16.35 and19.04 μM, respectively. Finally, SPR assay confirmed that polydatin and resveratrol had high affinity to SARS-CoV-2, SARS-CoV 3Clpro, MERS-CoV 3Clpro and PLpro protein. Conclusions : we identified the antiviral activity of flavonoids polydatin and resveratrol on RD cells. Polydatin and resveratrol were found to be specific and selective inhibitors for SARS-CoV-2, 3CLpro and PLpro, viral cysteine proteases. In summary, this study identifies P. cuspidatum as the potential broad-spectrum inhibitor for the treatment of coronaviruses infections., (© 2021 The Author(s). Published by BRI.)

Breast cancer is a leading cause of death. Anticancer treatment such as gold nanoparticles (AuNP) seems highly promising in this regard. Therefore, this study aimed to assess the beneficial effect of doxorubicin (Dox) and polydatin (PD) AuNP in Ehrlich ascites carcinoma (EAC) and the ability of PD-AuNP to protect the heart from Dox's deteriorating effects. EAC was induced in mice. The mice were divided into nine groups: normal, EAC, PD: received PD (20 mg/kg), Dox: received Dox (2 mg/kg), PD-AuNPH: received 10 ppm AuNP of PD, PD-AuNPL: received 5 ppm AuNP of PD, Dox-AuNP: received Dox-AuNP, PD-Dox-AuNP: received PD-Dox-AuNP, AuNP: received AuNP. On the 21st day from tumor inoculation, the mice were sacrificed and tumor and heart tissues were removed. Tumor β-catenin/Cyclin D1 and p53 were assessed by immunohistochemistry. IL-6 was determined by enzyme-linked immunosorbent assay. PD-AuNP and Dox-AuNP showed a significant reduction in tumor volume and weight more than their free forms. Also, PD-AuNP and Dox-AuNP showed markedly less dense tumor cells. β-catenin and Cyclin D1 were markedly decreased and p53 was highly upregulated by PD-AuNP and Dox-AuNP. Moreover, PD-AuNP and Dox-AuNP have the ability to decrease IL-6 production. PD-AuNP protected the heart from Dox-induced severe degeneration. Therefore, PD-AuNP could be a tool to decelerate the progression of breast cancer., (© 2021 Wiley Periodicals LLC.)

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The acquisition of resveratrol from Polygonum cuspidatum is complicated and costs organic solvents due to extraction and hydrolysis of its corresponding glycoside (polydatin). In this work, a novel one-pot method based on deep eutectic solvent (DES) was developed for simultaneous extraction and conversion of polydatin to resveratrol from Polygonum cuspidatum for the first time. The extraction yield of resveratrol by DES-based one-pot method were significantly higher than that of water, methanol and ethanol. After optimization by One-Variable-at-a-Time and response surface methodology, the extraction yield of resveratrol reached 12.26 ± 0.14 mg/g within 80 min. The conversation efficiency of polydatin to resveratrol in Polygonum cuspidatum from five different origins was more than 96.3%. Scanning electron microscope results indicated the selected DES disrupted plant cell walls to enhance the yield of resveratrol. The results indicated that one green method was successfully established for efficient extraction and conversion of polydatin to resveratrol from Polygonum cuspidatum., (Copyright © 2020. Published by Elsevier Ltd.)

Background: 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 H 2 O 2 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., Competing Interests: The authors declare that they have no conflicts of interest for this work., (© 2021 Bi et al.)

A methodology based on off-line multidimensional thin-layer chromatography was developed for isolation of several secondary metabolites from bark of Japanese knotweed (Fallopia japonica Houtt.) rhizomes. Successive fractionation steps using PLC silica gel and HPTLC silica gel or HPTLC cellulose plates in combination with various developing solvents enabled isolation of (+)-catechin, (-)-epicatechin, (-)-epicatechin gallate, procyanidin B1, procyanidin B2, procyanidin B3, proanthocyanidin B dimer gallate, emodin, emodin-8-O-glucoside and emodin-8-O-malonyl-glucoside. Their identity was confirmed by HPTLC, HPTLC-MS n and for most of them also by 1 H NMR and 2D NMR analyses. To the best of our knowledge emodin-8-O-malonyl-glucoside, procyanidins B1 and B2 were for the first time isolated from this plant material. HPTLC and HPTLC-MS n analyses were also performed as support of fractionation/isolation process, leading to first detection of some compounds in bark of Japanese knotweed rhizomes and Japanese knotweed rhizomes in general: procyanidins B1 and B2, methyl derivatives of emodin bianthrone and emodin bianthrone-hexose, resveratrol-malonyl-hexoside and taxifolin derivatives. Characterization of flavan-3-ols and proanthocyanidins was facilitated by post-chromatographic derivatization of the corresponding chromatographic zones with 4-dimethylaminocinnamaldehyde (DMACA) detection reagent., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A novel resveratrol molecularly imprinted polymer (p-CM@MPS@MIP-Res) was prepared on the surface of silanized porous cellulose microspheres (p-CM@MPS) for the first time, and was successfully applied for the efficient enrichment of targeted resveratrol in Polygonum cuspidatum. The adsorption kinetics and adsorption equilibrium of p-CM@MPS@MIP-Res were also studied in detail. Compared with non-molecularly imprinted polymer (p-CM@MPS@NIP), the prepared p-CM@MPS@MIP-Res showed high adsorption capacity for resveratrol, the adsorption capacity of the p-CM@MPS@MIP-Res could reach to 11.56 mg/g. Furthermore, the stability of the p-CM@MPS@MIP-Res was evaluated and the result showed that the p-CM@MPS@MIP-Res could be reused for 5 runs. Finally, the p-CM@MPS@MIP-Res was applied to enrich the resveratrol in Polygonum cuspidatum sample, the content of resveratrol in the extraction solution could be increased greatly from 4.23 % to 23.74 %, indicating the p-CM@MPS@MIP-Res was a promising adsorbent for efficiently separation and enrichment of resveratrol in Polygonum cuspidatum., (Copyright © 2020. Published by Elsevier Ltd.)

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.

Off-line two-dimensional countercurrent chromatography has been widely applied to the isolation of complex samples, but little research on the investigation of orthogonality in the selection of biphasic solvent systems is available. In the present work, the orthogonality in the selection of a biphasic solvent system for liquid-liquid chromatographic separation of aqueous extract and ether extract from the traditional Chinese medicinal plant Polygonum cuspidatum Sieb. et Zucc was evaluated by the correlation coefficient and space occupancy rate. In total, 25 different biphasic solvent systems were tested, and 313 system combinations were analysed. A convex hull methodology was used to determine the separation space and to optimize separation conditions. The correlation coefficient matrix was transformed into dendrograms and a colour map to visualize the dissimilarity between, and orthogonality for, all solvent systems. The aqueous extracts from Polygonum cuspidatum were separated using selected biphasic solvent systems with high orthogonality: ethyl acetate-ethanol-water (70:1:70, v/v) and petroleum ether-ethyl acetate-water (1:5:5, v/v). The ether extracts from Polygonum cuspidatum were also separated using selected biphasic solvent systems with high orthogonality: petroleum-ethyl acetate-methanol-aqueous 0.25 M NH 3 •H 2 O (5:5:5:5, v/v) and petroleum-ethyl acetate-methanol-water (5:5:5:5, v/v). Thirteen compounds were successfully obtained. The experimental results demonstrated that the evaluation of orthogonality provided an alternative strategy to select an applicable solvent system for the separation of complex samples using off-line two-dimensional countercurrent chromatography., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2020. Published by Elsevier B.V.)

Molecularly imprinted polymers (MIPs) based on polydatin were prepared by precipitation polymerization method. Synthesis process of MIPs was optimized by discussion of functional monomers, porogens and the molar ratio of template- functional monomer-cross linker. Then, MIPs were prepared with polydatin as the template, 4-vinyl pyridine as the functional monomer, ethylene glycol dimethyl acrylate as the cross linker, acetonitrile as the porogen and the molar ratio of template-monomer-cross linker at 1:10:20. Scanning electron microscopy and Fourier transform infrared spectrometer were used to inspect macroscale and chemical bond of MIPs. Adsorption capability and selectivity of MIPs to polydatin were investigated by carrying out the static, dynamic and selective experiments. The results showed MIPs performed high adsorption ability and selectivity to polydatin, indicating MIPs could be used to separate and enrich polydatin from the complex systems. Finally, MIPs were applied as the adsorbent for isolation and purification of polydatin from the extract of Polygoni Cuspidati Rhizoma et Radix, rats' plasma and urine samples. MIPs were successfully used to separate polydatin from the Polygoni Cuspidati Rhizoma et Radix and recovery ranged from 89.2% to 91.6%. The maximum concentration of polydatin in rats' plasma and urine samples was 2.84 ± 0.0748 µg mL -1 and 2.64 ± 0.485 µg mL -1 , respectively. Moreover, to compare with the MIPs method, organic solvent methods were used to analyze the polydatin in rats' plasma and urine samples. The results illustrated MIPs method was effective and selective for enrichment of polydatin from the medicinal plants and biological samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Dengue virus (DENV) is a mosquito-borne pathogen that is becoming a serious global threat, owing to its rising incidence in inter-tropical regions that yield over 50 million annual infections. There are currently no approved antiviral agents for the management of dengue, and recent shortcomings in its immunization called for immediate action to develop effective drugs with prophylactic ability to better manage its infection. In an attempt to discover novel antiviral sources, we identified the medicinal herb Polygonum cuspidatum (PC) as a bioactive botanical material against DENV infectivity. Specifically, the methanolic extract from PC rhizomes (PCME) potently inhibited DENV infection without causing significant cytotoxicity. Further examination on the viral life cycle demonstrated that PCME particularly targeted the initial stages of DENV infection, while pre- and post-infection treatments had no effect. More importantly, the PCME could efficiently inactivate DENV free virus particles and block the viral attachment and entry/fusion events without apparently influencing viral replication, egress, and cell-to-cell spread. The antiviral effect of PCME was also recapitulated in infection analysis using DENV pseudoparticles displaying viral structural proteins that mediate DENV particle entry. Besides, PCME treatment also inhibited direct DENV entry into several cell types relevant to its infection and reduced viral infectivity of other members of the Flaviviridae family, including the hepatitis C virus (HCV) and Zika virus (ZIKV). Due to its potency against DENV entry, we suggest that the phytobioactive extract from PC is an excellent starting point as an antiviral source material for further development of therapeutic strategies in the prophylactic management of DENV infection.

Four new compounds including two new phenylpropanoid esters of sucrose, polygonusucroside A (1) and B (2); two new anthraquinones, 8-O-β-d-(6'-galloyl)-glucopyranoside (3) and polyanthraquinoside A (4), together with six known compounds were isolated from Polygonum cuspidatum. Their structures were established using UV, IR, HRESIMS, and NMR data. All compounds were evaluated for their α-glucosidase inhibitory activities and neuroprotective effects. Compounds 5, 7 and 9 showed significant α-glucosidase inhibitory activities with IC 50 values of 27.30, 5.51, and 1.09 μmol/L, respectively (acarbose as positive control, IC 50  = 6.17 μmol/L). In addition, the assessment of neuroprotective effect showed that compound 3 exhibited remarkable effect against PC12 cells injured by serum-deprivation and compounds 2, 7, and 9 exhibited moderate effects against PC12 cells injured by rotenone., Competing Interests: Conflict of interest No potential conflict of interest was reported by the authors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Solid phase extraction applied to plant matrices is nowadays a well validated technique allowing the concentration and purification of selected secondary metabolites for subsequent analysis. In this short communication we screened the efficiency of 16 selected solid supports including layered structures (hydrotalcites and zirconium phosphate), magnesium oxide and hydroxide, and finally the phyllosilicates talc and bentonite for the selective concentration of the anthraquinone emodin from raw solid extracts of Polygonum cuspidatum Siebold & Zucc. (sin. Reynoutria japonica Houtt.) (Polygonaceae), commonly known as " Japanese knotweed " . An ethanolic solution of sample extract from this plant was vigorously mixed with fixed quantities of each solid support. Subsequent HPLC analysis, coupled to photodiode array detection, revealed that, among the solid supports assayed, the hydrotalcite zinc aluminum oleate and magnesium oxide were largely the most effective to this concern. Both were able to extract emodin from the raw extract in percentages of 81.5 % and 92.4 %, respectively. The application of the title supports for the extraction and concentration in the solid phase of anthraquinones from raw plant extracts have been reported herein for the first time., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Most breast cancer survivors receiving chemotherapy have severe cognitive impairment, often referred to as "chemobrain." Polydatin (PLD) is known to have many biological activities. Thus, this study aimed to determine whether symptoms of chemobrain can be prevented or relieved by PLD. The chemobrain models were established by intraperitoneal injection of doxorubicin (DOX, 2 mg/kg) in rats once a week for 4 weeks (DOX group and DOX+PLD group). In the PLD group and DOX+PLD group, PLD (50 mg/kg) was administered orally to rats every day. We found that PLD treatment significantly protected against DOX-induced learning and memory impairment, restored hippocampal histopathological architecture. Furthermore, PLD suppressed DOX-induced oxidative stress through up-regulating Nrf2, inhibited inflammatory response by activating the NF-κB pathway, and reduced hippocampal apoptosis. Therefore, the present study indicated that PLD offered neuroprotection against DOX-induced chemobrain. PLD may assist in preventing chemobrain after chemotherapy in patients with cancers.

Off-line comprehensive two-dimensional reversed-phase countercurrent chromatography with high-performance liquid chromatography was investigated in separation of crude ethanol extract from traditional Chinese medicinal herb Polygonum cuspidatum Sieb. et Zucc. Two-dimensional contour plots for countercurrent chromatography with high-performance liquid chromatography was obtained after comprehensive separation was completed. Total peak capacity was evaluated and approximately 810 peaks were obtained through a comprehensive two-dimensional separation. A highly orthogonality of 52.23% and a large separation space occupancy of 88.86% were achieved. Meanwhile, it was found that several components could be well separated by countercurrent chromatography while they could not be separated by high-performance liquid chromatography, and vice versa, which further indicated the orthogonality of the two separation methods. The off-line comprehensive two-dimensional countercurrent chromatography with high-performance liquid chromatography provided a promising and powerful method for separation of complex natural products., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Natural products are widely used due to their various biological activities which include antiinflammatory, antioxidant, and anti-obesity effects. In this study, we determined the antioxidative and anti-obesity effects of Polygonum cuspidatum 50% ethanol extract (PEE). The antioxidative effect of PEE was evaluated using its radical scavenging activity, total phenolic content, and reducing power. The anti-obesity effect of PEE was investigated using 3T3-L1 adipocytes. The antioxidative activity of PEE was progressively increased in various concentrations, mainly due to the presence of phenolic compounds. PEE also alleviated lipid accumulation on 3T3-L1 adipocytes and downregulated the mRNA and protein production of adipogenesis-related (SREBP-1c, PPARγ, C/EBPα) and lipogenesis-related (aP2, FAS, ACC) markers. Furthermore, we found that the inhibitory effect on lipid accumulation via PEE was caused by the alleviation of NF-κB, p38 MAPK, ERK1/2, and JNK at the protein level. Taken together, our results imply that PEE is a potential antioxidant that can prevent obesityassociated disorders.

Resveratrol is a phytoalexin, stilbenoid compound with antioxidant properties attributable to its bioactive trans -resveratrol content. This study characterized the effects of over-the-counter (OTC) resveratrol nutritional supplements and a HPLC-purified resveratrol formulation, in human transmitochondrial age-related macular degeneration (AMD) retinal pigment epithelial (RPE) patient cell lines. These cell lines, which were created by fusing blood platelets obtained from dry and wet AMD patients with mitochondria-deficient (Rho0) ARPE-19 cells, had identical nuclei (derived from ARPE-19 cells) but different mitochondria that were derived from AMD patients. After resveratrol treatment, the levels of cell viability and reactive oxygen species production were measured. Results demonstrated that treatment with different resveratrol formulations improved cell viability and decreased reactive oxygen species generation in each AMD patient cell line. Although further studies are required to establish the cytoprotective potential of resveratrol under different physiological conditions, this novel study established the positive effects of OTC resveratrol supplements in macular degeneration patient cybrid cell lines in vitro.

A semi-automated online platform was established successfully for preliminary screening of potential active flavonoids of traditional Chinese medicines (TCMs) in multicomponent system. Online coupling of the in vitro intestinal absorption model, solid phase extraction (SPE) and high-performance liquid chromatography (HPLC) was actualized at the first time. The Ussing chamber model was selected to absorb the constituents of TCMs. A mini chromatographic column filled with C18 was used as a SPE column for online enrichment of flavonoids. HPLC was applied to analyze the constituents screened by platform. With the use of rutin as a model flavonoid, the specifications of SPE column, eluting solvent, elution time and flow rate of eluent were systematically investigated to optimize online system. Under the optimal conditions, the linear range of rutin was 0.125-368 µg/mL with the correlation coefficient (R 2 ) greater than 0.9947. The limit of detection (LOD) was as low as 0.0500 µg/mL and the limit of quantification (LOQ) was 0.125 µg/mL. The intra-day relative standard deviation (RSD) and inter-day RSD was 2.5% and 3.8%, respectively. The recoveries of rutin in the intestinal absorption samples ranged from 93.2% to 94.0%. Finally, the online system was applied to screen the potential active flavonoids of Scutellaria baicalensis Georgi (Huangqin, HQ) and Polygoni Cuspidati Rhizoma et Radix (Huzhang, HZ). A total of 14 flavonoids of these two TCMs were identified by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and 12 flavonoids of them were screened as the potential active components by online Ussing chamber-SPE-HPLC. In comparison with offline method and gavage in rats, the online system can screen the active constituents from TCMs more accurately and completely. The results demonstrated that the online system was reliable and sufficiently accurate for screening and determination of the potential active flavonoids of TCMs in multicomponent system., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Polydatin(PD), a natural active ingredient isolated from traditional Chinese herb Polygonum cuspidatum, is also found in daily foods such as grapes and red wine. It might play a potential therapeutic role in human health through its anti-inflammatory, anti-oxidant, anti-ischemia injury, anti-apoptosis, conditioning blood lipids and other effects, which makes it increasingly become a hotspot of research. Various studies have shown that PD has a protective effect in the ischemia-reperfusion injury of heart, lungs, kidneys, gastrointestinal tract, cerebra and other organs. However, the specific mechanism of action is less and not completely clear. In this study, we aim to review the protective mechanism of PD in the ischemia-reperfusion injury of various organs, and provide inspiration for future studies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Polydatin (also named pieceid, (E)-piceid, (E)-polydatin, trans-polydatin, or 3,5,4'-trihydroxystilbene-3-b-D-glucoside) is a monocrystalline compound isolated from the root and rhizome of Polygonum cuspidatum Sieb. et Zucc. (Polygonaceae). A previous study showed that polydatin has antioxidant and anti-inflammatory effects. However, the effect of polydatin in dry eye disease (DED) has not been elucidated. DED rat models were induced by exorbital lacrimal gland-excision. In vivo, the present study showed that the excision of lacrimal glands induced changes such as reduced tear fluid, severe corneal irregularity, damage, tear film break, and goblet cell loss as well as increased inflammation cytokine and NLRP3 expression in conjunctival tissue. However, these changes were restored by polydatin eye dropping. In vitro, polydatin inhibited hyperosmolar stress-induced inflammation through attenuation of the translocation of NF-κB to the nucleus and the mRNA expression of TNF-α, IL-6, IL-1β, and MMP9. In addition, the hyperosmolar stress-induced NLRP3 inflammasome pathway and ROS production were inhibited by polydatin. Our findings provided insight into the effect of polydatin as a candidate reagent for the treatment of DED.

Background: Polygonum cuspidatum has been used in traditional Chinese medicine to treat liver disorders associated with oxidative stress, inflammation and lipid accumulation for centuries in patients., Purpose: The aim of this study was to examine whether P. cuspidatum extract (PCE) prevented against fructose-induced liver lipid accumulation via regulating Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway., Method: PCE was administered orally to male Sprague-Dawley rats given 10% fructose drinking water for 6 weeks at 80 and 160 mg/kg once daily for 11 weeks., Results: PCE significantly alleviated liver lipid accumulation in fructose-fed rats with metabolic syndrome. It also inhibited Keap1, activated Nrf2 antioxidant pathway, resulting in the suppression of oxidative stress, evidenced by reducing hydrogen peroxide (H 2 O 2 ), malondialdehyde (MDA) and hydroxy radical (OH • ) levels, and increasing glutathione (GSH)/oxidized glutathione (GSSG) ratio as well as superoxidase dismutase (SOD) and catalase (CAT) activity in the liver of fructose-fed rats. Additionally, PCE up-regulated peroxisome proliferator activated receptor-α (PPAR-α), and down-regulated sterol regulatory element binging protein 1 (SREBP-1), fatty acid synthetase (FAS) and stearoyl-CoA desaturase-1 (SCD-1) in this animal model, being consistent with its reduction of triglyceride (TG) levels., Conclusion: These results demonstrate that PCE reduces oxidative stress, and prevent lipid accumulation in the liver of fructose-fed rats possibly by targeting the Keap1/Nrf2 pathway. PCE may be a promising therapeutic strategy for fructose-associated liver lipid accumulation., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Currently, processed meats appear increasingly as a nonhealthy food because of their content of fat, salt, nitrite, and particularly in red meat, for the heme-iron concerning oxidant effect and radicals formation in human gut. Polygonum cuspidatum and rosemary extract has been tested to counteract these effects and experiments were carried out to add polyphenols into whole meat cuts with the aims to improve their healthiness. The addition of these extracts can reduce the oxidation-reduction potential of products, increasing the antioxidant power. Nevertheless, a low percentage of polyphenols were found in the products because of the process effects and an interaction with the ascorbate residue was observed. In addition, some drawbacks were a decrease in of yield and a worsening of some sensorial properties when large amount of extract was added. The balance between the improvement of the wholesomeness content and the acceptability of products is the challenge the current research have to overcome.

We developed the first four HPTLC methods for the separation of proanthocyanidins according to degree of polymerization on HPTLC diol F 254S plates. Acetonitrile, ethyl acetate, ethyl acetate-formic acid (9:0.1, v/v) and toluene-acetone-formic acid (3:6:1, v/v) were used as developing solvents and 4-dimethylaminocinnamaldehyde (DMACA) as the detection reagent. Each of these methods enables separation of standards of procyanidin dimers from procyanidin trimer (procyanidin C1) and separation of B-type dimers (procyanidins B1, B2, B3) from A-type dimers (procyanidins A1, A2). Based on these HPTLC methods we developed four new HPTLC-MS/MS methods for analyses of proanthocyanidins on HPTLC diol F 254S plates and we identified B-type proanthocyanidins from monomers up to decamers in crude extracts of invasive Japanese knotweed (Fallopia japonica Houtt., Polygonum cuspidatum Sieb. & Zucc.) rhizomes. Monomers, monomer gallates, dimers, dimer gallates, dimer digallates, trimers, trimer gallates, tetramers, tetramer gallates, pentamers, pentamer gallates, hexamers, hexamer gallates, heptamers, octamers, nonamers and decamers were tentatively identified in Japanese knotweed rhizomes using developing solvents acetonitrile and toluene-acetone-formic acid (3:6:1, v/v). Ethyl acetate enabled separation from monomers up to hexamer gallates and ethyl acetate-formic acid (9:0.1, v/v) from monomers up to hexamers. During the five hours of stability testing of (-)-epicatechin and procyanidin B2 standards on HPTLC diol plates developed with all solvents we observed enhanced absorption at 280 nm. This was a totally unexpected phenomenon. This new discovery confirmed what we reported in our previous study on HPTLC silica gel. Enhanced absorption is influenced by the developing solvent (more than 30%), the stationary phase (up to 24%) and the light (up to 15%)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Many types of cancer cells show a characteristic increase in glycolysis, which is called the "Warburg effect." By screening plant extracts, we identified one that decreases cellular adenosine triphosphate (ATP) levels and suppresses proliferation of malignant melanoma B16F10 cells, but not of noncancerous MEF cells. We showed that its active ingredient is emodin, which showed strong antiproliferative effects on B16F10 cells both in vitro and in vivo. Moreover, we also found that emodin can function as a mitochondrial uncoupler. Consistently, three known mitochondrial uncouplers also displayed potent antiproliferative effects and preferential cellular ATP reduction in B16F10 cells, but not in MEF cells. These uncouplers provoked comparable mitochondrial uncoupling in both cell types, but they manifested dramatically different cellular effects. Namely in MEF cells, these uncouplers induced three to fivefold increases in glycolysis from the basal state, and this compensatory activation appeared to be responsible for the maintenance of cellular ATP levels. In contrast, B16F10 cells treated with the uncouplers showed less than a twofold enhancement of glycolysis, which was not sufficient to compensate for the decrease of ATP production. Together, these results raise the possibility that uncouplers could be effective therapeutic agents specifically for cancer cells with prominent "Warburg effect.", (© 2019 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

The aim of this study was to determine the content of triterpenoids and polyphenols, and antioxidative activity in leaves, stalks, and roots of plants from the species Fallopia as well as to present the main relationship between them. Polyphenolic compounds and triterpenoids were identified with liquid chromatography-photodiode detector-mass spectrometry/quadrupole time of flight (LC-MS-Q/TOF; qualitatively) and quantified with an ultra-performance liquid chromatography-photodiode detector (UPLC-PDA (quantitatively), and their antioxidative activity was determined with radical scavenging capacity (ABTS) and oxygen radical absorbance capacity (ORAC) assays. Generally, the wild Fallopia japonica Houtt. species had 1.2 times higher content of bioactive compounds and antioxidative activity than Fallopia sachalinensis . Contents of polyphenolic compounds determined in leaves, stalks, and roots were on average 17.81, 10.60, and 9.02 g/100 g of dry weight (DW), whereas the average contents of triterpenoids reached 0.78, 0.70, and 0.50 g/100 g DW, respectively. The leaves were a better source of polymeric procyanidins, phenolic acids, flavones, and flavonols, as well as oleanolic and ursolic acids than the other morphological parts of the tested plants. However, the roots were an excellent source of flavan-3-ols (monomeric and oligomer) and stilbenes, such as resveratrol, and their derivatives. The results obtained showed significant differences between plants of the wild Fallopia species and their morphological parts, and enabled selecting the most valuable morphological part of the tested plants to be used for food enrichment and nutraceuticals production. Therefore, the leaves seem to be the best as potential food additives for health, due to the above-average content of polyphenolic compounds and triterpenoids. In turn, roots, with their high contents of stilbenes and polyphenolic compounds, represent a good material for the medical, pharmaceutical, and cosmetic industries. The principal component analysis of the plants of wild Fallopia species and their morphological parts confirmed significant differences in their chemical composition.

Polygonum cuspidatum (Hu Zhang) is a traditional Chinese medicine (TCM) and has been revealed to exert anticancer, anti‑angiogenesis, anti‑human immunodeficiency virus (HIV), anti‑hepatitis B virus, anti‑microbial, anti‑inflammatory, and neuro‑protective bio‑activities. However, the effect of P. cuspidatum extract (PCE) on drug‑resistant human oral cancer cells regarding cell death is not fully understood yet. The present study was undertaken to explore the induction of autophagic and apoptotic cell death and to investigate their underlying molecular mechanisms in PCE‑treated cisplatin‑resistant human oral cancer CAR cells. Our results revealed that PCE was determined via HPLC analytic method, and it was revealed that resveratrol may be a major compound in PCE. The data also demonstrated that PCE reduced CAR cell viability in a concentration‑ and time‑dependent response via an MTT assay. PCE had an extremely low toxicity in human normal gingival fibroblasts (HGF). Autophagic and apoptotic cell death was found after PCE treatment by morphological determination. PCE was revealed to induce autophagy as determined using acridine orange (AO), LC3‑GFP, monodansylcadaverine (MDC) and LysoTracker Red staining in CAR cells. In addition, PCE was revealed to induce apoptosis in CAR cells via 4',6‑diamidino‑2‑phenylindole (DAPI)/terminal deoxynucleotidyl transferase dUTP nick‑end labeling (TUNEL) double staining. PCE significantly stimulated caspase‑9 and ‑3 activities as revealed using caspase activity assays. PCE markedly increased the protein levels of Atg5, Atg7, Atg12, Beclin‑1, LC3, Bax and cleaved caspase‑3, while it decreased the protein expression of Bcl‑2 in CAR cells as determined by western blotting. In conclusion, our findings are the first to suggest that PCE may be potentially efficacious for the treatment of cisplatin‑resistant human oral cancer.

Background: The anti-inflammatory actions of Polygonum cuspidatum, Angelica gigas, Sophora flavescens and Arctium fruit are well known. Nonetheless, effects of herbal combination (PASA) or its fermentation by microorganisms (F-PASA) on the allergic response remain unknown., Purpose: We investigated whether PASA or F-PASA could inhibit IgE/antigen complex (IgE/Ag)-mediated allergic responses., Methods: To evaluate and compare anti-allergic actions of PASA and F-PASA, we performed cell viability, β-hexosaminidase activity, ELISA assays for cytokines and eicosanoids, immunoblot analysis, HPLC analysis and passive cutaneous anaphylaxis (PCA) models., Results: F-PASA had stronger anti-degranulation actions (IC 50 , 510.9  µg/ml) than PASA (IC 50 , 1,261  µg/ml) without cytotoxicity until 2000  µg/ml in IgE/Ag-activated RBL-2H3 cells. Additionally, F-PASA inhibited formation of tumor necrosis factor-α (IC 50 , 147.4  µg/ml), interleukin-4 (IC 50 , 213.4  µg/ml), prostaglandin D 2 (IC 50 , 42.40  µg/ml) and leukotriene C 4 (IC 50 , 157.9  µg/ml). Moreover, F-PASA dose-dependently inhibited the phosphorylation and expression of proteins that are related to the FcεRI and arachidonate cascades. Consistent with in vitro studies, F-PASA from 25 to 100  mg/kg also suppressed IgE/Ag-induced PCA reaction more than PASA did in mice. In phytochemical analysis, using PASA and F-PASA, F-PASA showed a higher level of emodin-8-O-β-d-glucoside, whereas the level of arctiin, an artigenin glycoside, was reduced compared with that using PASA., Conclusion: These findings indicate that F-PASA, including both artigenin and emodin-8-O-β-d-glucoside, possesses stronger anti-allergic properties. Therefore, F-PASA may be useful as a functional food or as a phytomedicine for allergic diseases., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

The aim of this paper was to study the effect and mechanism of alcohol extract from Polygonum cuspidatum(PCE) on acute gouty arthritis in C57 BL/6 mice through NLRP3/ASC/caspase-1 axis. The model mice which injected with ankle joint injection of sodium urate crystals(MSU) were orally administrated with three different concentration of PCE, with colchicine as positive control. HE staining was used for observing the morphological changes of synovial tissue; concentration of IL-1β, IL-6 and TNF-α secreted by synovial tissue of the ankle joint were detected by ELISA; mRNA and protein expression of NLRP3, ASC and caspase-1 in synovial tissue were detected by RT-PCR and Western blot respectively. The results showed that the swelling degree of ankle joint in model mice were significantly elevated; expression of IL-1β, IL-6 and TNF-α were significantly increased; mRNA and protein expression of NLRP3, ASC and caspase-1 also significant increase, compared with normal control group. The swelling degree of ankle joint significantly relief; expression of IL-1β, IL-6 and TNF-α in joint synovium significantly decrease; mRNA and protein expression of NLRP3, ASC and caspase-1 were significantly decrease in PCE treatment group compared with model group. Our research implied that alcohol extract from P. cuspidatum had positive effect on acute gouty arthritis in mice, and the regulation of NLRP3/ASC/caspase-1 axis may be its mechanism.

Background: Signal transducer and activator of transcription 3 (STAT3) is an oncogene constitutively activated in hepatocellular carcinoma (HCC) cells and HCC cancer stem cells (CSCs). Constitutively activated STAT3 plays a pivotal role in holding cancer stemness of HCC CSCs, which are essential for hepatoma initiation, relapse, metastasis and drug resistance. Therefore, STAT3 has been validated as a novel anti-cancer drug target and the strategies targeting HCC CSCs may bring new hopes to HCC therapy. This study aimed to isolate and identify small-molecule STAT3 signaling inhibitors targeting CSCs from the ethyl acetate (EtOAc) extract of the roots of Polygonum cuspidatum and to evaluate their in vitro anti-cancer activities., Methods: The chemical components of the EtOAc extract and the subfractions of P. cuspidatum were isolated by using various column chromatographies on silical gel, Sephadex LH-20, and preparative HPLC. Their chemical structures were then determined on the basis of spectroscopic data including NMR, MS and IR analysis and their physicochemical properties. The inhibitory effects of the isolated compounds against STAT3 signaling were screened by a STAT3-dependent luciferase reporter gene assay. The tyrosine phosphorylation of STAT3 was examined by Western Blot analysis. In vitro anti-cancer effects of the STAT3 pathway inhibitor were further evaluated on cell growth of human HCC cells by a MTT assay, on self-renewal capacity of HCC CSCs by the tumorsphere formation assay, and on cell cycle and apoptosis by flow cytometry analysis, respectively., Results: The EtOAc extract of the roots of P. cuspidatum was investigated and a novel juglone analogue 2-ethoxystypandrone (1) along with seven known compounds (2-8) was isolated. Among the eight isolated compounds 1-8, 2-ethoxystypandrone was a novel and potent STAT3 signaling inhibitor (IC 50  = 7.75 ± 0.18 μM), and inhibited the IL-6-induced and constitutive activation of phosphorylation of STAT3 in HCC cells. Moreover, 2-ethoxystypandrone inhibited cell survival of HCC cells (IC 50  = 3.69 ± 0.51 μM ~ 20.36 ± 2.90 μM), blocked the tumorspheres formation (IC 50  = 2.70 ± 0.28 μM), and induced apoptosis of HCC CSCs in a dose-dependent manner., Conclusion: A novel juglone analogue 2-ethoxystypandrone was identified from the EtOAc extract of the roots of P. cuspidatum and was demonstrated to be a potent small-molecule STAT3 signaling inhibitor, which strongly blocked STAT3 activation, inhibited proliferation, and induced cell apoptosis of HCC cells and HCC CSCs. 2-Ethoxystypandrone as a STAT3 signaling inhibitor might be a promising lead compound for further development into an anti-CSCs drug.

Ionic liquid-based salt-induced liquid-liquid extraction was developed for the first time and applied to the extraction of four active constituents, including polydatin, resveratrol, emodin, and physcion in Polygonum cuspidatum (P. cuspidatum). In this study, ionic liquid was used as extraction solvent. The dried P. cuspidatum samples purchased from the pharmacy were triturated and passed through a 120-mesh sieve. The obtained sample powders were dried to constant weight at 55 ℃, and then mixed with extraction solvent. The extraction was carried out with the aid of ultrasound. Three phases, including ionic liquid-rich, salt-rich and solid sample phases were formed in the presence of salt. The target analytes were enriched in ionic liquid phase and then determined by high performance liquid chromatography. The experimental parameters, such as type and volume of ionic liquid, type and amount of salt, pH value of extraction medium, ultrasound power, ultrasound time and centrifugal condition, were optimized. The calibration curves showed good linear relationship (r > 0.9994). The limits of detection and quantification were in the range of 2.8-29.5 and 9.4-98.3 ng mL -1 , respectively. The spiked recoveries were between 92.16% and 105.41%. Compared with hot reflux extraction and ultrasound-assisted extraction, the proposed method requires less extraction solvent and time. The present method can be applied to the determination of polyphenols and anthraquinones in P. cuspidatum., (Copyright © 2018 Elsevier B.V. All rights reserved.)