Ischemic stroke (IS) is a prevalent neurological disorder often resulting in significant disability or mortality. Resveratrol, extracted from Polygonum cuspidatum Sieb. et Zucc. (commonly known as Japanese knotweed), has been recognized for its potent neuroprotective properties. However, the neuroprotective efficacy of its derivative, (E)-4-(3,5-dimethoxystyryl) quinoline (RV02), against ischemic stroke remains inadequately explored. This study aimed to evaluate the protective effects of RV02 on neuronal ischemia-reperfusion injury both in vitro and in vivo. The research utilized an animal model of middle cerebral artery occlusion/reperfusion and SH-SY5Y cells subjected to oxygen-glucose deprivation and reperfusion to simulate ischemic conditions. The findings demonstrate that RV02 attenuates neuronal mitochondrial damage and scavenges reactive oxygen species (ROS) through mitophagy activation. Furthermore, Parkin knockdown was found to abolish RV02's ability to activate mitophagy and neuroprotection in vitro. These results suggest that RV02 shows promise as a neuroprotective agent, with the activation of Parkin-mediated mitophagy potentially serving as the primary mechanism underlying its neuroprotective effects.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Mitophagy/drug effects* ; Resveratrol/analogs & derivatives* ; Neuroprotective Agents/pharmacology* ; Humans ; Neurons/metabolism* ; Reactive Oxygen Species/metabolism* ; Ischemic Stroke/genetics* ; Male ; Quinolines/pharmacology* ; Mice ; Fallopia japonica/chemistry* ; Mitochondria/metabolism* ; Reperfusion Injury/metabolism* ; Rats ; Mice, Inbred C57BL ; Disease Models, Animal

Traditional Chinese medicine of Polygonum cuspidatum has been utilized in China for thousands of years. Its primary active compound, polydatin, exhibits a variety of pharmacological effects including the regulation of glucose and lipid metabolism, suppression of cough and asthma, as well as antibacterial and anti-inflammatory properties. However, conventional methods for polydatin production are inadequate to satisfy the market demand. This study aims to explore the green and efficient preparation of polydatin. With resveratrol as the substrate, we efficiently synthesized polydatin by using the triple mutant IGW (Y14I/I62G/M315W) of the glycosyltransferase UGT_BS based on a strategy of two-enzyme coupled with one-pot and realized the recycling of uridine diphosphate-glucose (UDPG). The conditions of the two-enzyme reaction were optimized. Under the conditions of 35 ℃, pH 8.0, IGW: AtSuSy1 activity ratio of 3:4, dimethyl sulfoxide (DMSO) volume fraction of 5%, uridine diphosphate (UDP) concentration of 0.10 mmol/L, and sucrose concentration of 0.6 mol/L, the conversion of 2 mmol/L resveratrol reached 80.6% within 1 h, and the proportion of polydatin was over 90%. This study achieved the recycling of UDPG via a two-enzyme coupling system and shortened the reaction time. At the same time, the fed-batch strategy was adopted, and the yield of polydatin reached 6.28 g/L after 24 h in the one-pot coupling reaction, which provided a new strategy for green and efficient preparation of polydatin.
Stilbenes/chemistry* ; Glucosides/biosynthesis* ; Resveratrol ; Fallopia japonica/chemistry* ; Glycosyltransferases/genetics*

Polygonum cuspidatum polyketide synthase 1 (PcPKS1) has the catalytic activity of chalcone synthase (CHS) and benzylidene acetone synthase (BAS), which can catalyze the production of polyketides naringenin chalcone and benzylidene acetone, and then catalyze the synthesis of flavonoids or benzylidene acetone. In this study, three amino acid sites (Thr133, Ser134, Ser33) that may affect the function of PcPKS1 were identified by analyzing the sequences of PcPKS1, the BAS from Rheum palmatum and the CHS from Arabidopsis thaliana, as well as the conformation of the catalytic site of the enzyme. Molecular modification of PcPKS1 was carried out by site-directed mutagenesis, and two mutants were successfully obtained. The in vitro enzymatic reactions were carried out, and the differences in activity were detected by high performance liquid chromatography (HPLC). Finally, mutants T133LS134A and S339V with bifunctional activity were obtained. In addition to bifunctional activities of BAS and CHS, the modified PcPKS1 had much higher BAS activity than that of the wild type PcPKS1 under the conditions of pH 7.0 and pH 9.0, respectively. It provides a theoretical basis for future use of PcPKS1 in genetic engineering to regulate the biosynthesis of flavonoids and raspberry ketones.
Amino Acid Sequence ; Fallopia japonica/metabolism* ; Polyketide Synthases/chemistry* ; Acetone ; Mutagenesis, Site-Directed ; Flavonoids/metabolism* ; Acyltransferases/metabolism*

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.
Animals ; Ankle Joint ; physiopathology ; Arthritis, Gouty ; drug therapy ; CARD Signaling Adaptor Proteins ; metabolism ; Caspase 1 ; metabolism ; Fallopia japonica ; chemistry ; Interleukin-1beta ; metabolism ; Interleukin-6 ; metabolism ; Mice ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein ; metabolism ; Plant Extracts ; pharmacology ; Tumor Necrosis Factor-alpha ; metabolism ; Uric Acid

The present study investigated the chemical composition of ethylacetate extracts from an endophytic actinomycete Streptomyces sp. A0916 and its host Polygonum cuspidatum. A comparative analysis of the antimicrobial and antioxidant properties of the extracts was also conducted. 32 compounds of P. cuspidatum and 23 compounds of Streptomyces sp. A0916 were isolated and identified by GC/MS. Antimicrobial activities of the extracts were evaluated using eight microbial strains (3 Gram-positive bacteria, 3 Gram-negative bacteria, and 2 fungi). The Streptomyces sp. A0916 extracts showed a wide range of antimicrobial activities and presented greater antimicrobial effectiveness than the P. cuspidatum extracts. The minimum inhibitory concentration (MIC) of Streptomyces sp. A0916 extracts against the ampicillin-resistant strain Enterococcus faecium SIIA843 was 32 μg·mL(-1). Furthermore, the extracts had greater antimicrobial effect against Gram-positive bacteria than Gram-negative bacteria. Finally, the antioxidant activity of the Streptomyces sp. A0916 extracts was equal to that of the P. cuspidatum extracts. In conclusion, our results suggest that the endophytic actinomycetes of the medicinal plants are an important source of bioactive substances.
Anti-Infective Agents ; chemistry ; isolation & purification ; pharmacology ; Antioxidants ; chemistry ; isolation & purification ; pharmacology ; Bacteria ; drug effects ; Fallopia japonica ; chemistry ; microbiology ; Fungi ; drug effects ; Plant Extracts ; chemistry ; isolation & purification ; pharmacology ; Streptomyces ; chemistry ; classification ; genetics ; isolation & purification

OBJECTIVETo observe the effect of detoxifying and blood circulation activating Chinese herb extraction of polygonum cuspidatum and hawthorn on carotid intima-media thickness (IMT), plaque integral and plaque stability related serum indexes of patients with carotid atherosclerosis.

METHODSixty and four cases of carotid artery atherosclerosis patients were assigned randomly to 2 groups: detoxifying and blood circulation activating treatment group (treatment group, 32 cases) and control group (32 cases). Patients in treatment group were treated with capsules of extraction of polygonum cuspidatum and hawthorn, 1 pill po, bid (dosage of administration: polygonum cuspidatum extraction 5.33 mg x kg(-1) x d(-1), hawthorn extraction 5.0 mg x kg(-1) x d(-1)); patients in control group were treated with lovastatin 20 mg po, qd (dosage of administration: 0.33 mg x kg(-1) x d(-1)). The course of treatment was six months. To observe changes of IMT, plaque integral, and detect the level of plaque stability related serum indexes such as Hs-CRP, MMP-1 and TIMP-1.

RESULTAfter 6 months of treatment, in control group one patient quit the clinical trial because of liver dysfunction and one patient was rejected because of having not followed the therapeutic regimen. 32 cases in treatment group and 30 cases in control group were analyzed. The results showed that IMT and plaque integral of treatment group decreased significantly after the treatment (P < 0.05, P < 0.01), and there was no significant difference compared with control grope. Serum Hs-CRP, MMP-1 and MMP-1/TIMP-1 decreased after the treatment (P < 0.05, P < 0.01), and the treatment group was superior to control group in decreasing serum Hs-CRP (P < 0.05).

CONCLUSIONDetoxifying and blood circulation activating Chinese herb extraction of polygonum cuspidatum and hawthorn has good effect of anti-atherosclerosis and promoting plaque stability. Its mechanism might be related with anti-inflammation and inhibiting degradation of extracellular matrix, and deserves further studies.

C-Reactive Protein ; metabolism ; Carotid Artery Diseases ; blood ; drug therapy ; Crataegus ; chemistry ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; therapeutic use ; Fallopia japonica ; chemistry ; Female ; Humans ; Male ; Matrix Metalloproteinase 1 ; blood ; Middle Aged ; Safety ; Tissue Inhibitor of Metalloproteinase-1 ; blood

Through searching some domestic or abroad literatures of rhizoma polygoni cuspidati in recent years, the paper summarized its pharmacological effects, including antibacterial, antiviral, anti-inflammatory, analgesic, cardiovascular system protection, liver protection, anti tumor, improving immunity pharmacology and so on. These studies indicated Polygoni Cuspidati Rhizoma was a kind of drugs with exploiting and using value. [Key words]
Animals ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Fallopia japonica ; chemistry ; Rhizome ; chemistry

An HPLC method has been developed to determine polydatin in giant knotweed rhizome. In order to systematically validate the method, specificity, precision, linearity of reference solution and test solution, repeatability, reproducibility, accuracy, stability and robustness were measured. In the robustness test, a one-variable-at-a-time procedure was applied to evaluate the influence of slight variations in method factors, including the flow rate, the column temperature, the extraction time, and etc., on the assay result of polydatin. No significant differences were found when the process parameters changed during the experimental domain. And system suitability test limits were defined based on the robustness test. Results showed that the developed method was accurate, reproducible and robust.
Chromatography, High Pressure Liquid ; methods ; Drug Stability ; Fallopia japonica ; chemistry ; Glucosides ; analysis ; Plants, Medicinal ; chemistry ; Reproducibility of Results ; Rhizome ; chemistry ; Sensitivity and Specificity ; Stilbenes ; analysis

AIM: To establish the Spectrum-Effect integrated fingerprint of Polygonum cuspidatum to evaluate the quality of P. cuspidatum. METHODS: An on-line HPLC-DAD-flow injection chemiluminescence (FICL) method was developed to investigate the quality of P. cuspidatum from different habitats based on the established Spectrum-Effect integrated fingerprint. RESULTS: Nineteen batches of samples of P. cuspidatum were evaluated for the similarity of their chromatographic and free radical scavenging fingerprints, and the results compared. Main antioxidants were estimated by regression analysis between peak areas of thirteen compounds and their activities. Some active compounds were identified by HPLC-ESI-MS. CONSULSIONS The results indicated that main antioxidants in P. cuspidatum could be rapidly screened by the established Spectrum-Effect integrated fingerprint based on on-line HPLC-DAD-FICL, and would be more efficient and objective method to evaluate the quality of P. cuspidatum.
Antioxidants ; analysis ; Chromatography, High Pressure Liquid ; instrumentation ; methods ; Drugs, Chinese Herbal ; analysis ; Fallopia japonica ; chemistry ; Flow Injection Analysis ; Luminescence ; Quality Control

OBJECTIVETo isolate and identify active neuraminidase constituents of Polygonum cuspidatum against influenza A (H1N1) influenza virus.

METHODOn the basis of the bioassay-guided fractionation,such chromatographic methods as silica gel, sephadex LH-20 and HPLC were adopted to isolate active constituents of extracts from Polygonum cuspidatum, and their molecular structures were identifiied on the basis of their spectral data such as NMR and MS and physico-chemical properties.

RESULTSeven compounds were isolated from the ethyl acetate extract of P. cuspidatum and identified as 2-methoxystypandrone (1), emodin (2), resveratrol (3), polydatin (4), emodin-8-O-beta-D-glucopyranoside (5), (E)-3, 5, 12-trihydroxystilbene-3-O-beta-D-glucopyranoside-2'-(3", 4", 5"-trihydroxybenzoate) (6) and catechin-3-O-gallate (7), respectively. Among them, the NA test showed that compounds 3, 6 and 7 had inhibitory effect against NAs activity, with IC50 values of 129.8, 44.8 and 21.3 micromol x L(-1), respectively. Moreover, the further CPE test showed compounds 6 and 7 had significant inhibitory effect against H1N influenza virus (EC50 = 5.9, 0.9 micromol x L(-1), respectively), with very low cytotoxicity to the host cells, their therapeutic selective index(SI) in MDCK cells ranged from 56 to 269.

CONCLUSIONThe neuraminidase inhibitors against H1N1 anti-influenza virus isolated from extracts of P. cuspidatum on the basis of the bioassay-guided fractionation are significant in specifying their therapeutic material basis and drug R&D against influenza.

Cell Line ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Enzyme Inhibitors ; chemistry ; isolation & purification ; pharmacology ; Fallopia japonica ; chemistry ; Humans ; Influenza A Virus, H1N1 Subtype ; drug effects ; enzymology ; Influenza, Human ; virology ; Molecular Structure ; Neuraminidase ; antagonists & inhibitors