BACKGROUND:Clinacanthus nutans (for abbreviation thereafter) is often used as medicine in the form of fresh juice in the folk to treat many kinds of cancers, including renal cell carcinoma (RCC). It is speculated that its active ingredient may have heat sensitivity, but there are currently no reports on this aspect. Therefore, based on the folk application for fresh juice of C nutans, this study used metabonomics and network pharmacology to explore the material basis and mechanism of action of C nutans against RCC.METHODS:Firstly, untargeted metabolomics profiling was performed by Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry to screen the metabolites down-regulated by heat in the extract of C nutans. Secondly, we collected the targets of metabolites in the Swiss Target Prediction platform. In addition, the targets of RCC were obtained in the GeneCards database. The "component-target-disease" network was established by Cytoscape3.9.0 software. Then we constructed a protein-protein interaction network in the STRING network platform to screen core targets. The gene ontology and kyoto encyclopedia of genes and genomes enrichment analysis of core targets were carried out to predict the relevant pathway of C nutans in the treatment of RCC. Finally, the molecular docking verification of the core targets were carried out.RESULTS:In this study, 35 potential active ingredients and 125 potential targets were obtained. And the core targets were Cellular tumor antigen p53, Signal transducer and activator of transcription 3, and so on. Then, 48 biological processes, 30 cell components, and 36 molecular functions were obtained by gene ontology enrichment analysis. Besides, 44 pathways were obtained by Kyoto encyclopedia of genes and genomes enrichment analysis, including Pathway in cancer, PI3K-Akt signal pathway, P53 signal pathway, and so on. The docking model between the core target and its corresponding components was stable.CONCLUSION:This research is based on the folk application of C nutans, showed its potential active ingredients by metabonomics, and predicted the potential mechanism of C nutans in the treatment of RCC by network pharmacology. It provides new references for follow-up research and new drug development.

Background: Human brain tumor glioblastoma (GBM) is the most hostile malignancy, currently lacking a successful cure and good prognosis. Objective: To examine the anticancer effects of syringic acid (SA) on human cancer GBM cells. Methodology: The different doses of SA were added to GBM cells to study its effect on viability, invasion, relocation, apoptosis, and mRNA and protein levels. Hence, we explored the antiproliferative, anti-invasive, and apoptotic activity of SA on GBM human U-251 cells. Results: MTT assay and live/dead assay revealed the anti-proliferative activity of SA on U-251 glioma cells. Apoptotic activity of SA was shown by DAPI staining, caspase-3, Bax, and Bcl-2 mRNA expressions. The cell cycle regulation was also confirmed by reducing the mRNA expression of cyclinD1, CDK4, and CDK6. Treatment of SA with U-251 cells suppressed MMPs expressions and enhanced TIMPs protein levels. Conclusion: Our findings put forward that SA could prevent GBM cells’ invasion and relocation. SA is an ideal neuroprotective agent for controlling brain malignancy.

Since the global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a symptom of the onset of SARS-CoV-2, olfactory dysfunction (OD), has attracted tremendous attention. OD is not only a negative factor for quality of life but also an independent hazard and early biomarker for various diseases, such as Parkinson’s and Huntington’s diseases. Therefore, early identification and treatment of OD in patients are critical. Many etiological factors are responsible for OD based on current opinions. Sniffin’Sticks are recommended to identify the initial position (central or peripheral) for OD when treating patients clinically. It is worth emphasizing that the olfactory region in nasal cavity is recognized as the primary and critical olfactory receptor. Many nasal diseases, such as those with traumatic, obstructive and inflammatory causes, can lead to OD. The key question is no refined diagnosis or treatment strategy for nasogenic OD currently. This study summarizes the differences in medical history, symptoms, auxiliary examination, treatment and prognosis of different types of nasogenic OD by analyzing the current studies. We propose using olfactory training after 4–6 weeks of initial treatment for nasogenic OD patients with no significant improvement in olfaction. We hope that our research can provide valuable clinical guidance by systematically summarizing the clinical characteristics of nasogenic OD.

The nasal mucosa, which performs the crucial functions of filtering, humidifying and temperature regulation, is one of the most vulnerable areas of nasopharyngeal carcinoma (NPC) patients after radiotherapy (RT). Following RT, NPC patients experience a series of pathological changes in the nasal mucosa, ultimately leading to physiological dysfunction of the nasal epithelium. This article systematically reviews the clinical and pathological manifestations of RT-related nasal damage in NPC patients and summarizes the potential mechanism of damage to the human nasal epithelium by RT. Finally, we outline the current mechanistic models of nasal epithelial alterations after RT in NPC patients and provide additional information to extend the in-depth study on the impairment mechanisms of the nasal mucosa resulting from RT. We also describe the relationship between structural and functional alterations in the nasal mucosa after RT to help mitigate and treat this damage and provide insights informing future clinical and fundamental investigations.

OBJECTIVE:Cortex Mori Radicis (CMR) has been reported to possess antipyretic, anticonvulsant, anti-allergic, anti-inflammatory, and anti-diabetic effects. In this study, we aimed to investigate the effect of CMR on streptozotocin (STZ)-induced diabetic renal injury in mice and explore the underlying mechanism.METHODS:Mice were gavaged with different doses of CMR for continuous 7 days. Then, STZ (50 mg/kg) was applied to induce renal injury associated with type 1 diabetes. Firstly, blood glucose levels and metabolic parameters were evaluated, including weight, food intake, and excrement. HE and PAS staining were performed to examine renal histological changes. Renal inflammation, fibrosis, and oxidative stress were assayed by real-time PCR and ELISA, separately. Additionally, podocyte- related markers, such as nephrin and wilms' tumor-1 (WT-1), were detected by immunohistochemical staining and Western blot separately. Lastly, expression of transient receptor potential canonical channel 6 (TRPC6) and activation of MAPK signaling pathways were assayed.RESULTS:CMR pretreatment significantly lowered the blood glucose levels, suppressed renal inflammation, fibrosis, and oxidative stress, and relieved renal pathological injury, accompanying the inhibition of nephrin and WT-1 expression in STZ-induced diabetic mice. Moreover, CMR decreased the expression of TRPC6 and suppressed the phosphorylation of ERK, but not P38 MAPK and JNK. Notably, the application of hyperforin, a specific activator of TRPC6, significantly abrogated the hypoglycemic effect of CMR and reversed the suppression of CMR on TRPC6 expression and ERK activation in the diabetic mice.CONCLUSION:Our findings indicated that CMR attenuated early renal injury in STZ-induced diabetic mice by inhibiting ERK signaling via regulation of TRPC6, suggesting that CMR can be considered as a promising candidate for the management of diabetes-related renal complications.

OBJECTIVE:To observe the effect of electroacupuncture (EA) pretreatment on apoptosis of renal tubular epithelial cells in mice with hyperglycemia, so as to explore its mechanisms underlying protecting the kidney from hyperglycemia-induced injury.METHODS:Eighty male C57BL/6 mice were equally and randomly divided into control, model, EA and sham EA groups. The hyperglycemia model was established by intraperitoneal injection of streptozocin (STZ, 50 mg·kg-1·d-1) for 5 consecutive days. Before modeling, EA (2 Hz/15 Hz, 0.3-0.5 mA) was applied to bilateral "Zusanli" (ST36) and "Shenshu" (BL23) for 30 min, once daily for 7 days, while mice in the sham EA group were treated with the same acupoints but without electrical stimulation. The blood glucose values were measured after fasting for 6 hours after 3 days of modeling. The degree of renal tissue injury was observed by microscope after H.E. staining, and the apoptosis level of renal tubular epithelial cells observed by TUNEL staining. The expression levels of transient receptor potential channel 6 (TRPC6) and related apoptotic proteins Caspase-3, Bax and Bcl-2 in the renal tissue were detected by Western blot and immunohistochemistry, separately.RESULTS:Compared with the control group, the blood glucose content and the expression levels of TRPC6, Caspase-3 and Bax proteins, as well as the level of the renal apoptotic cells were significantly increased (P<0.001, P<0.000 1), while the expression level of Bcl-2 protein and the ratio of Bcl-2/Bax were remarkably decreased in the model group (P<0.000 1). In comparison with the model and sham EA groups, the blood glucose content, percentage of apoptotic cells and the expression levels of TRPC6, Caspase-3 and Bax were significantly decreased (P<0.01, P<0.000 1, P<0.05, P<0.001), and the expression level of Bcl-2 and the ratio of Bcl-2/Bax were apparently increased in the EA group (P<0.01, P<0.05, P<0.001). HE statin showed abnormal dilation of the capillary lumen and disappearance of the proximal tubules in the model group, which was relatively milder in the EA group.CONCLUSION:EA pretreatment can lower blood glucose level and reduce renal apoptosis in hyperglycemia mice, which may be related to its effects in down-regulating the expression of TRPC6 and Caspase-3 and up-regulating the ratio of Bcl-2/Bax.

Aim Accumulating evidence suggests that lncRNAs are potential biomarkers and key regulators of tumor development and progression. However, the precise function of most lncRNAs in glioma remains unknown. In this study, we explored the role of long intergenic non-protein coding RNA 1018 (LINC01018) in human glioma. Methods Expression levels of LINC01018 and miR-182-5p in clinical glioma tissues and cell lines were detected by quantitative real-time PCR (qRT-PCR). Cell proliferation, migration, and invasion were determined by Cell Counting Kit-8 (CCK-8) assay and Transwell assay. Epithelial-mesenchymal transition (EMT) related proteins were measured by Western blotting. Direct relationship between LINC01018 and miR-182-5p was tested by dual-luciferase reporter assay, RNA immunoprecipitation assay (RIP), and rescue assays. Lastly, bioinformatics analyses were conducted to predict the downstream factors of LINC01018/miR-182-5p axis in glioma. Results LINC01018 was significantly down-regulated in glioma tissues and cell lines. Overexpression of LINC01018 dramatically inhibited cell proliferation, migration, and invasion and reverse EMT process in glioma. LINC01018 directly target to miR-182-5p. Forced up-regulation of miR-182-5p reversed the inhibitory effects on proliferative and metastatic abilities of glioma cells with LINC01018 overexpression. Lastly, the bioinformatics analyses revealed that LINC01018/miR-182-5p axis mediated a cluster of downstream genes (ADRA2C, RAB6B, RAB27B, RAPGEF5, STEAP2, TAGLN3, and UNC13C), which were potential key factors in the development of glioma. Conclusion LINC01018 inhibits cell proliferation and metastasis in human glioma by targeting miR-182-5p, and should be considered as a potential therapeutic target in this cancer.

SERPINE1 protein is one important member of the serine proteinase inhibitor E superfamily that plays a crucial role in the fibrinolytic system. It has been identified which is related to chronic inflammatory lung diseases like allergic asthma and lung fibrosis. Recently, researchers have focused on the impact of SERPINE1 and its genetic polymorphisms on inflammatory diseases of the upper respiratory tract. In this review, we conclude that SERPINE1 is widely involved in the pathological process of chronic rhinosinusitis and allergic rhinitis (AR) and may play a pivotal role in tissue remodelling in chronic rhinosinusitis without nasal polyps. It is also found that the 4G allele of SERPINE1 gene is associated with the risk of upper respiratory diseases. More studies are needed to further clarify how SERPINE1 influences chronic rhinosinusitis and AR, which would be conducive to improving the therapeutic efficacy of treatments for upper respiratory diseases.

OBJECTIVE:To investigate the effects of acupuncture on ovary morphology and function in dehydroepiandrosterone (DHEA)-induced polycystic ovary syndrome (PCOS) model rats. METHODS:A total of 40 adult female Wistar rats were randomly allocated to 4 groups by a random number table, including control, model, metformin and acupuncture groups, 10 rats in each group. PCOS rat model was developed by injecting with DHEA (6 mg/100 g body weight) in 0.2 mL of oil subcutaneously. Electrical stimulation (2 Hz, 3 mA) was applied to Guanyuan (CV 4), Zigong (EX-CA1) and Qihai (CV 6) acupoints for 30 min daily in the acupuncture group, and metformin (200 mg/kg) was given to rats in the metformin group, both once per day for 21 consecutive days, and rats in the normal group was fed with normal saline and fed regularly. After 21 days of administration, the rat blood samples were collected for detecting the reproductive hormonal levels [luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), progesterone (P), testosterone (T)] and inflammatory factors (visfatin, IL-6) analysis. Ovary tissue was used for histopathological analysis. RESULTS:Compared with the model group, rats in the acupuncture and metformin groups were significantly lower in weight gain, FSH, LH and T levels, and E2 and P levels significantly increased (alll P<0.05). Meanwhile, LH and FSH levels were significantly decreased, and P, T and E2 levels significantly increased in the acupuncture group, compared with the metformin group (P<0.05). Compared with the model group, IL-6 and visfatin levels were significantly decreased in the acupuncture and metformin groups (P<0.05). There were no significant differences in IL-6 and visfatin levels between the acupuncture and metformin groups (P>0.05). Ovarian diameter in the acupuncture and metformin groups were smaller than the model group (P<0.05). However, there were no significant differences in ovarian diameters between the acupuncture and metformin groups (P>0.05). CONCLUSION:Acupuncture might improve ovary morphology and its function in DHEA-induced PCOS model rats.

ViceninII is a naturally flavonoid glycoside extracted from Dendrobium officinale, a precious Chinese traditional herb, has been proven to be valuable for cancer treatment. Transforming growth factor-β1 (TGF-β1), promotes the induction of epithelial–mesenchymal transition (EMT), a process involved in the metastasis of cells that leads to enhanced migration and invasion. However, there is no previously evidence that ViceninII has an inhibitory effect on cancer metastasis, specifically on the TGF-β1-induced EMT process in lung adenocarcinoma cells. In this experiment, we used UV, ESIMS, and NMR to identify the structure of ViceninII.A549 and H1299 cells were treated with TGF-β1 in the absence and presence of ViceninII, and subsequent migration and invasion were measured by wound-healing and transwell assays. The protein localization and expressions were detected by immunofluorescence and Western blotting. The results indicated that TGF-β1 induced spindle-shaped changes, increased migration and invasion, and upregulated or downregulated the relative expression of EMT biomarkers. Meanwhile, these alterations were significantly inhibited when co-treated with ViceninII and inhibitors LY294002 and SB431542. In conclusion, ViceninII inhibited TGF-β1-induced EMT via the deactivation of TGF-β/Smad and PI3K/Akt/mTOR signaling pathways.This is the first time that the anti-metastatic effects of ViceninII have been demonstrated, and their molecular mechanisms provided.

A simple, accurate, and reliable liquid chromatography-mass spectrometry (LC-MS/MS) method was developed and validated for the determination of mangiferin in rat plasma and tissue homogenates using rutin as an internal standard (IS). Chromatographic separation was achieved on a Shiseido CAPCELL PAK C18 column (150 × 2.0 mm, 5 μm) using a gradient elution of 1% acetic acid in water and methanol at a flow rate of 300 μL·min-1. Quantification was performed on an API 4000+ triple-quadrupole mass spectrometer equipped with a turbo electrospray ionization (ESI) source in positive ion multiple reaction monitoring (MRM) mode. Selected ion monitoring transitions of 423.1 → 273.1 and 611.4 → 303.3 were chosen to quantify mangiferin and IS. Biological samples were pretreated via protein precipitation with acetonitrile-acetic acid. The standard calibration curves were above the ranges of 2 to 500 ng·mL-1 and 5 to 2000 ng·mL-1 for tissues, and 1 to 600 ng·mL-1 for plasma. All calibration curves for tissue and plasma samples showed good linearity (r ≥ 0.9974) over the concentration ranges. Intra- and inter-day precisions were <14.0%, and accuracy ranged from 97.2% to 111.7%. The established method was successfully applied on mangiferin tissue distribution following the intragastric administration of mangiferin, Rhizoma Anemarrhenae (A. Rhizoma) decoction, or Rhizoma Anemarrhenae-Phellodendron (herb pair, HP) decoction under healthy or diabetic conditions. Mangiferin was detected from all the tested tissues (except for brain) after monomer administration, and the concentrations were lower compared with the decoction groups. Distributions in the HP group were lower than those in the A. Rhizoma group, but mangiferin content in pancreas was obviously higher than in other tissues and in the A. Rhizoma group. Compared with healthy rats, mangiferin distributions in pancreas and intestine were lower in diabetic rats administered with the same dose of the herb pair, but still higher than those in other tissues. In addition, distributions in liver, spleen, lung, kidney, stomach, and plasma were higher than those in the normal group.

Searching novel hypouricemic agents of high efficacy and safety has attracted a great attention. Previously, we reported the hypouricemic effect of Ganoderma applanatum, but its bioactives, was not referred. Herein, we report the hypouricemic effect of 2,5-dihydroxyacetophenone (DHAP), a compound screened from Ganoderma applanatum computationally. Serum parameters, such as uric acid (SUA), xanthine oxidase (XOD) activity, blood urea nitrogen (BUN), and creatinine were recorded. Real-time reverse transcription PCR (RT-PCR) and Western blot were exploited to assay RNA and protein expressions of organic anion transporter 1 (OAT1), glucose transporter 9 (GLUT9), uric acid transporter 1 (URAT1), and gastrointestinal concentrative nucleoside transporter 2 (CNT2). DHAP at 20, 40, and 80 mg/kg exerted excellent hypouricemic action on hyperuricemic mice, reducing SUA from hyperuricemic control (407 ± 31 μmol/L, p < 0.01) to 180 ± 29, 144 ± 13, and 139 ± 31 μmol/L, respectively. In contrast to the renal toxic allopurinol, DHAP showed some kidney-protective effects. Moreover, its suppression on XOD activity, in vivo and in vitro, suggested that XOD inhibition may be a mechanism for its hypouricemic effect. Given this, its binding mode to XOD was explored by molecular docking and revealed that three hydrogen bonds may play key roles in its binding and orientation. It upregulated OAT1 and downregulated GLUT9, URAT1, and CNT2 too. In summary, its hypouricemic effect may be mediated by regulation of XOD, OAT1, GLUT9, URAT1, and CNT2.

Conventionally, benzophenone-type molecules are beneficial for alleviating the UV exposure of humans. More importantly, various compounds with this skeleton have demonstrated various biological activities. In this paper, we report the anti-hyperuricemic effect of the benzophenone compound 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (HMS). Preliminarily, its molecular docking score and xanthine oxidase (XOD) inhibition suggested a good anti-hyperuricemic effect. Then, its anti-hyperuricemic effect, primary mechanisms and general toxicity were examined on a hyperuricemic mouse model which was established using potassium oxonate and hypoxanthine together. HMS demonstrated a remarkable anti- hyperuricemic effect which was near to that of the control drugs, showing promising perspective. General toxicity was assessed and it showed no negative effects on body weight growth and kidney function. Moreover, anti-inflammatory action was observed for HMS via spleen and thymus changes. Its anti-hyperuricemic mechanisms may be ascribed to its inhibition of XOD and its up-regulation of organic anion transporter 1 (OAT1) and down-regulation of glucose transporter 9 (GLUT9).

BACKGROUND:Acupuncture and moxibustion has been widely applied to hyperlipidemia treatment in clinical practice in China, serving as an alternative treatment to statins. Warm-needling acupuncture and medicinal cake-separated moxibustion have been separately reported with potential therapeutic effects on hyperlipidemia treatment in several studies but with limitations in study methodology. Combining these two modalities may provide a more advantageous strategy in treating hyperlipidemia. Therefore, a strict evaluation through well-designed randomized controlled trials (RCT) is necessary to determine their efficacy and safety on hyperlipidemia.METHODS:The study a multicenter, open-label, randomized, stratified, active-controlled, noninferiority trial with two parallel groups. Subjects with hyperlipidemia will be stratified into different groups by risk levels of heart diseases. They then will be instructed to the Therapeutic Lifestyle Change (TLC) diet. Those who have not reached the target lipid level will be randomly assigned to the treatments of either acupuncture and moxibustion or simvastatin with a 1:1 allocation. One hundred and thirty subjects are aimed to be recruited. The duration of intervention for this study will be 12 weeks, followed by another 4 weeks for post-treatment assessment. The primary outcome is percentage change from baseline to the end of the study in low-density lipoprotein cholesterol (LDL-C). Other indicators in lipid change, safety and adherence will also be assessed secondarily. The repeated measures, linear mixed-effects model will be applied to the analysis.DISCUSSION:Acupuncture and moxibustion could be a potentially effective treatment alternative for hyperlipidemia. A study with careful design is developed to evaluate the efficacy and safety of combined acupuncture and moxibustion, by integrating the traditional Chinese Medicine (TCM) regimens with the standardized Western medicine appraisal approach.TRIAL REGISTRATION:ClinicalTrials.gov, NCT02269046 . Registered on 26 September 2014.

To observe the effect of herbal cake-partitioned moxibustion on the expressions of mitogen-activated protein kinase (MEK1/2) and extracellular regulatory protein kinase (ERK1/2) in gastric tissues of rats with spleen deficiency syndrome, and to explore the possible mechanisms of herbal cake-partitioned moxibustion in treating spleen deficiency syndrome.

Objective: To explore the clinical effects of electroacupuncture (EA) at Zusanli (ST 36) and Fenglong (ST 40) in treating senile dementia. Methods:A total of74 patients were randomly divided into an EA group and a medication group based upon the random digital table, 37 cases in each group. EA at Zusanli (ST 36) and Fenglong (ST 40) was given in the EA group, once every day, for six treatments per week. Donepezil Hydrochloride Tablets were given to the medication group, 5 mg per time and once a day in the former four weeks, 10 mg per time and once a day after 4 weeks, oral administration before sleep at night. The courses of the treatment were 12 weeks in both groups. The scores of mini-mental state examination (MMSE) and Barthel index (BI) were observed before and after the treatment, for processing the comparative analysis of the clinical effects after the course of the treatment. Results:The total effective rate was 86.5% in the EA group and 70.3% in the medication group. The therapeutic effect was better in the EA group than that in the medication group, and the difference between the two groups was statistically significant (P<0.05). MMSE and BI scores after the treatment in the two groups were all elevated than those of the same groups before the treatment (P<0.05,P<0.01). The improving situation was obviously better in the EA group than that in the medication group, and the difference between the two groups was statistically significant (P<0.05). Conclusion:EA at Zusanli (ST 36) and Fenglong (ST 40) is affirmative in the therapeutic effect for senile dementia and can also improve the cognitive function and enhance the patients’ quality of life .

OBJECTIVE:To investigate the protective effects of Chinese medicine formulation Chaihu Shugan San (, CHSGS) on nonalcoholic fatty liver disease (NAFLD) in rats with insulin resistance (IR) and its molecular mechanisms.METHODS:Male Sprague-Dawley rats were randomly divided into six groups: the control group, the model group, Dongbao Gantai group (, DBGT, 0.09 g methionine/kg), CHSGS high-dose group (CHSG-H, 12.6 g crude drug/kg), CHSGS medium-dose group (CHSG-M, 6.3 g crude drug/kg), and CHSGS low-dose group (CHSG-L, 3.15 g crude drug/kg). After establishing the NAFLD rat model and treatment for 8 weeks, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), free fatty acid (FFA), fasting blood glucose (FBG), fasting insulin (FINS) contents in blood serum, and TC, TG contents in the hepatic homogenate were measured by an automatic biochemical analyzer, and a homeostasis model assessment was applied to assess the status of IR, insulin sensitivity index (ISI), and homeostasis model assessment for insulin secretion (HOMA-IS). The expression levels of adiponectin and leptin mRNA in liver tissue were analyzed by reverse transcription polymerase chain reaction. Pathological changes of livers were observed by hematoxylin-eosin staining of paraffin section.RESULTS:Compared with the model group, the serum levels of TC, TG, FFA, FBG, FINS, IRI, ISI, and the liver levels of TC and TG in CHSG-H, CHSG-M, CHSG-L groups showed significant declines (P<0.01 or P<0.05); the serum levels of HDL-C, HOMA-IS were significantly increased (P<0.01 or P<0.05); the expression of leptin mRNA was dramatically decreased and the expression of adiponectin mRNA was increased in the hepatic tissue (P<0.01 or P<0.05). The fatty deposition of liver cells could also be alleviated.CONCLUSION:CHSGS could up-regulate the expression of adiponectin mRNA and down-regulate the expression of leptin mRNA on the liver, suggesting the CHSGS had positive therapeutic effect on NAFLD in rats with IR.

Methylglyoxal (MGO), a very reactive metabolite of glucose, plays a pivotal role in the pathogenesis of several chronic diseases associated with diabetes, and it has been validated as an attractive target for them. In the present study, a simple and effective method, namely pre-column incubation followed by fast high performance liquid chromatography based on superficially porous particles (shell), coupled with diode array detection and tandem mass spectrometry (UHPLC-DAD-MSn), was proposed for rapid and high-throughput screening of natural MGO scavengers directly from the crude extract of Polygonum cuspidatum Sieb. et Zucc, a well-known traditional Chinese medicine which was used for treatment of diabetic complications. The hypothesis is that upon reaction with MGO, the peak areas of components with MGO scavenging potency in the chromatogram will be significantly reduced or disappear, and the structural characterization could be achieved by UHPLC-DAD-MSn hyphenated technique. First of all, 12 compounds in P. cuspidatum were well separated within shorter time (similar to 12 min) than previous methods and identified, and two of them, i.e. 3,5,4'-trihydroxystilbene-3-O-(6 ''-galloyl)-glucoside (3) and emodin-8-O-(6'-malonyl)-glucoside (8) were firstly reported ingredients. After incubation with MGO, four stilbene derivatives were demonstrated to possess potential MGO trapping activities. Furthermore, it was proved that both polydatin (piceid) and resveratrol exhibited effective MGO-trapping capacity by UHPLC analysis, and they could significantly inhibit the formation of advanced glycation end products (AGEs) in the human serum albumin (HSA)-MGO assay, indicating that they were potential candidate agents for delaying and preventing diabetic complications. Additionally, MGO trapping mechanism exploration by UHPLC-MSn showed that the positions 2 and 4 of the A ring of stilbene were major active sites for trapping MGO to form both mono- and di-MGO adducts, however, the glucosylation of the hydroxyl group would significantly decrease the trapping efficiency. Collectively, the current work provides a very promising method for rapid discovery of natural MGO scavengers directly from complex matrices such as herbal medicines with huge resources. (c) 2013 Elsevier B.V. All rights reserved.