Discovery and Bioinspired Synthesis of Salpratone A.

Salpratone A (1), a novel abietane diterpenoid containing a unique cis-fused A/B ring, was isolated from Salvia prattii. Bioactivity studies showed that 1 has potent activity in inhibiting platelet aggregation induced by multiple agonists as well as antithrombotic efficacy in the FeCl3-induced rat in vivo thrombosis model. Furthermore, a bioinspired synthesis of 1 from the abundant natural product ferruginol was achieved in 6 steps with a 22% overall yield. The key steps include a stereoselective allyl oxidation and a subsequent regioselective Meinwald rearrangement.

11,12-seco-Abietane-type diterpene lactones with potential antiplatelet activity from Salvia prattii.

Eleven new abietane-type diterpene lactones, salpratlactones D-N (1-11), including five 11,12-seco-11-nor-abietane diterpenes (1-5), four 11,12-seco-abietane diterpenes (6-9), two 20(10 â†’ 5)-abeo-4,5;11,12-bis-seco-abietane diterpenes (10-11), and two known analogues (12-13), were characterized from Salvia prattii. Notably, compounds 1-3 were characterized by a unique linear 6/6/6 tricyclic skeleton. The structures were established by spectroscopic data interpretation, calculated NMR-DP4+ and electronic circular dichroism analysis, as well as single-crystal X-ray diffraction. A bioactivity study showed that 1, 2, 5, 11, and 12 can potently inhibit platelet aggregation induced by arachidonic acid (AA), with IC50 values of 5.66-16.10 µg/ml, stronger than aspirin. In addition, the lactate dehydrogenase assay showed that they had no effect on platelet integrity. Structurally, the same 1,2-benzopyrone fragments of 1, 2, and 5 should be the important pharmacophore for antiplatelet activity.

[Diagnostic and Prognostic Value of 18F-FDG PET/CT in Bone Marrow Infiltration of Newly Diagnosed Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To explore the diagnostic value of 18F-FDG PET/CT in bone marrow infiltration (BMI) of newly diagnosed diffuse large B-cell lymphoma (DLBCL), compared with the results of bone marrow biopsy (BMB) and investigate whether the BMI diagnosed by 18F-FDG PET/CT and other factors have independent prognostic values. METHODS: Ninety-four newly diagnosed DLBCL patients who underwent PET/CT in Clinical Medical College of Shanghai General Hospital of Nanjing Medical University were included. BMB was performed within 2 weeks before or after PET/CT, and standardized treatment was performed after PET/CT. The manifestations of bone marrow (BM) FDG uptake were recorded. The diagnostic criteria of BMI were BMB positive or focal BM FDG uptake confirmed by imaging follow-up. The relationship between clinical features and BM FDG uptake and the values of PET/CT and BMB in the diagnosis of BMI was analyzed. The progression-free survival (PFS) was analyzed by Kaplan-Meier survival curves, log-rank test was used to compare PFS rate, and Cox regression model was used to analyze the independent risk factors affecting PFS. RESULTS: Among 94 DLBCL patients, 34 patients showed focal BM uptake (fPET), 7 patients showed super BM uptake (sBMU), 11 patients showed diffuse homogenous uptake higher than liver (dPET), and the other 42 patients had normal BM uptake (nPET) (lower than liver). BMB positive was found in all sBMU patients, in 20.6%(7/34) of fPET patients, and in 27.3% (3/11) of dPET patients. All nPET patients had negative BMB results. dPET patients were associated with lower hemoglobin level and leukocyte count compared with nPET group (P < 0.001, P =0.026). Compared with fPET patients, sBMU patients were more likely to have B symptoms and elevated lactate dehydrogenase (LDH). A total of 44 patients were diagnosed BMI, including 17 cases with BMB+. The sensitivity and specificity of BMB in the diagnosis of BMI was 38.6% (17/44) and 100% (50/50), respectively. Using fPET and sBMU as criteria of PET BMI, the diagnostic sensitivity and specificity of PET/CT was 93.2% (41/44) and 100% (50/50), respectively. Kaplan-Meier analysis showed that there was no significant difference in 2-year PFS rate between nPET and dPET patients (P >0.05), while sBMU patients had lower 2-year PFS rate compared with fPET patients (P < 0.001). Multivariate analysis showed that higher Ann Arbor stage (HR=9.010, P =0.04) and sBMU (HR=3.964, P =0.002) were independent risk factors affecting PFS. CONCLUSIONS: Increased BM FDG uptake of DLBCL can be manifested as dPET, fPET and sBMU. fPET and sBMU can replace BMB to diagnose BMI. Although dPET cannot completely exclude the possibility of BMI, it does not affect the prognosis, so it can be diagnosed as PET BMI negative. sBMU is an independent prognostic risk factor.

Tax1 banding protein 1 exacerbates heart failure in mice by activating ITCH-P73-BNIP3-mediated cardiomyocyte apoptosis.

Tax1 banding protein 1 (Tax1bp1) was originally identified as an NF-κB regulatory protein that participated in inflammatory, antiviral and innate immune processes. Tax1bp1 also functions as an autophagy receptor that plays a role in autophagy. Our previous study shows that Tax1bp1 protects against cardiomyopathy in STZ-induced diabetic mice. In this study we investigated the role of Tax1bp1 in heart failure. Pressure overload-induced heart failure model was established in mice by aortic banding (AB) surgery, and angiotensin II (Ang II)-induced heart failure model was established by infusion of Ang II through osmotic minipump for 4 weeks. We showed that the expression levels of Tax1bp1 in the heart were markedly increased 2 and 4 weeks after AB surgery. Knockdown of Tax1bp1 in mouse hearts significantly ameliorated both AB- and Ang II infusion-induced heart failure parameters. On the contrary, AB-induced heart failure was aggravated in cardiac-specific Tax1bp1 transgenic mice. Similar results were observed in neonatal rat cardiomyocytes (NRCMs) under Ang II insult. We demonstrated that the pro-heart failure effect of Tax1bp1 resulted from its interaction with the E3 ligase ITCH to promote the transcription factor P73 ubiquitination and degradation, causing enhanced BCL2 interacting protein 3 (BNIP3)-mediated cardiomyocyte apoptosis. Knockdown ITCH or BNIP3 in NRCMs significantly reduced Ang II-induced apoptosis in vitro. Similarly, BNIP3 knockdown attenuated heart failure in cardiac-specific Tax1bp1 transgenic mice. In the left ventricles of heart failure patients, Tax1bp1 expression level was significantly increased; Tax1bp1 gene expression was negatively correlated with left ventricular ejection fraction in heart failure patients. Collectively, the Tax1bp1 increase in heart failure enhances ITCH-P73-BNIP3-mediated cardiomyocyte apoptosis and induced cardiac injury. Tax1bp1 may serve as a potent therapeutic target for the treatment of heart failure.• Cardiac Tax1bp1 transgene mice were more vulnerable to cardiac dysfunction under stress.• Cardiac Tax1bp1 transgene mice were more vulnerable to cardiac dysfunction under stress.• Knockout of Tax1bp1 in mouse hearts ameliorated heart failure induced by pressure overload.• Tax1bp1 interacts with the E3 ligase Itch to promote P73 ubiquitination and degradation, causing enhanced BNIP3-mediated apoptosis.• Tax1bp1 may become a target of new therapeutic methods for treating heart failure.

Indirect influence in social networks as an induced percolation phenomenon.

Percolation theory has been widely used to study phase transitions in network systems. It has also successfully explained various macroscopic spreading phenomena across different fields. Yet, the theoretical frameworks have been focusing on direct interactions among nodes, while recent empirical observations have shown that indirect interactions are common in many network systems like social and ecological networks, among others. By investigating the detailed mechanism of both direct and indirect influence on scientific collaboration networks, here we show that indirect influence can play the dominant role in behavioral influence. To address the lack of theoretical understanding of such indirect influence on the macroscopic behavior of the system, we propose a percolation mechanism of indirect interactions called induced percolation. Surprisingly, our model exhibits a unique anisotropy property. Specifically, directed networks show first-order abrupt transitions as opposed to the second-order continuous transition in the same network structure but with undirected links. A mix of directed and undirected links leads to rich hybrid phase transitions. Furthermore, a unique feature of the nonmonotonic pattern is observed in network connectivities near the critical point. We also present an analytical framework to characterize the proposed induced percolation, paving the way to further understanding network dynamics with indirect interactions.

[Prognostic Value of Interim 18F-FDG PET/CT in Extranodal NK/T-Cell Lymphoma, Nasal Type].

OBJECTIVE: To explore the value of interim 18F-FDG PET/CT in the prognosis of patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL). METHODS: Twenty-one patients with ENKTL who were pathologically diagnosed at Shanghai General Hospital of Nanjing Medical University (Shanghai General Hospital) from January 2015 to December 2018 were retrospectively collected, and 18F-FDG PET/CT imaging was performed before and during treatment (3 weeks after 2-4 chemotherapy courses or 6 weeks after radiotherapy). The complete clinical data of the patients were followed up. The progression-free survival (PFS) and overall survival (OS) were analyzed by the Korean prognostic index (KPI), Deauville score (DS) and the maximum standard uptake reduction rate (ΔSUVmax). The independent risk factors affecting survival were evaluated by COX regression. RESULTS: After treatment, 11 patients had complete remission (CR), 3 had partial remission (PR), 1 had stable disease (SD), and 6 had disease progression (PD). The CR patients' △SUVmax was significantly higher than non-CR patients ï¼»(66.07±22.33)% vs (36.87±23.28)%, t=2.927, P=0.009ï¼½. Calculated from the receiver operating curve (ROC), the optimal cut-off point of ΔSUVmax was 51.45%. The median follow-up time was 32 months. Kaplan-Meier survival analysis showed that KPI, DS and ΔSUVmax had significance in predicting PFS and OS (P<0.05). COX regression analysis showed that DS was an independent risk factor affecting PFS (P<0.05), and KPI and ΔSUVmax were independent risk factors affecting OS (P<0.05). CONCLUSION: Interim 18F-FDG PET/CT imaging has some value in the prognostic evaluation of patients with ENKTL.

Clinical characteristics and outcomes in coronavirus disease 2019 (COVID-19) patients with and without hypertension: a retrospective study.

The novel coronavirus disease (COVID-19) has spread all over the world in a short time. Information about the differences between COVID-19 patients with and without hypertension is limited. To explore the characteristics and outcomes differences between COVID-19 patients with and without hypertension, the medical records and cardiac biomarkers of 414 patients were analyzed. A total of 149 patients had a history of hypertension, while 265 patients did not have hypertension, and the groups were compared based on their clinical characteristics and laboratory findings as well as the hazard risk for composite outcomes, including intensive care unit (ICU) admission, mechanical ventilation, or death. The results are as follows. On admission, 22.1% of patients in hypertension group had elevated high sensitivity troponin I (hs-TNI > 26 pg/mL), which was higher than the proportion in the nonhypertension group (6.4%). Median NT-proBNP levels in patients with hypertension (141.9 pg/mL) were higher than those in patients without hypertension (77.3 pg/mL). Patients in the hypertension group had a higher risk for in-hospital death [HR: 2.57, 95% CI (1.46~4.51)]. However, the impact of hypertension on the prognosis was not significant after adjusting for age and sex. Multivariate Cox hazard regression confirmed that NT-proBNP levels in the highest tertile (upper 75 % of patients with hypertension) was an independent risk factor for in-hospital death in all COVID-19 patients. Taken together, hypertension per se had a modest impact on the prognosis in COVID-19 patients. In COVID-19 patients with and without hypertension, NT-proBNP may be a better predictor of prognosis than hs-TNI.

Usnic acid derivatives as tau-aggregation and neuroinflammation inhibitors.

Accumulation of tau protein aggregation plays a crucial role in neurodegenerative diseases, such as Alzheimer's disease (AD). Uncontrollable neuroinflammation and tau pathology form a vicious circle that further aggravates AD progression. Herein, we reported the synthesis of usnic acid derivatives and evaluation of their inhibitory activities against tau-aggregation and neuroinflammation. The inhibitory activity of the derivatives against the self-fibrillation of the hexapeptide AcPHF6 was initially screened by ThT fluorescence assay. Using circular dichroism and transmission electron microscopy, compound 30 showed the most potent inhibitory activity against AcPHF6 self-fibrillation. Compound 30 was further confirmed to inhibit the aggregation of full-length 2N4R tau protein by a heparin-induced mechanism. In addition, we investigated the anti-inflammatory activity of compound 30, and showed that compared with sodium usnate, it reduced NO release in LPS-stimulated mouse microglia BV2 cells. More importantly, 30 showed significant protective effects against okadaic acid-induced memory impairment in rats. Thus, 30 was a novel tau-aggregation and neuroinflammation inhibitor that represented a potential therapeutic candidate for AD.

Clinical outcomes and prognostic factors in patients with no less than three distant organ system metastases from differentiated thyroid carcinoma.

OBJECTIVES: For patients with differentiated thyroid carcinoma (DTC), distant metastases are commonly identified in the lungs and bones. However, they are relatively rare in other distant organs, such as the liver, kidneys, or brain. The aim of the current study was to describe the clinical outcomes and evaluate the prognostic factors of patients with no less than three different distant organ system metastases from DTC. METHODS: This study retrospectively identified 717 patients diagnosed with DTC with distant metastases between January 2005 and December 2017. Patient response to radioactive iodine (RAI) therapy was monitored by changes in serum thyroglobulin levels and imaging changes. Five-year and 10-year overall survival (OS) rates were calculated by the Kaplan-Meier methods and Cox proportional hazards. RESULTS: Among the 717 participants, 37 (5.16%) patients had no less than three different distant organ system metastases from DTC. Five-year and 10-year OS were 45.9% and 37.8% in patients with three or more distant organ system metastases while 74.5% and 64.9% in individuals with one or two distant organ system metastases, respectively. RAI avidity and RAIR-DTC were main independent prognostic factors influencing the clinical outcomes for both groups of patients. The presence of 3 or more different distant organ system metastases was the only independent prognostic factors for 10-year OS by multivariate analysis. CONCLUSIONS: Patients with no less than three distant organ system metastases from DTC had poor prognosis. RAI avidity and RAIR-DTC were main factors influencing overall survival for patients with distant metastases from DTC in both groups.

A hemicyanine derivative for near-infrared imaging of ß-amyloid plaques in Alzheimer's disease.

The formation of amyloid-ß (Aß) plaques in the brain is one of the main pathological features of Alzheimer's disease (AD). The imaging probes, capable of detecting Aß deposition, are important tools for early diagnosis of AD. In this article, we designed, synthesized and evaluated a cyanine-based near-infrared fluorescence (NIRF) probe ZT-1 for the detection of Aß deposits in the brain. The probe had excellent fluorescent properties with an emission maximum above 720 nm upon binding to Aß aggregates with affinity of 445.0 nM (Kd). Furthermore, ZT-1 exhibited good biostability, photostability, and binding selectivity toward Aß1-42 aggregates by in vitro fluorescence staining experiments. In vivo NIRF imaging result also revealed that our probe could efficiently differentiate transgenic and wild-type mice. All these studies indicated that ZT-1 is a promising fluorescent probe for Aß plaques in the AD brains.

Synthesis of trisaccharide repeating unit of fucosylated chondroitin sulfate.

We described the chemical synthesis of a sulfated trisaccharide repeating unit of fucosylated chondroitin sulfate (FCS), which has significant anticoagulant activity. Well-functionalized monosaccharides were readily prepared, and highly efficient glycosylations using a common activator (NIS/TfOH) were also presented. The synthesized trisaccharide 4 could be used to extend oligosaccharide sequences.

Controllability and maximum matchings of complex networks.

Previously, the controllability problem of a linear time-invariant dynamical system was mapped to the maximum matching (MM) problem on the bipartite representation of the underlying directed graph, and the sizes of MMs on random bipartite graphs were calculated analytically with the cavity method at zero temperature limit. Here we present an alternative theory to estimate MM sizes based on the core percolation theory and the perfect matching of cores. Our theory is much more simplified and easily interpreted, and can estimate MM sizes on random graphs with or without symmetry between out- and in-degree distributions. Our result helps to illuminate the fundamental connection between the controllability problem and the underlying structure of complex systems.

Anti-metastatic effect of 131I-labeled Buthus martensii Karsch chlorotoxin in gliomas.

The present study investigated the underlying molecular mechanism by which Buthus martensii Karsch chlorotoxin (BmK CT) inhibits the invasion and metastasis of glioma cells and the possibility of 131I­labeled BmK CT (131I­BmK CT) as a novel targeted agent for the treatment of glioma. The impact of BmK CT with and without 131I radiolabeling on the invasion and metastasis of glioma cells in vitro was studied. Cell viability was assessed using Cell Counting Kit­8 and plate colony formation assays in order to confirm the cytotoxicity of BmK CT and 131I­BmK CT at different concentrations. Transwell invasion and wound­healing assays were conducted in order to investigate the inhibitory effects BmK CT and 131I­BmK CT on cell migration and invasion. Furthermore, western blotting, ELISA immunofluorescence and a gelatin zymography assay were performed to evaluate changes in the protein expression levels of glioma cells following treatment with BmK CT or 131I­BmK CT. The results indicated that BmK CT inhibits the invasion and metastasis of glioma cells via regulation of tissue inhibitor of metalloproteinase­2 expression and that 131I­BmK CT has the potential to be a novel targeted therapeutic drug for glioma.

A new abietane diterpenoid from the roots of Tripterygium regelii.

A new abietane diterpenoid, tripterregeline A (1), together with six known diterpenoids (2-7), were isolated from the roots of Tripterygium regelii. The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparison with data reported in the literature. All isolated compounds were evaluated for their cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Compounds 1-7 showed significant inhibitory effects against various human cancer cell lines with IC50 values ranging from 0.58 to 21.06 µM.

Association analyses identify two susceptibility loci 5q31 and 5q22.1 for atopic dermatitis in Chinese Han population.

BACKGROUND: Atopic dermatitis (AD) and other atopic diseases often share some common genetic and pathogenic bases. Recent genome-wide association studies (GWAS) have identified several loci associated with atopic diseases, allergic sensitization and asthma in different populations. The aim of this study was to investigate whether these susceptibility loci were related to AD in Chinese Han population. METHODS: Eight single nucleotide polymorphisms (SNPs) from recent atopic diseases and allergic sensitization GWAS were genotyped in 3,013 AD patients and 5,483 healthy controls in Chinese Han population using Sequenom MassArray system. Data was analyzed with PLINK 1.07 software. RESULTS: We identified that the susceptibility loci at 5q31 (RAD50/IL13, rs2158177, P = 1.08×10-3, OR = 1.15) and 5q22.1 (TSLP, rs1837253, P = 2.66×10-3, OR = 0.91) were significantly associated with AD. Genotype-based association testing revealed that the dominant model provided the best fit for both rs2158177 (P = 3.75×10-3) and rs1837253 (P = 5.30×10-3). Pathway analysis conformed that both loci were associated with the JAK-STAT signaling pathway. CONCLUSIONS: We identified two susceptibility loci 5q31 and 5q22.1 for AD that might bear candidate genes conferring susceptibility to AD.

Anti-Inflammatory Effects of Schisandrin B on LPS-Stimulated BV2 Microglia via Activating PPAR-γ.

Schisandrin B (Sch B), a dibenzocyclooctadiene lignan isolated from Schisandra chinensis (Turcz.) Baill, has been shown to have anti-inflammatory effect. The purpose of this study was to evaluate the effect of Sch B on LPS-induced inflammation in microglia and to investigate the molecular targets of Sch B. BV2 cells were stimulated by LPS in the presence or absence of Sch B. The results showed that the levels of TNF-α, IL-6, IL-1ß, and PGE2 upregulated by LPS were significantly suppressed by Sch B. LPS-induced NF-κB activation was also inhibited by Sch B. Furthermore, Sch B was found to upregulate the expression of PPAR-γ in a concentration-dependent manner. In addition, the inhibition of Sch B on TNF-α, IL-6, IL-1ß, and PGE2 production were reversed by PPAR-γ antagonist GW9662. In conclusion, these results suggested that Sch B inhibited LPS-induced inflammatory response by activating PPAR-γ.

[(18)F-FDG PET/CT for extranodular natural killer/T-cell lymphoma nasal type: imaging findings and clinical value].

OBJECTIVE: To explore the value of (18)F-FDG PET/CT in the diagnosis and treatment evaluation in patients with pretreatment or recurrent extranodular natural killer/T-cell lymphoma nasal type (ENTCL). METHODS: (18)F-FDG PET/CT images and clinical records of 35 cases (67 scans) of pathologically confirmed ENTCL treated in our hospital within the last 9 years were analyzed. The imaging characteristics of the upper aerodigestive tract (UAT) and the non-aerodigestive tract (NUAT) lesions were analyzed. Lesion distribution, clinical stages, SUVmax and patient survival data were compared between pretreatment and recurrent cases. RESULTS: s All the ENTCL lesions were hypermetabolic. The UAT lesions involved mainly the nasal cavity and pharynx, while the NUAT lesions may involve the lymph nodes and all the organs. UAT lesions were more common in pretreatment cases while NUAT lesions tended to increase in recurrent cases. The SUVmax of pretreatment and recurrent lesions were 10.4∓4.4 and 9.6∓5.2, and showed no significant difference among patients with different lesion distribution patterns, clinical stages, or treatment history. The tumor remission rate evaluated by PET/CT were higher in cases with an initial diagnosis than in those with recurrence [(89.5% (17/19) vs 33.3% (5/15), P<0.005)]. Cox regression analysis revealed no significant differences in the survival rates among patients with different treatment history, clinical stages, lesion distribution patterns, or SUVmax levels (P>0.05). CONCLUSION: (18)F-FDG PET/CT can sensitively detect the pretreatment or recurrent lesions in ENTCL patients and helps in accurate tumor staging and curative effect evaluation.

Association of the chromosome 11p13.5 variant and atopic dermatitis with a family history of atopy in the Chinese Han population.

BACKGROUND: Recent genome-wide association studies (GWAS) and a meta-analysis of GWAS for atopic dermatitis (AD) have identified some AD genetic loci in European and Japanese populations. OBJECTIVE: To investigate whether some novel susceptibility loci are associated with AD in the Chinese Han population. METHODS: We first selected eight novel susceptibility loci to replicate in 2,205 AD patients and 2,116 healthy controls using the Sequenom platform. Data were analyzed with PLINK 1.07 software. RESULTS: We found that rs12634229 (3q13.2), rs7927894 (11p13.5) and rs878860 (11p15.4) showed a slight association with AD (P = 0.012, P = 0.033, P = 0.020, respectively); rs6780220 (3p21.33) was preferentially related to AD with keratosis pilaris, but did not reach the threshold of significance after correction. The frequency of rs7927894 allele T was significantly different between AD patients with a positive and negative family history of atopy. CONCLUSION: The loci rs7927894 (11p13.5) are related to AD with a positive family history of atopy in Chinese Han population, providing novel insight into the genetic pathogenesis of AD.

[Investigation of psychological state and its influencing factors in children with epilepsy].

OBJECTIVE: To evaluate the psychological state of children with epilepsy and analyze its influencing factors. METHODS: The Mental Health Scale for Child and Adolescent was used to survey 113 children with epilepsy and 114 normal children to evaluate and compare their psychological state. Questionnaires were used to investigate the general status of all subjects and the disease condition and treatment of children with epilepsy. The possible influencing factors for the psychological state of children with epilepsy were analyzed. RESULTS: The mental health status of children with epilepsy was poorer than that of normal children in cognition, thinking, emotion, will-behavior, and personality traits (P<0.05). Multivariate logistic regression analysis showed that family education, family relations, seizure frequency, seizure duration, EEG epileptiform discharges in the last six months, and number of types of antiepileptic drugs were correlated with the psychological state of children with epilepsy. CONCLUSIONS: There is a wider range of psychological health problems in children with epilepsy than in normal children. Poor family living environment, poor seizure control, and use of many antiepileptic drugs are the risk factors affecting the psychological state of children with epilepsy. Improving family living environment, controlling seizures, and monotherapy help to improve the psychological state of children with epilepsy.

Lignans and aromatic glycosides from Piper wallichii and their antithrombotic activities.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper wallichii (Miq.) Hand.-Mazz. is a medicinal plant used widely for the treatment of rheumatoid arthritis, inflammatory diseases, cerebral infarction and angina in China. Previous study showed that lignans and neolignans from Piper spp. had potential inhibitory activities on platelet aggregation. In the present study, we investigated the chemical constituents of Piper wallichii and their antithrombotic activities, to support its traditional uses. MATERIALS AND METHODS: The methanolic extract of the air-dried stems of Piper wallichii was separated and purified using various chromatographic methods, including semi-preparative HPLC. The chemical structures of the isolates were determined by detailed spectroscopic analysis, and acidic hydrolysis in case of the new glycoside 2. Determination of absolute configurations of the new compound 1 was facilitated by calculated electronic circular dichroism using time-dependent density-functional theory. All compounds were tested for their inhibitory effects on platelet aggregation induced by platelet activating factor (PAF) in rabbits׳ blood model, from which the active ones were further evaluated the in vivo antithrombotic activity in zebrafish model. RESULTS: A new neolignan, piperwalliol A (1), and four new aromatic glycosides, piperwalliosides A-D (2-5) were isolated from the stems of Piper wallichii, along with 25 known compounds, including 13 lignans, six aromatic glycosides, two phenylpropyl aldehydes, and four biphenyls. Five known compounds (6-10) showed in vitro antiplatelet aggregation activities. Among them, (-)-syringaresinol (6) was the most active compound with an IC50 value of 0.52 mM. It is noted that in zebrafish model, the known lignan 6 showed good in vivo antithrombotic effect with a value of 37% at a concentration of 30 µM, compared with the positive control aspirin with the inhibitory value of 74% at a concentration of 125µM. CONCLUSION: This study demonstrated that lignans, phenylpropanoid and biphenyl found in Piper wallichii may be responsible for antithrombotic effect of the titled plant.