Two new Nb-oxide indole alkaloids with ß-hematin inhibitory activity from the stems and leaves of Rauvolfia dichotoma.

Rauvolfia dichotoma, a shrub of Apocynaceae, was collected from the Islands of SAO Tome and Principe and cultivated locally for medicinal purpose. Phytochemical investigation of 95% ethanol extract from the stems and leaves of R. dichotoma led to the isolation of two new Nb-oxide indole alkaloids, namely Nb-oxide-mitoridine (1) and Nb-oxide-raucaffricine (2), together with two known alkaloids (3-4) and eleven known lignans (5-15). Their chemical structures were elucidated by extensive NMR and HR-ESI-MS data analysis. All compounds (except 13) were tested for their ß-hematin inhibitory activity. Compounds 2, 4, 14, and 15 showed certain inhibitory activity, indicating that they may have an antimalarial effect.

Exploring the mechanism of Si-Miao-Yong-An decoction on heart failure based on molecular docking and network pharmacology.

The SwissTargetPrediction was employed to predict the potential drug targets of the active component of Si-Miao-Yong-An decoction (SMYAD). The therapeutic targets for HF were searched in the Genecard database, and Cytoscape3.9.1 software was used to construct the "drug-component-target-disease network" diagram. In addition, the String platform was used to construct Protein-Protein Interaction (PPI) network, and the DAVID database was used for GO and KEGG analysis. AutoDockTools-1.5.6 software was used for molecular docking verification. Network pharmacology studies have shown that AKT 1, ALB, and CASP 3 are the key targets of action of SMYAD against heart failure. The active compounds are quercetin and kaempferol.

[Associations Between Insulin Resistance Indexes and Hyperuricemia in Hypertensive Population].

Objective To explore the relationship between insulin resistance (IR) indexes and hyperuricemia (HUA) among the people with hypertension. Methods From July to August in 2018,hypertension screening was carried out in Wuyuan county,Jiangxi province,and the data were collected through questionnaire survey,physical measurement,and biochemical test.Logistic regression was performed to analyze the relationship between HUA and IR indexes including metabolic score for IR (METS-IR),triglyceride-glucose (TyG) index,TyG-body mass index (BMI),TyG-waist circumference (WC),visceral adiposity index (VAI),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and lipid accumulation product (LAP).The penalty spline method was used for the curve fitting between IR indexes and HUA.The area under the receiver operating characteristic curve (AUC) was employed to reveal the correlation between each index and HUA. Results The 14 220 hypertension patients included 6 713 males and 7 507 females,with the average age of (63.8±9.4) years old,the average uric acid level of (418.9±120.6) mmol/L,and the HUA detection rate of 44.4%.The HUA group had higher proportions of males,current drinking,current smoking,diabetes,and using antihypertensive drugs,older age,higher diastolic blood pressure,WC,BMI,homocysteine,total cholesterol,TG,low-density lipoprotein cholesterol,blood urea nitrogen,creatinine,aspartate aminotransferase,alanine aminotransferase,total protein,albumin,total bilirubin,direct bilirubin, METS-IR, TyG, TyG-BMI, TyG-WC, VAI, TG/HDL-C, and LAP, and lower systolic blood pressure and HDL-C than the normal uric acid group (all P<0.05).Multivariate Logistic regression showed that METS-IR (OR=1.049,95%CI=1.038-1.060, P<0.001), TyG (OR=1.639,95%CI=1.496-1.797, P<0.001), TyG-BMI (OR=1.008,95%CI=1.006-1.010, P<0.001), TyG-WC (OR=1.003,95%CI=1.002-1.004, P<0.001), lnVAI (OR=1.850, 95%CI=1.735-1.973, P<0.001), ln(TG/HDL-C) (OR=1.862,95%CI=1.692-2.048, P<0.001),and lnLAP (OR=1.503,95%CI=1.401-1.613,P<0.001) were associated with the risk of HUA.Curve fitting indicated that METS-IR,TyG,TYG-BMI,TYG-WC,lnVAI,ln(TG/HDL-C),and lnLAP were positively correlated with HUA (all P<0.001),and the AUC of TyG index was higher than that of other IR indexes (all P<0.05). Conclusion Increased IR indexes,especially TyG,were associated with the risk of HUA among people with hypertension.

[Predictive Effects of Different Insulin Resistance Indexes on Diabetes Risk in Hypertensive Population].

Objective To explore the roles of different insulin resistance indexes[triglyceride-glucose (TyG),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and metabolic score for insulin resistance (METS-IR)]and combinations of two indexes in predicting diabetes risk in hypertensive population. Methods The survey of hypertension was conducted for the residents in Wuyuan county,Jiangxi province from March to August in 2018.The basic information of hypertensive residents was collected by interview.Blood was drawn on an empty stomach in the morning and physical measurements were carried out.Logistic regression model was employed to analyze the relationship between different insulin resistance indexes and diabetes,and the area under the receiver operating characteristic curve was used for evaluating the predictive effects of each index on diabetes risk. Results A total of 14 222 hypertensive patients with an average age of (63.8±9.4) years old were included in this study,including 2616 diabetic patients.The diabetic hypertensive population had higher TyG (t=50.323,P<0.001),TG/HDL-C (Z=17.325,P<0.001),and METS-IR (t=28.839,P<0.001) than the non-diabetic hypertensive population.Multivariate analysis showed that each insulin resistance index was positively correlated with diabetes risk.The area under curve of each insulin index was in a descending order of TyG (0.770)> METS-IR (0.673)> TG/HDL-C (0.620).The difference in the area under curve between two indexes was statistically significant[TyG vs.TG/HDL-C (Z=42.325,P<0.001);TyG vs.METS-IR(Z=17.517,P<0.001);METS-IR vs.TG/HDL-C (Z=10.502,P<0.001)]. Conclusions Elevated insulin resistance indexes can increase the risk of diabetes.TyG and the combination of indexes outperform TG/HDL-C and METS-IR in the prediction of diabetes.

[Relationship of Cognitive Function With Menarche Age,Menopause Age, and Reproductive Period in Female Patients With Hypertension].

Objective To explore the relationship of menarche age,menopause age,and reproductive period with cognitive function in the female patients with hypertension.Methods Hypertension screening was carried out in Wuyuan county of Jiangxi province from July to August in 2018.Data were collected through a face-to-face questionnaire survey,physical measurement,and biochemical tests.The cognitive function was scored according to the mini-mental state examination(MMSE)scale.Multiple linear regression and Logistic regression were employed to analyze the effects of menarche age,menopause age,and reproductive period on cognitive function,and the penalized spline regression to fit the curves.Results A total of 4595 postmenopausal women with hypertension were included in the analysis,with the mean age of(65.1±8.4)years,mean menarche age of(16.6±2.2)years,mean menopause age of(48.2±5.0)years,mean reproductive period of(31.7±5.5)years,mean MMSE score of(19.0±6.3)points,and total cognitive impairment detection rate of 40.4%(1859/4595).The detection rates of cognitive impairment were 28.4%,39.1%,and 45.8% in the females with the menarche ages of <15,15-16,and ≥17 years,47.9%,39.7%,and 38.3% in the females with the menopausal ages of <45,45-49,and ≥50 years,and 56.0%,44.4%,40.6%,and 32.6% in the females with the reproductive periods of <25,25-29,30-34,and ≥35 years,respectively.Moreover,the detection rates of cognitive impairment among different age groups were statistically significant(all P<0.05).Compared with the group with the menarche age <15 years,the groups with the menarche ages of 15-16 years and ≥17 years showed increased detection rates of cognitive impairment(OR=1.45,95%CI=1.19-1.75,P<0.001;OR=1.65,95%CI=1.37-1.98,P<0.001).Compared with the group with the menopausal age <45 years,the groups with the menopausal ages of 45-49 years and ≥50 years showed decreased detection rates of cognitive impairment(OR=0.80,95%CI=0.66-0.95,P=0.013;OR=0.78,95%CI=0.65-0.93,P<0.001).Compared with the group with the reproductive period <25 years,the groups with the reproductive periods of 25-29,30-34,and ≥35 years showed decreased detection rates of cognitive impairment(OR=0.66,95%CI=0.52-0.84,P<0.001;OR=0.62,95%CI=0.50-0.76,P<0.001;OR=0.51,95%CI=0.41-0.63,P<0.001).Conclusion The detection rate of cognitive impairment had a positive correlation with menarche age and negative correlations with menopause age and reproductive period in the female patients with hypertension.

[Association Between Plasma Homocysteine Level and Hyperuricemia in Elderly Patients With Hypertension].

Objective To explore the association between plasma homocysteine (Hcy) level and hyper-uricemia (HUA) in the elderly patients with hypertension.Methods From March to August in 2018,9902 hypertensive patients ≥ 60 years were routinely tested for blood biochemical indicators in Wuyuan county,Jiangxi province.The patients were assigned into a HUA group and a normal uric acid group.Multivariate Logistic regression was adopted to analyze the relationship between Hcy level and the risk of HUA.Results Compared with the normal uric acid group,the HUA group showed increased incidence of hyperhomocysteinemia (99.9% vs.98.7%,P<0.001) and elevated Hcy level[16.8 (13.8-21.5) µmol/L vs.14.4 (12.3-17.7) µmol/L,P<0.001].The multivariate Logistic regression analysis showed that after adjusting for influencing factors,the risk of HUA in the patients with hyperhomocysteinemia was 2.92 times of that in the patients with a normal Hcy level.The threshold effect analysis showed that the Hcy level was positively correlated with the occurrence of HUA in the case of Hcy<20 µmol/L (OR=1.05,95%CI=1.04-1.07,P<0.001).In the case of Hcy ≥ 20 µmol/L,there was no correlation between Hcy level and HUA (OR=1.00,95%CI=0.99-1.00,P=0.055),and the likelihood ratio test showed statistically significant results (P<0.001).Conclusion The elderly with hypertension should pay attention to control the Hcy level,which will be helpful to prevent the occurrence of HUA.

[A new bibenzyl derivative from stems of Dendrobium officinale].

Eleven compounds were isolated from the 95% ethanol extract of the stems of Dendrobium officinale after water extraction by various modern chromatographic techniques, such as silica gel column chromatography(CC), octadecyl-silica(ODS) CC, Sephadex LH-20 CC, preparative thin layer chromatography(PTLC) and preparative high performance liquid chromatography(PHPLC). According to spectroscopic analyses(MS, 1D-NMR, 2D-NMR) combined with optical rotation data and calculated electronic circular dichroism(ECD), their structures were identified as dendrocandin Y(1), 4,4'-dihydroxybibenzyl(2), 3-hydroxy-4',5-dimethoxybibenzyl(3), 3,3'-dihydroxy-5-methoxybibenzyl(4), 3-hydroxy-3',4',5-trimethoxybibenzyl(5), crepidatin(6), alternariol(7), 4-hydroxy-3-methoxypropiophenone(8), 3-hydroxy-4,5-dimethoxypropiophenone(9), auriculatum A(10) and hyperalcohol(11). Among them, compound 1 was a new bibenzyl derivative; compounds 2 and 7-11 have not been previously reported from Dendrobium plants; compound 6 was reported from D.officinale for the first time. Compounds 3-6 exhibited potent antioxidant activity with IC_(50) values of 3.11-9.05 µmol·L~(-1) in ABTS radical scavenging assay. Compound 4 showed significant inhibitory effect on α-glucosidase, with IC_(50) value of 17.42 µmol·L~(-1), indicating that it boasted hypoglycemic activity.

[Heterocyclic compounds and phenolic glycosides from flowers of Dendrobium officinale].

Eight heterocyclic compounds and twelve phenolic glycosides were separated from the water extract of Dendrobium officinale flowers through chromatographic techniques, such as Diaion HP-20 macroporous adsorption resin column chromatography(CC), silica gel CC, ODS CC, Sephadex LH-20 CC, and preparative high performance liquid chromatography(PHPLC). According to the spectroscopic analyses(MS, ~1H-NMR, and ~(13)C-NMR) and optical rotation data, the compounds were identified as dendrofurfural A(1), 2'-deoxyadenosine(2), 4-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl] butanoic acid(3), 4-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl] butanoic acid(4), 1-(2-hydroxyethyl)-5-(methoxymethyl)-1H-pyrrole-2-carbaldehyde(5), 5-(methoxymethyl)-1H-pyrrole-2-carbaldehyde(6), methyl 5-(hydroxymethyl)-furan-2-carboxylate(7),(S)-5-hydroxymethyl-5H-furan-2-one(8), 2-methoxyphenyl-1-O-ß-D-glucopyranoside(9), arbutin(10), isotachioside(11), 2,6-dimethoxy-4-hydroxyphenol-1-O-ß-D-glucopyranoside(12), orcinol glucoside(13), tachioside(14), gastrodin(15), 4-O-ß-D-glucopyranosylvanillyl alcohol(16), 2,6-dimethoxy-4-hydroxymethylphenol-1-O-ß-D-glucopyranoside(17), icariside D_2(18), 4-formylphenyl-ß-D-glucopyranoside(19), and vanillin-4-O-ß-D-glucopyranoside(20). Among them, compound 1 is a new furfural benzyl alcohol condensate, with the skeleton first found in Dendrobium. Compounds 2-9, 11, 13, and 19 are reported from Dendrobium for the first time, and compounds 14 and 18 are reported for the first time from D. officinale. Compounds 11 and 14 showed moderate DPPH radical scavenging capacity, and compounds 11-14 demonstrated potent ABTS radical scavenging capacity, possessing antioxidant activity.

Potential Target Genes in the Development of Atrial Fibrillation: A Comprehensive Bioinformatics Analysis.

BACKGROUND Atrial fibrillation (AF) is the most prevalent arrhythmia worldwide. Although it is not life-threatening, the accompanying rapid and irregular ventricular rate can lead to hemodynamic deterioration and obvious symptoms, especially the risk of cerebrovascular embolism. Our study aimed to identify novel and promising genes that could explain the underlying mechanism of AF development. MATERIAL AND METHODS Expression profiles GSE41177, GSE79768, and GSE14975 were acquired from the Gene Expression Omnibus Database. R software was used for identifying differentially expressed genes (DEGs), and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were subsequently performed. A protein-protein interaction network was constructed in Cytoscape software. Next, a least absolute shrinkage and selection operator (LASSO) model was constructed and receiver-operating characteristic curve analysis was conducted to assess the specificity and sensitivity of the key genes. RESULTS We obtained 204 DEGs from the datasets. The DEGs were mostly involved in immune response and cell communication. The primary pathways of the DEGs were related to the course or maintenance of autoimmune and chronic inflammatory diseases. The top 20 hub genes (high scores in cytoHubba) were selected in the PPI network. Finally, we identified 6 key genes (FCGR3B, CLEC10A, FPR2, IGSF6, S100A9, and S100A12) via the LASSO model. CONCLUSIONS We present 6 target genes that are potentially involved in the molecular mechanisms of AF development. In addition, these genes are likely to serve as potential therapeutic targets.

Saturation Effects of Plasma Homocysteine on Chronic Kidney Disease in Chinese Adults With H-type Hypertension: A Cross-sectional Study.

OBJECTIVE: Data on the association between homocysteine (Hcy) and the risk of chronic kidney disease (CKD) in patients with H-type hypertension were limited. This study aimed to examine the relation of Hcy with the prevalence of CKD and estimated glomerular filtration rate (eGFR) among Chinese adults with H-type hypertension. METHODS: A total of 12,873 Chinese adults with H-type hypertension aged 27-75 years were enrolled in the final analysis. Hcy concentrations were divided into 11 groups at 2 µmol/L interval. The outcome was CKD, defined as eGFR <60 mL/min/1.73 m2. RESULTS: The prevalence of CKD was 7.58%, and the mean Hcy was 17.58 ± 10.96 µmol/L. The smoothing curve indicated that with the increase of Hcy, the prevalence of CKD increases first and then flattens, eGFR decreases first and then flattens, which supports the L-shaped association of Hcy with the prevalence of CKD and eGFR. Moreover, we further found the inflection point of Hcy was 22 µmol/L. OR (95% CI) of risk of CKD was 1.31 (1.28, 1.35) on the left side of an inflection point and 1.00 (0.99, 1.01) on the right of an inflection point, ß (95% CI) of eGFR was -1.58 (-1.65, -1.50) on the left side of an inflection point and 0.00 (-0.03, 0.03) on the right of an inflection point, respectively. Similar results were found in various subgroups. CONCLUSIONS: Our study suggested saturation effects of Hcy on the prevalence of CKD and eGFR among Chinese patients with H-type hypertension.

Flavonoid glycosides from the fruits of Embelia ribes and their anti-oxidant and α-glucosidase inhibitory activities.

Three new flavonoid glycosides, embeliaflavosides A-C (1-3), together with eight known flavonoid glycosides (4-11), were isolated from the fruits of Embelia ribes. Their structures were established based on the analyses of spectroscopic data. Compounds 1-11 were evaluated for antioxidant and α-glucosidase inhibitory activities. The results revealed that compounds 1-11 owned significant ABTS radical scavenging activity with IC50 values of 2.52-9.78 µM, and DPPH scavenging activity with IC50 values of 7.56-26.47 µM, respectively. However, α-glucosidase inhibition assay indicated that all the isolates were inactive.[Formula: see text].

Two new dibenzyl derivatives from the stems of Dendrobium catenatum.

Two new dibenzyl derivatives, dendrocandins V-W (1-2), together with six known compounds (3-8), have been isolated from the dried stems of Dendrobium catenatum. Their structures were mainly elucidated on the basis of HRESIMS, one- and two-dimensional NMR techniques. The isolated compounds 5-8 were evaluated in vitro for their antioxidant and hypoglycemic activities. Compound 8 showed moderate potent DPPH scavenging activity with IC50 value of 34.45 ± 1.07 µM. And compounds 5, 7-8 exhibited significant ABTS radical scavenging activities with IC50 values of 10.03 ± 0.88, 5.32 ± 1.13 and 9.01 ± 1.39 µM. Compounds 6-7 showed potent α-glucosidase inhibitory activities with IC50 values of 36.05 ± 0.67 and 159.59 ± 0.86 µM.

Long noncoding RNA CDKN2B-AS1 interacts with transcription factor BCL11A to regulate progression of cerebral infarction through mediating MAP4K1 transcription.

The effective therapeutic approach of cerebral infarction is limited because of its underlying complexity. Recently, multiple long noncoding RNAs (lncRNAs) have been identified in the pathogenesis of cerebral infarction. Here, the current study aims to explore the interaction among lncRNA cyclin-dependent kinase inhibitor-2B-antisense RNA 1 (CDKN2B-AS1), transcription factor B-cell lymphoma/leukemia 11A (BCL11A), and MAPKK kinase kinase 1 (MAP4K1) and further investigate whether they affect cerebral infarction progression. The expression of CDKN2B-AS1, BCL11A, and MAP4K1 was altered in lymphocytes extracted from patients with cerebral infarction. In order to identify their roles in regulatory T (Treg) cells, the proliferation and apoptosis of the CD4+CD25+ Treg cells were examined, and levels of IL-4, IL-10, and TGF-ß were determined. Also, the RNA crosstalk among CDKN2B-AS1, BCL11A, and MAP4K1 was validated. Finally, we established a rat model of middle cerebral arterial occlusion to evaluate the neurologic impairment and cerebral infarction volume. The results revealed that lymphocytes in patients with cerebral infarction presented with the up-regulated expression of CDKN2B-AS1. Moreover, BCL11A could specifically bind to CDKN2B-AS1 and MAP4K1 promoter so as to inhibit MAP4K1. Moreover, it was observed that down-regulated CDKN2B-AS1 inhibited CD4+CD25+ Treg-cell proliferation, reduced levels of IL-4, IL-10, and TGF-ß and cerebral infarction volume, and elevated MAP4K1 expression. Collectively, our study provides evidence that CDKN2B-AS1 silencing could increase MAP4K1 expression to inhibit the CD4+CD25+ Treg-cell proliferation by reducing enrichment of transcription factor BCL11A, thereby protecting against cerebral infarction progression, highlighting a promising therapeutic strategy for treating cerebral infarction.-Lei, J.-J., Li, H.-Q., Mo, Z.-H., Liu, K.-J., Zhu, L.-J., Li, C.-Y., Chen, W.-L., Zhang, L. Long noncoding RNA CDKN2B-AS1 interacts with transcription factor BCL11A to regulate progression of cerebral infarction through mediating MAP4K1 transcription.

Baphicacanthcusines A-E, Bisindole Alkaloids from the Leaves of Baphicacanthus cusia (Nees) Bremek.

Four pairs of stereoisomeric indole alkaloids, (±)-baphicacanthcusines A-D (1-4), and one new indole alkaloid, baphicacanthcusine E (5), together with nine known compounds were identified from the leaves of Baphicacanthus cusia. (±)-1 and -2 possess an unprecedented skeleton in which two indole moieties are bridged by a phenylpropane unit. (±)-3 represents the first natural dispiro-oxazolidinone bisoxindoles. The absolute configurations in 1-5 were assigned based on quantum chemical calculations, including the calculated chemical shift with DP4plus analysis, the calculated optical rotation values, and the calculated electronic circular dichroism spectra. A plausible biosynthetic pathway for 1-5 was proposed. Compounds (±)-1, (-)-2, and 11 exhibited cytotoxicity against MCF-7 cells with IC50 values of 20.0-78.5 µM.

Matteuinterins A-C, three new glycosides from the rhizomes of Matteuccia intermedia.

Phytochemical investigation on the rhizomes of Matteuccia intermedia C.Chr. led to the isolation of three new compounds, named matteuinterins A-C (1-3), together with seven known compounds (4-10). Their structures were elucidated by extensive NMR analyses and chemical derivatization. Compounds 5-10 were evaluated for their anti-inflammatory activities on PGE2 release in LPS-stimulated RAW 264.7 murine macrophages. Compounds 5 and 10 exhibited inhibitory effect on PGE2 production in LPS-activated murine macrophages with IC50 values of 17.8 ± 1.5 and 30.3 ± 2.1 µM, respectively.[Formula: see text].

Two new alcohol glycosides from the roots of Paeonia intermedia C. A. Meyer.

Two new alcohol glycosides, 1-O-ß-d-glucopyranosyl-deoxypaeonisuffrone (1) and 9-O-ß-d-apiofuranoyl-(1→6)-ß-d-glucopyranosyl-xanthoarnol (2), together with eight known compounds (3-10), have been isolated from the dried roots of Paeonia intermedia C. A. Meyer. Their structures were mainly elucidated on the basis of ESIMS, one- and two-dimensional NMR techniques. Antibacterial activities of compounds 1-10 were evaluated, and compounds 9 and 10 showed antibacterial activities against Staphylococcus argenteus CMCC26003 and Escherichia coli CMCC44103. [Formula: see text].

Matteucens I-J, phenolics from the rhizomes of Matteuccia orientalis.

Two new phenolics, named matteucens I-J (1-2), were isolated from the 60% EtOH extract of the rhizomes of Matteuccia orientalis (HOOK.) TREV. Their structures were elucidated by means of extensive spectroscopic analysis (HRESIMS, NMR).

Antiviral phenolics from Antenoron filiforme var. neofiliforme.

Two new phenolics, 1,3-di-O-p-coumaroyl-2',6'-di-O-acetylsucrose (1) and quercetin 3-O-ß-D-apiofuranoyl-(1→2)-α-L-rhamnopyranoside (2), along with nine known compounds (3-11), were isolated from the whole plants of Antenoron filiforme var. neofiliforme. Their chemical structures were characterized on the basis of various spectroscopic techniques. This is the first report of the isolation of phenylpropanoid sucrose (1, 3-4) from the genus Antenoron. The bioassay results showed that compound 11 exhibited antiviral activity against the Coxsackie virus B3 (CVB3).

C-glycosides from the stems of Calophyllum membranaceum.

Three new C-glycosides, calophymembransides D-F (1-3), were isolated from the stems of Calophyllum membranaceum Gardn. et Champ.. The structures were assigned on the basis of spectroscopic data. RXRα transcriptional inhibition and α-glucosidase inhibition assays indicated that all the isolates were inactive.

Characterization of HJ-PI01 as a novel Pim-2 inhibitor that induces apoptosis and autophagic cell death in triple-negative human breast cancer.

AIM: Pim-2 is a short-lived serine/threonine kinase, which plays a key role in metastasis of breast cancer through persistent activation of STAT3. Although the crystal structure of Pim-2 has been reported, but thus far no specific Pim-2-targeted compounds have been reported. In this study, we identified a novel Pim-2 inhibitor, HJ-PI01, by in silico analysis and experimental validation. METHODS: The protein-protein interaction (PPI) network, chemical synthesis, molecular docking, and molecular dynamics (MD) simulations were used to design and discover the new Pim-2 inhibitor HJ-PI01. The anti-tumor effects of HJ-PI01 were evaluated in human breast MDA-MB-231, MDA-MB-468, MDA-MB-436, MCF-7 cells in vitro and in MDA-MB-231 xenograft mice, which were treated with HJ-PI01 (40 mg·kg(-1)·d(-1), ig) with or without lienal polypeptide (50 mg·kg(-1)·d(-1), ip) for 10 d. The apoptosis/autophage-inducing mechanisms of HJ-PI01 were elucidated using Western blots, immunoblots, flow cytometry, transmission electron microscopy and fluorescence microscopy. RESULTS: Based on the PrePPI network, the potential partners interacting with Pim-2 in regulating apoptosis (160 protein pairs) and autophagy (47 protein pairs) were identified. Based on the structural characteristics of Pim-2, a total of 15 compounds (HJ-PI01 to HJ-P015) were synthesized, which showed moderate or remarkable anti-proliferative potency in the human breast cancer cell lines tested. The most effective compound HJ-PI01 exerted a robust inhibition on MDA-MB-231 cells compared with chlorpromazine and the pan-Pim inhibitor PI003. Molecular dynamics (MD) simulation revealed that HJ-PI01 had a good binding score with Pim-2. Moreover, HJ-PI01 (300 nmol/L) induced death receptor-dependent and mitochondrial apoptosis as well as autophagic death in MDA-MB-231 cells. In MDA-MB-231 xenograft mice, administration of HJ-PI01 remarkably inhibited the tumor growth and induced tumor cell apoptosis in vivo. Co-administration of HJ-PI01 with lienal polypeptide could improve the anti-tumor activity of HJ-PI01 and reduce its toxicity. CONCLUSION: The newly synthesized compound, HJ-PI01, can induce death receptor/mitochondrial apoptosis and autophagic cell death by targeting Pim-2 in human breast cancer cells in vitro and in vivo.