OBJECTIVE: To investigate the effect of honokiol (HKL) for reducing doxorubicin (DOX)-induced cardiotoxicity in H9c2 cells and the underlying mechanisms. METHODS: H9c2 cells were divided into control group, DOX group, HKL + DOX group, and HKL+compound C+DOX group. After 24 h of corresponding treatment, the cells were examined for morphological changes and cell viability using CCK-8 assay. The mRNA expressions of the inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were detected by RT-PCR, and the protein levels of cleaved caspase-3, cytochrome c, NOD-like receptor pyrin domain containing 3 (NLRP3), caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC), p-AMPK and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) were detected with Western blotting; the expressions of NLRP3 and p-AMPK also detected with immunofluorescence staining. RESULTS: DOX treatment caused swelling and significantly lowered the viability of H9c2 cells (P < 0.05), resulting also in increased mRNA expressions of TNF-α, IL-6 and IL-1β (P < 0.05) and protein expressions of cleaved caspase-3, cytochrome c, NLRP3, caspase-1 and ASC (P < 0.05) but reduced protein levels of p-AMPK and Nrf2 (P < 0.05); fluorescence staining showed significantly increased NLRP3 expression and decreased expression of p-AMPK in DOX-treated cells (P < 0.05). All these changes in COX-treated cells were significantly alleviated by HKL treatment (P < 0.05). The application of compound C obviously mitigated the protective effects of HKL against DOX-induced cardiotoxicity in H9c2 cells. CONCLUSIONS HKL can alleviate DOX-induced cardiotoxicity by inhibiting pyroptosis in H9c2 cells, and this effect is mediated by activation of AMPK to regulate Nrf2 signaling.
AMP-Activated Protein Kinases/metabolism* ; Allyl Compounds ; Biphenyl Compounds ; Cardiotoxicity/pathology* ; Caspase 3/metabolism* ; Cytochromes c ; Doxorubicin/adverse effects* ; Humans ; Interleukin-6/metabolism* ; Myocytes, Cardiac ; NF-E2-Related Factor 2/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Phenols ; Pyroptosis ; RNA, Messenger/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

Objective: To investigate the protective effect of diallyl sulfide (DAS) , against benzene-induced genetic damage in rat. Methods: In September 2018, Sixty adult male adaptive feeding 5 days, were randomly divided into six groups according to their weight. Control groups, DAS control groups, benzene model groups, benzene+low DAS groups, benzene+middle DAS groups, benzene+High DAS group, 10 in each group. Rats in the DAS and DAS control group were orally given DAS at 40, 80, 160, 160 mg/kg, blank control and benzene model groups were given corn oil in the same volume. 2 h later, the rats in the benzene model and DAS treatment groups were given gavage administration of benzene (1.3 g/kg) mixed with corn oil (50%, V/V) , blank and DAS control groups were given corn oil in the same volume. Once a day, for 4 weeks. Samples were collected for subsequent testing. Results: Compared with the blank control group, In benzene treated rat, peripheral WBC count was reduced 65.06% (P=0.003) , lymphocyte ratiowas reduced (P=0.000) , micronucleus rate was increased (P=0.000) , Mean fluorescent intensity and relative fluorescence intensity of γH2AX in BMCs were increased 32.69%、32.64% (P=0.001、0.008) , Mean fluorescent intensity and relative fluorescence intensity of γH2AX in PBLs were increased 397.70%、396.26% (P=0.000、P=0.003) respectively. Compared with the benzene model group, the WBC count increased respectively (P=0.000、0.003、0.006) and the micronucleus rate decreased (P=0.000、0.000、0.000) in the DAS groups, Mean fluorescent intensity and relative fluorescence intensity ofγH2AX in BMCs were significantly reduced in the high DAS groups (P=0.000、0.000) , Mean fluorescent intensity and relative fluorescence intensity ofγH2AX in PBLs were significantly reduced in the low, middle, high DAS groups (P=0.000、0.000) . Conclusion: DAS can effectively suppress benzene induced genotoxic damage in rats.
4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid/analogs & derivatives* ; Allyl Compounds/pharmacology* ; Animals ; Benzene/toxicity* ; Corn Oil ; DNA Damage ; Male ; Rats ; Sulfides/pharmacology*

Allyl Compounds ; Animals ; Lung ; Male ; Paraquat/pharmacology* ; Poisons ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Sulfides

OBJECTIVES: To evaluate whether garlicin post-conditioning can attenuate myocardial ischemiareperfusion injury in a catheter-based porcine model of acute myocardial infarction (AMI) by affecting adhesion molecules integrin β1/CD29 and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31). METHODS: Twenty-two swine were devided into 3 groups: 6 in a sham-operation group, and 8 each in the model and garlicin groups. AMI porcine model was established in the model and garlicin groups. The distal parts of the left anterior descending coronary artery in the animals of the model and garlicin groups were occluded by dilated balloon for 2 h, followed by reperfusion for 3 h. Garlicin (1.88 mg/kg) was injected over a period of 1 h, beginning just before reperfusion, in the garlicin group. Real-time polymerase chain reaction, immunohistochemistry and Western blot were carried out to detect mRNA and protein expressions of CD29 and CD31 3 h after reperfusion. RESULTS: Hematoxylin-eosin staining showed a better myocardial structure in the garlicin group after reperfusion. Compared to the model group, garlicin inhibited both the mRNA and protein expression of CD29 and CD31 in reperfusion area and no-reflflow area (P<0.05 respectively). CONCLUSIONS Garlicin post-conditioning induced cardio-protection against myocardial ischemia-reperfusion injury in this catheter-based porcine model of AMI. The cardio-protective effect of garlicin is possibly owing to suppression of production of CD29 and CD31, by inhibition of the mRNA expression of CD29 and CD31.
Allyl Compounds ; pharmacology ; Animals ; Disease Models, Animal ; Disulfides ; pharmacology ; Integrin beta1 ; analysis ; genetics ; physiology ; Ischemic Postconditioning ; Male ; Myocardial Reperfusion Injury ; prevention & control ; Platelet Endothelial Cell Adhesion Molecule-1 ; analysis ; antagonists & inhibitors ; genetics ; RNA, Messenger ; analysis ; Swine

Objective To explore the effects of diallyl disulfide(DADS)-induced G2/M phase arrest on proliferation and apoptosis of ovarian cancer cells and its possible molecular mechanism.Methods DADS was used to incubate SK-OV-3 and OVCAR-3 cells,respectively,in different concentrations. Cell proliferation was measured by MTT assay and cell apoptosis rate was detected by flow cytometry assay. Xenograft model assay were performed to analyze the antitumor effect in vivo. Cell cycle phase distribution was detected by flow cytometry. Expressions of cell cycle G2/M phase as well as proliferation- and apoptosis-related proteins were measured by Western blotting.Results MTT assay showed that,after treatment of SK-OV-3(F=247.86,P=0.000)and OVCAR-3 cells(F=302.54,P=0.000)with different concentrations of DADS,the cell proliferation inhibition rate was significantly elevated with the increase of DADS concentrations in a concentration-dependent manner. The inhibition rate of SK-OV-3(F=335.12,P=0.000)and OVCAR-3 cells(F=347.43,P=0.000)at 24 h was significantly higher than that at 12 h and 48 h,showing a significant time-dependence manner. Flow cytometry showed that,after SK-OV-3 and OVCAR-3 cells were treated with different concentrations of DADS,the apoptosis rates increased significantly with the increase of DADS concentration in a concentration-dependent manner(P<0.05). The apoptotic rates of SK-OV-3 and OVCAR-3 cells treated with DADS at 24 h was significantly higher than that at 12 h and 48 h in a significant time-dependence manner(P<0.05). Compared with the blank treatment group,intraperitoneal injection of DADS solution significantly inhibited the xenograft volume of ovarian cancer cells in nude mice(F=548.23,P=0.000;F=311.84,P=0.000). After 30 mg/L of DADS was applied to SK-OV-3 and OVCAR-3 cells for 24 h,the percentage of cells in G2 phase of SK-OV-3 and OVCAR-3 cells increased significantly(F=375.11,P=0.000;F=256.48,P=0.000),compared with the blank cells. After 30 mg/L DADS was applied to SK-OV-3 and OVCAR-3 cells for 24 h,the expressions of p-Chk1(ser345)(F=108.89,P=0.013;F=97.58,P=0.018),p-CDC25C(ser216)(F=87.25,P=0.025;F=114.25,P=0.009),p-P53(ser15)(F=112.41,P=0.011;F=255.87,P=0.000),P21WAF1(F=246.38,P=0.001;F=141.36,P=0.005)and p-CDK1(Thr14/Tyr15)protein(F=298.12,P=0.000;F=233.15,P=0.000)were significantly increased,whereas the expressions of CDK1(F=308.24,P=0.000;F=257.55,P=0.000)and CyclinB1 protein(F=223.15,P=0.001;F=241.28,P=0.000)were significantly reduced.The expressions of proliferation and apoptosis-related proteins PCNA(F=77.36,P=0.031;F=157.28,P=0.001),Ki-67(F=205.64,P=0.007;F=315.22,P=0.000)and Survivin(F=122.13,P=0.013;F=188.24,P=0.000)were significantly decreased and Cleaved-caspase3 protein was significantly increased(F=86.46,P=0.023;F=99.11,P=0.009).Conclusion DADS can inhibit the proliferation of ovarian cancer cells and induce their apoptosis,which may be related to the activation of Chk1-CDC25C and P53-P21WAF1 signaling pathways in G2/M checkpoint,decreased kinase activity of CDK1,down-regulated expressions of CDK1 and CyclinB1 proteins,and ultimately cell cycle arrest at G2/M phase.
Allyl Compounds ; Animals ; Apoptosis ; Carcinoma, Ovarian Epithelial ; Cell Cycle Checkpoints ; Cell Line, Tumor ; Cell Proliferation ; Disulfides ; Female ; Humans ; Mice ; Mice, Nude

The biocompatible hydrogel was fabricated under suitable conditions with natural dextran and polyethylene glycol (PEG) as the reaction materials. The oligomer (Dex-AI) was firstly synthesized with dextran and allylisocyanate (AI). This Dex-AI was then reacted with poly (ethyleneglycoldiacrylate) (PEGDA) under the mass ratio of 4∶6 to get hydrogel (DP) with the maximum water absorption of 810%. This hydrogel was grafted onto the surface of medical catheter via diphenyl ketone treatment under ultraviolet (UV) initiator. The surface contact angle became lower from (97 ± 6.1)° to (25 ± 4.2)° after the catheter surface was grafted with hydrogel DP, which suggests that the catheter possesses super hydrophilicity with hydrogel grafting. The evaluation after they were implanted into ICR rats subcutaneously verified that this catheter had less serious inflammation and possessed better histocompatibility comparing with the untreated medical catheter. Therefore, it could be concluded that hydrogel grafting is a good technology for patients to reduce inflammation due to catheter implantation, esp. for the case of retention in body for a relative long time.
Allyl Compounds ; Animals ; Biocompatible Materials ; Catheters ; Dextrans ; Hydrogel, Polyethylene Glycol Dimethacrylate ; Hydrogels ; Hydrophobic and Hydrophilic Interactions ; Isocyanates ; Polyethylene Glycols ; Rats ; Water

OBJECTIVETo investigate the inducing effect of down-regulation of MCL-1 by diallyl disulfide(DADS) on the G/M arrest of human leukemia K562 cells and its mechanisms.

METHODSCCK-8 was used to detect the effect of DADS on proliferation of K562 cells, flow cytometry was employed to observe the effect of cycle arrest by DADS and RNAi silencing MCL-1 gene in K562 cells. The expressions of MCL-1, PCNA and CDK1 in K562 cells treated with DADS were detected by Western blot. The amphigamy of MCL-1 with PCNA and CDK1 was detected by Coimmunoprecipitation.

RESULTSCCK-8 detection showed that the inhibition rates of K562 cells treated with 15, 30, 60, 120, 240 µmol/L DADS were 32.48%, 59.34%, 66.42%, 77.06%, 81.05% respectively (P<0.05). Flow cytometry analysis revealed that the perecentages of G/M cells were increased to 18.6% and 34.4%, 17.5% and 28.5%, respectively at 24 and 48 h after treating K562 cells with 60 and 120 µmol/L DADS (P<0.05). And the perecentage of G/M cells of silencing MCL-1 was significantly increased (P<0.05). Silencing effects of MCL-1+DADS on the cells were enhanced more significantly as compared with DADS or MCL-1 alone (P<0.05). Western blot exhibited that DADS could markedly downregulate the expression of MCL-1, PCNA and CDK1(P<0.05). Coimmunoprecipitation revealed that MCL-1 bound with PCNA and CDK1, then forming heterodimers, which were downregulated respectively more significantly than that in the control group after treating K562 cells with DADS for 8 h (P<0.05).

CONCLUSIONDADS can inhibit the K562 cell proliferation and induce them arrest G/M through downregulation of MCL-1, then decreasing the expression of PCNA and CDK1 in hunan leukemia K562 cells. Moreover, silencing MCL-1 can enhance the effect of DADS.

Allyl Compounds ; Apoptosis ; Cell Line, Tumor ; Disulfides ; Down-Regulation ; G2 Phase Cell Cycle Checkpoints ; Humans ; K562 Cells ; Leukemia ; M Phase Cell Cycle Checkpoints ; Myeloid Cell Leukemia Sequence 1 Protein

OBJECTIVETo investigate the effect of diallyl disulfide (DADS) on invasion and metastasis of human breast cancer MCF-7 cells and explore the possible mechanism.

METHODSMCF-7 cells treated with 100, 200, and 400 µmol/L of DADS for 24 h were examined for cell invasion and migration capacities using Transwell assay and wound healing assay, respectively. The protein expression of E-cadherin, vimentin, MMP-9 and p-p38 in the cells were detected with Western blotting. The effect of transforming growth factor-β1 (TGF-β1) as the agonist of p38 activity was tested in antagonizing the effects of DADS.

RESULTSDADS inhibited the invasion and migration of MCF-7 cells in a dose-dependent manner, down-regulated the protein expression of Vimentin and MMP-9 and up-regulated E-cadherin expression in the cells. Treatment with TGF-β1 to up-regulate p38 activity obviously antagonized the inhibitory effect of DADS on the invasion and metastasis of MCF-7 cells.

CONCLUSIONDADS can inhibit the invasion and metastasis of MCF-7 cells in vitro by down-regulating p38 activity.

Allyl Compounds ; pharmacology ; Breast Neoplasms ; pathology ; Cadherins ; metabolism ; Disulfides ; pharmacology ; Gene Expression Regulation, Neoplastic ; Humans ; MAP Kinase Signaling System ; drug effects ; MCF-7 Cells ; drug effects ; Matrix Metalloproteinase 9 ; metabolism ; Mitogen-Activated Protein Kinase 11 ; metabolism ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Transforming Growth Factor beta1 ; pharmacology ; Vimentin ; metabolism

OBJECTIVETo study the role of the PI3K/AKT signaling pathway in the diallyl disulfide (DADS)-induced apoptosis of K562 cells.

METHODSK562 cells in the logarithmic growth phase were treated with 10, 20, 40, or 80 mg/L DADS for 48 hours, then fixed and stained with acridine orange/ethidium bromide (AO/EB), and examined for cellular morphological changes under an inverted microscope. Annexin V-FITC/PI staining was used for determining the apoptotic rates, and Western blot for measuring the expression of AKT, p-AKT, and Caspase-3. Two control groups, blank and solvent, were used as references.

RESULTSK562 cells treated with DADS for 48 hours exhibited the characteristic morphological features of apoptosis including cell shrinkage, irregular cell shape, and membrane blebbing. AO/EB staining results demonstrated that the number of apoptotic cells with cell shrinkage, pyknotic or bead-like nuclei, chromatin condensation, and orange staining increased with the increasing DADS concentration, and 40 mg/L DADS had the most significant effect. The apoptotic rates of cells treated with 10, 20, 40, and 80 mg/L DADS were all significantly higher than those in the control groups (P<0.05). There were no significant differences in AKT protein expression between the K562 cells treated with different concentrations of DADS; the p-AKT protein expression decreased with the increasing DADS concentration, while the Caspases-3 protein expression increased with the increasing DADS concentration (P<0.05).

CONCLUSIONSDADS induces the apoptosis of K562 cells, probably through inhibiting the protein expression in the PI3K/AKT signaling pathway.

Allyl Compounds ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Disulfides ; pharmacology ; Dose-Response Relationship, Drug ; Humans ; K562 Cells ; Phosphatidylinositol 3-Kinases ; physiology ; Proto-Oncogene Proteins c-akt ; physiology ; Signal Transduction ; physiology

OBJECTIVETo explore the effect of diallyl disulfide (DADS) on hippocampal synapses and learning and memory abilities in a mouse model of A1zheimer's disease (AD).

METHODSMouse models of AD established by agglutinated Aβ1-42 injection in the lateral cerebral ventricle were randomized into 4 groups and treated with DADS at the daily doses of 0, 10, 50 and 100 mg/kg by gavage for 30 consecutive days. The learning and memory abilities of the mice were assessed with Morris water maze test; the structures of the dendritic spines and synapses in CA1 region of the hippocampus were observed under transmission electron microscope with silver staining; PSD95 and SYP protein and mRNA expressions in the hippocampus were detected with Western blotting and RT-PCR.

RESULTSCompared with the AD model mice, the mice treated with 50 and 100 mg/kg DADS showed enhanced learning and memory abilities in Morris water maze test. The dendritic spines and synapses in CA1 region of the hippocampus increased obviously and hippocampal expressions of PSD95 and SYP were enhanced in mice treated with 50 and 100 mg/kg DADS.

CONCLUSIONDADS at the daily doses of 50 and 100 mg/kg can improve the learning and memory abilities and increase the number of dendritic spines and synapses in the hippocampus in mouse models of AD.

Allyl Compounds ; pharmacology ; Alzheimer Disease ; drug therapy ; Animals ; CA1 Region, Hippocampal ; drug effects ; Disease Models, Animal ; Disulfides ; pharmacology ; Learning ; Male ; Memory ; Mice ; Synapses ; drug effects