Piceatannol alleviates host inflammation in chronic kidney disease model mice through regulating gut microbiota / 药学学报

The purpose of this research is to study the effect of small molecule compound piceatannol (PIC) on host inflammation in adenine induced chronic kidney disease (CKD) mice, and then to explore its mechanism based on the regulation of gut microbiota. All procedures were approved by the Institutional Animal Care and Use Committee of the Nanjing University of Chinese Medicine. The level of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was detected by enzyme linked immunosorbent assay (ELISA); UPLC-TQ/MS technology was used to monitor the level of proinflammatory uremic toxin indoxyl sulfate (IS) and p-cresol sulfate (PCS); the expression of occludin was tested by Western blot; in vitro anaerobic culture of gut bacteria was used to produce indole; the abundance of gut microbiota was evaluated by 16S rDNA sequencing. The results showed that PIC had no effect on inflammatory infiltration in kidney tissue of CKD mice, but could decrease IL-6 level in blood and IL-6/TNF-α level in colon tissue. PIC did not improve intestinal occludin protein expression in CKD mice; while it could significantly reduce the levels of IS and PCS in blood and liver of CKD mice. Further mechanism studies showed that PIC could inhibit the synthesis of IS precursor indole in gut bacteria. Moreover, PIC could decrease the abundance of gut bacteria which producing uremic toxin, such as reducing the abundance of indole and p-cresol producing gut bacteria. In conclusion, PIC could regulate gut microbiota and inhibit the synthesis of uremic toxin precursor, thereafter reducing the accumulation of IS and PCS in vivo, ultimately relieving the inflammation of CKD mice.

Anti-tumor Effect of Piceatannol on Triple Negative Breast Cancer Cell Line MDA-MB-468 and Its Mechanism / 中国实验方剂学杂志

Objective:To investigate the effect of piceatannol （PIC） on the proliferation， apoptosis and cell cycle of MDA-MB-468 triple negative breast cancer cells and its mechanism. Method:The methylthiazolyldiphenyl-tetrazoliu bromide （MTT） colcorimetry method was used to investigate the effect of different concentrations of PIC （0， 2.5， 5.0， 10.0， 20.0， 40.0， 80.0， 160.0 μmol·L^-1） on the cell viabilities of triple negative breast cancer MDA-MB-468 cells and calculate the half maximal inhibitory concentration （IC₅₀） value， the effect of different concentrations of PIC （5.0， 10.0， 20.0 μmol·L^-1） on the cell cycle of MDA-MB-468 were investigated by flow cytometry with propidium iodide （PI） staining. The apoptotic effect of PIC （5.0， 10.0， 20.0 μmol·L^-1） on MDA-MB-468 cells in triple negative breast cancer was investigated by flow cytometry with cell apoptosis detection Annexin V-FITC and PI double staining. Western blot was used to investigate the effect of different concentrations of PIC （5.0， 10.0， 20.0 μmol·L^-1） on the proliferation and apoptosis of MDA-MB-468 cells and detect the expressions ofsecreted glycoprotein Wnt/<italic>β</italic>-catenin pathway related proteins. Result:MTT results showed that compared with the blank group， PIC could inhibit the proliferation of MDA-MB-468 cells in a concentration-dependent manner （<italic>P</italic><0.05， <italic>P</italic><0.01）， with IC₅₀ at（39.4±4.6）μmol·L^-1. Compared with the blank group， PIC could increase the percentage of MDA-MB-468 cells in G₀/G₁ phase about cell cycle in a concentration-dependent manner （<italic>P</italic><0.01）. Compared with the blank group， 5.0， 10.0， 20.0 μmol·L^-1 PIC could induce apoptosis of MDA-MB-468 cells for 48 h（<italic>P</italic><0.01）， and the apoptosis rate of MDA-MB-468 cells reached 49.87% when treated with 20.0 μmol·L^-1 for 48 h. Compared with the blank group， PIC could significantly reduce the expressions of <italic>β</italic>-catenin， proto-oncogene （C-myc） and adhesion factor （CD44） proteins in MDA-MB-468 cells， significantly inhibit the phosphorylation of<italic> </italic>protein kinase B （Akt） and p38 mitogen activated protein kinase （p38 MAPK） proteins and the protein expression of B lymphocyte tumor-2 （Bcl-2）， and enhance cysteine aspartic acid protease-3 （Caspase-3）， Bcl-2 related X protein （Bax） and phosphorylated <italic>β</italic>-catenin protein expression（<italic>P</italic><0.01）. Conclusion:PIC may inhibit the proliferation of MDA-MB-468 cells by inhibiting the Wnt/<italic>β</italic>-catenin signaling pathway， block the cell cycle in G0/G1 phase， and induce its apoptosis.

Effect of piceatannol against malignant melanoma / 华西口腔医学杂志

OBJECTIVES@#To study the antitumor effect of piceatannol (PIC) on malignant melanoma @*METHODS@#B16F10 cells were cultured @*RESULTS@#The cell viability of B16F10 decreased with increasing PIC concentration. The results of the Transwell assay showed that invasion ability decreased with increasing PIC concentration, and healing time was prolonged at increased PIC concentration in the wound healing assay. Western blot results showed that PIC mainly inhibited the phosphorylation of Syk and inhibited the expression of MMP-2, MMP-9, and VEGF. RNA interference pointed out that blocking the expression of Syk can reveal the same inhibition effect on B16F10 cells as PIC. @*CONCLUSIONS@#PIC might block the progression of malignant melanoma by inhibiting spleen tyrosine kinase.

Isolation, Characterisation and Antimicrobial Activity of Chemical Constituents from the Root of Mezoneuron angolense (Caesalpiniaceae)

Aims: In Ivory Coast, Mezoneuron angolenseroots are well-known in traditional medicine for their efficiency in the treatment of diarrhoea. The goal of this study was to determine the antibacterial constituents of these roots.Methodology:The chemical investigations of the roots of the plant havebeen undertaken and the structure of isolated compounds was elucidated through spectral studies including IR, UV, MS, 1D-NMR (1H and 13C NMR) and 2D-NMR experiments (HSQC, HMBC, COSY, and NOESY). The isolated compounds were screened against three enteropathogenic bacteria, Vibrio cholerae, Salmonella typhiand Shiguella fleneii,usingmicrobroth dilution method. Results:These investigations conducted to the isolation of two sterols, two stilbenes, one phthalate,and one carbohydrate. All tested compoundsexcept Bis (2-methylheptyl) phtalate (2) were active against all pathogens with MICs and MBCs ranging from 312.50 to 625 mg/ml. Piceatannol (5) and Trans-resveratrol (3) were the most active compounds.Conclusion:The results from the current study confirm and justify the popular use of the roots of this plant in the treatment of infectiousdiarrhoea. All obtained compounds were isolated from this species for the first time.

Protective effects of piceatannol on retinal ganglion cells in experimental glaucoma rats / 眼科新进展

Objective To investigate the protective effects of piceatannol on retinal ganglion cells (RGCs) in rats with glaucoma.Methods Forty rats were randomly divided into 4 groups:control group,model group,low dose piceatannol treatment group and high dose piceatannol treatment group.Photocoagulation method was used to establish the experimental glaucoma model in rats,and then rats were given 100 mg· kg-1 or 200 mg · kg-1 of piceatannol by gavage.The intraocular pressure was measured before and after the model was established.Rat retinal ganglion cells were labeled and counted using FG staining.Retinal tissue pathological morphology was observed by HE staining.The protein expression of p-JNK,p-c-Jun,p-ERK,p-p38 MAPK and TNF-α were measured by western blot.Results Compared with control group,the intraocular pressure,the protein expressions of p-JNK,p-c-Jun p-ERK,p-p38 MAPK and TNF-α were significantly increased in model group (all P ＜ 0.05).However,the number of RGCs were lower in model group(P ＜0.05).Furthermore,there were cavitation and edema changes in retinal tissue of model group.Compared with model group,piceatannol treatment markediy increased the number of RGCs(P =0.003,0.002),improved the pathological morphology of retinal tissue,and reduced the protein expressions of p-JNK,p-c-Jun p-ERK,p-p38 MAPK and TNF-α (all P ＜ 0.05),especially for the high concentration.Conclusion Piceatannol can protect against RGCs injury in glaucoma rats,and the mechanism may be associated with inhibition of MARK signaling pathway.

Piceatannol inhibits prostate cancer cell proliferation, migration and invasion / 中国病理生理杂志

AIM:To investigate the effect of piceatannol on the viability, and the abilities of migration and invasion in the prostate cancer cells.METHODS:DU145 cells were treated with piceatannol at different doses (0, 5, 10, 20, 40 and 80 μmol/L) for different time (12, 24, 36 and 48 h) as indicated.The cell viability was assessed by CCK-8 assay.The migration and invasion abilities of the cells were analyzed by wound healing assay and Transwell assay, respectively.The protein levels of p-JAK2 and p-STAT3 were detected by Western blot.RESULTS:Piceatannol dose-dependently decreased the cell viability.After treatment with piceatannol, the abilities of migration and invasion of the cells were significantly inhibited.Moreover, treatment with piceatannol resulted in marked decreases in the protein levels of p-JAK2 and p-STAT3.CONCLUSION:Piceatannol inhibits the viability, migration and invasion of the prostate cancer cells via regulating the JAK2/STAT3 signaling pathway.

Effects of piceatannol on rat kidney with diabetic nephropathy in early stage / 中国病理生理杂志

AIM: To observe the effect of piceatannol on the kidney of diabetic nephropathy rats in early stage, and to explore the possible mechanisms.METHODS: The rats were randomly divided into 5 groups: control group, model group, low dose of piceatannol treatment group, medium dose of piceatannol treatment group and high dose of piceatannol treatment group.The rat model of diabetic nephropathy was induced accordingly, and the rats received 20 mg/kg, 40 mg/kg or 60 mg/kg of piceatannol by gavage once a day for 4 weeks.Blood glucose was detected by glucometer.The urea nitrogen and creatinine levels in the serum were measured by urease-glutamate dehydrogenase enzymatic and inosine acid oxidase methods, respectively, and 24 h urinary microalbumin was analyzed by immune transmission turbidimetry test.Moreover, the pathological changes of the kidney tissues were observed under microscope with HE staining.The protein expression of TGF-β1 and Smad 7 and the phosphorylation levels of Smad2 and Smad3 were determined by Western blot.RESULTS: Compared with model group, piceatannol treatment significantly decreased the levels of blood glucose, blood urea nitrogen and urinary microalbumin, but had no effects on serum creatinine.Furthermore, HE staining showed that the increased mesangial cells, matrix hyperplasia and degenerated epithelial cells in model group were markedly inhibited after piceatannol treatment.Additionally, piceatannol treatment also reduced the protein expression of TGF-β1 and Smad 7, and the phosphorylation levels of Smad2 and Smad3.CONCLUSION: Piceatannol attenuates pathological progression in the kidney of diabetic nephropathy rats in early stage, which may be through inhibiting TGF-β/Smad signaling pathway.

Piceatannol induced apoptosis through up-regulation of microRNA-181a in melanoma cells

BACKGROUND: Melanoma took top position among the lethal cancers and, despite there have been some great attempts made to increase the natural life of patients with metastatic disease, long-lasting and complete remissions are few. Piceatannol, owns the similar function as resveratrol, has been defined as an anti-cancer agent playing important role in inhibition of proliferation, migration and metastasis in various cancer. Thus, we aim to investigate the anti-cancer effect and mechanisms of piceatannol in melanoma cells. METHODS: Melanoma cell lines WM266-4 and A2058 were treated either with or without piceatannol. Cell viability and cell apoptosis were assessed by using MTT and Annexin V/PI assay, respectively. Cells were transfected with specific miRNA using Lipfectamine 2000. miRNA bingding ability to 3'-UTR region within specific gene was assed by firefly luciferase analysis. Gene and protein expression was eveluated by qRT-PCR and western blot analysis, respectively. RESULTS: Our study showed that piceatannol inhibited WM266-4 and A2058 cells growth and induced apoptosis. Totally, 16 differentially expressed miRNAs were screened out including 8 up-regulated and 8 down-regulated miRNAs. Expression level of miR-181a is significantly higher in piceatannol-treated cells than normal control and is lower in melanoma cancer tissues than its adjacent normal tissues. Bcl-2 is a target gene of miR-181a. Moreover, silencing of miR-181a reverses the decrease of cell viability induced by piceatannol in WM266-4 and A2058 cells. Taken together, present study uncovered the ability of piceatannol to repress melanoma cell growth and clarified the contribution of miR-181a in the anticancer role of piceatannol. CONCLUSION: The present study proposes that piceatannol can be taken into account to be a hopeful anticancer agent for melanoma.

Intravenous administration of piceatannol, an arginase inhibitor, improves endothelial dysfunction in aged mice

Advanced age is one of the risk factors for vascular diseases that are mainly caused by impaired nitric oxide (NO) production. It has been demonstrated that endothelial arginase constrains the activity of endothelial nitric oxide synthase (eNOS) and limits NO generation. Hence, arginase inhibition is suggested to be vasoprotective in aging. In this study, we examined the effects of intravenous injection of Piceatannol, an arginase inhibitor, on aged mice. Our results show that Piceatannol administration reduced the blood pressure in aged mice by inhibiting arginase activity, which was associated with NO production and reactive oxygen species generation. In addition, Piceatannol administration recovered Ca²⁺/calmodulin-dependent protein kinase II phosphorylation, eNOS phosphorylation and eNOS dimer stability in the aged mice. The improved NO signaling was shown to be effective in attenuating the phenylephrine-dependent contractile response and in enhancing the acetylcholine-dependent vasorelaxation response in aortic rings from the aged mice. These data suggest Piceatannol as a potential treatment for vascular disease.

Piceatanol: Anti-Cancer Compound From Gewang Seed Extract.

Piceatannol (Compound 1), brownish white solids compound, is a stilbene compound has been isolated from methanol seeds extract of Corypha utan Lamk. Isolation and purification conducted by chromatographic methods. Structure elucidation deduced on the basis of spectroscopic data (UV spectrometer, FTIR, NMR and HRMS). MTT assay method of cytotoxicity activity showed that Compound 1 has a very strong cytotoxic activity against Murine leukemia P-388 cell lines with IC50 value 1.56 ppm.