Advanced search
Publication Cover
International Journal of Nanomedicine Volume 12, 2017 - Issue
Submit an article Journal homepage
135
Views
48
CrossRef citations to date
0
Altmetric
Original Research

Quercetin nanoparticle complex attenuated diabetic nephropathy via regulating the expression level of ICAM-1 on endothelium

Fei Tong1 Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen;2 Department of Pathology and Pathophysiology, Provincial Key Discipline of Pharmacology, Jiaxing University Medical College, Jiaxing, Zhejiang
,
Suhuan Liu1 Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen
,
Bing Yan1 Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen
,
Xuejun Li1 Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen
,
Shiwei Ruan3 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China
&
Shuyu Yang1 Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, XiamenCorrespondence[email protected]
Pages 7799-7813 | Published online: 24 Oct 2017

Figures & data

Figure 1 Characterization of PEG-b-(PELG-g-PZLL) and QUE/P.

Notes: (A) a, PEG-b-PBLG; b, PEG-b-PELG; c, PEG-b-(PELG-G-PZLL). FTIS of PEG-b-(PELG-g-PZLL); (B) TEM image of QUE/P; (C) a, particle size of P; b, particle size of QUE/P; (D) cumulative release profile of QUE/P; (E) cellular viability of HeLa cells cultured with different concentrations of PEG-b-(PELG-g-PZLL); (F) blood concentration of free QUE and QUE from QUE/P; (G) solution color of QUE and QUE/P.

Abbreviations: PEG-b-(PELG-g-PZLL), poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)); QUE/P, quercetin/PEG-b-(PELG-g-PZLL); FTIS, Fourier transform infrared spectroscopy; TEM, transmission electron microscopy.

Figure 1 Characterization of PEG-b-(PELG-g-PZLL) and QUE/P.Notes: (A) a, PEG-b-PBLG; b, PEG-b-PELG; c, PEG-b-(PELG-G-PZLL). FTIS of PEG-b-(PELG-g-PZLL); (B) TEM image of QUE/P; (C) a, particle size of P; b, particle size of QUE/P; (D) cumulative release profile of QUE/P; (E) cellular viability of HeLa cells cultured with different concentrations of PEG-b-(PELG-g-PZLL); (F) blood concentration of free QUE and QUE from QUE/P; (G) solution color of QUE and QUE/P.Abbreviations: PEG-b-(PELG-g-PZLL), poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)); QUE/P, quercetin/PEG-b-(PELG-g-PZLL); FTIS, Fourier transform infrared spectroscopy; TEM, transmission electron microscopy.
Figure 1 Characterization of PEG-b-(PELG-g-PZLL) and QUE/P.Notes: (A) a, PEG-b-PBLG; b, PEG-b-PELG; c, PEG-b-(PELG-G-PZLL). FTIS of PEG-b-(PELG-g-PZLL); (B) TEM image of QUE/P; (C) a, particle size of P; b, particle size of QUE/P; (D) cumulative release profile of QUE/P; (E) cellular viability of HeLa cells cultured with different concentrations of PEG-b-(PELG-g-PZLL); (F) blood concentration of free QUE and QUE from QUE/P; (G) solution color of QUE and QUE/P.Abbreviations: PEG-b-(PELG-g-PZLL), poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)); QUE/P, quercetin/PEG-b-(PELG-g-PZLL); FTIS, Fourier transform infrared spectroscopy; TEM, transmission electron microscopy.

Table 1 Molecular weight, PDI, TEM, particle size, and QUE-loading capacity of P

Figure 2 The distribution of quercetin/PEG-b-(PELG-g-PZLL) compound in rats.

Note: The distribution of quercetin/PEG-b-(PELG-g-PZLL) in rats and results expressed as mean ± standard deviation.

Abbreviations: PEG-b-(PELG-g-PZLL), poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)); DPM, disintegrations per minute.

Figure 2 The distribution of quercetin/PEG-b-(PELG-g-PZLL) compound in rats.Note: The distribution of quercetin/PEG-b-(PELG-g-PZLL) in rats and results expressed as mean ± standard deviation.Abbreviations: PEG-b-(PELG-g-PZLL), poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)); DPM, disintegrations per minute.

Figure 3 Histopathologic assessment of kidney damage.

Notes: Light microscope images (×400) in Sham group, DN group, QUE group, QUE/P group, respectively (A); quantitative injury scores, expressed as mean ± SD, are shown in (B); gross appearance in Sham group, DN group, QUE group, QUE/P group, respectively (C). A remarkable augment relative to Sham group is denoted by “*” (p<0.01), a remarkable decrease relative to DN group is denoted by “**” (p<0.01), and a remarkable decrease relative to DN group is denoted by “***” (p<0.01).

Abbreviations: DN, diabetic nephropathy; QUE/P, quercetin/poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)); SD, standard deviation.

Figure 3 Histopathologic assessment of kidney damage.Notes: Light microscope images (×400) in Sham group, DN group, QUE group, QUE/P group, respectively (A); quantitative injury scores, expressed as mean ± SD, are shown in (B); gross appearance in Sham group, DN group, QUE group, QUE/P group, respectively (C). A remarkable augment relative to Sham group is denoted by “*” (p<0.01), a remarkable decrease relative to DN group is denoted by “**” (p<0.01), and a remarkable decrease relative to DN group is denoted by “***” (p<0.01).Abbreviations: DN, diabetic nephropathy; QUE/P, quercetin/poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)); SD, standard deviation.

Figure 4 The activity of SOD and the levels of blood glucose, BUN, Scr, MDA, HDL, LDL, TG, urine protein, and albumin/creatinine ratio.

Notes: (A) Level of blood glucose in control group, QUE group, QUE/P group, respectively; (B) level of BUN in Sham group, DN group, QUE group, QUE/P group, respectively; (C) level of Scr in Sham group, DN group, QUE group, QUE/P group, respectively; (D) activity of SOD in Sham group, DN group, QUE group, QUE/P group, respectively; (E) level of MDA in Sham group, DN group, QUE group, QUE/P group, respectively; (F) level of HDL, LDL, and TG in Sham group, DN group, QUE group, QUE/P group, respectively; (G) level of urine protein in Sham group, DN group, QUE group, QUE/P group, respectively; (H) albumin/creatinine ratio. (B, C, E, F-LDL and TG, G, H) A remarkable augment relative to the Sham group is denoted by “*” (p<0.01), a remarkable decrease relative to DN group is denoted by “**” (p<0.01), and a remarkable decrease relative to DN group is denoted by “***” (p<0.01); (D, F-HDL) a remarkable decrease relative to the Sham group is denoted by “*” (p<0.01), a remarkable increase relative to DN group is denoted by “**” (p<0.01), and a remarkable increase relative to DN group is denoted by “***” (p<0.01).

Abbreviations: SOD, superoxide dismutase; BUN, blood urea nitrogen; Scr, serum creatinine; MDA, malonyldialdehyde; HDL, high-density lipoprotein; LDL, low-density lipoprotein; TG, triglyceride; QUE/P, quercetin/poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)); DN, diabetic nephropathy.

Figure 4 The activity of SOD and the levels of blood glucose, BUN, Scr, MDA, HDL, LDL, TG, urine protein, and albumin/creatinine ratio.Notes: (A) Level of blood glucose in control group, QUE group, QUE/P group, respectively; (B) level of BUN in Sham group, DN group, QUE group, QUE/P group, respectively; (C) level of Scr in Sham group, DN group, QUE group, QUE/P group, respectively; (D) activity of SOD in Sham group, DN group, QUE group, QUE/P group, respectively; (E) level of MDA in Sham group, DN group, QUE group, QUE/P group, respectively; (F) level of HDL, LDL, and TG in Sham group, DN group, QUE group, QUE/P group, respectively; (G) level of urine protein in Sham group, DN group, QUE group, QUE/P group, respectively; (H) albumin/creatinine ratio. (B, C, E, F-LDL and TG, G, H) A remarkable augment relative to the Sham group is denoted by “*” (p<0.01), a remarkable decrease relative to DN group is denoted by “**” (p<0.01), and a remarkable decrease relative to DN group is denoted by “***” (p<0.01); (D, F-HDL) a remarkable decrease relative to the Sham group is denoted by “*” (p<0.01), a remarkable increase relative to DN group is denoted by “**” (p<0.01), and a remarkable increase relative to DN group is denoted by “***” (p<0.01).Abbreviations: SOD, superoxide dismutase; BUN, blood urea nitrogen; Scr, serum creatinine; MDA, malonyldialdehyde; HDL, high-density lipoprotein; LDL, low-density lipoprotein; TG, triglyceride; QUE/P, quercetin/poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)); DN, diabetic nephropathy.
Figure 4 The activity of SOD and the levels of blood glucose, BUN, Scr, MDA, HDL, LDL, TG, urine protein, and albumin/creatinine ratio.Notes: (A) Level of blood glucose in control group, QUE group, QUE/P group, respectively; (B) level of BUN in Sham group, DN group, QUE group, QUE/P group, respectively; (C) level of Scr in Sham group, DN group, QUE group, QUE/P group, respectively; (D) activity of SOD in Sham group, DN group, QUE group, QUE/P group, respectively; (E) level of MDA in Sham group, DN group, QUE group, QUE/P group, respectively; (F) level of HDL, LDL, and TG in Sham group, DN group, QUE group, QUE/P group, respectively; (G) level of urine protein in Sham group, DN group, QUE group, QUE/P group, respectively; (H) albumin/creatinine ratio. (B, C, E, F-LDL and TG, G, H) A remarkable augment relative to the Sham group is denoted by “*” (p<0.01), a remarkable decrease relative to DN group is denoted by “**” (p<0.01), and a remarkable decrease relative to DN group is denoted by “***” (p<0.01); (D, F-HDL) a remarkable decrease relative to the Sham group is denoted by “*” (p<0.01), a remarkable increase relative to DN group is denoted by “**” (p<0.01), and a remarkable increase relative to DN group is denoted by “***” (p<0.01).Abbreviations: SOD, superoxide dismutase; BUN, blood urea nitrogen; Scr, serum creatinine; MDA, malonyldialdehyde; HDL, high-density lipoprotein; LDL, low-density lipoprotein; TG, triglyceride; QUE/P, quercetin/poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)); DN, diabetic nephropathy.

Figure 5 QUE/P inhibits neutrophil adhesion in vivo (immunofluorescence photomicrographs).

Notes: (A) The image displaying CFSE-labeled HL-60 adhesion to HUVECs. HUVECs are administrated with QUE, QUE/P, and control oligonucleotide for 24 h and then administrated with or without TNF-α for 6 h. CFSE-labeled HL-60 are put into the HUVECs and incubated at 37°C for 45 min, and then the mixtures were washed. (B) Amount of neutrophil (CFSE-labeled HL-60) adhering to HUVECs in NC group, NC + TNF-α group, QUE + TNF-α group, QUE/P + TNF-α group, respectively. Data are shown as mean ± SD. A remarkable augment relative to the NC group is denoted by “*” (p<0.01), a remarkable decrease relative to NC + TNF-α group is denoted by “**” (p<0.01), and a remarkable decrease relative to NC + TNF-α group is denoted by “***” (p<0.01).

Abbreviations: QUE/P, quercetin/poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)); CFSE, carboxyfluorescein diacetate succinimidyl ester; HL-60, acute promyelocytic leukemia; HUVECs, human umbilical vein endothelial cells; TNF-α, tumor necrosis factor-α; SD, standard deviation; NC, normal control.

Figure 5 QUE/P inhibits neutrophil adhesion in vivo (immunofluorescence photomicrographs).Notes: (A) The image displaying CFSE-labeled HL-60 adhesion to HUVECs. HUVECs are administrated with QUE, QUE/P, and control oligonucleotide for 24 h and then administrated with or without TNF-α for 6 h. CFSE-labeled HL-60 are put into the HUVECs and incubated at 37°C for 45 min, and then the mixtures were washed. (B) Amount of neutrophil (CFSE-labeled HL-60) adhering to HUVECs in NC group, NC + TNF-α group, QUE + TNF-α group, QUE/P + TNF-α group, respectively. Data are shown as mean ± SD. A remarkable augment relative to the NC group is denoted by “*” (p<0.01), a remarkable decrease relative to NC + TNF-α group is denoted by “**” (p<0.01), and a remarkable decrease relative to NC + TNF-α group is denoted by “***” (p<0.01).Abbreviations: QUE/P, quercetin/poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)); CFSE, carboxyfluorescein diacetate succinimidyl ester; HL-60, acute promyelocytic leukemia; HUVECs, human umbilical vein endothelial cells; TNF-α, tumor necrosis factor-α; SD, standard deviation; NC, normal control.

Figure 6 QUE/P downregulates ICAM-1 expression in vivo.

Notes: (A) Expression of ICAM-1 in PBS group, NC group, QUE group, QUE/P group, respectively. (B) Expression of ICAM-1 in DN+1 week group, DN+2 week group, DN+4 week group, DN+8 week group, respectively. (C) Expression of ICAM-1 in Sham group, DN group, QUE group, QUE/P group, respectively. A remarkable decrease relative to the NC group is denoted by “*” (p<0.01), a remarkable decrease relative to NC group is denoted by “**” (p<0.01) (A); a remarkable augment relative to the DN+1 week group is denoted by “*” (p<0.01), a remarkable increase relative to DN+2 week group is denoted by “**” (p<0.01), and a remarkable increase relative to DN+4 week group is denoted by “***” (p<0.01) (B); a remarkable augment relative to the DN group is denoted by “*” (p<0.01), a remarkable decrease relative to DN group is denoted by “**” (p<0.01), and a remarkable decrease relative to DN group is denoted by “***” (p<0.01) (C).

Abbreviations: QUE/P, quercetin/poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)); ICAM-1, intercellular adhesion molecular-1; PBS, phosphate-buffered saline; DN, diabetic nephropathy; NC, normal control.

Figure 6 QUE/P downregulates ICAM-1 expression in vivo.Notes: (A) Expression of ICAM-1 in PBS group, NC group, QUE group, QUE/P group, respectively. (B) Expression of ICAM-1 in DN+1 week group, DN+2 week group, DN+4 week group, DN+8 week group, respectively. (C) Expression of ICAM-1 in Sham group, DN group, QUE group, QUE/P group, respectively. A remarkable decrease relative to the NC group is denoted by “*” (p<0.01), a remarkable decrease relative to NC group is denoted by “**” (p<0.01) (A); a remarkable augment relative to the DN+1 week group is denoted by “*” (p<0.01), a remarkable increase relative to DN+2 week group is denoted by “**” (p<0.01), and a remarkable increase relative to DN+4 week group is denoted by “***” (p<0.01) (B); a remarkable augment relative to the DN group is denoted by “*” (p<0.01), a remarkable decrease relative to DN group is denoted by “**” (p<0.01), and a remarkable decrease relative to DN group is denoted by “***” (p<0.01) (C).Abbreviations: QUE/P, quercetin/poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)); ICAM-1, intercellular adhesion molecular-1; PBS, phosphate-buffered saline; DN, diabetic nephropathy; NC, normal control.

Figure 7 QUE/P decreases inflammatory cell infiltration to the DN.

Notes: (A) Image of immunohistochemical staining for CD11b+ myeloid cells in NC-DN group, QUE group, QUE/P group, respectively; (B) quantitative value in NC-DN group, QUE group, QUE/P group, respectively. A remarkable decrease relative to the NC-DN group is denoted by “*” (p<0.01) and a remarkable decrease relative to NC-DN group is denoted by “**” (p<0.01).

Abbreviations: QUE/P, quercetin/poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)); DN, diabetic nephropathy; NC, normal control.

Figure 7 QUE/P decreases inflammatory cell infiltration to the DN.Notes: (A) Image of immunohistochemical staining for CD11b+ myeloid cells in NC-DN group, QUE group, QUE/P group, respectively; (B) quantitative value in NC-DN group, QUE group, QUE/P group, respectively. A remarkable decrease relative to the NC-DN group is denoted by “*” (p<0.01) and a remarkable decrease relative to NC-DN group is denoted by “**” (p<0.01).Abbreviations: QUE/P, quercetin/poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)); DN, diabetic nephropathy; NC, normal control.

Scheme 1 The structure of quercetin/PEG-b-(PELG-g-PZLL).

Abbreviation: PEG-b-(PELG-g-PZLL), poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)).

Scheme 1 The structure of quercetin/PEG-b-(PELG-g-PZLL).Abbreviation: PEG-b-(PELG-g-PZLL), poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)).

Figure S1 Synthesis of PEG-b-(PELG-g-PZLL).

Abbreviations: PEG-NH2, poly(ethylene glycol) amine; PEG-b-PBLG, poly(ethylene glycol)-b-poly(γ-benzyl l-glutamate); PEG-b-PELG, poly(ethylene glycol)-b-poly(ethylen-ediamine l-glutamate); PEG-b-(PELG-g-PZLL), poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)).

Figure S1 Synthesis of PEG-b-(PELG-g-PZLL).Abbreviations: PEG-NH2, poly(ethylene glycol) amine; PEG-b-PBLG, poly(ethylene glycol)-b-poly(γ-benzyl l-glutamate); PEG-b-PELG, poly(ethylene glycol)-b-poly(ethylen-ediamine l-glutamate); PEG-b-(PELG-g-PZLL), poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)).

Figure S2 Characterization of PEG-b-(PELG-g-PZLL).

Notes: (A) 1HNMR of PEG-b-(PELG-g-PZLL); (B) GPCs of PEG-b-(PELG-g-PZLL).

Abbreviations: PEG-b-(PELG-g-PZLL), poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)); 1HNMR, 1H-nuclear magnetic resonance; GPC, gel permeation chromatogram.

Figure S2 Characterization of PEG-b-(PELG-g-PZLL).Notes: (A) 1HNMR of PEG-b-(PELG-g-PZLL); (B) GPCs of PEG-b-(PELG-g-PZLL).Abbreviations: PEG-b-(PELG-g-PZLL), poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyloxycarbonyl-l-lysine)); 1HNMR, 1H-nuclear magnetic resonance; GPC, gel permeation chromatogram.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.