Anti-Diabetic Nephropathy Activities of Polysaccharides Obtained from Termitornyces albuminosus via Regulation of NF-κB Signaling in db/db Mice
Abstract
:1. Introduction
2. Results
2.1. Characterization of PTA
2.2. PTA Regulates Lipid Metabolism in db/db Mice
2.3. Renal Protection by PTA in db/db Mice
2.4. Anti-Inflammation and Anti-Oxidation Pathways are Involved in PTA-Mediated Renal Protection
2.5. NF-κB Signaling Might be Involved in PTA-Mediated Renal Protection
3. Discussion
4. Materials and Methods
4.1. Preparation of Polysaccharides from T. albuminosus Fruiting Body
4.2. Characteristic Analysis of PTA
4.2.1. Ultraviolet (UV) Spectra Measurement.
4.2.2. FT-IR Spectra Analysis.
4.2.3. Molecular Weight Analysis.
4.2.4. Monosaccharides Analysis.
4.3. Experimental Protocol Performed in db/db Mice
4.4. Histopathological Examination
4.5. Antibody Array Assay of Kidney
4.6. Biochemical Indexes Measurement
4.7. Western Blotting
5. Conclusions
Author Contributions
Acknowledgments
Conflicts of Interest
Abbreviations
AKT | Protein Kinase B |
ALB | Albumin |
Ara | L-Arabinose |
ATP | Adenosine Triphosphate |
AUC | Area Under the Curve |
BCA | Butyleyanoacrylate |
BSA | Bovine Serum Albumin |
BUN | Blood Urea Nitrogen |
CAT | Catalase |
CTRL | Control Group |
DEAE−52 | Diethylethanolamine-52 |
DM | Diabetes Mellitus |
DN | Diabetic Nephropathy |
ECL | Electrochemiluminescence |
ELISA | Enzyme-Linked Immunosorbent Assay |
FT-IR | Fourier Transform Infrared |
Gal | D-Galactose |
GHbA1c | Glycosylated Hemoglobin A1c |
Glc | D-Glucose |
H and E | Hematoxylin Eosin |
GAPDH | Glyceraldehyde-3-Phosphate Dehydrogenase |
GSH-Px | Glutathione Peroxide |
HDL-C | High Density Lipid Cholesterol |
HPLC | High Performance Liquid Chromatography |
IFN-γ | Interferon-Γ |
IκBα | Inhibitor Of ΚB Alpha |
IKKα+β | Inhibitor Of ΚB Kinase Alpha + Beta |
ILs | Interleukins |
INS | Insulin |
LDL-C | Low Density Lipid Cholesterol |
LEP | Leptin |
Man | D-Mannose |
MCP-1 | Monocyte Chemotactic Protein-1 |
M-CSF | Macrophage Colony-Stimulating Factor |
Met | Metformin |
MMP-9 | Matrix Metalloproteinase-9 |
NAG | N-Acetyl-Β-D-Glucosidase |
NF-κB | Nuclear Factor-ΚB |
OGTT | Oral Glucose Tolerance Test |
PKA | cAMP-Dependent Protein Kinase |
PMSF | Phenylmethanesulfonyl Fluoride |
PVDF | Polyvinylidene Difluoride |
Rha | L-Rhamnose |
RIPA | Radio Immunoprecipitation Assay |
ROS | Reactive Oxygen Species |
SDS-PAGE | Sodium Dodecyl Sulfate–Polyacrylamide Gel Electrophoresis |
SOD | Superoxide Dismutase |
T2DM | Type 2 DM |
TNF-α | Tumor Necrosis Factor-A |
UV | Ultraviolet |
Xyl | D-Xylose |
6-K-PGF1α | 6-Keto Prostaglandin F 1A |
Appendix A
Week | db/m+ | db/db | db/db | |||
---|---|---|---|---|---|---|
Met (100 mg/kg) | PTA (25 mg/kg) | PTA (100 mg/kg) | ||||
Body weights (g) | 1 | 20.4 ± 2.2 | 41.6 ± 2.3### | 40.6 ± 2.9 | 40.8 ± 3.0 | 40.3 ± 2.6 |
2 | 18.4 ± 2.5 | 42.7 ± 2.6### | 39.3 ± 3.2* | 40.0 ± 3.0* | 40.1 ± 2.4* | |
3 | 20.3 ± 2.1 | 45.4 ± 1.9### | 42.9 ± 3.0* | 41.8 ± 2.8** | 42.6 ± 1.8** | |
4 | 21.4 ± 1.1 | 46.6 ± 2.2### | 43.8 ± 3.7* | 43.8 ± 2.9* | 44.3 ± 2.1* | |
5 | 22.1 ± 0.9 | 48.8 ± 2.9### | 45.4 ± 2.9* | 45.3 ± 2.4** | 46.0 ± 2.1* | |
6 | 22.0 ± 0.8 | 51.5 ± 2.6### | 45.9 ± 3.1** | 45.6 ± 3.2*** | 46.9 ± 2.1** | |
7 | 23.0 ± 0.8 | 51.1 ± 3.2### | 45.3 ± 3.0** | 45.9 ± 2.9** | 47.8 ± 2.4* | |
8 | 22.7 ± 1.4 | 51.1 ± 3.1### | 45.5 ± 1.9*** | 46.1 ± 2.7** | 48.0 ± 2.8* | |
Plasma glucose (mmol/L) | 1 | 5.0 ± 2.3 | 17.0 ± 6.2### | 16.9 ± 6.4 | 15.6 ± 6.5 | 17.9 ± 3.5 |
2 3 | 6.6 ± 1.3 6.8 ± 1.6 | 20.4 ± 3.8### 20.2 ± 3.9### | 17.8 ± 3.3 18.8 ± 3.2 | 16.6 ± 3.6* 17.3 ± 2.1 | 17.9 ± 1.7 17.4 ± 2.3 | |
4 5 | 6.7 ± 0.9 6.8 ± 0.8 | 20.3 ± 3.9### 21.0 ± 3.6### | 19.0 ± 1.1 17.3 ± 2.9* | 18.1 ± 3.2 17.6 ± 3.1 | 17.2 ± 2.5* 16.7 ± 2.3** | |
6 7 | 6.1 ± 1.0 7.0 ± 1.3 | 21.2 ± 2.2### 21.7 ± 2.2### | 17.2 ± 2.3** 17.8 ± 2.6** | 18.9 ± 2.3* 18.9 ± 2.7* | 16.2 ± 2.7*** 16.1 ± 2.1*** | |
8 | 6.7 ± 0.7 | 23.4 ± 2.3### | 17.1 ± 2.0*** | 17.4 ± 3.0*** | 16.4 ± 2.2*** |
Coordinate | Target | Fold | |
---|---|---|---|
db/db (vs.db/m+) | db/db+100 mg/kg PTA (vs.db/db) | ||
A 3; A 4 | Adiponectin/Acrp30 | −24.8% | −0.4% |
A 5; A 6 | Amphiregulin | 18.6% | −6.7% |
A 7; A 8 | Angiopoietin-1 | 15.0% | −3.9% |
A 9; A 10 | Angiopoietin-2 | 29.8% | 3.4% |
A 11; A 12 | Angiopoietin-like 3 | 43.6% | −7.8% |
A 13; A 14 | BAFF/BLyS/TNFSF13B | −1.9% | 21.2% |
A 15; A 16 | C1q R1/CD93 | 14.1% | 9.9% |
A 17; A 18 | CCL2/JE/MCP-1 | −3.6% | 30.9% |
A 19; A 20 | CCL3/CCL4 MIP-1 alpha/beta | 0.7% | 13.9% |
A 21; A 22 | CCL5/RANTES | −6.0% | −12.3% |
B 3; B 4 | CCL6/C10 | 31.9% | −17.4% |
B 5; B 6 | CCL11/Eotaxin | 23.3% | −5.9% |
B 7; B 8 | CCL12/MCP-5 | 12.7% | −9.8% |
B 9; B 10 | CCL17/TARC | 17.1% | −11.0% |
B 11; B 12 | CCL19/MIP-3 beta | 3.2% | 1.9% |
B 13; B 14 | CCL20/MIP-3 alpha | −12.6% | 13.9% |
B 15; B 16 | CCL21/6Ckine | 3.2% | 0.9% |
B 17; B 18 | CCL22/MDC | −3.4% | 20.2% |
B 19; B 20 | CD14 | 5.5% | 11.1% |
B 21; B 22 | CD40/TNFRSF5 | 29.0% | −11.6% |
C 3; C 4 | CD160 | 8.9% | 5.7% |
C 5; C 6 | Chemerin | 20.7% | −5.1% |
C 7; C 8 | Chitinase 3-like 1 | 187.7% | −60.1% |
C 9; C 10 | Coagulation Factor III/ Tissue Factor | −4.9% | −1.2% |
C 11; C 12 | Complement Component C5/C5a | −7.6% | 1.7% |
C 13; C 14 | Complement Factor D | −60.4% | 17.6% |
C 15; C 16 | C-Reactive Protein/CRP | 44.5% | −8.6% |
C 17; C 18 | CX3CL1/Fractalkine | −20.9% | 6.8% |
C 19; C 20 | CXCL1/KC | 2.4% | 7.6% |
C 21; C 22 | CXCL2/MIP-2 | 11.3% | 6.9% |
D 1; D 2 | CXCL9/MIG | 4.8% | −25.2% |
D 3; D 4 | CXCL10/IP-10 | 8.7% | −20.1% |
D 5; D 6 | CXCL11/I-TAC | −0.3% | −6.8% |
D 7; D 8 | CXCL13/BLC/BCA-1 | 31.4% | −28.2% |
D 9; D 10 | CXCL16 | 20.5% | −6.3% |
D 11; D 12 | Cystatin C | −1.0% | −6.7% |
D 13; D 14 | DKK-1 | −8.5% | 16.9% |
D 15; D 16 | DPPIV/CD26 | −13.1% | 3.0% |
D 17; D 18 | EGF | −4.5% | −3.2% |
D 19; D 20 | Endoglin/CD105 | −6.2% | −2.3% |
D 21; D 22 | Endostatin | 3.2% | −9.9% |
D 23; D 24 | Fetuin A/AHSG | −11.2% | −16.1% |
E 1; E 2 | FGF acidic | −2.6% | −2.9% |
E 3; E 4 | FGF-21 | −7.4% | −5.0% |
E 5; E 6 | Flt-3 Ligand | −6.4% | 1.8% |
E 7; E 8 | Gas 6 | 9.7% | −7.1% |
E 9; E 10 | G-CSF | 2.7% | 7.0% |
E 11; E 12 | GDF-15 | 4.5% | 18.4% |
E 13; E 14 | GM-CSF | −8.8% | 19.0% |
E 15; E 16 | HGF | −16.4% | 26.5% |
E 17; E 18 | ICAM-1/CD54 | −10.9% | 1.1% |
E 19; E 20 | IFN-gamma | −14.9% | 45.9% |
E 21; E 22 | IGFBP-1 | 32.6% | −2.9% |
E 23; E 24 | IGFBP-2 | −53.4% | −2.0% |
F 1; F 2 | IGFBP-3 | −3.0% | 4.9% |
F 3; F 4 | IGFBP-5 | −4.3% | 4.5% |
F 5; F 6 | IGFBP-6 | −11.0% | −5.2% |
F 7; F 8 | IL-1 alpha/IL-1F1 | 5.0% | −1.8% |
F 9; F 10 | IL-1 beta/ IL-1F2 | 17.8% | −10.7% |
F 11; F 12 | IL-1ra/IL-1F3 | 58.9% | −31.1% |
F 13; F 14 | IL-2 | 19.2% | 0.4% |
F 15; F 16 | IL-3 | −9.8% | 12.1% |
F 17; F 18 | IL-4 | −25.4% | 18.2% |
F 19; F 20 | IL-5 | −0.7% | −10.7% |
F 21; F 22 | IL-6 | 32.4% | 0.7% |
F 23; F 24 | IL-7 | 4.4% | −8.8% |
G 1; G 2 | IL-10 | 6.0% | 3.9% |
G 3; G 4 | IL-11 | −4.1% | 8.2% |
G 5; G 6 | IL-12p40 | 3.6% | 6.4% |
G 7; G 8 | IL-13 | 8.6% | −4.4% |
G 9; G 10 | IL-15 | 17.8% | −12.5% |
G 11; G 12 | IL-17A | 22.4% | 12.9% |
G 13; G 14 | IL-22 | 5.3% | −2.2% |
G 15; G 16 | IL-23 | 0.3% | 3.1% |
G 17; G 18 | IL-27p28 | −8.5% | 0.7% |
G 19; G 20 | IL-28 | −10.8% | −1.9% |
G 21; G 22 | IL-33 | 20.7% | 26.1% |
G 23; G 24 | LDL R | 9.6% | −2.5% |
H 1; H 2 | Leptin | 156.9% | −14.2% |
H 3; H 4 | LIF | 11.9% | −17.0% |
H 5; H 6 | Lipocalin-2/NGAL | 97.3% | −34.9% |
H 7; H 8 | LIX | 31.5% | −29.8% |
H 9; H 10 | M-CSF | 21.6% | −11.2% |
H 11; H 12 | MMP-2 | 20.1% | −18.8% |
H 13; H 14 | MMP-3 | 24.6% | −25.1% |
H 15; H 16 | MMP-9 | 64.0% | −33.7% |
H 17; H 18 | Myeloperoxidase | 83.5% | −49.4% |
H 19; H 20 | Osteopontin (OPN | 62.5% | −17.2% |
H 21; H 22 | Osteoprotegerin/ TNFRSF11B | 13.2% | −14.3% |
H 23; H 24 | PD-ECGF/ Thymidine phosphorylase | 13.7% | −2.1% |
I 1; I 2 | PDGF-BB | 21.4% | −36.0% |
I 3; I 4 | Pentraxin 2/SAP | 14.3% | −15.2% |
I 5; I 6 | Pentraxin 3/ TSG-14 | 21.5% | −17.7% |
I 7; I 8 | Periostin/OSF-2 | 42.9% | −16.2% |
I 9; I 10 | Pref-1/DLK-1/FA1 | 28.1% | −19.2% |
I 11; I 12 | Proliferin | 16.8% | −3.7% |
I 13; I 14 | Proprotein Convertase 9/ PCSK9 | 3.5% | −26.6% |
I 15; I 16 | RAGE | 16.6% | −16.2% |
I 17; I 18 | RBP4 | 15.4% | −28.8% |
I 19; I 20 | Reg3G | 13.9% | −11.2% |
I 21; I 22 | Resistin | −39.9% | −0.5% |
J 3; J 4 | E-Selectin/CD62E | 7.8% | −23.9% |
J 5; J 6 | P-Selectin/CD62P | −14.3% | −7.8% |
J 7; J 8 | Serpin E1/PAI-1 | 20.4% | −27.4% |
J 9; J 10 | Serpin F1/PEDF | 4.1% | −29.5% |
J 11; J 12 | Thrombopoietin | 17.0% | −12.3% |
J 13; J 14 | TIM-1/KIM-1/ HAVCR | 388.0% | −62.9% |
J 15; J 16 | TNF-alpha | 32.0% | −24.4% |
J 17; J 18 | VCAM-1/CD106 | 28.3% | −30.9% |
J 19; J 20 | VEGF | −3.9% | −11.7% |
J 21; J 22 | WISP-1/CCN4 | −2.2% | −18.9% |
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Kidney (pg/mgprot) | db/m+ | db/db | db/db | ||
---|---|---|---|---|---|
Met (0.1g/kg) | PTA (0.025g/kg) | PTA (0.1g/kg) | |||
IL-2 | 54.8 ± 2.5 | 72.4 ± 9.3## | 59.7 ± 6.9* | 53.6 ± 3.9** | 59.4 ± 7.0* |
IL-4 | 2.7 ± 0.1 | 2.4 ± 0.1# | 2.9 ± 0.3** | 2.8 ± 0.3** | 3.0 ± 0.5** |
IL-12 | 0.80 ± 0.08 | 1.35 ± 0.14### | 0.93 ± 0.11*** | 0.96 ± 0.09*** | 1.05 ± 0.06** |
TNF-α | 100.2 ± 6.7 | 132.7 ± 11.7## | 116.1 ± 14.0 | 100.7 ± 10.0** | 102.4 ± 4.3** |
LEP | 0.66 ± 0.05 | 0.37 ± 0.02### | 0.65 ± 0.04*** | 0.65 ± 0.09*** | 0.66 ± 0.09*** |
M-CSF | 21.2 ± 1.9 | 26.1 ± 0.6## | 20.9 ± 1.6** | 18.9 ± 2.2*** | 20.9 ± 1.9** |
IFN-γ | 2.5 ± 0.3 | 3.4 ± 0.2## | 2.4 ± 0.2*** | 2.2 ± 0.1*** | 2.7 ± 0.2** |
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Yang, C.; Feng, Q.; Liao, H.; Yu, X.; Liu, Y.; Wang, D. Anti-Diabetic Nephropathy Activities of Polysaccharides Obtained from Termitornyces albuminosus via Regulation of NF-κB Signaling in db/db Mice. Int. J. Mol. Sci. 2019, 20, 5205. https://doi.org/10.3390/ijms20205205
Yang C, Feng Q, Liao H, Yu X, Liu Y, Wang D. Anti-Diabetic Nephropathy Activities of Polysaccharides Obtained from Termitornyces albuminosus via Regulation of NF-κB Signaling in db/db Mice. International Journal of Molecular Sciences. 2019; 20(20):5205. https://doi.org/10.3390/ijms20205205
Chicago/Turabian StyleYang, Chang, Qi Feng, Huan Liao, Xinlei Yu, Yang Liu, and Di Wang. 2019. "Anti-Diabetic Nephropathy Activities of Polysaccharides Obtained from Termitornyces albuminosus via Regulation of NF-κB Signaling in db/db Mice" International Journal of Molecular Sciences 20, no. 20: 5205. https://doi.org/10.3390/ijms20205205