Aqueous Extract of Mori Folium Exerts Bone Protective Effect Through Regulation of Calcium and Redox Homeostasis via PTH/VDR/CaBP and AGEs/RAGE/Nox4/NF-κB Signaling in Diabetic Rats
Purpose: The present study is aimed to explore whether the aqueous extract of Mori Folium (MF) exhibits bone protective effect by regulating calcium and redox homeostasis in diabetic rats, and to identify the signaling pathways involved in this process.Methods: Diabetic rats were established using h...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.01239/full |
| _version_ | 1818854257521065984 |
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| author | Chenyue Liu Chenyue Liu Ruyuan Zhu Haixia Liu Lin Li Beibei Chen Qiangqiang Jia Lili Wang Lili Wang Rufeng Ma Rufeng Ma Simin Tian Min Wang Min Fu Jianzhao Niu Alexander N. Orekhov Sihua Gao Dongwei Zhang Baosheng Zhao |
| author_facet | Chenyue Liu Chenyue Liu Ruyuan Zhu Haixia Liu Lin Li Beibei Chen Qiangqiang Jia Lili Wang Lili Wang Rufeng Ma Rufeng Ma Simin Tian Min Wang Min Fu Jianzhao Niu Alexander N. Orekhov Sihua Gao Dongwei Zhang Baosheng Zhao |
| author_sort | Chenyue Liu |
| collection | DOAJ |
| description | Purpose: The present study is aimed to explore whether the aqueous extract of Mori Folium (MF) exhibits bone protective effect by regulating calcium and redox homeostasis in diabetic rats, and to identify the signaling pathways involved in this process.Methods: Diabetic rats were established using high-sugar and high-fat diet and streptozotocin (STZ) (30 mg/kg for 3 consecutive days). The serum levels of osteocalcin (OC), insulin-like growth factor-1 (IGF-1), tartrate-resistant acid phosphatase (TRAP), phosphorus (P), calcium (Ca), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], parathormone (PTH), advanced glycation end products (AGEs), superoxide dismutase (SOD), and malondialdehyde (MDA), total antioxidant capacity (TAC), 8-hydroxy-2′-deoxyguanosine (8-OH-dG), and interleukin 6 (IL-6) were determined by ELISA or biochemical assays. Histopathological alterations in the femurs were evaluated by the stainings of hematoxylin-eosin (H&E) and alizarin red S. In addition, femoral strength was detected by a three-point bending assay, bone microstructure was detected with micro-computer tomography. Bone material properties were examined by Fourier-transform infrared spectroscopy. Furthermore, the expressions of IGF-1, runt-related transcription factor 2 (Runx2), osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), cathepsin K, AGEs, receptor of advanced glycation end products (RAGE), NADPH oxidase 4 (Nox4), and nuclear factor kappa-B (NF-κB) in the femurs and tibias, and the alterations in the levels of calcium-binding protein-28k (CaBP-28k), transient receptor potential V6 (TRPV6), and vitamin D receptor (VDR) in the kidneys and duodenums were determined by western blot and immunohistochemical analysis.Results: Treatment of diabetic rats with MF aqueous extract induces an increase in the levels of OC and IGF-1 as well as a decrease in TRAP level in serum. MF treatment also upregulates the expression of OPG, downregulates the expressions of AGEs, RAGE, Nox4, NF-κB, and RANKL, which leads to improve bone microstructure and strength exhibited by an increase in cortical area ratio, cortical thickness, and trabecular area ratio as well as ultimate load, elastic modulus, and bending stress in the femurs and tibias of diabetic rats. In addition, MF aqueous extract preserves bone material properties by decreasing the ratio of fatty acid/collagen and increasing the ratio of mineral/matrix in the femurs of diabetic rats. Moreover, MF treatment increases the levels of P, Ca, and 1,25(OH)2D3, and decreases the level of PTH in the serum, as well as upregulates the expressions of TRPV6 and VDR in the duodenums and CaBP-28k in the kidneys of diabetic rats. Additionally, MF has ability of rebuilding redox homeostasis and eliminating inflammatory stress by increasing the levels of SOD and TAC as well as decreasing the levels of IL-6, AGEs, MDA, and 8-OH-dG.Conclusions: MF treatment may improve bone quality through maintenance of calcium homeostasis via regulating the PTH/VDR/CaBP signaling, and elimination of oxidative stress via regulating the AGEs/RAGE/Nox4/NF-κB signaling. These results may suggest the potential of MF in preventing the development of diabetic osteoporosis. |
| first_indexed | 2024-12-19T07:49:50Z |
| format | Article |
| id | doaj.art-b1363888b5064339a8ba5ce56dfbe2a8 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-19T07:49:50Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-b1363888b5064339a8ba5ce56dfbe2a82022-12-21T20:30:12ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-11-01910.3389/fphar.2018.01239409252Aqueous Extract of Mori Folium Exerts Bone Protective Effect Through Regulation of Calcium and Redox Homeostasis via PTH/VDR/CaBP and AGEs/RAGE/Nox4/NF-κB Signaling in Diabetic RatsChenyue Liu0Chenyue Liu1Ruyuan Zhu2Haixia Liu3Lin Li4Beibei Chen5Qiangqiang Jia6Lili Wang7Lili Wang8Rufeng Ma9Rufeng Ma10Simin Tian11Min Wang12Min Fu13Jianzhao Niu14Alexander N. Orekhov15Sihua Gao16Dongwei Zhang17Baosheng Zhao18School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing, ChinaDiabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, ChinaDiabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, ChinaDiabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, ChinaDiabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, ChinaDiabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, ChinaDiabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing, ChinaDiabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, ChinaDiabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, ChinaGuang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaSchool of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing, ChinaThe Research Institute of McGill University Health Center, Montreal, QC, CanadaDiabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, ChinaLaboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Moscow, RussiaDiabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, ChinaDiabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, ChinaBeijing Research Institute of Chinese medicine, Beijing University of Chinese Medicine, Beijing, ChinaPurpose: The present study is aimed to explore whether the aqueous extract of Mori Folium (MF) exhibits bone protective effect by regulating calcium and redox homeostasis in diabetic rats, and to identify the signaling pathways involved in this process.Methods: Diabetic rats were established using high-sugar and high-fat diet and streptozotocin (STZ) (30 mg/kg for 3 consecutive days). The serum levels of osteocalcin (OC), insulin-like growth factor-1 (IGF-1), tartrate-resistant acid phosphatase (TRAP), phosphorus (P), calcium (Ca), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], parathormone (PTH), advanced glycation end products (AGEs), superoxide dismutase (SOD), and malondialdehyde (MDA), total antioxidant capacity (TAC), 8-hydroxy-2′-deoxyguanosine (8-OH-dG), and interleukin 6 (IL-6) were determined by ELISA or biochemical assays. Histopathological alterations in the femurs were evaluated by the stainings of hematoxylin-eosin (H&E) and alizarin red S. In addition, femoral strength was detected by a three-point bending assay, bone microstructure was detected with micro-computer tomography. Bone material properties were examined by Fourier-transform infrared spectroscopy. Furthermore, the expressions of IGF-1, runt-related transcription factor 2 (Runx2), osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), cathepsin K, AGEs, receptor of advanced glycation end products (RAGE), NADPH oxidase 4 (Nox4), and nuclear factor kappa-B (NF-κB) in the femurs and tibias, and the alterations in the levels of calcium-binding protein-28k (CaBP-28k), transient receptor potential V6 (TRPV6), and vitamin D receptor (VDR) in the kidneys and duodenums were determined by western blot and immunohistochemical analysis.Results: Treatment of diabetic rats with MF aqueous extract induces an increase in the levels of OC and IGF-1 as well as a decrease in TRAP level in serum. MF treatment also upregulates the expression of OPG, downregulates the expressions of AGEs, RAGE, Nox4, NF-κB, and RANKL, which leads to improve bone microstructure and strength exhibited by an increase in cortical area ratio, cortical thickness, and trabecular area ratio as well as ultimate load, elastic modulus, and bending stress in the femurs and tibias of diabetic rats. In addition, MF aqueous extract preserves bone material properties by decreasing the ratio of fatty acid/collagen and increasing the ratio of mineral/matrix in the femurs of diabetic rats. Moreover, MF treatment increases the levels of P, Ca, and 1,25(OH)2D3, and decreases the level of PTH in the serum, as well as upregulates the expressions of TRPV6 and VDR in the duodenums and CaBP-28k in the kidneys of diabetic rats. Additionally, MF has ability of rebuilding redox homeostasis and eliminating inflammatory stress by increasing the levels of SOD and TAC as well as decreasing the levels of IL-6, AGEs, MDA, and 8-OH-dG.Conclusions: MF treatment may improve bone quality through maintenance of calcium homeostasis via regulating the PTH/VDR/CaBP signaling, and elimination of oxidative stress via regulating the AGEs/RAGE/Nox4/NF-κB signaling. These results may suggest the potential of MF in preventing the development of diabetic osteoporosis.https://www.frontiersin.org/article/10.3389/fphar.2018.01239/fullMori Foliumbone qualitydiabetescalcium homeostasisredox equilibriumPTH/VDR/CaBP |
| spellingShingle | Chenyue Liu Chenyue Liu Ruyuan Zhu Haixia Liu Lin Li Beibei Chen Qiangqiang Jia Lili Wang Lili Wang Rufeng Ma Rufeng Ma Simin Tian Min Wang Min Fu Jianzhao Niu Alexander N. Orekhov Sihua Gao Dongwei Zhang Baosheng Zhao Aqueous Extract of Mori Folium Exerts Bone Protective Effect Through Regulation of Calcium and Redox Homeostasis via PTH/VDR/CaBP and AGEs/RAGE/Nox4/NF-κB Signaling in Diabetic Rats Frontiers in Pharmacology Mori Folium bone quality diabetes calcium homeostasis redox equilibrium PTH/VDR/CaBP |
| title | Aqueous Extract of Mori Folium Exerts Bone Protective Effect Through Regulation of Calcium and Redox Homeostasis via PTH/VDR/CaBP and AGEs/RAGE/Nox4/NF-κB Signaling in Diabetic Rats |
| title_full | Aqueous Extract of Mori Folium Exerts Bone Protective Effect Through Regulation of Calcium and Redox Homeostasis via PTH/VDR/CaBP and AGEs/RAGE/Nox4/NF-κB Signaling in Diabetic Rats |
| title_fullStr | Aqueous Extract of Mori Folium Exerts Bone Protective Effect Through Regulation of Calcium and Redox Homeostasis via PTH/VDR/CaBP and AGEs/RAGE/Nox4/NF-κB Signaling in Diabetic Rats |
| title_full_unstemmed | Aqueous Extract of Mori Folium Exerts Bone Protective Effect Through Regulation of Calcium and Redox Homeostasis via PTH/VDR/CaBP and AGEs/RAGE/Nox4/NF-κB Signaling in Diabetic Rats |
| title_short | Aqueous Extract of Mori Folium Exerts Bone Protective Effect Through Regulation of Calcium and Redox Homeostasis via PTH/VDR/CaBP and AGEs/RAGE/Nox4/NF-κB Signaling in Diabetic Rats |
| title_sort | aqueous extract of mori folium exerts bone protective effect through regulation of calcium and redox homeostasis via pth vdr cabp and ages rage nox4 nf κb signaling in diabetic rats |
| topic | Mori Folium bone quality diabetes calcium homeostasis redox equilibrium PTH/VDR/CaBP |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.01239/full |
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