SiJunZi decoction ameliorates bone quality and redox homeostasis and regulates advanced glycation end products/receptor for advanced glycation end products and WNT/β-catenin signaling pathways in diabetic mice

被引:16
作者
Dai, Xuan [1 ]
Liu, Yage [1 ]
Liu, Tianyuan [1 ]
Zhang, Yueyi [1 ]
Wang, Shan [1 ]
Xu, Tianshu [1 ]
Yin, Jiyuan [1 ]
Shi, Hanfen [1 ]
Ye, Zimengwei [1 ]
Zhu, Ruyuan [1 ]
Gao, Junfeng [2 ]
Dong, Guangtong [3 ]
Zhao, Dandan [1 ]
Gao, Sihua [1 ]
Wang, Xinxiang [2 ]
Prentki, Marc [4 ,5 ,6 ,7 ]
Bromme, Dieter [8 ]
Wang, Lili [9 ]
Zhang, Dongwei [1 ,10 ]
机构
[1] Beijing Univ Chinese Med, Diabet Res Ctr, Sch Tradit Chinese Med, Beijing 100029, Peoples R China
[2] Beijing Univ Chinese Med, Dongfang Hosp, Sci Res Ctr, Beijing 100078, Peoples R China
[3] Beijing Univ Chinese Med, Sch Chinese Med, Dept Chinese Med Formulas, Beijing 102488, Peoples R China
[4] CRCHUM, Dept Nutr, Montreal, PQ, Canada
[5] CRCHUM, Dept Biochem, Montreal, PQ, Canada
[6] CRCHUM, Montreal Diabet Res Ctr, Montreal, PQ, Canada
[7] Univ Montreal, Montreal, PQ, Canada
[8] Univ British Columbia, Fac Dent, Dept Oral Biol & Med Sci, Vancouver, BC V6T 1Z3, Canada
[9] Beijing Univ Chinese Med, Chinese Mat Med Sch, Dept TCM Pharmacol, Beijing 102488, Peoples R China
[10] Beijing Univ Chinese Med, Diabet Res Ctr, Beijing 100029, Peoples R China
基金
中国国家自然科学基金;
关键词
SiJunZi decoction; Type; 2; diabetes; Bone remodeling; AGEs/RAGE/NF-kappa B; Wnt/beta-catenin signaling; ATRACTYLODES-MACROCEPHALA; GINSENOSIDE RB2; KAPPA-B; INFLAMMATION; RECEPTOR; STRESS; AGES; WNT;
D O I
10.1016/j.jep.2023.117167
中图分类号
Q94 [植物学];
学科分类号
071001 [植物学];
摘要
Ethnopharmacological relevance: SiJunZi decoction (SJZD), one of the traditional Chinese medicine formulas, has been clinically and traditionally used to improve glucose and lipid metabolism and promote bone remodeling.Aim of the study: To study the actions and mechanisms of SJZD on bone remodeling in a type 2 diabetes mouse model.Materials and methods: Diabetic mice generated with a high-fat diet (HFD) and streptozotocin (STZ) were subjected to SJZD treatment for 8 weeks. Blood glucose and lipid profile, redox status and bone metabolism were determined by ELISA or biochemical assays. Bone quality was evaluated by micro-CT, three-point bending assay and Fourier transform infrared spectrum (FTIR). Bone histomorphometry alterations were evaluated by Hematoxylin-Eosin (H&E), tartrate resistant acid phosphatase (TRAP) staining and Safranin O-fast green stain-ing. The expressions of superoxide dismutase 1 (SOD1), advanced glycation end products (AGEs), receptor for advanced glycosylation end products (RAGE), phosphorylated nuclear factor kappa-B (p-NF-kappa B), NF-kappa B, cathepsin K, semaphorin 3A (Sema3A), insulin-like growth factor 1 (IGF1), p-GSK-3 beta, (p)-beta-catenin, Runt-related transcription factor 2 (Runx2) and Cyclin D1 in the femurs and/or tibias were examined by Western blot or immunohistochemical staining. The main constituents in the SJZD aqueous extract were characterized by a HPLC/MS.Results: SJZD intervention improved glucose and lipid metabolism and preserved bone quality in the diabetic mice, in particular glucose tolerance, lipid profile, bone microarchitecture, strength and material composition. SJZD administration to diabetic mice preserved redox homeostasis in serum and bone marrow, and prevented an increase in AGEs, RAGE, p-NF-kappa B/NF-kappa B, cathepsin K, p-GSK-3 beta, p-beta-catenin expressions and a decrease in Sema3A, IGF1, beta-catenin, Runx2 and Cyclin D1 expressions in tibias and/or femurs. Thirteen compounds were identified in SJZD aqueous extract, including astilbin, liquiritin apioside, ononin, ginsenoside Re, Rg1, Rb1, Rb2, Ro, Rb3, Rd, notoginsenoside R2, glycyrrhizic acid, and licoricesaponin B2.Conclusions: SJZD ameliorates bone quality in diabetic mice possibly via maintaining redox homeostasis. The mechanism governing these alterations are possibly related to effects on the AGEs/RAGE and Wnt/B-catenin signaling pathways. SJZD may offer a novel source of drug candidates for the prevention and treatment of type 2 diabetes and osteoporosis.
引用
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页数:16
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