Diabetes Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
The Scientific Research Center, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China.
J Ethnopharmacol. 2024 Jan 30;319(Pt 2):117167. doi: 10.1016/j.jep.2023.117167. Epub 2023 Sep 14.
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.
To study the actions and mechanisms of SJZD on bone remodeling in a type 2 diabetes mouse model.
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 staining. 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-κB), NF-κB, cathepsin K, semaphorin 3A (Sema3A), insulin-like growth factor 1 (IGF1), p-GSK-3β, (p)-β-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.
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-κB/NF-κB, cathepsin K, p-GSK-3β, p-β-catenin expressions and a decrease in Sema3A, IGF1, β-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.
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/β-catenin signaling pathways. SJZD may offer a novel source of drug candidates for the prevention and treatment of type 2 diabetes and osteoporosis.
ETHNOPHARMACOLOGICAL 相关性：四君子汤（SJZD）是一种中药方剂，临床上和传统上用于改善葡萄糖和脂质代谢，促进骨重塑。
在 2 型糖尿病小鼠模型中研究 SJZD 对骨重塑的作用和机制。
用高脂肪饮食（HFD）和链脲佐菌素（STZ）生成的糖尿病小鼠接受 SJZD 治疗 8 周。通过 ELISA 或生化测定法测定血糖和血脂谱、氧化还原状态和骨代谢。通过 micro-CT、三点弯曲试验和傅里叶变换红外光谱（FTIR）评估骨质量。通过苏木精-伊红（H&E）、抗酒石酸酸性磷酸酶（TRAP）染色和番红 O-快绿染色评估骨组织形态计量学改变。通过 Western blot 或免疫组织化学染色检测股骨和/或胫骨中超氧化物歧化酶 1（SOD1）、晚期糖基化终产物（AGEs）、晚期糖基化终产物受体（RAGE）、磷酸化核因子 kappa-B（p-NF-κB）、NF-κB、组织蛋白酶 K、信号素 3A（Sema3A）、胰岛素样生长因子 1（IGF1）、p-GSK-3β、（p）-β-连环蛋白、成骨相关转录因子 2（Runx2）和细胞周期蛋白 D1 的表达。SJZD 水提物中的主要成分通过 HPLC/MS 进行了表征。
SJZD 干预改善了糖尿病小鼠的葡萄糖和脂质代谢，保持了骨质量，特别是葡萄糖耐量、血脂谱、骨微结构、强度和材料组成。SJZD 给药可维持糖尿病小鼠血清和骨髓中的氧化还原平衡，并防止 AGEs、RAGE、p-NF-κB/NF-κB、组织蛋白酶 K、p-GSK-3β、p-β-连环蛋白表达增加，以及 Sema3A、IGF1、β-连环蛋白、Runx2 和细胞周期蛋白 D1 表达减少。SJZD 水提物中鉴定出 13 种化合物，包括淫羊藿素、甘草素阿糖苷、芒柄花素、人参皂苷 Re、Rg1、Rb1、Rb2、Ro、Rb3、Rd、三七皂苷 R2、甘草酸和甘草皂甙 B2。
SJZD 可能通过维持氧化还原平衡来改善糖尿病小鼠的骨质量。这些变化的机制可能与对 AGEs/RAGE 和 Wnt/β-连环蛋白信号通路的影响有关。SJZD 可能为 2 型糖尿病和骨质疏松症的预防和治疗提供新的药物候选物来源。
