<br>Biochanin A 基于分子对接和实验验证，通过调节 ROS/MAPK 信号通路消除 2 型糖尿病骨质疏松症中的破骨细胞生成,BMC Complementary Medicine and Therapies

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Biochanin A 基于分子对接和实验验证，通过调节 ROS/MAPK 信号通路消除 2 型糖尿病骨质疏松症中的破骨细胞生成
BMC Complementary Medicine and Therapies Pub Date : 2024-01-08 , DOI: 10.1186/s12906-023-04332-x
Qi He _{1,

2} , Junzheng Yang _{2,

3} , Weijian Chen ₃ , Zhaofeng Pan _{1,

2} , Baihao Chen _{1,

2} , Jiaxu Zeng _{1,

2} , Nenling Zhang ₄ , Yuewei Lin _{1,

2} , Chuyi Chen _{1,

2} , Jiacong Xiao _{1,

2} , Miao Li _{1,

2} , Shaocong Li _{1,

2} , Haibin Wang ₅ , Peng Chen ₅

Affiliation

背景

同时患有骨质疏松症的2型糖尿病患者不断增多。应该发现更有效的治疗策略。生物鸡素A（BCA）已被证明可以发挥改善2型糖尿病代谢紊乱和预防骨质疏松的作用。但BCA是否可以治疗2型糖尿病骨质疏松症尚未研究。

目的

探讨 BCA 是否可以预防 2 型糖尿病骨质疏松症并阐明其机制。

方法

通过显微 CT 和组织学检测来检测骨小梁并分析 BCA 的骨组织形态学效果。采用CCK-8法检测BCA的毒性。采用TRAcP染色、免疫荧光和羟基磷灰石吸收实验观察破骨细胞的分化和吸收活性。分子对接通过算法预测提供了BCA调节MAPK轴的证据。采用QRT-PCR和Western Blotting检测破骨细胞生成相关标志物和MAPK信号通路的表达。

结果

基于3D重建可以发现BCA治疗后骨量的积累。此外，用BCA处理的db/db小鼠中的破骨细胞比用盐水处理的db/db小鼠少。在体外，我们发现BCA对破骨细胞前体没有毒性，而且还能抑制破骨细胞的分化。此外，我们发现BCA通过ROS/MAPK信号通路抑制破骨细胞生成。

结论

BCA可以通过ROS/MAPK信号通路限制破骨细胞分化来预防2型糖尿病骨质疏松症。

"点击查看英文标题和摘要"

Biochanin A abrogates osteoclastogenesis in type 2 diabetic osteoporosis via regulating ROS/MAPK signaling pathway based on integrating molecular docking and experimental validation

Background

There are accumulating type 2 diabetes patients who have osteoporosis simultaneously. More effective therapeutic strategies should be discovered. Biochanin A (BCA) has been indicated that can play a role in improving metabolic disorders of type 2 diabetes and preventing osteoporosis. But whether BCA can treat type 2 diabetic osteoporosis has not been studied.

Purpose

To investigate if the BCA can protect against type 2 diabetic osteoporosis and clarify the mechanism.

Methods

Micro-CT and histology assays were performed to detect the trabecular bone and analyze the bone histomorphology effect of BCA. CCK-8 assay was performed to detect the toxicity of BCA. TRAcP staining, immunofluorescence and hydroxyapatite resorption assay were used to observe osteoclasts differentiation and resorptive activity. Molecular docking provided evidence about BCA regulating the MAPK axis via prediction by the algorithm. QRT-PCR and Western Blotting were utilized to detect the expression of osteoclastogenesis-related markers and MAPK signaling pathway.

Results

Accumulation of bone volume after BCA treatment could be found based on the 3D reconstruction. Besides, there were fewer osteoclasts in db/db mice treated with BCA than db/db mice treated with saline. In vitro, we found that BCA hadn’t toxicity in osteoclasts precursor, but also inhibited differentiation of osteoclasts. Further, we found that BCA suppresses osteoclastogenesis via ROS/MAPK signaling pathway.