Bajitianwan formula extract ameliorates bone loss induced by iron overload via activating RAGE/PI3K/AKT pathway based on network pharmacology and transcriptomic analysis

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Journal of Natural Medicines Pub Date : 2024-03-26 DOI:10.1007/s11418-024-01779-1

Weifan Xu, Tao Jiang, Luying Ding, Yiping Jiang, Lichao Zhang, Tianshuang Xia, Hailiang Xin

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引用次数: 0

Abstract

Osteoporosis (OP) is closely related to iron overload. Bajitianwan (BJTW) is a traditional Chinese medicine formulation used for treating senile diseases such as dementia and osteoporosis. Modern pharmacological researches have found that BJTW has beneficial effect on bone loss and memory impairment in aging rats. This paper aimed to explore the role and mechanism of BJTW in ameliorating iron overload-induced bone loss. Furthermore, BJTW effectively improved the bone micro-structure of the femur in mice, and altered bone metabolism biomarkers alkaline phosphatase (ALP) and osteocalcin (OCN) in serum, as well as oxidative indexes superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) glutathione (GSH) and malondialdehyde (MDA) in liver. As for network pharmacology, 73 components collected from BJTW regulated 99 common targets merged in the BJTW and OP. The results of RNA-seq indicated that there were 418 potential targets in BJTW low dose group (BJTW-L) and 347 potential targets in BJTW high dose group (BJTW-H). Intriguingly, both PI3K-AKT signaling pathway and the AGEs-RAGE signaling pathway were contained in the KEGG pathways enrichment results of network pharmacology and transcriptomics, which were considered as the potential mechanism. Additionally, we verified that BJTW regulated the expression of related proteins in RAGE/PI3K-AKT pathways in MC3T3-E1 cells. In summary, BJTW has potent effect on protecting against iron overload-induced OP, and its mechanism may be related to the activation of the RAGE/PI3K-AKT signaling pathways.

Graphic abstract

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基于网络药理学和转录组学分析，八吉田湾配方提取物通过激活RAGE/PI3K/AKT通路，改善铁超载引起的骨质流失。

骨质疏松症（OP）与铁超载密切相关。八味天丸是一种用于治疗老年痴呆和骨质疏松症等老年性疾病的传统中药配方。现代药理研究发现，八味天丸对衰老大鼠的骨质疏松和记忆力减退有一定疗效。本文旨在探讨 BJTW 在改善铁超载引起的骨质流失中的作用和机制。此外，BJTW还能有效改善小鼠股骨的骨微结构，改变血清中骨代谢生物标志物碱性磷酸酶（ALP）和骨钙素（OCN），以及肝脏中氧化指标超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽还原酶（GR）、谷胱甘肽（GSH）和丙二醛（MDA）。在网络药理学方面，从 BJTW 中收集的 73 个成分调控了 BJTW 和 OP 中合并的 99 个共同靶标。RNA-seq结果显示，BJTW低剂量组（BJTW-L）有418个潜在靶点，BJTW高剂量组（BJTW-H）有347个潜在靶点。有趣的是，PI3K-AKT 信号通路和 AGEs-RAGE 信号通路都包含在网络药理学和转录组学的 KEGG 通路富集结果中，被认为是潜在的机制。此外，我们还验证了BJTW能调节MC3T3-E1细胞中RAGE/PI3K-AKT通路相关蛋白的表达。综上所述，BJTW 对铁超载诱导的 OP 具有有效的保护作用，其机制可能与激活 RAGE/PI3K-AKT 信号通路有关。

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来源期刊

Journal of Natural Medicines 医学-药学

CiteScore

6.90

自引率

3.00%

发文量

审稿时长

1.7 months

期刊介绍： The Journal of Natural Medicines is an international journal publishing original research in naturally occurring medicines and their related foods and cosmetics. It covers: -chemistry of natural products -biochemistry of medicinal plants -pharmacology of natural products and herbs, including Kampo formulas and traditional herbs -botanical anatomy -cultivation of medicinal plants. The journal accepts Original Papers, Notes, Rapid Communications and Natural Resource Letters. Reviews and Mini-Reviews are generally invited.