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Abstract Title:

Ginsenoside Rb1 prevents osteoporosis via the AHR/PRELP/NF-κB signaling axis.

Abstract Source:

Phytomedicine. 2022 May 25 ;104:154205. Epub 2022 May 25. PMID: 35716470

Abstract Author(s):

Dan Zhang, Jian Du, Min Yu, Linna Suo

Article Affiliation:

Dan Zhang

Abstract:

BACKGROUND: Accumulating clinical and experimental evidence shows multiple biological effects of ginsenoside Rb1 (GRb1) in the treatment of aging related diseases such as osteoporosis (OP). Recently, GRb1 has attracted extensive attention as an anti-osteoporosis agent. Here, we sought to identify the mechanism by which GRb1 improves OP.

METHODS: A dexamethasone (DEX)-induced rat model of OP was constructed and the rats were treated with GRb1 to examine its role in OP. We screened the action targets of GRb1 online and validated by performing functional experiments. The correlation between aryl hydrocarbon receptor (AHR) and proline/arginine-rich end leucine-rich repeat protein (PRELP) was identified through luciferase and chromatin immunoprecipitation assays. In the isolated osteoblasts from DEX-induced OP rats, the expression of osteogenic differentiation-associated genes, and nuclear factor-kappa B (NF-κB) pathway-related genes, mineralization, and number of calcium nodules were assessed.

RESULTS: GRb1 enhanced the differentiation of osteoblasts, the mechanism of which was related to upregulation of AHR. AHR could promote the transcription of PRELP by binding to the PRELP promoter region and consequently caused its upregulation. Meanwhile, PRELP inhibited the activation of the NF-κB pathway, which underlay the promoting impact of AHR in the osteogenic differentiation. Additionally, GRb1 could ameliorate OP in DEX-induced rats via the AHR/PRELP/NF-κB axis.

CONCLUSIONS: Our findings demonstrate that GRb1 might function as an effective candidate to prevent the progression of OP via regulation of the AHR/PRELP/NF-κB axis, revealing a new molecular mechanism underpinning the impact of GRb1 in the progression of OP and offering a theoretical contribution to the treatment of OP.

Study Type : Animal Study

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