Guo Chun, Li Yangyang, Yang Ruijuan, Xie Mingzhang, Chen Xiangfeng, Che Zhiqun, Wang Zhixia, Zhong Bin, Luo Yanhong, Leng Xiao-Min
Modern Industrial College of Biomedicine and Great Health, Youjiang Medical University for Nationalities, 98 Chengxiang Road, Youjiang District, Baise, 533000, Guangxi, China.
Department of Human Anatomy, School of Basic Medical Sciences, Youjiang Medical University for Nationalities, 98 Chengxiang Road, Youjiang District, Baise, 533000, Guangxi, China.
BMC Complement Med Ther. 2025 Feb 11;25(1):48. doi: 10.1186/s12906-025-04793-2.
Astragaloside IV (AS-IV) is a bioactive saponin extracted from Radix Astragali, and it is reported to promote osteoblast differentiation while inhibiting osteoclastogenesis. However, the mechanism of AS-IV in glucocorticoid-induced osteoclastogenesis (GIO) remains undetermined. Herein, we examined the influence of AS-IV on GIO and bone loss.
RAW264.7 cells were incubated with dexamethasone (Dex) alone or Dex and receptor activator of nuclear factor-B ligand (RANKL) (Dex and RANKL) for 2 days, and then treated with Dex or Dex and RANKL through AS-IV for the timeframes indicated. Following, mice were intraperitoneally administered with an intermediate-acting glucocorticoid, methylprednisolone (MP), or MP and AS-IV for 6 weeks.
AS-IV significantly decreased Dex-induced osteoclast nucleus and area, however, it did not impact the number of Dex-induced osteoclasts in RAW264.7 cells. AS-IV also significantly decreased the osteoclastic marker protein expressions in Dex-induced RAW264.7 cells with concentration of dose dependent fashion. Additionally, AS-IV promoted p38 phosphorylation (p-) and p-p65 translocation to the nucleus, while inhibiting phosphorylation of extracellular signal-regulated kinase (ERK) (p-ERK) and inhibitor of Nuclear factor κB (NF-κB) (p-IκB) levels. However, the AS-IV-mediated action on p-MAPK, p-NF-κB, and osteoclastic marker expressions were reversed by MAPK or IκB inhibitor in Dex-induced RAW264.7 cells. Furthermore, our in vivo evaluation revealed that AS-IV also attenuated the MP-mediated bone loss, and suppressed osteoclastogenesis.
This study demonstrates that AS-IV inhibits GIO and attenuates bone loss via the MAPK/NF-κB pathway. This also suggested that AS-IV could be a potential promising therapeutic agent for glucocorticoid-triggered bone loss.
黄芪甲苷IV（AS-IV）是从黄芪中提取的一种生物活性皂苷，据报道它能促进成骨细胞分化，同时抑制破骨细胞生成。然而，AS-IV在糖皮质激素诱导的破骨细胞生成（GIO）中的作用机制仍不明确。在此，我们研究了AS-IV对GIO和骨质流失的影响。
将RAW264.7细胞单独与地塞米松（Dex）或与核因子-κB受体活化因子配体（RANKL）及地塞米松（Dex和RANKL）共同孵育2天，然后在所示时间内用AS-IV处理Dex或Dex和RANKL。随后，给小鼠腹腔注射中效糖皮质激素甲泼尼龙（MP）或MP与AS-IV，持续6周。
AS-IV显著降低了Dex诱导的破骨细胞核及面积，但对RAW264.7细胞中Dex诱导的破骨细胞数量没有影响。AS-IV还以剂量依赖的方式显著降低了Dex诱导的RAW264.7细胞中破骨细胞标志物蛋白的表达。此外，AS-IV促进了p38磷酸化（p-p38）和p-p65向细胞核的转位，同时抑制细胞外信号调节激酶（ERK）磷酸化（p-ERK）和核因子κB抑制剂（IκB）水平。然而，在Dex诱导的RAW264.7细胞中，MAPK或IκB抑制剂可逆转AS-IV对p-MAPK、p-NF-κB和破骨细胞标志物表达的作用。此外，我们的体内评估显示，AS-IV还减轻了MP介导的骨质流失，并抑制了破骨细胞生成。
本研究表明，AS-IV通过MAPK/NF-κB途径抑制GIO并减轻骨质流失。这也提示AS-IV可能是治疗糖皮质激素引起的骨质流失的一种有潜力的治疗药物。
