Abstract：
Secondary osteoporosis is frequently due to the use of high-dose glucocorticoids (GCs). The existing strategy for managing glucocorticoid-induced osteoporosis (GIOP) is considered insufficient and remains in a state of ongoing evolution. Therefore, it is crucial to develop more precise and effective agents for the treatment of GIOP. The constituents of Reynoutria multiflora (Thunb.) Moldenke, specifically Polygonum multiflorum (PM) Thunb, have previously shown promise in mitigating osteopenia. This study aimed to investigate the therapeutic effects of an ethanolic PM extract (PMR30) against GIOP in male rats. Prednisone (6 mg/kg/day, GC) was continuously administered to rats to induce GIOP, and they were subjected to treatment with or without ethanolic PMR30 for a duration of 120 days. Serum was collected for biochemical marker analysis. Bone histomorphometric, histological, and TUNEL analyses were performed on tibia samples. The protein expressions of LC3, Agt5, and Beclin 1 in the femur underwent examination through western blotting. Prolonged and excessive GC treatment significantly impeded bone formation, concomitant with reduced bone mass and body weight. It also suppressed OCN and OPG/RANKL in serum, and decreased Beclin 1 and LC3 in bone. Simultaneously, there was an elevation in bone resorption markers and apoptosis. Treatments with both high dose and low dose of PMR30 alleviated GIOP, stimulated bone formation, and upregulated OCN and OPG/RANKL, while suppressing TRACP-5b, CTX-I, and apoptosis. The impact of PMR30 possibly involves the enhancement of autophagy proteins (LC3, Agt5, and Beclin 1) and the inhibition of apoptosis within the bone. PMR30 holds promise as a prospective therapeutic agent for preventing and treating GIOP.
摘要：
继发性骨质疏松症通常是由于使用高剂量糖皮质激素（GC）。现有的治疗糖皮质激素诱导的骨质疏松症（GIOP）的策略被认为是不够的，并且仍处于持续发展的状态。因此,开发更精确和有效的治疗GIOP的药物至关重要.多花Reynoutria（Thunb。)Moldenke,特别是何首乌（PM），以前在减轻骨质减少方面表现出了希望。本研究旨在研究PM乙醇提取物（PMR30）对雄性大鼠GIOP的治疗作用。泼尼松（6mg/kg/天，GC）连续给大鼠以诱导GIOP，他们接受有或没有PMR30乙醇的治疗，持续120天。收集血清用于生化标记物分析。骨组织形态计量学,组织学,对胫骨样本进行TUNEL分析。通过蛋白质印迹法检查股骨中LC3，Agt5和Beclin1的蛋白表达。长期和过量的GC治疗显著阻碍骨形成，伴随着骨量和体重的减少。它还抑制血清中的OCN和OPG/RANKL，骨中Beclin1和LC3减少。同时,骨吸收标志物和细胞凋亡升高。高剂量和低剂量PMR30治疗可缓解GIOP，刺激骨形成，并上调OCN和OPG/RANKL，在抑制TRACP-5b的同时，CTX-I,和凋亡。PMR30的影响可能涉及自噬蛋白（LC3，Agt5和Beclin1）的增强和骨内细胞凋亡的抑制。PMR30有望成为预防和治疗GIOP的前瞻性治疗剂。
