Exploring the mechanism of Bushen Zhuangjin Decoction on improving cartilage damage in a rabbit model of knee osteoarthritis via ACSL4-mediated ferroptosis pathway

Feng Lina, Yan Liang, Wang Shangzeng, Xue Shuina

Chinese Journal of Clinical Anatomy ›› 2026, Vol. 44 ›› Issue (2) : 182-188.

PDF(4555 KB)
PDF(4555 KB)
Chinese Journal of Clinical Anatomy ›› 2026, Vol. 44 ›› Issue (2) : 182-188. DOI: 10.13418/j.issn.1001-165x.2026.2.09

Exploring the mechanism of Bushen Zhuangjin Decoction on improving cartilage damage in a rabbit model of knee osteoarthritis via ACSL4-mediated ferroptosis pathway

  • Feng Lina1, Yan Liang2*, Wang Shangzeng3, Xue Shuina3
Author information +
History +

Abstract

Objective    To investigate the effects of Bushen Zhuangjin Decoction on cartilage injury and the long-chain acyl-CoA synthase 4 (ACSL4) pathway in rabbits with knee osteoarthritis (KOA).  Methods   Rabbits were randomly divided into the normal, the KOA, the low-dose and high-dose Bushen Zhuangjin Decoction, the celecoxib, and the high-dose Bushen Zhuangjin Decoction + rosiglitazone groups, with 12 rabbits in each group. The levels of serum interleukin (IL) -18, IL-6 and tumor necrosis factor -α (TNF-α) were monitored; The pathology of articular cartilage was detected by safranin O-green staining. The mitochondrial structure of articular cartilage was observed by transmission electron microscopy. Prussian blue staining was used to detect iron deposition in articular cartilage. The levels of Fe2+, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) in articular cartilage, as well as glutathione peroxidase 4 (GPX4), plasma vector family 7 member 11 (SLC7A11), and ACSL4 proteins were analyzed respectively. Results    Compared with KOA group, the pathological and mitochondrial damage of articular cartilage tissue in the low-dose and high-dose Bushen Zhuangjin Decoction groups and cecoxib group were alleviated, iron deposition reduced, the levels of serum IL-6, IL-18, and TNF-α decreased, and the levels of Fe2+ and MDA, the average fluorescence intensity of ROS, and the ACSL4 protein in articular cartilage tissue decreased. The levels of GSH and the proteins of GPX4 and SLC7A11 increased (P<0.05); Rosiglitazone reversed the inhibitory effect of high-dose Bushen Zhuangjin Decoction on ferroptosis in KOA rabbits.   Conclusions Bushen Zhuangjin Decoction may inhibit ferroptosis in KOA rabbits by suppressing the ACSL4 pathway, thereby regulating articular cartilage injury.

Key words

Bushen Zhuangjin Decoction /   /   / Knee osteoarthritis /   /   / Ferroptosis /   /   / Oxidative stress / Long-chain acyl-CoA synthetase 4

Cite this article

Download Citations
Feng Lina, Yan Liang, Wang Shangzeng, Xue Shuina. Exploring the mechanism of Bushen Zhuangjin Decoction on improving cartilage damage in a rabbit model of knee osteoarthritis via ACSL4-mediated ferroptosis pathway[J]. Chinese Journal of Clinical Anatomy. 2026, 44(2): 182-188 https://doi.org/10.13418/j.issn.1001-165x.2026.2.09

References

[1] He Q, Yang J, Pan Z, et al. Biochanin A protects against iron overload associated knee osteoarthritis via regulating iron levels and NRF2/System xc-/GPX4 axis[J]. Biomed Pharmacother, 2023,157:113915. DOI:10.1016/j.biopha.2022.113915.
[2] Kuang S, Liu Z, Liu L, et al. Polygonatum sibiricum polysaccharides protect against knee osteoarthritis by inhibiting the TLR2/NF-κB signaling pathway in vivo and in vitro[J]. Int J Biol Macromol, 2024,274(Pt 1):133137. DOI:10.1016/j.ijbiomac.2024.133137. 
[3]  Guan Z, Jin X, Guan Z, et al. The gut microbiota metabolite capsiate regulate SLC2A1 expression by targeting HIF-1α to inhibit knee osteoarthritis-induced ferroptosis[J]. Aging Cell, 2023,22(6):e13807. DOI:10.1111/acel.13807. 
[4]  许云腾, 陈达, 谭雪, 等. 补肾壮筋汤抑制膝骨关节炎软骨退变机制研究[J]. 中华中医药杂志, 2021, 36(7):4178-4181.
       Xu YT, Chen D, Tan X, et al. Research on the mechanism of Bushen Zhuangjin Decoction in inhibiting cartilage degeneration in knee osteoarthritis [J]. Chin J Trad Chin Med, 2021, 36(7): 4178-4181.
[5] Habaxi K, Wang W, Taximaimaiti M, et al. Methylation regulation of LPCAT3 improves osteoarthritis by regulating ACSL4 to inhibit chondrocyte ferroptosis[J]. Crit Rev Eukaryot Gene Expr, 2024,34(2):77-86. DOI:10.1615/CritRevEukaryotGeneExpr.2023049244. 
[6]  贺琳钦, 李鹏飞, 李小冬, 等.独活寄生汤调控PI3K/Akt/mTOR信号通路介导细胞焦亡对膝骨关节炎模型兔的影响[J].中国中药杂志,2025, 50(1): 187-197. DOI:10.19540/j.cnki.cjcmm.20240912.401.
      He LQ, Li PF, Li XD, et al. The effect of Duhuo Jishi Decoction regulating the PI3K/Akt/mTOR signaling pathway to mediate pyroptosis on a rabbit model of knee osteoarthritis [J]. China J Chin Mater Med, 2025, 50 (1):187-197. DOI:10.19540/j.carol carroll nki CJCMM.20240912.401.
[7]  梁杰, 柳维林, 韩平, 等.补肾壮筋汤对兔膝骨关节炎软骨形态学和骨架蛋白ROCK、Cofilin、Phospho-Cofilin、LIMK1和Phospho-LIMK1的影响[J]. 中华中医药杂志, 2015, 30(10): 3732-3735.
      Liang J, Liu WL, Han P, et al. The effects of Bushen Zhuangjin Decoction on cartilage morphology and skeletal proteins ROCK, Cofilin, Phospho-Cofilin, LIMK1 and Phospho-LIMK1 in rabbit knee osteoarthritis [J]. Chin J Trad Chin Med, 2015, 30(10): 3732-3735.
[8]  叶子丰, 院一蔚, 邱礼国, 等.加味独活寄生合剂调控PI3K/Akt/mTOR通路对膝骨关节炎兔滑膜细胞焦亡的影响[J]. 中国实验方剂学杂志,2026, 32(1): 170-179. DOI:10.13422/j.cnki.syfjx.20250739
       Ye ZF, Yuan YW, Qiu LG, et al. The effect of modified Duhuo Parasitic Agent regulating the PI3K/Akt/mTOR pathway on pyroptosis of synovial cells in rabbits with knee osteoarthritis [J]. Chin J Exp Tradit Med Form, 2026, 32(1): 170-179. DOI:10.13422/j.cnki.syfjx.20250739
[9] Dai Y, Chen Y, Mo D, et al. Inhibition of ACSL4 ameliorates tubular ferroptotic cell death and protects against fibrotic kidney disease[J]. Commun Biol, 2023, 6(1): 907. DOI:10.1038/s42003-023-05272-5. 
[10] Wang K, Zhang X, Li X, et al. Non-weight-bearing exercise attenuates papain-induced knee osteoarthritis in rats via the TLR4/MyD88/NF-κB signaling pathway[J]. J Orthop Surg Res, 2023,18(1):695. DOI: 10.1186/s13018-023-04201-w. 
[11]Sun W, Yue M, Xi G, et al. Knockdown of NEK7 alleviates anterior cruciate ligament transection osteoarthritis (ACLT)-induced knee osteoarthritis in mice via inhibiting NLRP3 activation[J]. Autoimmunity, 2022,55(6):398-407. DOI:10.1080/08916934.2022. 2093861. 
[12] Mahfouz R, H El-Rewini S, I Ghoneim A, et al. L-Carnitine augments probenecid anti-inflammatory effect in monoiodoacetate-induced knee osteoarthritis in rats: involvement of miRNA-373/P2X7/NLRP3/NF-κB milieu[J]. Inflammopharmacology, 2024, 32(1):715-731. DOI: 10.1007/s10787-023-01376-w. 
[13]Zhang Z, Yuan D, Jin X, et al. Asperosaponin VI suppresses ferroptosis in chondrocytes and ameliorates osteoarthritis by modulating the Nrf2/GPX4/HO-1 signaling pathway[J]. Front Pharmacol, 2025,16:1539092. DOI: 10.3389/fphar.2025.1539092. 
[14]Xiao J, Luo C, Li A, et al. Icariin inhibits chondrocyte ferroptosis and alleviates osteoarthritis by enhancing the SLC7A11/GPX4 signaling[J]. Int Immunopharmacol, 2024,133:112010. DOI:10.1016/j.intimp.2024. 112010. 
[15]Li F, Li J, Hao J, et al. HINT2 deficiency deteriorates oxidative stress in a mouse model of myocardial infarction[J]. ESC Heart Fail, 2023,10(2):1305-1313. DOI:10.1002/ehf2.14292. 
[16]Chen R, Ying C, Zou Y, et al. Sarsasapogenin inhibits YAP1-dependent chondrocyte ferroptosis to alleviate osteoarthritis[J]. Biomed Pharmacother, 2023, 168:115772. DOI:10.1016/j.biopha.2023.115772. 
[17]Yang M, Chen X, Cheng C, et al. Cucurbitacin B induces ferroptosis in oral leukoplakia via the SLC7A11/mitochondrial oxidative stress pathway[J]. Phytomedicine, 2024,129:155548. DOI:10.1016/j.phymed. 2024.155548. 
[18]Kou Z, Tran F, Colon T, et al. AhR signaling modulates ferroptosis by regulating SLC7A11 expression[J]. Toxicol Appl Pharmacol, 2024,486:116936. DOI:10.1016/j.taap.2024.116936. 
[19]杨彬, 程韶, 杨顺, 等. 基于miR-146a-5p/Notch1信号通路探讨补肾壮筋汤对骨质疏松小鼠骨密度及成骨分化的影响[J]. 药物评价研究,2025, 48(1): 73-84. DOI:10.7501/j.issn.1674-6376.2025.01.007.
      Yang B, Cheng S, Yang S, et al. To explore the effect of Bushen Zhuangjin Decoction on bone mineral density and osteogenic differentiation in osteoporotic mice based on the miR-146a-5p/Notch1 signaling pathway [J]. Drug Eval Res, 2025, 48(1): 73-84. DOI: 10.7501/j.issn.1674-6376.2025.01.007.
[20]黄艳峰, 马德尊, 付长龙, 等. 基于SDF-1/CXCR4轴探讨补肾壮筋汤促进小鼠BMSCs归巢和保护关节软骨的机制研究[J]. 康复学报, 2024, 34(1): 44-54. DOI:10.3724/SP.J.1329.2024.01007.
       Huang YF, Ma DZ, Fu CL, et al. Research on the mechanism of Bushen Zhuangjin Decoction in promoting the homing of BMSCs and protecting articular cartilage in Mice based on the SDF-1/CXCR4 axis [J]. J Rehabil, 2024, (1) : 44-54. DOI:10.3724/SP. J.1329.2024.1007.
[21]邓纯国.补肾壮筋汤治疗肝肾不足型膝关节骨性关节炎的临床疗效研究[J].中医临床研究, 2019, 11(12): 68-69. DOI:10.3969/j.issn.1674-7860.2019.12.024
      Deng CG. Clinical efficacy study of Bushen Zhuangjin Decoction in the treatment of knee osteoarthritis with insufficiency of liver and kidney [J]. Clin J Chin Med, 2019,11(12): 68-69. DOI:10.3969/j.issn.1674-7860.2019.12.024
[22]Xu S, Tuo QZ, Meng J, et al. Thrombin induces ferroptosis in triple-negative breast cancer through the cPLA2α/ACSL4 signaling pathway[J]. Transl Oncol, 2024, 39:101817. DOI:10.1016/j.tranon.2023. 101817. 
[23]He W, Lin X, Chen K. Specificity protein 1-mediated ACSL4 transcription promoted the osteoarthritis progression through suppressing the ferroptosis of chondrocytes[J]. J Orthop Surg Res, 2023, 18(1): 188. DOI:10.1186/s13018-023-03673-0. 
PDF(4555 KB)

Accesses

Citation

Detail

Sections
Recommended

/