Effect and mechanism of glycyrrhizic acid in improving steroid-induced ischemic necrosis of the femoral head

doi:10.16098/j.issn.0529-1356.2026.06.017

PDF(6676 KB)

Acta Anatomica Sinica ›› 2026, Vol. 57 ›› Issue (5) : 648-655. DOI: 10.16098/j.issn.0529-1356.2026.06.017

Histology and embryology and Developmental Biology

Effect and mechanism of glycyrrhizic acid in improving steroid-induced ischemic necrosis of the femoral head

LIU Chang^1*, PANG Jiao-yang¹, ZHAO Liang², LI Dan-yang1

Author information +

History +

Abstract

Objective To explore the effect and mechanism of glycyrrhizic acid(GLY) in improving steroid-induced avascular necrosis of the femoral head (SANFH) in rats. Methods Totally 72 SD rats were randomly assigned into normal control(NC) group, SANFH group, GLY low-dose (GLY-L) group, GLY high-dose (GLY-H) group, GLY-H+YC-1C ［hypoxia-inducible factor-1α(HIF-1α) inhibitor］ group, and alendronate sodium (ALN) group, with 12 rats in each group. Except for the NC group, the rats in the other groups were injected with 25 mg/kg dexamethasone by intramuscular injection every week for 8 consecutive weeks to establish the SANFH model. ELISA was used to detect the interleukin (IL)-18, IL-6, tumor necrosis factor α(TNF-α), osteocalcin (OCN), bone-specific alkaline phosphatase (BALP), tartrate resistant acid phosphatase 5b (TRACP-5b), collagen typeⅠcross-linked N-telopeptide (NTX-1), and collagen typeⅠcross-linked C-telopeptide (CTX-1) in serum. The femoral structure and apoptosis of bone tissue cells were detected. HE staining was used to detect the morphology of femoral tissue. Western blotting was used to detect the Runt related transcription factor 2(Runx2), bone morphogenetic protein-2(BMP-2), cleaved Caspase-3 (c-Casp-3), and HIF-1α/Bcl-2 interacting protein 3(BNIP3) pathway proteins. Results Compared with the NC group, the SANFH group showed conspicuous damage to the femoral head, sparse and obvious fracture of bone trabeculae, increased serum IL-18, IL-6, TNF-α, TRACP-5b, NTX-1 and CTX-1, empty bone resorption rate, bone trabecular separation degree (Tb.Sp), apoptosis rate of bone tissue cells, and c-Casp-3 protein, and decreased serum OCN and BALP levels, bone volume fraction (BV/TV), number of bone trabeculae (Tb.N), thickness of bone trabeculae (Tb.Th), Runx2, BMP-2, HIF-1α, and BNIP3 proteins (P<0.05). Compared with the SANFH group, the GLY-L group, GLY-H group, and ALN group showed reduced degree of femoral head injury, improved trabecular morphology, decreased serum IL-18, IL-6, TNF-α, TRACP-5b, NTX-1 and CTX-1, empty bone resorption rate, bone trabecular separation degree (Tb.Sp), apoptosis rate of bone tissue cells, and c-casp 3 protein, and increased serum OCN and BALP levels, BV/TV, Tb.N, Tb.Th, Runx2, BMP-2, HIF-1α, and BNIP3 proteins (P<0.05). CY-1 could reduce the improvement effect of GLY on the femoral head of SANFH rats (P<0.05). The above indicators of rats in GLY-H group and ALN group were at the same level (P>0.05). Conclusion GLY can reduce inflammation and osteoclast apoptosis in SANFH rats, promote new bone formation, and improve the shape of the femoral head. This may be related to the activation of the HIF-1α/BNIP3 pathway.

Key words

Glycyrrhizic acid

/ Steroid-induced avascular necrosis of femoral head / Hypoxia-inducible factor-1α/Bcl-2 interacting protein 3 pathway / Western blotting / Rat

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

LIU Chang, PANG Jiao-yang, ZHAO Liang, LI Dan-yang. Effect and mechanism of glycyrrhizic acid in improving steroid-induced ischemic necrosis of the femoral head[J]. Acta Anatomica Sinica. 2026, 57(5): 648-655 https://doi.org/10.16098/j.issn.0529-1356.2026.06.017

References

［1］Wu J, Chen T, Zhang M, et al. Atorvastatin exerts a preventive effect against steroid-induced necrosis of the femoral head by modulating Wnt5a release［J］. Arch Toxicol, 2024, 98(10):3365-3380.

［2］Chai JL, Lu BW, Du HT, et al. Pyroptosis-related potential diagnostic biomarkers in steroid-induced osteonecrosis of the femoral head［J］. BMC Musculoskelet Disord, 2023, 24(1):609-618.

［3］Lv W, Yu M, Yang Q, et al. Total flavonoids of Rhizoma drynariae ameliorate steroidinduced avascular necrosis of the femoral head via the PI3K/AKT pathway［J］. Mol Med Rep, 2021, 23(5):345-356.

［4］Jiang H, Lu Q, Huang X, et al. Sinomenine-glycyrrhizic acid self-assembly enhanced the anti-inflammatory effect of sinomenine in the treatment of rheumatoid arthritis［J］. J Control Release, 2025, 382(1):113718-113729.

［5］Xu H, Fang L, Zeng Q, et al. Glycyrrhizic acid alters the hyperoxidative stress-induced differentiation commitment of MSCs by activating the Wnt/β-catenin pathway to prevent SONFH［J］. Food Funct, 2023, 14(2):946-960.

［6］Hu ZhP, He ShQ, Wang ChM, et al. Glycyrrhizic acid inhibits PI3K/AKT/NF-κB to alleviate inflammatory response in collagen-induced rheumatoid arthritis rats［J］. Chinese Journal of Gerontology, 2020, 40(13): 2852-2856. (in Chinese)

胡志平, 何绍前, 王传明, 等. 甘草酸抑制PI3K/AKT/NF-κB减轻胶原诱导型类风湿关节炎大鼠炎症反应［J］. 中国老年学杂志, 2020, 40(13):2852-2856.

［7］Wang X, Wu Z, Zhang Y, et al. Autophagy induced by hypoxia in pulpitis is mediated by HIF-1α/BNIP3［J］. Arch Oral Biol, 2024, 159(1):105881-105890.

［8］Han J, Chai Y, Zhang XY, et al. Gujiansan ameliorates avascular necrosis of the femoral head by regulating autophagy via the HIF-1α/BNIP3 pathway［J］. Evid Based Complement Alternat Med, 2021, 2021(3):6683007-6683019.

［9］Zhang SY, Wang F, Zeng XJ, et al. Astragalus polysaccharide ameliorates steroid-induced osteonecrosis of femoral head through miR-206/HIF-1α/BNIP3 axis［J］. Kaohsiung J Med Sci, 2021, 37(12):1089-1100.

［10］Jia JJ, Xing HF, Zhang QZ, et al. Mechanism study on the improvement of renal injury in diabetic nephropathy rats by hypoxia-inducible factor-1α Inhibitor YC-1 ［J］. Journal of Shanghai Jiao Tong University (Medical Sciences), 2023, 43(9): 1089-1098. (in Chinese)

贾君杰, 邢海帆, 张群子, 等. 缺氧诱导因子-1α抑制剂YC-1改善糖尿病肾病大鼠肾脏损伤的机制研究［J］. 上海交通大学学报(医学版), 2023, 43(9):1089-1098.

［11］Liu JJ, Chen YX, Zhang XG, et al. The mechanism of baicalin derivatives regulating the PI3K/AKT/NF-κB signaling pathway in the treatment of steroid-induced ischemic necrosis of the femoral head ［J］. Chinese Journal of TCM, 2025, 40(3): 1397-1402.(in Chinese)

刘建军, 陈一新, 张晓刚, 等. 藁本内酯衍生物调控PI3K/AKT/NF-κB信号通路对激素性股骨头缺血性坏死的作用机制［J］. 中华中医药杂志, 2025, 40(3):1397-1402.

［12］Ren Z, Tang L, Ding Z, et al. Dried root of Rehmannia glutinosa extracts prevents steroid-induced avascular necrosis of femoral head by activating the wingless-type (Wnt)/β-catenin signal pathway［J］. Toxicon, 2023, 230(1):107174-107185.

［13］Zhang Y, Ma L, Lu E, et al. Atorvastatin upregulates microRNA-186 and inhibits the TLR4-Mediated MAPKs/NF-κB pathway to relieve steroid-induced avascular necrosis of the femoral head［J］. Front Pharmacol, 2021, 12(1):583975.

［14］zmen E, zol zmen H, Atasoy S, et al. The effects of prophylactic tadalafil use on VEGF expression in the rabbit model of steroid-induced femoral head avascular necrosis［J］. Acta Orthop Traumatol Turc, 2023, 57(5):237-242.

［15］Jia Z, Zhang J, Yang X, et al. Bioactive components and potential mechanisms of Biqi Capsule in the treatment of osteoarthritis: based on chondroprotective and anti-inflammatory activity［J］. Front Pharmacol, 2024, 15(2):1347970-134982.

［16］Fan Y, Niu Z, Yin L, et al. Membrane biomimetic nanoenzyme-incorporated hybrid glycyrrhizic acid hydrogel for precise mitochondrial ROS scavenging for osteoarthritis treatment［J］. Mater Today Bio, 2025, 32(1):101778-101788.

［17］Wang Y, Zhan Y, Ji C, et al. Houttuynia cordata Thunb repairs steroid-induced avascular necrosis of the femoral head through regulating NF-κB signaling pathway［J］. Toxicon, 2023, 233(1):107270-107282.

［18］Al-Rawaf HA, Gabr SA, Iqbal A, et al. MicroRNAs as potential biopredictors for premenopausal osteoporosis: a biochemical and molecular study［J］. BMC Womens Health, 2023, 23(1):481-492.

［19］Zhang XY, Li HN, Chen F, et al. Icariin regulates miR-23a-3p-mediated osteogenic differentiation of BMSCs via BMP-2/Smad5/Runx2 and WNT/β-catenin pathways in osteonecrosis of the femoral head［J］. Saudi Pharm J, 2021, 29(12):1405-1415.

［20］Zhang T, Ji Y, Yu S, et al. Rspo1 inhibited apoptosis of glucocorticoid-induced osteoblasts via Wnt/β-catenin pathway in Legg-Calve-Perthes disease［J］. Adv Clin Exp Med, 2023, 32(6):643-654.

［21］Hou Z, Wang Z, Zhang J, et al. Effects of cannabidiol on AMPKα2/HIF-1α/BNIP3/NIX signaling pathway in skeletal muscle injury［J］. Front Pharmacol, 2024, 15(2):1450513-1450524.

［22］Li S, Jiang J, Fang J, et al. Naringin protects H9C2 cardiomyocytes from chemical hypoxia-induced injury by promoting the autophagic flux via the activation of the HIF-1α/BNIP3 signaling pathway［J］. Int J Mol Med, 2021, 47(6):102-114.

［23］Wang X, Fan MY, Wang P. The effect of shanzhisan on IL-1β-induced autophagy and apoptosis of chondrocytes through regulating the HIF-1α/BNIP3 signaling pathway ［J］. Chinese Journal of Geriatrics, 2024, 44(23): 5807-5810.(in Chinese)

王欣, 范明宇, 汪平. 山姜素调节HIF-1α/BNIP3信号通路对IL-1β诱导的软骨细胞自噬和凋亡的影响［J］. 中国老年学杂志, 2024, 44(23):5807-5810.

［24］Zhang XX, Liang X, Li SR, et al. Bone marrow mesenchymal stem cells overexpressing HIF-1α prevented the progression of glucocorticoid-Induced avascular osteonecrosis of femoral heads in mice［J］. Cell Transplant, 2022, 31(4):9636897221082687.