# Identification and validation of biomarkers of Shenggu Zaizao Wan in the treatment of steroid-induced osteonecrosis of the femoral head by integrating network pharmacology and bulk transcriptomic **Authors:** Tao Ma, Duoxian Wang, Qingsheng Xie, Yin Li, Jinpeng Wang, Xiaogang Zhang, Lingwei Yuan, Hairong He, Xianfu Han, Xuerui Liu, Jianjun Liu, Haiyang Yu, Jinqiu Wu PMC · DOI: 10.3389/fmed.2026.1732825 · Frontiers in Medicine · 2026-02-04 ## TL;DR This study identifies IKBKB and PRKCA as potential biomarkers for treating steroid-induced femoral head osteonecrosis using Shenggu Zaizao Wan. ## Contribution Novel biomarkers IKBKB and PRKCA are identified and validated for SZW treatment of SONFH using integrated network pharmacology and transcriptomic analysis. ## Key findings - IKBKB and PRKCA were identified as potential biomarkers for SZW treatment of SONFH. - Biomarkers influence pathways related to the ribosome based on GSEA. - Molecular docking showed strong affinity between SZW compounds and the biomarkers. ## Abstract Steroid-induced osteonecrosis of the femoral head (SONFH) is a debilitating condition. Research has shown that Shenggu Zaizao Wan (SZW) may have therapeutic effects on SONFH. This study aimed to elucidate the mechanisms by which SZW treats SONFH. SONFH and control samples were retrieved from a database to identify differentially expressed genes (DEGs). Biomarkers were obtained through the intersection of DEGs and potential targets, machine learning, and expression validation. A nomogram was constructed, followed by gene set enrichment analysis (GSEA) of biomarkers and immune infiltration analysis. Molecular docking was conducted, and the expression of biomarkers was evaluated using real-time quantitative reverse transcription PCR (RT-qPCR). A total of 69 potential SZW targets and 1,671 DEGs were identified. IKBKB and PRKCA were established as biomarkers for SONFH, and a nomogram was developed. GSEA indicated that IKBKB and PRKCA may influence pathways related to the ribosome. Immune infiltration analysis revealed that CD4+ T cells play a role in SONFH. Molecular docking showed a strong affinity between SZW compounds and biomarkers. The expression of biomarkers in clinical samples aligned with the results from bioinformatics analysis. This study identified IKBKB and PRKCA as potential biomarkers and targets for SZW treatment in SONFH. ## Linked entities - **Genes:** IKBKB (inhibitor of nuclear factor kappa B kinase subunit beta) [NCBI Gene 3551], PRKCA (protein kinase C alpha) [NCBI Gene 5578] ## Full-text entities - **Genes:** CASP1 (caspase 1) [NCBI Gene 834] {aka ICE, IL1BC, P45}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, PRKCA (protein kinase C alpha) [NCBI Gene 5578] {aka AAG6, PKC-alpha, PKCA, PKCI+/-, PKCalpha}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, SPI1 (Spi-1 proto-oncogene) [NCBI Gene 6688] {aka AGM10, OF, PU.1, SFPI1, SPI-1, SPI-A}, RHOG (ras homolog family member G) [NCBI Gene 391] {aka ARHG}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, F3 (coagulation factor III, tissue factor) [NCBI Gene 2152] {aka CD142, TF, TFA}, BCL11B (BCL11 transcription factor B) [NCBI Gene 64919] {aka ATL1, ATL1-alpha, ATL1-beta, ATL1-delta, ATL1-gamma, CTIP-2}, MAP3K14 (mitogen-activated protein kinase kinase kinase 14) [NCBI Gene 9020] {aka FTDCR1B, HS, HSNIK, IMD112, NIK}, SCRT2 (scratch family transcriptional repressor 2) [NCBI Gene 85508] {aka ZNF898B}, IKBKB (inhibitor of nuclear factor kappa B kinase subunit beta) [NCBI Gene 3551] {aka IKK-2, IKK-beta, IKK2, IKKB, IMD15, IMD15A}, NFKBIA (NFKB inhibitor alpha) [NCBI Gene 4792] {aka EDAID2, IKBA, MAD-3, NFKBI}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, RAF1 (Raf-1 proto-oncogene, serine/threonine kinase) [NCBI Gene 5894] {aka CMD1NN, CRAF, NS5, Raf-1, c-Raf}, CLEC4D (C-type lectin domain family 4 member D) [NCBI Gene 338339] {aka CD368, CLEC-6, CLEC6, CLECSF8, Dectin-3, MCL}, RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970] {aka AIF3BL3, CMCU, NFKB3, p65}, SNHG11 (small nucleolar RNA host gene 11) [NCBI Gene 128439] {aka C20orf198, LINC00101, NCRNA00101}, CHUK (component of inhibitor of nuclear factor kappa B kinase complex) [NCBI Gene 1147] {aka BPS2, IKBKA, IKK-1, IKK-alpha, IKK1, IKKA}, MLLT1 (MLLT1 super elongation complex subunit) [NCBI Gene 4298] {aka ENL, LTG19, YEATS1}, H19 (H19 imprinted maternally expressed transcript) [NCBI Gene 283120] {aka ASM, ASM1, BWS, D11S813E, GMRSP, LINC00008}, FBP1 (fructose-bisphosphatase 1) [NCBI Gene 2203] {aka FBP}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, ADNP (activity dependent neuroprotector homeobox) [NCBI Gene 23394] {aka ADNP1, HVDAS, MRD28}, MDS2 (myelodysplastic syndrome 2 translocation associated) [NCBI Gene 259283], Prkca (protein kinase C, alpha) [NCBI Gene 18750] {aka Pkca}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, IKBKG (inhibitor of nuclear factor kappa B kinase regulatory subunit gamma) [NCBI Gene 8517] {aka AMCBX1, EDAID1, FIP-3, FIP3, Fip3p, IKK-gamma} - **Diseases:** Gastrointestinal Disorders (MESH:D005767), coagulation disorders (MESH:D001778), XL (MESH:D000080345), osteoporosis (MESH:D010024), joint diseases (MESH:D007592), osteonecrosis of the jaw (MESH:D059266), MFs (MESH:C567116), vascular damage (MESH:D057772), metastasis (MESH:D009362), DICs (MESH:C537655), necrosis (MESH:D009336), sepsis (MESH:D018805), severe combined immunodeficiency (MESH:D016511), breast cancer (MESH:D001943), orthopedic (MESH:D009140), tumor (MESH:D009369), osteonecrosis (MESH:D010020), skeletal disorder (MESH:C564967), femoral head necrosis (MESH:D005271), acute lung injury (MESH:D055371), osteosarcoma (MESH:D012516), inflammation (MESH:D007249), developmental abnormalities (MESH:D006130), fractures (MESH:D050723), hip pain (MESH:D010146), osteoarticular disease (MESH:D014394), degenerative arthritis (MESH:D010003), collapse of the femoral head (MESH:D000070603), TsI (MESH:D006969), abnormal bone resorption (MESH:D001862), functional (MESH:D003291) - **Chemicals:** Icariin (MESH:C056599), SONFH (-), hydrogen (MESH:D006859), luteolin (MESH:D047311), bisphosphonate (MESH:D004164), Steroid (MESH:D013256), astragaloside IV (MESH:C052064), LPS (MESH:D008070), taxifolin (MESH:C003377), water (MESH:D014867), Tanshinone I (MESH:C021751), TRIzol (MESH:C411644), hederagenin (MESH:C025763) - **Species:** Davallia trichomanoides (species) [taxon 328206], Homo sapiens (human, species) [taxon 9606], Cullen corylifolium (species) [taxon 429560], Sphingobacterium deserti (species) [taxon 1229276], Salvia miltiorrhiza (Chinese salvia, species) [taxon 226208], Panax notoginseng (notoginseng, species) [taxon 44586], Mus musculus (house mouse, species) [taxon 10090], Epimedium brevicornu (species) [taxon 253618], Astragalus membranaceus (species) [taxon 649199], Crataegus pinnatifida (Chinese hawthorn, species) [taxon 510735], Wolfiporia cocos (species) [taxon 81056] ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12913513/full.md ## Figures 9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12913513/full.md ## References 60 references — full list in the complete paper: https://tomesphere.com/paper/PMC12913513/full.md --- Source: https://tomesphere.com/paper/PMC12913513