Tao-Hong-Si-Wu Decoction ameliorates steroid-induced avascular necrosis of the femoral head by regulating the HIF-1α pathway and cell apoptosis

Wu, Jian; Yao, Li; Wang, Bing; Liu, Zhen; Ma, Keyong

doi:10.5582/bst.2016.01099

Cited by 18 publications

(11 citation statements)

References 37 publications

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“…In addition, THSWD suppressed caspase-3 expression and induced bcl-2 expression in femoral head tissues. Like in our study, they concluded that THSWD can suppress ANFH by regulating the HIF-1α pathway and cell apoptosis [ 20 ]. Another study pointed out that was able to reduce steroid-induced bone cellular apoptosis, reduce the occurrence of necrosis of the femoral head and, through in vivo metabolism, it may promote the synthesis and release of IGF-1 [ 21 ].…”

Section: Discussionsupporting

confidence: 74%

Cortisol inhibits mTOR signaling in avascular necrosis of the femoral head

Liao

Zhang

et al. 2017

J Orthop Surg Res

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BackgroundANFH is a major health problem, to which long lasting and definitive treatments are lacking. The aim of this study is to study RNA alterations attributed to cortisol-induced ANFH.MethodsRat models were stratified into three groups: in vitro group (n = 20) for molecular biological assays, control group (n = 3), and ANFH group induced using lipopolysaccharide and dexamethasone (n = 3). Bone marrow-derived endothelial progenitor cells (BM-EPCs) were extracted from the rats. An RNA expression array was performed on BM-EPCs, and enriched genes were subject to pathway analysis. In vitro studies following findings of array results were also performed using the isolated BM-EPCs.ResultsSignificant alterations in mammalian target of rapamycin (mTOR) and HIF signaling pathways were identified in BM-EPCs of ANFH. By applying cortisol and dexamethasone to BM-EPCs, significant changes in mTOR and HIF elements were identified. The alteration of HIF pathways appeared to be downstream of mTOR signaling. Glucocorticoid receptor (GR) expression was related to glucocorticoid-dependent mRNA expression of mTOR/HIF genes. mTOR-dependent angiogenesis but not anabolism was the target of GR in ANFH. Inhibition of mTOR signaling also induced apoptosis of BM-EPCs via CHOP-dependent DR5 induction in response to GR stimulation.ConclusionDecreased mTOR signaling in response to GR stimulation leading to downregulated HIF pathway as well as increased apoptosis could be the pathophysiology.Electronic supplementary materialThe online version of this article (10.1186/s13018-017-0656-2) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 74%

Cortisol inhibits mTOR signaling in avascular necrosis of the femoral head

Liao

Zhang

et al. 2017

J Orthop Surg Res

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“…G. lucidum triterpene extract (GLT) induces the formation of autophagic vacuoles and upregulates the protein expression of Beclin-1 and LC-3 [ 33 ]. Tao-Hong-Si-Wu decoction significantly promotes the expression of HIF-1 α and VEGF in the femoral head tissue of rabbits and markedly inhibits the apoptosis of osteocytes, chondrocytes, and bone marrow cells [ 34 ]. In rats with SANFH, Gujiansan increased the levels of HIF-1 α , BNIP3, LC3, and Beclin-1 in a dose- and time-dependent manner, indicating that Gujiansan could activate autophagy and the HIF-1 α /BNIP3 pathway in SANFH.…”

Section: Discussionmentioning

confidence: 99%

Gujiansan Ameliorates Avascular Necrosis of the Femoral Head by Regulating Autophagy via the HIF-1α/BNIP3 Pathway

Han

Chai

Zhang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Clinically, the traditional Chinese medicine compound Gujiansan has been widely used in the treatment of steroid-induced avascular necrosis of the femoral head (SANFH). The present study aimed to investigate the mechanisms underlying the therapeutic effect of Gujiansan. Methods. A rat model of SANFH was established by the injection of dexamethasone (DEX) at a high dosage of 25 mg/kg/d. Then, Gujiansan was intragastrically administered for 2 weeks, 4 weeks, and 8 weeks, and histological examination of the femoral head was performed. The expression levels of related mRNAs and proteins were analyzed by qRT-PCR, Western blotting, and immunohistochemistry, and the levels of bone biochemical markers and cytokines were detected with ELISA kits. Results. Gujiansan administration ameliorated SANFH and induced the expression of hypoxia-inducible factor-1α (HIF-1α), Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), LC3, and Beclin-1 in the rat model in a dose- and time-dependent manner, and Gujiansan promoted osteocalcin secretion at the femoral head. In addition, Gujiansan increased the levels of bone formation- and bone resorption-specific markers (osteocalcin (OC), bone-specific alkaline phosphatase (BAP), tartrate resistant acid phosphatase-5b (TRACP-5b), N-terminal telopeptides of type I collagen (NTX-1), and C-terminal telopeptide of type I collagen (CTX-1)) and decreased the levels of proinflammatory cytokines (TNF-α, IL-6, and CRP) in a dose- and time-dependent manner. Conclusions. Gujiansan accelerates the formation of a new bone, promotes the absorption of the damaged bone, inhibits the inflammatory response, induces autophagy of the femoral head via the HIF-1α/BNIP3 pathway, and ultimately ameliorates SANFH.

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“…The THSWT formula is frequently administered in patients with ONFH in China. Data from animal testing suggest that the THSWT formula may help ameliorate the progression of steroid-induced avascular necrosis [ 17 ]. However, the active compounds and potential targets, as well as action pathways, remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms and Molecular Targets of the Tao‐Hong‐Si‐Wu‐Tang Formula for Treatment of Osteonecrosis of Femoral Head: A Network Pharmacology Study

Huang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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The Tao-Hong-Si-Wu-Tang (THSWT) formula, a classic prescription of traditional Chinese medicine, has long been used for the treatment of osteonecrosis of femoral head (ONFH). However, its mechanisms of action and molecular targets are not comprehensively clear. In the present study, the Traditional Chinese Medicine System Pharmacology (TCMSP) database was employed to retrieve the active compounds of each herb included in the THSWT formula. After identifying the drug targets of active compounds and disease targets of ONFH, intersection analysis was conducted to screen out the shared targets. The protein-protein network of the shared targets was built for further topological analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were then carried out. A gene pathway network was constructed to screen the core target genes. We identified 61 active compounds, 155 drug targets, and 5443 disease targets. However, intersection analysis only screened out 37 shared targets. Kaempferol, luteolin, and baicalein regulated the greatest number of targets associated with ONFH. The THSWT formula may regulate osteocyte function through specific biological processes, including responses to toxic substances and oxidative stress. The regulated pathways included the relaxin, focal adhesion, nuclear factor-κB, toll-like receptor, and AGE/RAGE signaling pathways. RELA, VEGFA, and STAT1 were the important target genes in the gene network associated with the THSWT formula for the treatment of ONFH. Therefore, the present study suggested that the THSWT formula has an action mechanism involving multiple compounds and network targets for the treatment of ONFH.

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Tao-Hong-Si-Wu Decoction ameliorates steroid-induced avascular necrosis of the femoral head by regulating the HIF-1α pathway and cell apoptosis

Cited by 18 publications

References 37 publications

Cortisol inhibits mTOR signaling in avascular necrosis of the femoral head

Cortisol inhibits mTOR signaling in avascular necrosis of the femoral head

Gujiansan Ameliorates Avascular Necrosis of the Femoral Head by Regulating Autophagy via the HIF-1α/BNIP3 Pathway

Mechanisms and Molecular Targets of the Tao‐Hong‐Si‐Wu‐Tang Formula for Treatment of Osteonecrosis of Femoral Head: A Network Pharmacology Study

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