Inhibition of osteoclastogenesis for periprosthetic osteolysis therapy through the suppression of p38 signaling by fraxetin

Wei, Zhaoxia; Zhao, Chang; Ma, Zhigui; Cai, Daozhang

doi:10.3892/ijmm.2018.3698

Cited by 3 publications

(6 citation statements)

References 39 publications

(44 reference statements)

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“…Naringin has also shown nephroprotective activity against chemical-induced toxicity and renal ischemia/reperfusion injury (Amini et al, 2022a) mitochondria dysfunction induced by renal ischemia/reperfusion injury in rats (Amini et al, 2022b). Previous research has highlighted fraxetin's potential as a novel antioxidant (Kostova et al, 2011), its ability to inhibit osteoblast apoptosis (Liao et al, 2018), and its role in preventing human hepatoma cell apoptosis induced by mitochondrial dysfunction (Song et al, 2021). However, the specific anti-damage effect of fraxetin CKI and its underlying molecular mechanism remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Fraxetin pretreatment alleviates cisplatin‐induced kidney injury by antagonizing autophagy and apoptosis via mTORC1 activation

Yuan,

Yang,

et al. 2024

Phytotherapy Research

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Cisplatin‐induced kidney injury (CKI) is a common complication of chemotherapy. Fraxetin, derived from Fraxinus bungeana A. DC. bark, has antioxidant, anti‐inflammatory, and anti‐fibrotic effects. This study aims to investigate fraxetin's effects on CKI and its underlying mechanism in vivo and in vitro. Tubular epithelial cells (TECs) and mice were exposed to cisplatin with and without fraxetin preconditioning assess fraxetin's role in CKI. TECs autophagy was observed using transmission electron microscopy. Apoptosis levels in animal tissues were measured using TUNEL staining. The protective mechanism of fraxetin was explored through pharmacological and genetic regulation of mTORC1. Molecular docking was used to identify potential binding sites between fraxetin and mTORC1. The results indicated that fraxetin pretreatment reduced cisplatin‐induced kidney injury in a time‐ and concentration‐dependent way. Fraxetin also decreased autophagy in TECs, as observed through electron microscopy. Tissue staining confirmed that fraxetin pretreatment significantly reduced cisplatin‐induced apoptosis. Inhibition of mTORC1 using rapamycin or siRNA reversed the protective effects of fraxetin on apoptosis and autophagy in cisplatin‐treated TECs, while activation of mTORC1 enhanced fraxetin's protective effect. Molecular docking analysis revealed that fraxetin can bind to HEAT‐repeats binding site on mTORC1 protein. In summary, fraxetin pretreatment alleviates CKI by antagonizing autophagy and apoptosis via mTORC1 activation. This provides evidence for the potential therapeutic application of fraxetin in CKI.

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Section: Discussionmentioning

confidence: 99%

Fraxetin pretreatment alleviates cisplatin‐induced kidney injury by antagonizing autophagy and apoptosis via mTORC1 activation

Yuan,

Yang,

et al. 2024

Phytotherapy Research

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“…To inhibit titanium particle-mediated osteolysis in BMM cells via p38 signaling suppression [93] In vivo 5 mg/kg, ip To inhibit titanium particle-mediated osteolysis in mice via p38 signaling suppression [93] In vitro 10-50 µM To inhibit IL-1β-induced apoptosis, inflammation, and matrix degradation in chondrocytes [94] In vivo 5 mg/kg, ip To inhibit iodoaceate-mediated osteoarthritis mice [94] In vitro 10 µM To inhibit the anti-Fas IgM-mediated apoptosis and apoptotic synergetic effect of TNF-α and IL-1β in MG-63 cells via Fas pathway inhibition [95] Lung protective activity…”

Section: In Vitro 12 µMmentioning

confidence: 99%

“…Periprosthetic osteolysis occurs when the rate between osteoclast and osteoblast is imbalanced. [ 93 ] Fraxetin inhibited titanium particle‐mediated osteolysis in bone marrow‐derived macrophages (BMMs) cells in vitro and in mice in vivo via p38 signaling suppression. [ 93 ] Herein, it is found that fraxetin suppressed receptor activator of nuclear factor‐κB ligand (RANKL) osteoclast differentiation and bone resorption.…”

Section: Pharmacologymentioning

confidence: 99%

“…[ 93 ] Fraxetin inhibited titanium particle‐mediated osteolysis in bone marrow‐derived macrophages (BMMs) cells in vitro and in mice in vivo via p38 signaling suppression. [ 93 ] Herein, it is found that fraxetin suppressed receptor activator of nuclear factor‐κB ligand (RANKL) osteoclast differentiation and bone resorption. [ 93 ] Osteoarthritis is defined as the deterioration of the joint complex as a result of cartilage degradation.…”

Section: Pharmacologymentioning

confidence: 99%

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Health benefits of fraxetin: From chemistry to medicine

Ha,

Son

2024

Archiv der Pharmazie

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Fraxetin is a bioactive molecule present in various natural plants, especially Cortex Fraxini. Evidenced outcomes in phytochemical and biological analyses for this agent are now available in the literature, but an insightful review is yet unknown. The goal of the current research is to offer a panoramic illustration of natural observation, biosynthesis, synthesis, pharmacology, and pharmacokinetics for fraxetin. Esculetin and ferulic acid acted as precursors in the enzymatic biosynthetic route, whereas fraxetin could be easily synthesized from simple phenols. A great deal of interest was obtained in using this molecule for pharmacological targets. Herein, its pharmacological value included anticancer, antioxidative, anti‐inflammatory, antidiabetic, antiobesity, and antimicrobial activities, as well as the protection of the liver, neurons, heart, bone, lung, kidney, and others. Anticancer activity may involve the inhibition of proliferation, invasion, and migration, together with apoptotic induction. Health benefits from this molecule were deduced from its ability to suppress cytokines and protect the immune syndrome. Various signaling pathways, such as Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3), phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt), nuclear factor kappa B (NF‐κB)/NLRP3, Akt/AMPK, have been proposed for in vitro and in vivo mechanisms of action. Fraxetin is highly distributed to rat plasma and several organs. However, more pharmacokinetic studies to improve its bioavailability are needed since its solubility in water is still limited.

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“…Based on the mass spectra and retention times, WEAD was identified to comprise one hydroxycinnamic acid (caffeic acid) along with fourteen coumarins: esculin, scopolin, fraxetin, scopoletin, isofraxidin, xanthotoxol, scoparone, oxypeucedanin hydrate, apaensin, methoxsalen, byakangelicol, oxypeucedanin, imperatorin and phellopterin (Figure 6 and Table 1). Among these, esculin [32,33], scopoline [34,35], caffeic acid [36,37], fraxetin [38,39], scopoletin [40,41], isofraxidin [42,43], scoparone [44,45] and imperatorin [46,47] have been previously reported to exhibit hepatoprotective effects, along with inhibitory effects on osteoclastogenesis or anti-osteoporotic effects. Furthermore, bergapten has been demonstrated to hinder osteoclast differentiation and mitigate bone loss in OVX mice [48], while oxypeucedanin and phellopterin have exhibited anti-obesity properties [49].…”

Section: Phytochemical Constituents Of Weadmentioning

confidence: 99%

Water Extract of Angelica dahurica Inhibits Osteoclast Differentiation and Bone Loss

Gu,

Yang,

Kim

et al. 2023

IJMS

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Angelica dahurica radix has a long history of traditional use in China and Korea for treating headaches, cold-damp pain and skin diseases. Despite various pharmacological studies on A. dahurica, its impact on bones remains unclear. Hence, this study investigated the inhibitory effect of A. dahurica’s radix water extract (WEAD) on osteoclast differentiation. In vitro experiments showed that WEAD effectively suppresses osteoclast differentiation. Treatment of an osteoclast precursor with WEAD significantly suppressed the expression of nuclear factor of activated T-cells 1 (NFATc1), essential transcription factor for osteoclastogenesis, while increasing the expression of negative regulators, interferon regulatory factor 8 (Irf8) and v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MafB). Consistent with the in vitro findings, the oral administration of WEAD (100 and 300 mg/kg/day) to mice subjected to surgical ovariectomy for a duration of six weeks alleviated bone loss, while also mitigating weight gain and liver fat accumulation. In addition, we also identified phytochemicals present in WEAD, known to regulate osteoclastogenesis and/or bone loss. These results suggest the potential use of WEAD for treating various bone disorders caused by excessive bone resorption.

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Inhibition of osteoclastogenesis for periprosthetic osteolysis therapy through the suppression of p38 signaling by fraxetin

Cited by 3 publications

References 39 publications

Fraxetin pretreatment alleviates cisplatin‐induced kidney injury by antagonizing autophagy and apoptosis via mTORC1 activation

Fraxetin pretreatment alleviates cisplatin‐induced kidney injury by antagonizing autophagy and apoptosis via mTORC1 activation

Health benefits of fraxetin: From chemistry to medicine

Water Extract of Angelica dahurica Inhibits Osteoclast Differentiation and Bone Loss

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