Fraxetin inhibits interleukin-1β-induced apoptosis, inflammation, and matrix degradation in chondrocytes and protects rat cartilage in vivo

Wang, Qing; Zhuang, Di; Feng, Wenchang; Ma, Bitao; Qin, Liping; Jin, Lilun

doi:10.1016/j.jsps.2020.09.016

Cited by 22 publications

(29 citation statements)

References 37 publications

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“… 2015 ; Wang et al. 2020 ). Therefore, exploring the mechanism of chondrocyte dysfunction will help to provide an understanding of the pathogenesis of OA.…”

Section: Introductionmentioning

confidence: 99%

Senkyunolide A inhibits the progression of osteoarthritis by inhibiting the NLRP3 signalling pathway

Shao

Zhou

et al. 2022

Pharmaceutical Biology

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Context Osteoarthritis (OA) is a degenerative disease. Senkyunolide A (SenA) is an important phthalide from Ligusticum chuanxiong Hort (Umbelliferae) with anti-spasmodic and neuroprotective effects. Objective We explored the effect of SenA on IL-1β-stimulated chondrocytes and OA mice Materials and methods Chondrocytes were stimulated by IL-1β (10 ng/mL) to establish an OA model in vitro . Cells were treated with SenA (20, 40, 80 and 160 μg/mL) for 48 h. The in vivo OA model was established by cutting off the medial meniscus tibial ligament (MMTL) at right knee incision of male C57BL/6 mice. One week after surgery, mice were injected with SenA (intraperitoneally one week) and divided into four groups ( n = 6 per group): Sham, OA, OA + SenA 20 mg/kg and OA + SenA 40 mg/kg. The OA progression was examined by haematoxylin and eosin (H&E) staining. Results SenA treatment increased cell viability (33%), proliferation (71%), inhibited apoptosis (21%), decreased levels of catabolic marker proteins (MMP13, 23%; ADAMTS4, 31%; ADAMTS5, 19%), increased levels of anabolic marker proteins (IGF-1, 57%; aggrecan, 75%; Col2a1, 48%), reduced levels of inflammation cytokines (TNF-α, 31%; IL-6, 19%; IL-18, 20%) and decreased levels of NLRP3 (21%), ASC (20%) and caspase-1 (29%) of chondrocytes. However, NLRP3 agonist nigericin increased levels of MMP13 (55%), ADAMTS4 (70%), ADAMTS5 (53%), decreased levels of IGF-1 (36%), aggrecan (26%), Col2a1 (25%), inhibited proliferation (61%) and promoted apoptosis (76%). Discussion and conclusions SenA alleviates OA progression by inhibiting NLRP3 signalling pathways. These findings provide an experimental basis for the clinical application of drugs in the treatment of OA.

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“… 2015 ; Wang et al. 2020 ). Therefore, exploring the mechanism of chondrocyte dysfunction will help to provide an understanding of the pathogenesis of OA.…”

Section: Introductionmentioning

confidence: 99%

Senkyunolide A inhibits the progression of osteoarthritis by inhibiting the NLRP3 signalling pathway

Shao

Zhou

et al. 2022

Pharmaceutical Biology

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“…Then, the DNA fragmentation of apoptotic chondrocyte bound the terminal deoxynucleotidyl transferase (TdT) enzyme in a reaction buffer. Slides were mounted with DAPI (Sigma, USA) for nuclear staining after rinsing with PBS for 10 minutes at room temperature [ 32 ]. In 6 different fields, the number of TUNEL-positive chondrocytes was counted and they were photographed blindly for each section using a laser scanning confocal microscope (Olympus FV1000, Japan).…”

Section: Methodsmentioning

confidence: 99%

Effect of Warm Acupuncture Combined with Bone Marrow Mesenchymal Stem Cells Transplantation on Cartilage Tissue in Rabbit Knee Osteoarthritis

Liu

Wei

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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The current study was designed to investigate the effect and underlying mechanism of warm acupuncture combined with bone marrow mesenchymal stem cells (BMSC) transplantation on cartilage tissue injury in rabbit knee osteoarthritis (KOA). In the study, 50 rabbits were randomly divided into 5 groups: blank group, KOA group, warm acupuncture group, BMSCs group, and warm acupuncture combined with BMSCs group. After warm acupuncture combined with BMSCs, the Modified Lequesne MG knee joint assessment scale was used to evaluate the degree of knee joint behavior, the Taiping Peng method generally observed the histomorphology changes of KOA rabbit cartilage, and hematoxylin-eosin staining, safranin O green staining, and toluidine blue staining were conducted to evaluate the extent of cartilage tissue pathology. Furthermore, transmission electron microscopy and TUNEL staining were used to observe cell apoptosis, and immunohistochemistry and qPCR analysis were used to detect the expression of apoptosis-related proteins and mRNA. Results showed that administration of warm acupuncture combined with BMSCs recovered the joint function and significantly decreased Lequesne MG score. The degree of cartilage tissue pathological damage has been improved, cartilage ultrastructure degeneration has recovered, peripheral blood vessels have mild edema, blood supply has gradually recovered, and even small amounts of red blood cells have appeared. In addition, warm acupuncture combined with BMSCs treatment suppressed chondrocyte apoptosis in rabbits with knee osteoarthritis by reduced TUNEL-positive chondrocytes and simultaneously reversed the mRNA expression of Bax, Bcl-2, and Caspase-3. These results indicate that warm acupuncture combined with BMSCs transplantation has a potential protective effect on rabbit KOA, which may be mediated by inhibiting chondrocyte apoptosis.

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“…It was demonstrated that fraxetin exerted hepatoprotective effect on ethanolinduced hepatic fibrosis by enhancing ethanol metabolism and inhibiting oxidative stress and inflammatory response in rats (Chen et al, 2018). Fraxetin was also reported to delay the destruction of cartilage in monosodium iodoacetate-induced osteoarthritis rats (Wang et al, 2020). In consideration of the protective effects of fraxetin in vivo might be different from those observed in vitro, the roles of fraxetin in isoflurane-induced neurotoxicity in animals need further investigation.…”

Section: Pi3k/akt Inactivation Resisted the Suppressive Role Of Fraxe...mentioning

confidence: 99%

Fraxetin suppresses reactive oxygen species‐dependent autophagy by the PI3K/Akt pathway to inhibit isoflurane‐induced neurotoxicity in hippocampal neuronal cells

Zhang

Zhou

Sun

et al. 2021

J of Applied Toxicology

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Isoflurane, a common volatile anesthetic, has been widely used to provide general anesthesia in operations. However, exposure to isoflurane may cause widespread neurotoxicity in the developing animal brain. Fraxetin, a natural coumarin derivative extracted from the bark of Fraxinus rhynchophylla, possesses versatile pharmacological properties including anti-oxidative, anti-inflammatory, and neuroprotective effects. However, the effect and action mechanism of fraxetin on neurotoxicity induced by isoflurane are unknown. Reactive oxygen species (ROS) generation, cell viability, lactate dehydrogenase (LDH) release, and apoptosis were estimated by 2 0 ,7 0 -dichlorofluorescin-diacetate (DCFH-DA) staining, MTT, LDH release, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick endlabeling (TUNEL) staining assays, respectively. The protein levels of light chain 3 (LC3)-I, LC3-II, p62, protein kinase B (Akt), and phosphorylated Akt (p-Akt) were detected by western blot analysis. Isoflurane induced ROS, LDH release, apoptosis, and autophagy, but inhibited the viability in HT22 cells, which were overturned by fraxetin or ROS scavenger N-acetyl-L-cysteine. Fraxetin suppressed isofluraneinduced PI3K/Akt inactivation in HT22 cells. PI3K/Akt inactivation by LY294002 resisted the effects of fraxetin on isoflurane-induced autophagy and autophagy-modulated neurotoxicity in HT22 cells. In conclusion, fraxetin suppressed ROS-dependent autophagy by activating the PI3K/Akt pathway to inhibit isofluraneinduced neurotoxicity in hippocampal neuronal cells.

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Fraxetin inhibits interleukin-1β-induced apoptosis, inflammation, and matrix degradation in chondrocytes and protects rat cartilage in vivo

Cited by 22 publications

References 37 publications

Senkyunolide A inhibits the progression of osteoarthritis by inhibiting the NLRP3 signalling pathway

Senkyunolide A inhibits the progression of osteoarthritis by inhibiting the NLRP3 signalling pathway

Effect of Warm Acupuncture Combined with Bone Marrow Mesenchymal Stem Cells Transplantation on Cartilage Tissue in Rabbit Knee Osteoarthritis

Fraxetin suppresses reactive oxygen species‐dependent autophagy by the PI3K/Akt pathway to inhibit isoflurane‐induced neurotoxicity in hippocampal neuronal cells

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