Senkyunolide H attenuates osteoclastogenesis and postmenopausal osteoporosis by regulating the NF-κB, JNK and ERK signaling pathways

Yang, Daishui; Jiang, Guangyao; Hu, Xuantao; Zheng, Tao; Li, Tao; Gao, Zhi Ping; Ouyang, Zhengxiao; Zhu, Baoyu

doi:10.1016/j.bbrc.2020.09.054

Cited by 13 publications

(13 citation statements)

References 24 publications

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“…Several other studies have reported that SNH markedly improves the symptoms of nervous system disease and diseases of other organs 12,13 . Specifically, studies have also found that SNH attenuates osteoclast genesis and osteoporosis via NF‐κB, JNK, and ERK signaling 8 . Recently, the role of SNH in MPP‐induced apoptosis in PC12 cells via activating ROS‐mediated MAPK pathway has been demonstrated 7 .…”

Section: Discussionmentioning

confidence: 96%

“…For example, SNH protects PC12 cells from MPP (+)‐induced apoptosis and oxidative stress by regulating the mitogen‐activated protein kinase (MAPK) pathway, providing a new scheme for the treatment of Parkinson's disease 7 . SNH reduces the generation of osteoclasts and treats postmenopausal osteoporosis by suppressing the NF‐κB, JNK, and ERK pathways 8 . In addition, SNH inhibits the activation of microglial cells in the hippocampus of mice with intracerebral hemorrhage by downregulating TLR4 and p‐NF‐κB p65 9 .…”

Section: Introductionmentioning

confidence: 99%

“…7 SNH reduces the generation of osteoclasts and treats postmenopausal osteoporosis by suppressing the NF-κB, JNK, and ERK pathways. 8 In addition, SNH inhibits the activation of microglial cells in the hippocampus of mice with intracerebral hemorrhage by downregulating TLR4 and p-NF-κB p65. 9 However, there are very few reports on SNH in the therapy of neuropathic pain, and the mechanism is unclear.…”

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confidence: 99%

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Senkyunolide H inhibits activation of microglia and attenuates lipopolysaccharide‐mediated neuroinflammation and oxidative stress in BV2 microglia cells via regulating ERK and NF‐κB pathway

Tan

Teng

et al. 2021

The Kaohsiung J of Med Scie

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Neuropathic pain is one of the common surgical diseases, which leads to abnormal chronic pain and pain hypersensitivity reaction. Microglia are important glial cells in the spinal cord, which are conducive to sensitization and maintenance of chronic pain. Recently, Senkyunolide H (SNH) has been reported to play an anti-inflammatory and antioxidant role. However, the mechanisms by which SNH improves neuropathic pain symptoms remain unknown. This study aimed to evaluate and identify the role of SNH in lipopolysaccharide (LPS)-mediated neuroinflammation and oxidative stress in BV2. Western blot and immunostaining assays revealed that SNH treatment attenuated LPS-mediated activation of BV2 in a dose-dependent manner. Flow cytometry further verified that BV2 microglial cells gradually shifted from an M1 (pro-inflammatory) phenotype to an M2 (anti-inflammatory) phenotype after SNH administration. Furthermore, quantitative real-time polymerase chain reaction and ELISA assays demonstrated that SNH treatment attenuated LPS-mediated neuroinflammation and oxidative stress in BV2 microglial cells. Lastly, western blot assays suggested that SHN could inactivate the ERK and NF-κB signaling pathways. Altogether, our findings have demonstrated that SNH could reverse LPS-mediated activation of microglia, LPS-mediated neuroinflammation and oxidative stress in BV2 via regulating the ERK and NF-κB pathways.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Senkyunolide H inhibits activation of microglia and attenuates lipopolysaccharide‐mediated neuroinflammation and oxidative stress in BV2 microglia cells via regulating ERK and NF‐κB pathway

Tan

Teng

et al. 2021

The Kaohsiung J of Med Scie

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“…To assess the cytotoxicity of CIM, RAW264.7 or BMM cells were seeded at 3 × 10 3 /well in triplicate in 96-well plates and incubated overnight to allow adhesion. Then, CIM was added to the medium at a gradient of concentrations (0, 10, 20, 40, 80, 160, 320, 640, 1,280, 2,560 μM) for 48 or 96 h. The medium was replaced every 48 h. Then, the medium in each well was replaced with 100 µL of fresh medium supplemented with a 10% CCK-8 buffer solution, and the 96-well plates were incubated under the same conditions for 1 h. The absorbance was measured at a wavelength of 450 nm using an ELX800 absorbance microplate reader (Bio-Tek, United States), and phosphate-buffered saline (PBS) served as the reference ( Yang et al, 2020 ). Cell viability was calculated as a percentage relative to the vehicle-treated control group.…”

Section: Methodsmentioning

confidence: 99%

Cimifugin Suppresses NF-κB Signaling to Prevent Osteoclastogenesis and Periprosthetic Osteolysis

Duan

et al. 2021

Front. Pharmacol.

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Background: Aseptic loosening of prosthesis (ALP) is one of the most common long-term complications of knee and hip arthroplasty. Wear particle-induced osteoclastogenesis and subsequent periprosthetic osteolysis account for the morbidity of ALP. Here, we investigate the potential of cimifugin (CIM), a natural extract from Cimicifuga racemosa and Saposhnikovia divaricata, as a bone-protective drug in the treatment of ALP.Method: First, we performed cell viability and osteoclast formation assays to assess the effect of noncytotoxic CIM on osteoclast differentiation in vitro. Bone slice resorption and F-actin ring immunofluorescence assays were adopted to assess the effects of CIM on bone-resorption function. Then, quantitative real-time polymerase chain reaction (qRT–PCR) analysis was performed to further assess the repressive effects of CIM on osteoclastogenesis at the gene expression level. To elucidate the mechanisms underlying the above findings, Western blot and luciferase reporter gene assays were used to assess the regulatory effects of CIM on the NF-κB and MAPK signaling pathways. Moreover, a Ti particle-induced murine calvarial osteolysis model and subsequent histomorphometric analysis via micro-CT and immunohistochemical staining were used to elucidate the effect of CIM on periprosthetic osteolysis in vivo.Result: CIM dose-dependently inhibited both bone marrow-derived macrophage (BMM)- and RAW264.7 cell-derived osteoclastogenesis and bone resorption pit formation in vitro, which was further supported by the reduced expression of F-actin and osteoclast-specific genes. According to the Western blot analysis, inhibition of IκBα phosphorylation in the NF-κB signaling pathway, not the phosphorylation of MAPKs, was responsible for the suppressive effect of CIM on osteoclastogenesis. Animal experiments demonstrated that CIM alleviated Ti particle-induced bone erosion and osteoclast accumulation in murine calvaria.Conclusion: The current study suggested for the first time that CIM can inhibit RANKL-induced osetoclastogenesis by suppressing the NF-κB signaling pathway in vitro and prevent periprosthetic osteolysis in vivo. These findings suggest the potential of CIM as a therapeutic in ALP.

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“…Then, cells were treated with CIM of gradient concentrations (0, 10, 20, 40, 80, 160, 320, 640, 1280, 2560 mM) in the medium for 48 or 96 h respectively. The medium was replaced every 48 h. Then, the medium in each well was replaced with 100 ul fresh medium containing 10% CCK-8 buffer solution, and the 96-well plates were incubated in the same conditions for 1 h. The absorbance was measured at a wavelength of 450 nm with phosphate buffer saline (PBS) well as reference using ELX800 absorbance microplate reader (Bio-Tek, USA) 19 . Cell viability was calculated relative to the vehicle-treated control group in percentage.…”

Section: Cell Viabilitymentioning

confidence: 99%

Cimifugin Suppresses NF-κB Signaling to Prevent Osteoclastogenesis and Periprosthetic Osteolysis

Duan

et al. 2021

Preprint

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Background: Aseptic loosening of prosthesis (ALP) is one of the most common long-term complication of knee and hip arthroplasty. Wear paticle-induced osteoclastogenesis and subsequent periprosthetic osteolysis accounts for the morbidity of ALP. Here, we investigate cimifugin (CIM), a natural extract from Cimicifuga Racemosa and Saposhnikovia Divaricata, as a bone protective drug in treatment of ALP.Method: First, we deployed cell viability and osteoclast formation assays to detect the effect of noncytotoxic CIM on osteoclast differentiation in vitro. Bone slice resorption evaluation and F-actin ring immunofluorescence assays were adopted to measure bone-resorbing function affected by CIM. Then, we introduce quantitative real-time polymerase chain reaction (qRT-PCR) analysis to further identify the repressed osteoclastogenesis by CIM in gene expression level. To reveal underlying mechanism of findings above, we used Western blotting and luciferase reporter gene assay to determine the regulation manner of CIM in NF-κB and MAPKs signaling pathways. Moreover, Ti particle-induced murine calvarial osteolysis model and following histomorphometric analysis via micro-CT and immunohistochemical staining were used to demonstrate the effect of CIM on periprosthetic osteolysis in vivo. Result: CIM administration dose-dependently inhibited both bone marrow-derived macrophages (BMMs) and RAW264.7 cells derived osteoclastogenesis and bone resorption pit formation in vitro, which further supported by reduced expression of F-actin and osteoclast specific genes. According to the Western blotting analysis, inhibition of IkBa phosphorylation in NF-κB signaling pathway, not the phosphorylation of MAPKs, was detected as the suppressive effect of CIM on osteoclastogenesis. In vivo animal experiment demonstrated that CIM alleviated Ti particle-induced bone erosion and osteoclast accumulation in murine calvaria. Conclusion: The current study for the first time proved that CIM could dose-dependently inhibit RANKL-induced osetoclastogenesis via suppressing NF-κB signaling pathway in vitro and prevent periprosthetic osteolysis in vivo. These findings suggest the potential therapeutic use of CIM in ALP.

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Senkyunolide H attenuates osteoclastogenesis and postmenopausal osteoporosis by regulating the NF-κB, JNK and ERK signaling pathways

Cited by 13 publications

References 24 publications

Senkyunolide H inhibits activation of microglia and attenuates lipopolysaccharide‐mediated neuroinflammation and oxidative stress in BV2 microglia cells via regulating ERK and NF‐κB pathway

Senkyunolide H inhibits activation of microglia and attenuates lipopolysaccharide‐mediated neuroinflammation and oxidative stress in BV2 microglia cells via regulating ERK and NF‐κB pathway

Cimifugin Suppresses NF-κB Signaling to Prevent Osteoclastogenesis and Periprosthetic Osteolysis

Cimifugin Suppresses NF-κB Signaling to Prevent Osteoclastogenesis and Periprosthetic Osteolysis

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