Leonurine hydrochloride inhibits osteoclastogenesis and prevents osteoporosis associated with estrogen deficiency by inhibiting the NF-κB and PI3K/Akt signaling pathways

Yuan, Feng-Lai; Xu, Ruirong; Jiang, Donglin; He, X. M.; Su, Qiang; Chen, Jin; Li, Xia

doi:10.1016/j.bone.2015.02.017

Cited by 83 publications

(60 citation statements)

References 44 publications

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“…Previous studies showed that natural compounds not only suppressed the osteoclast formation in vitro, but also reversed the bone loss in ovariectomized (OVX) model mice . One of the limitations in this study was that the animal experiments had not been performed.…”

Section: Discussionmentioning

confidence: 92%

Asperpyrone A attenuates RANKL‐induced osteoclast formation through inhibiting NFATc1, Ca²⁺ signalling and oxidative stress

Chen

Wang

Qiu

et al. 2019

J Cellular Molecular Medi

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Imbalance of osteoblast and osteoclast in adult leads to a variety of bone‐related diseases, including osteoporosis. Thus, suppressing the activity of osteoclastic bone resorption becomes the main therapeutic strategy for osteoporosis. Asperpyrone A is a natural compound isolated from Aspergillus niger with various biological activities of antitumour, antimicrobial and antioxidant. The present study was designed to investigate the effects of Asperpyrone A on osteoclastogenesis and to explore its underlining mechanism. We found that Asperpyrone A inhibited RANKL‐induced osteoclastogenesis in a dose‐dependent manner when the concentration reached 1 µm, and with no cytotoxicity until the concentration reached to 10 µm. In addition, Asperpyrone A down‐regulated the mRNA and protein expression of NFATc1, c‐fos and V‐ATPase‐d2, as well as the mRNA expression of TRAcP and Ctsk. Furthermore, Asperpyrone A strongly attenuated the RNAKL‐induced intracellular Ca2+ oscillations and ROS (reactive oxygen species) production in the process of osteoclastogenesis and suppressed the activation of MAPK and NF‐κB signalling pathways. Collectively, Asperpyrone A attenuates RANKL‐induced osteoclast formation via suppressing NFATc1, Ca2+ signalling and oxidative stress, as well as MAPK and NF‐κB signalling pathways, indicating that this compound may become a potential candidate drug for the prevention or treatment of osteoporosis.

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Section: Discussionmentioning

confidence: 92%

Asperpyrone A attenuates RANKL‐induced osteoclast formation through inhibiting NFATc1, Ca²⁺ signalling and oxidative stress

Chen

Wang

Qiu

et al. 2019

J Cellular Molecular Medi

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“…As the downstream target of NF‐κB and MAPK pathways, NFATc1 was the most important transcription factor for osteoclastogenesis . The activation of NFATc1 triggers the expression of osteoclastogenesis‐related marker genes, such as TRAP, Cathepsin K, CTR and MMP‐9.…”

Section: Discussionmentioning

confidence: 99%

l‐tetrahydropalmatine suppresses osteoclastogenesis in vivo and in vitro via blocking RANK‐TRAF6 interactions and inhibiting NF‐κB and MAPK pathways

Zhi

Wang

Chen

et al. 2019

J Cellular Molecular Medi

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Bone homeostasis is delicately orchestrated by osteoblasts and osteoclasts. Various pathological bone loss situations result from the overactivated osteoclastogenesis. Receptor activator of nuclear factor κB ligand (RANKL)‐activated NF‐κB and MAPK pathways is vital for osteoclastogenesis. Here, we for the first time explored the effects of l‐tetrahydropalmatine (l‐THP), an active alkaloid derived from corydalis, on the formation and function of osteoclasts in vitro and in vivo. In RAW264.7 cells and bone marrow monocytes cells (BMMCs), l‐THP inhibited osteoclastic differentiation at the early stage, down‐regulated transcription level of osteoclastogenesis‐related genes and impaired osteoclasts functions. Mechanically, Western blot showed that l‐THP inhibited the phosphorylation of P50, P65, IκB, ERK, JNK and P38, and the electrophoretic mobility shift assay (EMSA) revealed that DNA binding activity of NF‐κB was suppressed, ultimately inhibiting the expression of nuclear factor of activated T cells (NFATc1). Besides, Co‐immunoprecipitation indicated that l‐THP blocked the interactions of RANK and TNF receptor associated factor 6 (TRAF6) at an upstream site. In vivo, l‐THP significantly inhibited ovariectomy‐induced bone loss and osteoclastogenesis in mice. Collectively, our study demonstrated that l‐THP suppressed osteoclastogenesis by blocking RANK‐TRAF6 interactions and inhibiting NF‐κB and MAPK pathways. l‐THP is a promising agent for treating osteoclastogenesis‐related diseases such as post‐menopausal osteoporosis.

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“…It was proved that leonurine exerted beneficial effects in treating osteoclast-related diseases or acute kidney injury through inhibiting NF-κB signaling [17,18]. P65 is the most common form of NF-κB, which has been implicated in inflammation and tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Leonurine Attenuates Hyperalgesia in Mice with Induced Adenomyosis

Nie

Liu

2017

Med Sci Monit

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BackgroundAdenomyosis, defined as the invasion of endometrial glands and stroma into the myometrium, is a common gynecological disorder. In the present study we report on the effect of leonurine on ICR mice with adenomyosis induced by neonatal tamoxifen.Material/MethodAfter being treated with tamoxifen for 4, 8, and 12 weeks, we assessed body weight and pain modulation in mice in hotplate tests. The mice were divided into 5 groups: a low-dose leonurine treatment group, a high-dose leonurine treatment group, a valproic acid (VPA) treatment group, a vehicle only treatment group, and a blank control group. We evaluated body weight, pain modulation in hotplate tests, and the depth of myometrial infiltration. Immunoreactivity staining of progesterone receptor (PR), nuclear factor-κB phosphorylated-p65 (p-p65), cyclooxygenase-2 (COX-2), and oxytocin receptor (OTR) was evaluated by immunohistochemistry.ResultsThe measurement of the body weight, myometrial infiltration, and pain modulation showed that neonatal tamoxifen treatment led to adenomyosis. Leonurine treatment appeared to decrease hyperalgesia and myometrial infiltration. Immunoreactivity staining showed decreased p-p65, COX-2, and OTR protein expressions.ConclusionsOur results indicate that leonurine attenuates hyperalgesia in mice with induced adenomyosis via down-regulating expressions of p-P65, COX-2, and OTR, and could be beneficial for treating adenomyosis.

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Leonurine hydrochloride inhibits osteoclastogenesis and prevents osteoporosis associated with estrogen deficiency by inhibiting the NF-κB and PI3K/Akt signaling pathways

Cited by 83 publications

References 44 publications

Asperpyrone A attenuates RANKL‐induced osteoclast formation through inhibiting NFATc1, Ca²⁺ signalling and oxidative stress

Asperpyrone A attenuates RANKL‐induced osteoclast formation through inhibiting NFATc1, Ca²⁺ signalling and oxidative stress

l‐tetrahydropalmatine suppresses osteoclastogenesis in vivo and in vitro via blocking RANK‐TRAF6 interactions and inhibiting NF‐κB and MAPK pathways

Leonurine Attenuates Hyperalgesia in Mice with Induced Adenomyosis

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Leonurine hydrochloride inhibits osteoclastogenesis and prevents osteoporosis associated with estrogen deficiency by inhibiting the NF-κB and PI3K/Akt signaling pathways

Cited by 83 publications

References 44 publications

Asperpyrone A attenuates RANKL‐induced osteoclast formation through inhibiting NFATc1, Ca2+ signalling and oxidative stress

Asperpyrone A attenuates RANKL‐induced osteoclast formation through inhibiting NFATc1, Ca2+ signalling and oxidative stress

l‐tetrahydropalmatine suppresses osteoclastogenesis in vivo and in vitro via blocking RANK‐TRAF6 interactions and inhibiting NF‐κB and MAPK pathways

Leonurine Attenuates Hyperalgesia in Mice with Induced Adenomyosis

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Asperpyrone A attenuates RANKL‐induced osteoclast formation through inhibiting NFATc1, Ca²⁺ signalling and oxidative stress

Asperpyrone A attenuates RANKL‐induced osteoclast formation through inhibiting NFATc1, Ca²⁺ signalling and oxidative stress