Stachydrine prevents LPS‐induced bone loss by inhibiting osteoclastogenesis via NF‐κB and Akt signalling

Meng, Jinghui; Zhou, Chenhe; Zhang, Wenkan; Wang, Wei; He, Bin; Hu, Bin; Jiang, Guangyao; Wang, Yangxin; Hong, Jianqiao; Li, Sihao; He, Jiamin; Yan, Shigui; Yan, Wei

doi:10.1111/jcmm.14551

Cited by 30 publications

(27 citation statements)

References 44 publications

(81 reference statements)

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“…Another previous study demonstrated that stachydrine suppressed traumatic brain injury via anti-inflammatory mechanisms (Yu et al, 2018). The effects of stachydrine on immunity and inflammation have also been reported in recent studies (Cao et al, 2017;Meng et al, 2019).…”

Section: Discussionmentioning

confidence: 65%

Protective Effect of Stachydrine Against Cerebral Ischemia-Reperfusion Injury by Reducing Inflammation and Apoptosis Through P65 and JAK2/STAT3 Signaling Pathway

Sun

Qiu

et al. 2020

Front. Pharmacol.

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Stachydrine, a constituent of Leonurus japonicus Houtt which also called Japanese motherwort has been shown to improve vascular microcirculation and ameliorate endothelial dysfunction. This study investigated the neuroprotective effect of stachydrine. Male Sprague-Dawley (SD) rats were randomly divided into sham, control, and stachydrine groups. The neurological deficit score was evaluated and the infarct size of the brain was measured using 2,3,5-triphenyltetra-zolium (TTC) chloride staining assay, and the pathological changes in the brain tissues were examined by HE staining. Nissl and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) staining were performed to assess the numbers of Nissl bodies and the levels of apoptosis in the neurons. The activities of superoxide dismutase (SOD) and the levels of malondialdehyde (MDA) were also measured. The release of inflammatory factors IL-1b and TNF-a were detected by Enzyme-linked immunosorbent assay (ELISA). Compared with the control group, the stachydrine group showed a significant prevention of neurological deficit, as indicated by the reduced infarct volume in the brain. Moreover, the stachydrine treatment reduced the activities of SOD, the levels of MDA and decreased the amount of IL-1b, and TNF-a, indicating that it could function to decrease the level of inflammation, thus reducing brain damage. The ischemic stroke model of PC12 cells was prepared via oxygen-glucose deprivation (OGD) protocol for 6 h. The expression of P65 and JAK2/STAT3 signaling pathway related proteins was measured by western blot. The treatment group was found to have the survival rate of PC12 cells improved and the release of inflammatory factors reduced when compared with the OGD group. This study demonstrated that stachydrine could improve nerve function by inhibiting the phosphorylation of P65/JAK2 and STAT3. FIGURE 1 | The chemical structure of stachydrine. Stachydrine (purity> 97%) purchased from Dalian Meilun Biology Technology Co. (Dalian, China). Li et al. Stachydrine Protects Against Cerebral Ischemia-Reperfusion InjuryFrontiers in Pharmacology | www.frontiersin.org February 2020 | Volume 11 | Article 64 absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Section: Discussionmentioning

confidence: 65%

Protective Effect of Stachydrine Against Cerebral Ischemia-Reperfusion Injury by Reducing Inflammation and Apoptosis Through P65 and JAK2/STAT3 Signaling Pathway

Sun

Qiu

et al. 2020

Front. Pharmacol.

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“…Among the 4 identified alkaloids, a series of inflammatory models have been applied to explore the anti-inflammatory activities and mechanisms of stachydrine and betaine. Intriguingly, stachydrine could effectively inhibit LPS-induced inflammatory bone loss by suppressing NF-κB and Akt signal pathway ( Meng et al, 2019 ), suggesting its future use in the treatment of postpartum osteoporosis. Peng and his coworkers reviewed the anti-inflammatory mechanism of betaine, that is, betaine improves sulfur amino acid metabolism against oxidative stress, suppresses NF-κB activity and NOD-like receptor protein 3 (NLRP3) inflammasome activation ( Zhao et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Comparative Lipidomic and Metabolomic Analyses Reveal the Mystery of Lacquer Oil from Toxicodendron vernicifluum for the Treatment of “Yuezi” Disease in Nujiang, China: From Anti-Inflammation and Anti-Postpartum Depression Perspective

Liu

Cai

et al. 2022

Front. Pharmacol.

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Background: In southwest China, especially in Nujiang, lacquer oil from the drupes of Toxicodendron vernicifluum (Stokes) F. A. Barkley, including black lacquer oil (BLO) and white lacquer oil (WLO), is one of the most important edible oils for the local people. Through the field investigation, the locals believe that lacquer oil has benefits for parturient women and for the treatment of “Yuezi” disease. However, studies on bioactivities and the chemical compositions of lacquer oil are limited.Purpose: This study was designed to reveal the mystery of lacquer oil for the treatment of “Yuezi” disease by testing its anti-inflammatory and anti-postpartum depressant activities and related bioactive compounds.Methods: The anti-inflammatory effects of lacquer oil were examined by establishing a lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model and detecting the level of pro-inflammatory factors such as NO, IL-6 and TNF-α. The antidepressant effects of lacquer oil were studied by building a mouse model of postpartum depression (PPD), and the animal behavior changes of PPD model mice were assessed by open field test (OFT), forced swimming test (FST) and tail suspension test (TST). The chemical profiles of BLO and WLO were detected by lipidomic and the untargeted metabolomic research methods based on UPLC-MS/MS.Results: The results showed that BLO and WLO exerted anti-inflammatory effects by reducing the release of pro-inflammatory factors and BLO had better anti-inflammatory effects than WLO. While only BLO had anti-postpartum depressant activities, as evidenced by the significantly reduced the immobility time of the BLO-treated PPD mice in TST and FST compared to the PPD model mice. The comparative lipidomic analysis revealed that BLO contained high levels of Diacylglycerols (DAG) and Diacylglyceryl trimethylhomoserines (DGTS) but low level of ceramides (Cer), sphingomyelines (SM), phosphatidylcholines (PC) and phosphatidylethanolamines (PE) compared with WLO. Metabolomics analysis showed that there were 57 chemical markers between BLO and WLO, of which 17 potential biomarkers have been declared to possess anti-inflammatory and/or antidepressant activities.Conclusion: The findings of this study furnish a scientific support for the traditional uses of lacquer oil for the treatment of “Yuezi” disease from anti-inflammation and anti-postpartum depression perspective.

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“…Its activation and increased expression are key events in osteoclast differentiation. Embryonic stem cells knocked out by NFATc1 cannot differentiate into osteoclasts under the stimulation of RANKL (Meng et al, 2019). Both NF-κB and AKT signals regulate osteoclast differentiation related to NFATc1 (Ye et al, 2018;Wu et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

The effects of Pinoresinol diglucoside on the differentiation and bone resorption of osteoclast RAW264.7

Jin

Li²,

et al. 2022

Food Sci. Technol

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The paper aimed to investigate the effect of Pinoresinol diglucoside on the differentiation and bone resorption of osteoclast RAW264.7, and to evaluate the effect of Pinoresinol diglucoside on osteoclasts.In order to study the effect of Pinoresinol diglucoside on osteoclast differentiation, RANKL was used to induce RAW264.7 cells to differentiate into osteoclasts, and different concentrations of Pinoresinol diglucoside was added to intervene. CCK-8 method was applied to detect cell viability. TRAP staining was employed to observe cell morphology. Annexin V/PI flow cytometry was used to detect cell apoptosis. Phalloidin was used to detect F-actin formation of osteoclasts and to observe the effect on bone resorption. WB was employed to detect the effects of differentiation-related proteins and RANKL/RANK signaling pathways, and immunofluorescence detection technology was used to measure the distribution and nuclear translocation of p65. Pinoresinol diglucoside can effectively inhibit RANKL-induced osteoclast differentiation, especially in the early stage. The drug can inhibit the formation of F-actin of osteoclasts and inhibit bone resorption. Through inhibiting the ubiquitination and degradation of the homologous phosphatase tensin (PTEN), the drug up-regulated the viability of PTEN. The up-regulated PTEN viability then inhibited the NF-κB and AKT signaling pathways, resulting in a decrease in the expressions of nuclear factor c1 (NFATc1) in activated T cells. Pinoresinol diglucoside effectively inhibited the formation of F-actin and bone resorption in mature osteoclasts. The mechanism is through inhibiting the expression levels of osteoclast-related proteins NFATc1, c-Fos, CSTK and TRAP and RNAKL/RANK signaling pathways, and also inhibiting the activation of NF-κB and AKT signaling pathways.

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Stachydrine prevents LPS‐induced bone loss by inhibiting osteoclastogenesis via NF‐κB and Akt signalling

Cited by 30 publications

References 44 publications

Protective Effect of Stachydrine Against Cerebral Ischemia-Reperfusion Injury by Reducing Inflammation and Apoptosis Through P65 and JAK2/STAT3 Signaling Pathway

Protective Effect of Stachydrine Against Cerebral Ischemia-Reperfusion Injury by Reducing Inflammation and Apoptosis Through P65 and JAK2/STAT3 Signaling Pathway

Comparative Lipidomic and Metabolomic Analyses Reveal the Mystery of Lacquer Oil from Toxicodendron vernicifluum for the Treatment of “Yuezi” Disease in Nujiang, China: From Anti-Inflammation and Anti-Postpartum Depression Perspective

The effects of Pinoresinol diglucoside on the differentiation and bone resorption of osteoclast RAW264.7

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