Stachydrine ameliorates carbon tetrachloride-induced hepatic fibrosis by inhibiting inflammation, oxidative stress and regulating MMPs/TIMPs system in rats

Zhang, Jinlin; Ai, Yang; Wu, Yu; Guan, Wei; Xiong, Biao; Peng, Xiaoqing; Wei, Xuan; Chen, Chang; Liu, Zhaoguo

doi:10.1016/j.biopha.2017.11.117

Cited by 54 publications

(36 citation statements)

References 36 publications

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“…Indeed, adequate literature support exists on stachydrine, trigonelline, and the glucosinolate breakdown products. In vitro and in vivo studies show that stachydrine exhibits inhibition of the NF-κB signalling pathways [34,71,72]. Likewise, trigonelline showed antidiabetic effects and counteracted insulin resistance by suppressing inflammation [34,73].…”

Section: Discussionmentioning

confidence: 99%

Induction of peroxisome proliferator activated receptor γ (PPARγ) mediated gene expression and inhibition of induced nitric oxide production by Maerua subcordata (Gilg) DeWolf

Hiben

Haan

Spenkelink

et al. 2020

BMC Complement Med Ther

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Background: The health benefits of botanicals is linked to their phytochemicals that often exert pleiotropic effects via targeting multiple molecular signaling pathways such as the peroxisome proliferator-activated receptors (PPARs) and the nuclear factor kappaB (NFκB). The PPARs are transcription factors that control metabolic homeostasis and inflammation while the NF-κB is a master regulator of inflammatory genes such as the inducible nitric-oxide synthase that result in nitric oxide (NO) overproduction. Methods: Extracts of Maerua subcordata (MS) and selected candidate constituents thereof, identified by liquid chromatography coupled to mass spectroscopy, were tested for their ability to induce PPARγ mediated gene expression in U2OS-PPARγ cells using luciferase reporter gene assay and also for their ability to inhibit lipopolysaccharide (LPS) induced NO production in RAW264.7 macrophages. While measuring the effect of test samples on PPARγ mediated gene expression, a counter assay that used U2OS-Cytotox cells was performed to monitor cytotoxicity or any non-specific changes in luciferase activity.

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Section: Discussionmentioning

confidence: 99%

Induction of peroxisome proliferator activated receptor γ (PPARγ) mediated gene expression and inhibition of induced nitric oxide production by Maerua subcordata (Gilg) DeWolf

Hiben

Haan

Spenkelink

et al. 2020

BMC Complement Med Ther

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“…Over several years, our group has screened natural compounds for treating osteoclast‐related diseases . Stachydrine (STA), a bioactive constituent extracted from a medicinal herb Leonurus heterophyllus Sweet, has extensive pharmacological properties, including antioxidant, anti‐inflammatory, anticancer and cardioprotective properties . Recent studies have reported that STA inhibits NF‐κB and MAPK pathways in different cell types .…”

Section: Introductionmentioning

confidence: 99%

“…[13][14][15][16] Stachydrine (STA), a bioactive constituent extracted from a medicinal herb Leonurus heterophyllus Sweet, has extensive pharmacological properties, including antioxidant, anti-inflammatory, anticancer and cardioprotective properties. [17][18][19][20] Recent studies have reported that STA inhibits NF-κB and MAPK pathways in different cell types. [20][21][22] As the NF-κB and MAPK pathways are crucial for osteoclastogenesis and because STA exerts inhibitory effects on these pathways, we hypothesized that STA may represent a novel candidate for treating osteoclast-related diseases by inducing the targeted suppression of osteoclastogenesis.…”

mentioning

confidence: 99%

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

Meng

Zhou

Zhang

et al. 2019

J Cellular Molecular Medi

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Osteoclast overactivation‐induced imbalance in bone remodelling leads to pathological bone destruction, which is a characteristic of many osteolytic diseases such as rheumatoid arthritis, osteoporosis, periprosthetic osteolysis and periodontitis. Natural compounds that suppress osteoclast formation and function have therapeutic potential for treating these diseases. Stachydrine (STA) is a bioactive alkaloid isolated from Leonurus heterophyllus Sweet and possesses antioxidant, anti‐inflammatory, anticancer and cardioprotective properties. However, its effects on osteoclast formation and function have been rarely described. In the present study, we found that STA suppressed receptor activator of nuclear factor‐κB (NF‐κB) ligand (RANKL)‐induced osteoclast formation and bone resorption, and reduced osteoclast‐related gene expression in vitro. Mechanistically, STA inhibited RANKL‐induced activation of NF‐κB and Akt signalling, thus suppressing nuclear factor of activated T cells c1 induction and nuclear translocation. In addition, STA alleviated bone loss and reduced osteoclast number in a murine model of LPS‐induced inflammatory bone loss. STA also inhibited the activities of NF‐κB and NFATc1 in vivo. Together, these results suggest that STA effectively inhibits osteoclastogenesis both in vitro and in vivo and therefore is a potential option for treating osteoclast‐related diseases.

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“…We initially evaluated the effect of celastrol on CCl4 -induced hepatic injury in vivo. Rats received CCl 4 injection resulted in obvious changes in liver morphology, and celastrol improved the morphology changes in livers (Figure 2A).…”

mentioning

confidence: 99%

Celastrol exerts anti‐inflammatory effect in liver fibrosis via activation of AMPK‐SIRT3 signalling

Wang

et al. 2019

J Cellular Molecular Medi

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Celastrol, a pentacyclic tritepene extracted from Tripterygium Wilfordi plant, showing potent liver protection effects on several liver‐related diseases. However, the anti‐inflammatory potential of celastrol in liver fibrosis and the detailed mechanisms remain uncovered. This study was to investigate the anti‐inflammatory effect of celastrol in liver fibrosis and to further reveal mechanisms of celastrol‐induced anti‐inflammatory effects with a focus on AMPK‐SIRT3 signalling. Celastrol showed potent ameliorative effects on liver fibrosis both in activated hepatic stellate cells (HSCs) and in fibrotic liver. Celastrol remarkably suppressed inflammation in vivo and inhibited the secretion of inflammatory factors in vitro. Interestingly, celastrol increased SIRT3 promoter activity and SIRT3 expression both in fibrotic liver and in activated HSCs. Furthermore, SIRT3 silencing evidently ameliorated the anti‐inflammatory potential of celastrol. Besides, we found that celastrol could increase the AMPK phosphorylation. Further investigation showed that SIRT3 siRNA decreased SIRT3 expression but had no obvious effect on phosphorylation of AMPK. In addition, inhibition of AMPK by employing compound C (an AMPK inhibitor) or AMPK1α siRNA significantly suppressed SIRT3 expression, suggesting that AMPK was an up‐stream protein of SIRT3 in liver fibrosis. We further found that depletion of AMPK significantly attenuated the inhibitory effect of celastrol on inflammation. Collectively, celastrol attenuated liver fibrosis mainly through inhibition of inflammation by activating AMPK‐SIRT3 signalling, which makes celastrol be a potential candidate compound in treating or protecting against liver fibrosis.

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Stachydrine ameliorates carbon tetrachloride-induced hepatic fibrosis by inhibiting inflammation, oxidative stress and regulating MMPs/TIMPs system in rats

Cited by 54 publications

References 36 publications

Induction of peroxisome proliferator activated receptor γ (PPARγ) mediated gene expression and inhibition of induced nitric oxide production by Maerua subcordata (Gilg) DeWolf

Induction of peroxisome proliferator activated receptor γ (PPARγ) mediated gene expression and inhibition of induced nitric oxide production by Maerua subcordata (Gilg) DeWolf

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

Celastrol exerts anti‐inflammatory effect in liver fibrosis via activation of AMPK‐SIRT3 signalling

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