Astilbin ameliorates pulmonary fibrosis via blockade of Hedgehog signaling pathway

Zhang, Jie; Liu, Hanchen; Song, Chenguang; Zhang, Jinjin; Wang, Youlei; Lv, Changjun; Song, Xiaodong

doi:10.1016/j.pupt.2018.03.006

Cited by 22 publications

(24 citation statements)

References 37 publications

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“…Therefore, the miR‐29b‐2‐5p targeted genes were predicted based on TargetScan, MiRanda data and miRBase (Figure A). Among the miR‐29b‐2‐5p targeted genes, we focused on STAT3 and Gli2 because they are the main regulatory factors of lung fibrosis in our previous study . STAT3 and Gli2 decreased under astilbin treatment compared with BLM treatment (Figure B).…”

Section: Resultsmentioning

confidence: 99%

“…All animals were bred and maintained in a 12 hours light/dark cycle and allowed free access to food and water, and randomly divided into four groups: sham group, 40 mg/kg astilbin alone group (AST group), bleomycin‐treated group (BLM group) and BLM + 40 mg/kg AST‐treated group. BLM animal model was administered with 5 mg/kg BLM dissolved in saline via single intratracheal instillation under anaesthesia as previously described . At day 14, astilbin was orally administered every day.…”

Section: Methodsmentioning

confidence: 99%

“…The cells were maintained in advanced minimum essential medium and supplemented with 10% newborn calf serum, 100 U/mL penicillin and 100 µg/mL streptomycin at 37°C under a humidified atmosphere of 5% CO 2 and 95% air. The cells were first administered with 5 ng/mL transforming growth factor beta 1 (TGF‐β1) for 6 hours and then co‐treated with 40 µg/mL AST for 48 hours as previously described …”

Section: Methodsmentioning

confidence: 99%

“…In addition, astilbin can promote angiotensin‐converting enzyme inhibition in vitro and protect diabetic rat heart against ischaemia‐reperfusion injury . In a previous study, we reported that astilbin ameliorates fibrosis via blockade of the Hedgehog signalling pathway, in which we mainly focused on the role of coding RNAs under astilbin treatment . However, high‐throughput sequencing technology on RNA transcriptomes revealed that most of these transcripts are not translated to protein which are named as non‐coding RNAs (ncRNAs), such as microRNA (miRNA), long ncRNA (lncRNA) and circular RNA (circRNA).…”

Section: Introductionmentioning

confidence: 99%

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Regulatory network of two circRNAs and an miRNA with their targeted genes under astilbin treatment in pulmonary fibrosis

Zhang

Liu

et al. 2019

J Cellular Molecular Medi

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Circular RNAs (circRNAs) are becoming new therapeutic drug targets. However, their profiles under astilbin treatment have not been reported yet. In this study, we analysed the global reprogramming of circRNA transcriptome and a regulatory network of circRNAs with their targeted genes under astilbin treatment in pulmonary fibrosis. A total of 145 circRNAs were differentially expressed in the astilbin‐treated group compared with the bleomycin‐treated group using RNA sequencing. In the bleomycin‐ and astilbin‐treated groups, 29 coexpressed circRNAs were found. The maximum number of circRNAs was distributed on chromosome two, and their length varieties were mainly within 1000 bp. Four differentially expressed circRNAs (circRNA‐662, 949, 394 and 986) were tested to validate the RNA sequencing data, and their targeted microRNAs and genes were analysed by qRT‐PCR, Western blot, Pearson correlation coefficient, a dual‐luciferase reporter system and anti‐AGO2 RNA immunoprecipitation. The results showed that circRNA‐662 and 949 can act as “miR‐29b sponges” targeting Gli2 and STAT3 to exert their functions. Our work suggests that the transcriptome complexity at the circRNA level under astilbin treatment. These circRNAs may be potential molecular targets for drug action.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Regulatory network of two circRNAs and an miRNA with their targeted genes under astilbin treatment in pulmonary fibrosis

Zhang

Liu

et al. 2019

J Cellular Molecular Medi

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“…Seven days after surgery, astilbin (10 mg/kg) was intraperitoneally injected into the mice in the OVX + astilbin group, and PBS was intraperitoneally injected into the mice in the sham and OVX groups. The concentrations of astilbin in vivo studies were determined according the results in vitro, references and the clinical application of this compound . The injections were continued every two days for a total of 6 weeks.…”

Section: Methodsmentioning

confidence: 99%

Astilbin prevents bone loss in ovariectomized mice through the inhibition of RANKL‐induced osteoclastogenesis

Jin

Wang

Chen

et al. 2019

J Cellular Molecular Medi

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Osteoporosis is the most common osteolytic disease characterized by excessive osteoclast formation and resultant bone loss, which afflicts millions of patients around the world. Astilbin, a traditional herb, is known to have anti‐inflammatory, antioxidant and antihepatic properties, but its role in osteoporosis treatment has not yet been confirmed. In our study, astilbin was found to have an inhibitory effect on the RANKL‐induced formation and function of OCs in a dose‐dependent manner without cytotoxicity. These effects were attributed to its ability to suppress the activity of two transcription factors (NFATc1 and c‐Fos) indispensable for osteoclast formation, followed by inhibition of the expression of bone resorption‐related genes and proteins (Acp5/TRAcP, CTSK, V‐ATPase‐d2 and integrin β3). Furthermore, we examined the underlying mechanisms and found that astilbin repressed osteoclastogenesis by blocking Ca2+ oscillations and the NF‐κB and MAPK pathways. In addition, the therapeutic effect of MA on preventing bone loss in vivo was further confirmed in an ovariectomized mouse model. Therefore, considering its ability to inhibit RANKL‐mediated osteoclastogenesis and the underlying mechanisms, astilbin might be a potential candidate for treating osteolytic bone diseases.

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Interaction study of astilbin, isoastilbin and neoastilbin toward CYP2D6 by multi‐spectroscopy and molecular docking

et al. 2021

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Astilbin, isoastilbin and neoastilbin are the three flavonoid isomers prevalent in Rhizoma Smilax glabra. The interactions between human cytochrome P450 2D6 (CYP2D6) and the three isomers were investigated by multiple spectroscopic coupled with molecular docking. As a result, the fluorescence intensity of CYP2D6 was quenched statically by the three isomers. Meanwhile, astilbin had the strongest binding ability to CYP2D6, followed by isoastilbin and neoastilbin under the identical temperature. Synchronous fluorescence, three‐dimensional fluorescence, ultraviolet‐visible spectroscopy, circular dichroism and Fourier‐transform infrared spectra confirmed that the conformation and micro‐environment of CYP2D6 protein were changed after binding with the three isomers. As suggested from molecular docking, the three isomers had strong binding affinity to CYP2D6 via the bonding of hydrogen and van der Waals forces, and the results were in agreement with the fluorescence results. The findings here suggested that astilbin, isoastilbin and neoastilbin may cause the herb–drug interactions for their inhibition of CYP2D6 activity.

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Astilbin ameliorates pulmonary fibrosis via blockade of Hedgehog signaling pathway

Cited by 22 publications

References 37 publications

Regulatory network of two circRNAs and an miRNA with their targeted genes under astilbin treatment in pulmonary fibrosis

Regulatory network of two circRNAs and an miRNA with their targeted genes under astilbin treatment in pulmonary fibrosis

Astilbin prevents bone loss in ovariectomized mice through the inhibition of RANKL‐induced osteoclastogenesis

Interaction study of astilbin, isoastilbin and neoastilbin toward CYP2D6 by multi‐spectroscopy and molecular docking

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