<i>In vivo</i> pharmacokinetics of and tissue distribution study of physalin B after intravenous administration in rats by liquid chromatography with tandem mass spectrometry

Zheng, Yang; Chen, Jing; Liu, Lin; Liang, Xiaoyang; Hong, Dongsheng

doi:10.1002/bmc.3678

Cited by 16 publications

(9 citation statements)

References 20 publications

(25 reference statements)

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“…A recent study reported that physalin B has a relative long dwell time with a half-life of 321.2 ± 29.5 min and clearance of 175.4 ± 25.7 ml/min/kg in rats after intravenous injection (19). Although widely distributed in tissues, physalin B penetration was particularly high in the lungs.…”

Section: Discussionmentioning

confidence: 99%

Physalin D inhibits RANKL-induced osteoclastogenesis and bone loss via regulating calcium signaling

Ding

Cui

et al. 2020

BMB Rep.

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We investigated the effects of physalin A, B, D, and F on osteoclastogenesis induced by receptor activator of nuclear factor B ligand (RANKL). The biological functions of different physalins were first predicted using an in silico bioinformatic tool (BATMAN-TCM). Afterwards, we tested cell viability and cell apoptosis rate to analyze the cytotoxicity of different physalins. We analyzed the inhibitory effects of physalins on RANKL-induced osteoclastogenesis from mouse bone-marrow macrophages (BMMs) using a tartrate-resistant acid phosphatase (TRAP) stain. We found that physalin D has the best selectivity index (SI) among all analyzed physalins. We then confirmed the inhibitory effects of physalin D on osteoclast maturation and function by immunostaining of F-actin and a pit-formation assay. On the molecular level, physalin D attenuated RANKLevoked intracellular calcium ([Ca(2＋)](i)) oscillation by inhibiting phosphorylation of phospholipase C2 (PLC2) and thus blocked the downstream activation of Ca2＋/calmodulindependent protein kinases (CaMK)IV and cAMP-responsive element-binding protein (CREB). An animal study showed that physalin D treatment rescues bone microarchitecture, prevents bone loss, and restores bone strength in a model of rapid bone loss induced by soluble RANKL. Taken together, these results suggest that physalin D inhibits RANKL-induced osteoclastogenesis and bone loss via suppressing the PLC2-CaMK-CREB pathway. [BMB Reports 2020; 53(3): 154-159] BMB Rep. 2020; 53(3): 154-159 www.bmbreports.org 157 http://bmbreports.org BMB Reports

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Section: Discussionmentioning

confidence: 99%

Physalin D inhibits RANKL-induced osteoclastogenesis and bone loss via regulating calcium signaling

Ding

Cui

et al. 2020

BMB Rep.

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“…Physalin B (purity [? ]98%) were separated and purified in our laboratory; their structures, shown in Figure 1A, were confirmed by comparing the IR, 1H and 13C nuclear magnetic resonance and MS data with reported data (Zheng, Chen, Liu, Liang & Hong, 2016). Calyx Seu Fructus Physalis (3 kg) were extracted with 95% ethanol for three times.…”

Section: Reagentsmentioning

confidence: 61%

Physalin B attenuates liver fibrosis via suppressing LAP2α-HDAC1 mediated deacetylation of GLI1 and hepatic stellate cell activation

Zhu

et al. 2020

Preprint

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Background and Purpose: Liver fibrosis is one of the leading causes of morbidity and mortality worldwide of which no acceptable therapy exists. Accumulating evidence supports that glioma-associated oncogene homologue 1(GLI1) is a potentially important therapeutic target for liver fibrosis. This study investigates the antifibrotic activities and potential mechanisms of Physalin B (PB), a natural Solanaceae compound. Experimental Approach: Mice subjected to CCl4 challenge and bile duct ligation were used to study the antifibrotic effects of PB in vivo. Mouse primary hepatic stellate cells (pHSCs) and human HSC line LX‐2 also served as an in vitro liver fibrosis model. Liver fibrogenic genes, GLI1 downstream genes were examined using western blot and real-time PCR analyses. GLI1 acetylation and LAP2α-HDAC1 interaction were analyzed by coimmunoprecipitation. Key Results: In animal models, PB administration attenuated hepatic histopathological injury, collagen accumulation, and reduced the expression of fibrogenic genes. PB dose‐dependently suppressed fibrotic marker expression in LX‐2 cells and mouse pHSCs. Mechanistic studies showed PB inhibited GLI activity in a non-canonical Hedgehog signaling. PB blocked lamina-associated polypeptide 2 α (LAP2α)/ histone deacetylase 1 (HDAC1) complex formation thereby inhibited HDAC1mediated GLI1 deacetylation. PB downregulated the acetylation and expression of GLI1, and subsequently inhibiting HSC activation. Conclusions and Implications: PB exerted potent antifibrotic effects in vitro and in vivo by disrupting the LAP2α/HDAC1 complex, increasing GLI1 acetylation and inactivating GLI1. This indicates that PB may be a potential therapeutic candidate for the treatment of liver fibrosis.

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“…Physalin B (purity ≥98%) was extracted and purified in our laboratory and the structure, shown in Figure 1a, was confirmed by comparing the IR, 1 H and 13 C NMR, and MS data with reported data (Zheng et al, 2016). Physalis Calyx seu Fructus (3 kg) were extracted three times, with 95% ethanol.…”

Section: Methodsmentioning

confidence: 77%

Physalin B attenuates liver fibrosis via suppressing LAP2α–HDAC1‐mediated deacetylation of the transcription factor GLI1 and hepatic stellate cell activation

Zhu

et al. 2021

British J Pharmacology

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Background and Purpose Liver fibrosis is one of the leading causes of morbidity and mortality worldwide but lacks any acceptable therapy. The transcription factor glioma‐associated oncogene homologue 1 (GLI1) is a potentially important therapeutic target in liver fibrosis. This study investigates the anti‐fibrotic activities and potential mechanisms of the phytochemical, physalin B. Experimental Approach Two mouse models (CCl4 challenge and bile duct ligation) were used to assess antifibrotic effects of physalin B in vivo. Mouse primary hepatic stellate cells (pHSCs) and human HSC line LX‐2 also served as in vitro liver fibrosis models. Liver fibrogenic genes, GLI1 and GLI1 downstream genes were examined using Western blot and quantitative real‐time PCR (qRT‐PCR). GLI1 acetylation and LAP2α–HDAC1 interaction were analysed by co‐immunoprecipitation. Key Results In vivo, physalin B administration attenuated hepatic histopathological injury and collagen accumulation and decreased expression of fibrogenic genes. Physalin B dose‐dependently suppressed fibrotic marker expression in LX‐2 cells and mouse pHSCs. Mechanistic studies showed that physalin B inhibited GLI activity by non‐canonical Hedgehog signalling. Physalin B blocked formation of lamina‐associated polypeptide 2α (LAP2α)/histone deacetylase 1 (HDAC1) complexes, thus inhibiting HDAC1‐mediated GLI1 deacetylation. Physalin B up‐regulated acetylation of GLI1, down‐regulated expression of GLI1 and subsequently inhibited HSC activation. Conclusion and Implications Physalin B exerted potent antifibrotic effects in vitro and in vivo by disrupting LAP2α/HDAC1 complexes, increasing GLI1 acetylation and inactivating GLI1. This indicates that the phytochemical physalin B may be a potential therapeutic candidate for the treatment of liver fibrosis.

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In vivo pharmacokinetics of and tissue distribution study of physalin B after intravenous administration in rats by liquid chromatography with tandem mass spectrometry

Cited by 16 publications

References 20 publications

Physalin D inhibits RANKL-induced osteoclastogenesis and bone loss via regulating calcium signaling

Physalin D inhibits RANKL-induced osteoclastogenesis and bone loss via regulating calcium signaling

Physalin B attenuates liver fibrosis via suppressing LAP2α-HDAC1 mediated deacetylation of GLI1 and hepatic stellate cell activation

Physalin B attenuates liver fibrosis via suppressing LAP2α–HDAC1‐mediated deacetylation of the transcription factor GLI1 and hepatic stellate cell activation

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