Physalin D attenuates hepatic stellate cell activation and liver fibrosis by blocking TGF-β/Smad and YAP signaling

Xiang, Dejuan; Zou, Jie; Zhu, Xiaoyun; Chen, Xinling; Luo, Jian‐Guang; Kong, Ling‐Yi; Zhang, Hao

doi:10.1016/j.phymed.2020.153294

Cited by 71 publications

(49 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…M1 macrophages promote fibrosis by producing TGF-β, and M2 macrophages can also be pro-fibrogenic by secreting TGF-β during chronic inflammation [99,107]. Inhibition of the TGF-β signaling pathway of HSCs significantly improves collagen deposition [108]. Chronic inflammation is often the cause of liver fibrosis.…”

Section: Roles Of Trem In Hepatic Fibrosismentioning

confidence: 99%

Function of TREM1 and TREM2 in Liver-Related Diseases

Sun

Feng

Tang

2020

Cells

View full text Add to dashboard Cite

TREM1 and TREM2 are members of the triggering receptors expressed on myeloid cells (TREM) family. Both TREM1 and TREM2 are immunoglobulin superfamily receptors. Their main function is to identify foreign antigens and toxic substances, thereby adjusting the inflammatory response. In the liver, TREM1 and TREM2 are expressed on non-parenchymal cells, such as liver sinusoidal endothelial cells, Kupffer cells, and hepatic stellate cells, and cells which infiltrate the liver in response to injury including monocyte-derived macrophages and neutrophils. The function of TREM1 and TREM2 in inflammatory response depends on Toll-like receptor 4. TREM1 mainly augments inflammation during acute inflammation, while TREM2 mainly inhibits chronic inflammation to protect the liver from pathological changes. Chronic inflammation often induces metabolic abnormalities, fibrosis, and tumorigenesis. The above physiological changes lead to liver-related diseases, such as liver injury, nonalcoholic steatohepatitis, hepatic fibrosis, and hepatocellular carcinoma. Here, we review the function of TREM1 and TREM2 in different liver diseases based on inflammation, providing a more comprehensive perspective for the treatment of liver-related diseases.

show abstract

Section: Roles Of Trem In Hepatic Fibrosismentioning

confidence: 99%

Function of TREM1 and TREM2 in Liver-Related Diseases

Sun

Feng

Tang

2020

Cells

View full text Add to dashboard Cite

show abstract

“…Upregulation of endogenous HO-1 expression may modify immunity and protect cells from harm, according to a prior study (Sun et al, 2011). Another study stated that ciplukan's active ingredient physalin D reduced liver fibrosis by blocking the TGF-β/ SMAD and YAP (Yes-associated Protein) signaling pathway (Xiang et al, 2020).…”

Section: Discussionmentioning

confidence: 94%

Antifibrotic effect of the ethyl acetate fraction of ciplukan (Physalis angulata Linn.) in rat liver fibrosis induced by CCI4

Rohmawaty¹,

Rosdianto²,

Usman³

et al. 2021

J Appl Pharm Sci

View full text Add to dashboard Cite

Ciplukan (Physalis angulata Linn.) is a Solanaceae family species and contains various active compounds with diverse therapeutic potential. The goal of this investigation was to see if the ethyl acetate fraction of ciplukan had an antifibrotic impact on liver fibrosis. The oral administration of 20% carbon tetrachloride (CCl 4 ) twice weekly for 8 weeks was used to cause liver fibrosis. Four weeks following fibrosis induction, ciplukan ethyl acetate fractions of 1.11 mg (CPL-1) and 2.22 mg (CPL-2) were given orally. As a positive control group, vitamin E was used. When compared to the negative control, the ethyl acetate portion of 2.22 mg (CPL-2) lowered serum alanine aminotransaminase levels (83.95 ± 27.675 vs 175.23 ± 5.641, p-value < 0.05). Microscopic histopathological changes based on the better Metavir score (CPL-2 vs. negative control = 1.25 ± 1.893 vs. 3.50 ± 0.577; p-value < 0.05) and Ishak score (CPL-2 vs. negative control = 1.50 ± 1.000 vs. 4.75 ± 0.957 p-value < 0.05) were demonstrated. Overall, in rat liver fibrosis induced by CCl 4 , these findings suggest that the ethyl acetate fraction of ciplukan has an antifibrotic effect.

show abstract

“…TGF-β1-induced activation of LX-2 cells predisposes to liver fibrosis, resulting from chronic LI developing into cirrhosis that ultimately leads to liver failure (Bestion et al, 2020;Xiang et al, 2020). We chose hesperidin and naringenin to evaluate our prediction results further to validate changes in several relevant proteins in LX-2 cells with or without TGF-β1 (5 ng/ ml) treatment.…”

Section: Target Validationmentioning

confidence: 99%

Systems Pharmacology Study of the Anti-Liver Injury Mechanism of Citri Reticulatae Pericarpium

Yang

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Liver diseases are mostly triggered by oxidative stress and inflammation, leading to extracellular matrix overproduction and prone to develop into liver fibrosis, cirrhosis and hepatocellular carcinoma. Liver injury (LI) refers to various pathogenic factors leading to the destruction of stem cells that then affect the liver’s normal function, causing a series of symptoms and abnormal liver function indicators. Citri Reticulatae Pericarpium (CRP) is one of the most commonly used traditional Chinese medicines; it contains flavonoids including hesperidin, nobiletin, and tangeretin. CRP has antibacterial, antioxidant, and antitumor effects that reduce cholesterol, prevent atherosclerosis and decrease LI. Here we analyzed the components of CRP and their targets of action in LI treatment and assessed the relationships between them using a systems pharmacology approach. Twenty-five active ingredients against LI were selected based on ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry results and databases. The drug targets and disease-related targets were predicted. The 117 common targets were used to construct a protein-protein interaction network. We identified 1719 gene ontology items in LI treatment, including 1,525 biological processes, 55 cellular components, and 139 molecular functions. These correlated with 49 Kyoto Encyclopedia of Genes and Genomes pathways. These findings suggest that CRP may counteract LI by affecting apoptotic, inflammatory, and energy metabolism modules. In vitro experiments suggested that the mechanism may involve hesperidin and naringenin acting on CASP3, BAX, and BCL2 to affect the apoptosis pathway, attenuating liver fibrosis. Naringenin significantly inhibited AKT1 phosphorylation, which in turn mediated activation of the phosphoinositide 3-kinase-Akt signaling pathways against LI. This study provides a reference for systematically exploring the mechanism of CRP’s anti-LI action and is also expands of the application of systems pharmacology in the study of traditional Chinese medicine.

show abstract

Physalin D attenuates hepatic stellate cell activation and liver fibrosis by blocking TGF-β/Smad and YAP signaling

Cited by 71 publications

References 46 publications

Function of TREM1 and TREM2 in Liver-Related Diseases

Function of TREM1 and TREM2 in Liver-Related Diseases

Antifibrotic effect of the ethyl acetate fraction of ciplukan (Physalis angulata Linn.) in rat liver fibrosis induced by CCI4

Systems Pharmacology Study of the Anti-Liver Injury Mechanism of Citri Reticulatae Pericarpium

Contact Info

Product

Resources

About