ArticleClinical and translational medicine2021
Rebalancing TGF-β/Smad7 signaling via Compound kushen injection in hepatic stellate cells protects against liver fibrosis and hepatocarcinogenesis.
Article in Clinical and translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 2 of them syntheses that pooled it.
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Who cites it
52 citing papers in PubMed, 2 syntheses or guidelines pooled it, 92 citations in OpenAlex.
- Immune effect of Traditional Chinese Medicine combined with transcatheter arterial chemoembolization in treatment of liver cancer: a meta-analysis.BMC cancer · 2026Pooled it
- Effect of compound kushen injection on immune function in patients with primary liver cancer: a systematic review and meta-analysis.Frontiers in pharmacology · 2026Pooled it
- Inhibition of PERK signaling suppresses tumor progression and blocks GP73-GRP78-dependent stromal activation in hepatocellular carcinoma.Neoplasia (New York, N.Y.) · 2026Article
- Matrine and oxymatrine: a comprehensive review of multitarget mechanisms and therapeutic potential.Journal of natural medicines · 2026Review
- Herb-derived immunometabolic modulators: traditional Chinese medicine at the crossroads of metabolism and antitumor immunity.Chinese medicine · 2026Review
- Mechanism of matrine inhibiting retinoblastoma cell growth by downregulating NR1D2 to regulate phosphorylation of the PI3K/AKT signaling pathway.Scientific reports · 2026Article
- Review
- Cerenkov radiation modulates the extracellular matrix for improved pancreatic cancer chemotherapy.Cell biomaterials · 2026Article
- EWSR1 as a regulatory target in hepatic stellate cell apoptosis and liver fibrosis therapy.Biochemistry and biophysics reports · 2026Review
- Integrative multiomics analysis reveals the ameliorative effects of Xiasangju on metabolic dysfunction-associated steatohepatitis.Chinese medicine · 2026Article
- Hepatitis C virus core protein-induced myeloid-derived suppressor cells promote hepatic fibrosis by regulating hepatic stellate cell function via TGF-β.Frontiers in immunology · 2026Article
- CombinedFrontiers in pharmacology · 2026Article
- Interplay between TGF-β signaling and long non-coding RNAs in digestive system cancers: mechanisms and biological implications.Human cell · 2025Review
- Oxymatrine Alleviates Cerebral Ischemia/Reperfusion Injury By Targeting HDAC1 to Regulate Mitochondria-Related Autophagy and Oxidative Stress.Molecular neurobiology · 2025Article
- Article
- LGALS3 promotes liver fibrosis by enhancing the expression and phosphorylation of ERK1/2.European journal of medical research · 2025Article
- The Protective Effect of Phenolic Acids on Liver Disease: A Review of Possible Mechanisms.Antioxidants (Basel, Switzerland) · 2025Review
- Oxymatrine attenuates pulmonary fibrosis via APE1‑mediated regulation of the PINK1/Parkin pathway.Molecular medicine reports · 2025Article
- Article
- Prognostic value of immune-inflammation and nutritional indices in advanced hepatocellular carcinoma patients receiving immunotherapy with compound Kushen injection.World journal of gastrointestinal oncology · 2025Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLiver fibrosis and fibrosis-related hepatocarcinogenesis are a rising cause for morbidity and death worldwide. Although transforming growth factor-β (TGF-β) is a critical mediator of chronic liver fibrosis, targeting TGF-β isoforms and receptors lead to unacceptable side effect. This study was designed to explore the antifibrotic effect of Compound kushen injection (CKI), an approved traditional Chinese medicine formula, via a therapeutic strategy of rebalancing TGF-β/Smad7 signaling.
methodsA meta-analysis was performed to evaluate CKI intervention on viral hepatitis-induced fibrosis or cirrhosis in clinical randomized controlled trials (RCTs). Mice were given carbon tetrachloride (CCl
resultsBased on meta-analysis results, CKI improved the liver function and relieved liver fibrosis among patients. In our preclinical studies by using two mouse models, CKI treatment demonstrated promising antifibrotic effects and postponed hepatocarcinogenesis with improved liver function and histopathologic features. Mechanistically, we found that CKI inhibited HSCs activation by stabilizing the interaction of Smad7/TGF-βR1 to rebalance Smad2/Smad3 signaling, and subsequently decreased the extracellular matrix formation. Importantly, Smad7 depletion abolished the antifibrotic effect of CKI in vivo and in vitro. Moreover, matrine, oxymatrine, sophocarpine, and oxysophocarpine were identified as material basis responsible for the antifibrosis effect of CKI.
conclusionsOur results unveil the approach of CKI in rebalancing TGF-β/Smad7 signaling in HSCs to protect against hepatic fibrosis and hepatocarcinogenesis in both preclinical and clinical studies. Our study suggests that CKI can be a candidate for treatment of hepatic fibrosis and related oncogenesis.
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