ArticleEvidence-based complementary and alternative medicine : eCAM2015
Rhein Elicits In Vitro Cytotoxicity in Primary Human Liver HL-7702 Cells by Inducing Apoptosis through Mitochondria-Mediated Pathway.
Article in Evidence-based complementary and alternative medicine : eCAM, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Potential Hepatotoxins Found in Herbal Medicinal Products: A Systematic Review.International journal of molecular sciences · 2020Pooled it
- Rhein and its derivatives: potential anti-tumor drugs and corresponding targeted mechanism.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Review
- Comprehensive Review on the Toxicity of Five Main AQ Constituents from Rhubarb: Mechanisms, Challenges and Future Perspectives.Drug design, development and therapy · 2026Review
- Generalizability of Enzyme-Based Isolation Approach for Extracellular Vesicles From Traditional Medicinal Plants.Journal of extracellular biology · 2025Article
- Mechanism of activation of TLR4/NF-κB/NLRP3 signaling pathway induced by heat stress disrupting the filtration barrier in broiler.BMC veterinary research · 2024Article
- A Biomimetic Multifunctional Nanoframework for Symptom Relief and Restorative Treatment of Acute Liver Failure.ACS nano · 2024Article
- Design of Oral Sustained-Release Pellets by Modeling and Simulation Approach to Improve Compliance for Repurposing Sobrerol.Pharmaceutics · 2022Article
- Hepatotoxic metabolites inFrontiers in pharmacology · 2022Article
- Herb-Induced Liver Injury Related toFrontiers in pharmacology · 2021Review
- Therapeutic Emergence of Rhein as a Potential Anticancer Drug: A Review of Its Molecular Targets and Anticancer Properties.Molecules (Basel, Switzerland) · 2020Review
- Effects of Starvation on Antioxidant-Related Signaling Molecules, Oxidative Stress, and Autophagy in Juvenile Chinese Perch Skeletal Muscle.Marine biotechnology (New York, N.Y.) · 2020Article
- Pramipexole Inhibits MPPNeurochemical research · 2020Article
- Protein profiling of SH-SY5Y neuroblastoma cells: The effect of rhein.Journal of biosciences · 2019Article
- Heat stress-induced renal damage in poultry and the protective effects of HSP60 and HSP47.Cell stress & chaperones · 2018Article
- Inhibition of MDM2 by a Rhein-Derived Compound AQ-101 Suppresses Cancer Development in SCID Mice.Molecular cancer therapeutics · 2018Article
- Rhein Induces Oxidative Stress and Apoptosis in Mouse Blastocysts and Has Immunotoxic Effects during Embryonic Development.International journal of molecular sciences · 2017Article
- Molecular mechanisms of ampelopsin fromOncology letters · 2017Article
- Rhein exhibits antioxidative effects similar to Rhubarb in a rat model of traumatic brain injury.BMC complementary and alternative medicine · 2017Article
- A Comprehensive and System Review for the Pharmacological Mechanism of Action of Rhein, an Active Anthraquinone Ingredient.Frontiers in pharmacology · 2016Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Objective. To study rhein-induced apoptosis signaling pathway and to investigate its molecular mechanisms in primary human hepatic cells. Results. Cell viability of HL-7702 cells treated with rhein showed significant decrease in dose-dependent manner. Following rhein treatment (25 μM, 50 μM, and 100 μM) for 12 h, the detection of apoptotic cells was significantly analyzed by flow cytometry and nuclear morphological changes by Hoechst 33258, respectively. Fatty degeneration studies showed upregulation level of the relevant hepatic markers (P < 0.01). Caspase activities expressed significant upregulation of caspase-3, caspase-9, and caspase-8. Moreover, apoptotic cells by rhein were significantly inhibited by Z-LEHD-FMK and Z-DEVD-FMK, caspase-9 inhibitor, and caspase-3 inhibitor, respectively. Overproduction of reactive oxygen species, lipid peroxidation, and loss of mitochondrial membrane potential were detected by fluorometry. Additionally, NAC, a ROS scavenger, significantly attenuated rhein-induced oxidative damage in HL-7702 cells. Furthermore, real-time qPCR results showed significant upregulation of p53, PUMA, Apaf-1, and Casp-9 and Casp-3 mRNA, with no significant changes of Fas and Cytochrome-c. Immunoblotting revealed significant Cytochrome-c release from mitochondria into cytosol and no change in Fas expression. Conclusion. Taken together, these observations suggested that rhein could induce apoptosis in HL-7702 cells via mitochondria-mediated signal pathway with involvement of oxidative stress mechanism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.