ArticleArthritis research & therapy2010
Pomegranate extract inhibits the interleukin-1β-induced activation of MKK-3, p38α-MAPK and transcription factor RUNX-2 in human osteoarthritis chondrocytes.
Article in Arthritis research & therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Effects of plant active substances in rheumatoid arthritis-a systematic review and network meta-analysis.Frontiers in pharmacology · 2025Pooled it
- Blueberries Improve Pain, Gait Performance, and Inflammation in Individuals with Symptomatic Knee Osteoarthritis.Nutrients · 2019Trial
- Pomegranate extract alleviates disease activity and some blood biomarkers of inflammation and oxidative stress in Rheumatoid Arthritis patients.European journal of clinical nutrition · 2017Trial
- Obeticholic acid attenuates complete freund's adjuvant-induced arthritis in rats through FXR-mediated modulation of TGF-β/TAK1/MKK3/p38 MAPK signaling, inflammation, and oxidative stress.Inflammopharmacology · 2026Article
- Natural products in the treatment of osteoarthritis: Current status and prospects.Journal of orthopaedic translation · 2025Review
- Nutritional Epigenomics: Bioactive Dietary Compounds in the Epigenetic Regulation of Osteoarthritis.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Suppression of CGRP and TRPV1 Expression in Dorsal Root Ganglia of Knee Osteoarthritis Rats by Huojing Decoction via TrkA/MKK3/6/p38 Pathway.Journal of inflammation research · 2024Article
- Effects of Pomegranate (Punica granatum L.) Peel Extract Supplementation on Markers of Inflammation and Serum Matrix Metalloproteinase 1 in Women With Knee Osteoarthritis: A Randomized Double-Blind Placebo-Controlled Study.Nutrition and metabolic insights · 2024Article
- Do Pomegranate Hydrolyzable Tannins and Their Derived Metabolites Provide Relief in Osteoarthritis? Findings from a Scoping Review.Molecules (Basel, Switzerland) · 2022Article
- Polyphenols Targeting MAPK Mediated Oxidative Stress and Inflammation in Rheumatoid Arthritis.Molecules (Basel, Switzerland) · 2021Review
- Quercetin suppresses apoptosis of chondrocytes induced by IL-1β via inactivation of p38 MAPK signaling pathway.Experimental and therapeutic medicine · 2021Article
- Systematic review of the effects of pomegranate (Health promotion perspectives · 2021Review
- Mitochondrial dysfunction triggers a catabolic response in chondrocytes via ROS-mediated activation of the JNK/AP1 pathway.Journal of cell science · 2020Article
- Role of iNOS in osteoarthritis: Pathological and therapeutic aspects.Journal of cellular physiology · 2020Review
- Oxidative stress and inflammation in osteoarthritis pathogenesis: Role of polyphenols.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2020Review
- Herbal Remedies as Potential in Cartilage Tissue Engineering: An Overview of New Therapeutic Approaches and Strategies.Molecules (Basel, Switzerland) · 2020Review
- Unraveling Natural Products' Role in Osteoarthritis Management-An Overview.Antioxidants (Basel, Switzerland) · 2020Review
- Anti-Osteoarthritic Effects of a Mixture of Dried Pomegranate Concentrate Powder, Eucommiae Cortex, and Achyranthis Radix 5:4:1 (Nutrients · 2020Article
- Chondrocyte-Specific RUNX2 Overexpression Accelerates Post-traumatic Osteoarthritis Progression in Adult Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Article
- Wnt and RUNX2 mediate cartilage breakdown by osteoarthritis synovial fibroblast-derived ADAMTS-7 and -12.Journal of cellular and molecular medicine · 2019Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
introductionPomegranate has been revered throughout history for its medicinal properties. p38-MAPK is a major signal-transducing pathway in osteoarthritis (OA) and its activation by interleukin-1β (IL-1β) plays a critical role in the expression and production of several mediators of cartilage catabolism in OA. In this study we determined the effect of a standardized pomegranate extract (PE) on the IL-1β-induced activation of MKK3/6, p38-MAPK isoforms and the activation of transcription factor RUNX-2 in primary human OA chondrocytes.
methodsHuman chondrocytes were derived from OA cartilage by enzymatic digestion, treated with PE and then stimulated with IL-1β. Gene expression of p38-MAPK isoforms was measured by RT-PCR. Western immunoblotting was used to analyze the activation of MAPKs. Immunoprecipitation was used to determine the activation of p38-MAPK isoforms. DNA binding activity of RUNX-2 was determined using a highly sensitive and specific ELISA. Pharmacological studies to elucidate the involved pathways were executed using transfection with siRNAs.
resultsHuman OA chondrocytes expressed p38-MAPK isoforms p38α, -γ and -δ, but not p38β. IL-1β enhances the phosphorylation of the p38α-MAPK and p38γ-MAPK isoforms but not of p38δ-MAPK isoform in human OA chondrocytes. Activation of p38-MAPK in human OA chondrocytes was preferentially mediated via activation of MKK3. In addition, we also demonstrate that polyphenol rich PE inhibited the IL-1β-induced activation of MKK3, p38α-MAPK isoform and DNA binding activity of the transcription factor RUNX-2.
conclusionsOur results provide an important insight into the molecular basis of the reported cartilage protective and arthritis inhibitory effects of pomegranate extract. These novel pharmacological actions of PE on IL-1β stimulated human OA chondrocytes impart a new suggestion that PE or PE-derived compounds may be developed as MKK and p38-MAPK inhibitors for the treatment of OA and other degenerative/inflammatory diseases.
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Registered trials
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